PATHOGENESIS AND PATHOPHYSIOLOGY OF EXPERIMENTAL CORONARY ARTERY SPASM

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Although coronary artery spasm has been documented in patients with variant angina pectoris, its pathogenesis or mechanism has been debated not only in clinical observations but also in experimental studies. The goal of this study was 1) to characterize the pathophysiology of coronary spasm in atherosclerotic animals, 2) to determine angiographically the role of hypercholesterolemia or intimal thickening (geometric effects) on histamine-induced coronary spasm and 3) to elucidate the mechanism of arterial hypercontraction in vitro without influences of neural, humoral and hemodynamic factors. Under anesthetized condition, the left coronary artery of Gottingen miniature pigs was denuded regionally by a balloon catheter except 5 pigs in which coronary spasm was provoked by an intracoronary administration of histamine without denudation (group 1). Thirty one pigs were allotted to two groups for 3 months; a group fed a 2% cholesterol diet (group 2) and a group fed a regular diet (group 3). … More Histamine-induced luminal narrowing of the coronary artery at the spastic site was 75 <-!+> 4, 78 <-!+> 3 and 74 <-!+> 4% in groups 1, 2 and 3 , respectively. Phenylephrine, indomethacin or thiothromboxane <A_2> did not enhance coronary narrowing at the site with histamine-hypersensitivity. The serum cholesterol level 3 months after denudation was 222 <-!+> 27 and 55 <-!+> 6mg/dl in groups 2 and 3, respectively (p<0.01 between groups). Percent luminal reduction produced by histamine was exponentially related to the degree of the intimal thickening (r=0.92), however, the contribution of the intimal thickening on coronary narrowing via geometric effect was small and was about 7 %. These hearts were isolated, and were perfused by Krebs-Henseleit solution. Coronary artery hyperconstriction was provoked in vitro by histamine dose-dependently at the same site of spasm in vivo. The degree of luminal reduction (%) was similar angiographically to that in vivo. Accordingly, the vessel with intimal thickening may accompany functional alterations of contractile properties to autacoids in an experimental coronary spasm of Gottingen miniature pigs. Less