IONIC BASIS OF THE DIFFERENTIAL-EFFECTS OF INTRAVENOUS ANESTHETICS ONERYTHROMYCIN-INDUCED PROLONGATION OF VENTRICULAR REPOLARIZATION IN THE GUINEA-PIG HEART

Background: Dysrhythmias and death occur in patients with acquired lon g 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 concen trations (0, 10, 25, and 50 mu M) of propofol, ketamine, and thiopenta l an ventricular repolarization were evaluated by measuring the monoph asic action potential duration at 90% repolarization (MAPD(90)) in gui nea pig Langendorff-perfused hearts in the absence or presence of eryt hromycin (100 mu M). If an anesthetic enhanced erythromycin-induced pr olongation of MAPD(90), its effects on the delayed rectifier (I-K) and inward rectifier (I-KI) potassium currents were measured using the wh ole-cell patch-clamp technique. Results: At clinically relevant concen trations, only thiopental significantly modulated erythromycin's effec t on MAPD(90). Thiopental at 10, 25, and 50 mu M prolonged MAPD(90) fr om a control of 163 +/- 6 ms by 18 +/- 4, 30 +/- 5, and 31 +/- 4 ms,re spectively. 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 e rythromycin, thiopental at 10, 25, and 50 ECM caused significantly gre ater prolongation from a control of 171 +/- 2 ms by 39 +/- 2, 58 +/- 3 , and 72 +/- 6 ms, respectively. Whole-sell patch-clamp experiments in dicated that thiopental inhibited I-K and I-KI. Conclusions: intraveno us anesthetics caused markedly different effects on ventricular repola rization. Thiopental, unlike propofol and ketamine, potentiated the ef fects of erythromycin on ventricular repolarization by inhibiting I-K and I-KI.