Effects Of Trimetazidine On Vessel Endothelial Cells In Rats During Myocardial Ischemia Reperfusion Injury

Myocardial ischaemia-reperfusion injury induces function obstcle of myocardium, evil arrhythmia, heart failure, increases mortality rate of heart and blood vessel disease. On clinic, it is seen that dissolve thrombus, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), and heart transplant et al. At present we have known deeply on mechanism of myocardial ischaemia-reperfusion injury. It is one of very important mechanism that injury of endothelial cells in the coronary vessels. In preventative mearures, it is special important that protect endothelial cells in the coronary vessels to alleviate myocardial damage. Trimitazidine (TMZ) is a new cell protector, metabolize drug. We have known the protective effect of trimitazidine on myocardium but on endothelial cells in the coronary vessels still unknown. Our study is to investigate the effect of trimitazidine on endothelial cells in the coronary vessels and its mechanism. One hundred and twenty mice of male and female in half were divided into sham, ischaemia-reperfusion, TMZ (10mg/kg) and TMZ (20mg/kg) groups. Before establishment of ischaemia reperfusion model, the mice in sham and ischaemia-reperfusion groups were additionally fed with 0.9%NaCl solution (1ml/100mg), two pretreatment groups were fed 10mg/kg and 20mg/kg TMZ respectively for six days. All animals were fed once more before experiment. In ischaemia-reperfusion and two pretreatment groups, the heart was exposed after the chest had been opended, and the mice were subjected to a one-hour coronary occlusion followed by a six-hour reperfusion, in sham group, coronary artery was not ligated. After seven hours, the heart sample were drawn and blood sample was drawn from abdomen artery. We observed the changes of endothelial cells in the coronary vessels and myocyte ultrastructure and plasma 6-Keto-PGF1α, TXB2, serum CK,LDH, SOD, MDA, myocardial SOD, MDA, and the extent of myocardial infarction. Result: Compared with sham group, there were significantly lower plasma 6-Keto-PGF1α, serum and myocardial SOD in ischaemia-reperfusion groups (P <0.05); significantly higher plasma TXB2, serum and myocardial MDA, serum CK,LDH, and the extent of myocardial infarction. Compared with ischaemia-reperfusion groups, in two pretreatment groups the degree of endothelial cells in the coronary vessels and myocardial damage were significantly reduced, plasma 6-Keto-PGF1α, serum and myocardial SOD were higher (P <0.05); plasma TXB2, serum and myocardial MDA, serum CK,LDH, and the extent of myocardial infarction were lower (P <0.05). Conclsion: Trimitazidine is regard as a cell protector, it may play an important role. It protects not only ischemic myocardium but also endothelial cells in the coronary vessels. The mechanism may be inhibition of fatty acid beta-oxidation together with an increase in glucose oxidation, optimizing the oxygen demand in mitochondria and preventing the decrease in adenosine triphosphate (ATP) levels to protect endothelial cells in the coronary vessels. Trimitazidine reduces intracellular acidosis, counteracts calcium overload, the production of free radicals and the infiltration of neutrophils. Trimitazidine still protects endothelial cells in the coronary vessels via antioxidant, stabilization of membranous. Trimitazidine may be a useful drug in reprefusive therapy to prevent ischaemia-reperfusion injury.