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 a nd 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 p erformed. The following parameters were recorded: AP amplitude (APA), resting membrane potential (RMP), AP duration at 95 and 50% repolariza tion (APD(95), APD(50)), maximal upstroke velocity (V-max), and effect ive refractory period (ERP) at cycle lengths (CL) of 0.5, I Hz, and 1. 5 Hz. APD(50), APD(95), and ERP were significantly prolonged in endoca rdium at D-sotalol concentration greater than or equal to 10(-4)M at a ll CL. In epicardium, APD(50), APD(95), and ERP were significantly pro longed at lower D-sotalol concentrations (starting at 3 x 10(-5)M). In contrast to parameters in endocardium, APD(50), APD(95), and ERP were shortened in epicardial cells at D-sotalol concentrations greater tha n or equal to 3 x 10(-4)M at drive CL of 0.5 and 1 Hz with no effect o n V-max and APA. In endocardium, the prolongation of APD(95) and ERP w as less at a CL of 1.5 Hz compared with 0.5 Hz at a concentration of 1 0(-4)M. This frequency-dependent effect was not observed in epicardium . No effects were observed on RMP, APA, or V-max. These data indicate a differential effect of D-sotalol in endo- and epicardial human ventr icular myocardium, which may be an important mechanism of action of D- sotalol.