脳血管攣縮の成因に関する実験的検討

抄録

Experimental subarachnoid hemorrhage was produced by the injection of fresh arterial blood (2-4 ml) into the cisterna magna of adult cats. Spasm of intracranial major vessels with more than 50 per cent decrease in the size of the vessels was observed angiographically, and lasted for 60 to 90 minutes in all the cases studied. Repeat angiograms revealed biphasic vasospasm in 10 out of 21 cases. The late spasm occurred in 3 days, reaching a maximum in 3 to 5 days after the hemorrhage.
The basilar artery was microscopically exposed by a transclival approach in the normal cats as well as those at 3 days after the cisternal injection of blood. Vasospasm of the basilar artery in normal cats lasted for 20 to 30 minutes with a 2 minute period of topical application of those vasoactive substances such as noradrenaline (100 ng/ml), serotonin (100 ng/ml), prostaglandin E₁ and F₂α (10 μg/ml), fresh blood and a 3 days long incubated CSF-blood mixture. In cats 3 days after the subarachnoid hemorrhage, spasm was produced with much lower concentration of noradrenaline (5-10 ng/ml) and lasted for longer time up to 40 minutes. Blood and incubated CSF-blood mixture also produced marked arterial spasm for more than 60 minutes.
Serotonin, noradrenaline, prostaglandin E₁ and F₂α were determined in the blood mixed with CSF in cats. Concentrations of those vasoactive substances were less than 10 ng/ml of the mixed fluid, except that of serotonin. An incubation of the mixed fluid at 37 °C for 3 days lowered concentrations of these vasoactive substances down to less than 5 ng/ml of the fluid.
Enzyme dopamine-β-hydroxylase (DBH) activity and noradrenaline concentration of major vessels at the base of the brain and locus ceruleus area were determined in normal (control) cats and in those with experimental subarachnoid hemorrhage. Subarachnoid hemorrhage produced a biphasic response in the DBH activity of the vessels and locus ceruleus, consisting of a reduction to 60% of control during the first 24 hours followed by a marked increase to approximately 250% of control reaching a maximum at 3 days, and a gradural recovery to the control level by 7 days after the hemorrhage. Noradrenaline concentration of the vessels and locus ceruleus showed biphasic response similar to that of DBH activity.
Several agents were used to relieve the vasospasm produced by the topical application of noradrenaline (5-10 ng/ml) to the exposed basilar artery 3 days after the cisternal injection of blood. Phenoxybenzamine (α-adrenergic blocker) and fusaric acid (DBH enzyme inhibitor) were more effective in reversing the vasospasm than dopamine and salbutamol (β₂-adrenergic stimulant), when applied topically.
These results demonstrated that late cerebral vasospasm is likely due to a hyperreaction of cerebral vessels to spasmogenic substances which would remain in the subarachnoid space, in the ciscumstances of excessive accumulation of DBH enzyme and noradrenaline in cerebral vessel wall.