SUPEROXIDE ANIONS IN THE PATHOGENESIS OF TALC-INDUCED CEREBRAL VASOCONTRACTION

We have recently reported that sustained contraction of the canine bas ilar artery induced by the intrathecal injection of talc (crystallized hydrous magnesium silicate) mimicked delayed vasospasm following suba rachnoid haemorrhage. The present study aims to examine the pathomecha nism underlying talc-induced vasocontraction, from the viewpoint of fr ee radical theory, which has been established as a cause of delayed va sospasm. We estimated the effects of a prolonged intrathecal infusion of human recombinant Cu/Zn superoxide dismutase (hr SOD) on the contra ction of the basilar artery caused by the intrathecal injection of tal c in beagle dogs, which were assigned to the three groups: G1, sham op eration with saline treatment; G2, talc injection with saline treatmen t; and G3, talc injection with 2 ml of hr SOD (7 x 10(4) U/ml) treatme nt. Talc administration resulted in the reduction in the angiographic calibre of the basilar artery by 63 and 61% on days 3 and 7 (G2), The treatment with hr SOD (G3) led to a significant: attenuation of talc-i nduced contraction of the basilar artery on days 3 (P<0.05 vs. G2) and 7 (P<0.05 vs. G2). In the basilar artery wall of days 3 and 7 in G2, pathological changes such as myonecrosis, cytoplasmic vacuolation and detached intercellular junctions were observed. However, these patholo gical changes almost disappeared in G3. The present findings suggest t hat superoxide anions may initiate and/or mediate talc-induced vasocon traction and subsequent structural damage of the basilar artery.