Leukotriene C4- and D4-induced diffuse peripheral constriction of swine coronary artery accompanied by ST elevation...

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 Göttingen 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 less than .01) in the denuded and nondenuded areas by the intracoronary administration of 10 micrograms/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 micrograms into the left coronary artery, or selectively into the left circumflex and left anterior descending coronary arteries in a dose of 5 micrograms, 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.(ABSTRACT TRUNCATED AT 250 WORDS)