Voltage-dependent effects of volatile anesthetics on cardiac sodium current.
Cardiac dysrhythmias during inhaled anesthesia are well documented and may, in part, involve depression of the fast inward Na+ current (INa) during the action potential upstroke. In this study, we examined the effects of halothane, isoflurane, and sevoflurane at clinically relevant concentrations on INa in single ventricular myocytes isolated enzymatically from adult guinea pig hearts. INa was recorded using standard whole-cell configuration of the patch clamp technique. Halothane at 0.6 mM and 1.2 mM produced significant (P < 0.05) depressions of peak INa of 12.3% +/- 1.8% and 24.4% +/- 4.1% (mean +/- SEM, n = 12), respectively. Isoflurane (0.5 mM, n = 12; 1.0 mM, n = 15) and sevoflurane (0.6 mM, n = 14; 1.2 mM, n = 12) were less potent than halothane, decreasing peak INa by 4.8% +/- 1.1% and 11.4% +/- 1.4% (isoflurane) and 3.0% +/- 0.7% and 10.7% +/- 3.9% (sevoflurane). The depressant effects on INa were reversible in all cases. For all anesthetics tested, the degree of block increased at more depolarizing potentials. Anesthetics induced significant shifts in the steady-state inactivation and activation of the channel toward more hyperpolarizing potentials. The present findings indicate that volatile anesthetics at clinical concentrations decrease the cardiac INa in a dose- and voltage-dependent manner. At approximately equianesthetic concentrations, the decrease of INa caused by halothane was twice that observed with isoflurane or sevoflurane.
Weigt
H U
HU
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Kwok
W M
WM
Rehmert
G C
GC
Turner
L A
LA
Bosnjak
Z J
ZJ
D000200:Action Potentials / Q000187:drug effects; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D004987:Ethers / Q000494:pharmacology; D006168:Guinea Pigs; D006221:Halothane / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology; D008738:Methyl Ethers; D009206:Myocardium / Q000166:cytology; D018408:Patch-Clamp Techniques; D000077149:Sevoflurane; D015222:Sodium Channels / Q000502:physiology*
D018685:Anesthetics, Inhalation; D004987:Ethers; D008738:Methyl Ethers; D015222:Sodium Channels; D000077149:Sevoflurane; D007530:Isoflurane; D006221:Halothane