Effect of sevoflurane on phosphorylation of connexin 43 at ser368 in ventricular myocardium in isolated hearts of diabetic rats

Abstract

Objective To evaluate the effect of sevoflurane on phosphorylation of connexin 43 (Cx43) at Ser368 (Cx43 Ser368) in ventricular myocardium in isolated hearts of diabetic rats. Methods Twenty-four clean-grade healthy adult male Sprague-Dawley rats, aged 3 months, weighing 180-220 g, were used in this study.The diabetic model was established by intraperitoneally injecting streptozotocin 60 mg/kg.The hearts were rapidly excised and retrogradely perfused with K-H solution saturated with 95% O2-5% CO2 at 37 ℃ in a Langendorff apparatus.Sixteen Langendorff-perfused diabetic hearts were divided into 3 groups (n=8 each) using a random number table method: diabetes mellitus group (group D) and sevoflurane group (group DS). Another 8 Langendorff-perfused normal hearts of rats were selected and served as control group (group C). After 15 min equilibration with K-H solution, the hearts were continuously perfused for 30 min with K-H solution in group C and group D and with K-H solution saturated with 2.5% sevoflurane in group DS.S1S2 program-controlled stimulation was performed at the end of perfusion, the occurrence of induced ventricular arrhythmia (VA) and the maximal pacing cycle length (PCL) of induced VA were recorded, and conduction velocity (CV) was calculated.The expression of phosphorylated Cx43 at Ser368 (p-Cx43 Ser368) in ventricular myocytes was determined by Western blot. Results Compared with group C, the incidence of induced VA was significantly increased, the maximal PCL of induced VA was prolonged, the CV was decreased, and the expression of p-Cx43 Ser368 was up-regulated in group D (P<0.05). Compared with the incidence of induced VA was significantly decreased, the maximal PCL of induced VA was shortened, the CV was increased, and the expression of p-Cx43 Ser368 was down-regulated in group DS (P<0.05). Conclusion The mechanism by which sevoflurane stabilizes the ventricular electrical conduction is associated with decreasing the phosphorylation of Cx43 at Ser368 in diabetic rats. Key words: Anesthetics, inhalation; Diabetes mellitus; Connexins