Reflex constriction of significant coronary stenosis as a mechanism contributing to ischemic left ventricular dysfunction during isometric exercise.

Brown, B. Greg; Lee, A B; Bolson, Edward L.; Dodge, H.T.

doi:10.1161/01.cir.70.1.18

Cited by 216 publications

(66 citation statements)

References 50 publications

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Section: Exercise-induced Stenosis Constrictionmentioning

confidence: 82%

“…With respect to more recent findings on the predisposition of vessels with endothelial dysfunction and atherosclerosis to undergo ␣-adrenergic coronary vasoconstriction, stenosis constriction can be viewed as an extreme variant of this process. Isometric exercise (handgrip) decreased the angiographically determined minimal luminal area and induced angina in some patients, 45 an effect that was also elicited by combined propranolol and epinephrine, 44 supporting the ␣-adrenergic nature of the observed stenosis constriction.Stenosis constriction is also induced by dynamic exercise (supine bicycle) in patients with coronary artery disease and associated with angina in 2 of 3 patients studied. 25 The vasomotor nature of stenosis constriction during exercise is evidenced by its reversal with nitroglycerin, 25,45 but its ␣-adrenergic nature became evident only recently.…”

mentioning

confidence: 80%

“…25 The vasomotor nature of stenosis constriction during exercise is evidenced by its reversal with nitroglycerin, 25,45 but its ␣-adrenergic nature became evident only recently. In patients with coronary artery disease, intracoronary phentolamine, …”

Section: Exercise-induced Stenosis Constrictionmentioning

confidence: 99%

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α-Adrenergic Coronary Vasoconstriction and Myocardial Ischemia in Humans

et al. 2000

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Abstract-The use of quantitative coronary angiography, combined with Doppler and PET, has recently been directed at the study of ␣-adrenergic coronary vasomotion in humans. Confirming prior animal experiments, there is no evidence of ␣-adrenergic coronary constrictor tone at rest. Again confirming prior experiments, responses to ␣-adrenoceptor activation are augmented in the presence of coronary endothelial dysfunction and atherosclerosis, involving both ␣ 1 -and ␣ 2 -adrenoceptors in epicardial conduit arteries and microvessels. Such augmented ␣-adrenergic coronary constriction is observed during exercise and coronary interventions, and it is powerful enough to induce myocardial ischemia and limit myocardial function. Recent studies indicate a genetic determination of ␣ 2 -adrenergic coronary constriction. (Circulation. 2000;101:689-694.)Key Words: coronary disease Ⅲ ischemia Ⅲ microcirculation Ⅲ nervous system Ⅲ receptors, adrenergic, alpha U nder normal circumstances, small coronary arteries and arterioles with a diameter of Ͻ300 m are the principal determinants of coronary vascular resistance. 1 These vessels receive autonomic innervation, and their diameter is altered by activation of these nerves. 2 In animal experiments, there is little ␣-adrenergic coronary vasomotor tone at rest, and the increase in coronary blood flow during sympathetic activation is only somewhat blunted. When the coronary circulation, however, is impaired by hypercholesterolemia, 3 endothelial dysfunction, 4 exhaustion of autoregulation, 5 or severe coronary stenosis, 6,7 ␣-adrenergic vasoconstriction becomes unrestrained and powerful enough to reduce coronary blood flow and initiate myocardial ischemia. 8 Both ␣ 1 -and ␣ 2 -adrenoceptors mediate coronary vasoconstriction, and there is a gradient with ␣ 1 -adrenoceptors more predominant in larger vessels and a reverse gradient with ␣ 2 -adrenoceptors more predominant in the microcirculation. 5,9 Surprisingly, isolated coronary arterioles of a size that constricts in vivo to ␣ 1 -adrenoceptor activation are unresponsive in vitro, 10 and cardiomyocytes on ␣ 1 -adrenergic activation release endothelin, which causes arteriolar constriction. 11 In the past, the study of ␣-adrenergic coronary vasoconstriction in humans has been limited by a lack of adequate techniques to quantify coronary blood flow and myocardial perfusion. In the last decade, quantitative coronary angiography has allowed quantification of the diameter of coronary arteries to Ϸ0.5 mm. Study of the human coronary microcirculation is indirect 12 and relies on parameters such as coronary flow velocity, measured invasively with Doppler flow probes, or myocardial blood flow, quantified noninvasively with PET. 13 Recently, these techniques have become widely available and directed toward the study of ␣-adrenergic coronary vasoconstriction in humans. Moreover, selective ␣ 1 -and ␣ 2 -agonists and -antagonists are now available for clinical use. The antagonist approach is used to study the endogenous ␣-adrenergic coronary vasocon...

