Comparison of the protective effects of verapamil, diltiazem, nifedipine, and buffer containing low calcium upon global myocardial ischemic injury

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This study was designed to compare the effects of the Ca2+ slow channel blocking agents verapamil (2 X 10(-6) M), diltiazem (7.5 X 10(-7) M), and buffer containing reduced Ca2+ content (0.95 mM) on myocardial ischemic injury. These treatments were equiactive, reducing cardiac function to 20% of the control value, and fully reversible in nonischemic, isolated, working rat hearts. Hearts which were reperfused (30 min) following 27 min of global ischemia recovered 17% of control cardiac function and had a markedly reduced ATP and creatine phosphate content and ATP/ADP ratio compared to nonischemic hearts. When verapamil, diltiazem, nifedipine, or low Ca2+ treatments were given before and during ischemia, equal improvement in cardiac function was observed upon reperfusion, and tissue ATP levels, creatine phosphate levels, and ATP/ADP ratio were significantly higher than in hearts which did not receive the treatments or which received the drug vehicle. Large increases in recovery of contractile function were observed with a partial preservation of ATP reserves. These treatments, which were equiactive in nonischemic hearts, provided equivalent preservation of cardiac function, ATP, and creatine phosphate in the reperfused ischemic hearts. When the ischemic period was increased to 33 min and the effective concentrations reduced to depress cardiac function to 40% of the control value (4.5 X 10(-7) M verapamil, 2.5 X 10(-6) M diltiazem, 3 X 10(-7) M Nifedipine, 1.25 mM Ca2+), equal improvement in cardiac function was again observed. Thus, major differences among these Ca2+ slow channel blockers or low Ca2+ treatment were not detected in this experimental system.