Antifibrillatory and Proarrhythmic Effects of d,l-Sotalol Mediated by the Action Potential Duration Restitution Kinetics

摘要: Background and Objectives：The action potential duration (APD) restitution kinetics has been known to play a crucial role in the initiation maintenance of ventricular tachycardia (VT)/fibrillation (VF). We hypothesized that “the anti-arrhythmic proarrhythmic effects d,l-sotalol are mediated by changing APD (APDR) kinetics”. Materials Methods：The purposes this study were: 1) assess d,lsotalol on APDR kinetics, 2) correlate using kinetics. recorded transmembrane potentials (TMPs), microelectrode technique, seven isolated perfused swine right ventricles, at baseline, with 1, 5, 10 20 mg/L d,l-sotalol, washout period 1 hour. The effective refractory periods (VERP), 90% repolarization (APD90), spontaneous defibrillation rate VF inducibility were measured each concentration. plotted curves S1-S2 pacing against VF, calculated maximal slopes (Smax) APDR. Results： Sotalol (10 mg/L) prolonged APD90 (p<0.001) reducing Smax (by pacing, p<0.01; during p<0.05). Accordingly, 41.7% VT/VF was terminated spontaneously, reduced from 91.1% baseline 25% sotalol. A higher dose sotalol (20 increased Smax, despite continuous prolongation VERP APD90, resulting increase (36.4%). Conclusion：Sotalol produces its anti-fibrillatory effect parallel flattening therapeutic doses. However, concentration tissue. (Korean Circulation J 2005;35:282-289)