Limitation of myocardial necrosis with verapamil during sustained coronary occlusion in the closed-chest dog.

Abstract

Studies were undertaken to determine whether cardioprotection afforded by verapamil could be sustained in the dog heart during permanent coronary artery occlusion. In 48 dogs a coronary artery was occluded for 24 or 48 hours using a closed-chest embolization procedure. Dogs were assigned to either untreated control or to verapamil-treated (200 micrograms/kh, intravenous bolus within 5 minutes after coronary occlusion and then 5 micrograms/kg/min as a continuous intravenous infusion for 24 or 48 hours) groups. After 24 or 48 hours of permanent coronary occlusion, tissue necrosis was evaluated using tetrazolium staining and was related to the major baseline predictors of infarct size including anatomic risk zone (radiolabeled microsphere autoradiography) and coronary collateral flow. The correlation between infarct size and subepicardial coronary collateral flow was calculated in untreated control dogs (r = -0.91 and -0.80 for 24 and 48 hour controls, respectively); analysis of covariance indicated that verapamil treatment shifted this relation downward in both the 24- and 48-hour drug treatment groups. The equation of this regression was used to calculate the size of the infarct that would have occurred in treated dogs if drug treatment had not been initiated. The ratio of observed and calculated infarct size provides a "salvage index." In conclusion, verapamil was able to limit the extent of tissue necrosis and this cardioprotection appears to be sustained during 48 hours of permanent coronary occlusion.