Effect of Guanethidine and Bretylium on the Dog Heart-Lung Preparation

Abstract

Inotropic and chronotropic effects of guanethidine and bretylium have been observed in heart-lung preparations made from normal and chronically reserpinized dogs. Guanethidine (0.3 to 30 mg.) in the untreated preparation had marked positive inotropic and chronotropic effects, whereas after pretreatment with reserpine it had a striking negative inotropic effect and no effect on heart rate. Guanethidine given to preparations made from animals pretreated with guanethidine had a negative inotropic effect smaller than that seen after reserpine pretreatment. Bretylium (0.3 to 30 mg.) in the untreated preparation had both positive inotropic and positive chronotropic effects. In the chronically reserpinized animal, the positive inotropic effect of bretylium persisted though it was reduced to about one-quarter of the original size. The positive chronotropic effect of bretylium in this circumstance was reversed to a negative chronotropic effect. These effects are interpreted as indirect but strong evidence that: (1) guanethidine and bretylium exert at least part of their initial positive inotropic and chronotropic effects by a release of catecholamines; and (2) in the amine-depleted heart, guanethidine has an intrinsic negative inotropic effect, whereas bretylium has an intrinsic positive inotropic effect.