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Simats A, Sager HB, Liesz A. Heart-brain axis in health and disease: role of innate and adaptive immunity. Cardiovasc Res 2025; 120:2325-2335. [PMID: 39180327 DOI: 10.1093/cvr/cvae185] [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: 03/15/2024] [Revised: 05/24/2024] [Accepted: 06/13/2024] [Indexed: 08/26/2024] Open
Abstract
The importance of the brain-heart interaction has been increasingly recognized as a critical physiological axis that is altered in disease. In this review, we explore the intricate relationship between the central nervous system and cardiovascular health, focusing particularly on immunological mechanisms that influence the course of both neurological and cardiovascular diseases. While previous studies have established a key role of the autonomic nervous system (ANS) in linking brain and the heart, more recent studies have expanded our understanding of the multifaceted inter-organ interactions. As such, circulating mediators include immune cells of the adaptive and innate immune system and their secreted immunogenic factors have come into the focus as mediators along this bidirectional communication. Hence, in this review we briefly discuss the contribution of the ANS and then focus on innate and adaptive immune mechanisms along the heart-to-brain and brain-to-heart axes, illustrating how cardiovascular diseases affect cognitive functions and how brain pathologies lead to cardiac complications.
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Affiliation(s)
- Alba Simats
- Department of Neuroscience and Experimental Therapeutics, Institute of Biomedical Research of Barcelona (IIBB), Spanish National Research Council (CSIC), c/Rosselló 161, 08036 Barcelona, Spain
| | - Hendrik B Sager
- DZHK (German Center for Cardiovascular Research), Partner site Munich Heart Alliance, Munich, Germany
- Department of Cardiology, German Heart Centre Munich, Technical University of Munich, Munich, Germany
| | - Arthur Liesz
- Institute for Stroke and Dementia Research (ISD), University Medical Center Munich, Feodor-Lynen-Straße 17, 81377 Munich, Germany
- Munich Cluster for Systems Neurology (SyNergy), Feodor-Lynen-Str. 17, 81377 Munich, Germany
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Bird F, Wilson M, Aziz S, Shebl M, Pickard A, Sims D, Grier G, Lockey D, Davenport R. The incidence and outcomes of hyperacute cardiovascular dysfunction following isolated traumatic brain injury: an observational cohort study. Int J Surg 2025; 111:2516-2524. [PMID: 39903519 DOI: 10.1097/js9.0000000000002266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 01/09/2025] [Indexed: 02/06/2025]
Abstract
BACKGROUND The relationship between early cardiovascular dysfunction (CVD) in isolated traumatic brain injury (iTBI) and outcome has not been fully described. We aimed to (1) determine the prevalence and phenotype of CVD after iTBI in the hyper-acute phase and (2) compare treatment and outcomes in those with CVD vs non-CVD. METHODS An observational cohort database study of severe iTBI patients (Head AIS 3+) at a level 1 trauma centre (2008-2019) and physician-led air ambulance service (2019-2020). CV dysfunction was defined as tachycardia or bradycardia, with hypotension. Physiology, laboratory results, 24-hour transfusion, and computer-topography (CT) findings were recorded. Outcomes were 28-day mortality and Glasgow Outcome Score (GOS). RESULTS A total of 168 patients met inclusion criteria, average age 46 years (IQR 30-61), 77% male, median ISS 25 (IQR 17-29) with 51% Head AIS 5. Time from injury to pre-hospital assessment was 31 minutes (IQR 20-42) with 20% demonstrating CVD on initial observations. The CVD group were more shocked (lactate 6.1 (1.7-10.9) vs. 2.4 (1.4-3.3), P < 0.001) and coagulopathic (43% vs. 15%, P = 0.001). There was no difference in Head AIS or CT findings between groups, except frequency of hypoxic ischemic encephalopathy (HIE) (CVD: 21% vs. non-CVD: 1%, P < 0.001). 24-hour transfusion was higher in CVD patients: 3 (0-8) vs. 0 (0-0) units, P < 0.001. Mortality was greater in CVD vs non-CVD iTBI (61% vs. 31%, P = 0.002), but in patients with AIS 5 there was no difference ( P = 0.262). One-third of CVD survivors (13/33) were discharged home, and 4/18 patients with recorded GOS had good neurological outcome. CONCLUSION One in five patients with severe iTBI develop early CVD, associated with increased mortality, coagulopathy, and HIE. However, mortality and neurological outcome is highly variable in those with CVD across the iTBI severity spectrum. Further research is needed to define the pathophysiology and optimal treatment to improve outcomes for this subgroup of iTBI.
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Affiliation(s)
- Flora Bird
- London's Air Ambulance, The Royal London Hospital, Barts NHS Trust, London, United Kingdom
| | - Mark Wilson
- Imperial College Healthcare NHS Trust, London, United Kingdom
| | - Shadman Aziz
- The Royal London Hospital, Barts NHS Trust, London, United Kingdom
| | - Moustafa Shebl
- Queen Elizabeth the Queen Mother Hospital. East Kent Hospitals University NHS Foundation Trust, Kent, United Kingdom
| | - Alexander Pickard
- St George's University Hospitals, NHS Foundation Trust, London, United Kingdom
| | - David Sims
- Kings College Hospital, London, United Kingdom
| | - Gareth Grier
- Queen Mary University London, London, United Kingdom
| | - David Lockey
- London's Air Ambulance, The Royal London Hospital, Barts NHS Trust, London, United Kingdom
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Fukushima K, Ogawa K, Kawai M, Yoshimura M. Effect of heart rate on B-type natriuretic peptide in sinus rhythm. Sci Rep 2024; 14:31711. [PMID: 39738157 PMCID: PMC11685466 DOI: 10.1038/s41598-024-81922-w] [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: 06/14/2024] [Accepted: 11/29/2024] [Indexed: 01/01/2025] Open
Abstract
B-type natriuretic peptide (BNP) levels accurately reflect the degree of cardiac overload in heart failure. Considering cardiac morphology and intracardiac pressure, including the left ventricular end-systolic volume index (LVESVI) and left ventricular end-diastolic volume index (LVEDVI), is essential for cardiac overload assessment. These indexes influence plasma BNP levels, and high heart rate is likely associated with cardiac morphology. However, the direct relationship between high heart rate and plasma BNP levels remains unknown. In this study, we simultaneously measured various hemodynamic parameters and plasma BNP levels during cardiac catheterization in 5,429 inpatients with sinus rhythm at our hospital. Furthermore, we examined how heart rate is associated with cardiac morphology, intracardiac pressure, and plasma BNP levels via regression analysis and structure equation modeling (SEM). Univariate regression analysis revealed a significant positive correlation between heart rate and log BNP. The path model with SEM revealed significant positive relations of heart rate and LVESVI with left ventricular end-diastolic pressure, in addition to a significant negative relation of heart rate and LVEDVI with log BNP. Collectively, these findings suggest no positive relation (rather, a negative relation) between heart rate and log BNP and that high heart rate is indirectly associated with increased plasma BNP levels by altering cardiac morphology and intracardiac pressure.
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Affiliation(s)
- Keisuke Fukushima
- Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
| | - Kazuo Ogawa
- Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Makoto Kawai
- Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Michihiro Yoshimura
- Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan
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Heidari A, Ghorbani M, Hassanzadeh S, Rahmanipour E. A review of the interplay between Takotsubo cardiomyopathy and adrenal insufficiency: Catecholamine surge and glucocorticoid deficiency. Prog Cardiovasc Dis 2024; 87:18-25. [PMID: 39389334 DOI: 10.1016/j.pcad.2024.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2024] [Accepted: 10/06/2024] [Indexed: 10/12/2024]
Abstract
BACKGROUND Takotsubo Cardiomyopathy (TCM) is a transient heart condition often precipitated by stress and characterized by atypical ventricular ballooning. The interplay between TCM and Adrenal Insufficiency (AI), particularly the influence of catecholamine excess and glucocorticoid deficiency on TCM's pathogenesis in individuals with AI, warrants comprehensive exploration for a better understanding of TCM pathophysiology and establishment of potential therapeutic strategies. METHODS We conducted an extensive literature search via PubMed and Google Scholar, targeting reports on AI, heart failure, and cardiomyopathy, supplemented by forward and backward citation tracing. We analyzed 46 cases from 45 reports, assessing the clinical presentation and outcomes in the context of AI categorization. RESULTS In patients with AI, a glucocorticoid deficit appears to exacerbate the myocardial vulnerability to catecholamine toxicity, precipitating TCM. Most conditions were reversible; however, three pre-1990 cases resulted in irreversible outcomes. CONCLUSIONS The investigation into the AI and TCM intersection highlights the pathogenic significance of catecholamines in the absence of glucocorticoids. The data consolidates the hypothesis that glucocorticoid scarcity exacerbates the cardiac susceptibility to catecholaminergic toxicity, potentially triggering TCM. The study affirms glucocorticoids' cardioprotective roles and elucidates how catecholamine surges contribute to TCM pathogenesis, suggesting strategic clinical management adjustments for AI patients to reduce TCM incidence.
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Affiliation(s)
- Afshin Heidari
- School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran; Health Policy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Mohammad Ghorbani
- Health Policy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Orthopedic Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sara Hassanzadeh
- School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran; Health Policy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Radiology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | - Elham Rahmanipour
- Health Policy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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Chiu YC, Katsura M, Takahashi K, Matsushima K, Demetriades D. Resuscitative endovascular balloon occlusion of the aorta (REBOA) in the presence of associated severe traumatic brain injury: A propensity-score matched study. Am J Surg 2024; 237:115798. [PMID: 38944625 DOI: 10.1016/j.amjsurg.2024.115798] [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: 05/12/2024] [Revised: 06/04/2024] [Accepted: 06/12/2024] [Indexed: 07/01/2024]
Abstract
BACKGROUND Experimental work suggested that resuscitative Endovascular Balloon Occlusion of the aorta (REBOA) preserves cerebral circulation in animal models of traumatic brain injury. No clinical work has evaluated the role of REBOA in the presence of associated severe traumatic brain injury (TBI). We investigated the impacts of REBOA on neurological and survival outcomes. METHODS Propensity-score matched study, using the American College of Surgeons Trauma Quality Improvement Program database. Patients with severe TBI patients (Abbreviated Injury Scale ≥3) receiving REBOA within 4 h from arrival were matched with similar patients not receiving REBOA. Neurological matching included head AIS, pupils, and midline shift. Clinical outcomes were compared between the two groups. RESULTS 434 REBOA patients were matched with 859 patients without REBOA. Patients in the REBOA group had higher rates of in-hospital mortality (63.6 % vs 44.2 %, p < 0.001), severe sepsis (4.4 % vs 2.2 %, p = 0.029), acute kidney injury (10.1 % vs 6.6 %, p = 0.029), and withdrawal of life support (25.4 % vs 19.6 %, p = 0.020) despite of lower craniectomy/craniotomy rate (7.1 % vs 12.7 %, p < 0.002). CONCLUSION In patients with severe TBI, REBOA use is associated with an increased risk of in-hospital mortality, AKI, and infectious complications.
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Affiliation(s)
- Yu Cheng Chiu
- Division of Acute Care Surgery, University of Southern California, Los Angeles, CA, USA; Department of General Surgery, Tri-Service General Hospital, Taiwan.
| | - Morihiro Katsura
- Division of Acute Care Surgery, University of Southern California, Los Angeles, CA, USA.
| | - Kyosuke Takahashi
- Division of Acute Care Surgery, University of Southern California, Los Angeles, CA, USA.
| | - Kazuhide Matsushima
- Division of Acute Care Surgery, University of Southern California, Los Angeles, CA, USA.
| | - Demetrios Demetriades
- Division of Acute Care Surgery, University of Southern California, Los Angeles, CA, USA.
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Schanche T, Han YS, Jensen CW, Arteaga GM, Tveita T, Sieck GC. β-adrenergic stimulation after rewarming does not mitigate hypothermia-induced contractile dysfunction in rat cardiomyocytes. Cryobiology 2024; 116:104927. [PMID: 38857777 DOI: 10.1016/j.cryobiol.2024.104927] [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: 01/09/2024] [Revised: 06/06/2024] [Accepted: 06/06/2024] [Indexed: 06/12/2024]
Abstract
Victims of severe accidental hypothermia are frequently treated with catecholamines to counteract the hemodynamic instability associated with hypothermia-induced cardiac contractile dysfunction. However, we previously reported that the inotropic effects of epinephrine are diminished after hypothermia and rewarming (H/R) in an intact animal model. Thus, the goal of this study was to investigate the effects of Epi treatment on excitation-contraction coupling in isolated rat cardiomyocytes after H/R. In adult male rats, cardiomyocytes isolated from the left ventricle were electrically stimulated at 0.5 Hz and evoked cytosolic [Ca2+] and contractile responses (sarcomere length shortening) were measured. In initial experiments, the effects of varying concentrations of epinephrine on evoked cytosolic [Ca2+] and contractile responses at 37 °C were measured. In a second series of experiments, cardiomyocytes were cooled from 37 °C to 15 °C, maintained at 15 °C for 2 h, then rewarmed to 37 °C (H/R protocol). Immediately after rewarming, the effects of epinephrine treatment on evoked cytosolic [Ca2+] and contractile responses of cardiomyocytes were determined. At 37 °C, epinephrine treatment increased both cytosolic [Ca2+] and contractile responses of cardiomyocytes in a concentration-dependent manner peaking at 25-50 nM. The evoked contractile response of cardiomyocytes after H/R was reduced while the cytosolic [Ca2+] response was slightly elevated. The diminished contractile response of cardiomyocytes after H/R was not mitigated by epinephrine (25 nM) and epinephrine treatment reduced the exponential time decay constant (Tau), but did not increase the cytosolic [Ca2+] response. We conclude that epinephrine treatment does not mitigate H/R-induced contractile dysfunction in cardiomyocytes.
