Antiarrhythmic effect of antazoline in experimental models of acquired short- and long-QT-syndromes

Abstract

Aims Antazoline is a first-generation antihistamine with antiarrhythmic properties. This study examines potential electrophysiological effects of antazoline in short-QT-syndrome (SQTS) and long-QT-syndrome (LQTS). Methods and results Sixty-five rabbit hearts were Langendorff-perfused. Action potential duration at 90% of repolarization (APD90), QT-interval, spatial dispersion (DISP), and effective refractory period (ERP) were measured. The IK, ATP-opener pinacidil (1 μM, n = 14) reduced APD90 (-14 ms, P<0.01), QT-interval (-14 ms, P<0.01), and ERP (-11 ms, P<0.01), thus simulating acquired SQTS. Additional infusion of 20 μM antazoline prolonged repolarization. Under baseline conditions, ventricular fibrillation (VF) was inducible in 5 of 14 hearts (10 episodes) and in 5 of 14 pinacidil-treated hearts (21 episodes, P = ns). Antazoline significantly reduced induction of VF (0 episodes, P<0.05 each). Further 17 hearts were perfused with 100 μM sotalol and 17 hearts with 300 μM erythromycin to induce acquired LQTS2. In both groups, prolongation of APD90, QT-interval, and ERP was observed. Spatial dispersion was increased (sotalol: +26 ms, P< 0.01; erythromycin: +31 ms, P<0.01). Additional infusion of antazoline reduced DISP (sotalol: -22 ms, P<0.01; erythromycin: -26 ms, P < 0.01). Torsade de pointes (TdP) occurred in 6 of 17 sotalol-treated (22 episodes, P<0.05 each) and in 8 of 17 erythromycin-treated hearts (96 episodes P<0.05 each). Additional infusion of antazoline completely suppressed TdP in both groups (P<0.05 each). Acquired LQTS3 was induced by veratridine (0.5 μM, n = 17) and similar results were obtained (APD90: +24 ms, P<0.01, QT-interval: +58 ms, P<0.01, DISP: +38 ms, P<0.01). Torsade de pointes occurred in 10 of 17 hearts (41 episodes, P<0.05 each). Antazoline significantly reduced TdP (2 of 17 hearts, 4 episodes, P<0.05 each). Conclusion Antazoline significantly reduced induction of VF in an experimental model of acquired SQTS. In three experimental models of acquired LQTS, antazoline effectively suppressed TdP.