Role of sarcolemmal KATP channel in sevoflurane-induced maintenance of electrophysiological stability of ventricular myocardium in diabetic rats

Abstract

Objective To evaluate the role of sarcolemmal ATP-sensitive potassium (sarcKATP) channel in sevoflurane-induced maintenance of electrophysiological stability of ventricular myocardium in diabetic rats. Methods Clean-grade healthy male Sprague-Dawley rats, aged 3 months, weighing 280-320 g, in which diabetes mellitus (DM) was induced by intraperitoneal streptozotocin 60 mg/kg and confirmed by blood glucose ≥16.7 mmol/L, were used in this study.Their hearts were excised after anesthesia and retrogradely perfused in a Langendorff apparatus at 4 weeks after establishing the DM model.Twenty-four Langendorff-perfused hearts were divided into 3 groups (n=8 each) using a random number table method: DM group (group D), DM plus sevoflurane group (group DS) and DM plus sevoflurane plus HMR-1098 group (group DSH). Another 8 Langendorff-perfused hearts of normal rats were selected as control group (group C). Hearts were perfused with 37 ℃ K-H solution via the aorta in each group, 15 min of equilibration later hearts were continuously perfused for 30 min with K-H solution in C and D groups, with K-H solution saturated with 2.5% sevoflurane in group DS, or with K-H solution saturated with 10 μmol/L HMR-1098 and 2.5% sevoflurane in group DSH.Monophasic action potential (MAP) duration at 50% and 90% repolarization (MAPD50 and MAPD90) in the endocardium and epicardium of the left ventricular anterior wall were recorded at 15 min of equilibration (T0) and 15 and 30 min of reperfusion (T1, 2), transmural dispersion of repolarization (TDR) was calculated.S1S2 program-controlled stimulation was performed at the end of perfusion to record the effective refractory period (ERP), ventricular arrhythmia (VA) induced and the longest pacing cycle length (PCL) of ventricular fibrillation threshold (VFT)induced.ERP/MAPD90 ratio was calculated. Results Compared with group C, TDR was significantly increased at T0, ERP/MADP90 ratio was decreased, the incidence of VA induced was increased, and the longest PCL of VFT induced was prolonged in group D (P<0.05). Compared with group D, TDR was significantly decreased at T2 in group DS (P<0.05), and ERP/MADP90 ratio was significantly increased, the incidence of VA induced was decreased, and the longest PCL of VFT induced was shortened in DS and DSH groups (P<0.05). TDR was significantly smaller at T2 in group DSH than in group DS (P<0.05). Conclusion sarcKATP channel is involved in sevoflurane-induced maintenance of electrophysiological stability of ventricular myocardium in diabetic rats. Key words: KATP channels; Anesthetics, inhalation; Diabetes mellitus; Cardiac electrophysiology