EFFECTS OF CALCIUM ENTRY BLOCKERS ON CORONARY CONSTRICTION AND MYOCARDIAL ISCHEMIA DUE TO LEUKOTRIENE-D4

  • 1 January 1985
    • journal article
    • research article
    • Vol. 233  (1) , 229-234
Abstract
Effects of intracoronary LTD4 [leukotriene D4] before and during treatment with calcium entry blockers in the in situ, blood-perfused hearts of domestic pigs were compared. I.v. administration of verapamil (0.1-1.6 mg/kg), nifedipine (10 or 100 .mu.g/kg) or diltiazem (0.6-2.0 mg/kg) sufficient to increase base-line coronary blood flow (CBF) and decrease mean arterial pressure did not change decrement in CBF after LTD4. Infusion of verapamil (0.01-0.04 mg/min) into the left anterior descending coronary artery raised pre-LTD4 CBF almost 2-fold without alteration in mean arterial pressure, heart rate or left ventricular end-diastolic pressure. Intracoronary boluses of LTD4 (0.3, 1.0 and 3.0 .mu.g) during verapamil infusion into the same vessel caused dose-dependent decreases in CBF identical to those observed when LTD4 doses were injected during control infusion. ECG showed myocardial ischemia during severe flow reduction after high dose intracoronary verapamil, electrocardiographic changes did not occur despite similar decreases in CBF. The capacity of verapamil to prevent LTD4-induced ischemia may be caused by higher residual CBF after LTD4 even though the magnitude of LTD4-induced CBF decrement was unaltered. LTD4-induced coronary constriction seems to be mediated by a mechanism unrelated to Ca entry channels blocked by verapamil, nifedipine or diltiazem.