Ionic basis of the differential effects of intravenous anesthetics on erythromycin-induced prolongation of ventricular repolarization in the guinea pig heart

Background: Dysrhythmias and death occur in patients with acquired long QT syndrome (LQTS), Little information exists regarding interactions between anesthetics and drugs that prolong ventricular repolarization Therefore the effects of three commonly used intravenous anesthetics on ventricular repolarization were investigated in the setting of drug-induced, long BT syndrome, Methods:: The effects of increasing concentrations (0, 10, 25, and 50 mu M) of propofol, ketamine, and thiopental an ventricular repolarization were evaluated by measuring the monophasic action potential duration at 90% repolarization (MAPD(90)) in guinea pig Langendorff-perfused hearts in the absence or presence of erythromycin (100 mu M). If an anesthetic enhanced erythromycin-induced prolongation of MAPD(90), its effects on the delayed rectifier (I-K) and inward rectifier (I-KI) potassium currents were measured using the whole-cell patch-clamp technique. Results: At clinically relevant concentrations, only thiopental significantly modulated erythromycin's effect on MAPD(90). Thiopental at 10, 25, and 50 mu M prolonged MAPD(90) from a control of 163 +/- 6 ms by 18 +/- 4, 30 +/- 5, and 31 +/- 4 ms,respectively. in a separate group, erythromycin prolonged MAPD(90) from 155 +/- 2 ms to 171 +/- 2 ms (n = 21, P < 0.001). In the presence of erythromycin, thiopental at 10, 25, and 50 ECM caused significantly greater prolongation from a control of 171 +/- 2 ms by 39 +/- 2, 58 +/- 3, and 72 +/- 6 ms, respectively. Whole-sell patch-clamp experiments indicated that thiopental inhibited I-K and I-KI. Conclusions: intravenous anesthetics caused markedly different effects on ventricular repolarization. Thiopental, unlike propofol and ketamine, potentiated the effects of erythromycin on ventricular repolarization by inhibiting I-K and I-KI.