Effect of diltiazem on ischemia in the perfused working rat heart.

Abstract

We reported that diltiazem, a calcium antagonist, attenuated myocardial acidosis produced by coronary artery ligation in dogs (J.P.E.T. 222: 720, 1982). This finding suggests the beneficial effect of diltiazem on ischemic myocardium. The present study was undertaken to examine whether diltiazem protected the myocardium from irreversible ischemic damage in the isolated perfused working rat heart. Ischemia was produced by lowering afterload pressure of the perfused working rat heart until the heart was reperfused by raising the after-load. After ischemia, the following changes were observed: decreases in the pressure-rate product and coronary flow, depletion of ATP and CrP, and accumulation of lactate. The pressure-rate product and ATP level of the heart that had been made ischemic for 20 min did not return to the preischemic level during reperfusion, suggesting that irreversible ischemic damage occurred. Diltiazem (1, 5 and 10 mg/1) was provided to the heart 5 min before the onset of ischemia. In the presence of diltiazem, the levels of ATP and CrP did not decrease even after 20 min of ischemia. Reperfusion with the normal buffer after 20 min of ischemia recovered the pressure-rate product that had been decreased by ischemia, depending upon the concentration of diltiazem provided. These results indicate that diltiazem has a protective effect on the ischemic myocardium.