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Inhibitory Effect of a Hydrophilicα-Tocopherol Analogue, MDL 74, 405, on Generation of ...
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Inhibitory Effect of a Hydrophilicα-Tocopherol Analogue, MDL 74, 405, on Generation of Free Radicals in Stunned Myocardium in Dogs
作者:
LiangXian,
McCayPaul B.,
ZhongJian,
HartleyCraig J.,
SchlemanMargo,
BolliRoberto,
期刊:
Free Radical Research
(Taylor Available online 1995)
卷期:
Volume 22,
issue 4
页码: 293-302
ISSN:1071-5762
年代: 1995
DOI:10.3109/10715769509145641
出版商: Taylor&Francis
关键词: Free radical generation;hydrophilicα-tocopherol analogue;myocardial stunning;open-chest dogs.
数据来源: Taylor
摘要:
A previous study has demonstrated that the hydrophilic (α-tocopherol analogue, MDL 74, 405, attenuates postischemic myocardial dysfunction (“stunning”) in dogs. The present study was undertaken to determine directly whether the salutary effect of this drug on myocardial stunning results from inhibition of the generation of oxygen-derived free radicals. Open-chest dogs undergoing a 15-min coronary artery occlusion and 3 h of reperfusion received an intravenous infusion of either saline (controls,n= 7) or MDL 74, 405 (n = 6) starting 30 min before coronary occlusion and ending 60 min after reflow at a dose of 0.3 mg/kg/h. To measure free radical production, all dogs received an intravenous infusion of the spin trapα-phenylN-tert-butyl nitrone (PBN) and local coronary venous plasma was analyzed by electron paramagnetic resonance (EPR). In control dogs, the myocardial production of PBN adducts exhibited an initial burst immediately after the onset of reflow and remained elevated until 10 min after reperfusion. Dogs treated with MDL 74, 405 demonstrated a marked decrease in PBN adduct production. This effect of MDL 74, 405 could not be attributed to nonspecific factors such as differences in ischemic zone size, collateral flow, arterial pressure, heart rate, coronary flow or other hemodynamic variables. These results demonstrate that the hydrophilic vitamin E analogue, MDL 74, 405, inhibits free radical generation after myocardial ischemia-reperfusionin vivo. This finding provides direct evidence that the salutary effects of MDL 74, 405 on myocardial stunning are due to attenuation of oxidative stress.
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