Experimental evaluation of the beneficial effect of an antioxidant on cerebral vasospasm

Based on the previously suggested hypothesis that generation of free radicals leading to lipid peroxidation is involved in the genesis of vasospasm following SAH, the therapeutic effect of an antioxidant on experimental vasospasm was examined. As an antioxidant suitable for this purpose, AVS(1,2-bis(nicotinamide)-propane) was used. Experimental SAH was induced in dogs by intracisternal injection of blood and subsequent changes in the basilar artery diameter was evaluated by angiography. First, intrathecal administration of AVS 3 days after SAH caused prompt resolution of pre-existing chronic vasospasm for 3-4 h. Next, the effect of continuous intravenous administration of saline (control) or AVS was started and continued for 4 days. In the control group, early and chronic spasm was observed on the daily angiography. In the AVS-treated group, early spasm was only moderately inhibited, but the occurrence of chronic spasm was remarkably suppressed in a dose-dependent manner. In these experiments, no adverse effect of AVS on the neurological or systemic conditions was observed. The data indicate that AVS may be beneficial in the treatment of vasospasm following SAH, thereby reinforcing the concept that generation of free radicals is involved in the genesis of vasospasm.