ABSTRACT
Objective To explore the protective effects of duloxetine on ventricular arrhythmia in rats with ischemia reperfusion injury.Methods Thirty Sprague Dawley (SD) rats were randomly divided into 3 groups:Sham group,ischemia reperfusion group (IR group),duloxetine-treated group (Dulo group).The rats in IR group were subjected to 30min-ischemia of left anterior descending artery ligation followed by 120min of reperfusion,while intraperitoneal injection of duloxetine 40mg/kg were give prior ischemia in Dulo group,and the remaining experiment protocols were same as IR group.The left anterior descending artery of rats in sham group was exposed without being clamped.Two biopotential leads ECG monitor was used to record the arrhythmia in each group,and ECG parameters were analyzed by LabChart 8 software.Triphenyltetrazolium chloride (TTC) was used for determination of infarct area.The protein expressions of Akt,extracellular regulated protein kinases (Erk),caspase-3,superoxide dismutase (SOD) 1,SOD2 and Connexin 43 (Cx 43) were measured by western blot analysis.Results As compared to IR group,the incidences of both ventricular extrasystoles and tachycardia were decreased during ischemic period (P ＜0.05),and the incidence of ventricular tachycardia was decreased with no significant changes in ventricular extrasystoles during reperfusion period in Dulo group (P ＜ 0.05).Duloxetine decreased the prolonged QTc and infraeted area during IR injury (P ＜ 0.05).Duloxetine inhibited the phosphorylation of Akt and Erk,and downregulated the protein expressions of cleaved caspase-3,cytochrome C,while upregulated SOD1,SOD2 and Cx 43 protein expression during I/R injury (P ＜ 0.05).Conclusion Duloxetine decreases the phosphorylation of Akt and Erk,inhibits oxidative stress and apoptosis,exerts anti-arrhythmogenic effects and decreases the occurrence of ventricular arrhythmia and infracted area induced by myocardial IR.