Mechanisms Of Coronary Artery Spasm Research Articles

Mechanisms of Coronary Artery Spasm.

Recent clinical trials have highlighted that percutaneous coronary intervention in patients with stable angina provides limited additional benefits on top of optimal medical therapy. This has led to much more attention being paid to coronary vasomotion abnormalities regardless of obstructive or non-obstructive arterial segments. Coronary vasomotion is regulated by multiple mechanisms that include the endothelium, vascular smooth muscle cells (VSMCs), myocardial metabolic demand, autonomic nervous system and inflammation. Over the years, several animal models have been developed to explore the central mechanism of coronary artery spasm. This review summarises the landmark studies on the mechanisms of coronary vasospasm demonstrating the central role of Rho-kinase as a molecular switch of VSMC hypercontraction and the important role of coronary adventitial inflammation for Rho-kinase upregulation in VSMCs.

Identification of cell-biologic mechanisms of coronary artery spasm and its ex vivo diagnosis using peripheral blood-derived iPSCs

BackgroundAlthough vasospastic angina (VSA) is known to be caused by coronary artery spasm, no study has fully elucidated the exact underlying mechanism. Moreover, in order to confirm VSA, patients should undergo invasive coronary angiography with spasm provocation test. Herein, we investigated the pathophysiology of VSA using peripheral blood-derived induced pluripotent stem cells (iPSCs) and developed an ex vivo diagnostic method for VSA.Methods and resultsWith 10 mL of peripheral blood from patients with VSA, we generated iPSCs and differentiated these iPSCs into target cells. As compared with vascular smooth muscle cells (VSMCs) differentiated from iPSCs of normal subjects with negative provocation test, VSA patient-specific iPSCs-derived VSMCs showed very strong contraction in response to stimulants. Moreover, VSA patient-specific VSMCs exhibited a significant increase in stimulation-induced intracellular calcium efflux (Changes in the relative fluorescence unit [ΔF/F]; Control group vs. VSA group, 2.89 ± 0.34 vs. 10.32 ± 0.51, p < 0.01), and exclusively induced a secondary or tertiary peak of calcium efflux, suggesting that those findings could be diagnostic cut-off values for VSA. The observed hyperreactivity of VSA patient-specific VSMCs were caused by the upregulation of sarco/endoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) due to its enhanced small ubiquitin-related modifier (SUMO)ylation. This increased activity of SERCA2a was reversed by treatment with ginkgolic acid, an inhibitor of SUMOylated E1 molecules (pi/µg protein; VSA group vs. VSA + ginkgolic acid, 52.36 ± 0.71 vs. 31.93 ± 1.13, p < 0.01).ConclusionsOur findings showed that abnormal calcium handling in sarco/endoplasmic reticulum could be induced by the enhanced SERCA2a activity in patients with VSA, leading to spasm. Such novel mechanisms of coronary artery spasm could be useful for drug development and diagnosis of VSA.

Cellular Mechanisms of Coronary Artery Spasm.

Coronary artery spasm (CAS) is a reversible phenomenon caused by spontaneous excessive vascular smooth muscle contractility and vascular wall hypertonicity, which results in partial or complete closure of the lumen of normal or atherosclerotic coronary arteries. The clinical picture of CAS includes chest discomfort which is similar in quality to that of stable effort angina. Mechanisms underlying the development of CAS are still unclear. CAS certainly is a multifactorial disease. In this review, we paid attention to the role of the main pathophysiologic mechanisms in CAS: endothelial dysfunction, chronic inflammation, oxidative stress, smooth muscle hypercontractility, atherosclerosis and thrombosis, and mutations leading to deficient aldehyde dehydrogenase 2 (ALDH2) activity. These findings might shed novel insight on the underlying mechanisms and identify potential diagnostic and therapeutic targets for cardiovascular diseases in the future.

Vasospastic angina: pathophysiology and clinical significance

The review discusses an analysis of the literature on various aspects of the pathogenesis, diagnosis and treatment of vasospastic angina (VA). Data on the prevalence of coronary artery spasm (CAS) in various populations, as well as risk factors and triggers, are presented. We considered pathophysiological mechanisms of CAS, including hyperreactivity of coronary smooth muscle cells, endothelial dysfunction, nonspecific inflammation, oxidative stress, magnesium deficiency, autonomic imbalance, etc. The relationship of CAS with coronary atherosclerosis and thrombosis is emphasized. Modern recommendations for the diagnosis and treatment of VA are presented. Invasive verification of CAS is performed by pharmacological provocation tests with certain contraindications. Calcium antagonists and their combination with long-acting nitrates play a key role in the treatment of VA. Medications with a prospect for use in VA are Rho-kinase inhibitors, ATP-sensitive potassium channel activators, alpha-1 blockers. The management of patients with refractory VA and the prospects for endovascular treatment are discussed. It was noted that patients with multi-vessel VA are more likely to develop life-threatening arrhythmias and sudden death.

