Effects of Glucagon on a Multistressed Circulation

Abstract

The effectiveness of intravenous glucagon in improving myocardial function during conditions when exceptional loads have been added has been evaluated in three groups of eight instrumented, anesthetized, open-chest dogs. Glucagon (5 mg/kg/min) was infused continuously for 20 minutes after a series of hemodynamic stresses had been applied. These stresses consisted of cardiovascular depression secondary to propranolol (2 mg/kg) and volume loading (20 ml/kg); experimental myocardial infarction produced by coronary artery ligation; and ligation of the thoracic aorta. Depression due to beta blockade alone resulted in significant increases in mean left atrial pressure and systemic vascular resistance and decreases in left ventricular dp/dt, right ventricular contractile force, heart rate, and cardiac output. The induction of myocardial infarction caused significant increase in mean atrial pressures and marked decreases in left ventricular systolic pressure, cardiac output, and stroke volume, while ligation of the thoracic aorta after myocardial infarction produced marked elevation of systemic vascular resistance, mean aortic pressure, left ventricular systolic pressure and decreases in heart rate as well. Significant hemodynamic improvement after the administration of glucagon was observed during each stress or combination of stresses, and consisted of marked increases in left ventricular dp/dt, right ventricular contractile force, heart rate, and cardiac output and decreases in mean right and left atrial pressures and in systemic vascular resistance. Elevation of aortic pressure and left ventricular systolic pressure, in addition, was seen in maximally stressed animals. Glucagon also attenuated rises in atrial pressure produced by volume loading of stressed animals. Improvement in hemodynamic variables was probably not due to the positive chronotropic actions of the drug, but due to its positive inotropic effects, since pacing to rates equivalent to those attained by the administration of glucagon did not improve significantly the hemodynamic status of the animals.