CEREBROVASCULAR RESPONSES TO SUBARACHNOID BLOOD AND SEROTONIN IN THE MONKEY

Preliminary in vitro experiments were performed to determine the serum concentration of serotonin in the monkey, and the ability of cyproheptadine to block serotonin and serum-induced contractions in monkey cerebral arteries. Thirty-four cynomolgus monkeys were subsequently used to study changes in regional cerebral blood flow (CBF) obtained by the intracarotid 133Xe technique, and in the angiographic cerebral arterial caliber resulting from subarachnoid injection of artificial cerebrospinal fluid (CSF), blood, and serotonin. Five animals in each injection group were given 1.0 mg/kg intravenous cyproheptadine (a serotonin-blocking agent) during the post-injection period. Subarachnoid injection of artificial CSF produced no change in CBF or arterial caliber. Post-injection administration of cyproheptadine also had no effect on these parameters. A subarachnoid injection of fresh autogenous blood produced a significant but transient (less than 1 hour) decrease in CBF and moderate vasospasm, which lasted at least 3 hours. This vasospasm was essentially unaffected by intravenous cyproheptadine. The CBF and arterial caliber were unchanged following a subarachnoid injection of serotonin at concentrations (5x10-6 M) present in normal monkey serum. In contrast, 5x10-6 M serotonin invariably produced near maximal contractions in the in vitro cerebral artery preparations. Higher (x10) serotonin concentrations caused a transient CBF response similar to that obtained with blood. However, the cerebral vasospasm induced was of shorter duration than that obtained with blood. These results do not support a major role for serotonin in the production of post-subarachnoid hemorrhage vasospasm. Moreover, the authors' data indicate that in vitro experiments do not reflect the ability of serotonin to constrict cerebral arteries in the intact animal.