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Affiliation(s)
- Torstein Schanche
- Department of Physiology & Biomedical Engineering, Mayo Clinic Rochester, MN, USA; Anesthesia and Critical Care Research Group, Department of Clinical Medicine, UiT, The Arctic University of Norway, 9037, Tromsø, Norway
| | - Young Soo Han
- Department of Physiology & Biomedical Engineering, Mayo Clinic Rochester, MN, USA
| | - Cole W Jensen
- Department of Physiology & Biomedical Engineering, Mayo Clinic Rochester, MN, USA
| | - Grace M Arteaga
- Department of Physiology & Biomedical Engineering, Mayo Clinic Rochester, MN, USA
| | - Torkjel Tveita
- Department of Physiology & Biomedical Engineering, Mayo Clinic Rochester, MN, USA; Anesthesia and Critical Care Research Group, Department of Clinical Medicine, UiT, The Arctic University of Norway, 9037, Tromsø, Norway; Division of Surgical Medicine and Intensive Care, University Hospital of North Norway, 9038, Tromsø, Norway
| | - Gary C Sieck
- Department of Physiology & Biomedical Engineering, Mayo Clinic Rochester, MN, USA.
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Underwood L, Jiang CS, Oh JY, Sato PY. Unheralded Adrenergic Receptor Signaling in Cellular Oxidative Stress and Death. CURRENT OPINION IN PHYSIOLOGY 2024; 40:100766. [PMID: 39070968 PMCID: PMC11271747 DOI: 10.1016/j.cophys.2024.100766] [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: 07/30/2024]
Abstract
Catecholamines (CAs) bind and activate adrenergic receptors (ARs), thus exuding a key role in cardiac adaptations to global physiological queues. Prolonged exposure to high levels of CAs promotes deleterious effects on the cardiovascular system, leading to organ dysfunction and heart failure (HF). In addition to the prominent role of ARs in inotropic and chronotropic responses, recent studies have delved into elucidating mechanisms contributing to CA toxicity and cell death. Central to this process is understanding the involvement of α1AR and βAR in cardiac remodeling and mechanisms of cellular survival. Here, we highlight the complexity of AR signaling and the fundamental need for a better understanding of its contribution to oxidative stress and cell death. This crucial informational nexus remains a barrier to the development of new therapeutic strategies for cardiovascular diseases.
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Affiliation(s)
- Lilly Underwood
- Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL
| | - Chun-Sun Jiang
- Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL
| | - Joo-Yeun Oh
- Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL
| | - Priscila Y Sato
- Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL
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Zulfaj E, Nejat A, Haamid A, Elmahdy A, Espinosa A, Redfors B, Omerovic E. Animal models of Takotsubo syndrome: bridging the gap to the human condition. Front Cardiovasc Med 2024; 11:1351587. [PMID: 38841261 PMCID: PMC11152046 DOI: 10.3389/fcvm.2024.1351587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Accepted: 03/18/2024] [Indexed: 06/07/2024] Open
Abstract
Modelling human diseases serves as a crucial tool to unveil underlying mechanisms and pathophysiology. Takotsubo syndrome (TS), an acute form of heart failure resembling myocardial infarction, manifests with reversible regional wall motion abnormalities (RWMA) of the ventricles. Despite its mortality and clinical similarity to myocardial infarction, TS aetiology remains elusive, with stress and catecholamines playing central roles. This review delves into current animal models of TS, aiming to assess their ability to replicate key clinical traits and identifying limitations. An in-depth evaluation of published animal models reveals a variation in the definition of TS among studies. We notice a substantial prevalence of catecholamine-induced models, particularly in rodents. While these models shed light on TS, there remains potential for refinement. Translational success in TS research hinges on models that align with human TS features and exhibit the key features, including transient RWMA. Animal models should be comprehensively evaluated regarding the various systemic changes of the applied trigger(s) for a proper interpretation. This review acts as a guide for researchers, advocating for stringent TS model standards and enhancing translational validity.
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Affiliation(s)
- Ermir Zulfaj
- Department of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg University, Gothenburg, Sweden
| | - AmirAli Nejat
- Department of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg University, Gothenburg, Sweden
| | - Abdulhussain Haamid
- Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Ahmed Elmahdy
- Department of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg University, Gothenburg, Sweden
| | - Aaron Espinosa
- Department of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg University, Gothenburg, Sweden
| | - Björn Redfors
- Department of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg University, Gothenburg, Sweden
- Core Facilities - Experimental Biomedicine, Sahlgrenska Academy, Gothenburg, Sweden
| | - Elmir Omerovic
- Department of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg University, Gothenburg, Sweden
- Core Facilities - Experimental Biomedicine, Sahlgrenska Academy, Gothenburg, Sweden
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Paulino ET. Development of the cardioprotective drugs class based on pathophysiology of myocardial infarction: A comprehensive review. Curr Probl Cardiol 2024; 49:102480. [PMID: 38395114 DOI: 10.1016/j.cpcardiol.2024.102480] [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: 02/20/2024] [Accepted: 02/20/2024] [Indexed: 02/25/2024]
Abstract
The cardiovascular system is mainly responsible for the transport of substances necessary to cellular metabolism. However, for the good performance of this function, there is need for adequate control of blood pressure levels of tissue perfusion and systemic arterial. Acute myocardial infarction is one of the complications of the cardiovascular system, that most affects the population around the world. This condition can be defined as a disease generated by an imbalance of oxygen concentrations used in cardiovascular metabolism, this change usually occurs because coronary occlusion, which prevents myocardial blood flow. The diagnosis is based on the set of clinical and laboratory investigations, which are in the release of cardiac enzyme biomarkers, cardiovascular and hemodynamic changes and cardiac accommodations. The treatment consists in the use of concomitant cardiovascular drugs, such as: antihypertensive, antiplatelet and hypolipidemic. Despite improvements in clinical and pharmacological management, acute myocardial infarction remains the leading cause of death worldwide. This finding encourages the scientific research of new drugs for the treatment of myocardial infarction or supporting therapies aimed at reducing the levels of deaths and comorbities generated by cardiovascular diseases.
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Affiliation(s)
- Emanuel Tenório Paulino
- Cardiovascular Pharmacology Laboratory, Institute of Pharmaceutical Sciences, Federal University of Alagoas, Av. Lourival Melo Mota, S/N. Postal Box Code: 57.072.900, Brazil.
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Petrák O, Krátká Z, Holaj R, Zítek M, Nguyen Nikrýnová T, Klímová J, Kološová B, Waldauf P, Michalský D, Novák K, Markvartová A, Zlatohlávek L, Grus T, Dušková J, Widimský J, Zelinka T. Cardiovascular Complications in Pheochromocytoma and Paraganglioma: Does Phenotype Matter? Hypertension 2024; 81:595-603. [PMID: 38152977 DOI: 10.1161/hypertensionaha.123.21902] [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: 08/10/2023] [Accepted: 12/10/2023] [Indexed: 12/29/2023]
Abstract
BACKGROUND Adrenaline-producing tumors are mostly characterized by a sudden release of catecholamines with episodic symptoms. Noradrenergic ones are usually less symptomatic and characterized by a continuous overproduction of catecholamines that are released into the bloodstream. Their effects on the cardiovascular system can thus be different. The aim of this study was to determine the prevalence of cardiovascular complications by catecholamine phenotype. METHODS We retrospectively analyzed data on the prevalence of cardiovascular events in 341 consecutive patients with pheochromocytoma and paraganglioma treated from 1995 to 2023. Biochemical catecholamine phenotype was determined based on plasma or urinary catecholamines and metanephrines. RESULTS According to the phenotype, 153 patients had noradrenergic pheochromocytoma and paraganglioma and 188 had adrenergic pheochromocytoma and paraganglioma. In the whole sample, the incidence of serious cardiovascular complications was 28% (95 patients), with no difference between the phenotypes or sexes. The noradrenergic phenotype had significantly more atherosclerotic complications (composite end point of type 1 myocardial infarction and symptomatic peripheral artery disease; odds ratio, 3.58 [95% CI, 1.59-8.83]; P=0.003), while the adrenergic phenotype more often had type 2 myocardial infarction and takotsubo-like cardiomyopathy (OR, 0.24 [95% CI, 0.09-0.57]; P=0.002). These changes remained even after adjustment for conventional risk factors of atherosclerosis. CONCLUSIONS We found a 28% incidence of cardiovascular complications in a consecutive group of patients with pheochromocytoma and paraganglioma. Patients presenting with a noradrenergic phenotype have a higher incidence of atherosclerotic complications, while the adrenergic phenotype is associated with a higher incidence of acute myocardial damage due to takotsubo-like cardiomyopathy.
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Affiliation(s)
- Ondřej Petrák
- 3rd Department of Internal Medicine, Endocrinology and Metabolism, 1st Faculty of Medicine (O.P., Z.K., R.H., M.Z., T.M.P.N.N., J.K., B.K., A.M., L.Z., J.W., T.Z.), Charles University and General University Hospital in Prague, Czech Republic
| | - Zuzana Krátká
- 3rd Department of Internal Medicine, Endocrinology and Metabolism, 1st Faculty of Medicine (O.P., Z.K., R.H., M.Z., T.M.P.N.N., J.K., B.K., A.M., L.Z., J.W., T.Z.), Charles University and General University Hospital in Prague, Czech Republic
| | - Robert Holaj
- 3rd Department of Internal Medicine, Endocrinology and Metabolism, 1st Faculty of Medicine (O.P., Z.K., R.H., M.Z., T.M.P.N.N., J.K., B.K., A.M., L.Z., J.W., T.Z.), Charles University and General University Hospital in Prague, Czech Republic
| | - Matěj Zítek
- 3rd Department of Internal Medicine, Endocrinology and Metabolism, 1st Faculty of Medicine (O.P., Z.K., R.H., M.Z., T.M.P.N.N., J.K., B.K., A.M., L.Z., J.W., T.Z.), Charles University and General University Hospital in Prague, Czech Republic
| | - Thi Nguyen Nikrýnová
- 3rd Department of Internal Medicine, Endocrinology and Metabolism, 1st Faculty of Medicine (O.P., Z.K., R.H., M.Z., T.M.P.N.N., J.K., B.K., A.M., L.Z., J.W., T.Z.), Charles University and General University Hospital in Prague, Czech Republic
| | - Judita Klímová
- 3rd Department of Internal Medicine, Endocrinology and Metabolism, 1st Faculty of Medicine (O.P., Z.K., R.H., M.Z., T.M.P.N.N., J.K., B.K., A.M., L.Z., J.W., T.Z.), Charles University and General University Hospital in Prague, Czech Republic
| | - Barbora Kološová
- 3rd Department of Internal Medicine, Endocrinology and Metabolism, 1st Faculty of Medicine (O.P., Z.K., R.H., M.Z., T.M.P.N.N., J.K., B.K., A.M., L.Z., J.W., T.Z.), Charles University and General University Hospital in Prague, Czech Republic
| | - Petr Waldauf
- Department of Anesthesiology, Third Faculty of Medicine, University Hospital Královské Vinohrady, Charles University, Czech Republic (P.W.)
| | - David Michalský
- Department of Urology, 1st Faculty of Medicine (D.M.), Charles University and General University Hospital in Prague, Czech Republic
| | - Květoslav Novák
- 1st Surgical Clinic, Thoracic, Abdominal and Injury Surgery, 1st Faculty of Medicine (K.N.), Charles University and General University Hospital in Prague, Czech Republic
| | - Alice Markvartová
- 3rd Department of Internal Medicine, Endocrinology and Metabolism, 1st Faculty of Medicine (O.P., Z.K., R.H., M.Z., T.M.P.N.N., J.K., B.K., A.M., L.Z., J.W., T.Z.), Charles University and General University Hospital in Prague, Czech Republic
| | - Lukáš Zlatohlávek
- 3rd Department of Internal Medicine, Endocrinology and Metabolism, 1st Faculty of Medicine (O.P., Z.K., R.H., M.Z., T.M.P.N.N., J.K., B.K., A.M., L.Z., J.W., T.Z.), Charles University and General University Hospital in Prague, Czech Republic
| | - Tomáš Grus
- 2nd Surgical Clinic, Cardiovascular Surgery, 1st Faculty of Medicine (T.G.), Charles University and General University Hospital in Prague, Czech Republic
| | - Jaroslava Dušková
- Institute of Pathology, 1st Faculty of Medicine (J.D.), Charles University and General University Hospital in Prague, Czech Republic
| | - Jiří Widimský
- 3rd Department of Internal Medicine, Endocrinology and Metabolism, 1st Faculty of Medicine (O.P., Z.K., R.H., M.Z., T.M.P.N.N., J.K., B.K., A.M., L.Z., J.W., T.Z.), Charles University and General University Hospital in Prague, Czech Republic
| | - Tomáš Zelinka
- 3rd Department of Internal Medicine, Endocrinology and Metabolism, 1st Faculty of Medicine (O.P., Z.K., R.H., M.Z., T.M.P.N.N., J.K., B.K., A.M., L.Z., J.W., T.Z.), Charles University and General University Hospital in Prague, Czech Republic
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Szabo B. Presynaptic Adrenoceptors. Handb Exp Pharmacol 2024; 285:185-245. [PMID: 38755350 DOI: 10.1007/164_2024_714] [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] [Indexed: 05/18/2024]
Abstract
Presynaptic α2-adrenoceptors are localized on axon terminals of many noradrenergic and non-noradrenergic neurons in the peripheral and central nervous systems. Their activation by exogenous agonists leads to inhibition of the exocytotic release of noradrenaline and other transmitters from the neurons. Most often, the α2A-receptor subtype is involved in this inhibition. The chain of molecular events between receptor occupation and inhibition of the exocytotic release of transmitters has been determined. Physiologically released endogenous noradrenaline elicits retrograde autoinhibition of its own release. Some clonidine-like α2-receptor agonists have been used to treat hypertension. Dexmedetomidine is used for prolonged sedation in the intensive care; It also has a strong analgesic effect. The α2-receptor antagonist mirtazapine increases the noradrenaline concentration in the synaptic cleft by interrupting physiological autoinhibion of release. It belongs to the most effective antidepressive drugs. β2-Adrenoceptors are also localized on axon terminals in the peripheral and central nervous systems. Their activation leads to enhanced transmitter release, however, they are not activated by endogenous adrenaline.
