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Lim ETA, Jardine D, Frampton C, Pemberton CJ, Troughton R, Roake J, Khanafer A. Sympathetic Nerve Activity following Acute Type B Aortic Dissection: A Pilot Study. J Vasc Res 2024; 62:88-95. [PMID: 39733774 DOI: 10.1159/000543340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Accepted: 12/23/2024] [Indexed: 12/31/2024] Open
Abstract
INTRODUCTION Control of blood pressure following acute type B aortic dissection usually requires sympatholytic antihypertensive medication. Although sympathetic nerve activity is central to blood pressure control, its role in the hypertensive response to acute aortic dissection has not been assessed. METHODS A prospective pilot study was performed over an 18-month period. Patients presenting with acute type B aortic dissection confirmed on computed tomographic angiography were recruited. We measured blood pressure, heart rate, muscle sympathetic nerve activity (MSNA), and plasma catecholamine levels in patients following acute type B dissection and controls. Comparisons between groups were made 1 week (acute phase) and 3 months after dissection (recovery phase). RESULTS Five patients and four controls were recruited in the study. MSNA was higher in patients than controls during the acute phase of aortic dissection: 62 (60-62) versus 46 (29-60) bursts/min (effect size 0.88) and 88 (54-96) versus 71 (44-101) bursts/100 beats (effect size 0.60). Plasma normetanephrines were also increased acutely: 821.0 (489.0-884.0) versus 417.0 (348.5-561.5) pmol/L (effect size 0.85). CONCLUSION Sympathetic nerve activity is increased acutely during the first week after type B aortic dissection, resolving towards control values after 3 months. Immediate sympatholytic drug treatment is likely to be crucial in order to prevent the acute and chronic complications of this response. This may confer benefits over and above simply lowering the blood pressure to protect the aorta in the acute phase.
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Affiliation(s)
- Eric T A Lim
- Department of Vascular, Endovascular and Transplant Surgery, Christchurch Hospital, Christchurch, New Zealand
- Department of Surgery, University of Otago Christchurch, Christchurch, New Zealand
| | - David Jardine
- Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand
| | - Christopher Frampton
- Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand
| | | | - Richard Troughton
- Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand
| | - Justin Roake
- Department of Vascular, Endovascular and Transplant Surgery, Christchurch Hospital, Christchurch, New Zealand
- Department of Surgery, University of Otago Christchurch, Christchurch, New Zealand
| | - Adib Khanafer
- Department of Vascular, Endovascular and Transplant Surgery, Christchurch Hospital, Christchurch, New Zealand
- Department of Surgery, University of Otago Christchurch, Christchurch, New Zealand
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Klassen SA, Limberg JK, Harvey RE, Wiggins CC, Spafford JE, Iannarelli NJ, Senefeld JW, Nicholson WT, Curry TB, Joyner MJ, Shoemaker JK, Baker SE. Human sympathetic neuronal discharge and recruitment patterns regulate neuropeptide Y bioavailability. Am J Physiol Heart Circ Physiol 2024; 327:H1599-H1605. [PMID: 39453430 PMCID: PMC11684957 DOI: 10.1152/ajpheart.00639.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 10/11/2024] [Accepted: 10/18/2024] [Indexed: 10/26/2024]
Abstract
What is the purpose of sympathetic neuronal action potential (AP) discharge and recruitment patterns for human vascular regulation? This study tested the hypothesis that sympathetic neuronal discharge and recruitment patterns regulate neuropeptide Y (NPY) bioavailability. We used microneurography to record muscle sympathetic nerve activity and a continuous wavelet transform to detect sympathetic APs during a baseline condition and intravenous dexmedetomidine infusion (α2-adrenergic agonist, 10-min loading infusion of 0.225 µg·kg-1; maintenance infusion of 0.1-0.5 µg·kg·h-1) in six healthy individuals (5 females, 27 ± 6 yr). Arterial blood samples provided NPY (enzyme-linked immunosorbent assay) and norepinephrine (liquid chromatography-tandem mass spectrometry) levels at baseline and the dexmedetomidine maintenance infusion. Linear mixed-model regressions assessed the relationships between AP discharge, recruitment, and neurotransmitter levels. Across baseline and the dexmedetomidine condition, NPY levels were positively related to mean arterial pressure (β = 1.63 [0.34], P = 0.002), total AP clusters (β = 0.90 [0.22], P = 0.005), and AP frequency (β = 0.11 [0.03], P = 0.003). Norepinephrine levels were not related to mean arterial pressure (β = 0.03 [0.02], P = 0.133) but were positively related to total AP clusters (β = 19.50 [7.07], P = 0.030) and AP frequency (β = 2.66 [0.81], P = 0.014). These data suggest that sympathetic neuronal discharge and recruitment patterns regulate NPY and norepinephrine bioavailability in healthy adults. As such, sympathetic neuronal firing strategies are important for human vascular regulation.NEW & NOTEWORTHY The purpose of sympathetic neuronal discharge and the recruitment of neuronal subpopulations for human circulatory homeostasis remains unknown. This study tested the hypothesis that sympathetic neuronal discharge and recruitment patterns regulate neuropeptide Y (NPY) bioavailability. Across baseline and an intravenous dexmedetomidine infusion (α2-adrenergic agonist) sympathetic action potential (AP) frequency and total sympathetic AP clusters were associated with NPY bioavailability. This is the first study to report that sympathetic neuronal discharge and recruitment patterns regulate NPY bioavailability to support circulatory homeostasis in humans.
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Affiliation(s)
- Stephen A Klassen
- Department of Kinesiology, Brock University, St. Catharines, Ontario, Canada
| | - Jacqueline K Limberg
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri, United States
| | - Ronée E Harvey
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, United States
| | - Chad C Wiggins
- Department of Kinesiology, Michigan State University, East Lansing, Michigan, United States
| | - Julia E Spafford
- Department of Kinesiology, Brock University, St. Catharines, Ontario, Canada
| | | | - Jonathon W Senefeld
- Department of Health and Kinesiology, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States
| | - Wayne T Nicholson
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, United States
| | - Timothy B Curry
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, United States
| | - Michael J Joyner
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, United States
| | - J Kevin Shoemaker
- School of Kinesiology, Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada
| | - Sarah E Baker
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, United States
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Boyes NG, Klassen SA, Baker SE, Nicholson WT, Joyner MJ, Shoemaker JK, Limberg JK. Interaction of simultaneous hypoxia and baroreflex loading on control of sympathetic action potential subpopulations. J Neurophysiol 2024; 132:1087-1097. [PMID: 39140588 PMCID: PMC11427050 DOI: 10.1152/jn.00277.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 08/05/2024] [Accepted: 08/09/2024] [Indexed: 08/15/2024] Open
Abstract
Efferent muscle sympathetic nerve activity (MSNA) is under tonic baroreflex control. The arterial baroreflex exerts the strongest influence over medium-sized sympathetic action potential (AP) subpopulations in efferent MSNA recordings. Prior work from multiunit MSNA recordings has shown baroreflex loading selectively abolishes the sympathetic response to hypoxia. The purpose of the study was to examine baroreflex control over different-sized AP clusters and characterize the neural recruitment strategies of sympathetic AP subpopulations with baroreflex and combined baroreflex/chemoreflex (i.e., hypoxia) activation. We loaded the arterial baroreceptors [intravenous phenylephrine (PE)] alone and in combination with systemic hypoxia ([Formula: see text] 80%) in nine healthy young men. We extracted sympathetic APs using the wavelet-based methodology and quantified baroreflex gain for individual AP clusters. AP baroreflex threshold gain was measured as the slope of the linear relationship between AP probability versus diastolic blood pressure for 10 normalized clusters. Baroreflex loading with phenylephrine decreased MSNA and AP firing compared with baseline (all P < 0.05). However, the phenylephrine-mediated decrease in AP firing was lost with concurrent hypoxia (P = 0.384). Compared with baseline, baroreflex loading reduced medium-sized AP cluster baroreflex threshold slope (condition P = 0.005) and discharge probability (condition P < 0.0001); these reductions from baseline were maintained during simultaneous hypoxia (both P < 0.05). Present findings indicate a key modulatory role of the baroreceptors on medium-sized APs in blood pressure regulation that withstands competing signals from peripheral chemoreflex activation.NEW & NOTEWORTHY This study provides a novel understanding on baroreflex control of efferent sympathetic nervous system activity during competing stressors: baroreflex loading and peripheral chemoreflex activation. We show chemoreflex activation buffers baroreflex-mediated reductions in sympathetic nervous system activity. More importantly, baroreflex loading reduced baroreflex threshold gain of sympathetic action potential clusters and this reduction withstood chemoreflex activation. These data suggest the arterial baroreflex holds a primary regulatory role over medium-sized sympathetic neurons despite competing chemoreflex signals.
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Affiliation(s)
- Natasha G Boyes
- Department of Nutrition & Exercise Physiology, University of Missouri, Columbia, Missouri, United States
| | - Stephen A Klassen
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, United States
- School of Kinesiology, Brock University, St. Catharines, Ontario,Canada
| | - Sarah E Baker
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, United States
| | - Wayne T Nicholson
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, United States
| | - Michael J Joyner
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, United States
| | - J Kevin Shoemaker
- School of Kinesiology, University of Western Ontario, London, Ontario, Canada
| | - Jacqueline K Limberg
- Department of Nutrition & Exercise Physiology, University of Missouri, Columbia, Missouri, United States
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, United States
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Lundblad LC, Eskelin JJ, Karlsson T, Elam M. Inhibition of muscle sympathetic nerve activity in premenopausal women: responses to sudden sensory stimuli predict responses to mental stress. J Appl Physiol (1985) 2024; 137:757-764. [PMID: 39052769 DOI: 10.1152/japplphysiol.00748.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Revised: 07/05/2024] [Accepted: 07/22/2024] [Indexed: 07/27/2024] Open
Abstract
Muscle sympathetic nerve responses to sudden sensory stimuli have been elucidated in several studies on young healthy men, showing reproducible interindividual differences ranging from varying degrees of inhibition to no significant change, with very few subjects showing significant excitation. These individual response patterns have been shown to predict the neural response to mental stress and coupled blood pressure responses. The aim of this study was to investigate whether premenopausal healthy women show similar neural and blood pressure responses. Muscle sympathetic nerve recordings from the peroneal nerve were performed in 34 healthy women (mean age 27 ± 8 yr) during sudden sensory stimuli (electrical stimuli to a finger) and 3 min of mental stress (forced arithmetics). After sensory stimuli, 18 women showed varying degrees of inhibition of muscle sympathetic nerve activity (burst amplitude mean reduction 60%, range 34-100%). The remaining 16 showed no inhibition (mean 5%, range -31 to 28%; one subject exhibiting excitation). During 3 min of mental stress, the normalized change in burst incidence for muscle sympathetic nerve activity correlated with the percentage change of muscle sympathetic nerve activity induced by the sensory stimulation protocol (r = 0.64, P = 0.0042). In contrast to men, the neural responses did not predict changes in blood pressure. Thus, premenopausal females show a similar range of individual differences in defense-related muscle sympathetic neural responses as men, but no associated differences in blood pressure responses. Whether these patterns are unchanged after menopause remains to be investigated.NEW & NOTEWORTHY Muscle sympathetic neural responses to sudden sensory stimuli in premenopausal women showed interindividual differences and the distribution of sympathetic responses was similar to that previously found in men. Despite this similarity, the associated differences in transient blood pressure responses seen in men were not found in women. The increased risk of developing hypertension in postmenopausal women warrants an investigation of whether these response patterns are altered after menopause.
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Affiliation(s)
- Linda C Lundblad
- Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
- Department of Clinical Neurophysiology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - John J Eskelin
- Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
| | - Tomas Karlsson
- Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
| | - Mikael Elam
- Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
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Berbrier DE, Adler TE, Leone CA, Paidas MJ, Stachenfeld NS, Usselman CW. Blood pressure responses to handgrip exercise but not apnea or mental stress are enhanced in women with a recent history of preeclampsia. Am J Physiol Heart Circ Physiol 2024; 327:H140-H154. [PMID: 38700469 PMCID: PMC11932533 DOI: 10.1152/ajpheart.00020.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 04/29/2024] [Accepted: 04/29/2024] [Indexed: 05/05/2024]
Abstract
Preeclampsia is a risk factor for future cardiovascular diseases. However, the mechanisms underlying this association remain unclear, limiting effective prevention strategies. Blood pressure responses to acute stimuli may reveal cardiovascular dysfunction not apparent at rest, identifying individuals at elevated cardiovascular risk. Therefore, we compared blood pressure responsiveness with acute stimuli between previously preeclamptic (PPE) women (34 ± 5 yr old, 13 ± 6 mo postpartum) and women following healthy pregnancies (Ctrl; 29 ± 3 yr old, 15 ± 4 mo postpartum). Blood pressure (finger photoplethysmography calibrated to manual sphygmomanometry-derived values; PPE: n = 12, Ctrl: n = 12) was assessed during end-expiratory apnea, mental stress, and isometric handgrip exercise protocols. Integrated muscle sympathetic nerve activity (MSNA) was assessed in a subset of participants (peroneal nerve microneurography; PPE: n = 6, Ctrl: n = 8). Across all protocols, systolic blood pressure (SBP) was higher in PPE than Ctrl (main effects of group all P < 0.05). Peak changes in SBP were stressor specific: peak increases in SBP were not different between PPE and Ctrl during apnea (8 ± 6 vs. 6 ± 5 mmHg, P = 0.32) or mental stress (9 ± 5 vs. 4 ± 7 mmHg, P = 0.06). However, peak exercise-induced increases in SBP were greater in PPE than Ctrl (11 ± 5 vs. 7 ± 7 mmHg, P = 0.04). MSNA was higher in PPE than Ctrl across all protocols (main effects of group all P < 0.05), and increases in peak MSNA were greater in PPE than Ctrl during apnea (44 ± 6 vs. 27 ± 14 burst/100 hb, P = 0.04) and exercise (25 ± 8 vs. 13 ± 11 burst/100 hb, P = 0.01) but not different between groups during mental stress (2 ± 3 vs. 0 ± 5 burst/100 hb, P = 0.41). Exaggerated pressor and sympathetic responses to certain stimuli may contribute to the elevated long-term risk for cardiovascular disease in PPE.NEW & NOTEWORTHY Women with recent histories of preeclampsia demonstrated higher systolic blood pressures across sympathoexcitatory stressors relative to controls. Peak systolic blood pressure reactivity was exacerbated in previously preeclamptic women during small muscle-mass exercises, although not during apneic or mental stress stimuli. These findings underscore the importance of assessing blood pressure control during a variety of experimental conditions in previously preeclamptic women to elucidate mechanisms that may contribute to their elevated cardiovascular disease risk.
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Affiliation(s)
- Danielle E Berbrier
- Cardiovascular Health and Autonomic Regulation Laboratory, Department of Kinesiology and Physical Education, McGill University, Montreal, Quebec, Canada
| | - Tessa E Adler
- Cardiovascular Health and Autonomic Regulation Laboratory, Department of Kinesiology and Physical Education, McGill University, Montreal, Quebec, Canada
- The John B. Pierce Laboratory, Yale School of Medicine, New Haven, Connecticut, United States
| | - Cheryl A Leone
- The John B. Pierce Laboratory, Yale School of Medicine, New Haven, Connecticut, United States
| | - Michael J Paidas
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut, United States
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami Miller School of Medicine, Miami, Florida, United States
| | - Nina S Stachenfeld
- The John B. Pierce Laboratory, Yale School of Medicine, New Haven, Connecticut, United States
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut, United States
| | - Charlotte W Usselman
- Cardiovascular Health and Autonomic Regulation Laboratory, Department of Kinesiology and Physical Education, McGill University, Montreal, Quebec, Canada
- The John B. Pierce Laboratory, Yale School of Medicine, New Haven, Connecticut, United States
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Esler MD, Osborn JW, Schlaich MP. Sympathetic Pathophysiology in Hypertension Origins: The Path to Renal Denervation. Hypertension 2024; 81:1194-1205. [PMID: 38557153 DOI: 10.1161/hypertensionaha.123.21715] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/04/2024]
Abstract
The importance of the sympathetic nervous system in essential hypertension has been recognized in 2 eras. The first was in early decades of the 20th century, through to the 1960s. Here, the sympathetic nervous system was identified as a target for the treatment of hypertension, and an extensive range of antiadrenergic therapies were developed. Then, after a period of lapsed interest, in a second era from 1985 on, the development of precise measures of human sympathetic nerve firing and transmitter release allowed demonstration of the importance of neural mechanisms in the initiation and maintenance of the arterial blood pressure elevation in hypertension. This led to the development of a device treatment of hypertension, catheter-based renal denervation, which we will discuss.
