Yokota M, Tani E, Maeda Y, Kokubu K
Stroke. 1987 Mar-Apr;18(2):512-8. doi: 10.1161/01.str.18.2.512.
Experimental delayed cerebral vasospasm was produced in canine basilar arteries by 2 successive injections, 2 days apart, of fresh autogenous arterial blood into the cisterna magna. When angiographic evidence of delayed vasospasm was confirmed 7 days after the initial intracisternal blood injection, a selective inhibitor of 5-lipoxygenase, 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-1,4-benzoqu inone (AA-861), was infused intravenously at 6.5 X 10(-4) mg/kg/min for 2 hours. However, angiographic evidence of delayed vasospasm was not reversed, and mean regional cerebral blood flow was not significantly increased. In other studies, oral doses of AA-861 at 100 mg/kg/day were given twice a day for 7 days after the initial intracisternal blood injection. In the treated group, angiographic evidence of delayed vasospasm was significantly reduced, and the contractile property of excised basilar arteries in response to vasoconstrictor agents was significantly improved. It is suggested that leukotrienes, 5-lipoxygenase products of arachidonic acid, might be important etiologic factors responsible for the development of delayed vasospasm and that AA-861 would have a therapeutic effect not on the reduction of delayed vasospasm once developed but on the prevention of the development of delayed vasospasm.
通过向犬的小脑延髓池分两次、间隔2天注射新鲜自体动脉血，在犬的基底动脉中诱发实验性迟发性脑血管痉挛。在首次脑池内注射血液7天后，当迟发性血管痉挛的血管造影证据得到证实时，以6.5×10⁻⁴毫克/千克/分钟的速度静脉输注5-脂氧合酶的选择性抑制剂2-(12-羟基十二碳-5,10-二炔基)-3,5,6-三甲基-1,4-苯醌(AA-861)，持续2小时。然而，迟发性血管痉挛的血管造影证据并未得到逆转，平均局部脑血流量也未显著增加。在其他研究中，在首次脑池内注射血液后，每天两次给予100毫克/千克/天的口服剂量AA-861，持续7天。在治疗组中，迟发性血管痉挛的血管造影证据显著减少，离体基底动脉对血管收缩剂的收缩特性也得到显著改善。提示白三烯（花生四烯酸的5-脂氧合酶产物）可能是迟发性血管痉挛发生的重要病因，且AA-861的治疗作用不是减轻已发生的迟发性血管痉挛，而是预防迟发性血管痉挛的发生。
