The Protection Of Adenosine On Myocardial Ischemia Reperfusion

With the acceleration of population's aging, the attack rates of cardial and cerebrovascular disease are becoming higher and higher gradually. PCI (percutaneous coronary intervention)has been the most important therapeutic method.However, 11 %～30 % of the acute myocardial infarction (AMI) patients with recanalization of occlusive coronary artery by emergency PCI may suffer slow flow or no flow phenomena.The rate of reoccurrence infarction ,malignant arrhythmia and heart failure increased dramatically,which influenced the prognosis of patients seriously.Therefore, it has been an international research field of how to improve myocardial reperfusion and reduce reperfusion injury.Adenosine has been studied widely as a myocardial protection drug which has been testified to protect the ischemia reperfusion injury myocardium in animal experiments. Adenosine can reduce infarction area, improve left ventricular function and increase coronary flow.Some foreign clinical trials have demonstrated that adenosine can reduce infarction area, reducing"no-reflow"area, increasing the long-term existence rate of AMI patients.However, there is few reports about the reperfusion injury myocardial protection of adenosine on AMI patients before emergency PCI in domestic clinical trials.This study consists of the basic experiment and the clinical trial . The rabbits were divided into four groups in basic experiment : control group,antagon group,postconditiong group and adenosine group.The protective effects of adenosine on instant reperfusion and postconditioning were observed through detecting the function of muscle contraction ,the extent of myocardial infarction by Evans blue and TTC,the activity of NF-κB by immunohistochemistry ,apoptosis cells by TUNEL,the activaty of MMP-2 and MMP-9 by gelatin zymography ,the expression of MMP-2 and MMP-9 by RT-PCR and Western Blot. The results showed that there was dramatic difference in LVSP , +dp/dtmax and -dp/dtmax after reperfusion between adenosine group ,postconditioning group and control group ,antagon group on instant reperfusion(P<0.05). The extent of myocardial infarction of adenosine group and postconditioning group was significantly lower than control group and antagon group(P<0.01).The occurrence of arrhythmia and outflow of LDH AND CK were much lower .There was dramatic diffenence between adenosine group ,postconditioning group and control group ,antagon group (P<0.01).The comparison showed that the expression of NF-κB decreased remarkably between adenosine group ,postconditioning group and control group ,antagon group( P<0.05). There was dramatic diffenence in the index of cell apoptosis between adenosine group ,postconditioning group and control group ,antagon group (P<0.05).The results of RT-PCR showed that the light density of MMP-2/ GAPDH(0. 76±0. 22) in adenosine group and postconditioning group was slightly lower than that of control group and antagon group0. 80±0. 20 (P>0.05). the light density of MMP-2/ GAPDH(0. 77±0. 12) in adenosine group and postconditioning group was significanty lower than that of control group and antagon group1.30±0. 10 (P <0.01).There was no dramitic difference between adenosine group and postconditioning group. The results of Western blot showed that MMP-9 and MMP-2 in adenosine group and postconditioning group was lower than control group and antagon group.The results of Zymography revealed that the light density of MMP-9 in adenosine group and postconditioning group much lower than those in control group and antagon group(P<0.05).There was no difference between adenosine group and postconditioning( P>0.05). The study results showed: there is no remarkable difference in protective effects on ischemia reperfusion myocardial between adenosine and postconditioning .Postconditioning can be inhibited by the blocker of adenosine receptor(8-phenyltheophylline )before ischemia, which confirms that adenosine and adenosine receptor are the most important mechanism of postconditioning.Adenosine can reduce the incidence and severity of reperfusion injury arrhythmy and the area of infarction,inhibite the inflammation ,decrease the apoptosis ,relieve the ischemia reperfusion injury and protect myocardium.In clinical trial ,60 AMI patients were divided randomly into two groups: adenosine group (n=30)and saline group(n=30).It is similar in sex,age,risk factors and infarction part between two groups. Patients of adenosine group were injected adenosine 3 hours before PCI. Patients of Saline group were injected saline 3 hours before PCI. Coronary arteriongraphies were performed through femoral artery, identifying related infarction artery,showing the criminal vessel by the suitable posture.The stents were implanted in related infarction artery after ballon expension .All patients were performed PCI successfully.The coronary flow was observed by CTFC. Myocardial perfusion was detected by TMP.Reperfusion arrhythmia,CK-MB,the activity of MMP-2 and MMP-9 were observed.The survival myocardium was monitored by IBS. (1)The results menifested that there was obvious difference in number of frames of blood flow between two groups on instant reperfusion.The adenosine group was dramatic lower than saline group (P<0.05).(2)No flow and slow flow occurred to 2 cases respectively in adenosine group. No flow occurred to4 cases and slow flow occurred to 6 cases(P<0.05). It revealed that there were No flow or slow flow phenomenna in part patients with acute myocardial infarction after successful PCI.(3)The TMP of saline was much lower than that of group (P<0.01) .(4)The occurrence of reperfusion arrhythmia was significantly lower than that of saline (P<0.01).(5)CK-MB was no dramatic difference between two group before PCI, while CK-MB in adenosine was much lower than that of saline after PCI (P<0.01).(6)It was observed that MMP-9 of patients in adenosine group was much lower than that of saline (P<0.05).(7)The comparison revealed that IBS of myocardium in saline group was dramatic higher than that of adenosine group , while CVIB of myocardium in saline group was significant lower than that of adenosine group(P<0.01) .The study results showed that adenosine injecting the AMI patients can relieve reperfusion injury and prevent from slow flow and no flow before emergency PCI.Adenosine can suppress the activity of MMP-9 and reduce the myocardial remodeling .It demonstrated that adenosine can reduce the extent of myocardial infarction.The suitable dose of adenosine is safe and endurable.It is viable for injecting adenosine before PCI..The effect of adenosine in postconditioning was investigated through animal experiment ,furthermore , the protection of adenosine in AMI patients was verified in clinical trial.Both basic and clinic experiments certified that adenosine can relieve myocardial reperfusion injury and protect myocardium.Therefore,it is feasible and effective that adenosine as a drug can be used in preconditioning and postconditioning,which offers the evidence for developing the clinical application of adenosine.