Effects of halothane on action potential configuration in sub-endocardial and sub-epicardial myocytes from normotensive and hypertensive rat left ventricle.

Abstract

Halothane shortens ventricular action potential duration (APD), as a consequence of its inhibitory effects on a variety of membrane currents, an effect that is greater in sub-endocardial than sub-epicardial myocytes. In hypertrophied ventricle, APD is prolonged as a consequence of electrical remodelling. In this study, we compared the effects of halothane on transmural APD in myocytes from normal and hypertrophied ventricle. Myocytes were isolated from the sub-endocardium and sub-epicardium of the left ventricle of spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Action potentials were recorded before, during, and after a 1-min exposure to 0.6 mM halothane and APD measured from the peak of the action potential to repolarization at -50 mV (APD(-50 mV)). Data are presented as mean (SEM). In WKY myocytes, halothane reduced APD(-50 mV) from 21 (2) to 18 (2) ms (P<0.001, n=15) in sub-epicardial myocytes but abbreviated APD(-50 mV) to a greater extent in sub-endocardial myocytes (37 (4) to 28 (3) ms; P<0.001, n=14). In SHR myocytes, APD(-50 mV) values were prolonged compared with WKY and APD(-50 mV) was reduced by halothane from 36 (6) to 27 (4) ms (P<0.016) and from 77 (10) to 38 (4) ms (P<0.001) in sub-epicardial and sub-endocardial myocytes, respectively. In the SHR, hypertrophic remodelling was not homogeneous; APD(-50 mV) was prolonged to a greater extent in sub-endocardial than sub-epicardial cells. Halothane reduced APD to a greater extent in sub-endocardium than sub-epicardium in both WKY and SHR but this effect was larger proportionately in SHR myocytes. The transmural gradient of repolarization was reduced in WKY and effectively abolished in SHR by halothane, which might disturb normal ventricular repolarization.