Do dofetilide and D-sotalol prolong action potential duration and effective refractory period in diseased human ventricular myocardium?
Both dofetilide and D-sotalol exhibit class III antiarrhythmic effects by prolonging action potential duration and effective refractory period in diseased human ventricular myocardium, with dofetilide being potent at lower concentrations.
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 x 10(-8)-10(-6) M) and D-sotalol (D-Sot) 10(-5)-5 x 10(-4) M) 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 (V(max)), 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 > or = 10(-7) M and at D-Sot concentrations > or = 10(-4) M. No effects were observed on RMP, APA, or V(max). 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.
Montero et al. (Mon,) studied this question.
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