Recording of Transmembrane Action Potentials in Chronic Ischemic Heart Disease and Dilated Cardiomyopathy and the Effects of the New Class III Antiarrhythmic Agents D-Sotalol and Dofetilide

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Abstract
Summary: We recorded intracellular endocardial action potentials (AP) in left ventricular specimens obtained from 10 patients with dilated cardiomyopathy (dil CMP) and 7 patients with chronic ischemic heart disease (CAD) in whom orthotopic heart transplantation had been performed. The concentration-dependent electrophysiological effects of the new class III antiarrhythmic agents dofetilide (Dof) (3 × 10-8-10-6M) and D-sotalol (D-Sot) 10-5-5 × 10-4M) were determined. The following parameters were recorded: action potential amplitude (APA), resting membrane potential (RMP), AP duration at 95 and 50% of repolarization (APD95, APD50), maximal upstroke velocity (Vmax), and effective refractory period (ERP) at a cycle length of 1 Hz. The measured AP parameters did not differ in dil CMP and CAD. APD50, APD95, and ERP were significantly prolonged at Dof concentration ≥ 10-7M and at D-Sot concentrations ≥10-4M. No effects were observed on RMP, APA, or Vmax. The AP characteristics of dil CMP and CAD did not differ. The data demonstrate class III effects of Dof and D-Sot on endocardial AP of diseased human ventricular myocardium. As compared with those of D-Sot, the effects of Dof on APD and ERP were similar but were obtained with lower concentrations.