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Basalay MV, Davidson SM, Gourine AV, Yellon DM. Neural mechanisms in remote ischaemic conditioning in the heart and brain: mechanistic and translational aspects. Basic Res Cardiol 2018; 113:25. [PMID: 29858664 PMCID: PMC5984640 DOI: 10.1007/s00395-018-0684-z] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 05/02/2018] [Accepted: 05/23/2018] [Indexed: 12/13/2022]
Abstract
Remote ischaemic conditioning (RIC) is a promising method of cardioprotection, with numerous clinical studies having demonstrated its ability to reduce myocardial infarct size and improve prognosis. On the other hand, there are several clinical trials, in particular those conducted in the setting of elective cardiac surgery, that have failed to show any benefit of RIC. These contradictory data indicate that there is insufficient understanding of the mechanisms underlying RIC. RIC is now known to signal indiscriminately, protecting not only the heart, but also other organs. In particular, experimental studies have demonstrated that it is able to reduce infarct size in an acute ischaemic stroke model. However, the mechanisms underlying RIC-induced neuroprotection are even less well understood than for cardioprotection. The existence of bidirectional feedback interactions between the heart and the brain suggests that the mechanisms of RIC-induced neuroprotection and cardioprotection should be studied as a whole. This review, therefore, addresses the topic of the neural component of the RIC mechanism.
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Affiliation(s)
- Marina V Basalay
- The Hatter Cardiovascular Institute, University College London, 67 Chenies Mews, London, WC1E 6HX, UK
| | - Sean M Davidson
- The Hatter Cardiovascular Institute, University College London, 67 Chenies Mews, London, WC1E 6HX, UK
| | - Andrey V Gourine
- Department of Cardiology, Karolinska University Hospital, 171 76, Stockholm, Sweden
| | - Derek M Yellon
- The Hatter Cardiovascular Institute, University College London, 67 Chenies Mews, London, WC1E 6HX, UK.
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Intrinsic cardiac ganglia and acetylcholine are important in the mechanism of ischaemic preconditioning. Basic Res Cardiol 2017; 112:11. [PMID: 28091727 PMCID: PMC5236079 DOI: 10.1007/s00395-017-0601-x] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Revised: 12/05/2016] [Accepted: 01/03/2017] [Indexed: 01/24/2023]
Abstract
This study aimed to investigate the role of the intrinsic cardiac nervous system in the mechanism of classical myocardial ischaemic preconditioning (IPC). Isolated perfused rat hearts were subjected to 35-min regional ischaemia and 60-min reperfusion. IPC was induced as three cycles of 5-min global ischaemia–reperfusion, and provided significant reduction in infarct size (IS/AAR = 14 ± 2% vs control IS/AAR = 48 ± 3%, p < 0.05). Treatment with the ganglionic antagonist, hexamethonium (50 μM), blocked IPC protection (IS/AAR = 37 ± 7%, p < 0.05 vs IPC). Moreover, the muscarinic antagonist, atropine (100 nM), also abrogated IPC-mediated protection (IS/AAR = 40 ± 3%, p < 0.05 vs IPC). This indicates that intrinsic cardiac ganglia remain intact in the Langendorff preparation and are important in the mechanism of IPC. In a second group of experiments, coronary effluent collected following IPC, from ex vivo perfused rat hearts, provided significant cardioprotection when perfused through a naïve isolated rat heart prior to induction of regional ischaemia–reperfusion injury (IRI) (IS/ARR = 19 ± 2, p < 0.05 vs control effluent). This protection was also abrogated by treating the naïve heart with hexamethonium, indicating the humoral trigger of IPC induces protection via an intrinsic neuronal mechanism (IS/AAR = 46 ± 5%, p < 0.05 vs IPC effluent). In addition, a large release in ACh was observed in coronary effluent was observed following IPC (IPCeff = 0.36 ± 0.03 μM vs Ceff = 0.04 ± 0.04 μM, n = 4, p < 0.001). Interestingly, however, IPC effluent was not able to significantly protect isolated cardiomyocytes from simulated ischaemia–reperfusion injury (cell death = 45 ± 6%, p = 0.09 vs control effluent). In conclusion, IPC involves activation of the intrinsic cardiac nervous system, leading to release of ACh in the ventricles and induction of protection via activation of muscarinic receptors.
