[Protection of oxyphenamone on myocardium against ischemia-reperfusion injury in rat heart].
OBJECTIVE
To study the protective effect of oxyphenamone, a novel inodilator against myocardial ischemia-reperfusion injury.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
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
Teng
Jian
J
Zhang
Run-Dong
RD
Zhao
De-Yu
DY
D000818:Animals; D003402:Creatine Kinase / Q000097:blood / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000097:blood / Q000378:metabolism; D017202:Myocardial Ischemia / Q000150:complications; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; 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; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase