Kokubu K, Tani E, Nakano M, Minami N, Shindo H
Department of Neurosurgery, Hyogo College of Medicine, Japan.
J Neurosurg. 1989 Dec;71(6):916-22. doi: 10.3171/jns.1989.71.6.0916.
Experimental delayed cerebral vasospasm was produced in a two-hemorrhage canine model. The spastic basilar artery was exposed via the transclival route under a surgical microscope and was dilated by the topical application of 1-(5-chloronaphthalenesulfonyl)-1H-hexa-1,4-diazepine (ML-9), a selective antagonist of myosin light chain kinase. Dilation was dose-dependent, with a median effective dose (+/- standard deviation) of 51.4 +/- 6.9 microM. In addition, 50 microM of ML-9 was injected into the cisterna magna until the intracranial pressure (ICP) reached 200 mm H2O for 30 minutes, including a complete reversal of angiographic delayed vasospasm in three of seven dogs; in contrast, 150 microM of ML-9 was infused at 1.52 ml/min into the vertebral artery for 30 minutes, producing little dilation of the spastic basilar artery. In another study, the intracisternal perfusion of 50 microM of ML-9 at 1.48 ml/min for 30 minutes in dogs with an ICP of less than 200 mm H2O produced no serious electroencephalographic abnormalities, and the mean arterial blood pressure and pulse rate remained normal; no neurological deficits or significant histological abnormalities ascribable to the intracisternal ML-9 were found.
在双出血犬模型中诱发实验性迟发性脑血管痉挛。在手术显微镜下经经斜坡入路暴露痉挛的基底动脉，通过局部应用1-(5-氯萘磺酰基)-1H-六氮杂-1,4-二氮杂卓（ML-9，一种肌球蛋白轻链激酶的选择性拮抗剂）使其扩张。扩张呈剂量依赖性，中位有效剂量（±标准差）为51.4±6.9微摩尔。此外，将50微摩尔的ML-9注入枕大池，直至颅内压（ICP）达到200毫米水柱并维持30分钟，7只犬中有3只的血管造影迟发性血管痉挛完全逆转；相比之下，以1.52毫升/分钟的速度将150微摩尔的ML-9注入椎动脉30分钟，痉挛的基底动脉几乎没有扩张。在另一项研究中，在颅内压低于200毫米水柱的犬中，以1.48毫升/分钟的速度将50微摩尔的ML-9注入枕大池30分钟，未产生严重的脑电图异常，平均动脉血压和脉搏率保持正常；未发现可归因于枕大池内ML-9的神经功能缺损或明显的组织学异常。