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Abstract
The aim of this paper is to explore the effect of intestinal ischemia/reperfusion (I/R) injury on leptin and orexin-A levels in peripheral blood and central secretory tissues, and to examine the roles of leptin and orexin-A in acute inflammatory responses. An intestinal I/R injury model of rats was made; the rats were grouped according to the time of after 60 min ischemia. Radioimmunoassay was employed to detect the levels of leptin in serum and adipose tissue and orexin-A levels in plasma and hypothalamus. Reverse transcriptase-polymerase chain reaction was used to detect mRNA expressions of adipose leptin and hypothalamus orexin-A. Compared with the levels before the injury, serum leptin in 60 min ischemia/30 min reperfusion (I60'R30') group decreased and that of I60'R360' group increased. Compared with sham-operation group (sham group) after injury, serum leptin level of I60'R360' group increased, adipose leptin levels of I60'R30' and I60'R90' decreased, and adipose leptin in I60'R360' group increased. After the injury, adipose leptin mRNA expressions of I60'R30', I60'R240' and I60'R360' increased, whereas that of I60'R150' group decreased as compared with the sham group. There was no significant difference in the protein levels of orexin-A, either between plasma and hypothalamus or between pre-and post-I/R injury. Compared with sham group, hypothalamus orexin-A mRNA expressions of I60'R30' and I60'R90' decreased gradually after the injury, with that of I60'R150' group reaching the lowest, and those of I60'R240' and I60'R360' recovering gradually, although they were still significantly lower than that of sham group. Leptin and orexin-A respond to intestinal I/R injury in a time-dependent manner, with leptin responding more quickly than orexin-A does, and both of them may contribute to the metabolic disorders in acute inflammation.
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Lupiński SŁ, Schlicker E, Pędzińska-Betiuk A, Malinowska B. Acute myocardial ischemia enhances the vanilloid TRPV1 and serotonin 5-HT3 receptor-mediated Bezold-Jarisch reflex in rats. Pharmacol Rep 2012; 63:1450-9. [PMID: 22358093 DOI: 10.1016/s1734-1140(11)70709-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2011] [Revised: 08/02/2011] [Indexed: 11/26/2022]
Abstract
The Bezold-Jarisch reflex is characterized by a sudden bradycardia associated with hypotension induced by the activation of the vanilloid TRPV1 and serotonin 5-HT(3) receptors. This reflex is associated with several health conditions, including myocardial infarction. The aim of the present study was to elucidate the influence of acute experimental myocardial ischemia on the reflex bradycardia induced by anandamide and phenylbiguanide, agonists of the TRPV1 and 5-HT(3) receptors, respectively. In urethane-anesthetized rats, the rapid iv injection of anandamide (0.6 μmol/kg) or phenylbiguanide (0.03 μmol/kg) decreased heart rate (HR) by about 7-10% of the basal values. Myocardial ischemia (MI) was induced by ligation of the left anterior coronary artery. The agonists were injected 5 min before MI (S(1)) and 10, 20 and 30 min thereafter (S(2)-S(4)). MI potentiated the anandamide-induced reflex bradycardia by approximately 105% at S(2) and 70% at S(3) but had no effect at S(4). This amplificatory effect of MI was virtually abolished by the TRPV1 receptor antagonist capsazepine (1 μmol/kg) and was not modified by the cannabinoid CB(1) receptor antagonist rimonabant (0.1 μmol/kg). MI also amplified the reflex bradycardia elicited by phenylbiguanide by approximately 110, 60 and 90% (S(2), S(3) and S(4), respectively), and this effect was sensitive to the 5-HT(3) receptor antagonist ondansetron (3 μmol/kg). In conclusion, our results suggest that acute myocardial ischemia augments the Bezold-Jarisch reflex induced via activation of TRPV1 and 5-HT(3) receptors located on sensory vagal nerves in the heart.
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Affiliation(s)
- Sebastian Ł Lupiński
- Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Mickiewicza 2A, PL 15-089 Białystok, Poland
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Della-Morte D, Guadagni F, Palmirotta R, Ferroni P, Testa G, Cacciatore F, Abete P, Rengo F, Perez-Pinzon MA, Sacco RL, Rundek T. Genetics and genomics of ischemic tolerance: focus on cardiac and cerebral ischemic preconditioning. Pharmacogenomics 2012; 13:1741-1757. [PMID: 23171338 DOI: 10.2217/pgs.12.157] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
A subthreshold ischemic insult applied to an organ such as the heart and/or brain may help to reduce damage caused by subsequent ischemic episodes. This phenomenon is known as ischemic tolerance mediated by ischemic preconditioning (IPC) and represents the most powerful endogenous mechanism against ischemic injury. Various molecular pathways have been implicated in IPC, and several compounds have been proposed as activators or mediators of IPC. Recently, it has been established that the protective phenotype in response to ischemia depends on a coordinated response at the genomic, molecular, cellular and tissue levels by introducing the concept of 'genomic reprogramming' following IPC. In this article, we sought to review the genetic expression profiles found in cardiac and cerebral IPC studies, describe the differences between young and aged organs in IPC-mediated protection, and discuss the potential therapeutic application of IPC and pharmacological preconditioning based on the genomic response.
