| Acute myocardial infarction is myocardial ischemic necrosis.On the basis of the coronary artery lesions,serious and lasting myocardial ischemia leads to acute myocardial necrosis because of drastically reducing or discontinuing coronary blood supply.With thrombolytic drugs,percutaneous transluminal coronary angioplasty,aortic stenting and coronary artery bypass grafting to be succeed application, patients, mortality has declined to some extent.However, successful restoration of cardiac blood flow sometimes does not mean the recovery of the myocardial function but the aggravation of the myocardial injury, which is called ischemia-reperfusion injury.On clinic,some patients emerge arrhythmias,heart failure,cardiogenic shock,multiple organs failure and even sudden cardiac death.In 1960, the concept of the myocardial IRI was first raised by Jennings, and gradually was thank highly of the medical profession.With the in-depth study of the myocardial IRI,the researchers confirmed that the myocardial IRI could trigger the acute inflammatory response at the end of 1970s, which included the generation of the reactive oxygen species,the production of the myocardial cell factors (CK) and the chemical factors,complement activation,increased microvascular permeabi- lity,the degradation of the extracellular matrix and the cells death.More and more evidences have showed that the infiltration of the neutrophils in inflammatory reaction is one of the most important mechanisms in the myocardial reperfusion injury.Aprotinin,as a natural small molecule inhibitor of serine protease,is a basic peptide which can inhibit the release of multiple serine proteases.The researchers have found that aprotinin which possesses anti-oxidation,antiprotease hydrolysis,inhibiting the release of the inflammatory mediators and so on,can reduce myocardial ischemia- reperfusion injury.However,the researches about aprotinin to protective effect of myocardial cells in the current domestic and foreign are still in the exploration and development of the initial stage on the whole.In this experiment,we utilized that peoples, cardiovascular system is more similar to canines and reproduced myocardial ischemia-reperfusion injury model in vivo.From the myocardial tissue morphology and the inflammatory response, we observed the impact of the aprotinin in myocardial ischemia-reperfusion injury,and its possible mechanism would been discussed.Objective: By observing serum interleukin-8 (Interleukin-8,IL-8) and tumor necrosis factor-α(Tumor necrosis factor-α,TNF-α) levels and the extent of myocardial necrosis, we investigated the protective effect of the aprotinin in myocardial ischemia-reperfusion injury.Methods:The model of canine myocardial ischemia-reperfusion was duplicaded by binding-relaxing coronary artery.18 healthy canines were randomly divided into three groups(Sham,Ischemia-reperfusion,Drug). Sham group did not block blood flow but separated blood vessels.Before ischemia,Sham group,I/R group respectively was intravenous injeced100ml sodium chloride(0.8ml/min) until the end of the experiment;In Drug group,aprotinin (8500KIU/kg)was dissolved in 100 ml sodium chloride at the same speed until the end of the experiment.Blood samples from the canine femoral vein were drawn at different time points.The concentrations of TNF-αand IL-6 were detected by radio-immune method at the end of the experiment.4×4×4mm sizes of myocardial tissue was removed from the apex of heart,and was been stained by conventional hematoxylin eosin(HE).Under light microscope,we observed the extent of the myocardial cells injury and the leukocyte infiltration.Results:1.Throughout the course of the experiment,the content of IL-8 in Sham group did not change significantly;Before ischemia,the concentration of IL-8 in serum was no significant difference in the three groups(P>0.05) ;The concentrations of IL-8 in I/R group and Drug group were higher than that in Sham group(P<0.01) at different time of ischemia-reperfusion ;However,the content of IL-8 in Drug group was the lowest than that in I/R group,the difference was significant between them(P<0.01);Compared with before ischemia,the expressions of IL-8 in I/R group and Drug group increased obviously(P<0.01) at ischemia 120 minutes and reperfusion 60 minutes.2.In the entire of experimental,the level of TNF-αin Sham group did not change significantly;After reperfusion,the serum concentration of TNF-αin I/R group increased significantly than that in Sham group(P<0.01) ;Compared with Sham group, the level of TNF-αin Drug group had increased but did not reach statistical significance(P>0.05);At reperfusion 60 minutes,the serum level of TNF-αwas 723±30.6pg/ml in I/R group,which was 590.5±26.2pg/ml in Drug group, So there was obviously difference between them(P<0.01).3. Myocardial tissue changed The observation of the light microscopy showed:In Sham group,myocardial cells structure was basically normal,myocardial fibers dying was uniform, myocardial cells boundaries were clear,myocardial interstitium had not edema and did not been infiltrated by inflammatory cells ;In Drug group, part of myocardial fibers were wavy,myocardial cytoplasm distributed uneven,myocardial interstitium had not edema and haemorrhage,but had the number of inflammatory cells.So myocardial tissue injury was lighter than that in I/R group.In I/R group, these changes were very obviously.Some myocardial cells swelled and had granular objects and irregular bands in cytoplasm,myocardial cells boundaries were dimness ;Cell nucleus were fragmented even disappeared ;Myocardial cells had necrosis and the infiltration of many leukocytes.6 Conclusions:Because aprotinin reduced the levels of IL-8 and TNF-α,lighten myocardial injury,restrained the infiltration of the leukocytes in ischemia-reperfusion,aprotinin could protect the myocardial ischemia- reperfusion injury.Mechanism could depressed the activity of white cell and diminished the synthesis or release of the cytokines.
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