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MESH Headings
- Animals
- Humans
- Receptors, Adrenergic, alpha-2/metabolism
- Receptors, Adrenergic, alpha-2/drug effects
- Receptors, Adrenergic, alpha-2/physiology
- Presynaptic Terminals/drug effects
- Presynaptic Terminals/metabolism
- Adrenergic alpha-2 Receptor Agonists/pharmacology
- Receptors, Presynaptic/drug effects
- Receptors, Presynaptic/physiology
- Receptors, Presynaptic/metabolism
- Synaptic Transmission/drug effects
- Receptors, Adrenergic, beta-2/metabolism
- Receptors, Adrenergic, beta-2/drug effects
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Affiliation(s)
- Bela Szabo
- Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
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12
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Chen Y, Guo X, Zeng Y, Mo X, Hong S, He H, Li J, Steinmetz R, Liu Q. Ferroptosis contributes to catecholamine-induced cardiotoxicity and pathological remodeling. Free Radic Biol Med 2023; 207:227-238. [PMID: 37499888 PMCID: PMC10529955 DOI: 10.1016/j.freeradbiomed.2023.07.025] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 07/06/2023] [Accepted: 07/24/2023] [Indexed: 07/29/2023]
Abstract
High levels of circulating catecholamines cause cardiac injury, pathological remodeling, and heart failure, but the underlying mechanisms remain elusive. Here we provide both in vitro and in vivo evidence that excessive β-adrenergic stimulation induces ferroptosis in cardiomyocytes, revealing a novel mechanism for catecholamine-induced cardiotoxicity and remodeling. We found that isoproterenol, a synthetic catecholamine, promoted glutathione depletion and glutathione peroxidase 4 (GPX4) degradation in cardiomyocytes, leading to GPX4 inactivation and enhanced lipid peroxidation. Isoproterenol also promoted heme oxygenase 1 (HO-1) expression by downregulating the transcription suppressor BTB and CNC homology 1 (Bach1), leading to increased labile iron accumulation through heme degradation. Moreover, isoproterenol markedly induced the accumulation of free iron and lipid reactive oxygen species (ROS) in the mitochondria, while targeted inhibition of iron overload and ROS accumulation within mitochondria effectively inhibited ferroptosis in cardiomyocytes. Importantly, isoproterenol administration markedly induced ferroptosis in the myocardium in vivo, associated with elevated non-heme iron accumulation driven by HO-1 upregulation. Strikingly, blockade of ferroptosis with ferrostatin-1 or inhibition of HO-1 activity with zinc protoporphyrin (ZnPP) effectively alleviated cardiac necrosis, pathological remodeling, and heart failure induced by isoproterenol administration. Taken together, our results reveal that catecholamine stimulation primarily induces ferroptotic cell death in cardiomyocyte through GPX4 and Bach1-HO-1 dependent signaling pathways. Targeting ferroptosis may represent a novel therapeutic strategy for catecholamine overload-induced myocardial injury and heart failure.
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Affiliation(s)
- Yi Chen
- Department of Physiology and Biophysics, University of Washington, Seattle, WA, 98195, USA
| | - Xiaoyun Guo
- Department of Physiology and Biophysics, University of Washington, Seattle, WA, 98195, USA
| | - Yachang Zeng
- Department of Physiology and Biophysics, University of Washington, Seattle, WA, 98195, USA
| | - Xiaoliang Mo
- Department of Physiology and Biophysics, University of Washington, Seattle, WA, 98195, USA
| | - Siqi Hong
- Department of Physiology and Biophysics, University of Washington, Seattle, WA, 98195, USA
| | - Hui He
- Department of Physiology and Biophysics, University of Washington, Seattle, WA, 98195, USA
| | - Jing Li
- Department of Physiology and Biophysics, University of Washington, Seattle, WA, 98195, USA
| | - Rachel Steinmetz
- Department of Physiology and Biophysics, University of Washington, Seattle, WA, 98195, USA
| | - Qinghang Liu
- Department of Physiology and Biophysics, University of Washington, Seattle, WA, 98195, USA.
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13
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Jiang H, Fang T, Cheng Z. Mechanism of heart failure after myocardial infarction. J Int Med Res 2023; 51:3000605231202573. [PMID: 37818767 PMCID: PMC10566288 DOI: 10.1177/03000605231202573] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Accepted: 08/14/2023] [Indexed: 10/13/2023] Open
Abstract
Despite the widespread use of early revascularization and drugs to regulate the neuroendocrine system, the impact of such measures on alleviating the development of heart failure (HF) after myocardial infarction (MI) remains limited. Therefore, it is important to discuss the development of new therapeutic strategies to prevent or reverse HF after MI. This requires a better understanding of the potential mechanisms involved. HF after MI is the result of complex pathophysiological processes, with adverse ventricular remodeling playing a major role. Adverse ventricular remodeling refers to the heart's adaptation in terms of changes in ventricular size, shape, and function under the influence of various regulatory factors, including the mechanical, neurohormonal, and cardiac inflammatory immune environments; ischemia/reperfusion injury; energy metabolism; and genetic correlation factors. Additionally, unique right ventricular dysfunction can occur secondary to ischemic shock in the surviving myocardium. HF after MI may also be influenced by other factors. This review summarizes the main pathophysiological mechanisms of HF after MI and highlights sex-related differences in the prognosis of patients with acute MI. These findings provide new insights for guiding the development of targeted treatments to delay the progression of HF after MI and offering incremental benefits to existing therapies.
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Affiliation(s)
- Huaiyu Jiang
- Department of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tingting Fang
- Department of Cardiology, The Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China
| | - Zeyi Cheng
- Department of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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14
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Zhang Z, Guo X, Wang J, Wang S, Wang Y. A case report and literature review: pheochromocytoma-mediated takotsubo cardiomyopathy, which is similar to acute myocardial infarction. Front Cardiovasc Med 2023; 10:1194814. [PMID: 37424925 PMCID: PMC10327548 DOI: 10.3389/fcvm.2023.1194814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 06/12/2023] [Indexed: 07/11/2023] Open
Abstract
A 52-year-old Chinese woman was admitted to a cardiac intensive care unit (CCU) due to nausea, vomiting, and dyspnea, which began a day before her hospitalization. Metoprolol succinate and conventional treatment for acute myocardial infarction (AMI) were initially administered to the patient based on electrocardiogram (ECG) findings and elevated cardiac troponin I (cTnI). However, the following day, she developed aggravated nausea, vomiting, fever, sweating, a flushed face, a rapid heart rate, and a significant rise in blood pressure. Furthermore, ultrasonic cardiography (UCG) displayed takotsubo-like changes; nevertheless, ECG indicated inconsistent cTnI peaks with extensive infarction. After coronary computed tomography angiography (CTA) ruled out (AMI), and in conjunction with the uncommon findings, we strongly suspected that the patient had a secondary condition of pheochromocytoma-induced takotsubo cardiomyopathy (Pheo-TCM). In the meanwhile, the use of metoprolol succinate was promptly discontinued. This hypothesis was further supported by the subsequent plasma elevation of multiple catecholamines and contrast-enhanced computed tomography (CECT). After one month of treatment with high-dose Phenoxybenzamine in combination with metoprolol succinate, the patient met the criteria for surgical excision and successfully underwent the procedure. This case report demonstrated that pheochromocytoma could induce TCM and emphasized the significance of distinguishing it from AMI (in the context of beta-blocker usage and anticoagulant management).
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15
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Kuzmiszyn AK, Selli AL, Furuholmen M, Smaglyukova N, Kondratiev T, Fuskevåg OM, Sager G, Dietrichs ES. Moderate but not severe hypothermia increases intracellular cyclic AMP through preserved production and reduced elimination. Cryobiology 2023; 110:18-23. [PMID: 36649914 DOI: 10.1016/j.cryobiol.2023.01.005] [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: 11/10/2022] [Revised: 01/12/2023] [Accepted: 01/12/2023] [Indexed: 01/15/2023]
Abstract
Rewarming from accidental hypothermia could be complicated by acute cardiac dysfunction but providing supportive pharmacotherapy at low core temperatures is challenging. Several pharmacological strategies aim to improve cardiovascular function by increasing cAMP in cardiomyocytes as well as cAMP and cGMP levels in vascular smooth muscle, but it is not clear what effects temperature has on cellular elimination of cAMP and cGMP. We therefore studied the effects of differential temperatures from normothermia to deep hypothermia (37 °C-20 °C) on cAMP levels in embryonic H9c2 cardiac cells and elimination of cAMP and cGMP by PDE-enzymes and ABC-transporter proteins. Our experiments showed significant elevation of intracellular cAMP in H9c2-cells at 30 °C but not 20 °C. Elimination of both cAMP and cGMP through ABC transport-proteins and PDE-enzymes showed a temperature dependent reduction. Accordingly, the increased cardiomyocyte cAMP-levels during moderate hypothermia appears an effect of preserved production and reduced elimination at 30 °C. This correlates with earlier in vivo findings of a positive inotropic effect of moderate hypothermia.
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Affiliation(s)
- Adrina Kalasho Kuzmiszyn
- Experimental and Clinical Pharmacology, Department of Medical Biology, UiT - the Arctic University of Norway, Tromsø, Norway; Norwegian Air Ambulance Foundation, Research and Development Department, Oslo, Norway; Division of Surgical Medicine and Intensive Care, University Hospital of North Norway, Tromsø, Norway
| | - Anders Lund Selli
- Experimental and Clinical Pharmacology, Department of Medical Biology, UiT - the Arctic University of Norway, Tromsø, Norway
| | - Markus Furuholmen
- Experimental and Clinical Pharmacology, Department of Medical Biology, UiT - the Arctic University of Norway, Tromsø, Norway
| | - Natalia Smaglyukova
- Experimental and Clinical Pharmacology, Department of Medical Biology, UiT - the Arctic University of Norway, Tromsø, Norway
| | - Timofei Kondratiev
- Anesthesia and Critical Care Research Group, Department of Clinical Medicine, UiT - the Arctic University of Norway, Tromsø, Norway
| | - Ole-Martin Fuskevåg
- Department of Laboratory Medicine, Division of Diagnostic Services, University Hospital of North Norway, Tromsø, Norway
| | - Georg Sager
- Experimental and Clinical Pharmacology, Department of Medical Biology, UiT - the Arctic University of Norway, Tromsø, Norway
| | - Erik Sveberg Dietrichs
- Experimental and Clinical Pharmacology, Department of Medical Biology, UiT - the Arctic University of Norway, Tromsø, Norway; Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.
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16
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Alswailmi FK. A Cross Talk between the Endocannabinoid System and Different Systems Involved in the Pathogenesis of Hypertensive Retinopathy. Pharmaceuticals (Basel) 2023; 16:ph16030345. [PMID: 36986445 PMCID: PMC10058254 DOI: 10.3390/ph16030345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 02/14/2023] [Accepted: 02/16/2023] [Indexed: 02/26/2023] Open
Abstract
The prognosis of hypertension leads to organ damage by causing nephropathy, stroke, retinopathy, and cardiomegaly. Retinopathy and blood pressure have been extensively discussed in relation to catecholamines of the autonomic nervous system (ANS) and angiotensin II of the renin–angiotensin aldosterone system (RAAS) but very little research has been conducted on the role of the ECS in the regulation of retinopathy and blood pressure. The endocannabinoid system (ECS) is a unique system in the body that can be considered as a master regulator of body functions. It encompasses the endogenous production of its cannabinoids, its degrading enzymes, and functional receptors which innervate and perform various functions in different organs of the body. Hypertensive retinopathy pathologies arise normally due to oxidative stress, ischemia, endothelium dysfunction, inflammation, and an activated renin–angiotensin system (RAS) and catecholamine which are vasoconstrictors in their biological nature. The question arises of which system or agent counterbalances the vasoconstrictors effect of noradrenaline and angiotensin II (Ang II) in normal individuals? In this review article, we discuss the role of the ECS and its contribution to the pathogenesis of hypertensive retinopathy. This review article will also examine the involvement of the RAS and the ANS in the pathogenesis of hypertensive retinopathy and the crosstalk between these three systems in hypertensive retinopathy. This review will also explain that the ECS, which is a vasodilator in its action, either independently counteracts the effect produced with the vasoconstriction of the ANS and Ang II or blocks some of the common pathways shared by the ECS, ANS, and Ang II in the regulation of eye functions and blood pressure. This article concludes that persistent control of blood pressure and normal functions of the eye are maintained either by decreasing systemic catecholamine, ang II, or by upregulation of the ECS which results in the regression of retinopathy induced by hypertension.