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Affiliation(s)
- David Della-Morte
- Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
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Kawada T, Akiyama T, Shimizu S, Kamiya A, Uemura K, Li M, Shirai M, Sugimachi M. Detection of endogenous acetylcholine release during brief ischemia in the rabbit ventricle: a possible trigger for ischemic preconditioning. Life Sci 2009; 85:597-601. [PMID: 19733187 DOI: 10.1016/j.lfs.2009.08.015] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2009] [Revised: 08/19/2009] [Accepted: 08/25/2009] [Indexed: 10/20/2022]
Abstract
AIMS To examine endogenous acetylcholine (ACh) release in the rabbit left ventricle during acute ischemia, ischemic preconditioning and electrical vagal stimulation. MAIN METHODS We measured myocardial interstitial ACh levels in the rabbit left ventricle using a cardiac microdialysis technique. In Protocol 1 (n=6), the left circumflex coronary artery (LCX) was occluded for 30min and reperfused for 30min. In Protocol 2 (n=5), the LCX was temporarily occluded for 5min. Ten minutes later, the LCX was occluded for 30min and reperfused for 30min. In Protocol 3 (n=5), bilateral efferent vagal nerves were stimulated at 20Hz and 40Hz (10V, 1-ms pulse duration). KEY FINDINGS In Protocol 1, a 30-min coronary occlusion increased the ACh level from 0.39+/-0.15 to 7.0+/-2.2nM (mean+/-SE, P<0.01). In Protocol 2, a 5-min coronary occlusion increased the ACh level from 0.33+/-0.07 to 0.75+/-0.11nM (P<0.05). The ACh level returned to 0.48+/-0.10nM during the interval. After that, a 30-min coronary occlusion increased the ACh level to 2.4+/-0.49nM (P<0.01). In Protocol 3, vagal stimulation at 20Hz and 40Hz increased the ACh level from 0.29+/-0.06 to 1.23+/-0.48 (P<0.05) and 2.44+/-1.13nM (P<0.01), respectively. SIGNIFICANCE Acute ischemia significantly increased the ACh levels in the rabbit left ventricle, which appeared to exceed the vagal stimulation-induced ACh release. Brief ischemia as short as 5min can also increase the ACh level, suggesting that endogenous ACh release can be a trigger for ischemic preconditioning.
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Affiliation(s)
- Toru Kawada
- Department of Cardiovascular Dynamics, Advanced Medical Engineering Center, National Cardiovascular Center Research Institute, Japan.
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Kawada T, Yamazaki T, Akiyama T, Kitagawa H, Shimizu S, Mizuno M, Li M, Sugimachi M. Vagal stimulation suppresses ischemia-induced myocardial interstitial myoglobin release. Life Sci 2008; 83:490-5. [DOI: 10.1016/j.lfs.2008.07.013] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2008] [Revised: 07/09/2008] [Accepted: 07/23/2008] [Indexed: 10/21/2022]
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Ding X, Mountain DJH, Subramanian V, Singh K, Williams CA. The effect of high cervical spinal cord stimulation on the expression of SP, NK-1 and TRPV1 mRNAs during cardiac ischemia in rat. Neurosci Lett 2007; 424:139-44. [PMID: 17714867 DOI: 10.1016/j.neulet.2007.07.040] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2007] [Revised: 07/13/2007] [Accepted: 07/26/2007] [Indexed: 10/23/2022]
Abstract
Spinal cord stimulation (SCS) is used to reduce angina that accompanies cardiac ischemia, but little is known about the molecular mechanisms mediating this effect. We studied the expression of SP, neurokinin-1 (NK-1) receptor, and transient receptor potential vanilloid type 1 (TRPV1) mRNA in the rat spinal cord at thoracic 4 (T4), cervical 2 (C2) and caudal brain stem by RT-PCR during intermittent occlusion of the left anterior descending coronary artery (CoAO), during sustained SCS by itself at the C2 spinal segment, and during sustained SCS plus intermittent CoAO. Only SP mRNA was increased significantly in T4 and brainstem during CoAO, while SCS decreased the mRNA levels of SP, NK-1 and TRPV1 significantly in T4 and the brainstem. SCS attenuated the increase of SP and TRPV1 mRNA levels at T4 level induced by intermittent CoAO when the stimulation was applied prior to the initiation of the cardiac ischemia. These results support the role for SP as a putative neurotransmitter for the myocardial ischemia-sensitive afferent neuron signal to the spinal level. They suggest that modification of the ischemic cardiac nociceptive afferent signal by SCS involves a change in SP and TRPV1 expression.
