The effects of glucagon-low insulin were studied on canine isolated papillary muscles incubated in Chenoweth-Kolle solution and in the pentobarbital anesthetized dog. Insulin, 12.5 mU/ml, increased developed isometric tension of papillary muscles which had equilibrated for 17 hrs, but not in muscles incubated up to 60 min. The decrease in isometric tension produced by propranolol, 10 −6 M, but not that due to pentobarbital sodium, 80 μg/ml, was reversed by insulin. The positive inotropic effect of insulin was obtained when pyruvate, fumarate and glutamate replaced glucose as substrate in the Chenoweth-Kolle solution. The intracoronary administration of insulin, 0.1 U/kg, increased left ventricular isometric tension and the rate of tension development in dog hearts depressed with propranolol, 2 mg/kg. Insulin exerts a direct positive inotropic effect upon canine heart muscle depressed by propranolol or due to prolonged incubation. The effect is not dependent upon catecholamines, glucagon or glucose. The positive inotropic effect is not observed in non-depressed hearts or in barbiturate depressed hearts.
