[A study on the protective effect of metallic chelators on ischemia-reperfusion injury of isolated rat heart].
A Langendorff isolated rat heart preparation was used to determine the effect of the metallic chelators, deferoxamine and penicillamine on the extent of myocardial ischemia reperfusion injury. Each heart was subjected to 15-60 minutes of total ischemia at 37 degrees C followed by 15-60 minutes of reperfusion with either saline, deferoxamine (0.61 mmol/L), or penicillamine (30 mmol/L) treated perfusate. Reperfusion injury was assessed by the production of free radicals with electronic spin resonance spectroscopy and spin trap PBN, by the amount of creatine phospholipase released into the perfusate, by the changes in the myocardial vascular resistance, and by pathologic examination of myocardium. The results showed that the drug treated groups released significantly less radical adducts of PBN (P < 0.01) and creatine phosphokinase into the perfusate than the saline treated group (P < 0.01). The mean vascular resistance significantly increased in the saline treated group than in the drug treated groups (P < 0.01). Ultrastructural examination showed prominent attenuation of mitochondrial swelling in drug treated groups in comparison with the saline one. These findings indicated that both deferoxamine and penicillamine can protect the isolated rat heart from ischemia reperfusion injury. The possible mechanism of which is that metallic chelators block the transitional metal-catalyzed fenton reaction, and subsequently decrease the production of hydroxyl radical.
Liu
L L
LL
Geriatric Research Institute, General Hospital, PLA, Beijing.
Zhao
B L
BL
D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology*; D005260:Female; D016166:Free Radical Scavengers; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010396:Penicillamine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D016166:Free Radical Scavengers; D003402:Creatine Kinase; D010396:Penicillamine; D003676:Deferoxamine