| Background:Several investigations indicated that reperfusion of ischemia myocardium induced ischemia reperfusion injury (IRI). This injury includes myocardial necrosis, arrhythmia, myocardial stunning and microvascular endothelial dysfunction including the no-reflow phenomenon. Myocardial reperfusion injury is a multifarious process including high lever of oxygen free radicals, neutrophil-endothelium interactions, apoptosis, intracellular calcium overload and low lever of ATP. As the development of investigations, people found gradually that inflammation also played a very important role in IRI.Preconditioning the heart with a brief period of ischemia followed by reperfusion renders it very resistant to injury from a subsequent prolonged ischemia. The protection by preconditioning mainly lies in limiting infarct size, reducing the incidence of ventricular arrhythmia and improving post ischemic cardiac function. Pharmacological preconditioning protection against heart injury is trigged by medicines which can mimic beneficial effects of cardiac ischemic preconditioning. That would be helpful to probe the mechanism of IPC and develop novel access to treatment of the cardiovascular diseases.Trimetazidine (TMZ), an antioxidant agent and metabolism medicine, has been extensively used in coronary artery disease and other cardiovascular disease, several experimental and clinical studies have demonstrated that it also exerts a cytoprotective effect, limiting IRI, through several mechanisms of action: potentiation of oxidative glucose metabolism, reduction of the degree of intracellular acidosis and hypercalcaemia, and attenuation of the inflammatory response and OFR production. L-Arginine (L-Arg) is a precursor of Nitric oxide (NO), NO is a free radical with extensive biological effect. It can maintain the tonicity of vascular smooth muscle, suppress platelet aggregation and adhesion, and regulate proliferation of vascular smooth muscle cell in cardio-vascular system, thus limit IRI. At present, the lots of reports about their limitation to IRI have emerged, but the effect of TMZ on inflammatory was blank in our country. Furthermore, the mechanism of TMZ on limiting IRI is different with L-Arg. It has not defined whether the combination of them would do more profit to myocardial preservation.Objective:This experiment plans to investigate the protective effects and mechanism of TMZ plus L-Arg on myocardial ischemia reperfusion injury in rat.Methods:Experiments were performed on adult male SD rats weighing 180-220g. They were randomly divided into four groups: the control group (A), the TMZ treated group (B), the L-Arg treated group (C) and the TMZ plus L-Arg group(D), 10 in each group. Myocardial ischemia-reperfusion injury models were made by ligating the coronary artery for 30min followed by reperfusion for 90 min. The electrocardiogram (ECG) was registered. Before establishment of ischemia reperfusion model, rats in group B were fed with 10mg/kg TMZ for six days. L-Arg (300mg/kg) was administered into peritoneal 30min before ischemia in C group, and both were applied in D group.Venous blood was collected before ischemia and at 30min,60min,90min after reperfusion, and then, tumor necrosis factor (TNF-α) was detected. After experiment, rats were executed and the hearts were taken out. Heart 10% tissue homogenate was made and then superoxide dismutase (SOD), malondialdehyde (MDA), ATP, was detected. The occurrence of arrhythmia and the generation of myocardial vascular cell adhesion molecule (VCAM-1) were compared among groups.Data was presented with statistical analysis, and analysis of Variances was used to determine changed between groups, Student's test was used to determine changed within group. Results were significant when P<0.05 and even significant when P<0.01. Results:1 The level of TNF-αin blood plasma 60min after reperfusion was higher than before ischemia in group A (P<0.05). Compared with the group A, the treated groups could lower the level of TNF-α(P<0.05 or P<0.01).And the difference was significant when the group D contrasted with the group B and the group C (P<0.05).2 The treated groups could significant lower the rising tendency of MDA; depress the occurrence and duration of arrhythmia; enhance the activity of SOD and the level of ATP; reduce the express of VCAM-1 (P<0.05 or P<0.01). And the difference was significant when the group D contrasted with the group B and the group C (P<0.05).Conclusions:1 Inflammation is one of the reasons causing myocardial ischemia reperfusion injury.2 Trimetazidine,L-arginine has notable protective effect on myocardial ischemia reperfusion injury through limiting the inflammation and enhancing ATP.3 Trimetazidine plus L-arginine is better than using the 2 medicines separately. |
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