Vasospastic angina: pathophysiology and clinical significance

The review discusses an analysis of the literature on various aspects of the pathogenesis, diagnosis and treatment of vasospastic angina (VA). Data on the prevalence of coronary artery spasm (CAS) in various populations, as well as risk factors and triggers, are presented. We considered pathophysiological mechanisms of CAS, including hyperreactivity of coronary smooth muscle cells, endothelial dysfunction, nonspecific inflammation, oxidative stress, magnesium deficiency, autonomic imbalance, etc. The relationship of CAS with coronary atherosclerosis and thrombosis is emphasized. Modern recommendations for the diagnosis and treatment of VA are presented. Invasive verification of CAS is performed by pharmacological provocation tests with certain contraindications. Calcium antagonists and their combination with long-acting nitrates play a key role in the treatment of VA. Medications with a prospect for use in VA are Rho-kinase inhibitors, ATP-sensitive potassium channel activators, alpha-1 blockers. The management of patients with refractory VA and the prospects for endovascular treatment are discussed. It was noted that patients with multi-vessel VA are more likely to develop life-threatening arrhythmias and sudden death.

Research Progress and Forensic Application on the Pathogenesis of Coronary Artery Spasm

Coronary artery spasm （CAS） is a hyper-contraction of segmental coronary artery in response to multiple stimuli. At present, it's still in lack of specific diagnostic indicators of sudden cardiac death caused by CAS. This review summarizes current researches on the mechanisms of CAS and describes the roles of vascular endothelial dysfunction and vascular smooth muscle hypersensitivity in the course of CAS. Furthermore, the molecular mechanisms of the endogenous NO and endothelin-1 cause vascular endothelial dysfunction, and the phosphorylation of MLC2, Rho kinase and endoplasmic reticulum stress related to vascular smooth muscle hypersensitivity are discussed. Meanwhile, the possibility of forensic application for the related molecules on the diagnosis of sudden cardiac death caused by CAS are also explored.

ATVB Named Lecture Review-Insight Into Author: Hiroaki Shimokawa.

HomeArteriosclerosis, Thrombosis, and Vascular BiologyVol. 37, No. 5ATVB Named Lecture Review—Insight Into Author: Hiroaki Shimokawa Free AccessNewsPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessNewsPDF/EPUBATVB Named Lecture Review—Insight Into Author: Hiroaki Shimokawa Originally published1 May 2017https://doi.org/10.1161/ATV.0000000000000053Arteriosclerosis, Thrombosis, and Vascular Biology. 2017;37:780ATVB Named Lecture Reviews–Plenary LectureInsight Into the Author: Hiroaki Shimokawa, MD, PhD, Tohoku University Graduate School of Medicine, Sendai, JapanDownload figureDownload PowerPointWhy did you choose the profession of scientific investigation?I chose the profession of scientific investigation because I thought (and think) that science is one of the most creative and stimulating fields and that medical research is one of the most important activities among scientific investigations.Who have been your role model(s) in your scientific and professional life?(1) Professor Akira Takeshita, an emeritus professor of Kyushu University, who served as an Asian Associate Editor of ATVB and unfortunately passed away in 2009. I worked with him at the Kyushu University as an assistant professor (1991–1994) and then as an associate professor (1995–2005), when I studied molecular mechanisms of coronary artery spasm and arteriosclerosis with a special reference to Rho-kinase.(2) Professor Paul Vanhoutte, a professor and chairman of the University of Hong Kong. I worked in his laboratory at Mayo Clinic from 1985–1988, where I studied endothelial functions with a special reference to endothelium-derived relaxing factors.What have been important influences on your professional life?Interactions with young medical students, doctors (graduate students and postgraduate fellows), and staff in my department.What are your scientific inspirations?It is very stimulating and inspiring to elucidate unknown facts and to develop new diagnostic and therapeutic strategies, all of which are useful to advance medicine.How have mentors contributed to your professional development?Professor Vanhoutte taught me the pleasure of research where we can discover unknown facts and contribute to society. I have learned from Professor Takeshita about the importance of continuation of research despite any difficult situations.If you knew then what you know now, would you do anything different?No. I only could have been able to save some time, if any, even if I knew then what I know now.What wisdom do you impart on new investigators?Three points: (1) the theme of research should be original; (2) should have good mentors; and (3) should continue research despite any difficult situations (there always are good solutions to overcome them).If you were not a scientist, which profession would you pick?I would like to work for the country as a government official, like finance or diplomacy field.Which direction do you envisage your science taking?My research is directed to develop noninvasive diagnostic and therapeutic strategies to achieve a healthy society.What are your nonscientific activities?Reading books, music (classic), and sports.What sports do you follow?Football and baseball. I used to play football at high school and university.What are your favorite books, movies, music (pick one or all)?Ryotaro Shiba (Japanese novelist), human dramas (movies), and Beethoven (music).What are you favorite foods and are they heart healthy?Sushi and sashimi, definitely good for your heart!FootnotesThis Insight Into ATVB Authors was originally published as part of the ATVB Named Lecture Review series. The original article is available online at http://atvb.ahajournals.org/content/35/8/1756.full Previous Back to top Next FiguresReferencesRelatedDetails May 2017Vol 37, Issue 5 Advertisement Article InformationMetrics © 2017 American Heart Association, Inc.https://doi.org/10.1161/ATV.0000000000000053PMID: 28446471 Originally publishedMay 1, 2017 PDF download Advertisement

