The intravenous administration of 3 or 5 mg of glucagon to 13 patients with heart disease resulted in a statistically significant increase in heart rate, cardiac index, stroke power index, mean rate of left ventricular ejection, and maximum rate of rise of left ventricular pressure, whereas systemic vascular resistance declined. A moderate increase in mean stroke volume index and stroke work index and a slight fall in left ventricular end-diastolic pressure also occurred, although these changes were not statistically significant. The increase in cardiac index averaged 19%, with nine of the patients demonstrating an increase exceeding 10% of their respective control value. These effects of glucagon generally reached a maximum within 15 min after drug administration and also were of short duration. Positive inotropic and chronotropic effects of glucagon were observed in most but not all of these patients. In addition, the magnitude of these effects varied considerably among patients; the variation, however, did not appear to be related to the severity or duration of the heart disease. In eight patients, the infusion of isoproterenol produced greater increases in cardiac index and decreases in left ventricular end-diastolic pressure than glucagon did. Although the effect of glucagon was short, the frequent improvement in hemodynamics which occurred in the absence of significant side effects, notably arrhythmias, indicates that the inotropic actions of this agent may be useful under certain clinical conditions.

A B S T R A C T The effect of acutely induced hypoxia, hypercapnic acidosis, and the combination of the two on the amount of acetylstrophanthidin (AS) required to produce cardiac arrhythmias was determined in anesthetized dogs. Each animal was studied during ventilation with room air and again during ventilation with gas mixtures of appropriate concentrations; 24 hr separated the study periods. AS was infused intravenously at a rate of 5 ptg/kg per min.Significantly less AS was required to produce arrhythmias during hypoxia and hypercapnic acidosis together than during the period with normal arterial Po,, Pco2, and pH (10 animals). Included in this group were two animals which had undergone previous bilateral adrenalectomy and four animals in which heart rate was maintained at the same frequency during both study periods. A significant reduction in the toxic dose of AS also was demonstrated in eight animals, two with constant heart rate, during hypoxia with normal arterial Pco2 and pH. Hypercapnic acidosis alone (eight animals) did not significantly alter the toxic dose of AS. After the administration of propranolol (six animals) or hexamethionium (six animals), no significant difference was observed between the toxic dose of AS during hypoxia and that during ventilation with room air. Thus although hypoxia and hypercapnic acidosis together do reduce the amount of AS required to produce arrhythmias, it is the hypoxia which exerts the