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Affiliation(s)
- Murray D Esler
- Human Neurotransmitter Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia (M.D.E., M.P.S.)
| | - John W Osborn
- Department of Surgery, Medical School, University of Minnesota, Minneapolis (J.W.O.)
| | - Markus P Schlaich
- Human Neurotransmitter Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia (M.D.E., M.P.S.)
- Dobney Hypertension Centre, Medical School, Royal Perth Hospital Unit and RPH Research Foundation, The University of Western Australia (M.P.S.)
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Teixeira AL, Nardone M, Fernandes IA, Millar PJ, Vianna LC. Intra- and interday reliability of sympathetic transduction to blood pressure in young, healthy adults. J Appl Physiol (1985) 2024; 136:917-927. [PMID: 38385178 DOI: 10.1152/japplphysiol.00009.2024] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 02/07/2024] [Accepted: 02/20/2024] [Indexed: 02/23/2024] Open
Abstract
Microneurographic recordings of muscle sympathetic nerve activity (MSNA) and the succeeding changes in beat-to-beat blood pressure (i.e., sympathetic transduction) provide important insights into the neural control of the circulation in humans. Despite its widespread use, the reliability of this technique remains unknown. Herein, we assessed the intra- and interday test-retest reliability of signal-averaging sympathetic transduction to blood pressure. Data were analyzed from 15 (9 M/6 F) young, healthy participants who completed two baseline recordings of fibular nerve MSNA separated by 60 min (intraday). The interday reliability was obtained in a subset of participants (n = 13, 9 M/4 F) who completed a follow-up MSNA study. Signal-averaging sympathetic transduction was quantified as peak change in diastolic (DBP) and mean arterial pressure (MAP) following a burst of MSNA. Analyses were also computed considering different MSNA burst sizes (quartiles of normalized MSNA) and burst patterns (singlets, couplets, triplets, and quadruplets+), as well as nonburst responses. Intraclass-correlation coefficients (ICCs) were used as the main reliability measure. Peak changes in MAP [intraday: ICC = 0.76 (0.30-0.92), P = 0.006; interday: ICC = 0.91 (0.63-0.97), P < 0.001] demonstrated very good to excellent reliability. Sympathetic transduction of MSNA burst size displayed moderate to very good reliability, though the reliability of MSNA burst pattern was poor to very good. Nonburst responses revealed poor intraday [ICC = 0.37 (-1.05 to 0.80), P = 0.21], but very good interday [ICC = 0.76 (0.18-0.93), P = 0.01] reliability. Intraday reliability measures were consistently lower than interday reliability. Similar results were obtained using DBP. Collectively, these findings provide evidence that the burst-triggering signal-averaging technique is a reliable measure of sympathetic transduction to blood pressure in young, healthy adults.NEW & NOTEWORTHY We found that signal-averaging sympathetic transduction to blood pressure displayed very good to excellent intra- and interday test-retest reliability in healthy, young adults. Reliability analyses according to muscle sympathetic burst size, burst pattern, and nonburst response were less consistent. Results were similar when using diastolic or mean arterial pressure in the transduction calculation. These findings suggest that the signal-averaging technique can be used with confidence to investigate sympathetic transduction to blood pressure in humans across time.
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Affiliation(s)
- André L Teixeira
- NeuroV̇ASQ̇ - Integrative Physiology Laboratory, Faculty of Physical Education, University of Brasília, Brasília, Brazil
- Human Cardiovascular Physiology Laboratory, Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
| | - Massimo Nardone
- Human Cardiovascular Physiology Laboratory, Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
| | - Igor A Fernandes
- Human Neurovascular Control Laboratory, Department of Health and Kinesiology, Purdue University, West Lafayette, Indiana, United States
| | - Philip J Millar
- Human Cardiovascular Physiology Laboratory, Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
| | - Lauro C Vianna
- NeuroV̇ASQ̇ - Integrative Physiology Laboratory, Faculty of Physical Education, University of Brasília, Brasília, Brazil
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Akins JD, Okada Y, Hendrix JM, Vongpatanasin W, Fu Q. Greater resting muscle sympathetic nerve activity reduces cold pressor autonomic reactivity in older women, but not older men. Am J Physiol Regul Integr Comp Physiol 2023; 324:R656-R665. [PMID: 36971420 PMCID: PMC10110704 DOI: 10.1152/ajpregu.00231.2022] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 03/20/2023] [Accepted: 03/20/2023] [Indexed: 03/29/2023]
Abstract
Previous work demonstrates augmented muscle sympathetic nerve activity (MSNA) responses to the cold pressor test (CPT) in older women. Given its interindividual variability, however, the influence of baseline MSNA on CPT reactivity in older adults remains unknown. Sixty volunteers (60-83y; 30 women) completed testing where MSNA (microneurography), blood pressure (BP), and heart rate (HR) were recorded during baseline and a 2-min CPT (~4°C). Participant data were terciled by baseline MSNA (n=10/group); comparisons were made between the high baseline men (HM) and women (HW), and low baseline men (LM) and women (LW). By design, HM and HW, vs. LM and LW, had greater baseline MSNA burst frequency (37±5 and 38±3 vs. 9±4 and 15±5 bursts/min) and burst incidence (59±14 and 60±8 vs. 16±10 and 23±7 bursts/100hbs; both P<0.001). However, baseline BP and HR were not different between the groups (all P>0.05). During the CPT, there were no differences in the increase in BP and HR (all P>0.05). Conversely, ΔMSNA burst frequency was lower in HW vs. LW (8±9 vs. 22±12 bursts/min; P=0.012) yet was similar in HM vs. LM (17±12 vs. 19±10 bursts/min, P=0.994). Further, ΔMSNA burst incidence was lower in HW vs. LW (9±13 vs. 28±16 bursts/100hbs; P=0.020), with no differences between HM vs. LM (21±17 vs. 31±17 bursts/100hbs; P=0.455). Our findings suggest that heightened baseline activity in older women attenuates the typical CPT-mediated increase in MSNA without changing cardiovascular reactivity. While the underlying mechanisms remain unknown, altered sympathetic recruitment or neurovascular transduction may contribute to these disparate responses.
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Affiliation(s)
- John D Akins
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, TX, United States
- The University of Texas Southwestern Medical Center, Dallas, TX, United States
| | - Yoshiyuki Okada
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, TX, United States
- The University of Texas Southwestern Medical Center, Dallas, TX, United States
| | - Joseph M Hendrix
- The University of Texas Southwestern Medical Center, Dallas, TX, United States
| | | | - Qi Fu
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, TX, United States
- The University of Texas Southwestern Medical Center, Dallas, TX, United States
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Teixeira AL, Vianna LC. The exercise pressor reflex: An update. Clin Auton Res 2022; 32:271-290. [PMID: 35727398 DOI: 10.1007/s10286-022-00872-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 05/25/2022] [Indexed: 02/07/2023]
Abstract
The exercise pressor reflex is a feedback mechanism engaged upon stimulation of mechano- and metabosensitive skeletal muscle afferents. Activation of these afferents elicits a reflex increase in heart rate, blood pressure, and ventilation in an intensity-dependent manner. Consequently, the exercise pressor reflex has been postulated to be one of the principal mediators of the cardiorespiratory responses to exercise. In this updated review, we will discuss classical and recent advancements in our understating of the exercise pressor reflex function in both human and animal models. Particular attention will be paid to the afferent mechanisms and pathways involved during its activation, its effects on different target organs, its potential role in the abnormal cardiovascular response to exercise in diseased states, and the impact of age and biological sex on these responses. Finally, we will highlight some unanswered questions in the literature that may inspire future investigations in the field.
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Affiliation(s)
- André L Teixeira
- NeuroV̇ASQ̇, Integrative Physiology Laboratory, Faculty of Physical Education, University of Brasília, DF, Brasília, Brazil
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada
| | - Lauro C Vianna
- NeuroV̇ASQ̇, Integrative Physiology Laboratory, Faculty of Physical Education, University of Brasília, DF, Brasília, Brazil.
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Kulas B, Klassen S, Moir ME, Shoemaker JK. Interactive effects of apneic and baroreflex stress on neural coding strategies in human muscle sympathetic nerve activity. J Neurophysiol 2022; 127:1086-1097. [PMID: 35294276 DOI: 10.1152/jn.00395.2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
The sympathetic nervous system exhibits patterns of action potential (AP) discharge in human muscle sympathetic nerve activity that suggest coding strategies express reflex specificity. This study explored the interactive effects of baroreceptor unloading using lower body negative pressure (LBNP) and volitional end-expiratory apnea (APN) on sympathetic postganglionic neuronal discharge patterns inferred from the firing patterns of differently sized sympathetic AP clusters. Seven individuals were studied using multi-unit microneurography (fibular) and a continuous wavelet approach to quantify AP discharge probability, recruitment, and latency during APN performed under ambient conditions, -10 and -40 mmHg LBNP. Compared to the ambient condition, LBNP increased AP discharge rate at -10 and -40 mmHg and recruited larger previously-silent sympathetic neurons at -40 mmHg. Compared to spontaneous breathing, APN increased AP discharge when performed during the ambient condition (∆351±132 AP/min), -10 mmHg (∆423±184 AP/min), and -40 mmHg (∆355±278 AP/min; main effect APN: P<0.01; LBNP-by-APN interaction: P=0.55). APN recruited larger previously-silent AP clusters during the ambient condition (∆4±3; P<0.02) and -10 mmHg (∆4±3; P<0.01), but not -40 mmHg (∆0±2; P=0.53; LBNP-by-APN: P<0.01). LBNP did not affect AP latency. However, APN reduced AP latency similarly during all conditions (ambient pressure: ∆-0.04±0.04s, -10 mmHg: ∆-0.03±0.03s, -40 mmHg: ∆-0.03±0.04s; main effect APN: P<0.01; LBNP-by-APN: P=0.48). These data indicate that apneic and baroreflex mechanisms appear to additively modify the axonal discharge rate of previously active sympathetic postganglionic neurons and interact to affect recruitment of previously-silent sympathetic neurons. Reductions in AP latency due to apneic stress were not impacted by baroreflex unloading.
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Affiliation(s)
- Bartek Kulas
- Neurovascular Research Laboratory, School of Kinesiology, University of Western Ontario, London, Ontario, Canada
| | - Stephen Klassen
- Neurovascular Research Laboratory, School of Kinesiology, University of Western Ontario, London, Ontario, Canada.,Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, United States
| | - M Erin Moir
- Neurovascular Research Laboratory, School of Kinesiology, University of Western Ontario, London, Ontario, Canada
| | - J Kevin Shoemaker
- Neurovascular Research Laboratory, School of Kinesiology, University of Western Ontario, London, Ontario, Canada.,Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada
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11
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Coovadia Y, Adler TE, Martin-Arrowsmith PW, Usselman CW. Sex differences in sympathetic neuro-vascular and neuro-hemodynamic relationships during the cold pressor test. Am J Physiol Regul Integr Comp Physiol 2022; 322:R411-R420. [PMID: 35293259 DOI: 10.1152/ajpregu.00223.2021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Muscle sympathetic nerve activity (MSNA) affects vascular resistance differently in women and men. However, whether this sex difference persists during pronounced increases in MSNA remains unclear. Therefore, the purpose of this study was to examine sex differences in neurovascular transduction during cold pressor test (CPT)-mediated sympatho-excitation. Integrated peroneal MSNA (microneurography) was measured at rest and during a 3-minute CPT in young healthy women (n=11) and men (n=10). Mean arterial pressure (MAP) was measured beat-by-beat (Finometer) and superficial femoral artery blood flow was measured using duplex ultrasound. Femoral vascular resistance (FVR) was quantified as MAP/femoral blood flow (mmHg/mL/min). Baseline MSNA was similar between women and men (14±9 vs 15±9 bursts/100hb, respectively; P=0.83), whereas MAP was lower (86±7 vs 92±4 mmHg; P=0.047), and FVR was greater in women than men (0.54±0.16 vs 0.36±0.15 mmHg/mL/min; P=0.02). CPT-induced increases in MSNA were similar between the sexes (+19±11 vs +26±14 bursts/100hb; P=0.26) while increases in MAP (+7±3 vs +10±3mmHg; P=0.03) and FVR (+3.2±18.6 vs +26.8±12.8%; P<0.01) were smaller in women than men. Within men, CPT- induced increases in MSNA predicted increases in MAP (R2=0.51, P=0.02) and FVR (R2=0.49, P=0.02). However, MSNA did not predict MAP (R2=0.11, P=0.35) or FVR (R2=0.07, P=0.46) in women. Our findings demonstrate that men experience robust CPT-induced MAP responses that are driven by both neuro-vascular (MSNA-FVR) and neuro-hemodynamic (MSNA-MAP) coupling. These relationships were not observed in women, indicating that even during pronounced increases in sympathetic outflow, MSNA is not predictive of vascular nor blood pressure outcomes in young healthy women.
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Affiliation(s)
- Yasmine Coovadia
- Cardiovascular Health and Autonomic Regulation Laboratory, McGill University, Montreal, Quebec, Canada
| | - Tessa E Adler
- Cardiovascular Health and Autonomic Regulation Laboratory, McGill University, Montreal, Quebec, Canada
| | - Patrick W Martin-Arrowsmith
- Exercise Metabolism and 6 Nutrition Research Lab, Department of Kinesiology and Physical Education, McGill University, Montreal, Quebec, Canada
| | - Charlotte W Usselman
- Cardiovascular Health and Autonomic Regulation Laboratory, McGill University, Montreal, Quebec, Canada.,McGill Research Centre for Physical Activity and Health, McGill University, Montreal, Quebec, Canada
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12
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Liu C, Lee CH, Lin SF, Tsai WC. Temporal Clustering of Skin Sympathetic Nerve Activity Bursts in Acute Myocardial Infarction Patients. Front Neurosci 2021; 15:720827. [PMID: 34916895 PMCID: PMC8669957 DOI: 10.3389/fnins.2021.720827] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 10/18/2021] [Indexed: 11/13/2022] Open
Abstract
Backgrounds: Acute myocardial infarction (AMI) affects the autonomic nervous system (ANS) function. The aim of our study is to detect the particular patterns of ANS regulation in AMI. We hypothesize that altered ANS regulation in AMI patients causes synchronized neural discharge (clustering phenomenon) detected by non-invasive skin sympathetic nerve activity (SKNA). Methods: Forty subjects, including 20 AMI patients and 20 non-AMI controls, participated in the study. The wide-band bioelectrical signals (neuECG) were continuously recorded on the body surface for 5 min. SKNA was signal processed to depict the envelope of SKNA (eSKNA). By labeling the clusters, the AMI subjects were separated into non-AMI, non-cluster appearing (AMINCA), and cluster appearing (AMICA) groups. Results: The average eSKNA was significantly correlated with HRV low-frequency (LF) power (rho = −0.336) and high-frequency power (rho = −0.372). The cross-comparison results demonstrated that eSKNA is a valid surrogate marker to assess ANS in AMI patients. The frequency of cluster occurrence was 0.01–0.03 Hz and the amplitude was about 3 μV. The LF/HF ratio of AMICA (median: 1.877; Q1–Q3: 1.483–2.413) revealed significantly lower than AMINCA (median: 3.959; Q1–Q3: 1.840–6.562). The results suggest that the SKNA clustering is a unique temporal pattern of ANS synchronized discharge, which could indicate the lower sympathetic status (by HRV) in AMI patients. Conclusion: This is the first study to identify SKNA clustering phenomenon in AMI patients. Such a synchronized nerve discharge pattern could be detected with non-invasive SKNA signals. SKNA temporal clustering could be a novel biomarker to classify ANS regulation ability in AMI patients. Clinical and Translational Significance: SKNA is higher in AMI patients than in control and negatively correlates with parasympathetic parameters. SKNA clustering is associated with a lower LF/HF ratio that has been shown to correlate with sudden cardiac death in AMI. The lack of SKNA temporal clustering could indicate poor ANS regulation in AMI patients.
