In healthy ventricular tissue, expression of the transient outward K⁺ current is greater in subepicardial (EPI) than subendocardial (ENDO) cells (Antzelevitch et al. 1991) contributing to the shorter action potential in the sub-epicardium. This transmural gradient of action potential duration (APD) is important for normal repolarisation of the ventricle. We have demonstrated previously that 0.6 mM halothane (~2 Ω MAC₅₀) decreased APD to a greater extent in ENDO than EPI cells (Rithalia et al. 2001), reducing the normal transmural dispersion of repolarisation which may contribute to the arrhythmogenic properties of halothane. Here we examine the effects of isoflurane and sevoflurane, volatile anaesthetics with less pronounced arrhythmogenic properties, on APD in ENDO and EPI cells.

Hearts were removed from male Wistar rats (weight, 200-250 g; Schedule 1 method) and cells isolated from the subendocardium and subepicardium of the left ventricle with a standard enzymatic dissociation protocol. Action potential recordings were made at 30 °C using the perforated-patch technique in current-clamp mode before, during and after a 1 min exposure to 0.6 mM isoflurane or sevoflurane (~2 Ω MAC₅₀ for both). APD was measured as time (ms) from the peak of the action potential to repolarisation at 0 mV (APD_{0 mV}) and -50 mV (APD_{-50 mV}). Data are expressed as means ± S.E.M. Significance was determined with paired or unpaired t tests.

In both control groups, APD was longer in ENDO than EPI cells at both 0 and -50 mV (P < 0.01 for both). Isoflurane decreased APD in ENDO cells; e.g. APD_{-50 mV} was reduced from 44 ± 7 to 33 ± 5 ms; P < 0.05, n = 7 (Fig. 1), but had no effect on APD in EPI cells. Sevoflurane significantly reduced APD_{-50 mV} from 39 ± 6 to 33 ± 5 ms (P < 0.05, n = 7) but not APD_{0 mV} in ENDO cells. In EPI cells, sevoflurane reduced APD_{-50 mV} from 16 ± 2 to 15 ± 1 ms (P < 0.05, n = 8) but with no change in APD_{0 mV}.Comparing the above data with halothane, all three anaesthetics (at 0.6 mM, ~2 Ω MAC₅₀) reduced APD to a greater extent in ENDO than EPI cells such that the mean transmural APD_{-50 mV} was decreased to 49, 64 and 78 % of control for halothane, isoflurane and sevoflurane, respectively. The differential effects on transmural APD of the three anaesthetics may help elucidate their differential transmural negative inotropic effects and arrhythmogenic properties.This work was supported by The British Heart Foundation.

Figure 1. Action potential duration (mean ± S.E.M.) of ENDO and EPI cells under control conditions and following a 1 min exposure to 0.6 mM isoflurane (ISO) or sevoflurane (SEVO). *P < 0.05, **P < 0.01, ***P < 0.001.

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Rithalia, A., Boyett, M.R., Hopkins, P.M. & Harrison, S.M. (2001). Br. J. Anaesth. 86 (2), 317P.