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Affiliation(s)
- Farhan Khashim Alswailmi
- Department of Pharmacy Practice, College of Pharmacy, University of Hafr Al Batin, Hafr Al Batin 39524, Saudi Arabia
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17
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Hayashi T, Tiwary SK, Lim KRQ, Rocha-Resende C, Kovacs A, Weinheimer C, Mann DL. Refining the reproducibility of a murine model of stress-induced reversible cardiomyopathy. Am J Physiol Heart Circ Physiol 2023; 324:H229-H240. [PMID: 36563015 PMCID: PMC9886343 DOI: 10.1152/ajpheart.00684.2022] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 12/21/2022] [Accepted: 12/22/2022] [Indexed: 12/24/2022]
Abstract
Despite the many advantages of isoproterenol (Iso)-induced models of cardiomyopathy, the extant literature suggests that the reproducibility of the Iso-induced stress cardiomyopathy phenotype varies considerably depending on the dose of Iso used, the mode of administration of Iso (subcutaneous vs. intraperitoneal), and the species of the animal that is being studied. Recently, we have shown that a single injection of Iso into female C57BL/6J mice provokes transient myocardial injury that is characterized by a brisk release of troponin I within 1 h, as well as a self-limited myocardial inflammatory response that is associated with increased myocardial tissue edema, inferoapical regional left ventricular (LV) wall motion abnormalities, and a transient decrease in global LV function, which were completely recovered by day 7 after the Iso injection (i.e., stress-induced reversible cardiomyopathy). Here we expand upon this initial report in this model by demonstrating important sexually dimorphic differences in the response to Iso-induced tissue injury, the ensuing myocardial inflammatory response, and changes in LV structure and function. We also provide information with respect to enhancing the reproducibility in this model by optimizing animal welfare during the procedure. The acute Iso-induced myocardial injury model provides a low-cost, relatively high-throughput small-animal model that mimics human disease (e.g., Takotsubo cardiomyopathy). Given that the model can be performed in different genetic backgrounds, as well as different experimental conditions, the acute Iso injury model should provide the cardiovascular community with a valuable nonsurgical animal model for understanding the myocardial response to tissue injury.NEW & NOTEWORTHY The present study highlights the importance of sexual dimorphism with respect to isoproterenol injury, as well as the importance of animal handling and welfare to obtain reproducible results from investigator to investigator. Based on serial observations of animal recovery (locomotor activity and grooming behavior), troponin I release, and inflammation, we identified that the method used to restrain the mice for the intraperitoneal injection was the single greatest source of variability in this model.
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Affiliation(s)
- Tomohiro Hayashi
- Cardiovascular Division, Department of Medicine, Center for Cardiovascular Research, Washington University School of Medicine, Saint Louis, Missouri
| | - Sajal K Tiwary
- Cardiovascular Division, Department of Medicine, Center for Cardiovascular Research, Washington University School of Medicine, Saint Louis, Missouri
| | - Kenji Rowel Q Lim
- Cardiovascular Division, Department of Medicine, Center for Cardiovascular Research, Washington University School of Medicine, Saint Louis, Missouri
| | - Cibele Rocha-Resende
- Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Attila Kovacs
- Cardiovascular Division, Department of Medicine, Center for Cardiovascular Research, Washington University School of Medicine, Saint Louis, Missouri
| | - Carla Weinheimer
- Cardiovascular Division, Department of Medicine, Center for Cardiovascular Research, Washington University School of Medicine, Saint Louis, Missouri
| | - Douglas L Mann
- Cardiovascular Division, Department of Medicine, Center for Cardiovascular Research, Washington University School of Medicine, Saint Louis, Missouri
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18
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Relationships among norepinephrine levels, exercise capacity, and chronotropic responses in heart failure patients. Heart Fail Rev 2023; 28:35-45. [PMID: 35325323 DOI: 10.1007/s10741-022-10232-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/15/2022] [Indexed: 02/07/2023]
Abstract
In heart failure (HF) patients, the pathophysiological mechanisms of severe exercise intolerance and impaired exercise capacity are related to both central and peripheral abnormalities. The central abnormalities in HF patients include impaired cardiac function and chronotropic incompetence (CI). Indeed, CI, the inability to adequately increase heart rate (HR) from rest to exercise often exhibited by HF patients, is related to activation of the sympathetic nervous system (SNS) yielding a rise in circulating norepinephrine (NE). CI may result from downregulation of β-adrenergic receptors, β-blocker usage, high baseline HR, or due to a combination of factors. This paper discusses the role of elevated NE in altering chronotropic responses in HF patients and consequently resulting in impaired exercise capacity. We suggest that future research should focus on the potential treatment of CI with rate-adaptive pacing, using a sensor to measure physical activity, without inducing deleterious hormonal activation of the sympathetic system.
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19
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Xu X, Xu H, Zhang Z. Cerebral amyloid angiopathy-related cardiac injury: Focus on cardiac cell death. Front Cell Dev Biol 2023; 11:1156970. [PMID: 36910141 PMCID: PMC9998697 DOI: 10.3389/fcell.2023.1156970] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Accepted: 02/16/2023] [Indexed: 03/14/2023] Open
Abstract
Cerebral amyloid angiopathy (CAA) is a kind of disease in which amyloid β (Aβ) and other amyloid protein deposits in the cerebral cortex and the small blood vessels of the brain, causing cerebrovascular and brain parenchymal damage. CAA patients are often accompanied by cardiac injury, involving Aβ, tau and transthyroxine amyloid (ATTR). Aβ is the main injury factor of CAA, which can accelerate the formation of coronary artery atherosclerosis, aortic valve osteogenesis calcification and cardiomyocytes basophilic degeneration. In the early stage of CAA (pre-stroke), the accompanying locus coeruleus (LC) amyloidosis, vasculitis and circulating Aβ will induce first hit to the heart. When the CAA progresses to an advanced stage and causes a cerebral hemorrhage, the hemorrhage leads to autonomic nervous function disturbance, catecholamine surges, and systemic inflammation reaction, which can deal the second hit to the heart. Based on the brain-heart axis, CAA and its associated cardiac injury can create a vicious cycle that accelerates the progression of each other.
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Affiliation(s)
- Xiaofang Xu
- Department of Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Huikang Xu
- Department of Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Zhaocai Zhang
- Department of Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.,Key Laboratory of the Diagnosis and Treatment for Severe Trauma and Burn of Zhejiang Province, Hangzhou, China.,Zhejiang Province Clinical Research Center for Emergency and Critical care medicine, Hangzhou, China
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20
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Moreno KGT, de Almeida TL, Marques AAM, Donadel G, Lourenço ELB, de Almeida DAT, Gasparotto A. Evidence of the Cardioprotective Effects of Aloysia polystachya in Isoproterenol-Induced Myocardial Infarction in Rats. J Med Food 2023; 26:36-39. [PMID: 36637440 DOI: 10.1089/jmf.2022.0027] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Aloysia polystachya is a plant species that is widely used in Brazilian folk medicine for the treatment of different disorders that affect the cardiovascular system. The aim of the study was to investigate the cardioprotective effects of an ethanol-soluble fraction of A. polystachya (ESAP) on isoproterenol-induced myocardial infarction in rats. Different groups of rats (n = 8) were orally treated with ESAP (30, 100, and 300 mg/kg), carvedilol (10 mg/kg), or vehicle (filtered water; 1 mL/100 g) for 7 days. Naive rats received no treatment. On the morning of day 6, acute myocardial infarction was induced by the acute oral administration of isoproterenol (100 mg/kg). On the morning of day 8, all rats underwent electrocardiography and transthoracic echocardiography. Blood samples were then collected, and serum levels of creatine kinase-MB fraction (CK-MB) and cardiac troponin T (cTNT) were quantified. ESAP significantly reduced electrocardiographic changes, improved the ventricular ejection fraction, and reduced serum levels of CK-MB and cTNT in infarcted rats. The cardioprotective effects of ESAP could be exploited as an effective tool against isoproterenol-induced myocardial infarction in rats.
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Affiliation(s)
- Karyne Garcia Tafarelo Moreno
- Laboratory of Cardiovascular Pharmacology, Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, Brazil
| | - Thiago Lima de Almeida
- Laboratory of Cardiovascular Pharmacology, Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, Brazil
| | - Aline Aparecida Macedo Marques
- Laboratory of Cardiovascular Pharmacology, Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, Brazil
| | - Guilherme Donadel
- Laboratory of Pre-Clinical Research of Natural Products, Postgraduate Program in Animal Science with Emphasis on Bioactive Products, Paranaense University, Umuarama, Brazil
| | - Emerson Luiz Botelho Lourenço
- Laboratory of Pre-Clinical Research of Natural Products, Postgraduate Program in Animal Science with Emphasis on Bioactive Products, Paranaense University, Umuarama, Brazil
| | - Danielle Ayr Tavares de Almeida
- Laboratory of Cardiovascular Pharmacology, Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, Brazil
| | - Arquimedes Gasparotto
- Laboratory of Cardiovascular Pharmacology, Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, Brazil
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21
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Beres E, Babes K, Beres ZL, Botea M, Davidescu L. Effect of home non-invasive ventilation on left ventricular function and quality of life in patients with heart failure and central sleep apnea syndrome. BALNEO AND PRM RESEARCH JOURNAL 2022. [DOI: 10.12680/balneo.2022.520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Central Sleep Apnea Syndrome (CSAS) and Cheyne-Stokes breathing are prevalent in patients with heart failure with reduced ejection fraction (HFrEF). Positive respiratory pressure therapy (PAP) associated with drug therapy for heart failure can improve quality of life, although tolerance to PAP therapy can be difficult to achieve.
Materials and method: Patients for this prospective, mono-center, cohort study were selected from patients with chronic heart failure who present at the Sleep Laboratory of the Medical Clinic of Pneumology, Oradea who underwent polysomnography. 38 HFrEF and CSAS patients were included between January 2019 to December 2021 in the study, with an apnea-hypopnea index (AHI) >=15/hour of sleep. Echocardiographic hemodynamic parameters (left ventricular ejection fraction-LVEF, mitral regurgitation score), PAP compliance, and quality of life using the severe respiratory failure questionnaire (SRI) at the initiation of PAP and after 3 months were included.
Results: After 3 months of PAP therapy LVEF increased significantly (from 31.4% ±12.2to 38.0%±10.9, p=0.0181), AHI decreased (from 40.1±18.7 to 6.8±6.1 events/h, p<0.0001) and all the categories of SRI showed improvement with significant general score increase (from 57.0±15.1 to 66.6±16.9, p<0.0001).
Conclusion: The association of PAP therapy with drug therapy in patients with HFrEF and CSAS improves hemodynamic parameters and quality of life.
Keywords: Chronic heart failure, positive airway pressure therapy, central sleep apnea syndrome
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Affiliation(s)
| | | | | | - Mihai Botea
- University of Oradea, Emergency Medicine Department;
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22
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Cao X, Wei M, Tang M, Jian Z, Liu H, Yue X, Luo G, Sun C, Guo F. Acute Myocardial Infarction and Concomitant Acute Intracranial Hemorrhage: Clinical Characteristics and Outcomes. J Investig Med 2022; 70:1713-1719. [PMID: 35858702 PMCID: PMC9726952 DOI: 10.1136/jim-2022-002334] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/15/2022] [Indexed: 01/25/2023]
Abstract
This study aimed to evaluate the demographic and clinical characteristics, treatments and outcomes of concomitant acute myocardial infarction (AMI) and acute intracranial hemorrhage (ICH). All patients diagnosed with concomitant AMI and acute ICH admitted to our institution were included retrospectively. The patient demographics, clinical characteristics, neuroimaging and treatment approaches were analyzed, and the outcomes of interest included disability as defined by the modified Rankin Scale (mRS) score and all-cause mortality within 1 year of follow-up. Of a total of 4972 patients with AMI, 8 patients (0.2%) with concomitant acute ICH were recruited for the study, including ST-segment elevation myocardial infarction (STEMI, 5 cases) and non-STEMI (3 cases). New-onset acute ICH in 4 of the 5 patients (80%) occurred within 24 hours after the AMI event, and all these patients had a sudden decrease in the level of consciousness, with an average decrease of 4.6 on the Glasgow Coma Scale. All 5 out of 8 patients had irregular shapes and uncommon sites of hematoma presentation documented on CT scans. Unfortunately, 2 patients died from a progression of ICH within 1 week, and 2 of the 6 survivors had poor functional outcomes (mRS ≥3) at the 1-year follow-up. Concomitant acute ICH and AMI are rare complications displaying unique iconography. Acute ICH caused serious prejudice in AMI with higher mortality and poor functional outcomes, and cardiac catheterization without the administration of antithrombotic or antiplatelet agents was feasible for patients who had unstable hemodynamics or STEMI.