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Affiliation(s)
- Chun Liu
- Department of Electrical and Computer Engineering, College of Electrical and Computer Engineering, National Chiao Tung University, Hsinchu, Taiwan
| | - Chien-Hung Lee
- Department of Public Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan.,Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shien-Fong Lin
- Department of Electrical and Computer Engineering, College of Electrical and Computer Engineering, National Chiao Tung University, Hsinchu, Taiwan.,Institute of Biomedical Engineering, College of Electrical and Computer Engineering, National Chiao Tung University, Hsinchu, Taiwan
| | - Wei-Chung Tsai
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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13
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La Fountaine MF, Hohn AN, Leahy CL, Testa AJ, Weir JP. Use of Mayer wave activity to demonstrate aberrant cardiovascular autonomic control following sports concussion injury. Ann N Y Acad Sci 2021; 1507:121-132. [PMID: 34480369 PMCID: PMC9291215 DOI: 10.1111/nyas.14683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 08/04/2021] [Accepted: 08/13/2021] [Indexed: 12/02/2022]
Abstract
Dysregulation of cardiovascular autonomic control is gaining recognition as a prevailing consequence of concussion injury. Characterizing the presence of autonomic dysfunction in concussed persons is inconsistent and conventional metrics of autonomic function cannot differentiate the presence/absence of injury. Mayer wave (MW) activity originates through baroreflex adjustments to blood pressure (BP) oscillations that appear in the low‐frequency (LF: 0.04–0.15 Hz) band of the BP and heart rate (HR) power spectrum after a fast Fourier transform. We prospectively explored MW activity (∼0.1 Hz) in 19 concussed and 19 noninjured athletes for 5 min while seated at rest within 48 h and 1 week of injury. MW activity was derived from the LF band of continuous digital electrocardiogram and beat‐to‐beat BP signals (LFHR, LF‐SBP, MWHR, and MW‐SBP, respectively); a proportion between MWBP and MWHR was computed (cMW). At 48 h, the concussion group had a significantly lower MWBP and cMW than controls; these differences were gone by 1 week. MWHR, LFHR, and LF‐SBP were not different between groups at either visit. Attenuated sympathetic vasomotor tone was present and the central autonomic mechanisms regulating MW activity to the heart and peripheral vasculature became transiently discordant early after concussion with apparent resolution by 1 week.
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Affiliation(s)
- Michael F La Fountaine
- Department of Physical Therapy, School of Health and Medical Sciences, Seton Hall University, Nutley, New Jersey.,Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, New Jersey.,Department of Neurology, Hackensack Meridian School of Medicine, Nutley, New Jersey
| | - Asante N Hohn
- Department of Physical Therapy, School of Health and Medical Sciences, Seton Hall University, Nutley, New Jersey.,Spectrum Physical Therapy and Athletic Training, Morristown, New Jersey
| | - Caroline L Leahy
- Department of Physical Therapy, School of Health and Medical Sciences, Seton Hall University, Nutley, New Jersey.,SportsCare Physical Therapy, Cedar Knolls, New Jersey
| | - Anthony J Testa
- Center for Sports Medicine, Seton Hall University, South Orange, New Jersey
| | - Joseph P Weir
- Department of Health, Sport and Exercise Sciences, University of Kansas, Lawrence, Kansas.,Osness Human Performance Laboratories, University of Kansas, Lawrence, Kansas
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14
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DeLorey DS. Sympathetic vasoconstriction in skeletal muscle: Modulatory effects of aging, exercise training, and sex. Appl Physiol Nutr Metab 2021; 46:1437-1447. [PMID: 34348066 DOI: 10.1139/apnm-2021-0399] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The sympathetic nervous system (SNS) is a critically important regulator of the cardiovascular system. The SNS controls cardiac output and its distribution, as well as peripheral vascular resistance and blood pressure at rest and during exercise. Aging is associated with increased blood pressure and decreased skeletal muscle blood flow at rest and in response to exercise. The mechanisms responsible for the blunted skeletal muscle blood flow response to dynamic exercise with aging have not been fully elucidated; however, increased muscle sympathetic nerve activity (MSNA), elevated vascular resistance and a decline in endothelium-dependent vasodilation are commonly reported in older adults. In contrast to aging, exercise training has been shown to reduce blood pressure and enhance skeletal muscle vascular function. Exercise training has been shown to enhance nitric oxide-dependent vascular function and may improve the vasodilatory capacity of the skeletal muscle vasculature; however, surprisingly little is known about the effect of exercise training on the neural control of circulation. The control of blood pressure and skeletal muscle blood flow also differs between males and females. Blood pressure and MSNA appear to be lower in young females compared to males. However, females experience a larger increase in MSNA with aging compared to males. The mechanism(s) for the altered SNS control of vascular function in females remain to be determined. Novelty: • This review will summarize our current understanding of the effects of aging, exercise training and sex on sympathetic vasoconstriction at rest and during exercise. • Areas where additional research is needed are also identified.
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Affiliation(s)
- Darren S DeLorey
- University of Alberta, Faculty of Kinesiology, Sport, and Recreation, Edmonton, Alberta, Canada;
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15
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Klassen SA, Joyner MJ, Baker SE. The impact of ageing and sex on sympathetic neurocirculatory regulation. Semin Cell Dev Biol 2021; 116:72-81. [PMID: 33468420 PMCID: PMC8282778 DOI: 10.1016/j.semcdb.2021.01.001] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Revised: 12/30/2020] [Accepted: 01/04/2021] [Indexed: 02/07/2023]
Abstract
The sympathetic nervous system represents a critical mechanism for homoeostatic blood pressure regulation in humans. This review focuses on age-related alterations in neurocirculatory regulation in men and women by highlighting human studies that examined the relationship between muscle sympathetic nerve activity (MSNA) acquired by microneurography and circulatory variables (e.g., blood pressure, vascular resistance). We frame this review with epidemiological evidence highlighting sex-specific patterns in age-related blood pressure increases in developed nations. Indeed, young women exhibit lower blood pressure than men, but women demonstrate larger blood pressure increases with age, such that by about age 60 years, blood pressure is greater in women. Sympathetic neurocirculatory mechanisms contribute to sex differences in blood pressure rises with age. Muscle sympathetic nerve activity increases with age in both sexes, but women demonstrate greater age-related increases. The circulatory adjustments imposed by MSNA - referred to as neurovascular transduction or autonomic (sympathetic) support of blood pressure - differ in men and women. For example, whereas young men demonstrate a positive relationship between resting MSNA and vascular resistance, this relationship is absent in young women due to beta-2 adrenergic vasodilation, which offsets alpha-adrenergic vasoconstriction. However, post-menopausal women demonstrate a positive relationship between MSNA and vascular resistance due to a decline in beta-2 adrenergic vasodilatory mechanisms. Emerging data suggest that greater aerobic fitness appears to modulate neurocirculatory regulation, at least in young, healthy men and women. This review also highlights recent advances in microneurographic recordings of sympathetic action potential discharge, which may nuance our understanding of age-related alterations in sympathetic neurocirculatory regulation in humans.
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Affiliation(s)
- Stephen A Klassen
- Human and Integrative Physiology and Clinical Pharmacology Laboratory, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA
| | - Michael J Joyner
- Human and Integrative Physiology and Clinical Pharmacology Laboratory, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA
| | - Sarah E Baker
- Human and Integrative Physiology and Clinical Pharmacology Laboratory, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA.
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16
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Takeda R, Stickford ASL, Best SA, Yoo JK, Hissen SL, Liu YL, Fu Q. Impact of high-salt versus low-salt intake on the response of sympathetic baroreflex sensitivity to orthostasis in women with a history of normal pregnancy. Am J Physiol Regul Integr Comp Physiol 2021; 321:R260-R270. [PMID: 34231375 DOI: 10.1152/ajpregu.00069.2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Previous studies have demonstrated that sympathetic baroreflex sensitivity (BRS) increases during orthostatic stress in humans. We recently showed that dietary salt intake affects sympathetic neural control in healthy premenopausal women. This study aimed to determine whether salt loading versus salt reduction would impact sympathetic BRS during orthostasis in premenopausal women with a history of normal pregnancy. Nine healthy women [42 ± 3 (SD) yr] were given a standardized isocaloric high-salt (250 mEq sodium/day) or low-salt (50 mEq sodium/day) diet for 1 wk each (∼2 mo apart with the order randomized), whereas water intake was ad libitum. Laboratory testing was performed following each high- and low-salt period in the midluteal phase of the menstrual cycle. Hemodynamics and muscle sympathetic nerve activity (MSNA) were measured at baseline (supine; 2 min) and during a graded head-up tilt (30° for 5 min and 60° for 20 min). Sympathetic BRS was assessed during baseline and head-up tilt. Hemodynamics were not different between salt conditions during baseline or tilt. Both supine and upright MSNA indices were lower in high salt than low salt (all P < 0.05), however, there was no interaction effect (P = 0.507-0.996). On moving from supine to upright, sympathetic BRS remained unchanged in high salt but increased in low salt (P = 0.028 for interaction). Thus, salt loading diminishes the responsiveness of sympathetic BRS during orthostasis compared with salt reduction in healthy premenopausal women with prior normal pregnancy. Whether this is one underlying mechanism for salt-induced development of hypertension during ambulation remains to be determined.
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Affiliation(s)
- Ryosuke Takeda
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.,The University of Texas Southwestern Medical Center, Dallas, Texas
| | - Abigail S L Stickford
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.,The University of Texas Southwestern Medical Center, Dallas, Texas
| | - Stuart A Best
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.,The University of Texas Southwestern Medical Center, Dallas, Texas
| | - Jeung-Ki Yoo
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.,The University of Texas Southwestern Medical Center, Dallas, Texas
| | - Sarah L Hissen
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.,The University of Texas Southwestern Medical Center, Dallas, Texas
| | - Yu-Lun Liu
- The University of Texas Southwestern Medical Center, Dallas, Texas
| | - Qi Fu
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.,The University of Texas Southwestern Medical Center, Dallas, Texas
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17
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Cardiorespiratory synchronisation and systolic blood pressure correlation of peripheral arterial stiffness during endoscopic thoracic sympathectomy. Sci Rep 2021; 11:5966. [PMID: 33727620 PMCID: PMC7966741 DOI: 10.1038/s41598-021-85299-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Accepted: 02/23/2021] [Indexed: 11/08/2022] Open
Abstract
Muscle sympathetic nerve activity (MSNA) is known as an effective measure to evaluate peripheral sympathetic activity; however, it requires invasive measurement with the microneurography method. In contrast, peripheral arterial stiffness affected by MSNA is a measure that allows non-invasive evaluation of mechanical changes of arterial elasticity. This paper aims to clarify the features of peripheral arterial stiffness to determine whether it inherits MSNA features towards non-invasive evaluation of its activity. To this end, we propose a method to estimate peripheral arterial stiffness [Formula: see text] at a high sampling rate. Power spectral analysis of the estimated [Formula: see text] was then performed on data acquired from 15 patients ([Formula: see text] years) who underwent endoscopic thoracic sympathectomy. We examined whether [Formula: see text] exhibited the features of MSNA where its frequency components synchronise with heart and respiration rates and correlates with the low-frequency component of systolic blood pressure. Regression analysis revealed that the local peak frequency in the range of heartbeat frequency highly correlate with the heart rate ([Formula: see text], [Formula: see text]) where the regression slope was approximately 1 and intercept was approximately 0. Frequency analysis then found spectral peaks of [Formula: see text] approximately 0.2 Hz that correspond to the respiratory cycle. Finally, cross power spectral analysis showed a significant magnitude squared coherence between [Formula: see text] and systolic blood pressure in the frequency band from 0.04 to 0.2 Hz. These results indicate that [Formula: see text] inherits the features observed in MSNA that require invasive measurements, and thus [Formula: see text] can be an effective non-invasive substitution for MSNA measure.
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18
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Macefield VG. Recording and quantifying sympathetic outflow to muscle and skin in humans: methods, caveats and challenges. Clin Auton Res 2021; 31:59-75. [PMID: 32588247 PMCID: PMC7907024 DOI: 10.1007/s10286-020-00700-6] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Accepted: 05/26/2020] [Indexed: 01/04/2023]
Abstract
The development of microneurography, in which the electrical activity of axons can be recorded via an intrafascicular microelectrode inserted through the skin into a peripheral nerve in awake human participants, has contributed a great deal to our understanding of sensorimotor control and the control of sympathetic outflow to muscle and skin. This review summarises the different approaches to recording muscle sympathetic nerve activity (MSNA) and skin sympathetic nerve activity (SSNA), together with discussion on the issues that determine the quality of a recording. Various analytical approaches are also described, with a primary emphasis on those developed by the author, aimed at maximizing the information content from recordings of postganglionic sympathetic nerve activity in awake humans.
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Affiliation(s)
- Vaughan G Macefield
- Human Autonomic Neurophysiology Laboratory, Baker Heart and Diabetes Institute, 75 Commercial Rd, Melbourne, VIC, 3004, Australia.
- Department of Physiology, University of Melbourne, Melbourne, VIC, Australia.
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19
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Abstract
Conclusive evidence demonstrates that the sympathetic nervous system activation is a hallmark of congestive heart failure. This has been shown via a variety of biochemical, neurophysiological, and neuroimaging approaches for studying human sympathetic neural function. The sympathetic activation appears to be an early phenomenon in the clinical course of the disease, closely related to its severity and potentiated by the concomitant presence of other comorbidities, such as obesity, diabetes mellitus, metabolic syndrome, hypertension, and renal failure. The adrenergic overdrive in heart failure is associated with other sympathetic abnormalities, such as the downregulation of beta-adrenergic adrenoreceptors at cardiac level, and exerts unfavorable consequences on the cardiovascular system. These include the endothelial dysfunction, the development of left ventricular hypertrophy, the atherosclerosis development, as well as the generation of atrial and ventricular arrhythmias, and, at very extreme levels of sympathetic activation, the occurrence of microscopic myocardial necrosis. Given the close direct independent relationships detected in heart failure between sympathetic activation and mortality, the adrenergic overdrive has become a target of neuromodulatory therapeutic interventions, which include non-pharmacological, pharmacological, and device-based interventions. For some of these approaches (specifically bilateral renal nerves ablation and carotid baroreceptor stimulation), additional studies are needed to better define their impact on the clinical course of the disease.
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Affiliation(s)
- Guido Grassi
- Clinica Medica, Department of Medicine and Surgery, University of Milano-Bicocca, Via Pergolesi 33, 20052, Monza, Italy.
| | - Fosca Quarti-Trevano
- Clinica Medica, Department of Medicine and Surgery, University of Milano-Bicocca, Via Pergolesi 33, 20052, Monza, Italy
| | - Murray D Esler
- Baker IDI Heart and Diabetes Institute, Melbourne, Australia
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20
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Vermeulen TD, Shafer BM, Incognito AV, Nardone M, Teixeira AL, Millar PJ, Shoemaker JK, Foster GE. Case Studies in Physiology: Sympathetic neural discharge patterns in a healthy young male during end-expiratory breath hold-induced sinus pause. J Appl Physiol (1985) 2020; 129:230-237. [PMID: 32644911 DOI: 10.1152/japplphysiol.00307.2020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
This case study reports the efferent muscle sympathetic nerve activity (MSNA) discharge patterns during a sinus pause observed during a maximal end-expiratory apnea in a young healthy male (age = 26 yr). During a 15.3-s end-expiratory apnea following a bout of intermittent hypercapnic hypoxia, we observed a 5.2-s (R-R interval) sinus pause and integrated MSNA recording, demonstrating a square-wave discharge pattern atypical of sharp MSNA burst peaks entrained to cardiac cycles or during preventricular contractions. This abnormal MSNA discharge pattern was observed again during a follow-up experiment, where an end-expiratory apnea at baseline resulted in pronounced bradycardia (R-R intervals >2.5-s) but failed to reproduce the 5.2-s sinus pause. Action potential (AP) discharge patterns during MSNA bursts were detected using a continuous wavelet transform approach. AP discharge increased by 300% during the end-expiratory apnea with 5.2-s sinus pause compared with baseline and involved increased firing (i.e., rate-coding) of AP clusters (bins of AP with similar morphology) already present during baseline and pronounced recruitment of larger-amplitude AP clusters not present at baseline. Large-amplitude AP clusters continued to discharge during sinus pause. In summary, we show MSNA discharge during sinus pause and pronounced bradycardia during end-expiratory apnea, which demonstrates a square-wave discharge with recruitment of latent larger-amplitude AP clusters. The MSNA discharge was terminated before systole following sinus pause potentially through an inhibitory influence of inspiration, or cardiac mechanoreceptor feedback causing burst termination.NEW & NOTEWORTHY We characterize the occurrence of a square-wave discharge pattern of efferent muscle sympathetic nerve activity during a sinus pause in a young healthy male. This discharge pattern comprised large recruited action potential clusters undetected at baseline that continuously discharged during the sinus pause. Notably, this discharge pattern was still contained within a single cardiac cycle.
