[Effect of nibentan on dispersion of repolarization of ventricular myocardium in the rabbit].
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.
Glukhov
A V
AV
Reznik
A V
AV
Kovalenko
N V
NV
Egorov
Iu V
IuV
Rozenshtraukh
L V
LV
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001549:Benzamides / Q000627:therapeutic use*; D018780:Body Surface Potential Mapping / Q000187:drug effects; D004195:Disease Models, Animal; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology*; D006352:Heart Ventricles / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology*; D011817:Rabbits; D017180:Tachycardia, Ventricular / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome
D001549:Benzamides; C105049:nibentan