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 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
M
M
Med. Klinik, Technische Universität, München, Germany.
Schmitt
C
C
D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000503:physiopathology; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D006321:Heart / Q000187:drug effects; D006352:Heart Ventricles; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D010627:Phenethylamines / Q000494:pharmacology*; D013015:Sotalol / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D010627:Phenethylamines; D013449:Sulfonamides; D013015:Sotalol; C063533:dofetilide