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Affiliation(s)
- Tyler D Vermeulen
- Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Sciences, University of British Columbia, Kelowna, Canada.,Neurovascular Research Laboratory, School of Kinesiology, University of Western Ontario, London, Canada
| | - Brooke M Shafer
- Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Sciences, University of British Columbia, Kelowna, Canada
| | - Anthony V Incognito
- Department of Human Health and Nutritional Sciences, University of Guelph, Canada
| | - Massimo Nardone
- Department of Human Health and Nutritional Sciences, University of Guelph, Canada
| | - André L Teixeira
- Department of Human Health and Nutritional Sciences, University of Guelph, Canada
| | - Philip J Millar
- Department of Human Health and Nutritional Sciences, University of Guelph, Canada
| | - J Kevin Shoemaker
- Neurovascular Research Laboratory, School of Kinesiology, University of Western Ontario, London, Canada.,Department of Physiology and Pharmacology, University of Western Ontario, Canada
| | - Glen E Foster
- Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Sciences, University of British Columbia, Kelowna, Canada
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21
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Cutaneous warmth, but not touch, increases muscle sympathetic nerve activity during a muscle fatigue hand-grip task. Exp Brain Res 2020; 238:1035-1042. [PMID: 32198543 PMCID: PMC7181540 DOI: 10.1007/s00221-020-05779-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Accepted: 03/10/2020] [Indexed: 12/05/2022]
Abstract
In homeostasis, somatosensory C fibre afferents are hypothesised to mediate input to the brain about interactions with external stimuli and sympathetic efference provides the output that regulates bodily functions. We aimed to test this hypothesis and whether different types of innocuous somatosensory input have differential effects. Healthy volunteers performed a muscle fatigue (hand-grip) task to exhaustion, which produces increased muscle sympathetic nerve activity (MSNA), as measured through microneurography. Participants completed the muscle fatigue task without concurrent cutaneous sensory stimulation (control) or we applied skin warming (heat pack) as a C fibre stimulation, slow brush stroking as C and Aβ fibre stimulation, or vibration as Aβ fibre stimulation, to the participant’s forearm. We also measured heart rate, the duration of the hand-grip task, and ratings of pain at the end of the task. Concurrent skin warming showed increased MSNA compared to the other conditions. Tactile stimuli (brushing, vibration) were not significantly different to the control (no intervention) condition. Warming increased the pain from the muscle contraction, whereas the tactile stimuli did not. We interpret the effect of warming on MSNA as providing relevant afferent information during muscle contraction, which needed to be counteracted via vasoconstriction to maintain homeostasis. Brushing and vibration were less homeostatically relevant stimuli for the muscle contraction and hence had no significant effect. The findings add sensory specificity to our current understanding of homeostatic regulation through somatosensory afferent and sympathetic efferent pathways.
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Barman SM. 2019 Ludwig Lecture: Rhythms in sympathetic nerve activity are a key to understanding neural control of the cardiovascular system. Am J Physiol Regul Integr Comp Physiol 2020; 318:R191-R205. [PMID: 31664868 PMCID: PMC7052600 DOI: 10.1152/ajpregu.00298.2019] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 10/25/2019] [Accepted: 10/25/2019] [Indexed: 02/07/2023]
Abstract
This review is based on the Carl Ludwig Distinguished Lecture, presented at the 2019 Experimental Biology Meeting in Orlando, FL, and provides a snapshot of >40 years of work done in collaboration with the late Gerard L. Gebber and colleagues to highlight the importance of considering the rhythmic properties of sympathetic nerve activity (SNA) and brain stem neurons when studying the neural control of autonomic regulation. After first providing some basic information about rhythms, I describe the patterns and potential functions of rhythmic activity recorded from sympathetic nerves under various physiological conditions. I review the evidence that these rhythms reflect the properties of central sympathetic neural networks that include neurons in the caudal medullary raphe, caudal ventrolateral medulla, caudal ventrolateral pons, medullary lateral tegmental field, rostral dorsolateral pons, and rostral ventrolateral medulla. The role of these brain stem areas in mediating steady-state and reflex-induced changes in SNA and blood pressure is discussed. Despite the common appearance of rhythms in SNA, these oscillatory characteristics are often ignored; instead, it is common to simply quantify changes in the amount of SNA to make conclusions about the function of the sympathetic nervous system in mediating responses to a variety of stimuli. This review summarizes work that highlights the need to include an assessment of the changes in the frequency components of SNA in evaluating the cardiovascular responses to various manipulations as well as in determining the role of different brain regions in the neural control of the cardiovascular system.
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Affiliation(s)
- Susan M Barman
- Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan
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Busch SA, Simpson LL, Sobierajski F, Riske L, Ainslie PN, Willie CK, Stembridge M, Moore JP, Steinback CD. Muscle sympathetic reactivity to apneic and exercise stress in high-altitude Sherpa. Am J Physiol Regul Integr Comp Physiol 2020; 318:R493-R502. [PMID: 31913686 DOI: 10.1152/ajpregu.00119.2019] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Lowland-dwelling populations exhibit persistent sympathetic hyperactivity at altitude that alters vascular function. High-altitude populations, such as Sherpa, have previously exhibited greater peripheral blood flow in response to acute stress than Lowlanders, which may be explained through lower sympathetic activity. Our purpose was to determine whether Sherpa exhibit lower sympathetic reactivity to stress than Lowlanders. Muscle sympathetic nerve activity (MSNA; microneurography) was measured at rest in Lowlanders (n = 14; age = 27 ± 6 yr) at 344 m and between 1 and 10 days at 5,050 m. Sherpa (age = 32 ± 11 yr) were tested at 5,050 m (n = 8). Neurovascular reactivity (i.e., change in MSNA patterns) was measured during maximal end-expiratory apnea, isometric hand grip (IHG; 30% maximal voluntary contraction for 2-min), and postexercise circulatory occlusion (PECO; 3 min). Burst frequency (bursts/min) and incidence (bursts/100 heartbeats) and total normalized SNA (arbitrary units/min) were analyzed at rest, immediately before apnea breakpoint, and during the last minute of IHG and PECO. Vascular responses to apnea, IHG, and PECO were also measured. MSNA reactivity to apnea was smaller in Sherpa than Lowlanders at 5,050 m, although blood pressure responses were similar between groups. MSNA increases in Lowlanders during apnea at 5,050 m were significantly lower than at 344 m (P < 0.05), indicating that a possible sympathetic ceiling was reached in Lowlanders at 5,050 m. MSNA increased similarly during IHG and PECO in Lowlanders at both 334 m and 5,050 m and in Sherpa at 5,050 m, while vascular changes (mean brachial arterial pressure, contralateral brachial flow and resistance) were similar between groups. Sherpa demonstrate overall lower sympathetic reactivity that may be a result of heightened vascular responsiveness to potential apneic stress at altitude.
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Affiliation(s)
- Stephen A Busch
- Neurovascular Health Lab, Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, Alberta, Canada
| | - Lydia L Simpson
- School of Sport, Health, and Exercise Sciences, Bangor University, Bangor, United Kingdom
| | - Frances Sobierajski
- Neurovascular Health Lab, Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, Alberta, Canada
| | - Laurel Riske
- Neurovascular Health Lab, Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, Alberta, Canada
| | - Philip N Ainslie
- Centre for Heart, Lung, and Vascular Health, University of British Columbia Okanagan, Kelowna, British Columbia, Canada
| | - Chris K Willie
- Centre for Heart, Lung, and Vascular Health, University of British Columbia Okanagan, Kelowna, British Columbia, Canada
| | - Mike Stembridge
- Cardiff Centre for Exercise and Health, Cardiff School of Sport and Health, Cardiff Metropolitan University, Cardiff, United Kingdom
| | - Jonathan P Moore
- School of Sport, Health, and Exercise Sciences, Bangor University, Bangor, United Kingdom
| | - Craig D Steinback
- Neurovascular Health Lab, Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, Alberta, Canada
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24
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Badrov MB, Okada Y, Yoo JK, Vongpatanasin W, Shoemaker JK, Levine BD, Fu Q. Sex Differences in the Sympathetic Neural Recruitment and Hemodynamic Response to Head-Up Tilt in Older Hypertensives. Hypertension 2019; 75:458-467. [PMID: 31813347 DOI: 10.1161/hypertensionaha.119.14009] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
This study tested the hypothesis that older hypertensive women display augmented pressor responses and aberrant sympathetic neural discharge patterning in response to orthostatic stress versus older hypertensive men. We evaluated, in older hypertensive and normotensive men and women (n=12 each group), blood pressure, heart rate, cardiac index (acetylene rebreathing), total peripheral resistance, and muscle sympathetic nerve activity (microneurography) at baseline (supine; 3 minutes) and during graded head-up tilt (30° for 5 minutes and 60° for 20 minutes). Sympathetic action potential discharge patterns were studied using wavelet-based methodology. In the upright posture, systolic and diastolic blood pressure responses were greater in hypertensive women versus hypertensive men and normotensive women (P<0.05). No differences existed in the heart rate, stroke index, or cardiac index response between groups; however, the total peripheral resistance response throughout graded head-up tilt was markedly greater in hypertensive women (P<0.01). Yet, the increase in integrated muscle sympathetic nerve activity burst frequency and burst incidence were similar between hypertensive women and men in the supine and upright postures. However, the increase in the mean action potential content per integrated burst and recruitment of previously dormant, larger-sized action potentials during 60° head-up tilt was greater in hypertensive women versus hypertensive men and normotensive women (P<0.001). Therefore, total sympathetic action potential firing frequency was markedly greater in hypertensive women throughout 60° head-up tilt (P<0.001). In conclusion, older hypertensive women displayed exaggerated pressor and peripheral vasoconstrictor responses to orthostasis versus hypertensive men, under conditions of augmented and aberrant sympathetic neural recruitment, rather than increased burst frequency, in the upright posture.
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Affiliation(s)
- Mark B Badrov
- From the Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas (M.B.B., Y.O., J.-K.Y., B.D.L., Q.F.).,University of Texas Southwestern Medical Center, Dallas (M.B.B., Y.O., J.-K.Y., W.V., B.D.L., Q.F.)
| | - Yoshiyuki Okada
- From the Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas (M.B.B., Y.O., J.-K.Y., B.D.L., Q.F.).,University of Texas Southwestern Medical Center, Dallas (M.B.B., Y.O., J.-K.Y., W.V., B.D.L., Q.F.).,Hiroshima University, Japan (Y.O.)
| | - Jeung-Ki Yoo
- From the Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas (M.B.B., Y.O., J.-K.Y., B.D.L., Q.F.).,University of Texas Southwestern Medical Center, Dallas (M.B.B., Y.O., J.-K.Y., W.V., B.D.L., Q.F.)
| | - Wanpen Vongpatanasin
- University of Texas Southwestern Medical Center, Dallas (M.B.B., Y.O., J.-K.Y., W.V., B.D.L., Q.F.)
| | - J Kevin Shoemaker
- School of Kinesiology (J.K.S.), Western University, London, Ontario, Canada.,Department of Physiology and Pharmacology (J.K.S.), Western University, London, Ontario, Canada
| | - Benjamin D Levine
- From the Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas (M.B.B., Y.O., J.-K.Y., B.D.L., Q.F.).,University of Texas Southwestern Medical Center, Dallas (M.B.B., Y.O., J.-K.Y., W.V., B.D.L., Q.F.)
| | - Qi Fu
- From the Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas (M.B.B., Y.O., J.-K.Y., B.D.L., Q.F.).,University of Texas Southwestern Medical Center, Dallas (M.B.B., Y.O., J.-K.Y., W.V., B.D.L., Q.F.)
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25
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Badrov MB, Park SY, Yoo JK, Hieda M, Okada Y, Jarvis SS, Stickford AS, Best SA, Nelson DB, Fu Q. Role of Corin in Blood Pressure Regulation in Normotensive and Hypertensive Pregnancy. Hypertension 2019; 73:432-439. [PMID: 30580684 DOI: 10.1161/hypertensionaha.118.12137] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Corin (an atrial natriuretic peptide-converting enzyme) represents a potential biomarker for gestational hypertensive disorders; yet, its role in blood pressure (BP) regulation throughout pregnancy remains unclear. We investigated the time course of change in blood corin content in relation to BP and sympathetic nerve activity throughout pregnancy. Forty-four women (29±0.9 years) participated. Following-term, 23 had low-risk (no personal history of gestational hypertensive disorders) normal pregnancies, 13 had high-risk (personal history of gestational hypertensive disorders) normal pregnancies, and 8 developed gestational hypertension. BP, heart rate, muscle sympathetic nerve activity, and serum corin were measured before pregnancy, during early (4-8 weeks) and late pregnancy (32-36 weeks), and postpartum (6-10 weeks). Overall, compared with prepregnancy, corin remained unchanged during early pregnancy, increased markedly during late pregnancy ( P<0.001), and returned to prepregnancy levels postpartum. In women who developed gestational hypertension, the change in corin from early to late pregnancy was greater than those with low-risk normal pregnancies (Δ971±134 versus Δ486±79 pg/mL; P<0.05). Throughout pregnancy, BP and muscle sympathetic nerve activity were augmented in women with gestational hypertension (all P<0.05). Finally, changes in corin from early to late pregnancy were related to all indices of BP ( R=0.454-0.551; all P<0.01) in late pregnancy, whereas burst frequency, burst incidence, and total muscle sympathetic nerve activity ( R=0.576-0.614; all P<0.001) in early pregnancy were related to changes in corin from early to late pregnancy. Corin plays a unique role in BP regulation throughout normotensive and, especially, hypertensive pregnancy and may represent a promising biomarker for determining women at high risk of adverse pregnancy outcome.
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Affiliation(s)
- Mark B Badrov
- From the Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas (M.B.B., S.Y.P., J.-K.Y., M.H., Y.O., S.S.J., A.S.S., S.A.B., Q.F.).,Internal Medicine, University of Texas Southwestern Medical Center, Dallas (M.B.B., S.Y.P., J.-K.Y., M.H., Y.O., S.S.J., A.S.S., S.A.B., D.B.N., Q.F.)
| | - Sun Young Park
- From the Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas (M.B.B., S.Y.P., J.-K.Y., M.H., Y.O., S.S.J., A.S.S., S.A.B., Q.F.).,Internal Medicine, University of Texas Southwestern Medical Center, Dallas (M.B.B., S.Y.P., J.-K.Y., M.H., Y.O., S.S.J., A.S.S., S.A.B., D.B.N., Q.F.)
| | - Jeung-Ki Yoo
- From the Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas (M.B.B., S.Y.P., J.-K.Y., M.H., Y.O., S.S.J., A.S.S., S.A.B., Q.F.).,Internal Medicine, University of Texas Southwestern Medical Center, Dallas (M.B.B., S.Y.P., J.-K.Y., M.H., Y.O., S.S.J., A.S.S., S.A.B., D.B.N., Q.F.)
| | - Michinari Hieda
- From the Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas (M.B.B., S.Y.P., J.-K.Y., M.H., Y.O., S.S.J., A.S.S., S.A.B., Q.F.).,Internal Medicine, University of Texas Southwestern Medical Center, Dallas (M.B.B., S.Y.P., J.-K.Y., M.H., Y.O., S.S.J., A.S.S., S.A.B., D.B.N., Q.F.)
| | - Yoshiyuki Okada
- From the Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas (M.B.B., S.Y.P., J.-K.Y., M.H., Y.O., S.S.J., A.S.S., S.A.B., Q.F.).,Internal Medicine, University of Texas Southwestern Medical Center, Dallas (M.B.B., S.Y.P., J.-K.Y., M.H., Y.O., S.S.J., A.S.S., S.A.B., D.B.N., Q.F.).,Department of Dentistry, Hiroshima University, Japan (Y.O.)
| | - Sara S Jarvis
- From the Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas (M.B.B., S.Y.P., J.-K.Y., M.H., Y.O., S.S.J., A.S.S., S.A.B., Q.F.).,Internal Medicine, University of Texas Southwestern Medical Center, Dallas (M.B.B., S.Y.P., J.-K.Y., M.H., Y.O., S.S.J., A.S.S., S.A.B., D.B.N., Q.F.).,Department of Biological Sciences, Northern Arizona University, Flagstaff (S.S.J.)
| | - Abigail S Stickford
- From the Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas (M.B.B., S.Y.P., J.-K.Y., M.H., Y.O., S.S.J., A.S.S., S.A.B., Q.F.).,Internal Medicine, University of Texas Southwestern Medical Center, Dallas (M.B.B., S.Y.P., J.-K.Y., M.H., Y.O., S.S.J., A.S.S., S.A.B., D.B.N., Q.F.).,Department of Health and Exercise Science, Appalachian State University, Boone, NC (A.S.S.)
| | - Stuart A Best
- From the Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas (M.B.B., S.Y.P., J.-K.Y., M.H., Y.O., S.S.J., A.S.S., S.A.B., Q.F.).,Internal Medicine, University of Texas Southwestern Medical Center, Dallas (M.B.B., S.Y.P., J.-K.Y., M.H., Y.O., S.S.J., A.S.S., S.A.B., D.B.N., Q.F.)
| | - David B Nelson
- Internal Medicine, University of Texas Southwestern Medical Center, Dallas (M.B.B., S.Y.P., J.-K.Y., M.H., Y.O., S.S.J., A.S.S., S.A.B., D.B.N., Q.F.)
| | - Qi Fu
- From the Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas (M.B.B., S.Y.P., J.-K.Y., M.H., Y.O., S.S.J., A.S.S., S.A.B., Q.F.).,Internal Medicine, University of Texas Southwestern Medical Center, Dallas (M.B.B., S.Y.P., J.-K.Y., M.H., Y.O., S.S.J., A.S.S., S.A.B., D.B.N., Q.F.)
