Pharmacologic Analysis of Ketamine-Induced Cardiac Actions in Isolated, Blood-Perfused Canine Atria

Abstract

Effects of ketamine were investigated on atrial rate and contractile force in the isolated, blood-perfused canine atrium. When a relatively small dose (3 .mu.g) of ketamine was injected into the sinus node artery, positive chronotropic and inotropic responses were consistently observed. With doses of 10-300 .mu.g i.a., biphasic (i.e., negative followed by positive) chronotropic and inotropic responses were induced. An extremely large dose of ketamine frequently produced biphasic chronotropic and only negative inotropic responses. The negative effects of ketamine were not affected by atropine pretreatment. After treatment with propranolol or imipramine, the positive effects were significantly suppressed. The effects were not influenced by tetrodotoxin. These results suggest that ketamine has (a) indirect cardioexcitatory properties mediated by a release of catecholamines which is due to a tyramine-like action, and (b) direct cardioinhibitory properties by which high doses depress the contractility rather than the pacemaker activity.