Effects of ML-9 on experimental delayed cerebral vasospasm

Publisher Website
Google Scholar
Abstract
✓ 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-hydro-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 µM. In addition, 50 µM 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 µM 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 µM 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 abnormaliti...