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26
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Klassen SA, Moir ME, Limberg JK, Baker SE, Nicholson WT, Curry TB, Joyner MJ, Shoemaker JK. Asynchronous action potential discharge in human muscle sympathetic nerve activity. Am J Physiol Heart Circ Physiol 2019; 317:H754-H764. [PMID: 31373511 DOI: 10.1152/ajpheart.00258.2019] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
What strategies are employed by the sympathetic system to communicate with the circulation? Muscle sympathetic nerve activity (MSNA) occurs in bursts of synchronous action potential (AP) discharge, yet whether between-burst asynchronous AP firing exists remains unknown. Using multiunit microneurography and a continuous wavelet transform to isolate APs, we studied AP synchronicity within human MSNA. Asynchronous APs were defined as those which occurred between bursts. Experiment 1 quantified AP synchronicity in eight individuals at baseline (BSL), -10 mmHg lower body negative pressure (LBNP), -40 mmHg LBNP, and end-expiratory apnea (APN). At BSL, 33 ± 12% of total AP activity was asynchronous. Asynchronous discharge was unchanged from BSL (67 ± 37 AP/min) to -10 mmHg LBNP (69 ± 33 AP/min), -40 mmHg LBNP (83 ± 68 AP/min), or APN (62 ± 39 AP/min). Across all conditions, asynchronous AP probability and frequency decreased with increasing AP size. Experiment 2 examined the impact of the ganglia on AP synchronicity by using nicotinic blockade (trimethaphan). The largest asynchronous APs were derecruited from BSL (11 ± 4 asynchronous AP clusters) to the last minute of the trimethaphan infusion with visible bursts (7 ± 2 asynchronous AP clusters). However, the 6 ± 2 smallest asynchronous AP clusters could not be blocked by trimethaphan and persisted to fire 100 ± 0% asynchronously without forming bursts. Nonnicotinic ganglionic mechanisms affect some, but not all, asynchronous activity. The fundamental behavior of human MSNA contains between-burst asynchronous AP discharge, which accounts for a considerable amount of BSL activity.NEW & NOTEWORTHY Historically, sympathetic nerve activity destined for the blood vessels supplying skeletal muscle (MSNA) has been characterized by spontaneous bursts formed by synchronous action potential (AP) discharge. However, this study found a considerable amount (~30% during baseline) of sympathetic AP discharge to fire asynchronously between bursts of human MSNA. Trimethaphan infusion revealed that nonnicotinic ganglionic mechanisms contribute to some, but not all, asynchronous discharge. Asynchronous sympathetic AP discharge represents a fundamental behavior of MSNA.
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Affiliation(s)
- Stephen A Klassen
- Neurovascular Research Laboratory, School of Kinesiology, University of Western Ontario, London, Ontario, Canada
| | - M Erin Moir
- Neurovascular Research Laboratory, School of Kinesiology, University of Western Ontario, London, Ontario, Canada
| | - Jacqueline K Limberg
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota
| | - Sarah E Baker
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota
| | - Wayne T Nicholson
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota
| | - Timothy B Curry
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota
| | - Michael J Joyner
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota
| | - J Kevin Shoemaker
- Neurovascular Research Laboratory, School of Kinesiology, University of Western Ontario, London, Ontario, Canada.,Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada
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27
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Ott EP, Baker SE, Holbein WW, Shoemaker JK, Limberg JK. Effect of varying chemoreflex stress on sympathetic neural recruitment strategies during apnea. J Neurophysiol 2019; 122:1386-1396. [PMID: 31389742 DOI: 10.1152/jn.00319.2019] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
We sought to examine the effect of varying chemoreflex stress on sympathetic neural recruitment strategies during end-expiratory apnea. We hypothesized that increases in the firing frequency and probability of low-threshold axons at the asphyxic "break point" would be exaggerated during hypoxia and attenuated during hyperoxia. Multiunit muscle sympathetic nervous system activity (MSNA) (peroneal nerve microneurography) was measured in 10 healthy male subjects (31 ± 2 yr, 25 ± 1 kg/m2). Individuals completed maximal voluntary end-expiratory apnea under normoxic, hypoxic (inspired O2 fraction: 0.17 ± 0.01), and hyperoxic (inspired O2 fraction: 0.92 ± 0.03) conditions. Action potential (AP) patterns were examined from the filtered raw signal with wavelet-based methodology. Multiunit MSNA was increased (P ≤ 0.05) during normoxic apnea, because of an increase in the frequency and incidence of AP spikes (243 ± 75 to 519 ± 134 APs/min, P = 0.048; 412 ± 133 to 733 ± 185 APs/100 heartbeats, P = 0.02). Multiunit MSNA increased from baseline (P < 0.01) during hypoxic apnea, which was due to an increase in the frequency and incidence of APs (192 ± 59 to 952 ± 266 APs/min, P < 0.01; 326 ± 89 to 1,212 ± 327 APs/100 heartbeats, P < 0.01). Hypoxic apnea also resulted in an increase in the probability of a particular AP cluster firing more than once per burst (P < 0.01). Hyperoxia attenuated any increase in MSNA with apnea, such that no changes in multiunit MSNA or frequency or incidence of AP spikes were observed (P > 0.05). We conclude that increases in frequency and incidence of APs during apnea are potentiated during hypoxia and suppressed when individuals are hyperoxic, highlighting the important impact of chemoreflex stress in AP discharge patterns. The results may have implications for neural control of the circulation in recreational activities and/or clinical conditions prone to apnea.NEW & NOTEWORTHY Our results demonstrate that, compared with normoxic end-expiratory apnea, hypoxic apnea increases the frequency and incidence of action potential spikes as well as the probability of multiple firing. We further show that this response is suppressed when individuals are hyperoxic. These data highlight the potentially important role of chemoreflex stress in neural firing and recruitment and may have implications for neural control of the circulation in recreational and/or clinical conditions prone to apnea.
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Affiliation(s)
- Elizabeth P Ott
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri
| | - Sarah E Baker
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota
| | - Walter W Holbein
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota
| | - J Kevin Shoemaker
- School of Kinesiology, University of Western Ontario, London, Ontario, Canada
| | - Jacqueline K Limberg
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri.,Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota
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28
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Carter JR. Microneurography and sympathetic nerve activity: a decade-by-decade journey across 50 years. J Neurophysiol 2019; 121:1183-1194. [PMID: 30673363 DOI: 10.1152/jn.00570.2018] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
The technique of microneurography has advanced the field of neuroscience for the past 50 years. While there have been a number of reviews on microneurography, this paper takes an objective approach to exploring the impact of microneurography studies. Briefly, Web of Science (Thomson Reuters) was used to identify the highest citation articles over the past 50 years, and key findings are presented in a decade-by-decade highlight. This includes the establishment of microneurography in the 1960s, the acceleration of the technique by Gunnar Wallin in the 1970s, the international collaborations of the 1980s and 1990s, and finally the highest impact studies from 2000 to present. This journey through 50 years of microneurographic research related to peripheral sympathetic nerve activity includes a historical context for several of the laboratory interventions commonly used today (e.g., cold pressor test, mental stress, lower body negative pressure, isometric handgrip, etc.) and how these interventions and experimental approaches have advanced our knowledge of cardiovascular, cardiometabolic, and other human diseases and conditions.
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Affiliation(s)
- Jason R Carter
- Department of Kinesiology and Integrative Physiology, Michigan Technological University , Houghton, Michigan
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29
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Busch SA, Bruce CD, Skow RJ, Pfoh JR, Day TA, Davenport MH, Steinback CD. Mechanisms of sympathetic regulation during Apnea. Physiol Rep 2019; 7:e13991. [PMID: 30693670 PMCID: PMC6349657 DOI: 10.14814/phy2.13991] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 12/26/2018] [Indexed: 12/11/2022] Open
Abstract
Volitional Apnea produces a robust peak sympathetic response through several interacting mechanisms. However, the specific contribution of each mechanism has not been elucidated. Muscle sympathetic activity was collected in participants (n = 10; 24 ± 3 years) that performed four maximal volitional apneas aimed at isolating lung-stretch (mechanical) and chemoreflex drive: (Ainslie and Duffin ) end-expiratory breath-hold, (Ainslie et al. ) end-inspiratory breath-hold, (Alpher et al. ) prehyperventilation breath-hold, and (Andersson and Schagatay ) prehyperoxia breath-hold. A final repeated rebreathe breath-hold protocol was performed to measure the peak sympathetic response during successive breath-holds at increasing chemoreflex stress. Finally, the influence of dynamic ventilation was assessed through asphyxic rebreathe. Muscle sympathetic activity was calculated as the change in burst frequency (burst/min), burst incidence (burst/100 heart-beats), and amplitude (au) between baseline and prevolitional breakpoint. Rebreathe was analyzed at similar chemoreflex stress as inspiratory breath-hold. All maneuvers increased muscle sympathetic activity compared to baseline (P < 0.01). However, prehyperoxia exhibited a smaller increase (+22.18 ± 9.13 burst/min; +25.52 ± 11.7 burst/100 heart-beats) compared to inspiratory, expiratory, and prehyperventilation breath-holds. At similar chemoreflex strain, rebreathe sympathetic activity was blunted compared to inspiratory breath-hold (P < 0.01). Finally, muscle sympathetic activity was not different between the repeated rebreathe trials, despite elevated chemoreflex stress and lower breath-hold duration with each subsequent breath-hold. We have demonstrated an obligatory role of the peripheral, but not central, chemoreflex (prehyperventilation vs. prehyperoxia) in producing peak sympathetic responses. At similar chemoreflex stresses the act of dynamic ventilation, but not static lung stretch per se, blunts muscle sympathetic activity. Finally, similar peak sympathetic responses during successive repeated breath-holds suggest a sympathetic ceiling may exist.
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Affiliation(s)
- Stephen A. Busch
- Neurovascular Health LaboratoryFaculty of Kinesiology, Sport, and RecreationUniversity of AlbertaEdmontonAlbertaCanada
| | - Christina D. Bruce
- Department of BiologyFaculty of Science and TechnologyMount Royal UniversityCalgaryAlbertaCanada
| | - Rachel J. Skow
- Neurovascular Health LaboratoryFaculty of Kinesiology, Sport, and RecreationUniversity of AlbertaEdmontonAlbertaCanada
| | - Jaime R. Pfoh
- Department of BiologyFaculty of Science and TechnologyMount Royal UniversityCalgaryAlbertaCanada
| | - Trevor A. Day
- Department of BiologyFaculty of Science and TechnologyMount Royal UniversityCalgaryAlbertaCanada
| | - Margie H. Davenport
- Neurovascular Health LaboratoryFaculty of Kinesiology, Sport, and RecreationUniversity of AlbertaEdmontonAlbertaCanada
| | - Craig D. Steinback
- Neurovascular Health LaboratoryFaculty of Kinesiology, Sport, and RecreationUniversity of AlbertaEdmontonAlbertaCanada
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30
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Klassen SA, Limberg JK, Baker SE, Nicholson WT, Curry TB, Joyner MJ, Shoemaker JK. The role of the paravertebral ganglia in human sympathetic neural discharge patterns. J Physiol 2018; 596:4497-4510. [PMID: 30054928 PMCID: PMC6138281 DOI: 10.1113/jp276440] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Accepted: 07/23/2018] [Indexed: 12/30/2022] Open
Abstract
KEY POINTS The mechanisms affecting recruitment patterns of postganglionic sympathetic nerves remain unclear. The divergent and convergent preganglionic innervation patterns of postganglionic neurons and the presence of differently sized postganglionic nerves suggest that the ganglia may participate in modifying the discharge patterns of single sympathetic postganglionic neurons innervating the skeletal muscle circulation. Whether the ganglia affect the ordered behaviour of varying sized postganglionic sympathetic neurons in humans has not been studied. Trimethaphan infusion produced an ordered pattern of action potential (AP) de-recruitment whereby the firing of larger, low probability APs present at baseline was abolished first, followed by progressive decreased probability of smaller APs. Although integrated sympathetic bursts were no longer detected after several minutes of trimethaphan, firing of the smallest APs was detected. These data suggest the ganglia affect the distribution of firing probabilities exhibited by differently sized sympathetic neurons. The ganglia may contribute to sympathetic neural emission patterns involved in homeostatic regulation. ABSTRACT Do the ganglia contribute to the ordered behaviour of postganglionic neuronal discharge within the sympathetic nervous system? To further understand the functional organization of the sympathetic nervous system we employed the microneurographic approach to record muscle sympathetic nerve activity (MSNA) and a continuous wavelet transform to study postganglionic action potential (AP) behaviour during nicotinic blockade at the ganglia (trimethaphan camsylate, 1-7 mg min-1 ) in seven females (37 ± 5 years). Trimethaphan elicited a progressive reduction in sympathetic outflow characterized by fewer integrated bursts with decaying amplitude. Underlying trimethaphan-mediated attenuations in integrated MSNA were reductions in AP incidence (186 ± 101 to 29 ± 31 AP (100 beats)-1 ) and AP content per integrated burst (7 ± 2 to 3 ± 1 APs burst-1 ) (both P < 0.01) in the final minute of detectable bursting activity in the trimethaphan condition, compared to baseline. We observed an ordered de-recruitment of larger to smaller AP clusters active at baseline (14 ± 3 to 8 ± 2 active AP clusters, P < 0.01). Following cessation of integrated bursts in the trimethaphan condition, the smallest 6 ± 2 sympathetic AP clusters persisted to fire in an asynchronous pattern (49 ± 41 AP (100 beats)-1 ) in all participants. Valsalva's manoeuvre did not increase the incidence of these persistent APs (60 ± 42 AP (100 beats)-1 , P = 0.52), or recruit any larger APs in six of seven participants (6 ± 1 total AP clusters, P = 0.30). These data suggest that the ganglia participate in the ordered recruitment of differently sized postganglionic sympathetic nerves.
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Affiliation(s)
- Stephen A. Klassen
- Neurovascular Research LaboratoryUniversity of Western OntarioLondonOntarioCanada
- School of KinesiologyUniversity of Western OntarioLondonOntarioCanada
| | | | - Sarah E. Baker
- Department of Anesthesiology and Perioperative MedicineMayo ClinicRochesterMNUSA
| | - Wayne T. Nicholson
- Department of Anesthesiology and Perioperative MedicineMayo ClinicRochesterMNUSA
| | - Timothy B. Curry
- Department of Anesthesiology and Perioperative MedicineMayo ClinicRochesterMNUSA
| | - Michael J. Joyner
- Department of Anesthesiology and Perioperative MedicineMayo ClinicRochesterMNUSA
| | - J. Kevin Shoemaker
- Neurovascular Research LaboratoryUniversity of Western OntarioLondonOntarioCanada
- School of KinesiologyUniversity of Western OntarioLondonOntarioCanada
- Department of Physiology and PharmacologyUniversity of Western OntarioLondonOntarioCanada
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Laurin A, Lloyd MG, Hachiya T, Saito M, Claydon VE, Blaber A. New indices from microneurography to investigate the arterial baroreflex. Physiol Rep 2018; 5:5/12/e13220. [PMID: 28663324 PMCID: PMC5492197 DOI: 10.14814/phy2.13220] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2016] [Revised: 02/20/2017] [Accepted: 02/23/2017] [Indexed: 12/05/2022] Open
Abstract
Baroreflex‐mediated changes in heart rate and vascular resistance in response to variations in blood pressure are critical to maintain homeostasis. We aimed to develop time domain analysis methods to complement existing cross‐spectral techniques in the investigation of the vascular resistance baroreflex response to orthostatic stress. A secondary goal was to apply these methods to distinguish between levels of orthostatic tolerance using baseline data. Eleven healthy, normotensive males participated in a graded lower body negative pressure protocol. Within individual neurogenic baroreflex cycles, the amount of muscle sympathetic nerve activity (MSNA), the diastolic pressure stimulus and response amplitudes, diastolic pressure to MSNA burst stimulus and response times, as well as the stimulus and response slopes between diastolic pressure and MSNA were computed. Coherence, gain, and frequency of highest coherence between systolic/diastolic arterial pressure (SAP/DAP) and RR‐interval time series were also computed. The number of MSNA bursts per low‐frequency cycle increased from 2.55 ± 0.68 at baseline to 5.44 ± 1.56 at −40 mmHg of LBNP. Stimulus time decreased (3.21 ± 1.48–1.46 ± 0.43 sec), as did response time (3.47 ± 0.86–2.37 ± 0.27 sec). At baseline, DAP‐RR coherence, DAP‐RR gain, and the time delay between decreases in DAP and MSNA bursts were higher in participants who experienced symptoms of presyncope. Results clarified the role of different branches of the baroreflex loop, and suggested functional adaptation of neuronal pathways to orthostatic stress.
