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

We recorded intracellular endocardial action potentials (AP) in left v entricular specimens obtained from 10 patients with dilated cardiomyop athy (dil CMP) and 7 patients with chronic ischemic heart disease (CAD ) in whom orthotopic heart transplantation had been performed. The con centration-dependent electrophysiological effects of the new class III antiarrhythmic agents dofetilide (Dof) (3 x 10(-8)-10(-6) M) and D-so talol (D-Sot) 10(-5)-5 x 10(-4) M) were determined. The following para meters were recorded: action potential amplitude (APA), resting membra ne potential (RMP), AP duration at 95 and 50% of repolarization (APD(9 5) APD(50)), maximal upstroke velocity (V-max), and effective refracto ry period (ERP) at a cycle length of 1 Hz. The measured AP parameters did not differ in dil CMP and CAD. APD(50), APD(95), and ERP were sign ificantly prolonged at Dof concentration greater than or equal to 10(- 7) M and at D-Sot concentrations greater than or equal to 10(-4) M. No effects were observed on RMP, APA, or V-max. The AP characteristics o f dil CMP and CAD did not differ. The data demonstrate class III effec ts of Dof and D-Sot on endocardial AP of diseased human ventricular my ocardium. As compared with those of D-Sot, the effects of Dof on APD a nd ERP were similar but were obtained with lower concentrations.