Effects of chlorpromazine on experimental delayed cerebral vasospasm

Experimental delayed cerebral vasospasm was produced in the canine basilar artery by intracisternal injections of blood 2 days apart. The spastic basilar artery was exposed via the transclival route under a surgical microscope, and was dilated by topical application of chlorpromazine, a calmodulin antagonist. Dilatation was dose-dependent, with a median effective dose of 37 +/- 16 microM. In addition, 100 microM chlorpromazine was inserted into the cisterna magna until the intracranial pressure (ICP) reached 200 mm H2O for 30 minutes, inducing a complete reversal of angiographic delayed cerebral vasospasm in two of five animals. In other studies, the intracisternal perfusion of 100 microM chlorpromazine at 1.48 ml/min for 30 minutes with an ICP of less than 200 mm H2O induced no serious abnormalities in mean arterial blood pressure and pulse rate of normal animals. Electroencephalography during the intracisternal perfusion of chlorpromazine showed a slight to moderate increase in occurrence of theta waves. No neurological deficits or significant histological abnormalities ascribable to intracisternal chlorpromazine were found.