Postconditioning Effects Of Oral Nicorandil Treatment On Patients With Acute Anterior Myocardial Infarction

BackgroundIn recent years, the development of thrombolysis and percutaneous coronaryintervention （PCI） have positive impacts on outcome of the patients with acutemyocardial infarction （AMI）, but the reperfusion injury followed by these treatmentsper se would lower the benefit.After carrying on a large amount of research, peoplehave found that ischemic preconditioning can decrease the reperfusion injury andreduce the infarct size, which is a strong endogenous myocardial protective form ofreducing reperfusion injury. But it must be operated in a transient time beforemyocardial ischemia, which is the bottleneck of its wide clinical application.Butrecent research has found that ischemic postconditioning can exert cardioprotectiveeffect as well when operated after a short period of myocardial ischemia, which hasbecome a hotspot of coronary heart disease therapy researches.Since the mitochondria potassium ATP(mito-K_ATP) channel is at the downstreamof signal pathway of preconditioning and postconditioning, the activation of mito-K_ATPchannel can directly induce preconditioning and postconditioning.Nicorandil is a medicine which can act as agonist of mito-K_ATP channel and hasnitrates effect. The pharmacologic preconditioning caused by Nicorandil has beenconfirmed in animal experiments and clinical tests. By activating mito-K_ATP channel, Nicorandil can cause pharmacologic postconditioning, theoretically. However, atpresent there is only a few animal experiments validating the postconditioningproperty of nicorandil. No further clinical experiments develops this topic.AimTo test whether nicorandil can induce pharmacologic postconditioning or not,and to test whether it can reduce the infarct size of the acute anterior myocardialinfarction, which achieve the result of limiting the injury of reperfusion.Materials and MethodsPatients with acute anterior ST-segment elevation myocardial infarction weretreated in the emergency department of Zhongshan People’s Hospital during theperiod of March2011to January2012. They were enrolled and randomly divided intogroup NIC and group ISDN. Patients in NIC group were taken10mg Nicorandil （NIC）orally before PCI procedure and treated with5mg Nicorandil three times a day for7days. Patients in ISDN group were given Isosorbide Dinitrate（ISDN） in the samemethod.By observing the changes of ECG ST-segment before operation and1hour afteroperation, the ST-segment resolution rate was gained; and the blood samples weretaken from all patients before operation and8h,16h,24h,48h,72h after operation,which are used to observe the dynamic changes of CKMB. At last, the ECTmyocardial perfusion examinations were performed in the patients on the7thday afteroperation, which can reflect the infarct size of the acute anterior myocardial infarction.ResultsAccording to the criteria of inclusion and exclusion, the final experimentalsubjects are43patients with acute anterior myocardial infarction.There were21patients in group NIC and22in group ISDN. Compared with the ISDN, nicorandil can considerably reduce the peak value ofcreatine kinase myocardial band. NIC group（171.6±105.7U/L） vs ISDN group（246.4±108.4U/L），p<0.05. They can also reduce the area under the curve. NICgroup （4309±2575） vs ISDN group （5854±2352），p<0.05.In addition, nicorandil can reduce the proportion of ECT myocardial pefusiondefect extent in left ventricle: NIC Group （30.38±11.83%） vs ISDNgroup（38.64±14.59%），p<0.05. And ECT perfusion defect score is: NIC Group（25.19±11.96） vs ISDN group （33.27±14.03），p<0.05.Moreover, NIC group had a better ECG ST-segment resolution. There are18patients in NIC group and13patients in ISDN group having experienced ST-segment completely resolution.The ST-segment resolution rate of the two groups are85.71%and59.09%，p<0.05, respectively.Conclusions1.Before giving reperfusion in the patients with acute anterior myocardial infarction,oral nicorandil treatment within1hour can improve ECG ST-segment resolution,reduce the peak value of CKMB and the area under the curve of CKMB, and decreasethe proportion of ECT myocardial pefusion defect extent in left ventricle and ECTperfusion defect score.2.By activating the mito-K_ATPchannel, nicorandil can induce pharmacologicpostconditioning effect, limit the infarct size of the acute anterior myocardialinfarction and decrease the reperfusion injury, which eventually form cardioprotectiveeffects. Besides，This effect is no related to nitrate effect.