Protection of oxyphenamone on myocardium against ischemia-reperfusion injury in rat heart / 药学学报

<p><b>AIM</b>To study the protective effect of oxyphenamone, a novel inodilator against myocardial ischemia-reperfusion injury.</p><p><b>METHODS</b>A model of regional myocardial ischemia-reperfusion injury was established by ligating the left anterior desending coronary artery (LAD) in rat heart 10 min followed by reperfusion 15 min in vitro or 30 min in vivo. The protective effects of oxyphenamone were evaluated from the incidence of arrhythmia and the changes of myocardial creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) activities, malondialdehyde (MDA) content, and myocardial ultrastructure.</p><p><b>RESULTS</b>In preparations of rat Langendorff hearts, infusion of oxyphenamone (1-10 micromol.L(-1)) diminished the incidence of ventricular fibrillation, decreased the activities of CPK and LDH in coronary efflux, and antagonized the increase of MDA content in ischemic myocardium significantly. The ischemia-reperfusion injury in anesthetized rats produced severe ventricular arrhythmia, decrease of CPK in myocardium, increase of CPK in serum, increase both of LDH and MDA both in myocardium and in serum, and severe damage of myocardial ultrastructure. Intravenous injection of oxyphenamone 0.1-1.0 mg.kg(-1) 5 min before ischemia ameliorated dose-dependently ventricular arrhythmia, antagonized the changes of CPK, LDH and MDA in both myocardium and serum induced by ischemia-reperfusion. It even maintained these parameters at normal level. The effects were somewhat similar to that of verapamil 1.0 mg.kg(-1) Intravenous injection of oxyphenamone 0.5 or 1.0 mg.kg(-1) 5 min after ligation of LAD also antagonized the ischemia-reperfusion induced changes in CPK, LDH and MDA in myocardium and serum significantly, and ameliorated the damage of myocardial ultrastructure markedly. The therapeutic effects of oxyphenamone were similar to that of propranolol 2. 0 mg.kg(-1).</p><p><b>CONCLUSION</b>From the examination of ECG, myocardial enzymes and ultrastructure, it appears that oxyphenamone can protect myocardium against ischemia-reperfusion injury induced by occlusion of LAD both in vitro and in vivo.</p>

Protection of oxyphenamone against cardiac arrest-reperfusion injury of isolated rat hearts / 药学学报

<p><b>AIM</b>To ascertain the protective effect of oxyphenamone, a novel inodilator, against myocardial ischemia-reperfusion injury.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>