Amplified Effects of d,l-Sotalol in Canine Dilated Cardiomyopathy

Authors


  • Supported in part by the Mayo Foundation Clinical Investigator Program (Dr. Packer).

Address for reprints: Sumeet S. Chugh, M.D., Cardiology Division, UHN-62, Oregon Health Sciences University 3181 SW Sam Jackson Park Rd., Portland OR 97201. FAX: (503) 494-8550; e-mail: chughs@ohsu.edu

Abstract

CHUGH, S.S., et al.: Amplified Effects of d,l-Sotalol in Canine Dilated Cardiomyopathy. Despite the presence of well-described cardiac repolarization abnormalities in heart failure, d,l-sotalol effects on cardiac repolarization have not been evaluated in animal models of CHF. The authors hypothesized that the d,l-sotalol effects on cardiac repolarization are altered in canine dilated cardiomyopathy when compared to controls. Effects of d,l-sotalol were compared in seven dogs with tachycardia induced cardiomyopathy (CHF) and six control animals. In an open-chest model, contact monophasic action potential recordings were obtained from RV and LV endocardium/epicardium during and after two doses of d,l-sotalol (1 mg/kg and 3 mg/kg, each over 20 minutes). Effects of d,l-sotalol on action potential duration at 90% repolarization (APD90) were examined at pacing cycle lengths of 300–1,000 ms. Plasma d,l-sotalol levels were measured at baseline, 10, and 40 minutes following each dose. Prolongation of APD90 by d,l-sotalol, was significantly exaggerated in CHF animals versus controls (P < 0.05, ANOVA). These differences were magnified at slow heart rates (P < 0.05, ANOVA). There were no significant differences in plasma d,l-sotalol levels between the two groups. Effects of d,l-sotalol on cardiac repolarization are exaggerated in CHF without significant alterations in plasma drug levels. While using d,l-sotalol in heart failure, independent additional effects due to ventricular electrical remodeling may be a consideration.

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