Response to Letter Regarding Article, “Mechanisms of Coronary Artery Spasm”

HomeCirculationVol. 125, No. 17Response to Letter Regarding Article, “Mechanisms of Coronary Artery Spasm” Free AccessReplyPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReplyPDF/EPUBResponse to Letter Regarding Article, “Mechanisms of Coronary Artery Spasm” Gaetano Antonio Lanza, MD, Giulia Careri, MD and Filippo Crea, MD Gaetano Antonio LanzaGaetano Antonio Lanza Department of Cardiovascular Medicine Catholic University of Sacred Heart Rome, Italy Search for more papers by this author , Giulia CareriGiulia Careri Department of Cardiovascular Medicine Catholic University of Sacred Heart Rome, Italy Search for more papers by this author and Filippo CreaFilippo Crea Department of Cardiovascular Medicine Catholic University of Sacred Heart Rome, Italy Search for more papers by this author Originally published1 May 2012https://doi.org/10.1161/CIRCULATIONAHA.112.098459Circulation. 2012;125:e633We very much appreciate the comments of Yasue et al on our review about coronary artery spasm (CAS).1 In our article, we questioned that endothelial dysfunction (ED) can by itself be the main pathophysiological substrate for CAS in the clinical setting for 2 main reasons: (1) the discrepancy between the high prevalence of ED and the low prevalence of vasospastic angina; (2) the lack of any significant relation between most cardiovascular risk factors (CVRFs) known to cause ED and CAS.In their letter, instead, Yasue et al propose that ED is the central abnormality in the mechanisms of CAS; specifically, they propose that smooth muscle cell (SMC) hyperreactivity, ultimately responsible for CAS, is caused by chronic ED.Yasue et al speculate that the reason why chronic ED does not frequently cause CAS in Western countries, despite its large diffusion, depends on the fact that the high prevalence of dyslipidemia in these populations also results in the frequent development of atherosclerotic coronary plaques, which would constitute an inadequate milieu for the development of SMC hyperreactivity. In contrast, in Japanese people, the low prevalence of dyslipidemia would result in a low prevalence of coronary plaques, whereas the high prevalence of smoking would induce a chronic ED that, in the absence of dyslipidemia-related coronary plaques, would result in SMC hyperreactivity and CAS.This hypothesis of a different phenotypic coronary manifestation of ED depending on specific CVRFs is intriguing. Epidemiological studies, however, showed that all CVRFs, including smoking, are associated both with ED and coronary atherosclerosis.2 Of note, a large number of patients do not develop coronary plaques despite the presence of CVRFs and ED. Accordingly, if chronic ED were the key factor for CAS in the absence of coronary plaques, it is not clear why, in this subset of subjects, smoking only shows a significant association with CAS, whereas other classical CVRFs (dyslipidemia, hypertension, and diabetes mellitus) do not.3In fact, the peculiar association of smoking with CAS rather suggests that, besides and beyond ED, and differently from other known CVRFs, smoking may have direct effects on SMCs resulting in SMC hyperreactivity, as suggested by in vitro experimental studies.4 Of note, the possibility to induce CAS by direct modifications of SMCs is confirmed by experimental models.5Importantly, the evidence of ED in patients with CAS deriving from the studies cited by Yasue et al, although showing an association between the 2 abnormal findings, does not prove a causal relation.Finally, we respectfully disagree with Yasue et al that CAS does not occur in the presence of atherosclerotic plaques. CAS in the early studies on vasospastic angina was indeed mainly described in patients with angiographically evident coronary atherosclerosis, and CAS inducibility at the level of atherosclerotic lesions has been reported in several studies.3In summary, although the notion that ED may favor CAS occurrence is shareable, we believe that current experimental, epidemiological, and clinical evidence suggests that endothelium-independent modifications of SMCs are responsible for SMC hyperreactivity and CAS in patients with vasospastic angina.Gaetano Antonio Lanza, MDGiulia Careri, MDFilippo Crea, MD Department of Cardiovascular Medicine Catholic University of Sacred Heart Rome, ItalyDisclosuresNone.