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Affiliation(s)
- Xiangqi Cao
- Department of Neurology, Xi'an Jiaotong University Medical College First Affiliated Hospital, Xi'an, Shaanxi, China
| | - Meng Wei
- Department of Neurology, Xi'an Jiaotong University Medical College First Affiliated Hospital, Xi'an, Shaanxi, China
| | - Manyun Tang
- Department of Cardiovascular Medicine, Xi'an Jiaotong University Medical College First Affiliated Hospital, Xi'an, Shaanxi, China
| | - Zhijie Jian
- Department of Medical Radiology, Xi'an Jiaotong University Medical College First Affiliated Hospital, Xi'an, Shaanxi, China
| | - Hui Liu
- Biobank, Xi'an Jiaotong University Medical College First Affiliated Hospital, Xi'an, Shaanxi, China
| | - Xin Yue
- Department of Cardiology, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Guogang Luo
- Department of Neurology, Xi'an Jiaotong University Medical College First Affiliated Hospital, Xi'an, Shaanxi, China
| | - Chaofeng Sun
- Department of Cardiovascular Medicine, Xi'an Jiaotong University Medical College First Affiliated Hospital, Xi'an, Shaanxi, China
| | - Fengwei Guo
- Department of Cardiovascular Medicine, Xi'an Jiaotong University Medical College First Affiliated Hospital, Xi'an, Shaanxi, China
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Kassab K, Soni R, Kassier A, Fischell TA. The Potential Role of Renal Denervation in the Management of Heart Failure. J Clin Med 2022; 11:jcm11144147. [PMID: 35887912 PMCID: PMC9324976 DOI: 10.3390/jcm11144147] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 07/14/2022] [Accepted: 07/15/2022] [Indexed: 12/10/2022] Open
Abstract
Sympathetic nervous system activation in patients with heart failure is one of the main pathophysiologic mechanisms associated with the worse outcomes. Pharmacotherapies targeting neurohormonal activation have been at the center of heart failure management. Despite the advancement of therapies and the available treatments, heart failure continues to have an overall poor prognosis. Renal denervation was originally developed to lower systemic blood pressure in patients with poorly controlled hypertension, by modulating sympathetic outflow. However, more recently, multiple studies have investigated the effect of renal denervation in heart failure patients with both preserved (HFpEF) and reduced ejection fractions (HFrEF). This paper provides an overview of the potential effect of renal denervation in altering the various pathophysiologic, sympathetically mediated pathways that contribute to heart failure, and reviews the literature that supports its future use in those patients.
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Affiliation(s)
- Kameel Kassab
- Division of Cardiology, Borgess Heart Institute, 1521 Gull Road, Kalamazoo, MI 49048, USA; (R.S.); (A.K.); (T.A.F.)
- Division of Cardiology, Michigan State University, Kalamazoo, MI 49048, USA
- Correspondence:
| | - Ronak Soni
- Division of Cardiology, Borgess Heart Institute, 1521 Gull Road, Kalamazoo, MI 49048, USA; (R.S.); (A.K.); (T.A.F.)
- Division of Cardiology, Michigan State University, Kalamazoo, MI 49048, USA
| | - Adnan Kassier
- Division of Cardiology, Borgess Heart Institute, 1521 Gull Road, Kalamazoo, MI 49048, USA; (R.S.); (A.K.); (T.A.F.)
- Division of Cardiology, Michigan State University, Kalamazoo, MI 49048, USA
| | - Tim A. Fischell
- Division of Cardiology, Borgess Heart Institute, 1521 Gull Road, Kalamazoo, MI 49048, USA; (R.S.); (A.K.); (T.A.F.)
- Division of Cardiology, Michigan State University, Kalamazoo, MI 49048, USA
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Tian P, Zhao X, Huang L, Feng J, Zhao L, Liang L, Huang B, Zhang Y, Zhang J. Prognostic value of high-sensitivity cardiac troponin I in patients with non-ischaemic heart failure: insights from China. ESC Heart Fail 2022; 9:3345-3357. [PMID: 35831235 DOI: 10.1002/ehf2.14065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 04/27/2022] [Accepted: 06/27/2022] [Indexed: 11/12/2022] Open
Abstract
AIMS Evidence of the prognostic value of high-sensitivity troponin in patients with non-ischaemic heart failure (NIHF) is scarce. This study aimed to assess the predictive value of high-sensitivity cardiac troponin I (hs-cTnI) in NIHF patients. METHODS Hs-cTnI was measured at baseline in 650 NIHF patients admitted to the Heart Failure Center. The prognostic value of hs-cTnI was assessed based on a well-established model (including age, sex, New York Heart Association class, left ventricular ejection fraction, haemoglobin, sodium, estimated glomerular filtration rate, diabetes mellitus, treatment with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, treatment with β-blockers, and NT-proBNP). RESULTS During a median follow-up of 1036 days, 163 patients died of various causes. In total, 46.92% of patients had high hs-cTnI (hs-cTnI >0.011 ng/ml). Over a 3-year follow-up, patients with high hs-cTnI (>0.011 ng/ml) had a 1.54 [95% confidence interval (95% CI) 1.11-2.15] fold higher all-cause mortality risk than those without. Increasing concertation of hs-cTnI was also associated with a 23.0% (95% CI 13-33%, per log2 increase) increment risk of all-cause mortality. The inclusion of hs-cTnI significantly improved the risk prediction and stratification of all-cause mortality (integrated discrimination improvement 1.58%, 95% CI 0.38-2.79%, absolute net reclassification improvement 23.41% 95% CI 4.52-44.49%, additive net reclassification improvement 27.8%, 95% CI 9.29-46.3%) of the well-established model. CONCLUSIONS Hs-cTnI provides significant prognostic value and could further remarkably improve risk stratification and prediction capabilities in NIHF patients.
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Affiliation(s)
- Pengchao Tian
- Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science, Peking Union Medical College, 10037, Beijing, China
| | - Xuemei Zhao
- Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science, Peking Union Medical College, 10037, Beijing, China
| | - Liyan Huang
- Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science, Peking Union Medical College, 10037, Beijing, China
| | - Jiayu Feng
- Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science, Peking Union Medical College, 10037, Beijing, China
| | - Lang Zhao
- Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science, Peking Union Medical College, 10037, Beijing, China
| | - Lin Liang
- Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science, Peking Union Medical College, 10037, Beijing, China
| | - Boping Huang
- Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science, Peking Union Medical College, 10037, Beijing, China
| | - Yuhui Zhang
- Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science, Peking Union Medical College, 10037, Beijing, China
| | - Jian Zhang
- Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science, Peking Union Medical College, 10037, Beijing, China.,Key Laboratory of Clinical Research for Cardiovascular Medications, National Health Committee, 10037, Beijing, China
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Cardioprotective Potential of Aqueous Extract of Fumaria indica on Isoproterenol-Induced Myocardial Infarction in SD Rats. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:2112956. [PMID: 35757502 PMCID: PMC9232377 DOI: 10.1155/2022/2112956] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 05/02/2022] [Accepted: 05/06/2022] [Indexed: 11/21/2022]
Abstract
Ischemic heart disease (IHD) treatments and preventions by using plant extract and its phytochemical constituents have achieved considerable attention globally due to its cardioprotective effects. This study is aimed at investigating the cardioprotective and vascular effects of Fumaria indica (F. indica) crude extract on isoproterenol- (ISO-) induced myocardial infarction (MI) in Sprague-Dawley (SD) rats. Rats treated with isoproterenol (85 mg/kg, s.c), administered. Twice at an interval of 24 h showed a significant ST-segment elevation in ECG, edema, and necrosis in histopathology and also in troponin I (cTnI), creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST). Pretreatment with F. indica (10, 30, and 100 mg/kg, p.o) for 21 days significantly reversed the effects of isoproterenol-induced ischemic changes in the ECG, levels of cTnI, CPK, LDH, and AST, and histopathological changes. In isolated rat atrial strips, F. indica induced negative chronotropic and inotropic effects which were not affected by pretreatment with atropine, excluding role of cardiac muscarinic receptors. Cumulative addition of the extract induced a vasorelaxant effect on phenylephrine-evoked contractions in isolated rat aortic rings, which remained unchanged when challenged with L-NAME, excluding role of endothelial NO. However, extract of F. indica concentration dependently reversed contractions evoked with high K+, indicating calcium entry blocking effect. In conclusion, the F. indica extract is a cardioprotective remedy that ameliorates the isoproterenol-induced cardiotoxic effects and reverses cardiac ischemia, and the calcium antagonistic effect might be of useful in the treatment of MI.
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Appiah D, Noamesi AT, Osaji J, Bolton C, Nwabuo CC, Ebong IA. The Association of Mental Health Disorders with Takotsubo Syndrome (Broken Heart Syndrome) Among Older Women. J Womens Health (Larchmt) 2022; 31:1334-1342. [PMID: 35244475 DOI: 10.1089/jwh.2021.0557] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Background: The prevalence of mental health disorders (MHD) and takotsubo syndrome (TS), also known as broken heart syndrome, is increasing and more common in older women. Mortality among persons with TS is comparable to that of persons with myocardial infarction. Although TS is poorly understood, it is thought to be precipitated by psychological stress. We examined the relationship between MHD and TS among elderly American women. Materials and Methods: Data consisted of 10.9 million hospitalizations among women aged ≥60 years recorded in the National Inpatient Sample from 2007 to 2015. International Classification of Diseases, Ninth Revision, codes were used to define TS, MHD, and other chronic conditions. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between MHD and TS. Results: The mean age of patients was 76 years, with 38% of them diagnosed with MHD. Over the 9-year period, the prevalence of TS hospitalizations increased by almost fourfold from 37.1/100,000 to 154.7/100,000, with a higher prevalence among patients with MHD. In multivariable adjusted models, MHD was associated with elevated odds of TS (OR = 1.25; 95% CI: 1.18-1.32), with the odds increasing with the frequency of MHD diagnosis. Among patients with one MHD, the odds of TS were significantly higher among those diagnosed with adjustment, anxiety, and mood disorders but lower among those with suicide ideations and personality disorders. Conclusions: The presence of MHD was associated with elevated odds of TS. Understanding underlying mechanisms linking MHD with TS will enhance MHD management.
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Affiliation(s)
- Duke Appiah
- Department of Public Health, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
| | - Anormeh T Noamesi
- Department of Public Health, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
| | - Joy Osaji
- Department of Public Health, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
| | - Coy Bolton
- Department of Public Health, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
| | - Chike C Nwabuo
- Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Imo A Ebong
- Department of Internal Medicine, Division of Cardiovascular Sciences, University of California, Davis, Sacramento, CA
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Abstract
Sleep disorders are prevalent in heart failure and include insomnia, poor sleep architecture, periodic limb movements and periodic breathing, and encompass both obstructive (OSA) and central sleep apnea (CSA). Polysomnographic studies show excess light sleep and poor sleep efficiency particularly in those with heart failure. Multiple studies of consecutive patients with heart failure show that about 50% of patients suffer from either OSA or CSA. While asleep, acute pathological consequences of apneas and hypopneas include altered blood gases, sleep fragmentation, and large negative swings in intrathoracic pressure. These pathological consequences are qualitatively similar in both types of sleep apnea, though worse in OSA than CSA. Sleep apnea results in oxidative stress, inflammation, and endothelial dysfunction, best documented in OSA. Multiple studies show that both OSA and CSA are associated with excess hospital readmissions and premature mortality. However, no randomized controlled trial (RCT) has been reported for OSA, but sensitivity analysis of two randomized controlled trials has concluded that use of positive airway pressure devices is associated with excess mortality in patients with heart failure and CSA. Phrenic nerve stimulation has shown improvement in sleep apnea events and daytime sleepiness; however, no randomized controlled trials have demonstrated improvement in survival in patients with heart failure. The correct identification and treatment of heart failure patients with sleep and breathing disorders could affect the long-term outcomes of these patients.
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Affiliation(s)
- Shahrokh Javaheri
- Division of Pulmonary and Sleep Medicine, Bethesda North Hospital, Cincinnati, OH, United States; Division of Pulmonary, Critical Care and Sleep Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States; Division of Cardiology, Ohio State University, Columbus, OH, United States.
| | - Robin Germany
- Division of Cardiovascular Disease, University of Oklahoma College of Medicine, Oklahoma City, OK, United States
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Giallauria F, Strisciuglio T, Cuomo G, Di Lorenzo A, D'Angelo A, Volpicelli M, Izzo R, Manzi MV, Barbato E, Morisco C. Exercise Training: The Holistic Approach in Cardiovascular Prevention. High Blood Press Cardiovasc Prev 2021; 28:561-577. [PMID: 34724167 PMCID: PMC8590648 DOI: 10.1007/s40292-021-00482-6] [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: 09/30/2021] [Accepted: 10/23/2021] [Indexed: 12/26/2022] Open
Abstract
Nowadays, there are robust clinical and pathophysiological evidence supporting the beneficial effects of physical activity on cardiovascular (CV) system. Thus, the physical activity is considered a key strategy for CV prevention. In fact, exercise training exerts favourable effects on all risk factors for CV diseases (i.e. essential hypertension, type 2 diabetes mellitus, hypercholesterolemia, obesity, metabolic syndrome, etc…). In addition, all training modalities such as the aerobic (continuous walking, jogging, cycling, etc.) or resistance exercise (weights), as well as the leisure-time physical activity (recreational walking, gardening, etc) prevent the development of the major CV risk factors, or delay the progression of target organ damage improving cardio-metabolic risk. Exercise training is also the core component of all cardiac rehabilitation programs that have demonstrated to improve the quality of life and to reduce morbidity in patients with CV diseases, mostly in patients with coronary artery diseases. Finally, it is still debated whether or not exercise training can influence the occurrence of atrial and ventricular arrhythmias. In this regard, there is some evidence that exercise training is protective predominantly for atrial arrhythmias, reducing the incidence of atrial fibrillation. In conclusion, the salutary effects evoked by physical acitvity are useful in primary and secondary CV prevention.
