Reactivity-based coronary vasospasm independent of atherosclerosis in rhesus monkeys

Kent Hermsmeyer, Koichi Miyagawa, Stephen T. Kelley, Josef Rösch, Arthur S. Hall, Michael K. Axthelm, Barry Greenberg

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Objectives. We studied the hypothesis that in the absence of vascular pathology, coronary artery vasospasm occurs as a result of local regions of vascular muscle hyperreactivity. We aimed to explore the basis for a functional etiology of those vasospasms not explained on a structural basis. Background. Ovariectomized rhesus monkeys (Macaca mulatta) without injury or significant vascular disease were stimulated with platelet release products, and angiograms were compared with those from vasospasms induced in human patients. Methods. We used intracoronary (IC) injections of serotonin, thromboxane A2 (U46619), endothelin I or angiotensin II in concentrations 3 to 10 times that which reduced coronary artery diameter by 50%. Results. Although no agent alone caused vasospasm, the combination of pathophysiologic concentrations of serotonin and the stable thromboxane A2 mimetic, U46619, injected through an IC catheter, synergistically caused coronary vasospasm on the second or third challenge in five of seven monkeys. These drug-induced vasospasms were similar to vasospasms induced by mechanical injury followed by serotonin, and to those stimulated in human IC diagnostic tests, as judged by onset, appearance, kinetics and vasodilator reversal. Conclusions. These studies in ovariectomized monkeys revealed that coronary vasospasm can be stimulated without preexisting vascular pathology, endothelial denudation or injury. Reproducible vasospasm of primate coronary arteries in response to these two endogenous pathophysiologic vasoconstrictors, which are thought to be precipitating stimuli in the etiology of vasospasm, suggests that structure-independent epicardial vasospasm can be an important element in serious cardiac ischemic events, particularly the focal, persistent vasospasms that occur without plaques or injury.

Original languageEnglish (US)
Pages (from-to)671-680
Number of pages10
JournalJournal of the American College of Cardiology
Volume29
Issue number3
DOIs
StatePublished - Mar 1 1997

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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