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Affiliation(s)
- Alexandre Laurin
- Department of Biomedical Physiology & Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada .,Inria, Université Paris-Saclay, Palaiseau, Île-de-France, France.,LMS, École Polytechnique, CNRS, Université Paris-Saclay, Palaiseau, Île-de-France, France
| | - Matthew G Lloyd
- Department of Biomedical Physiology & Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada
| | - Tesshin Hachiya
- Department of Aerospace Psychology, Nagoya University, Japan
| | - Mitsuru Saito
- Department of Aerospace Psychology, Nagoya University, Japan
| | - Victoria E Claydon
- Department of Biomedical Physiology & Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada
| | - Andrew Blaber
- Department of Biomedical Physiology & Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada
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32
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Klassen SA, De Abreu S, Greaves DK, Kimmerly DS, Arbeille P, Denise P, Hughson RL, Normand H, Shoemaker JK. Long-duration bed rest modifies sympathetic neural recruitment strategies in male and female participants. J Appl Physiol (1985) 2018; 124:769-779. [PMID: 29212669 PMCID: PMC5899270 DOI: 10.1152/japplphysiol.00640.2017] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Revised: 11/09/2017] [Accepted: 12/04/2017] [Indexed: 01/07/2023] Open
Abstract
To understand the impact of physical deconditioning with head-down tilt bed rest (HDBR) on the malleability of sympathetic discharge patterns, we studied 1) baseline integrated muscle sympathetic nerve activity (MSNA; microneurography) from 13 female participants in the WISE-2005 60-day HDBR study (retrospective analysis), 2) integrated MSNA and multiunit action potential (AP) analysis in 13 male participants performed on data collected at baseline and during physiological stress imposed by end-inspiratory apnea in a new 60-day HDBR study, and 3) a repeatability study (control; n = 6, retrospective analysis, 4 wk between tests). Neither baseline integrated burst frequency nor incidence were altered with HDBR (both P > 0.35). However, baseline integrated burst latency increased in both HDBR studies (male: 1.35 ± 0.02 to 1.39 ± 0.02 s, P < 0.01; female: 1.23 ± 0.02 to 1.29 ± 0.02 s, P < 0.01), whereas controls exhibited no change across two visits (1.25 ± 0.02 to 1.25 ± 0.02 s, group-by-time interaction, P = 0.02). With the exception of increased AP latency ( P = 0.03), male baseline AP data did not change with HDBR (all P > 0.19). The change in AP frequency on going from baseline to apnea (∆94 ± 25 to ∆317 ± 55 AP/min, P < 0.01) and the number of active sympathetic clusters per burst (∆0 ± 0.2 to ∆1 ± 0.2 clusters/burst, P = 0.02) were greater post- compared with pre-HDBR. The change in total clusters with apnea was ∆0 ± 0.5 clusters pre- and ∆2 ± 0.7 clusters post-HDBR ( P = 0.07). These data indicate that 60-day HDBR modified discharge characteristics in baseline burst latency and sympathetic neural recruitment during apneic stress. NEW & NOTEWORTHY Long-duration bed rest did not modify baseline sympathetic burst frequency in male and female participants, but examination of additional features of the multiunit signal provided novel evidence to suggest augmented synaptic delays or processing times at baseline for all sympathetic action potentials. Furthermore, long-duration bed rest increased reflex-sympathetic arousal to apneic stress in male participants primarily by mechanisms involving an augmented firing rate of action potential clusters active at baseline.
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Affiliation(s)
- Stephen A Klassen
- Neurovascular Research Laboratory, School of Kinesiology, University of Western Ontario , London, Ontario , Canada
| | | | - Danielle K Greaves
- Schlegel-University of Waterloo Research Institute for Aging , Waterloo, Ontario , Canada
| | - Derek S Kimmerly
- Division of Kinesiology, School of Health and Human Performance, Dalhousie University , Halifax, Nova Scotia , Canada
| | - Philippe Arbeille
- UMPS-CERCOM, School of Medicine, University of Tours , Tours , France
| | - Pierre Denise
- Normandie Université, Unicaen, INSERM, Caen , France
| | - Richard L Hughson
- Schlegel-University of Waterloo Research Institute for Aging , Waterloo, Ontario , Canada
| | - Hervé Normand
- Normandie Université, Unicaen, INSERM, Caen , France
| | - J Kevin Shoemaker
- Neurovascular Research Laboratory, School of Kinesiology, University of Western Ontario , London, Ontario , Canada
- Department of Physiology and Pharmacology, University of Western Ontario , London, Ontario , Canada
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Shoemaker JK, Klassen SA, Badrov MB, Fadel PJ. Fifty years of microneurography: learning the language of the peripheral sympathetic nervous system in humans. J Neurophysiol 2018; 119:1731-1744. [PMID: 29412776 DOI: 10.1152/jn.00841.2017] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
As a primary component of homeostasis, the sympathetic nervous system enables rapid adjustments to stress through its ability to communicate messages among organs and cause targeted and graded end organ responses. Key in this communication model is the pattern of neural signals emanating from the central to peripheral components of the sympathetic nervous system. But what is the communication strategy employed in peripheral sympathetic nerve activity (SNA)? Can we develop and interpret the system of coding in SNA that improves our understanding of the neural control of the circulation? In 1968, Hagbarth and Vallbo (Hagbarth KE, Vallbo AB. Acta Physiol Scand 74: 96-108, 1968) reported the first use of microneurographic methods to record sympathetic discharges in peripheral nerves of conscious humans, allowing quantification of SNA at rest and sympathetic responsiveness to physiological stressors in health and disease. This technique also has enabled a growing investigation into the coding patterns within, and cardiovascular outcomes associated with, postganglionic SNA. This review outlines how results obtained by microneurographic means have improved our understanding of SNA outflow patterns at the action potential level, focusing on SNA directed toward skeletal muscle in conscious humans.
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Affiliation(s)
- J Kevin Shoemaker
- School of Kinesiology, University of Western Ontario , London, Ontario , Canada
| | - Stephen A Klassen
- School of Kinesiology, University of Western Ontario , London, Ontario , Canada
| | - Mark B Badrov
- School of Kinesiology, University of Western Ontario , London, Ontario , Canada
| | - Paul J Fadel
- Department of Kinesiology, University of Texas at Arlington , Arlington, Texas
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Badrov MB, Barak OF, Mijacika T, Shoemaker LN, Borrell LJ, Lojpur M, Drvis I, Dujic Z, Shoemaker JK. Ventilation inhibits sympathetic action potential recruitment even during severe chemoreflex stress. J Neurophysiol 2017; 118:2914-2924. [PMID: 28835525 PMCID: PMC5686238 DOI: 10.1152/jn.00381.2017] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Revised: 08/18/2017] [Accepted: 08/21/2017] [Indexed: 01/26/2023] Open
Abstract
This study investigated the influence of ventilation on sympathetic action potential (AP) discharge patterns during varying levels of high chemoreflex stress. In seven trained breath-hold divers (age 33 ± 12 yr), we measured muscle sympathetic nerve activity (MSNA) at baseline, during preparatory rebreathing (RBR), and during 1) functional residual capacity apnea (FRCApnea) and 2) continued RBR. Data from RBR were analyzed at matched (i.e., to FRCApnea) hemoglobin saturation (HbSat) levels (RBRMatched) or more severe levels (RBREnd). A third protocol compared alternating periods (30 s) of FRC and RBR (FRC-RBRALT). Subjects continued each protocol until 85% volitional tolerance. AP patterns in MSNA (i.e., providing the true neural content of each sympathetic burst) were studied using wavelet-based methodology. First, for similar levels of chemoreflex stress (both HbSat: 71 ± 6%; P = NS), RBRMatched was associated with reduced AP frequency and APs per burst compared with FRCApnea (both P < 0.001). When APs were binned according to peak-to-peak amplitude (i.e., into clusters), total AP clusters increased during FRCApnea (+10 ± 2; P < 0.001) but not during RBRMatched (+1 ± 2; P = NS). Second, despite more severe chemoreflex stress during RBREnd (HbSat: 56 ± 13 vs. 71 ± 6%; P < 0.001), RBREnd was associated with a restrained increase in the APs per burst (FRCApnea: +18 ± 7; RBREnd: +11 ± 5) and total AP clusters (FRCApnea: +10 ± 2; RBREnd: +6 ± 4) (both P < 0.01). During FRC-RBRALT, all periods of FRC elicited sympathetic AP recruitment (all P < 0.001), whereas all periods of RBR were associated with complete withdrawal of AP recruitment (all P = NS). Presently, we demonstrate that ventilation per se restrains and/or inhibits sympathetic axonal recruitment during high, and even extreme, chemoreflex stress.NEW & NOTEWORTHY The current study demonstrates that the sympathetic neural recruitment patterns observed during chemoreflex activation induced by rebreathing or apnea are restrained and/or inhibited by the act of ventilation per se, despite similar, or even greater, levels of severe chemoreflex stress. Therefore, ventilation modulates not only the timing of sympathetic bursts but also the within-burst axonal recruitment normally observed during progressive chemoreflex stress.
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Affiliation(s)
- Mark B Badrov
- School of Kinesiology, Western University, London, Ontario, Canada
| | - Otto F Barak
- Department of Physiology, University of Split School of Medicine, Split, Croatia.,Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
| | - Tanja Mijacika
- Department of Physiology, University of Split School of Medicine, Split, Croatia
| | | | | | - Mihajlo Lojpur
- Department of Physiology, University of Split School of Medicine, Split, Croatia
| | - Ivan Drvis
- Faculty of Kinesiology, University of Zagreb, Zagreb, Croatia; and
| | - Zeljko Dujic
- Department of Physiology, University of Split School of Medicine, Split, Croatia
| | - J Kevin Shoemaker
- School of Kinesiology, Western University, London, Ontario, Canada; .,Department of Physiology and Pharmacology, Western University, London, Ontario, Canada
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35
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Greaney JL, Kenney WL. Measuring and quantifying skin sympathetic nervous system activity in humans. J Neurophysiol 2017; 118:2181-2193. [PMID: 28701539 DOI: 10.1152/jn.00283.2017] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2017] [Revised: 07/10/2017] [Accepted: 07/10/2017] [Indexed: 01/23/2023] Open
Abstract
Development of the technique of microneurography has substantially increased our understanding of the function of the sympathetic nervous system (SNS) in health and in disease. The ability to directly record signals from peripheral autonomic nerves in conscious humans allows for qualitative and quantitative characterization of SNS responses to specific stimuli and over time. Furthermore, distinct neural outflow to muscle (MSNA) and skin (SSNA) can be delineated. However, there are limitations and caveats to the use of microneurography, measurement criteria, and signal analysis and interpretation. MSNA recordings have a longer history and are considered relatively more straightforward from a measurement and analysis perspective. This brief review provides an overview of the development of the technique as used to measure SSNA. The focus is on the utility of measuring sympathetic activity directed to the skin, the unique issues related to analyzing and quantifying multiunit SSNA, and the challenges related to its interpretation.
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Affiliation(s)
- Jody L Greaney
- Noll Laboratory, Department of Kinesiology, The Pennsylvania State University, University Park, Pennsylvania
| | - W Larry Kenney
- Noll Laboratory, Department of Kinesiology, The Pennsylvania State University, University Park, Pennsylvania
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36
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Shen MJ, Coffey AC, Straka S, Adams DE, Wagner DB, Kovacs RJ, Clark M, Shen C, Chen LS, Everett TH, Lin SF, Chen PS. Simultaneous recordings of intrinsic cardiac nerve activity and skin sympathetic nerve activity from human patients during the postoperative period. Heart Rhythm 2017. [PMID: 28648667 DOI: 10.1016/j.hrthm.2017.06.030] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Intrinsic cardiac nerve activity (ICNA) and skin nerve activity (SKNA) are both associated with cardiac arrhythmias in dogs. OBJECTIVE The purpose of this study was to test the hypothesis that ICNA and SKNA correlate with postoperative cardiac arrhythmias in humans. METHODS Eleven patients (mean age 60 ± 13 years; 4 women) were enrolled in this study. Electrical signals were simultaneously recorded from electrocardiogram (ECG) patch electrodes on the chest wall and from 2 temporary pacing wires placed during open heart surgery on the left atrial epicardial fat pad. The signals were filtered to display SKNA and ICNA. Premature atrial contractions (PACs) and premature ventricular contractions were determined manually. The SKNA and ICNA of the first 300 minutes of each patient were calculated minute by minute to determine baseline average amplitudes of nerve activities and to determine their correlation with arrhythmia burden. RESULTS We processed 1365 ± 973 minutes of recording per patient. Low-amplitude SKNA and ICNA were present at all time, while the burst discharges were observed much less frequently. Both SKNA and burst ICNA were significantly associated with the onset of PACs and premature ventricular contractions. Baseline average ICNA (aICNA), but not average SKNA, had a significant association with PAC burden. The correlation coefficient (r) between aICNA and PAC burden was 0.78 (P < .01). A patient with the greatest aICNA developed postoperative atrial fibrillation. CONCLUSION ICNA and SKNA can be recorded from human patients in the postoperative period. The baseline magnitude of ICNA correlates with PAC burden and development of postoperative atrial fibrillation.
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Affiliation(s)
- Mark J Shen
- Krannert Institute of Cardiology and the Division of Cardiology, Indiana University School of Medicine and Indiana University Health Physicians, Indianapolis, Indiana
| | - Arthur C Coffey
- Department of Medicine, Indiana University School of Medicine and Indiana University Health Physicians, Indianapolis, Indiana; Division of Cardiothoracic Surgery, Department of Surgery, Indiana University School of Medicine and Indiana University Health Physicians, Indianapolis, Indiana
| | - Susan Straka
- Krannert Institute of Cardiology and the Division of Cardiology, Indiana University School of Medicine and Indiana University Health Physicians, Indianapolis, Indiana
| | - David E Adams
- Krannert Institute of Cardiology and the Division of Cardiology, Indiana University School of Medicine and Indiana University Health Physicians, Indianapolis, Indiana
| | - David B Wagner
- Krannert Institute of Cardiology and the Division of Cardiology, Indiana University School of Medicine and Indiana University Health Physicians, Indianapolis, Indiana
| | - Richard J Kovacs
- Krannert Institute of Cardiology and the Division of Cardiology, Indiana University School of Medicine and Indiana University Health Physicians, Indianapolis, Indiana
| | - Michael Clark
- Krannert Institute of Cardiology and the Division of Cardiology, Indiana University School of Medicine and Indiana University Health Physicians, Indianapolis, Indiana
| | - Changyu Shen
- Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Lan S Chen
- Department of Neurology, Indiana University School of Medicine and Indiana University Health Physicians, Indianapolis, Indiana
| | - Thomas H Everett
- Krannert Institute of Cardiology and the Division of Cardiology, Indiana University School of Medicine and Indiana University Health Physicians, Indianapolis, Indiana
| | - Shien-Fong Lin
- Krannert Institute of Cardiology and the Division of Cardiology, Indiana University School of Medicine and Indiana University Health Physicians, Indianapolis, Indiana; Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan
| | - Peng-Sheng Chen
- Krannert Institute of Cardiology and the Division of Cardiology, Indiana University School of Medicine and Indiana University Health Physicians, Indianapolis, Indiana.
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Zamir M, Badrov MB, Olver TD, Shoemaker JK. Cardiac Baroreflex Variability and Resetting during Sustained Mild Effort. Front Physiol 2017; 8:246. [PMID: 28529487 PMCID: PMC5418217 DOI: 10.3389/fphys.2017.00246] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Accepted: 04/07/2017] [Indexed: 11/13/2022] Open
Abstract
This exploratory study assessed the pattern of closed-loop baroreflex resetting using multi-logistic-curve analysis. Operating point gain and ranges of RR-interval (RRI) and systolic blood pressure (SBP) are derived to examine how these relate to sympathetic activation. Sustained low-intensity isometric handgrip exercise, with a period of post-exercise circulatory occlusion (PECO), provided a model to study baroreflex resetting because the progression toward fatigue at constant tension induces a continuous increase in volitional contribution to neuro-cardiovascular control. Continuous measurements of muscle sympathetic nerve activity (MSNA), blood pressure, and RRI were made simultaneously throughout the experimental session. Spontaneous sequence analysis was used to detect episodes of baroreflex “engagements”, but the results are examined with a view to the fundamental difference between experimental conditions that isolate the carotid sinus (open-loop) and intact physiological conditions (closed-loop). While baroreflex function under open-loop conditions can be described in terms of a single logistic curve, intact physiologic conditions require a family of logistic curves. The results suggest that the baroreflex is in a “floating” state whereby it is continuously resetting during the timeline of the experiment but with minute-by-minute average values that mimic the less complex step-wise resetting pattern reported under open-loop conditions. Furthermore, the results indicate that baroreflex function and resetting of the operating point gain is reflected not in terms of change in the values of blood pressure or RR-interval but in terms of change in the range of values of these variables prevailing under different experimental conditions.
