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Abstract-Ch ro not ropic and inotropic effects of glucagon were compared with those of norepinephrine using the excised SA node and the papillary muscle preparations cross-circulated with a donor dog. Glucagon was administered i.v. to the donor dog at doses of I to 30 μg/kg, which caused a marked chronotropic but less marked inotropic effect. Cardiohemodynamic response to glucagon of anesthetized dogs was simulated by an acceleration induced by atrial pacing. It was concluded that glucagon is more effective on chronotropism than on inotropism, and that its cardio hemodynamic effects are mainly ascribed to the increased heart rate.Since glucagon-induced positive chronotropic and inotropic effects were demonstrated not only in the isolated heart preparation but also in the intact heart of different species of animals, many investigatores have attempted to clarify the mode of action. It is gener ally accepted that the enhancement of cardiac performance induced by glucagon is not mediated by 13-adrenoceptor stimulation (1, 2, 3, 4). Recent studies suggest that its effects are due to an increase in the intracellular concentration of cyclic 3', 5'-AMP resulting from activation of adenyl cyclase (5, 6, 7). Even at present, when glucagon has already been introduced for clinical use as a cardiotonic drug, the difference between glucagon and the adrenergic effects is not clear. In the present study, chronotropic and inotropic effects of glucagon were compared with those of norepinephrine in the excised SA node and the papillary muscle preparations cross-circulated with a donor dog, and its cardiohemody namic effects were also investigated in the whole animal. MATERIALS AND METHODSMongrel dogs of both sexes were anesthetized with 30 mg/kg of sodium pentobarbital, i.v. After 200 units/kg of sodium heparin, i.v., the heart was excised and immersed into Tyrode's solution at about 4'C, equilibrated with a gas mixture consisting of 95% 02 and 5 % CO2. The excised SA node and the excised papillary muscle preparations were cross circulated by a donor dog as illustrated in a diagram (Fig. 1). The SA node and the papil lary muscle preparations have been previously described in detail by Kubota and Hashi moto (8) and Endoh and Hashimoto (9), respectively. Donor dogs were anesthetized with 30 mg/kg of sodium pentobarbital, i.v. Sodium heparin, 300 units/kg, was given at the beginning of the perfusion and maintenance dose of 100 units/kg was given every hour. Both preparations were perfused with the blood conducted from the left carotid

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