Letter by Yasue et al Regarding Article, “Mechanisms of Coronary Artery Spasm”

To the Editor: We welcome the appearance of the article “Mechanisms of Coronary Artery Spasm” by Lanza and colleagues in Circulation ,1 because coronary artery spasm (CAS) has been underestimated or even misunderstood in Western countries. However, we are concerned that their conclusion on the pathogenesis of CAS might lead to some misunderstandings. We think that it is a matter of course that hyperreactivity of smooth muscle cells, not impairment of endothelium itself, is responsible for CAS.1 The issue is what underlies smooth muscle cell hyperreactivity. We think that chronic endothelial injury or nitric oxide (NO) deficiency leads to coronary artery remodeling with resulting smooth muscle cell hyperplasia and hyperreactivity, thrombogenicity, oxidative stress, and chronic …

Mechanisms of Coronary Artery Spasm

The term coronary artery spasm (CAS) refers to a sudden, intense vasoconstriction of an epicardial coronary artery that causes vessel occlusion or near occlusion. Although CAS may be involved in other coronary syndromes, it represents the usual cause of variant angina. The variant form of angina was first described in 1959 by Prinzmetal et al,1 who used this term to indicate that angina attacks, unlike the most common form of effort angina, occurred at rest and were associated with ST-segment elevation, rather than ST-segment depression, on the ECG (Figure 1). Because myocardial ischemia occurred in the absence of any change in myocardial oxygen demand, the authors hypothesized that it was caused by an increased tonus of vessels at the level of coronary stenoses.1 Figure 1. (Top) ST-segment elevation in anterior leads, with reciprocal mild ST-segment depression in inferior leads and V6, during an angina attack in a patient with variant angina. (Bottom) Normalization of the ECG after spontaneous resolution of chest pain. Some years later, in fact, coronary angiography, performed during spontaneous angina attacks, demonstrated that CAS is the usual cause of variant angina.2–4 Coronary angiography also showed that CAS could occur at the site of a stenosis (either minor or severe) or in angiographically normal coronary arteries,5 usually at a localized segment of an epicardial artery (focal spasm) (Figure 2).6 However, sometimes CAS involves 2 or more segments of the same (multifocal spasm) or of different (multivessel spasm) epicardial coronary arteries, or may also involve diffusely one or multiple coronary branches.7 Figure 2. Occlusive spasm of the left circumflex coronary artery and near occlusive spasm of the left anterior descending coronary artery (arrows) during coronary angiography (left, top), associated with dramatic ST-segment elevation at monitoring ECG leads (left, bottom). Complete resolution of spasm (right, …

Recent Insights Into the Mechanisms of Vasospastic Angina

Coronary artery spasm plays an important role in the pathogenesis of many types of ischemic heart disease, not only in vasospastic angina but also in myocardial infarction and sudden death, particularly in the asian population. Patients with vasospastic angina are known to have defective endothelial function due to reduced nitric oxide bioavailability. Moreover, markers of oxidative stress and plasma levels of C-reactive protein are elevated. Smoking, polymorphysms of endothelial nitric oxide synthetase (eNOS), and low-grade inflammation have been regarded as the most important risk factors for vasospastic angina. The recent body of evidence indicates that RhoA and its down stream effector, ROCK/Rho-kinase, are associated with hypercontraction of vascular smooth muscle of the coronary artery and regulation of eNOS activity. Thus, endothelial dysfunction through abnormalities of eNOS and enhanced contractility of vascular smooth muscle in coronary artery segments are considered major mechanisms in vasospastic angina. However, the precise mechanisms for coronary vasospasm are not well understood. This article will review current understanding of the mechanism of coronary artery spasm.

