Effects of Phentolamine on the SA Node of the Dog Heart In Situ

Abstract

Direct perfusion of the sinus node artery at constant pressure of 100mm Hg was arranged in 6 canine hearts in situ. The injection of phentolamine into the sinus node artery usually induced dosedependent positive chronotropic effect. However, at a larger dose of 300μg, phentolamine frequently induced a biphasic chronotropic response, i.e., sinus deceleration followed by sinus acceleration. Phentolamine at a large dose of 1mg usually induced a negative chronotropic effect. The threshold dose for inducing sinus acceleration was about 1 to 10μg. The positive chronotropic response to phentolamine was blocked either by propranolol or by tetrodotoxin. That to norepinephrine was blocked by propranolol but not suppressed by tetrodotoxin. These results suggest that the phentolamineinduced sinus acceleration is due to catecholamine which is released by excitation of local adrenergic fibers. The sinus deceleration to higher doses of phentolamine was not blocked either by atropine or by tetrodotoxin. It suggests that phentolamine has a direct depressive effect on the SA node at extremely high dose levels.