THE CARDIOPROTECTIVE EFFECT OF MN-SUPEROXIDE DISMUTASE IS LOST AT HIGH-DOSES IN THE POSTISCHEMIC ISOLATED RABBIT HEART

被引：115

作者：

OMAR, BA

MCCORD, JM

机构：

[1] Webb-Warning Lung Institute, University of Colorado, Denver, CO 80262

来源：

FREE RADICAL BIOLOGY AND MEDICINE | 1990年 / 9卷 / 06期

关键词：

MYOCARDIAL ISCHEMIA; REPERFUSION INJURY; FREE RADICALS; SUPEROXIDE DISMUTASE; DOSE-RESPONSE;

D O I：

10.1016/0891-5849(90)90124-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The loss of protection by human recombinant (hr) Cu,Zn-superoxide dismutase (SOD) at higher doses reported previously may have been due to the weak peroxidase activity of this enzyme. To test this possibility we studied the dose-response relationship of hrMn-SOD, which lacks peroxidase activity. Isolated, buffer perfused rabbit hearts were subjected to 1 h of global ischemia followed by 1 h of reperfusion, and the percent recovery of developed tension (relative to preischemic) was measured via a left ventricular balloon connected through a pressure transducer to a polygraph recorder. The coronary effluent was assayed for lactate dehydrogenase (LDH) release. While hrMn-SOD almost completely protected against loss of function and LDH release at 2 and 5 mg/L (p < 0.01), it exacerbated the damage at 50 mg/L concentration (p < 0.05 against controls), thus giving an even sharper bell-shaped curve than seen with the hrCu,Zn-SOD. Therefore we conclude that, first, while the hrMn-SOD protects the reperfused heart at lower doses, it may exacerbate the damage at higher doses. Second, that the lack of protection seen at higher doses of hrCu,Zn-SOD is unlikely to be due only to its peroxidase activity.

引用

页码：473 / 478

页数：6

共 34 条

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