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Affiliation(s)
- Xiaohui Ding
- Department of Physiology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614-1708, United States
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Kawada T, Yamazaki T, Akiyama T, Li M, Ariumi H, Mori H, Sunagawa K, Sugimachi M. Vagal stimulation suppresses ischemia-induced myocardial interstitial norepinephrine release. Life Sci 2006; 78:882-7. [PMID: 16125731 DOI: 10.1016/j.lfs.2005.05.087] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2004] [Accepted: 05/31/2005] [Indexed: 11/29/2022]
Abstract
Although electrical vagal stimulation exerts beneficial effects on the ischemic heart such as an antiarrhythmic effect, whether it modulates norepinephrine (NE) and acetylcholine (ACh) releases in the ischemic myocardium remains unknown. To clarify the neural modulation in the ischemic region during vagal stimulation, we examined ischemia-induced NE and ACh releases in anesthetized and vagotomized cats. In a control group (VX, n = 8), occlusion of the left anterior descending coronary artery increased myocardial interstitial NE level from 0.46+/-0.09 to 83.2+/-17.6 nM at 30-45 min of ischemia (mean+/-SE). Vagal stimulation at 5 Hz (VS, n = 8) decreased heart rate by approximately 80 beats/min during the ischemic period and suppressed the NE release to 24.4+/-10.6 nM (P < 0.05 from the VX group). Fixed-rate ventricular pacing (VSP, n=8) abolished this vagally mediated suppression of ischemia-induced NE release. The vagal stimulation augmented ischemia-induced ACh release at 0-15 min of ischemia (VX: 11.1+/-2.1 vs. VS: 20.7+/-3.9 nM, P < 0.05). In the VSP group, the ACh release was not augmented. In conclusion, vagal stimulation suppressed the ischemia-induced NE release and augmented the initial increase in the ACh level. These modulations of NE and ACh levels in the ischemic myocardium may contribute to the beneficial effects of vagal stimulation on the heart during acute myocardial ischemia.
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Affiliation(s)
- Toru Kawada
- Department of Cardiovascular Dynamics, Advanced Medical Engineering Center, National Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan.
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Watanabe MA. Role of hypotension in heart rate turbulence. Heart Rhythm 2005; 2:828-9. [PMID: 16051117 DOI: 10.1016/j.hrthm.2005.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2005] [Indexed: 10/25/2022]
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Lin J, Yan GT, Hao XH, Wang LH, Zhang K, Xue H. Effect of intestinal ischemia-reperfusion injury on protein levels of leptin and orexin-A in peripheral blood and central secretory tissues. World J Gastroenterol 2005; 11:1000-4. [PMID: 15742403 PMCID: PMC4250760 DOI: 10.3748/wjg.v11.i7.1000] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To explore the effect of intestinal ischemia-reperfusion injury on protein levels of leptin and orexin-A in peripheral blood and their central secretory tissues and to find out the role leptin and orexin-A play in acute inflammatory responses.
METHODS: An intestinal ischemia-reperfusion (I/R) injury model of rats was established and rats were divided randomly into six groups: sham-operation group, 60 min ischemia/30 min reperfusion group (I60’R30’), I60’R90’, I60’R150’, I60’R240’ and I60’R360’, 9 rats each group. Two highly-sensitive radioimmunoassays for leptin and orexin-A were established and used to check the change of their concentrations in peripheral blood and central secretory tissues before and after intestinal I/R injury.
RESULTS: Compared with the serum leptin level before injury, it decreased significantly in I60’R30’ group and increased significantly in I60’R360’ group; compared to sham-operation group after injury, serum leptin level increased significantly in I60’R360’ group; compared to sham-operation group after injury, adipose leptin levels decreased significantly in I60’R30’ and I60’R90’ groups, while increased significantly in I60’R360’ group. There was no significant difference between the expression levels of orexin-A before and after I/R injury.
CONCLUSION: Leptin has a time-dependent response and orexin-A has a delayed response to acute inflammatory stimuli such as intestinal I/R injury and they may participate in metabolic disorders in injury as inflammatory cytokines.
