Effects Of Pretreating With Fluvastatin And Clopidogrel On Serum Interleukin-8 And Areas Of MI In AMI/R Rabbits

Background and objective. Recent studies suggest that interleukin-8 (IL-8) is involved in the neutrophil infiltration of subendothelial myocardial tissue in the ischaemia/reperfusion injury associated with acute myocardial infarction. Inhibitors of HMG-CoA-reductase reduce cardiovascularmortality though the mechanisms yet elucidated.The aim of this study was to investigate effects of pretreating with fluvastatin and clopidogrel on serum interleukin-8 and areas of MI in AMI/R Rabbits.Methods. Forty-two male New Zealand White rabbits were randomly divided into five groups: sham, control,fluvastatin,clopidogrel and fluvastatin+clopidogrel. Each group involves eight animals. The rabbits were fed daily with ordinary food. The animals of fluvastatin, clopidogrel and fluvastatin+clopidogrel groups were additionally respectively fed daily with fluvastatin(10mg/kg.d-1), clopidogrel(10mg/kg.d-1) and fluvastatin(10mg/kg.d-1)+clopidogrel(10mg/kg.d-1). Three days later the model of ischemia/reperfusion was established in both control and pretreatment animals. In the sham group,the heart was exposed after the chest had opened, but coronary artery wasn't ligated, two hundred and forty minutes after the procedure, the animals were killed. In the other four groups, the rabbits were subjected to a sixty minutes coronary occlusion followed by a three-hours reperfusion. Electrocardiogram was recorded before ischemia and postischemia respectively, and ST segment elevation means success in establishment of the model. Blood samples were extracted from right atrium before the animals were killed, and the blood was isolated with hypothermia high speed centrifugation. The serum was kept in hypothermia refrigeration(-70'C) for testing serum IL-8 and CK-MB. delineated the ischemia area at risk. After reperfusion, myocardial infarct size was determined by triphenyltetrazolium chloride staining.The cardiac muscle of MI was kept in hypothermia refrigeration(-70'C) for detecting MPO.Results. 1. The concentration of serum IL-8 in group control (5.2921±0.5076μg/l) was higher than that in group sham(0.6842±0.0337μg/l)(p<0.01); The concentration of serum IL-8 in group Fluvastatin(3.0876±0.5930μg/l) and in group Fluvastatin+Clopidogrel(2.6048±0.5102μg/l) were higher than that in group shame(p<0.05),but were lower than that in group control(p<0.05).2. Myocardial MPO in the group shame was lower than that in the groups control , Fluvastatin, Clopidogrel and Fluvastatin+Clopidogrel (p<0.05); Myocardial MPO was higher than that in the groups Fluvastatin, Clopidogrel and Fluvastatin+Clopidogrel (p<0.05).3.Myocardial infarct size and serumal enzyme (CK-MB)were significantly smaller in groups Fluvastatin,Clopidogrel and Fluvastatin+Clopidogrel than in group control (P<0.05). Conclusion.1.During myocardial ischemial/reperfusion, IL-8 was produced and increased gradually.2.Pretreating with Fluvastatin,Clopidogrel or Fluvastatin+Clopidogrel can reducing the myocardial inflammatory injury.3.Fluvastatin can inhibit the product of IL-8 in myocardial ischemia/reperfusion and this perhaps is one of its mechanism reducing the myocardial inflammatory injury.