Propofol abolishes torsade de pointes in different models of acquired long QT syndrome

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 (APD 90) in a concentrationdependent 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.

Safe electrophysiologic profile of dexmedetomidine in different experimental arrhythmia models

“…In this study, erythromycin and veratridine were employed for induction of long QT syndromes type 2 and a model of reduced repolarization reserve, respectively. Both agents are established for the pharmacological simulation of these models 17 , 24 and lead to a substantial arrhythmogenicity by prolonging cardiac repolarization duration and amplifying spatial dispersion of repolarization.…”

“…The experimental Langendorff setup has been described earlier by our group 17 , 18 . In brief, 50 New Zealand White rabbit hearts were excised, attached to a Langendorff apparatus and retrogradely perfused.…”

Cardiovascular risk of energy drinks: Caffeine and taurine facilitate ventricular arrhythmias in a sensitive whole‐heart model

“…The technique of the Langendorff‐perfused rabbit heart has been described earlier by our group 13–15 . Briefly, 25 hearts of female New Zealand White rabbits were explanted and mounted to the Langendorff apparatus.…”

“…The technique of the Langendorff-perfused rabbit heart has been described earlier by our group. [13][14][15] Briefly, 25 Atrioventricular nodes of the spontaneously beating hearts were mechanically ablated with surgical tweezers to conduct the following pacing protocol: Initially, all hearts were paced at seven different cycle lengths (900-300 ms), thereby obtaining cycle-length dependent ventricular action potential duration (vAPD 90 ) and QT interval. Afterward, a rapid ventricular burst stimulation (five trains per-protocol step) was performed.…”

Propofol Causes Sustained Ca2+ Elevation in Endothelial Cells by Stimulating Ryanodine Receptor and Suppressing Plasmalemmal Ca2+ Pump

“…For instance, in animal models of acquired long QT syndrome, propofol reverses erythromycin-induced or ondansetroninduced prolongation of repolarization and, hence, druginduced torsade de pointes. 4 Propofol protects rat H9C2 cardiomyocytes from hypoxia reoxygenation-induced injury by alleviating mitochondrial damage and enhancing mitochondrial biogenesis by caveolin-3 upregulation. 5 Beneficial effects of propofol on the vasculature have also been demonstrated.…”