Effect of BW755C in an occlusion-reperfusion model of ischemic myocardial injury.

Effect of BW755C in an occlusion-reperfusion model of ischemic myocardial injury.
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BW755C 在缺血性心肌损伤的闭塞再灌注模型中的作用。

DOI:
10.1016/0002-8703(83)90431-3
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发表时间:
1983
影响因子:
4.8
通讯作者:
Lucchesi,BR
Lucchesi,BR
中科院分区:
医学2区
文献类型:
--
作者:
Jolly,SR;Lucchesi,BR

文献摘要

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BW755C 是一种新型抗炎剂,主要抑制脂氧合酶而不是环氧合酶。 BW755C 的作用已在犬闭塞再灌注缺血性心肌损伤模型中进行了检验。在戊巴比妥麻醉的开胸犬中,将近端左回旋冠状动脉 (LCX) 闭塞 90 分钟,并使用千分尺驱动的闭塞器缓慢再灌注。闭塞前 30 分钟,动物通过静脉输注随机接受 BW755C、3 mg/kg (n = 7) 或 10 mg/kg (n = 8) 或生理盐水 (n = 16)。 24小时后关闭胸腔并处死动物。通过使用三苯基四唑和埃文蓝的双重染色技术确定取决于闭塞 LCX 的梗塞大小和解剖面积。无论结果以梗塞组织克数还是梗塞风险区域百分比表示,两种剂量的 BW755C 均显着降低了不可逆心肌缺血性损伤的最终程度。组间未观察到风险区域大小存在差异。未观察到 BW755C 对心率、动脉压或左回旋血流的影响。 BW755C (10 mg/kg) 不会显着抑制体外血小板对胶原、二磷酸腺苷或花生四烯酸的反应。这些结果表明,抑制脂氧合酶可以减轻心脏缺血性损伤的程度。
BW755C is a new antiinflammatory agent which predominantly inhibits lipoxygenase over cyclooxygenase. Effects of BW755C have been examined in a canine, occlusion-reperfusion, model of ischemic myocardial injury. In pentobarbital anesthetized open-chest dogs, the proximal left circumflex coronary artery (LCX) was occluded for 90 minutes and slowly reperfused using a micrometer-driven occluder. Thirty minutes before occlusion, animals randomly received BW755C, 3 mg/kg (n = 7), or 10 mg/kg (n = 8), or saline (n = 16) by intravenous infusion. The thoracotomy was closed and the animals subsequently were killed at 24 hours. Infarct size and anatomic area dependent on the occluded LCX were determined by a dual staining technique using triphenyltetrazolium and Evan's blue. Both doses of BW755C significantly reduced the ultimate extent of irreversible myocardial ischemic injury, whether results were expressed as grams of infarcted tissue or as percent of risk region infarcted. No difference in risk region size was observed between groups. No effects of BW755C on heart rate, arterial pressure, or left circumflex flow were observed. BW755C (10 mg/kg) did not significantly inhibit ex vivo platelet aggregation in response to collagen, adenosine diphosphate, or arachidonic acid. These results suggest that inhibition of lipoxygenase may reduce the extent of ischemic damage to the heart.