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Affiliation(s)
- Mair Zamir
- Department of Applied Mathematics, Western UniversityLondon, ON, Canada.,Department of Medical Biophysics, Western UniversityLondon, ON, Canada
| | - Mark B Badrov
- School of Kinesiology, Western UniversityLondon, ON, Canada
| | - T Dylan Olver
- School of Kinesiology, Western UniversityLondon, ON, Canada
| | - J Kevin Shoemaker
- School of Kinesiology, Western UniversityLondon, ON, Canada.,Department of Physiology and Pharmacology, Western UniversityLondon, ON, Canada
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38
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Hoye NA, Wilson LC, Wilkins GT, Jardine DL, Putt TL, Samaranayaka A, Schollum JBW, Walker RJ. Endovascular Renal Denervation in End-Stage Kidney Disease Patients: Cardiovascular Protection-A Proof-of-Concept Study. Kidney Int Rep 2017; 2:856-865. [PMID: 29270493 PMCID: PMC5733679 DOI: 10.1016/j.ekir.2017.04.012] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2017] [Revised: 04/17/2017] [Accepted: 04/26/2017] [Indexed: 01/28/2023] Open
Abstract
Introduction Sympathetic neural activation is markedly increased in end-stage kidney disease (ESKD). Catheter-based renal denervation (RDN) reduces sympathetic overactivity and blood pressure in resistant hypertension. We investigated the effect of RDN on sympathetic neural activation and left ventricular mass in patients with ESKD. Methods Nine ESKD (6 hemodialysis and 3 peritoneal dialysis) patients with dialysis vintage of ≥11 months were treated with RDN (EnligHTN system). Data were obtained on a nondialysis day; at baseline, 1, 3, and 12 months post-RDN. Results At baseline sympathetic neural activation measured by muscle sympathetic nervous activity (MSNA) and plasma norepinephrine concentrations were markedly elevated. Left ventricular hypertrophy (LVH) was evident in 8 of the 9 patients. At 12 months post-RDN, blind analysis revealed that MSNAfrequency (–12.2 bursts/min1, 95% CI [–13.6, –10.7]) and LV mass (–27 g/m2, 95% CI [–47, –8]) were reduced. Mean ambulatory BP (systolic: –24 mm Hg, 95% CI [–42, –5] and diastolic: –13 mm Hg, 95% CI [–22, –4]) was also reduced at 12 months. Office BP was reduced as early as 1 month (systolic: –25 mm Hg, 95% CI [–45, –5] and diastolic: –13 mm Hg, 95% CI [–24, –1]). Both ambulatory and office BP had clinically significant reductions in at least 50% of patients out to 12 months. Discussion Catheter-based RDN significantly reduced MSNA and LV mass as well as systemic BP in this group of patients with ESKD.
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Affiliation(s)
- Neil A Hoye
- Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, Otago, New Zealand.,Department of Renal Medicine, St. James's University Hospital, Leeds, UK
| | - Luke C Wilson
- Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, Otago, New Zealand
| | - Gerard T Wilkins
- Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, Otago, New Zealand
| | - David L Jardine
- Department of Medicine, University of Otago, Christchurch, Otago, New Zealand
| | - Tracey L Putt
- Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, Otago, New Zealand
| | - Ari Samaranayaka
- Department of Preventive and Social Medicine, Dunedin School of Medicine, University of Otago, Dunedin, Otago, New Zealand
| | - John B W Schollum
- Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, Otago, New Zealand
| | - Robert J Walker
- Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, Otago, New Zealand
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Hart EC, Head GA, Carter JR, Wallin BG, May CN, Hamza SM, Hall JE, Charkoudian N, Osborn JW. Recording sympathetic nerve activity in conscious humans and other mammals: guidelines and the road to standardization. Am J Physiol Heart Circ Physiol 2017; 312:H1031-H1051. [PMID: 28364017 DOI: 10.1152/ajpheart.00703.2016] [Citation(s) in RCA: 117] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2016] [Revised: 03/06/2017] [Accepted: 03/06/2017] [Indexed: 01/03/2023]
Abstract
Over the past several decades, studies of the sympathetic nervous system in humans, sheep, rabbits, rats, and mice have substantially increased mechanistic understanding of cardiovascular function and dysfunction. Recently, interest in sympathetic neural mechanisms contributing to blood pressure control has grown, in part because of the development of devices or surgical procedures that treat hypertension by manipulating sympathetic outflow. Studies in animal models have provided important insights into physiological and pathophysiological mechanisms that are not accessible in human studies. Across species and among laboratories, various approaches have been developed to record, quantify, analyze, and interpret sympathetic nerve activity (SNA). In general, SNA demonstrates "bursting" behavior, where groups of action potentials are synchronized and linked to the cardiac cycle via the arterial baroreflex. In humans, it is common to quantify SNA as bursts per minute or bursts per 100 heart beats. This type of quantification can be done in other species but is only commonly reported in sheep, which have heart rates similar to humans. In rabbits, rats, and mice, SNA is often recorded relative to a maximal level elicited in the laboratory to control for differences in electrode position among animals or on different study days. SNA in humans can also be presented as total activity, where normalization to the largest burst is a common approach. The goal of the present paper is to put together a summary of "best practices" in several of the most common experimental models and to discuss opportunities and challenges relative to the optimal measurement of SNA across species.Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/guidelines-for-measuring-sympathetic-nerve-activity/.
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Affiliation(s)
- Emma C Hart
- School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, United Kingdom;
| | - Geoffrey A Head
- Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia
| | | | | | - Clive N May
- Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia
| | | | - John E Hall
- Department of Physiology and Biophysics, Mississippi Center for Obesity Research, University of Mississippi Medical Center, Jackson, Mississippi
| | - Nisha Charkoudian
- United States Army Research Institute of Environmental Medicine, Natick, Massachusetts; and
| | - John W Osborn
- Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota
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40
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Badrov MB, Olver TD, Shoemaker JK. Central vs. peripheral determinants of sympathetic neural recruitment: insights from static handgrip exercise and postexercise circulatory occlusion. Am J Physiol Regul Integr Comp Physiol 2016; 311:R1013-R1021. [PMID: 27784689 DOI: 10.1152/ajpregu.00360.2016] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2016] [Revised: 10/11/2016] [Accepted: 10/24/2016] [Indexed: 11/22/2022]
Abstract
Sympathetic outflow is modified during acute homeostatic stress through increased firing of low-threshold axons, recruitment of latent axons, and synaptic delay modifications. However, the role of central mechanisms versus peripheral reflex control over sympathetic recruitment remains unknown. Here, we examined sympathetic discharge patterns during fatiguing static handgrip (SHG) exercise and postexercise circulatory occlusion (PECO) to study the central vs. peripheral reflex elements of sympathetic neural coding. Muscle sympathetic nerve activity (MSNA; microneurography) was measured in six males (25 ± 3 yr) at baseline (3 min) and during 5 min of SHG exercise completed at 20% maximal voluntary contraction. Isolation of the peripheral metaboreflex component was achieved by PECO for 3 min. Action potential (AP) patterns were studied using wavelet-based methodology. Compared with baseline, total MSNA increased by minute 3 of SHG, remaining elevated throughout the duration of exercise and PECO (all P < 0.05). The AP content per burst increased above baseline by minute 4 of SHG (Δ4 ± 2), remaining elevated at minute 5 (Δ6 ± 4) and PECO (Δ4 ± 4; all P < 0.05). Similarly, total AP clusters increased by minute 4 of SHG (Δ5 ± 5) and remained elevated at minute 5 (Δ6 ± 3) and PECO (Δ7 ± 5; all P < 0.01), indicating recruitment of latent subpopulations. Finally, the AP cluster size-latency profile was shifted downward during minutes 4 (-32 ± 22 ms) and 5 (-49 ± 17 ms; both P < 0.05) of SHG but was not different than baseline during PECO (P > 0.05). Our findings suggest that central perceptual factors play a specific role in the synaptic delay aspect of sympathetic discharge timing, whereas peripheral reflex mechanisms affect recruitment of latent axons.
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Affiliation(s)
- Mark B Badrov
- School of Kinesiology, Western University, London, Ontario, Canada
| | - T Dylan Olver
- School of Kinesiology, Western University, London, Ontario, Canada.,Department of Biomedical Sciences, University of Missouri, Columbia, Missouri; and
| | - J Kevin Shoemaker
- School of Kinesiology, Western University, London, Ontario, Canada; .,Department of Physiology and Pharmacology, Western University, London, Ontario, Canada
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41
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Notay K, Seed JD, Incognito AV, Doherty CJ, Nardone M, Burns MJ, Millar PJ. Validity and reliability of measuring resting muscle sympathetic nerve activity using short sampling durations in healthy humans. J Appl Physiol (1985) 2016; 121:1065-1073. [PMID: 27687563 DOI: 10.1152/japplphysiol.00736.2016] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2016] [Accepted: 09/27/2016] [Indexed: 11/22/2022] Open
Abstract
Resting muscle sympathetic nerve activity (MSNA) demonstrates high intraindividual reproducibility when sampled over 5-30 min epochs, although shorter sampling durations are commonly used before and during a stress to quantify sympathetic responsiveness. The purpose of the present study was to examine the intratest validity and reliability of MSNA sampled over 2 and 1 min and 30 and 15 s epoch durations. We retrospectively analyzed 68 resting fibular nerve microneurographic recordings obtained from 53 young, healthy participants (37 men; 23 ± 6 yr of age). From a stable 7-min resting baseline, MSNA (burst frequency and incidence, normalized mean burst amplitude, total burst area) was compared among each epoch duration and a standard 5-min control. Bland-Altman plots were used to determine agreement and bias. Three sequential MSNA measurements were collected using each sampling duration to calculate absolute and relative reliability (coefficients of variation and intraclass correlation coefficients). MSNA values were similar among each sampling duration and the 5-min control (all P > 0.05), highly correlated (r = 0.69-0.93; all P < 0.001), and demonstrated no evidence of fixed bias (all P > 0.05). A consistent proportional bias (P < 0.05) was present for MSNA burst frequency (all sampling durations) and incidence (1 min and 30 and 15 s), such that participants with low and high average MSNA underestimated and overestimated the true value, respectively. Reliability decreased progressively using the 30- and 15-s sampling durations. In conclusion, short 2 and 1 min and 30 s sampling durations can provide valid and reliable measures of MSNA, although increased sample size may be required for epochs ≤30 s, due to poorer reliability.
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Affiliation(s)
- Karambir Notay
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada; and
| | - Jeremy D Seed
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada; and
| | - Anthony V Incognito
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada; and
| | - Connor J Doherty
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada; and
| | - Massimo Nardone
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada; and
| | - Matthew J Burns
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada; and
| | - Philip J Millar
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada; and .,Toronto General Research Institute, Toronto General Hospital, Toronto, Ontario, Canada
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42
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Wehrwein EA, Orer HS, Barman SM. Overview of the Anatomy, Physiology, and Pharmacology of the Autonomic Nervous System. Compr Physiol 2016; 6:1239-78. [PMID: 27347892 DOI: 10.1002/cphy.c150037] [Citation(s) in RCA: 271] [Impact Index Per Article: 30.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Comprised of the sympathetic nervous system, parasympathetic nervous system, and enteric nervous system, the autonomic nervous system (ANS) provides the neural control of all parts of the body except for skeletal muscles. The ANS has the major responsibility to ensure that the physiological integrity of cells, tissues, and organs throughout the entire body is maintained (homeostasis) in the face of perturbations exerted by both the external and internal environments. Many commonly prescribed drugs, over-the-counter drugs, toxins, and toxicants function by altering transmission within the ANS. Autonomic dysfunction is a signature of many neurological diseases or disorders. Despite the physiological relevance of the ANS, most neuroscience textbooks offer very limited coverage of this portion of the nervous system. This review article provides both historical and current information about the anatomy, physiology, and pharmacology of the sympathetic and parasympathetic divisions of the ANS. The ultimate aim is for this article to be a valuable resource for those interested in learning the basics of these two components of the ANS and to appreciate its importance in both health and disease. Other resources should be consulted for a thorough understanding of the third division of the ANS, the enteric nervous system. © 2016 American Physiological Society. Compr Physiol 6:1239-1278, 2016.
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Affiliation(s)
- Erica A Wehrwein
- Department of Physiology, Michigan State University, East Lansing, Michigan, USA
| | - Hakan S Orer
- Department of Pharmacology, Koc University School of Medicine, Istanbul, Turkey
| | - Susan M Barman
- Department of Pharmacology &Toxicology, Michigan State University, East Lansing, Michigan, USA
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43
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Taylor KS, Kucyi A, Millar PJ, Murai H, Kimmerly DS, Morris BL, Bradley TD, Floras JS. Association between resting-state brain functional connectivity and muscle sympathetic burst incidence. J Neurophysiol 2016; 115:662-73. [PMID: 26538607 PMCID: PMC4752303 DOI: 10.1152/jn.00675.2015] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2015] [Accepted: 10/31/2015] [Indexed: 12/14/2022] Open
Abstract
The insula (IC) and cingulate are key components of the central autonomic network and central nodes of the salience network (SN), a set of spatially distinct but temporally correlated brain regions identified with resting-state (task free) functional MRI (rsMRI). To examine the SN's involvement in sympathetic outflow, we tested the hypothesis that individual differences in intrinsic connectivity of the SN correlate positively with resting postganglionic muscle sympathetic nerve activity (MSNA) burst incidence (BI) in subjects without and with obstructive sleep apnea (OSA). Overnight polysomnography, 5-min rsMRI, and fibular MSNA recording were performed in 36 subjects (mean age 57 yr; 10 women, 26 men). Independent component analysis (ICA) of the entire cohort identified the SN as including bilateral IC, pregenual anterior cingulate cortex (pgACC), midcingulate cortex (MCC), and the temporoparietal junction (TPJ). There was a positive correlation between BI and the apnea-hypopnea index (AHI) (P < 0.001), but dual-regression analysis identified no differences in SN functional connectivity between subjects with no or mild OSA (n = 17) and moderate or severe (n = 19) OSA. Correlation analysis relating BI to the strength of connectivity within the SN revealed large (i.e., spatial extent) and strong correlations for the left IC (P < 0.001), right pgACC/MCC (P < 0.006), left TPJ (P < 0.004), thalamus (P < 0.035), and cerebellum (P < 0.013). Indexes of sleep apnea were unrelated to BI and the strength of SN connectivity. There were no relationships between BI and default or sensorimotor network connectivity. This study links connectivity within the SN to MSNA, demonstrating several of its nodes to be key sympathoexcitatory regions.
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Affiliation(s)
- Keri S Taylor
- University Health Network and Mount Sinai Hospital Department of Medicine, University of Toronto, Toronto, Ontario, Canada;
| | - Aaron Kucyi
- Department of Psychiatry, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts; and
| | - Philip J Millar
- University Health Network and Mount Sinai Hospital Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Hisayoshi Murai
- University Health Network and Mount Sinai Hospital Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Derek S Kimmerly
- University Health Network and Mount Sinai Hospital Department of Medicine, University of Toronto, Toronto, Ontario, Canada; School of Health and Human Performance, Faculty of Health Professions, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Beverley L Morris
- University Health Network and Mount Sinai Hospital Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - T Douglas Bradley
- University Health Network and Mount Sinai Hospital Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - John S Floras
- University Health Network and Mount Sinai Hospital Department of Medicine, University of Toronto, Toronto, Ontario, Canada
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44
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Tamisier R, Tan CO, Pepin JL, Levy P, Taylor JA. Blood Pressure Increases in OSA due to Maintained Neurovascular Sympathetic Transduction: Impact of CPAP. Sleep 2015; 38:1973-80. [PMID: 26039959 DOI: 10.5665/sleep.5252] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2015] [Accepted: 04/13/2015] [Indexed: 12/19/2022] Open
Abstract
STUDY OBJECTIVES To test the hypothesis that greater resting sympathetic activity in obstructive sleep apnea (OSA) syndrome would not induce a lesser sympathetic neurovascular transduction. DESIGN Case-controlled cohort study. PARTICIPANTS 33 patients with newly diagnosed OSA without comorbidities and 14 healthy controls. INTERVENTIONS 6 months of continuous positive airway pressure (CPAP) treatment for OSA patients and follow-up for 9 healthy controls. MEASUREMENTS AND RESULTS We assessed resting sympathetic outflow and sympathetic neurovascular transduction. Sympathetic activity was directly measured (microneurography) at rest and in response to sustained isometric handgrip exercise. Neurovascular transduction was derived from the relationship of sympathetic activity and blood pressure to leg blood flow during exercise. Despite an elevated sympathetic activity of ∼50% in OSA compared to controls, neurovascular transduction was not different (i.e., absence of tachyphylaxis). After six months of CPAP, there were significant declines in diastolic pressure, averaging ∼4 mm Hg, and in sympathetic activity, averaging ∼20% with no change in transduction. CONCLUSIONS Greater sympathetic activity in obstructive sleep apnea does not appear to be associated with lesser neurovascular transduction. Hence, elevated sympathetic outflow without lesser transduction may underlie the prevalent development of hypertension in this population that is well controlled by continuous positive airway pressure treatment.