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Affiliation(s)
- Ji Lin
- Research Laboratory of Biochemistry, Basic Medical Institute, General Hospital of PLA, 28 Fuxing Road, Beijing 100853, China
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Lin J, Yan GT, Wang LH, Hao XH, Zhang K, Xue H. Leptin fluctuates in intestinal ischemia-reperfusion injury as inflammatory cytokine. Peptides 2004; 25:2187-93. [PMID: 15572209 DOI: 10.1016/j.peptides.2004.08.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2004] [Revised: 08/07/2004] [Accepted: 08/09/2004] [Indexed: 01/02/2023]
Abstract
As leptin is an active mediator mainly secreted by adipose tissue and is closely related with energy metabolism, we evaluate both the changes of leptin levels in serum and adipose tissue with a concise radioimmunoassay and the changes of leptin mRNA expression in adipose tissue with RT-PCR, during the severe metabolic impediment in rat intestinal ischemia-reperfusion (I/R) injury. Results show that not only leptin levels in serum and adipose tissue but also its mRNA expression in adipose tissue undergo a fluctuation according to different injury times. Therefore, we conclude that leptin has a time-dependent response to acute inflammatory stimuli and acts as an anti-inflammatory cytokine.
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Affiliation(s)
- Ji Lin
- Research Laboratory of Biochemistry, Basic Medical Institute, General Hospital of PLA, 28 Fuxing Road, Beijing 100853, PR China
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Hua F, Ricketts BA, Reifsteck A, Ardell JL, Williams CA. Myocardial ischemia induces the release of substance P from cardiac afferent neurons in rat thoracic spinal cord. Am J Physiol Heart Circ Physiol 2003; 286:H1654-64. [PMID: 14684370 DOI: 10.1152/ajpheart.00906.2003] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Antibody-coated microprobes were inserted into the thoracic (T3-4) spinal cord in urethane-anesthetized Sprague-Dawley rats to detect the differences in the release of immunoreactive substance P-like (irSP) substances in response to differential activation of cardiac nociceptive sensory neurons (CNAN). CNAN were stimulated either by intrapericardial infusion of an inflammatory ischemic exudate solution (IES) containing algogenic substances (i.e., 10 mM each of adenosine, bradykinin, prostaglandin E2, and 5-hydroxytryptamine), or by transient occlusion of the left anterior descending coronary artery (CoAO). There was widespread basal release of irSP from the thoracic spinal cord. Stimulation of the CNAN by IES did not alter the pattern of release of irSP. Conversely, CoAO augmented the release of irSP from T3-4 spinal segments from laminae I-VII. This CoAO-induced irSP release was eliminated after thoracic dorsal rhizotomy. These results indicate that heterogeneous activation of cardiac afferents, as with focal coronary artery occlusion, represents an optimum input for activation of the cardiac neuronal hierarchy and for the resultant perception of angina. Excessive stimulation of cardiac nociceptive afferent neurons elicited during regional coronary artery occlusion involves the release of SP in the thoracic spinal cord and suggests that local spinal cord release of SP may be involved in the neural signaling of angina.
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Affiliation(s)
- Fang Hua
- Department of Physiology, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614-1708, USA
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Kawada T, Yamazaki T, Akiyama T, Mori H, Uemura K, Miyamoto T, Sugimachi M, Sunagawa K. Disruption of vagal efferent axon and nerve terminal function in the postischemic myocardium. Am J Physiol Heart Circ Physiol 2002; 283:H2687-91. [PMID: 12388320 DOI: 10.1152/ajpheart.00291.2002] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Despite the importance of vagal control over the ventricle, little is known regarding vagal efferent conduction and nerve terminal function in the postischemic myocardium. To elucidate postischemic changes in the cardiac vagal efferent neuronal function, we measured myocardial interstitial acetylcholine (ACh) levels by using in vivo cardiac microdialysis and examined the ACh responses to electrical stimulation of the vagi or local administration of ouabain in anesthetized cats. Sixty-minute occlusions of the left anterior descending coronary artery (LAD) followed by 60-min reperfusion abolished electrical stimulation-induced ACh release (20.4 +/- 3.9 vs. 0.9 +/- 0.4 nmol/l; means +/- SE, P < 0.01). In different groups of animals, 60-min LAD occlusion followed by 60-min reperfusion decreased but did not completely abolish ouabain-induced release of ACh (9.2 +/- 1.8 vs. 3.9 +/- 0.7 nmol/l; P < 0.05). These results indicate that function of the vagal efferent axon was completely interrupted, whereas the local ACh release was partially suppressed in the postischemic myocardium. The postischemic disruption of vagal efferent neuronal function might exert deleterious effects on cardiac regulation.
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Affiliation(s)
- Toru Kawada
- Department of Cardiovascular Dynamics, National Cardiovascular Center Research Institute, Osaka 565 - 8565, Japan.
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