Protective effect of diltiazem on ultrastructural alterations induced by coronary occlusion and reperfusion in dog hearts.

This study was designed to examine whether diltiazem, a calcium channel-blocker, inhibits the cardiac ultrastructural alterations induced by coronary occlusion with or without reperfusion, in dogs anesthetized with pentobarbital. The left anterior descending coronary artery (LAD) was completely occluded for 60 min with or without reperfusion (induced by release of occlusion) for 20 min. Coronary occlusion increased ST segment in the ischemic area, and also produced typical ultrastructural alterations including decreased glycogen granules, destruction of mitochondria, and margination of the nuclear chromatin, especially in the subendocardium. Reperfusion of the ischemic area resulted in more severe alterations of the myocardial ultrastructure, including many myofibrillar contraction bands. Diltiazem was injected intravenously at the dose of 200 micrograms/kg (bolus injection) 20 min before LAD occlusion, and was then infused intravenously at the rate of 80 micrograms/kg/min for 10 min starting at the beginning of LAD occlusion, the total dose being 1 mg/kg. Diltiazem decreased heart rate and diastolic blood pressure, inhibited the increase in ST segment, and also inhibited the ultrastructural alterations induced by coronary occlusion, regardless of reperfusion. A bolus injection of diltiazem alone (200 micrograms/kg), however, did not inhibit markedly the ultrastructural alterations induced by coronary occlusion, regardless of reperfusion. It is concluded that the large dose of diltiazem (1 mg/kg) protects the myocardium from ischemic injury.