Effects of intracoronary verapamil administration in a sheep model of acute myocardial ischemia and reperfusion.

Abstract

We evaluated the efficacy of intracoronary administration of verapamil hydrochloride in reducing myocardial injury during acute ischemia and reperfusion. Ischemia was induced by 30% and 45% reductions of circumflex arterial blood flow for successive 2-hour periods. A reperfusion period (1 hour and 45 minutes) followed ischemia upon deflation of a pneumatic occluder. Verapamil (30 micrograms/kg) was slowly injected into the circumflex artery as a bolus 15 minutes after each blood flow reduction step. To prevent verapamil-induced decreases in heart rate, ventricular pacing was established at 170 beats/min before a baseline period and maintained throughout the protocol. Creatine kinase activities (international units per milligram protein) measured in samples obtained from posterior papillary muscles were 15 +/- 1 (mean +/- SEM) and 10 +/- 2 for animals receiving verapamil or its saline vehicle, respectively (p less than 0.05). Quantitative morphometry was performed on left ventricular myocardium after staining with p-nitro blue tetrazolium. Intracoronary administration of verapamil reduced the extent of left ventricular infarction, as disclosed by positive tetrazolium staining of the tissue, from 34 +/- 4% of the left ventricle in vehicle-treated animals to 21 +/- 4% of the left ventricle in verapamil-treated animals (p less than 0.05). We conclude that intracoronary administration of verapamil reduced the extent of myocardial infarction acutely, independent of increases in blood flow through the circumflex coronary artery or decreases in heart rate. Administration of verapamil was not associated with decreases in ventricular afterload, the pressure-rate index, cardiac output, or the maximum rate of pressure development in the left ventricle. Verapamil treatment of animals subjected to ischemia was not associated with sustained elevations of left atrial pressure to values above those measured in animals receiving the vehicle.