Prevention of cerebral vasospasm after SAH with a thromboxane synthetase inhibitor, OKY-1581.
Prevention of cerebral vasospasm after SAH with a thromboxane synthetase inhibitor, OKY-1581.
复制标题
使用血栓素合成酶抑制剂 OKY-1581 预防 SAH 后脑血管痉挛。
DOI：
10.3171/jns.1982.57.1.0074
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发表时间：
1982
影响因子：
4.1
通讯作者：
K. Sano
中科院分区：
文献类型：
--
作者：
T. Sasaki;S. Wakai;T. Asano;K. Takakura;K. Sano
在一项使用狗的长期实验中，评价了血栓素合成酶抑制剂预防蛛网膜下腔出血（SAH）后脑血管痉挛的疗效。基底动脉直径的变化，其次是血管造影，并通过光学显微镜和电子显微镜的形态学变化进行了研究。作为血栓素合成酶抑制剂，使用OKY-1581（（E）-3-（4（-3-吡啶基甲基）苯基）-2-甲基丙烯酸钠）。蛛网膜下腔血液注射后，立即静脉注射溶于2 ml生理盐水中的160 mg OKY-1581。随后，动物以4 gm/50 ml/24小时的速率连续静脉输注药物，直至诱导SAH后4天处死。对照犬接受蛛网膜下腔血液注射，未用OKY-1581处理。血管造影检查显示，用OKY-1581治疗几乎完全消除了晚期痉挛。早期痉挛也被阻止，但药物的效果不如对晚期痉挛的效果显著。形态学研究显示，在治疗组和未治疗组犬的基底动脉中，SAH后内皮发生退行性变化，图尼卡中膜发生肌坏死变化。然而，在给药犬中几乎完全不存在内弹性膜的松弛。上述结果表明，血栓素A2的不成比例合成在SAH后慢性脑血管痉挛的发展中起重要作用，选择性抑制血栓素合成酶的药物如OKY-1581可能有助于预防血管痉挛。
The efficacy of thromboxane synthetase inhibitor in the prevention of cerebral vasospasm after subarachnoid hemorrhage (SAH) was evaluated in a prolonged experiment using dogs. Changes in the diameter of the basilar artery were followed by angiography, and morphological changes were studied by photomicroscopy and electron microscopy. As a thromboxane synthetase inhibitor, OKY-1581 (sodium-(E)-3-(4(-3-pyridylmethyl)phenyl)-2-methylacrylate) was used. Dogs received intravenous injections of 160 mg of OKY-1581 dissolved in 2 ml of physiological saline immediately after subarachnoid blood injection. Subsequently, the animals received continuous intravenous infusion of the drug at the rate of 4 gm/50 ml/24 hours until sacrifice 4 days after induction of SAH. Control dogs received subarachnoid blood injection without treatment with OKY-1581. Angiographic examination revealed that the late spasm was almost completely abolished by the treatment with OKY-1581. Early spasm was also prevented, but the drug's effect was less prominent than it was on the late spasm. Morphological study revealed degenerative changes in the endothelium and myonecrotic changes in the tunica media following SAH in the basilar arteries of the treated as well as the untreated dogs. However, corrugation of the internal elastic lamina was almost completely absent in the treated dogs. The above results indicate that a disproportionate synthesis of thromboxane A2 plays an important role in the evolution of chronic cerebral vasospasm following SAH, and that drugs such as OKY-1581 that selectively inhibit thromboxane synthetase might be useful in the prevention of vasospasm.