Leukotriene C₄- and D₄-induced diffuse peripheral constriction of swine coronary artery accompanied by ST elevation on the electrocardiogram: Angiographic analysis

Effects of leukotriene (LT) C₄ and LTD₄ on coronary artery spasm in atherosclerotic miniature pigs were examined angiographically. Endothelial balloon denudation of the left circumflex coronary artery was performed in 15 Gottingen miniature pigs; 11 were fed a 2% cholesterol diet and four were fed a regular diet for 3 months. Three months after this denudation, the area of the coronary artery was reduced by 94 ± 2% and 43 ± 5% (p < .01) in the denuded and nondenuded areas by the intracoronary administration of 10 μg/kg histamine after pretreatment with 60 mg/kg iv cimetidine. The effects of LTC₄ and LTD₄ on coronary diameter and the preventive effects of FPL-55712, a LTC₄ and LTD₄-receptor blocker, or diphenhydramine, a histamine H₁-receptor blocker, on histamine-induced coronary spasm were then examined angiographically. Administration of LTC₄ or LTD₄ in doses of 1 and 10 μg into the left coronary artery, or selectively into the left circumflex and left anterior descending coronary arteries in a dose of 5 μg, led to the elevations in the ST segment on the electrocardiogram and there was delayed filling of the contrast medium in the peripheral coronary artery. However, these LTs provoked no augmented constrictions at any site on the epicardial coronary arteries (n = 15). Diphenhydramine, 1 mg/kg (n = 6), abolished the histamine-induced coronary spasm. FPL-55712, 0.1 mg/kg, with which the LT-induced myocardial ischemia was abolished, did not prevent the histamine-induced coronary artery spasm. Hence, in a swine preparation of coronary artery spasm, LTC₄ and LTD₄ constricted the coronary arteries at the level of small vessels and rendered the perfused myocardium ischemic. These compounds do not seem to play a primary role in the provocation of epicardial coronary artery spasm induced by histamine in this atherosclerotic swine preparation.