Cellular and molecular mechanisms of coronary artery spasm: lessons from animal models.

Coronary artery spasm plays an important role in the pathogenesis of a wide variety of ischemic heart diseases, especially in the Japanese population. Because coronary artery spasm can be induced by a variety of stimuli with different mechanisms of action, the occurrence of the spasm appears to be due to the local hyperreactivity of the coronary artery rather than to an enhanced stimulation with a single mechanism of action. Several lines of evidence indicate that coronary artery spasm is caused primarily by smooth muscle hypercontraction whereas the contribution of endothelial dysfunction may be minimal. In order to elucidate the cellular and molecular mechanisms of the spasm, porcine models of the spasm were developed. In the first model with balloon injury and high-cholesterol feeding, a close topological correlation between the early atherosclerotic lesions and the spastic sites was noted, whereas in the second model with an inflammatory cytokine the potential importance of coronary inflammatory changes, especially at the adventitia, was noted. Subsequent studies in vivo and in vitro demonstrated that protein kinase C (PKC) and Rho-kinase are substantially involved in the intracellular mechanism of the spasm, resulting in increases in the mono- and diphosphorylations of myosin light chain (MLC). Furthermore, molecular biological analyses demonstrated that Rho-kinase is upregulated at the spastic site (at all levels, including mRNA, protein, and activity), resulting in the inhibition of MLC phosphatase through the phosphorylation of its myosin binding subunit and thereby causing the increase in MLC phosphorylations. Preliminary results also suggest that the long-term inhibition of Rho-kinase is effective in inhibiting the development of arteriosclerotic vascular lesions in several porcine models. Thus, Rho-kinase could be regarded as a novel therapeutic target for coronary arteriosclerosis in general and coronary artery spasm in particular.

Coronary artery spasm: a hypothesis on prevention by progesterone

The mechanism of coronary artery spasm has been hypothesized as follows: the dormant gene of the smooth muscle of the human coronary artery is identical or similar to the active gene of the smooth muscle of ductus arteriosus, but can be activated by estrogen. The activation could be preventable by progesterone. The prevention is due to the reduction of the number of estrogen receptors of the smooth muscle of the coronary artery.

Role of protein kinase C-mediated pathway in the pathogenesis of coronary artery spasm in a swine model.

The intracellular mechanism of coronary artery spasm is still unknown. The pathway mediated by protein kinase C (PKC) is an important intracellular process of various cellular responses, including vascular smooth muscle contraction. Thus, we examined the role of the PKC-mediated pathway in the pathogenesis of coronary artery spasm in our in vivo swine model. Seven Göttingen miniature pigs underwent coronary balloon injury and x-ray irradiation to induce atherosclerotic lesion. After 6 to 18 months, intracoronary serotonin (3 micrograms/kg) or histamine (3 micrograms/kg) repeatedly induced coronary artery spasm at the atherosclerotic site. At the spastic site, intracoronary administration of phorbol-12,13-dibutyrate (PDBu) (10(-9) mol/kg), a PKC-activating phorbol ester, also induced coronary artery spasm, which was completely blocked by pretreatment with intracoronary staurosporine (10 micrograms/kg), a PKC inhibitor. Intracoronary administration of an inactive phorbol ester, phorbol-12,13-didecanoate (10(-9) mol/kg), did not induce coronary vasoconstriction. Coronary artery spasm induced by the autacoids was significantly augmented by pretreatment with intracoronary PDBu and partially inhibited by staurosporine. Intracoronary administration of Bay K 8644 (10 micrograms/kg), a dihydropyridine-sensitive L-type calcium channel agonist, also induced coronary artery spasm at the spastic site, which was significantly inhibited by pretreatment with intracoronary staurosporine or nifedipine (0.1 mg/kg). These results suggest (1) the PKC-mediated pathway is importantly involved in the pathogenesis of coronary artery spasm, (2) activation of the PKC-mediated pathway partially accounts for serotonin- and histamine-induced coronary artery spasm, and (3) at the spastic site, calcium influx through dihydropyridine-sensitive L-type calcium channel and/or calcium sensitivity of the contractile proteins may be augmented by the PKC-mediated pathway.

