Prevention of cerebral vasospasm by a capsaicin derivative, glyceryl nonivamide, in an experimental model of subarachnoid hemorrhage

BACKGROUND Cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH ) remains a major complication in patients suffering from SAH. In our previ ous study, we reported that stimulating vascular K+ channel activity preven ted the development of cerebral vasospasm. Recent evidence indicates that g lyceryl nonivamide (GLNVA), a capsaicin derivative, has a vasorelaxant effe ct on the aortic vascular smooth muscle due to the release of coronary calc itonin gene-related peptide, which in turn stimulates K+ channel opening. T he purpose of the present study was to examine the preventive effects of GL NVA on vasospasm. METHODS New Zealand white rabbits were subjected to experimental SAH by inj ecting autologous blood into the cisterna magna. GLNVA or vehicle was injec ted intrathecally immediately after the induction of SAH. All animals were killed by perfusion-fixation at 48 hours after SAH. The basilar arteries we re removed and sectioned, and their cross-sectional areas were measured. RESULTS The average cross-sectional areas of basilar arteries were reduced by 69% and 71% in the SAH only and SAH plus vehicle groups, respectively, w hen compared with the healthy controls. After treatment with 0.35, 1.75, an d 3.5 mg/kg GLNVA in rabbits subjected to SAH the average cross-sectional a rea was decreased by 46%, 12% and 2%, respectively, when compared with the healthy controls. The protective effect of GLNVA achieved statistical signi ficance at all dosages. Morphologically, corrugation of the internal elasti c lamina of vessels was often observed in the vehicle-treated group, but wa s not prominent in the GLNVA-treated groups or healthy controls. CONCLUSION The findings showed that GLNVA dose-dependently attenuated cereb ral vasospasm after SAH in the rabbit. These results suggest that intrathec al administration of GLNVA could be an effective strategy for preventing ce rebral vasospasm after SAH. (C) 2001 by Elsevier Science Inc.