Different effectiveness of glucagon on the pacemaker activity and contractility in intact dog hearts and in isolated...

In an isolated right atrial preparation, which was cross-perfused with heparinized arterial blood from a support dog, we investigated the effects of glucagon on heart rate and systemic arterial blood pressure of the support dog and on atrial rate and contractile force of the isolated perfused atrium when glucagon was injected into the external jugular vein of the support dog or into the sinus node artery of the isolated atrial preparation. Glucagon (0.3 to 3 micrograms/Kg i.v.) to the support dog dose-dependently induced a prominent increase in heart rate and a small increase in systemic arterial blood pressure. In the isolated, perfused atrium, marked positive chronotropic and slight, but significant, positive inotropic effects were evoked dose-dependently 1.5 min after intravenous injection of glucagon. These positive effects were not altered significantly by propranolol (1 mg/Kg i.v.). Direct injection of glucagon into the sinus node artery of isolated atria also induced marked positive chronotropic and small positive inotropic effects dose-dependently. CF/HR ratios, inotropic effect per chronotropic effect in isolated atria, of glucagon injected intravenously or intraarterially were less than 0.7 and they were much less than those of norepinephrine (more than 3.6). These results confirm that glucagon injected intravenously or regionally produces a prominent positive chronotropic effect and a small positive inotropic effect and suggest that glucagon may be less effective as a cardiotonic agent.