Pharmacological Post-conditioning On Acute Myocardial Ischemia/Reperfusion Injury In Rats

Objective:Preconditioning and postconditioning were known to effectively protect the heart from ischemia/reperfusion injury in acute myocardial infarction (AMI).Further research is needed to find new pharmacological agents that would mimic postconditioning in order to better deal with the patients with ongoing AMI and reperfusion.In the present study,it was investigated the effects and mechanism of diltiazem-related pharmacological postconditioning on acute myocardial ischemia/reperfusion injury in an in vivo model of AMI in rats, compared with the effects of ischemia-postconditioning.Methods:A total of 72 rats were randomly divided into 6 groups(n=12 in each group).Control group,Sham operation group,Post-conditioning group, Diltiazem 1(D1) group,(700 ug/kg,injected through the root of aorta),Diltiazem 2(D2) group,[initial 700 ug/kg followed by 5 ug/(kg·min )continual injection for 2 hours]and Diltiazem 3(D3) group,[initial 700 ug/kg followed by 10 ug/ (kg·min) continual injection for 2 hours].The rats were suffered from myocardial ischemia by left coronary artery occlusion followed with 3 hours of reperfusion.Infarct size,hemodynamics,serum concentrations of creatine kinase isoenzyme MB,and the levels of myocardial nitric oxide,superoxide dismutase and malondialdehyde were examined and western blot of bcl-2 and bax results were compared 3 hours after the infarction..Results:Compared with Control group,infarct size in post-conditioning and Diltiazem groups were significantly reduced(14.80±4.64%vs.7.37±2.22%, 9.32±2.96%,8.38±2.52%,5.22±2.30%,P＜0.01).The levels of serum creatine kinase isoenzyme MB,nitric oxide and malondialdehyde were significantly lower; the level of superoxide dismutase was significantly higher in Sham operation group,Diltiazem groups and Post-conditioning group.The level of±dp/dtmax in Sham operation and D3 group were significantly higher than in Control group. The expression of Bax and Bcl-2 was not altered significantly by treatment with diltiazem.Conclusion:Pharmacological postconditioning with diltiazem,by means of alleviating calcium overload and oxyradical over-production,could effectively reduces infarct size and improves cardiac function in AMI rats remarkbly.These protective effects are associated with the duration and dosage of diltiazem. Objective:To evaluate the beneficial effects and mechanism of pharmacological post-conditioning of ozagrel in acute myocardial ischemia/reperfusion rat model and whether myocardium cell necrosis could be inhibited by treatment with TXA₂ antagonist.Methods:A total of 48 rats were randomized into 4 groups:Ischemia-reperfusion (I/R),Sham,Ozagrel low dose(Ozagrel L),Ozagrel high dose (Ozagrel H).The rats were suffered from myocardial ischemia by coronary occlusion followed with 24 hours of reperfusion.5 minutes before reperfusion, ozagrel L group received an i.v.injection of ozagrel by 15 mg/kg and ozagrel H group received by 30 mg/kg.Hemodynamics,infaction size and the level of CK and CK-MB were analyzed.Apoptosis methods:TUNEL staining and western blot of bcl-2 and bax results were compared.Results:In comparison with I/R group,ozagrel L group and ozagrel H group significantly reduced infarct size(22.75±3.24 vs.18.73±3.12,16.98±2.96,P＜0.05, P＜0.01 ),decreased the level of CK and CK-MB and improved±dp/dtmax. Myocardium cell necroses were observed by the methods of TUNEL staining.The expression of Bcl-2 was increased significantly by treatment of ozagrel H group.Conclusion:Pharmacological post-conditioning of ozagrel could effectively reduce infarct size,inhibit myocardium cell necrosis and apoptosis,improves cardiac function in experimental rat acute ischemic/reperfusion injury model obviously.This benefit may due to the higher expression of bcl-2,and at certain point,associated with the dose of ozagrel.