Dissociation between the chronotropic and inotrophic actions of glucagon

Summary

The interaction between glucagon and veratramine was studied in anesthetized vagotomized dogs and in heart-lung preparations from dogs. In both preparations, veratramine administered when maximal effects of an infusion of glucagon became manifest, reduced heart-rate to either control or near control levels. In both preparations glucagon increased myocardial contractile force, as gauged by the maximal rate of rise of left ventricular pressure, dp/dt, markedly, but subsequent administration of veratramine lowered dp/dt significantly only in the intact preparations in which a concomitant substantial decrease in mean arterial pressure was noted after glucagon with further decrease after veratramine. Pentobarbital-induced myocardial failure in heart-lung preparations was successfully corrected with an infusion of glucagon. Subsequent administration of veratramine reduced the glucagon-induced tachycardia to near control level without affecting myocardial contractility. It may be concluded from this study that veratramine blocks the chronotropic but not the inotropic action of glucagon, an effect which is reminiscent of its inhibitory action on the chronotropic but not the inotropic effect of the catecholamines, first demonstrated by Krayer.