CALCIUM-CHANNEL BLOCKERS PRESERVE CORONARY ENDOTHELIAL REACTIVITY AFTER ISCHEMIA-REPERFUSION

Background. Calcium-channel blockers have been reported to improve myo cardial recovery after ischemia-reperfusion, but their effects on coro nary blood now regulation remain to be defined. Experiments were desig ned to evaluate the effects of calcium antagonists on coronary artery vasoregulation exposed to ischemia-reperfusion. Methods. Three groups of hearts (n = 6) were pretreated with a 10-minute infusion of either diltiazem, verapamil, or nifedipine at concentrations of 10(-9) mol/L to 10(-6) mol/L and exposed to 30 minutes of no-flow ischemia and 45 m inutes of reperfusion. Another group (n = 6) received no pretreatment and was used as control. Endothelium-dependent and -independent relaxa tions were tested by assessing coronary flow increase to 5-hydroxytryp tamine (10(-6) mol/L) and sodium nitroprusside (10(-5) mol/L) infusion , respectively. Left ventricular pressure, its first derivative, and c oronary basal now were recorded before and after ischemia as well as d uring calcium antagonist infusion. Results. Endothelium-dependent rela xation after ischemia was significantly improved with all three drugs in a dose-dependent fashion; nifedipine was found to be the more poten t. Endothelium-independent relaxation was also significantly preserved with calcium antagonists regardless of the type, whereas left ventric ular hemodynamics were not. During perfusion, nifedipine was found to have the most negative inotropic effect and to be the most potent vaso dilator on the coronary circulation. Diltiazem was the less effective drug on both left ventricular hemodynamics and coronary circulation. C onclusions. This study indicates that preischemic infusion of calcium antagonists enhance endothelium-dependent and -independent coronary ar tery relaxation in the isolated rat heart model in a dose- and drug-de pendent fashion. This can be achieved at low doses without affecting l eft ventricular hemodynamics and should contribute to preserve coronar y artery autoregulation. (C) 1997 by The Society of Thoracic Surgeons.