Abstract
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 rog/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.
Original language | English (US) |
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Pages (from-to) | 1783-1788 |
Number of pages | 6 |
Journal | PACE - Pacing and Clinical Electrophysiology |
Volume | 24 |
Issue number | 12 |
DOIs | |
State | Published - 2001 |
Keywords
- Action potentials
- Antiantiarrhythmia agents
- Congestive heart failure
- Potassium channels
- Torsades de pointes
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine