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 QT syndrome.


METHODS
The effects of increasing concentrations (0, 10, 25, and 50 microM) of propofol, ketamine, and thiopental on ventricular repolarization were evaluated by measuring the monophasic action potential duration at 90% repolarization (MAPD90) in guinea pig Langendorff-perfused hearts in the absence or presence of erythromycin (100 microM). If an anesthetic enhanced erythromycin-induced prolongation of MAPD90, its effects on the delayed rectifier (I[K]) and inward rectifier (I[Kl]) potassium currents were measured using the whole-cell patch-clamp technique.


RESULTS
At clinically relevant concentrations, only thiopental significantly modulated erythromycin's effect on MAPD90. Thiopental at 10, 25, and 50 microM prolonged MAPD90 from a control of 163 +/- 6 ms by 18 +/- 4, 30 +/- 3, and 31 +/- 4 ms, respectively. In a separate group, erythromycin prolonged MAPD90 from 155 +/- 2 ms to 171 +/- 2 ms (n = 21, P < 0.001). In the presence of erythromycin, thiopental at 10, 25, and 50 microM caused significantly greater prolongation from a control of 171 +/- 2 ms by 39 +/- 2, 58 +/- 3, and 72 +/- 6 ms, respectively. Whole-cell patch-clamp experiments indicated that thiopental inhibited I(K) and I(Kl).


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(Kl).
Morey
T E
TE
Department of Anesthesiology, University of Florida, Gainesville 32610-0254, USA.
Martynyuk
A E
AE
Napolitano
C A
CA
Raatikainen
M J
MJ
Guyton
T S
TS
Dennis
D M
DM
D000200:Action Potentials / Q000187:drug effects; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D004917:Erythromycin / Q000633:toxicity*; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles; D008133:Long QT Syndrome / Q000139:chemically induced*; D008297:Male; D015221:Potassium Channels / Q000187:drug effects
D018686:Anesthetics, Intravenous; D015221:Potassium Channels; D004917:Erythromycin