Cascade of Pathophysiological Events Leading to Spasm of Coronary Arteries

Abstract

Coronary spasm plays an important role in variant angina, effort angina, acute myocardial infarction, and/or sudden death [1–4]. Augmented responses of the coronary artery to vasotonic agents have been documented angiographically in patients with variant angina; however, the mechanisms of enhanced luminal narrowing remain unclarified, both clinically and experimentally. In order to elucidate factors involved in the enhanced responses of the coronary artery, we developed an animal model with the following features [5,6]: (1) transient changes in coronary diameter can be assessed angiographically, (2) coronary spasm can be repeatedly provoked, and (3) myocardial ischemia at the area distal to the site of the stenosed coronary artery can be documented. We chose Göttingen miniature swine as an animal model of coronary spasm [5], because (1) repeated examinations of coronary angiography and endothelial balloon-denudation were feasible using a catheterization technique and (2) pigs seem to be the most appropriate animal model for inducing atherosclerosis by changes which occur that closely resemble those seen in humans. We used mainly coronary arteriography for documentation of spastic events, because this technique is the only available tool for determining regional differences in vascular responsiveness to vasoactive substances in situ [6]. Regional intimai thickening along the left coronary artery was produced to mimic the diseased state of humans, this being the area in which the endothelial denudation had been one of procedures for inducing atherosclerotic lesions in experimental animals [7,8].

Experiments were done in the Research Institute of Angiocardiology and Cardiovascular Clinic, Faculty of Medicine, Kyushu University, Fukuoka, 812 Japan