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Affiliation(s)
- Francesco Giallauria
- Department of Translational Medical Sciences, "Federico II" University of Naples, 80131, Naples, Italy
| | - Teresa Strisciuglio
- Department of Advanced Biomedical Sciences, "Federico II" University of Naples, 80131, Naples, Italy
| | - Gianluigi Cuomo
- Department of Translational Medical Sciences, "Federico II" University of Naples, 80131, Naples, Italy
| | - Anna Di Lorenzo
- Department of Translational Medical Sciences, "Federico II" University of Naples, 80131, Naples, Italy
| | - Andrea D'Angelo
- Department of Translational Medical Sciences, "Federico II" University of Naples, 80131, Naples, Italy
| | - Mario Volpicelli
- Department of Cardiology, "Santa Maria della Pietà" Hospital (ASL Napoli 3 Sud), 80035, Nola, NA, Italy
| | - Raffaele Izzo
- Department of Advanced Biomedical Sciences, "Federico II" University of Naples, 80131, Naples, Italy
| | - Maria Virginia Manzi
- Department of Advanced Biomedical Sciences, "Federico II" University of Naples, 80131, Naples, Italy
| | - Emanuele Barbato
- Department of Advanced Biomedical Sciences, "Federico II" University of Naples, 80131, Naples, Italy
| | - Carmine Morisco
- Department of Advanced Biomedical Sciences, "Federico II" University of Naples, 80131, Naples, Italy.
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Medina YAC, López Blanco PF, González Niño RA. Hawk´s Beak Form in Midventricular Takotsubo Syndrome: Two Case Reports from Latin America. Open Cardiovasc Med J 2021. [DOI: 10.2174/1874192402115010052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Takotsubo syndrome is a type of acute reversible heart failure that can involve a form of acute catecholaminergic myocardial stunning. This clinical entity shows a pattern of temporary left ventricular dysfunction in the absence of occlusion of any coronary artery. A midventricular type is a form of Takotsubo syndrome where the atypical morphological variant is Hawk’s beak. The prevalence of this type is estimated to be 10-15% in several series in Asian and Western countries (predominantly Caucasian patients). In Latin America, there are no studies reporting this type of presentation. Two cases are reported in women initially diagnosed with acute myocardial infarction with the finding of the atypical hawk's beak morphology of Takotsubo syndrome, confirmed by left ventriculography. One of them was followed up early, observing recovery in her ventricular function without structural compromise at the level of contractility and with a good response to the outpatient treatment proposed. As there is a low prevalence and few published reports, these 2 cases are presented to promote long-term studies and increase the information regarding the evolution and morbidity/mortality of this type of presentation compared with the classical form of the syndrome.
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Julian K, Prichard B, Raco J, Jain R, Jain R. A review of cardiac autonomics: from pathophysiology to therapy. Future Cardiol 2021; 18:125-133. [PMID: 34547917 DOI: 10.2217/fca-2021-0041] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
The effective management of cardiovascular diseases requires knowledge of intrinsic and extrinsic innervation of the heart and an understanding of how perturbations of said components affect cardiac function. The innate cardiac conduction system, which begins with cardiac pacemaker cells and terminates with subendocardial Purkinje fibers, is modulated by said systems. The intrinsic component of the cardiac autonomic nervous system, which remains incompletely elucidated, consists of intracardiac ganglia and interconnecting neurons that tightly regulate cardiac electrical activity. Extrinsic components of the autonomic nervous system, such as carotid baroreceptors and renin-angiotensin-aldosterone system, modulate sympathetic input to the heart through the stellate ganglion and parasympathetic input via the vagus nerve. There remains a need for additional therapies to treat conditions, such as advanced heart failure and refractory arrhythmias, and a better understanding of autonomics may be key to their development.
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Affiliation(s)
| | | | - Joseph Raco
- Department of Internal Medicine, Penn State Milton S Hershey Medical Center, Hershey, PA, USA
| | - Rahul Jain
- Indiana University School of Medicine, Indianapolis, IN, USA
| | - Rohit Jain
- Department of Internal Medicine, Penn State Milton S Hershey Medical Center, Hershey, PA, USA
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Kaier TE, Alaour B, Marber M. Cardiac troponin and defining myocardial infarction. Cardiovasc Res 2021; 117:2203-2215. [PMID: 33458742 PMCID: PMC8404461 DOI: 10.1093/cvr/cvaa331] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 09/12/2020] [Indexed: 12/19/2022] Open
Abstract
The 4th Universal Definition of Myocardial Infarction has stimulated considerable debate since its publication in 2018. The intention was to define the types of myocardial injury through the lens of their underpinning pathophysiology. In this review, we discuss how the 4th Universal Definition of Myocardial Infarction defines infarction and injury and the necessary pragmatic adjustments that appear in clinical guidelines to maximize triage of real-world patients.
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Affiliation(s)
- Thomas E Kaier
- King’s College London BHF Centre, The Rayne Institute, 4th Floor, Lambeth Wing, St Thomas’ Hospital, Westminster Bridge Road, London SE1 7EH, UK
| | - Bashir Alaour
- King’s College London BHF Centre, The Rayne Institute, 4th Floor, Lambeth Wing, St Thomas’ Hospital, Westminster Bridge Road, London SE1 7EH, UK
| | - Michael Marber
- King’s College London BHF Centre, The Rayne Institute, 4th Floor, Lambeth Wing, St Thomas’ Hospital, Westminster Bridge Road, London SE1 7EH, UK
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32
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Association of marital status with takotsubo syndrome (broken heart syndrome) among adults in the United States. World J Cardiol 2021. [DOI: 10.4330/wjc.v13.i8.341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Appiah D, Farias R, Helo D, Appiah L, Olokede OA, Nwabuo CC, Nair N. Association of marital status with takotsubo syndrome (broken heart syndrome) among adults in the United States. World J Cardiol 2021; 13:340-347. [PMID: 34589169 PMCID: PMC8436683 DOI: 10.4330/wjc.v13.i8.340] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 03/28/2021] [Accepted: 07/27/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The pathophysiology of takotsubo syndrome (TTS) is not well understood, however, it is often precipitated by psychological or physical stress. Marital status is related to emotional stress, but its associations with TTS are limited.
AIM To explored the potential association between marital status and TTS.
METHODS We conducted a case-control study using data on patients aged ≥ 40 years with marital status data in the National Hospital Discharge Survey (2006-2010). The International Classification of Diseases Ninth Revision codes were used to identify cases with TTS and other comorbid conditions. Each case was matched to 5 controls by age, sex, year of TTS diagnosis and bed size of hospital. Two sets of controls were selected: Acute myocardial infarction (AMI) controls and non-cardiovascular disease (CVD) controls. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association of marital status with TTS.
RESULTS The 59 patients with TTS who had information on marital status were matched to 295 controls with AMI and 295 non-CVD controls, resulting in a sample of 649 patients. The average age of cases was 69.7 ± 11 years with 90% being women and 88% reporting White race. In multivariable-adjusted models, compared to singles, patients who were married had lower odds of TTS (OR = 0.86, 95%CI: 0.79–0.93) while those who were widowed (OR = 1.14, 95%CI: 1.05–1.23) or divorced/separated (OR = 1.32, 95%CI: 1.21–1.45) had elevated odds for TTS when compared to non-CVD controls. Similar results were observed when cases were compared to controls with AMI.
CONCLUSION In this study, being married was associated with lower odds for TTS while being divorced/separated or widowed was related to elevated odds for TTS. These novel findings that underscore the potential importance of social factors like marital status in the development of TTS need confirmation in larger studies.
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Affiliation(s)
- Duke Appiah
- Department of Public Health, Texas Tech University Health Sciences Center, Lubbock, TX 79430, United States
| | - Rachel Farias
- Department of Public Health, Texas Tech University Health Sciences Center, Lubbock, TX 79430, United States
| | - Dena Helo
- Department of Public Health, Texas Tech University Health Sciences Center, Lubbock, TX 79430, United States
| | - Linda Appiah
- College of Education, Texas Tech University, Lubbock, TX 79409, United States
| | - Olugbenga A Olokede
- Department of Public Health, Texas Tech University Health Sciences Center, Lubbock, TX 79430, United States
| | - Chike C Nwabuo
- Division of Cardiology, Johns Hopkins University, Baltimore, MD 21218, United States
| | - Nandini Nair
- School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, United States
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Selli AL, Kuzmiszyn AK, Smaglyukova N, Kondratiev TV, Fuskevåg OM, Lyså RA, Ravna AW, Tveita T, Sager G, Dietrichs ES. Treatment of Cardiovascular Dysfunction With PDE5-Inhibitors - Temperature Dependent Effects on Transport and Metabolism of cAMP and cGMP. Front Physiol 2021; 12:695779. [PMID: 34393818 PMCID: PMC8361756 DOI: 10.3389/fphys.2021.695779] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 07/09/2021] [Indexed: 01/24/2023] Open
Abstract
Introduction Cardiovascular dysfunction is a potentially lethal complication of hypothermia. Due to a knowledge gap, pharmacological interventions are not recommended at core temperatures below 30°C. Yet, further cooling is induced in surgical procedures and survival of accidental hypothermia is reported after rewarming from below 15°C, advocating a need for evidence-based treatment guidelines. In vivo studies have proposed vasodilation and afterload reduction through arteriole smooth muscle cGMP-elevation as a favorable strategy to prevent cardiovascular dysfunction in hypothermia. Further development of treatment guidelines demand information about temperature-dependent changes in pharmacological effects of clinically relevant vasodilators. Materials and Methods Human phosphodiesterase-enzymes and inverted erythrocytes were utilized to evaluate how vasodilators sildenafil and vardenafil affected cellular efflux and enzymatic breakdown of cAMP and cGMP, at 37°C, 34°C, 32°C, 28°C, 24°C, and 20°C. The ability of both drugs to reach their cytosolic site of action was assessed at the same temperatures. IC50- and Ki-values were calculated from dose–response curves at all temperatures, to evaluate temperature-dependent effects of both drugs. Results Both drugs were able to reach the intracellular space at all hypothermic temperatures, with no reduction compared to normothermia. Sildenafil IC50 and Ki-values increased during hypothermia for enzymatic breakdown of both cAMP (IC50: 122 ± 18.9 μM at 37°C vs. 269 ± 14.7 μM at 20°C, p < 0.05) and cGMP (IC50: 0.009 ± 0.000 μM at 37°C vs. 0.024 ± 0.004 μM at 32°C, p < 0.05), while no significant changes were detected for vardenafil. Neither of the drugs showed significant hypothermia-induced changes in IC50 and Ki–values for inhibition of cellular cAMP and cGMP efflux. Conclusion Sildenafil and particularly vardenafil were ableto inhibit elimination of cGMP down to 20°C. As the cellular effects of these drugs can cause afterload reduction, they show potential in treating cardiovascular dysfunction during hypothermia. As in normothermia, both drugs showed higher selectivity for inhibition of cGMP-elimination than cAMP-elimination at low core temperatures, indicating that risk for cardiotoxic side effects is not increased by hypothermia.
