Cerebral arterial spasm. II. Etiology and treatment of experimental cerebral vasospasm.
Delayed cerebral vasospams is caused by excessive accumulation of dopamine-beta-hydroxylase (DBH) and noradrenaline in cerebral vessel walls. This study demonstrates the mechanisms of delayed spasm, particularly the role of red blood cell components, and the successful relief of delayed cerebral vasospasm. Spasmogenic substances which contained a heme component, such as methemoglobin, methemalbumin and catalase enhanced DBH activity in human serum as measured by a one step chemical spectrophotometric assay. The concentration which gave the highest DBH activity caused the maximum constriction of the basilar artery, when the substances were applied topically. Among components of red cells, methemoglobin, methemalbumin, catalase and nicotinamid adenin dinucleotide (NADH) caused constriction of basilar artery in cats, when applied topically, whereas hematin, hemin and bilirubin caused no significant spasm. An oxyhemoglobin solution obtained by mixture with methemoglobin and ascorbic acid produced no significant vascular spasm either. Relief of delayed cerebral vasospasm was obtained with topical application of specific alpha adrenergic blocking drug such as phenoxybenzamine, specific inhibitors of DBH such as fusaric acid, o-phenanthroline and alphaalpha' dipyridyl beta2 adrenergic stimulants such as salbutamol, and a phosphodiesterase inhibitor, ascorbic acid.
D000420:Albuterol / Q000627:therapeutic use; D000818:Animals; D001205:Ascorbic Acid / Q000627:therapeutic use; D001488:Basilar Artery / Q000187:drug effects; D002374:Catalase / Q000097:blood / Q000494:pharmacology; D002415:Cats; D004298:Dopamine / Q000627:therapeutic use; D004299:Dopamine beta-Hydroxylase / Q000097:blood; D005669:Fusaric Acid / Q000627:therapeutic use; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000209:etiology*; D008705:Methemalbumin / Q000494:pharmacology; D008706:Methemoglobin / Q000032:analysis / Q000494:pharmacology; D009243:NAD / Q000494:pharmacology; D010618:Phenanthrolines / Q000627:therapeutic use; D010643:Phenoxybenzamine / Q000627:therapeutic use; D014661:Vasoconstriction / Q000187:drug effects
D008705:Methemalbumin; D010618:Phenanthrolines; D010643:Phenoxybenzamine; D009243:NAD; D008706:Methemoglobin; D002374:Catalase; D004299:Dopamine beta-Hydroxylase; D005669:Fusaric Acid; D001205:Ascorbic Acid; D000420:Albuterol; D004298:Dopamine