Effect of pharmacologic agents on the function of the ischemic heart

Abstract

Since isoproterenol, tachycardia induced by atrial pacing, propranolol and Hyaluronidase alter the extent and severity of cardiac damage after coronary occlusion, their effects on the function of the severely ischemic heart were studied. In 40 dogs, blood from the femoral artery perfused the cannulated left coronary artery with flow controlled by a roller pump. Total left coronary blood flow was reduced progressively every 3 minutes from a control value of 84.2 ml/min per 100 g of left ventricular myocardium until mean left atrial pressure exceeded 20 mm Hg. In control runs, coronary blood flow decreased by 49 percent; with infusion of isoproterenol (0.08 μg/kg per min) coronary blood flow was reduced by only 24 percent (no. = 12, P < 0.01); after pretreatment with propranolol (1 mg/kg) coronary blood flow could be reduced by 55 percent (no. = 8, P < 0.05); and after pretreatment with Hyaluronidase (2,000 National Formulary units/kg) coronary blood flow could be reduced by 65 percent (no. = 6, P < 0.01) until left atrial pressure increased to 20 mm Hg. With coronary blood flow at 67 ml/min per 100 g, that is, at 75 percent of control value, left atrial pressure averaged 4.9 mm Hg at a heart rate of 120 beats/min and increased to 12.7 mm Hg (no. = 9, P < 0.01) at a heart rate of 165 beats/min. Thus, contrary to the effects of isoproterenol and tachycardia in the normal and failing nonischemic heart, these interventions depress left ventricular function in the severely ischemic heart, whereas propranolol and Hyaluronidase improve this function. The effects of these interventions on ventricular function parallel those produced by these same interventions on the extent and severity of myocardial injury in the presence of coronary occlusion.