Functional interaction between DPI 201-106, a drug that mimics congenital long QT syndrome, and sevoflurane on the guinea-pig cardiac action potential.
1. Sevoflurane produces QT prolongation on the electrocardiogram, predominantly via inhibition of the slow delayed rectifier K(+) current. DPI 201-106 is an experimental drug that produces QT prolongation by reducing Na(+) channel inactivation, thereby mimicking congenital long QT syndrome type 3 (LQT3). The present study explores the electrophysiological consequences of administration of sevoflurane in the presence of impaired Na(+) channel activity. 2. We examined the effects of sevoflurane and DPI 201-106, alone and in combination, on the cardiac action potential of guinea-pig ventricular myocytes using standard microelectrode techniques. 3. Both sevoflurane and DPI-201-106 prolonged action potential duration, with the combination of the two drugs producing greater than additive effects. Similarly, instability and triangulation of the action potential waveform, measures of pro-arrhythmia, were more pronounced when both drugs were combined. 4. Sevoflurane treatment significantly alters cardiac action potential waveforms when administered in the presence of impaired Na(+) channel inactivation. These results indicate the potential for ventricular arrhythmia when sevoflurane is administered to LQT3 patients and suggests caution when using sevoflurane in this population.
Kang
Jiesheng
J
Department of Drug Safety Evaluation, Sanofi-Aventis US Inc., Bridgewater, NJ 08807, USA.
Chen
Xiao-Liang
XL
Reynolds
William P
WP
Rampe
David
D
D000200:Action Potentials / Q000187:drug effects; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology; D008133:Long QT Syndrome / Q000139:chemically induced / Q000151:congenital / Q000503:physiopathology*; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology*; D000077149:Sevoflurane
D018685:Anesthetics, Inhalation; D002316:Cardiotonic Agents; D008738:Methyl Ethers; D010879:Piperazines; D000077149:Sevoflurane; C046261:DPI 201-106