Direct and Vagally Mediated Chronotropic Effects of Morphine Studied by Selective Perfusion of the Sinus Node of Awake Dogs

Abstract

Two milliliters of a morphine sulfate solution (1 mg/ml) perfused selectively into the sinus node artery of five trained unanesthetized dogs caused an immediate brief sinus tachycardia followed by a delayed but prolonged sinus bradycardia. Beta-receptor blockade was achieved by selective perfusion of propranolol hydrochloride solution (10 mug/ml) into the sinus node artery and did not prevent the initial sinus tachycardia. Selective perfusion of the sinus node with atropine sulfate solution (1 mug/ml), however, did prevent morphine from causing further sinus rate increase. The immediate positive chronotropic action of morphine was thus attributable to a peripherally located vagolytic action. The exact opposite was true with regard to the delayed bradycardia; it was due to a centrally mediated generalized increase in vagal tone regularly elicited by morphine.