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.
Chugh
S S
SS
Department of Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA. chughs@ohsu.edu
Johnson
S B
SB
Packer
D L
DL
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002304:Cardiac Pacing, Artificial; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000503:physiopathology; D004285:Dogs; D005260:Female; D008297:Male; D013015:Sotalol / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D013015:Sotalol