| Objective : myocardial ischemic/reperfusive (I/R) injury is a common pathophysiologic process after myocardial ischemia. The primary mechanism involved in this process may include the damages of oxygen free radicals, accumulation of toxingenic fatty acid and its derivatives, adhesion of neutrophils and exudation as well as calcium overload. Recently studies documented that the pattern of energy metabolism after I/R has an important effect on the recovery of myocardial contractile and diastolic function, More and more attention has been paid to the drug intervention of metabolism in order to treat ischemic heart deseases. But the role of fatty acid p-oxidation in the I/R injury and the protective mechanism of L-CN on ischemic/reperfusive myocardium remainned not to be elucidated. In the present study, The pharmacological mechanisms of L-CN in the treatment of ischemic deseases were studied in rats. Methods:1. 30 Rats were randomly divided into three groups:①normal conrol group:the hearts of rats were mouted on a Langendorff apparatus and perfused retrogradely with modified Tyrode solution for 110min, ②I/R group:the hearts were perfused retrogradely with modified Tyrode solution for 20 min followed by global ischemia for 20 min, and then reperfused for 70 min.③L-CN group:10mmol/l L-carnitine added into modified Tyrode solution.20min of ischemia followed by 60min of reperfusion ,then 10min washoutwith modified Tyrode solution was carried out.2. The efflux from rat coronary artery was accumulated for the determination of the concentration of carnitine by radioenzymatical method.3. The myocardium were harvested after reperfusion for both 60min and 10min washout for observation of myocardial ultrastnctural changes.4. The remained myocardium was immediately frozen in liquid nitrogen and then stored in -80℃ enviroment. All these samples were for ①measurement of free adenine nucleotides by High performance liquid chromatography (HPLC), ②determination the concentration of L-CN by radioenzymatic assay and ③the assay of MD A and TAC by colorimetry. Results:1.Myocardial ultrostructural changes: the myocardial ultrostucture in ischemic/ reperfusive group was damaged,which characteristized by mitochondrial swelling and crack,disappearance of mitochondrial crista, disarrangement of sarcomere and/or disruption. As compared with normal myocardium, the changes in L-CN groups was subtle, with only slight swelling of sarcomere and mitochondrion.2.Content of free adenine in myocardium: The concentration of free adenine nucleotides decreased in I/R group, and the oxidative phosphorylation also decreased as compared with that in control group (P<001); The recovery of high energy phosphates in L-CN group was fast and the oxidative phosphorylation augmented as compared with I/R group(P < 0.05).3.CN concentration in myocardium and coronary artery efflux: Carnitine levels in myocardial tissues decreased significantly but increased in coronary efflux at the same tune in I/R group as compared with that in controlgroup(P<0.01).CN concentration in myocardium in L-CN group was significantly higher than that in I/R group, which suggested that the CN administrated exogenously can penetrate into cardiac myocytes.4.Content of MDA and TAC: MDA levels in I/R group were significantly higher and TAC levels were lower (P <0.01) than those in normal controlgroup, decreased(P <0.01). Compared with normal control group, the levels of MDA and TAC in L-CN group were slightly decreased( both p < 0.0)5. Conclusion:1. Intransient ischemic plus reperfusive myocardium,aerobic metabolism transferred to glycolysis in in rats.lipid peroxidation was aggravated, Aerobic oxidation of fatty acid was significantly inhibited. The myocardial ultrastructure wasseriously damaged,especially the mitochondrion.I/R leaded to the damaged of the membrane of cardiac myocytes,,CN was lost from myocytes.Secondary deficiency of carnitine occurred.Consequently,fatty acid oxidation disorder occurred, Which may be on...
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