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Affiliation(s)
- Renaud Tamisier
- Université Grenoble Alpes, HP2; Inserm U1042, Grenoble, France.,CHU de Grenoble, Clinique Physiologie, Sommeil et Exercice, Grenoble, France
| | - Can Ozan Tan
- Cardiovascular Research Laboratory, Spaulding Rehabilitation Hospital, and Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA
| | - Jean-Louis Pepin
- Université Grenoble Alpes, HP2; Inserm U1042, Grenoble, France.,CHU de Grenoble, Clinique Physiologie, Sommeil et Exercice, Grenoble, France
| | - Patrick Levy
- Université Grenoble Alpes, HP2; Inserm U1042, Grenoble, France.,CHU de Grenoble, Clinique Physiologie, Sommeil et Exercice, Grenoble, France
| | - J Andrew Taylor
- Cardiovascular Research Laboratory, Spaulding Rehabilitation Hospital, and Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA
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45
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Greaney JL, Kenney WL, Alexander LM. Sympathetic regulation during thermal stress in human aging and disease. Auton Neurosci 2015; 196:81-90. [PMID: 26627337 DOI: 10.1016/j.autneu.2015.11.002] [Citation(s) in RCA: 72] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2015] [Revised: 11/18/2015] [Accepted: 11/19/2015] [Indexed: 02/07/2023]
Abstract
Humans control their core temperature within a narrow range via precise adjustments of the autonomic nervous system. In response to changing core and/or skin temperature, several critical thermoregulatory reflex effector responses are initiated and include shivering, sweating, and changes in cutaneous blood flow. Cutaneous vasomotor adjustments, mediated by modulations in sympathetic nerve activity (SNA), aid in the maintenance of thermal homeostasis during cold and heat stress since (1) they serve as the first line of defense of body temperature and are initiated before other thermoregulatory effectors, and (2) they are on the efferent arm of non-thermoregulatory reflex systems, aiding in the maintenance of blood pressure and organ perfusion. This review article highlights the sympathetic responses of humans to thermal stress, with a specific focus on primary aging as well as impairments that occur in both heart disease and type 2 diabetes mellitus. Age- and pathology-related changes in efferent muscle and skin SNA during cold and heat stress, measured directly in humans using microneurography, are discussed.
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Affiliation(s)
- Jody L Greaney
- Department of Kinesiology, Noll Laboratory, The Pennsylvania State University, University Park, PA 16802, United States.
| | - W Larry Kenney
- Department of Kinesiology, Noll Laboratory, The Pennsylvania State University, University Park, PA 16802, United States
| | - Lacy M Alexander
- Department of Kinesiology, Noll Laboratory, The Pennsylvania State University, University Park, PA 16802, United States
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46
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Dumesic DA, Oberfield SE, Stener-Victorin E, Marshall JC, Laven JS, Legro RS. Scientific Statement on the Diagnostic Criteria, Epidemiology, Pathophysiology, and Molecular Genetics of Polycystic Ovary Syndrome. Endocr Rev 2015; 36:487-525. [PMID: 26426951 PMCID: PMC4591526 DOI: 10.1210/er.2015-1018] [Citation(s) in RCA: 608] [Impact Index Per Article: 60.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Polycystic ovary syndrome (PCOS) is a heterogeneous and complex disorder that has both adverse reproductive and metabolic implications for affected women. However, there is generally poor understanding of its etiology. Varying expert-based diagnostic criteria utilize some combination of oligo-ovulation, hyperandrogenism, and the presence of polycystic ovaries. Criteria that require hyperandrogenism tend to identify a more severe reproductive and metabolic phenotype. The phenotype can vary by race and ethnicity, is difficult to define in the perimenarchal and perimenopausal period, and is exacerbated by obesity. The pathophysiology involves abnormal gonadotropin secretion from a reduced hypothalamic feedback response to circulating sex steroids, altered ovarian morphology and functional changes, and disordered insulin action in a variety of target tissues. PCOS clusters in families and both female and male relatives can show stigmata of the syndrome, including metabolic abnormalities. Genome-wide association studies have identified a number of candidate regions, although their role in contributing to PCOS is still largely unknown.
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Affiliation(s)
- Daniel A Dumesic
- Department of Obstetrics and Gynecology (D.A.D.), David Geffen School of Medicine at UCLA, Los Angeles, California 90095; Division of Pediatric Endocrinology (S.E.O.), Children's Hospital of New York-Presbyterian, Columbia University College of Physicians and Surgeons, New York, New York 10032; Department of Physiology (E.S.-V.), Karolinska Institutet, 171 77 Stockholm, Sweden; Center for Research in Reproduction and Division of Endocrinology (J.C.M.), Department of Internal Medicine, University of Virginia Health System, Charlottesville, Virginia 22903; Division of Reproductive Medicine (J.S.L.), Department of Obstetrics and Gynecology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands; and Department of Obstetrics and Gynecology (R.S.L.), Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033
| | - Sharon E Oberfield
- Department of Obstetrics and Gynecology (D.A.D.), David Geffen School of Medicine at UCLA, Los Angeles, California 90095; Division of Pediatric Endocrinology (S.E.O.), Children's Hospital of New York-Presbyterian, Columbia University College of Physicians and Surgeons, New York, New York 10032; Department of Physiology (E.S.-V.), Karolinska Institutet, 171 77 Stockholm, Sweden; Center for Research in Reproduction and Division of Endocrinology (J.C.M.), Department of Internal Medicine, University of Virginia Health System, Charlottesville, Virginia 22903; Division of Reproductive Medicine (J.S.L.), Department of Obstetrics and Gynecology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands; and Department of Obstetrics and Gynecology (R.S.L.), Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033
| | - Elisabet Stener-Victorin
- Department of Obstetrics and Gynecology (D.A.D.), David Geffen School of Medicine at UCLA, Los Angeles, California 90095; Division of Pediatric Endocrinology (S.E.O.), Children's Hospital of New York-Presbyterian, Columbia University College of Physicians and Surgeons, New York, New York 10032; Department of Physiology (E.S.-V.), Karolinska Institutet, 171 77 Stockholm, Sweden; Center for Research in Reproduction and Division of Endocrinology (J.C.M.), Department of Internal Medicine, University of Virginia Health System, Charlottesville, Virginia 22903; Division of Reproductive Medicine (J.S.L.), Department of Obstetrics and Gynecology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands; and Department of Obstetrics and Gynecology (R.S.L.), Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033
| | - John C Marshall
- Department of Obstetrics and Gynecology (D.A.D.), David Geffen School of Medicine at UCLA, Los Angeles, California 90095; Division of Pediatric Endocrinology (S.E.O.), Children's Hospital of New York-Presbyterian, Columbia University College of Physicians and Surgeons, New York, New York 10032; Department of Physiology (E.S.-V.), Karolinska Institutet, 171 77 Stockholm, Sweden; Center for Research in Reproduction and Division of Endocrinology (J.C.M.), Department of Internal Medicine, University of Virginia Health System, Charlottesville, Virginia 22903; Division of Reproductive Medicine (J.S.L.), Department of Obstetrics and Gynecology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands; and Department of Obstetrics and Gynecology (R.S.L.), Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033
| | - Joop S Laven
- Department of Obstetrics and Gynecology (D.A.D.), David Geffen School of Medicine at UCLA, Los Angeles, California 90095; Division of Pediatric Endocrinology (S.E.O.), Children's Hospital of New York-Presbyterian, Columbia University College of Physicians and Surgeons, New York, New York 10032; Department of Physiology (E.S.-V.), Karolinska Institutet, 171 77 Stockholm, Sweden; Center for Research in Reproduction and Division of Endocrinology (J.C.M.), Department of Internal Medicine, University of Virginia Health System, Charlottesville, Virginia 22903; Division of Reproductive Medicine (J.S.L.), Department of Obstetrics and Gynecology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands; and Department of Obstetrics and Gynecology (R.S.L.), Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033
| | - Richard S Legro
- Department of Obstetrics and Gynecology (D.A.D.), David Geffen School of Medicine at UCLA, Los Angeles, California 90095; Division of Pediatric Endocrinology (S.E.O.), Children's Hospital of New York-Presbyterian, Columbia University College of Physicians and Surgeons, New York, New York 10032; Department of Physiology (E.S.-V.), Karolinska Institutet, 171 77 Stockholm, Sweden; Center for Research in Reproduction and Division of Endocrinology (J.C.M.), Department of Internal Medicine, University of Virginia Health System, Charlottesville, Virginia 22903; Division of Reproductive Medicine (J.S.L.), Department of Obstetrics and Gynecology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands; and Department of Obstetrics and Gynecology (R.S.L.), Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033
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47
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Greaney JL, Alexander LM, Kenney WL. Sympathetic control of reflex cutaneous vasoconstriction in human aging. J Appl Physiol (1985) 2015; 119:771-82. [PMID: 26272321 DOI: 10.1152/japplphysiol.00527.2015] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
This Synthesis highlights a series of recent studies that has systematically interrogated age-related deficits in cold-induced skin vasoconstriction. In response to cold stress, a reflex increase in sympathetic nervous system activity mediates reductions in skin blood flow. Reflex vasoconstriction during cold exposure is markedly impaired in aged skin, contributing to the relative inability of healthy older adults to maintain core temperature during mild cold stress in the absence of appropriate behavioral thermoregulation. This compromised reflex cutaneous vasoconstriction in healthy aging can occur as a result of functional deficits at multiple points along the efferent sympathetic reflex axis, including blunted sympathetic outflow directed to the skin vasculature, reduced presynaptic neurotransmitter synthesis and/or release, and altered end-organ responsiveness at several loci, in addition to potential alterations in afferent thermoreceptor function. Arguments have been made that the relative inability of aged skin to appropriately constrict is due to the aging cutaneous arterioles themselves, whereas other data point to the neural circuitry controlling those vessels. The argument presented herein provides strong evidence for impaired efferent sympathetic control of the peripheral cutaneous vasculature during whole body cold exposure as the primary mechanism responsible for attenuated vasoconstriction.
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Affiliation(s)
- Jody L Greaney
- Department of Kinesiology, Noll Laboratory, The Pennsylvania State University, University Park, Pennsylvania
| | - Lacy M Alexander
- Department of Kinesiology, Noll Laboratory, The Pennsylvania State University, University Park, Pennsylvania
| | - W Larry Kenney
- Department of Kinesiology, Noll Laboratory, The Pennsylvania State University, University Park, Pennsylvania
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48
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White DW, Shoemaker JK, Raven PB. Methods and considerations for the analysis and standardization of assessing muscle sympathetic nerve activity in humans. Auton Neurosci 2015; 193:12-21. [PMID: 26299824 DOI: 10.1016/j.autneu.2015.08.004] [Citation(s) in RCA: 86] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2015] [Revised: 08/01/2015] [Accepted: 08/03/2015] [Indexed: 01/20/2023]
Abstract
The technique of microneurography and the assessment of muscle sympathetic nerve activity (MSNA) are used in laboratories throughout the world. The variables used to describe MSNA, and the criteria by which these variables are quantified from the integrated neurogram, vary among studies and laboratories and, therefore, can become confusing to those starting to learn the technique. Therefore, the purpose of this educational review is to discuss guidelines and standards for the assessment of sympathetic nervous activity through the collection and analysis of MSNA. This review will reiterate common practices in the collection of MSNA, but will also introduce considerations for the evaluation and physiological inference using MSNA.
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Affiliation(s)
- Daniel W White
- The Department of Kinesiology & Nutrition, University of Illinois at Chicago, Chicago, IL, USA.
| | - J Kevin Shoemaker
- The School of Kinesiology, University of Western Ontario, London, ON, Canada
| | - Peter B Raven
- Department of Integrative Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, TX, USA
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49
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Badrov MB, Usselman CW, Shoemaker JK. Sympathetic neural recruitment strategies: responses to severe chemoreflex and baroreflex stress. Am J Physiol Regul Integr Comp Physiol 2015; 309:R160-8. [PMID: 25947171 DOI: 10.1152/ajpregu.00077.2015] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Accepted: 04/28/2015] [Indexed: 11/22/2022]
Abstract
This study tested the hypothesis that neural coding patterns exist within the autonomic nervous system. We investigated sympathetic axonal recruitment strategies in humans during chemoreflex- and baroreflex-mediated sympathoexcitation using a novel action potential (AP) analysis technique. Muscle sympathetic nerve activity (microneurography) was collected in 11 young individuals (6 females) during baseline and two subsequent protocols: 1) severe chemoreflex stimulation (maximal end-inspiratory apnea following rebreathe), and 2) severe baroreceptor unloading (-80 mmHg lower body negative pressure; LBNP). When compared with each respective baseline, apnea and LBNP increased AP frequency and mean AP content per sympathetic burst (all P < 0.01). When APs were binned according to peak-to-peak amplitude (i.e., into "clusters"), total clusters detected increased during both apnea (Δ7 ± 5; P = 0.0009) and LBNP (Δ11 ± 8; P = 0.0012) compared with baseline. This was concomitant to an increased number of active clusters per burst during apnea (Δ3 ± 1; P < 0.0001) and LBNP (Δ3 ± 3; P = 0.0076). At baseline and during apnea (R(2) = 0.98; P < 0.0001) and LBNP (R(2) = 0.95; P < 0.0001), a pattern emerged whereby AP cluster latency decreased as cluster size increased. Furthermore, the AP cluster latency profile was shifted downward during apnea (∼53 ms) and upward during LBNP (∼31 ms). The data indicate that variations in synaptic delays and latent subpopulations of larger axons exist as recruitment strategies for sympathetic outflow. The synaptic delay component appears to express reflex specificity, whereas latent subpopulation recruitment demonstrates sensitivity to stress severity.
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Affiliation(s)
- Mark B Badrov
- Neurovascular Research Laboratory, School of Kinesiology, Western University, London, Ontario, Canada; and
| | - Charlotte W Usselman
- Neurovascular Research Laboratory, School of Kinesiology, Western University, London, Ontario, Canada; and
| | - J Kevin Shoemaker
- Neurovascular Research Laboratory, School of Kinesiology, Western University, London, Ontario, Canada; and Department of Physiology and Pharmacology, Western University, London, Ontario, Canada
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50
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Charkoudian N, Wallin BG. Sympathetic neural activity to the cardiovascular system: integrator of systemic physiology and interindividual characteristics. Compr Physiol 2014; 4:825-50. [PMID: 24715570 DOI: 10.1002/cphy.c130038] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
The sympathetic nervous system is a ubiquitous, integrating controller of myriad physiological functions. In the present article, we review the physiology of sympathetic neural control of cardiovascular function with a focus on integrative mechanisms in humans. Direct measurement of sympathetic neural activity (SNA) in humans can be accomplished using microneurography, most commonly performed in the peroneal (fibular) nerve. In humans, muscle SNA (MSNA) is composed of vasoconstrictor fibers; its best-recognized characteristic is its participation in transient, moment-to-moment control of arterial blood pressure via the arterial baroreflex. This property of MSNA contributes to its typical "bursting" pattern which is strongly linked to the cardiac cycle. Recent evidence suggests that sympathetic neural mechanisms and the baroreflex have important roles in the long term control of blood pressure as well. One of the striking characteristics of MSNA is its large interindividual variability. However, in young, normotensive humans, higher MSNA is not linked to higher blood pressure due to balancing influences of other cardiovascular variables. In men, an inverse relationship between MSNA and cardiac output is a major factor in this balance, whereas in women, beta-adrenergic vasodilation offsets the vasoconstrictor/pressor effects of higher MSNA. As people get older (and in people with hypertension) higher MSNA is more likely to be linked to higher blood pressure. Skin SNA (SSNA) can also be measured in humans, although interpretation of SSNA signals is complicated by multiple types of neurons involved (vasoconstrictor, vasodilator, sudomotor and pilomotor). In addition to blood pressure regulation, the sympathetic nervous system contributes to cardiovascular regulation during numerous other reflexes, including those involved in exercise, thermoregulation, chemoreflex regulation, and responses to mental stress.
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Affiliation(s)
- N Charkoudian
- U.S. Army Research Institute of Environmental Medicine, Natick, Massachusetts
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