| Background:Ischemic preconditioning (IPC)was the most powerful measure of endogenous cardioprotection against ischemia/reperfusion injury,but it,s clinical application has been hampered by the requirement of intervention before onset of acute myocardial ischemia,which is clearly impossible in the setting of an acute myocardial infarction.Ischemic postconditioning(IPOC) can be triggered during the clinically applicable period of reperfusion,but it has the same limitation as the IPC,i.e.the requirement of an invasive protocal.Pharmacological postconditioning (PPOC) is an alternative method that may substitute invasive measures of the brief transient ischemia,but it was also limited for single treatment.Remote ischemic preconditioning(RIPC) is another method of endogenous cardioprotection,i.e.brief ischemia stimulus on organ or tissure outside of heart would render the heart more tolerant to the subsequential prolonged ischemia.Limb RIPC is triggered by brief limb ischemia,which can be manipulated with the simple tools like tourniquet.Because limb RIPC is simple,safe,non-invasive and cost less , it is feasible and has a great value in clinical practice . After the cardioprotective effect of IPOC against ischemia/reperfusion injury is confirmed,the brief limb ischemia during a prolonged period of myocardial ischemia and before coronary artery reperfusion , i.e.the limb remote ischemia postconditioning (RIPOC),has also been immediately shown to produce cardioprotection in some aminal models and clinical trials.In contrast to IPC and limb RIPC,RIPOC can be triggered after ischemia.Also,it doesn't need invasive intervention as IPOC does . Therefore , limb RIPOC may have a promising future in all clinical scenarios.However,the available data show that cardioprotection induced by RIPOC is weaker compared with IPC.Therefore,searching for more effective clinical measures becomes imperative.As we all know,free radical generated by a large number is one of the mechanisms in myocardial ischemia/reperfusion injury.Edaravone,a novel free radical scavenger,is widely used as a drug of treatment to acute cerebral infarction in clinical scenarios initially.Then people discovered it,s potential value of myocardial protection,therefore,we introduced the drug.Combination of measures is often more effective,and it has became one of the most popular research focuses.Therefore,we designed the research which was combined adaravone PPOC with limb RIPOC in order to provide more simple,rational and effective treatment against myocardial ischemia/reperfusion injury in clinical scenarios.Objective:To evaluate the influence of PPOC with low-dose edaravone and transient limb RIPOC on myocardial ischemia/reperfusion injury.At the same time,to investigate whether combination of the two meatures will offer additional benefit of myocardial protection.Material and methods:Forty anesthetized Sprague Dawley rats(weighted 250 to 300g)aged 8 weeks old were randomly divided into 5 groups.All rats underwent ligation of the left anterior descending coronary artery (LAD) to establish ischemia/reperfusion models,with the LAD occluded for 30 min and reperfused for 180 min.Group C underwent sham operation;Group I/R underwent occlusion of the LAD for 30 min and reperfusion for 180 min;Group E1 underwent injection of edaravone,3 mg/kg into the lingual vein 1 min before reperfusion;Group E2 underwent limb remote ischemic postconditioning 10 min before reperfusion;Group E3 underwent limb remote ischemic postconditioning 10 min and injection of edaravone,3 mg/kg into the lingual vein 1 min before reperfusion.Left ventricular performance(LVSP,LVEDP,±dp/dt) were examinated in different time.By the end of reperfusion arterial blood was collected to measure serum biochemical markers : lactate dehydrogenase(LDH) , creatine kinase(CK) , superoxide dismutase (SOD) and malondialdehyde(MDA).Myocardium tissues were analyzed under light microscope and electron microscope.The infarct size of myocardium were also measured by Evans blue and TTC staining respectively.Results:1.The hemodynamic parameters,LVSP,+dp/dtmax,-dp/dtmax were higher and LVEDP was lower in all experimental groups than those in group I/R during reperfusion(P<0.05);LVSP,+dp/dtmax,-dp/dtmax were higher and LVEDP was lower in group E3 than those in group E1 and E2 during reperfusion,and the difference of change was statistically significant(P<0.05).2.Serum biochemical markers,SOD was more increasing and LDH,CK,MDA were more decreasing in all experimental groups than those in group I/R at the end of reperfusion;SOD was more increasing and LDH,CK,MDA were more decreasing in group E3 than those in group E1 and E2 by the end of reperfusion ,respectively , and the difference of change was statistically significant ( P <0.05).3.Histomorphology of myocardium under light microscope and electron microscope were also improved in all experimental groups,and group E3 was improved more distinctly than those in group E1 and E2 after reperfusion for 180min.4.The infarct size of myocardium was smaller in all experimental groups than that in group I/R,and that in group E3 was smaller than that in group E1 and E2,the difference of change was statistically significant(P<0.05). Conclusion:PPOC with edaravone provided obviously protective effect against myocardial ischemia/reperfusion injury in rats,and brief transient limb RIPOC provided a certain level of protective effect,too.The combination of the two methods can produce an enhenced cardioprotection. |
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