Halothane sensitizes the canine heart to pharmacological IKr blockade

The effects of halothane and pentobarbital on the cardiovascular system were compared using the in vivo canine models. The ventricular repolarization process was longer under the halothane-anesthesia than pentobarbital-anesthesia. Intravenous administration of a selective blocker of rapidly activating delayed rectifier K+ currents (I-Kr) sematilide prolonged the ventricular repolarization period without affecting the intraventricular conduction under both anesthesia; however, the potency was about 1.5-folds greater under the halothane-anesthesia than pentobarbital-anesthesia. These results suggest that halothane can more effectively sensitize the heart to pharmacological I-Kr blockade, resulting in the excessive QT interval prolongation. Thus, the halothane-anesthetized canine model can be useful for predicting the in vivo I-Kr blocking property of new drugs. (C) 2004 Elsevier B.V. All rights reserved.