[Protection of oxyphenamone against cardiac arrest-reperfusion injury of isolated rat hearts].
OBJECTIVE
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.


CONCLUSIONS
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.
Fan
Li-li
LL
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. fanlili@public3.bta.net.cn
Li
Hua
H
Fan
Ming-jie
MJ
Zhang
Run-dong
RD
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D008929:Mitochondria, Heart / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D009200:Myocardial Contraction / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D009930:Organic Chemicals / Q000494:pharmacology; D020011:Protective Agents / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D009930:Organic Chemicals; D020011:Protective Agents; C442156:oxyphenamone; D002118:Calcium