Nibentan

Among factors determining development of polymorphic ventricular tachycardia torsades de pointes under influence of class III antiarrhythmic drugs great value is attributed to enhanced heterogeneity of repolarization of ventricular myocardium which can cause functional conduction blocks and development of re-entry of excitation. In this work with the help of optical mapping of electrical activity of the heart we investigated effect of nibentan (0.3 and 1 mM) on chronotopography of repolarization of epicardial surface of ventricles of isolated after Langendorf rabbit heart (n=5). For assessment of heterogeneity of repolarization we measured the following parameters: standard deviation of mean action potential duration (APDm) along mapped region (SD-APD), dispersion index (DI=1000 SD-APDm), maximal dispersion (Dmax=APDmax-APDmin). Nibentan in concentrations 0.3 and 1 mM increased APD at the level of 90% repolarization (APD90%) from 231 +/- 12 to 277 +/- 7 ms (p < 0.05) 318 +/- 7 ms (p < 0.001), respectively, but in concentration 1 mM it practically did not affect parameters of heterogeneity of repolarization (SD-APD: from 4.4 +/- 0.9 to 5.7 +/- 1.1 ms, p=0.4; DI: from 19.1 +/- 4.2 to 18.0+3.5, p=0.8; Dmax: from 16.6 +/- 2.5 to 24.8 +/- 4.3 ms, < 0.05). These results show that nibentan in the range of clinically used doses does not effect heterogeneity of ventricular myocardium. This can explain low proarrhythmic effect of nibentan.

The aim of the study was to compare the efficacy and safety of pharmacological cardioversion (PC) by nibentan, a class III antiarrhythmic agent, and electrical cardioversion (EC) in patients with persisting atrial fibrillation (AFib) and atrial flutter (AFI) receiving basic antiarrhythmic therapy. Ninety-seven patients with persisting AFib and AFI were included in the trial (45 patients constituted PC group, and 52 constituted EC group). Both groups were comparable according to basic demographic and clinical parameters as well as antiarrhythmic therapy being applied. The results of the study showed that the efficacy of PC did not differ from that of EC (86.7% and 92.3% respectively, p = 0.282). the frequency of arrhythmogenic effect did not differ between the groups either (p = 0.46). One case of non-stable ventricular tachycardia was registered in the PC group. The most significant adverse effect was bradicardia, which was registered more often in the PC group than in EC group (26.7% and 3.8%, respectively, p = 0.001). In conclusion, the efficacy and safety of PC with nibentan in patients with persisting AFib/AFI is comparable with those of EC.