Effect of intracoronary verapamil on infarct size in the ischemic, reperfused canine heart: critical importance of the timing of treatment

Abstract

In an effort to determine whether the beneficial effect of calcium blocking drugs occurs only during ischemia or during reperfusion as well, anesthetized dogs were subjected to 3 hours of occlusion of the left anterior descending coronary artery followed by 3 hours of reperfusion. In protocol A, intracoronary verapamil (0.01 mg/kg/min) was begun 90 minutes after coronary occlusion and continued for 1 hour into the reperfusion phase (n = 6) while a control group received an infusion of saline solution (n = 6). In vivo area at risk determined by dye injection was 29 +/- 3% of the left ventricle (+/- standard error of the mean) in the control group and 30 +/- 3% in the verapamil group (difference not significant [NS]), whereas the area of necrosis determined by triphenyltetrazolium staining and expressed as a percent of area at risk was smaller in the verapamil group (29 +/- 8%) than in the control group (57 +/- 8%, p less than 0.05). In protocol B, verapamil infusion into the left anterior descending coronary was begun 5 minutes before blood reperfusion and continued throughout the 3-hour reperfusion phase. Area at risk was similar in both groups (control, 25 +/- 1%, n = 8; verapamil, 28 +/- 2%, n = 8, NS); area of necrosis expressed as a percentage of area at risk was 49 +/- 6% in the control group and 45 +/- 10% in the verapamil group (NS). Therefore, calcium blockade of ischemic myocytes delays death and enhances salvage produced by reperfusion. However, calcium blockade begun after prolonged coronary occlusion does not enhance reperfusion-induced myocardial salvage.