5-Hydroxytryptamine-induced vasoconstriction after cerebral hematoma in piglets

Abstract

Subarachnoid hematoma produces cerebral vasoconstriction that may lead to death or permanent disability. After hematoma, enhanced pial arteriolar responses to vasoconstrictor agents have been reported in newborn pigs. The present study was designed to address the hypothesis that 5- hydroxytryptamine (5-HT) constricts piglet pial arterioles, and hematoma augments this constriction. Piglets (1-3 d old) anesthetized with ketamine and acepromazine received either 3 mL of artificial cerebrospinal fluid (control) or autologous nonheparinized blood (hematoma) injected onto the cortical surface. Four days after injection, closed cranial windows were implanted over the injected area under α-chloralose anesthesia. Vascular reactivity to 5-HT was examined. In control piglets, topical application of 5-HT (10-9, 10-7, and 10-5 M) induced very mild, dose-dependent constriction of pial arterioles (-6 ± 1, -10 ± 2, and -12 ± 4%, respectively). These constrictions were substantially augmented in piglets with hematoma (-12 ± 2, -19 ± 1, and -30 ± 2%, respectively). After topical application of 5-HT, cerebrospinal fluid samples were collected from under the window to determine the effects of 5-HT on the levels of 6-keto- prostaglandin F2α and thromboxane B2. The baseline levels of 6-keto- prostaglandin F1α and thromboxane B2 before 5-HT were 1791 ± 387 and 434 ± 74 pg/mL, respectively, in the control. 5-HT application had no significant effects on these prostanoid levels (levels at the highest concentration of 5-HT had a corresponding value of 1175 ± 301 and 288 ± 74 pg/mL for 6-keto-prostaglandin F1α and thromboxane B2, respectively). However, indomethacin (5 mg/kg, i.v.) treatment of the control piglets potentiated the constriction in response to 5-HT (-11 ± 1, -15 ± 2, and - 24 ± 3%, respectively) sufficiently to produce constriction similar to that in the hematoma group. 5-HT has little effect on normal pial arterioles of newborn piglets but is a more potent cerebral vasoconstrictor in conjunction with cerebral hematoma.