The Protective Effect of Calcium Antagonist on Myocardium in Coronary Reperfusion Following Experimental Myocardial Infarction

Chung, June Key; Lim, Sang Moo; Lee, Myung Chul; Koh, Chang Soon; Lee, Munho; Seo, Jeong Wook; LaFrance, Norman D

Abstract

Although it has been suggested that the calcium antagonist verapamil has beneficial effects on ischemic myocardium, its effect during coronary reperfusion has not been studied in detail. The purpose of this study was to investigate the inhibitory effect of verapamil on myocardial damage quantitatively using 111 In-anticardiac myosin antibody (ACM Ab) and qualitatively using electronmicroscopic method. Anesthetized open-chest dogs were subjected to 1 hour of occlusion of the left anterior descending coronary artery (LAD) followed by 90 minutes of reperfusion. Regional myocardial blood flow was determined by injecting 85Sr-microsphere prior to LAD reperfusion, and regional myocardial damage was measured by injecting 111In-ACm Ab at 30 minutes after LAD reperfusion. Six dogs were randomly selected as saline control and verapamil-treated (0.6 mg/kg. hr) groups each. Saline or verapamil was infused at 40 minutes after LAD occlusion and continued through the experiment. 1) Verapamil produced significant (P<0.05 by Wilcoxon rank sum test) decrease in heart rate, mean arterial blood pressure and double product. There was no significant change in pulmonary hemodynamics or cardiac output. 2) Stroke volume was reduced significantly (P<0.05 by Wilcoxon rank sum test) after 30 minutes of LAD reperfusion in the control group, but it was preserved in the verapamil-treated group. 3) There was an inverse exponential relationship between 111In-ACm Ab localization and regional blood flow in both control (r=-0.86) and verapamil treated (r=-0.71) groups. Significant difference between the two groups was found in exponential curve (p[t]<0.05). 4) A lesser uptake of 111in-ACM Ab was observed in the verapamil treated group compared with that in the control group in the region where the regional blood flow was lower than 30+/- of normal. 5) In the control group, the myocardium showed swelling, contraction bands, and electron dense granules in the mitochondria which were proven to be calcium aggregates. In the verapamiltreated grooup, the myocardium showed fewer electro dense granules and mild degree of contraction bands. This study supports the concept that verapamil reduces the myocardial damage following coronary reperfusion in myocardial infarction and may reduce contraction band necrosis.