Lubeluzole-induced prolongation of cardiac action potential in rabbit Purkinje fibres

Lubeluzole, a novel neuroprotective compound, has been associated with case s of QT interval prolongation but its effects on the cardiac action potenti al have not been described to date. Thus, the electrophysiological effects of lubeluzole were studied in rabbit isolated Purkinje fibres. The results demonstrate that lubeluzole (0.001-1 mu M) concentration-dependently length ened action potential duration at 50 % and 90 % of repolarization (APD(50) and APD(90)) without significantly modifying other parameters. Furthermore, APD lengthening induced by lubeluzole was not significantly decreased by r educing the basic cycle length (from 3 000 to 1 000 ms). The results demons trate that lubeluzole potently and concentration-dependently increases APD from 0.01 mu M, consistent with class III-type antiarrhythmic actions, whic h is likely to underlie QT interval prolongation induced by the drug. (C) 2 000 Editions scientifiques et medicales Elsevier SAS.