羟苯氨酮对离体鼠心停灌-复灌损伤的保护作用

目的研究羟苯氨酮对全心停灌-复灌损伤的影响。方法采用离体大鼠心脏停灌40 min-复灌30 min模型，从心脏功能、心肌能量代谢、抗氧化、线粒体钙超载及超微结构等方面观察药物作用。结果停灌前和复灌时给予羟苯氨酮(1~10 μmol·L^-1)明显增加复灌时心肌收缩力与冠脉流量，降低冠脉流出液的肌酸磷酸激酶(CPK)活性，对抗损伤所致的心肌三磷酸腺苷(ATP)与磷酸肌酸(PCr)含量降低，增强心肌抗氧化能力，对抗线粒体钙超载，使线粒体超微结构保持得比较完整。结论羟苯氨酮明显对抗停灌-复灌致心肌损伤，为该药保护再灌注损伤提出有力依据。

Protection of oxyphenamone against cardiac arrest-reperfusion injury of isolated rat hearts

AIM: To ascertain the protective effect of oxyphenamone, a novel inodilator, against myocardial ischemia-reperfusion injury. METHODS: A model of global myocardial ischemia-reperfusion injury (I-R) was established by arresting the infusion to heart 40 min followed by reperfusion 30 min in the preparations of rat Langendorff' s hearts. The protective effects of oxyphenamone were evaluated by the cardiac function, the activity of creatine phosphokinase (CPK) in coronary efflux, the myocardial energy metabolism and antioxidation, the membrane fluidity, the activity of ATPase, the calcium content and ultrastructure of mitochondria. RESULTS: Administration of oxyphenamone to the infused heart before cardiac arrest and during reperfusion ameliorated the decreases of myocardial contractile force and coronary flow and the increase of the activity of CPK in coronary efflux induced by cardiac arrest-reperfusion (A-R). At the concentration of 1-10 micromol x L(-1) oxyphenamone dose-dependently antagonized the decrease of myocardial adenosine triphosphate (ATP) and creatine phosphate (PCr) induced by A-R, increased the activities of myocardial superoxide dismutase (SOD) and glutathione peroxidase (GSH-px), decreased mitochondrial malondialdehyde (MDA) content and increased membrane fluidity, glutathione (GSH) content and the activities of GSH-px and ATPase of mitochondria. The parameters mentioned above even maintained at normal level when high concentration of oxyphenamone (10 micromol x L(-1)) was applied. Oxyphenamone also antagonized the mitochondrial calcium overload and the ultrastructure damage of mitochondria induced by A-R obviously. Addition of oxyphenamone (1-100 micromol x L(-1)) to the system of Fe2+-cysteine or Fe2+-H2O2, which could produce oxygen free radicals, decreased MDA content and increased GSH and membrane fluidity of mitochondria significantly. CONCLUSION: With the results of examinations of the cardiac physiological function, myocardial energy metabolism and antioxidation and the calcium content and ultrastructure of mitochondria, it is indicated that oxyphenamone could protect the isolated rat heart against cardiac arrest-reperfusion injury markedly and the mechanism of its action may be related to the antioxidative effect of this agent.