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Section: Exercise-induced Stenosis Constrictionmentioning

confidence: 82%

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confidence: 80%

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α-Adrenergic Coronary Vasoconstriction and Myocardial Ischemia in Humans

et al. 2000

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“…However, this percentage increases during high-flow states (e.g., exercise), especially if there is atherosclerotic narrowing of the artery. 15 Electrical stimulation of cardiac sympathetic nerves or intracoronary infusion of norepinephrine in a previously /3-blocked preparation results in an epicardial vasoconstriction that is about 65% of the increase in small vessel resistance. 16-20 Therefore the conclusion is that although epicardial arteries participate in adrenergic vasoconstriction, the dominant site of the resulting resistance change is in arterioles distal to the epicardial vessels, because the conduit vessels constitute a small fraction of the total resistance.…”

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confidence: 99%

“…70 Handgrip or supine bicycle ergometer exercise has been shown by angiography to result in an active constriction of stenotic segments of coronary arteries, which produces a dramatic increase in the flow resistance of the stenosis. 15 75 Another possible mechanism for the difference in response between normal arteries and diseased segments is that endothelial cell function may be impaired in atherosclerotic segments so that vasodilation mediated via endothelium-derived relaxing factor is blunted, thereby unmasking adrenergic vasoconstriction. 76 Cold pressor test.…”

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The paradox of adrenergic coronary vasoconstriction.

Feigl

1987

Circulation

129

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c Afn Official Journalof the 0American Heart cAssociation, Inc. RECENT OBSERVATIONS demonstrate adrenergic coronary vasoconstriction during exercise and other circumstances that result in generalized sympathetic activation. Coronary vasoconstriction seems paradoxic during tachycardia when coronary flow must increase to supply an augmented myocardial oxygen demand. However, there is evidence that adrenergic coronary vasoconstriction is beneficial in maintaining an even distribution of transmural blood flow. This essay will develop the theme that adrenergic coronary vasoconstriction is a normal part of generalized sympathetic activation and serves to help maintain a uniform transmural distribution of blood flow in the wall of the left ventricle. The experimental results from animal studies will be reviewed first, and the conclusions will then be used to interpret the findings from clinical studies of patients with angina.The physiologic basis of the concepts presented here has been extensively reviewed, and only a subset of the literature will be cited.'Experimental animal studies a-Receptor-mediated vasoconstriction. Electrical stimulation of sympathetic fibers that innervate the heart and coronary vessels results in tachycardia, increased myocardial contractility, and thus augmented myocardial oxygen consumption. The increased myocardial metabolism causes a secondary coronary vasodilation by a local mechanism. Paradoxically, there is a concomitant adrenergic coronary vasoconstrictor effect that limits the metabolic vasodilation and results in an augmented myocardial arteriovenous oxygen difference. Although the net effect of sympathetic activation is almost always an increase in coronary blood flow, the coronary vasoconstrictor effect retards the metabolic vasodilation by about 20% to 30%; hence, there is a coexisting coronary vasoconstriction while total 2 coronary flow is increasing.The cardiac chronotropic and inotropic effects of sympathetic activation are mediated via f8-receptors and can be blunted by fl-receptor-blocking agents. Thus it is possible to "unmask" sympathetic coronary vasoconstriction by prior fl-receptor blockade (since the vasoconstriction is mediated by a-receptors).' After fl-receptor blockade the usual response to sympathetic activation is a net decrease in coronary blood flow; hence, vasoconstriction is "unmasked."Intracoronary infusions of norepinephrine before and after fl-receptor blockade give results consistent with this interpretation of metabolic vasodilation secondary to myocardial fl-receptor activation and direct a-receptor-mediated vasoconstriction.4 Intracoronary infusion of selective a-receptor agonists such as phenylephrine also results in coronary vasoconstriction.5Thus, in the absence of fl-blockade, the interpretation is that a- Canine coronary vascular smooth muscle has ar-and a2-receptors and both subserve vasoconstriction.

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