Differential effects of D-sotalol on endocardial and epicardial action potentials of human ventricular myocardium in dilated cardiomyopathy.
The frequency- and concentration-dependent electrophysiologic effects of D-sotalol (3 x 10(-5)-10(-3) M) were evaluated in human epicardial and endocardial left ventricular (LV) myocardium. Intracellular action potentials (AP) were obtained from explanted hearts of 5 patients with dilated cardiomyopathy in whom orthotopic heart transplantation was performed. The following parameters were recorded: AP amplitude (APA), resting membrane potential (RMP), AP duration at 95 and 50% repolarization (APD95, APD50), maximal upstroke velocity (Vmax), and effective refractory period (ERP) at cycle lengths (CL) of 0.5, 1 Hz, and 1.5 Hz. APD50, APD95, and ERP were significantly prolonged in endocardium at D-sotalol concentration > or = 10(-4) M at all CL. In epicardium, APD50, APD95, and ERP were significantly prolonged at lower D-sotalol concentrations (starting at 3 x 10(-5) M). In contrast to parameters in endocardium, APD50, APD95, and ERP were shortened in epicardial cells at D-sotalol concentrations > or = 3 x 10(-4) M at drive CL of 0.5 and 1 Hz with no effect on Vmax and APA. In endocardium, the prolongation of APD95 and ERP was less at a CL of 1.5 Hz compared with 0.5 Hz at a concentration of 10(-4) M. This frequency-dependent effect was not observed in epicardium. No effects were observed on RMP, APA, or Vmax. These data indicate a differential effect of D-sotalol in endo- and epicardial human ventricular myocardium, which may be an important mechanism of action of D-sotalol.
Montero
M
M
Department of Cardiology, 1. Med. Klinik der TU, München, Germany.
Schmitt
C
C
D000200:Action Potentials / Q000187:drug effects; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy / Q000503:physiopathology; D004558:Electric Stimulation; D004594:Electrophysiology; D004699:Endocardium / Q000187:drug effects / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D013015:Sotalol / Q000494:pharmacology*; D016276:Ventricular Function
D013015:Sotalol