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Affiliation(s)
- Anders L Selli
- Experimental and Clinical Pharmacology, Department of Medical Biology, UiT - The Arctic University of Norway, Tromsø, Norway
| | - Adrina K Kuzmiszyn
- Experimental and Clinical Pharmacology, Department of Medical Biology, UiT - The Arctic University of Norway, Tromsø, Norway.,Division of Surgical Medicine and Intensive Care, University Hospital of North Norway, Tromsø, Norway
| | - Natalia Smaglyukova
- Experimental and Clinical Pharmacology, Department of Medical Biology, UiT - The Arctic University of Norway, Tromsø, Norway
| | - Timofei V Kondratiev
- Anesthesia and Critical Care Research Group, Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway
| | - Ole-Martin Fuskevåg
- Department of Laboratory Medicine, Division of Diagnostic Services, University Hospital of North Norway, Tromsø, Norway
| | - Roy A Lyså
- Experimental and Clinical Pharmacology, Department of Medical Biology, UiT - The Arctic University of Norway, Tromsø, Norway
| | - Aina W Ravna
- Experimental and Clinical Pharmacology, Department of Medical Biology, UiT - The Arctic University of Norway, Tromsø, Norway
| | - Torkjel Tveita
- Division of Surgical Medicine and Intensive Care, University Hospital of North Norway, Tromsø, Norway.,Anesthesia and Critical Care Research Group, Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway
| | - Georg Sager
- Experimental and Clinical Pharmacology, Department of Medical Biology, UiT - The Arctic University of Norway, Tromsø, Norway
| | - Erik S Dietrichs
- Experimental and Clinical Pharmacology, Department of Medical Biology, UiT - The Arctic University of Norway, Tromsø, Norway.,Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway
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Changes in miR 21 and 23b expression in postnatal hypertrophic heart derived from gestational diabetes precede dilated cardiomyopathy. J Biosci 2021. [DOI: 10.1007/s12038-021-00201-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Effect of Renal Denervation on Cardiac Function and Inflammatory Factors in Heart Failure After Myocardial Infarction. J Cardiovasc Pharmacol 2021; 76:602-609. [PMID: 32868626 PMCID: PMC7641177 DOI: 10.1097/fjc.0000000000000899] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Supplemental Digital Content is Available in the Text. Heart failure (HF) affects around 100 million people and is a staggering burden for health care system worldwide. Rapid and sustained activation of inflammatory response is an important feature of HF after myocardial infarction. Sympathetic overactivation is also an important factor in the occurrence and progression of HF. The beneficial effect of renal denervation (RDN) has been demonstrated in HF. In the current study, we hypothesized that RDN improves cardiac function in HF canine models due to acute myocardial infarction (AMI) and reduced inflammation might be involved. Twenty-four beagles were randomized into the control (n = 8), HF (n = 8), and HF + RDN group (n = 8). The HF model after AMI was established by embolization the anterior descending distal artery with anhydrous ethanol in the HF and HF + RDN group. Bilateral renal artery ablation was performed in the HF + RDN group. Cardiac function, serum creatine kinase, creatine kinase-MB and NT-Pro BNP level, and expression of inflammation-related proteins in myocardial were examined. Because the paraventricular nucleus of the hypothalamus might be involved in inflammation-induced central neural excitation in HF and plays an important role in regulating extracellular fluid volume and sympathetic activity, expression of inflammation-related proteins in hypothalamus was also examined. AMI and post-AMI HF model was created successfully. Compared with the HF group, dogs in the HF + RDN group showed better cardiac function 4 weeks after AMI: lower left ventricular end-diastolic pressure, left ventricular end-diastolic dimension, and left ventricular end-systolic dimension and higher LEVF and left ventricular systolic pressure (P < 0.05 for all) were observed in the HF + RDN group. In addition, dogs in the HF + RDN group had slightly less ventricular fibrosis. Interestingly, RDN had lower expression of inflammation-related proteins including interleukin-6, tumor necrosis factors-α, nuclear factor κB, and monocyte chemotactic protein 1 (P < 0.05 for all) in both myocardial tissue and hypothalamus. RDN can improve cardiac function in dogs with HF after myocardial infarction. Our results suggested that RDN might affect cytokine-induced central neural excitation in HF and later affect sympathetic activity. Our results suggested a potential beneficial mechanism of RDN independent of mechanism involving renal afferent and efferent sympathetic nerves.
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Abstract
Neurohormones and inflammatory mediators have effects in both the heart and the peripheral vasculature. In patients with heart failure (HF), neurohormonal activation and increased levels of inflammatory mediators promote ventricular remodeling and development of HF, as well as vascular dysfunction and arterial stiffness. These processes may lead to a vicious cycle, whereby arterial stiffness perpetuates further ventricular remodeling leading to exacerbation of symptoms. Although significant advances have been made in the treatment of HF, currently available treatment strategies slow, but do not halt, this cycle. The current treatment for HF patients involves the inhibition of neurohormonal activation, which can reduce morbidity and mortality related to this condition. Beyond benefits associated with neurohormonal blockade, other strategies have focused on inhibition of inflammatory pathways implicated in the pathogenesis of HF. Unfortunately, attempts to target inflammation have not yet been successful to improve prognosis of HF. Further work is required to interrupt key maladaptive mechanisms involved in disease progression.
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Perez DM. Targeting Adrenergic Receptors in Metabolic Therapies for Heart Failure. Int J Mol Sci 2021; 22:5783. [PMID: 34071350 PMCID: PMC8198887 DOI: 10.3390/ijms22115783] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 05/20/2021] [Accepted: 05/22/2021] [Indexed: 12/14/2022] Open
Abstract
The heart has a reduced capacity to generate sufficient energy when failing, resulting in an energy-starved condition with diminished functions. Studies have identified numerous changes in metabolic pathways in the failing heart that result in reduced oxidation of both glucose and fatty acid substrates, defects in mitochondrial functions and oxidative phosphorylation, and inefficient substrate utilization for the ATP that is produced. Recent early-phase clinical studies indicate that inhibitors of fatty acid oxidation and antioxidants that target the mitochondria may improve heart function during failure by increasing compensatory glucose oxidation. Adrenergic receptors (α1 and β) are a key sympathetic nervous system regulator that controls cardiac function. β-AR blockers are an established treatment for heart failure and α1A-AR agonists have potential therapeutic benefit. Besides regulating inotropy and chronotropy, α1- and β-adrenergic receptors also regulate metabolic functions in the heart that underlie many cardiac benefits. This review will highlight recent studies that describe how adrenergic receptor-mediated metabolic pathways may be able to restore cardiac energetics to non-failing levels that may offer promising therapeutic strategies.
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Affiliation(s)
- Dianne M Perez
- The Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, USA
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Kuo MJ, Chou RH, Lu YW, Guo JY, Tsai YL, Wu CH, Huang PH, Lin SJ. Premorbid β1-selective (but not non-selective) β-blocker exposure reduces intensive care unit mortality among septic patients. J Intensive Care 2021; 9:40. [PMID: 33985572 PMCID: PMC8116825 DOI: 10.1186/s40560-021-00553-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Accepted: 04/30/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND β-blockers may protect against catecholaminergic myocardial injury in critically ill patients. Long-term β-blocker users are known to have lower lactate concentrations and favorable sepsis outcomes. However, the effects of β1-selective and nonselective β-blockers on sepsis outcomes have not been compared. This study was conducted to investigate the impacts of different β-blocker classes on the mortality rate in septic patients. METHODS We retrospectively screened 2678 patients admitted to the medical or surgical intensive care unit (ICU) between December 2015 and July 2017. Data from patients who met the Sepsis-3 criteria at ICU admission were included in the analysis. Premorbid β-blocker exposure was defined as the prescription of any β-blocker for at least 1 month. Bisoprolol, metoprolol, and atenolol were classified as β1-selective β-blockers, and others were classified as nonselective β-blockers. All patients were followed for 28 days or until death. RESULTS Among 1262 septic patients, 209 (16.6%) patients were long-term β-blocker users. Patients with premorbid β-blocker exposure had lower heart rates, initial lactate concentrations, and ICU mortality. After adjustment for disease severity, comorbidities, blood pressure, heart rate, and laboratory data, reduced ICU mortality was associated with premorbid β1-selective [adjusted hazard ratio, 0.40; 95% confidence interval (CI), 0.18-0.92; P = 0.030], but not non-selective β-blocker use. CONCLUSION Premorbid β1-selective, but not non-selective, β-blocker use was associated with improved mortality in septic patients. This finding supports the protective effect of β1-selective β-blockers in septic patients. Prospective studies are needed to confirm it.
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Affiliation(s)
- Ming-Jen Kuo
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ruey-Hsing Chou
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Department of Critical Care Medicine, Taipei Veterans General Hospital, 112, No. 201, Sec. 2, Shih-Pai Road, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ya-Wen Lu
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Jiun-Yu Guo
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yi-Lin Tsai
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Cheng-Hsueh Wu
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. .,Department of Critical Care Medicine, Taipei Veterans General Hospital, 112, No. 201, Sec. 2, Shih-Pai Road, Taipei, Taiwan.
| | - Po-Hsun Huang
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. .,Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan. .,Department of Critical Care Medicine, Taipei Veterans General Hospital, 112, No. 201, Sec. 2, Shih-Pai Road, Taipei, Taiwan. .,Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
| | - Shing-Jong Lin
- Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.,Taipei Heart Institute, Taipei Medical University, Taipei, Taiwan.,Division of Cardiology, Heart Center, Cheng-Hsin General Hospital, Taipei, Taiwan
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Shah MI, Ullah I, Xingjian X, Haipeng H, Rehman A, Zeeshan M, Alam Afridi FE. Modeling Trade Openness and Life Expectancy in China. Risk Manag Healthc Policy 2021; 14:1689-1701. [PMID: 33935523 PMCID: PMC8079350 DOI: 10.2147/rmhp.s298381] [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: 12/21/2020] [Accepted: 03/11/2021] [Indexed: 12/03/2022] Open
Abstract
Objective This study investigates life expectancy and trade openness in China for the period 1960–2018. Methods We purposed a theoretical model that is tested for China by applying regime-switching regression. Results Our findings suggest that trade openness increases life expectancy in China; trade affects life expectancy from two aspects; firstly, trade expansion and industrialization lead to high economic activities and resulted in raise the income of the people in society leading to improve life expectancy. Secondly, industrial expansion increases the CO2 emissions which leads to imposes a negative implication on human health and thus reduces life expectancy. Conclusion Thus, the net effect of trade liberalization depends on the value of income effect and volume of CO2 emissions. Therefore, the government needs to support the trade policies which causes a low level of CO2 emissions, the government may provide incentives to exports and industrialists to adopted green energy in the production process. Besides, the government may impose some regulations such as carbon tax to mitigate the CO2 emissions in society.
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Affiliation(s)
- Muhammad Imran Shah
- School of Mathematics and Statistics, Wuhan University, Wuhan, People's Republic of China
| | - Irfan Ullah
- Reading Academy, Nanjing University of Information Science and Technology, Nanjing, People's Republic of China
| | - Xiao Xingjian
- Reading Academy, Nanjing University of Information Science and Technology, Nanjing, People's Republic of China
| | - Huang Haipeng
- Reading Academy, Nanjing University of Information Science and Technology, Nanjing, People's Republic of China
| | - Alam Rehman
- Faculty of Management Sciences, National University of Modern Languages Islamabad, Islamabad, Pakistan
| | - Muhammad Zeeshan
- College of Business Administration, Liaoning Technical University, XingCheng, Liaoning Province, 125105, People's Republic of China
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Paterek A, Sochanowicz B, Oknińska M, Śmigielski W, Kruszewski M, Mackiewicz U, Mączewski M, Leszek P. Ivabradine prevents deleterious effects of dopamine therapy in heart failure: No role for HCN4 overexpression. Biomed Pharmacother 2021; 136:111250. [PMID: 33450487 DOI: 10.1016/j.biopha.2021.111250] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 12/27/2020] [Accepted: 01/03/2021] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Exacerbations of chronic heart failure (CHF) are often treated with catecholamines to provide short term inotropic support, but this strategy is associated with long-term detrimental hemodynamic effects and increased ventricular arrhythmias (VA), possibly related to increased heart rate (HR). We hypothesized that ivabradine may prevent adverse effects of short-term dopamine treatment in CHF. METHODS Rats with post-myocardial infarction CHF received 2-week infusion of saline, dopamine(D), ivabradine(I) or D&I; cardiac function was assessed using echocardiography and pressure-volume loops while VA were assessed using telemetric ECG recording. Expression of HCN4, a potentially proarrhythmic channel blocked by ivabradine, was assessed in left ventricular (LV) myocardium. HCN4 expression was also assessed in human explanted normal and failing hearts and correlated with VA. FINDINGS Dopamine infusion had detrimental effects on hemodynamic parameters and LV remodeling and induced VA in CHF rats, while ivabradine completely prevented these effects. CHF rats demonstrated HCN4 overexpression in LV myocardium, and ivabradine and, unexpectedly, dopamine prevented this. Failing human hearts also exhibited HCN4 overexpression in LV myocardium that was unrelated to patient's sex, CHF etiology, VA severity or plasma NT-proBNP. INTERPRETATION HR reduction offered by ivabradine may be a feasible strategy to extract benefits of inotropic support in CHF exacerbations, avoiding detrimental effects on CHF biology or VA. Ivabradine may offer additional beneficial effects in this setting, going beyond pure HR reduction, however prevention of ventricular HCN4 overexpression is unlikely to play a major role.
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Affiliation(s)
- Aleksandra Paterek
- Department of Clinical Physiology, Centre of Postgraduate Medical Education, Warsaw, Poland
| | - Barbara Sochanowicz
- Centre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Warsaw, Poland
| | - Marta Oknińska
- Department of Clinical Physiology, Centre of Postgraduate Medical Education, Warsaw, Poland
| | - Witold Śmigielski
- Department of Epidemiology, Cardiovascular Disease Prevention and Health Promotion, The Cardinal Stefan Wyszyński National Institute of Cardiology, Warsaw, Poland
| | - Marcin Kruszewski
- Centre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Warsaw, Poland; Department of Molecular Biology and Translational Research, Institute of Rural Health, Lublin, Poland; Department of Medical Biology and Translational Research, Faculty of Medicine, University of Information Technology and Management, Rzeszów, Poland
| | - Urszula Mackiewicz
- Department of Clinical Physiology, Centre of Postgraduate Medical Education, Warsaw, Poland
| | - Michał Mączewski
- Department of Clinical Physiology, Centre of Postgraduate Medical Education, Warsaw, Poland.
| | - Przemysław Leszek
- Department of Heart Failure and Transplantology, The Cardinal Stefan Wyszyński National Institute of Cardiology, Warsaw, Poland
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Lymperopoulos A, Cora N, Maning J, Brill AR, Sizova A. Signaling and function of cardiac autonomic nervous system receptors: Insights from the GPCR signalling universe. FEBS J 2021; 288:2645-2659. [PMID: 33599081 DOI: 10.1111/febs.15771] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 02/02/2021] [Accepted: 02/16/2021] [Indexed: 12/16/2022]
Abstract
The two branches of the autonomic nervous system (ANS), adrenergic and cholinergic, exert a multitude of effects on the human myocardium thanks to the activation of distinct G protein-coupled receptors (GPCRs) expressed on the plasma membranes of cardiac myocytes, cardiac fibroblasts, and coronary vascular endothelial cells. Norepinephrine (NE)/epinephrine (Epi) and acetylcholine (ACh) are released from cardiac ANS terminals and mediate the biological actions of the ANS on the heart via stimulation of cardiac adrenergic or muscarinic receptors, respectively. In addition, several other neurotransmitters/hormones act as facilitators of ANS neurotransmission in the heart, taking part in the so-called nonadrenergic noncholinergic (NANC) part of the ANS's control of cardiac function. These NANC mediators also use several different cell membrane-residing GPCRs to exert their effects in the myocardium. Cardiac ANS dysfunction and an imbalance between the activities of its two branches underlie a variety of cardiovascular diseases, from heart failure and hypertension to coronary artery disease, myocardial ischemia, and arrhythmias. In this review, we present the main well-established signaling modalities used by cardiac autonomic GPCRs, including receptors for salient NANC mediators, and we also highlight the latest developments pertaining to cardiac cell type-specific signal transduction, resulting in cell type-specific cardiac effects of each of these autonomic receptors.
