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)