Reversal of delayed vasospasm by an inhibitor of the synthesis of 20-HETE
Reversal of delayed vasospasm by an inhibitor of the synthesis of 20-HETE
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DOI：
10.1152/ajpheart.00556.2005
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发表时间：
2005-11-01
影响因子：
4.8
通讯作者：
Roman, RJ
中科院分区：
文献类型：
--
作者：
Takeuchi, K;Renic, M;Roman, RJ
本研究描述了大鼠蛛网膜下腔出血 (SAH) 双出血模型中脑血流量 (CBF) 和血管直径变化的时间过程，并研究了用 N-(3-氯-4-吗啉-4-基)苯基-N'-羟基亚氨基甲酰胺 (TS-011) 急性阻断 20-羟基二十碳四烯酸 (20-HETE) 的合成是否可以逆转迟发性血管痉挛在这个模型中。大鼠在第0天接受脑池内注射血液（0.4ml），并在2天后接受第二次注射。使用激光多普勒血流计连续测量CBF，并在用铸模化合物填充脑血管系统后测定脑动脉的直径。第一次脑池内注射血液后，CBF 降至对照值的 67%，但 24 小时后又恢复到接近对照值。第二次脑池内注血后，CBF 再次降至对照值的 63%，并在 5 天内保持低于对照值 30%。第二次脑池内注血后 CBF 下降与大脑中动脉、后交通动脉和基底动脉直径持续减少 30% 相关。第二次 SAH 后 5 天，用 TS-011（0.1 mg/kg iv）急性阻断 20-HETE 的合成，增加了脑动脉的直径，CBF 恢复到控制。这些结果表明，在诱导SAH双重出血模型后，大鼠出现迟发性血管痉挛，并且阻断20-HETE的合成可完全逆转该模型中的脑血管痉挛。他们还表明 20-HETE 与迟发性脑血管痉挛的发生和维持有关。
This study characterized the time course of changes in cerebral blood flow (CBF) and vascular diameter in a dual-hemorrhage model of subarachnoid hemorrhage (SAH) in rats and examined whether acute blockade of the synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE) with N-(3-chloro-4-morpholin-4-yl)phenyl-N'-hydroxyimido formamide (TS-011) can reverse delayed vasospasm in this model. Rats received an intracisternal injection of blood (0.4 ml) on day 0 and a second injection 2 days later. CBF was sequentially measured using laser-Doppler flowmetry, and the diameters of the cerebral arteries were determined after filling the cerebral vasculature with a casting compound. CBF fell to 67% of control after the first intracisternal injection of blood but returned to a value near control 24 h later. CBF again fell to 63% of control after a second intracisternal injection of blood and remained 30% below control for 5 days. The fall in CBF after the second intracisternal injection of blood was associated with a sustained 30% reduction in the diameters of the middle cerebral, posterior communicating, and basilar arteries. Acute blockade of the synthesis of 20-HETE with TS-011 (0.1 mg/kg iv), 5 days after the second SAH, increased the diameters of the cerebral arteries, and CBF returned to control. These results indicate that the rats develop delayed vasospasm after induction of the dual-hemorrhage model of SAH and that blockade of the synthesis of 20-HETE fully reverses cerebral vasospasm in this model. They also implicate 20-HETE in the development and maintenance of delayed cerebral vasospasm.