Abstract
There is conflicting evidence regarding the impact of propofol on cardiac repolarization and the risk of torsade de pointes (TdP). The purpose of this study was to elucidate the risk of propofol-induced TdP and to investigate the impact of propofol in drug-induced long QT syndrome. 35 rabbit hearts were perfused employing a Langendorff-setup. 10 hearts were perfused with increasing concentrations of propofol (50, 75, 100 µM). Propofol abbreviated action potential duration (APD90) in a concentration-dependent manner without altering spatial dispersion of repolarization (SDR). Consequently, no proarrhythmic effects of propofol were observed. In 12 further hearts, erythromycin was employed to induce prolongation of cardiac repolarization. Erythromycin led to an amplification of SDR and triggered 36 episodes of TdP. Additional infusion of propofol abbreviated repolarization and reduced SDR. No episodes of TdP were observed with propofol. Similarly, ondansetron prolonged cardiac repolarization in another 13 hearts. SDR was increased and 36 episodes of TdP occurred. With additional propofol infusion, repolarization was abbreviated, SDR reduced and triggered activity abolished. In this experimental whole-heart study, propofol abbreviated repolarization without triggering TdP. On the contrary, propofol reversed prolongation of repolarization caused by erythromycin or ondansetron, reduced SDR and thereby eliminated drug-induced TdP.
Highlights
There is conflicting evidence regarding the impact of propofol on cardiac repolarization and the risk of torsade de pointes (TdP)
Some other experimental studies have investigated effects of propofol in different models of long QT syndrome (LQTS): In healthy and transgenic LQT2 and LQT3 rabbits, propofol administration resulted in an increase of QT index resulting in arrhythmia-related death in two LQT2 rabbits[5]
Infusion of propofol abbreviated APD90 in a concentration-dependent manner while QT interval remained relatively stable at the lowest propofol concentration and was slightly abbreviated under the influence of 75 and 100 μM propofol
Summary
There is conflicting evidence regarding the impact of propofol on cardiac repolarization and the risk of torsade de pointes (TdP). The purpose of this study was to elucidate the risk of propofol-induced TdP and to investigate the impact of propofol in drug-induced long QT syndrome. Repolarization was abbreviated, SDR reduced and triggered activity abolished In this experimental whole-heart study, propofol abbreviated repolarization without triggering TdP. Propofol reversed prolongation of repolarization caused by erythromycin or ondansetron, reduced SDR and thereby eliminated drug-induced TdP. Previous clinical and experimental studies report conflicting data regarding its impact on ventricular repolarization and potential proarrhythmic effects. An increased Tpeak-Tend interval is a surrogate for an amplified transmural dispersion of repolarization which in turn represents a major risk factor for drug-induced arrhythmias[8]. In another study employing a model of (drug-induced) LQTS, propofol reduced the action potential duration increase mediated by erythromycin[10]. This study aimed at elucidating further potential mechanisms in arrhythmia initiation induced by propofol
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