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

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.