Mechanisms of coronary artery spasm

Coronary artery spasm, the pathogenic mechanism most frequently observed in the syndrome of Prinzmetal's variant angina, appears to be caused by a local, nonspecific smooth muscle hyperreactivity. The relationship between coronary atherosclerosis, endothelial dysfunction, and coronary artery spasm is still speculative. Coronary artery spasm should be distinguished from other forms of coronary vasoconstriction, which may also play a role in angina pectoris. Occlusive coronary spasm causes complete interruption of coronary blood flow and may contribute to thrombus formation. Segmental coronary hyperreactivity may also be a component of acute coronary syndromes.

Mechanism of coronary artery spasm in atherosclerotic miniature swine

Mechanism of coronary artery spasm in atherosclerotic miniature swine

Significant role of alpha 2-adrenoceptors in coronary artery spasm.

Ergonovine, methoxamine and clonidine were administered intravenously in order to clarify the mechanism of coronary artery spasm in canine experiments. After these administrations, 27.5% of the dogs treated with ergonovine, 59.5% of the dogs treated with methoxamine and 72.7% of the dogs treated with clonidine showed ST segment elevation. The combined application of propranolol with ergonovine or methoxamine could more easily induce ST segment elevation than a single application of ergonovine or methoxamine. Most cases of elevated ST segment returned to the normal after the administration of nitroglycerin and phentolamine. Yohimbine was completely effective for the restoration of normal ST segment. Plasma norepinephrine decreased to 20 +/- 8.0% of the control when ST segment elevation was induced. This is a significantly greater decrease than that seen without ST segment elevation (p less than 0.001). Concomitant with the restoration of normal ST segment, plasma norepinephrine increased after the administration of yohimbine. Methoxamine and clonidine increased (p less than 0.01) and yohimbine decreased (p less than 0.01) coronary vascular resistance. Coronary spasm was visualized on coronary arteriogram after the application of clonidine; also coronary vasodilation was visualized after the administration of yohimbine. These results confirm the hypothesis that coronary artery spasm is mediated by pre- and postsynaptic alpha 2-adrenoceptors.

Cocaine and Acute Myocardial Infarction: A Probable Connection

Six young cocaine users, median age 35.5 years (range 27 to 44 years) experienced acute myocardial infarction. The close temporal correlation in two cases between cocaine use and clinical infarction and the relative paucity of atherosclerotic blockage of the coronary arteries in the others, as demonstrated by autopsy or angiography, suggest that cocaine, either by a mechanism of coronary artery spasm or by increased myocardial oxygen demand consequent to hypertension and tachycardia, is implicated in the precipitation of these infarctions.

Coronary artery spasm in the denervated transplanted human heart. A clue to underlying mechanisms : Buda AJ, Fowles RE, Schroeder JS, Hunt SA, Cipriano PR, Stinson EB, Harrison DC: Am J Med 1981; 70: 1144–1149

From the Division of Cardiology and Department of Cardiovascular Surgery, Stanford University School of Medicine, Stanford, California. This paper was supported in part by NIH Grant HL-21221 and the Ontario Heart Foundation (AJB). Requests for reprints should be addressed to Dr. Andrew J. Buda. Manuscript accepted June 11. 1980. * Present address: Division of Cardiology, Toronto Western Hospital. 399 Bathurst Street, Toronto, Ontario, M5T 2S8. Canada. The mechanism of coronary artery spasm has been poorly understood hut there has been some suggestion that cardiac autonomic innervation may play an important role. We report coronary artery spasm in a 43 year old man two years after he had received a transplant. Provocative pharmacologic testing suggested functional denervation of the patient’s heart. Thus, coronary artery spasm can occur in the transplanted, denervated human heart. Autonomic innervation of the heart is not essential in all cases of coronary spasm, and circulating catecholamines and/or metabolic or hormonal products may play an important role.

Coronary artery spasm in the denervated transplanted human heart: A clue to underlying mechanisms

The mechanism of coronary artery spasm has been poorly understood but there has been some suggestion that cardiac autonomic innervation may play an important role. We report coronary artery spasm in a 43 year old man two years after he had received a transplant. Provocative pharmacologic testing suggested functional denervation of the patient's heart. Thus, coronary artery spasm can occur in the transplanted, denervated human heart. Autonomic innervation of the heart is not essential in all cases of coronary spasm, and circulating catecholamines and/or metabolic or hormonal products may play an important role.