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CARDIOVASCULAR ANESTHESIA

The Effects of Halothane, Isoflurane, and Sevoflurane on Ca²⁺ Current and Transient Outward K⁺ Current in Subendocardial and Subepicardial Myocytes from the Rat Left Ventricle

Amber Rithalia, PhD^*, Philip M. Hopkins, MD, and Simon M. Harrison, PhD^*

*School of Biomedical Sciences and Academic Unit of Anaesthesia, University of Leeds, Leeds, United Kingdom

Address correspondence and reprint requests to Simon M. Harrison, PhD, School of Biomedical Sciences, University of Leeds, Leeds, LS2 9JT, UK. Address e-mail to S.M.Harrison{at}Leeds.ac.uk

Halothane, isoflurane, and sevoflurane abbreviate ventricular action potential duration (APD), and for halothane this effect is greater in the subendocardium than in the subepicardium. In this study we investigated mechanisms underlying the regional effects of these anesthetics on APD. The effect of 0.6 mM halothane, isoflurane, and sevoflurane on the action potential, L-type Ca²⁺ current, transient outward K⁺ current (I_to), and steady-state current was recorded in rat left ventricular subendocardial and subepicardial myocytes. Halothane and isoflurane (but not sevoflurane) reduced APD significantly (P < 0.05), more in subendocardial than subepicardial myocytes. Peak L-type Ca²⁺ current did not differ between regions and, compared with control, was reduced significantly in both regions by 40% (P < 0.001), 20% (P < 0.001), and 12% (P < 0.01) by halothane, isoflurane, and sevoflurane, respectively. I_to was greater in subepicardial (3.95 ± 0.29 nA) than subendocardial (1.12 ± 0.05 nA) myocytes. In subepicardial myocytes, peak I_to was reduced significantly by halothane (P < 0.01) and isoflurane (P < 0.05) (by 8% and 7%, respectively) but was unaffected by sevoflurane. No significant reduction of I_to was observed in subendocardial myocytes with the three anesthetics. The steady-state current was increased significantly (P < 0.05), but the extent of this increase did not differ between the two regions or among the three anesthetics. Therefore, greater inhibition of I_to in subepicardial than subendocardial myocytes by halothane and isoflurane could underlie their transmural effects on APD.

IMPLICATIONS: Halothane, isoflurane, and sevoflurane reduce action potential duration (APD) by virtue of inhibitory effects on membrane currents, principally the calcium current. The differential effects of anesthetics on APD in the subepicardium and subendocardium appear to be due to their inhibitory action on the transient outward K⁺ current.

This article has been cited by other articles:

				G. Bru-Mercier, P. M. Hopkins, and S. M. Harrison Halothane and sevoflurane inhibit Na/Ca exchange current in rat ventricular myocytes Br. J. Anaesth., September 1, 2005; 95(3): 305 - 309. [Abstract] [Full Text] [PDF]