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Affiliation(s)
- Anastasios Lymperopoulos
- Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences, Nova Southeastern University, Fort Lauderdale, FL, USA
| | - Natalie Cora
- Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences, Nova Southeastern University, Fort Lauderdale, FL, USA
| | - Jennifer Maning
- Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences, Nova Southeastern University, Fort Lauderdale, FL, USA
| | - Ava R Brill
- Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences, Nova Southeastern University, Fort Lauderdale, FL, USA
| | - Anastasiya Sizova
- Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences, Nova Southeastern University, Fort Lauderdale, FL, USA
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Waheed MA, Khalid M, Hashmi AT, Shani J, Malik B. Recurrent Takotsubo Cardiomyopathy Presenting With Anterior Wall ST-Elevation Myocardial Infarction. Cureus 2021; 13:e13458. [PMID: 33777547 PMCID: PMC7984958 DOI: 10.7759/cureus.13458] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Takotsubo cardiomyopathy (TC) or stress cardiomyopathy with the presence of transient apical ballooning of the left ventricle in the absence of obstructive coronary artery disease. The recurrence of TC is extremely rare, with an annual recurrence risk of 1.5% and approximately 5% recurrence risk after six years. We present a case of a patient with a history of TC who presented with chest pain and ST-segment elevation in her electrocardiogram and was found to have normal coronaries and diagnosed with recurrent TC.
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Affiliation(s)
- Maham A Waheed
- Department of Internal Medicine, Maimonides Medical Center, Brooklyn, USA
| | - Mazin Khalid
- Department of Cardiology, Maimonides Medical Center, Brooklyn, USA
| | | | - Jacob Shani
- Department of Cardiology, Maimonides Medical Center, Brooklyn, USA
| | - Bilal Malik
- Department of Cardiology, Maimonides Medical Center, Brooklyn, USA
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Rodriguez EA, Yamamoto BK. Toxic Effects of Methamphetamine on Perivascular Health: Co-morbid Effects of Stress and Alcohol Use Disorders. Curr Neuropharmacol 2021; 19:2092-2107. [PMID: 34344290 PMCID: PMC9185763 DOI: 10.2174/1570159x19666210803150023] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 07/09/2021] [Accepted: 07/19/2021] [Indexed: 12/04/2022] Open
Abstract
Methamphetamine (Meth) abuse presents a global problem and commonly occurs with stress and/or alcohol use disorders. Regardless, the biological causes and consequences of these comorbidities are unclear. Whereas the mechanisms of Meth, stress, and alcohol abuse have been examined individually and well-characterized, these processes overlap significantly and can impact the neural and peripheral consequences of Meth. This review focuses on the deleterious cardio- and cerebrovascular effects of Meth, stress, alcohol abuse, and their comorbid effects on the brain and periphery. Points of emphasis are on the composition of the blood-brain barrier and their effects on the heart and vasculature. The autonomic nervous system, inflammation, and oxidative stress are specifically highlighted as common mediators of the toxic consequences to vascular and perivascular health. A significant portion of the Meth abusing population also presents with stress and alcohol use disorders, prompting a need to understand the mechanisms underlying their comorbidities. Little is known about their possible convergent effects. Therefore, the purpose of this critical review is to identify shared mechanisms of Meth, chronic stress, and alcohol abuse that contributes to the dysfunction of vascular health and underscores the need for studies that directly address their interactions.
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Affiliation(s)
- Eric A. Rodriguez
- Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Bryan K. Yamamoto
- Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, USA
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Rachfalska N, Putowski Z, Krzych ŁJ. Distant Organ Damage in Acute Brain Injury. Brain Sci 2020; 10:E1019. [PMID: 33371363 PMCID: PMC7767338 DOI: 10.3390/brainsci10121019] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 12/15/2020] [Accepted: 12/18/2020] [Indexed: 02/07/2023] Open
Abstract
Acute brain injuries pose a great threat to global health, having significant impact on mortality and disability. Patients with acute brain injury may develop distant organ failure, even if no systemic diseases or infection is present. The severity of non-neurologic organs' dysfunction depends on the extremity of the insult to the brain. In this comprehensive review we sought to describe the organ-related consequences of acute brain injuries. The clinician should always be aware of the interplay between central nervous system and non-neurological organs, that is constantly present. Cerebral injury is not only a brain disease, but also affects the body as whole, and thus requires holistic therapeutical approach.
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Affiliation(s)
| | | | - Łukasz J. Krzych
- Department of Anaesthesiology and Intensive Care, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-055 Katowice, Poland; (N.R.); (Z.P.)
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Zhang J, Simpson PC, Jensen BC. Cardiac α1A-adrenergic receptors: emerging protective roles in cardiovascular diseases. Am J Physiol Heart Circ Physiol 2020; 320:H725-H733. [PMID: 33275531 DOI: 10.1152/ajpheart.00621.2020] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
α1-Adrenergic receptors (ARs) are catecholamine-activated G protein-coupled receptors (GPCRs) that are expressed in mouse and human myocardium and vasculature, and play essential roles in the regulation of cardiovascular physiology. Though α1-ARs are less abundant in the heart than β1-ARs, activation of cardiac α1-ARs results in important biologic processes such as hypertrophy, positive inotropy, ischemic preconditioning, and protection from cell death. Data from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) indicate that nonselectively blocking α1-ARs is associated with a twofold increase in adverse cardiac events, including heart failure and angina, suggesting that α1-AR activation might also be cardioprotective in humans. Mounting evidence implicates the α1A-AR subtype in these adaptive effects, including prevention and reversal of heart failure in animal models by α1A agonists. In this review, we summarize recent advances in our understanding of cardiac α1A-ARs.
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Affiliation(s)
- Jiandong Zhang
- McAllister Heart Institute, University of North Carolina, School of Medicine, Chapel Hill, North Carolina
| | - Paul C Simpson
- Department of Medicine and Research Service, San Francisco Veterans Affairs Medical Center and Cardiovascular Research Institute, University of California, San Francisco, California
| | - Brian C Jensen
- McAllister Heart Institute, University of North Carolina, School of Medicine, Chapel Hill, North Carolina
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The N-terminus of GPR37L1 is proteolytically processed by matrix metalloproteases. Sci Rep 2020; 10:19995. [PMID: 33203955 PMCID: PMC7673139 DOI: 10.1038/s41598-020-76384-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 10/22/2020] [Indexed: 12/11/2022] Open
Abstract
GPR37L1 is an orphan G protein-coupled receptor expressed exclusively in the brain and linked to seizures, neuroprotection and cardiovascular disease. Based upon the observation that fragments of the GPR37L1 N-terminus are found in human cerebrospinal fluid, we hypothesized that GPR37L1 was subject to post-translational modification. Heterologous expression of GPR37L1-eYFP in either HEK293 or U87 glioblastoma cells yielded two cell surface species of approximately equivalent abundance, the larger of which is N-glycosylated at Asn105. The smaller species is produced by matrix metalloprotease/ADAM-mediated proteolysis (shown by the use of pharmacological inhibitors) and has a molecular weight identical to that of a mutant lacking the entire N-terminus, Δ122 GPR37L1. Serial truncation of the N-terminus prevented GPR37L1 expression except when the entire N-terminus was removed, narrowing the predicted site of N-terminal proteolysis to residues 105–122. Using yeast expressing different G protein chimeras, we found that wild type GPR37L1, but not Δ122 GPR37L1, coupled constitutively to Gpa1/Gαs and Gpa1/Gα16 chimeras, in contrast to previous studies. We tested the peptides identified in cerebrospinal fluid as well as their putative newly-generated N-terminal ‘tethered’ counterparts in both wild type and Δ122 GPR37L1 Gpa1/Gαs strains but saw no effect, suggesting that GPR37L1 does not signal in a manner akin to the protease-activated receptor family. We also saw no evidence of receptor activation or regulation by the reported GPR37L1 ligand, prosaptide/TX14A. Finally, the proteolytically processed species predominated both in vivo and ex vivo in organotypic cerebellar slice preparations, suggesting that GPR37L1 is rapidly processed to a signaling-inactive form. Our data indicate that the function of GPR37L1 in vivo is tightly regulated by metalloprotease-dependent N-terminal cleavage.
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Mercurio I, Pellegrino A, Panata L, Filippucci F, Melai P, Gili A, Capano D, Troiano G, Rettagliata G, Lancia M, Bacci M. Toxicological findings in fatal intoxications from synthetic cathinones: a narrative review. AUST J FORENSIC SCI 2020. [DOI: 10.1080/00450618.2020.1841291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Affiliation(s)
- Isabella Mercurio
- Section of Legal Medicine, Forensic Science and Sports Medicine, University of Perugia, Perugia, Italy
| | | | - Laura Panata
- Section of Legal Medicine, Forensic Science and Sports Medicine, University of Perugia, Perugia, Italy
| | | | | | - Alessio Gili
- Department of Experimental Medicine, Hygiene and Public Health Section, University of Perugia, Perugia, Italy
| | | | | | - George Rettagliata
- Former Clinical Assistant Professor of Medicine at New York Medical College, New York, NY, USA
| | - Massimo Lancia
- Section of Legal Medicine, Forensic Science and Sports Medicine, University of Perugia, Perugia, Italy
| | - Mauro Bacci
- Section of Legal Medicine, Forensic Science and Sports Medicine, University of Perugia, Perugia, Italy
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Linganna RE, Leong RL, Yeom RS, Kopenitz J, Li RQ, Ram H, Dwarakanath S, Vasquez CR, Augoustides JGT. Takotsubo Cardiomyopathy-Navigating the Challenges of Diagnosis and Management in Heart Transplantation. J Cardiothorac Vasc Anesth 2020; 35:944-950. [PMID: 33262040 DOI: 10.1053/j.jvca.2020.10.054] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Accepted: 10/28/2020] [Indexed: 02/06/2023]
Affiliation(s)
- Regina E Linganna
- Department of Anesthesiology and Critical Care, Sidney Kimmel College of Medicine, Thomas Jefferson University, Philadelphia, PA
| | - Ron L Leong
- Department of Anesthesiology and Critical Care, Sidney Kimmel College of Medicine, Thomas Jefferson University, Philadelphia, PA
| | - Richard S Yeom
- Department of Anesthesiology and Critical Care, Sidney Kimmel College of Medicine, Thomas Jefferson University, Philadelphia, PA
| | - Jason Kopenitz
- Department of Anesthesiology and Critical Care, Sidney Kimmel College of Medicine, Thomas Jefferson University, Philadelphia, PA
| | - Rosie Q Li
- Cardiovascular and Thoracic Division, Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Harish Ram
- Department of Anesthesiology, School of Medicine, University of Kentucky, Lexington, KY
| | - Sanjay Dwarakanath
- Department of Anesthesiology, School of Medicine, University of Kentucky, Lexington, KY
| | - Charles R Vasquez
- Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - John G T Augoustides
- Cardiovascular and Thoracic Division, Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
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Abstract
OBJECTIVE To explore the epidemiology and outcomes of takotsubo cardiomyopathy in children. METHODS A retrospective analysis of the Healthcare Cost and Utilization 2012 and 2016 Kids' Inpatient Database was performed. Patients admitted with the diagnosis of takotsubo cardiomyopathy in the age group of 1 month-20 years were identified using International Classification of Diseases (ICD)-9 code 429.83 and ICD-10 code I51.81. RESULTS Among a total of 4,860,859 discharges, there were 153 with the diagnosis of takotsubo cardiomyopathy (3.1 per 100,000 discharges). Among patients with takotsubo cardiomyopathy, 55.0% were male, 62.4% were white, and 16.7% were black. Eighty-nine percent of patients were between 12 and 20 years. Psychiatric diagnosis was documented in 46% and substance use disorder in 36.2%. Sepsis was documented in 22.8% of patients. The median length of stay was 5 days (interquartile range: 2.7-15), and median total charges were $75,080 (interquartile range: 32,176-198,336). The overall mortality for takotsubo cardiomyopathy was 7%. On multivariable regression analysis, mortality was higher in the presence of anoxic injury (odds ratio = 34.42, 95% confidence interval: 4.85-320.11, p = 0.00). CONCLUSIONS Takotsubo cardiomyopathy is uncommon in children and carries a mortality rate of 7%. Most children with takotsubo cardiomyopathy are adolescent males, many of whom have psychiatric disorder or substance use disorder or both. Takotsubo cardiomyopathy should be considered in the differential diagnosis for patients who present with cardiac dysfunction and have underlying psychiatric disorders or drug abuse.
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