Kobayashi H, Ide H, Handa Y, Aradachi H, Arai Y, Kubota T
Department of Neurosurgery, Fukui Medical School, Japan.
Neurosurgery. 1992 Sep;31(3):550-5; discussion 555-6. doi: 10.1227/00006123-199209000-00018.
Experimental delayed cerebral vasospasm was produced in 16 adult mongrel dogs by the "two-hemorrhage" method of intracisternal injections of autologous arterial blood. Group 1 was a control group. Group 2 was a treatment group that received an intravenous injection of ONO-1078, a novel potent leukotriene antagonist, once a day for 7 days just after the first cisternal injection of the blood. Angiography was performed on Days 0 and 7, and the cerebrospinal fluid levels of leukotriene C4 (LTC4) were measured on Days 0, 3, and 7. The cisternal levels of LTC4 increased after subarachnoid hemorrhage in both groups. But the cerebrospinal fluid levels of LTC4 in the treatment group were significantly lower than those in the control group (P less than 0.05). The angiographic vasospasm after subarachnoid hemorrhage was partially prevented with the treatment of intravenous injections of ONO-1078 (P less than 0.001). These results suggest that LTC4 may play a role in the pathogenesis of delayed cerebral vasospasm, directly or indirectly, and ONO-1078 may have a therapeutic effect on the prevention of the development of delayed cerebral vasospasm.
通过脑池内注射自体动脉血的“两次出血”方法，在16只成年杂种犬中诱发实验性迟发性脑血管痉挛。第1组为对照组。第2组为治疗组，在首次脑池内注射血液后，每天静脉注射一次新型强效白三烯拮抗剂ONO-1078，共7天。在第0天和第7天进行血管造影，并在第0天、第3天和第7天测量脑脊液中白三烯C4（LTC4）的水平。两组蛛网膜下腔出血后，脑池内LTC4水平均升高。但治疗组脑脊液中LTC4水平明显低于对照组（P<0.05）。静脉注射ONO-1078治疗可部分预防蛛网膜下腔出血后的血管造影血管痉挛（P<0.001）。这些结果表明，LTC4可能直接或间接在迟发性脑血管痉挛的发病机制中起作用，且ONO-1078可能对预防迟发性脑血管痉挛的发生具有治疗作用。
