SUMATRIPTAN-INDUCED CEREBRAL VASOCONSTRICTION AS TREATMENT OF EXPERIMENTAL INTRACRANIAL HYPERTENSION

Background: Increased intracranial pressure (ICP) is a major cause of mortality in severe head injuries and pharmacologically induced cerebr al vasoconstriction has been suggested as a possible treatment. In the present study a porcine model of increased ICP was utilized to study the changes in cerebral haemodynamics and energy metabolism induced by a selective 5-hydroxytryptamine(1) agonist (sumatriptan). Methods: IC P was raised by inflation of two balloons covering both parieto-occipi tal regions extradurally. The animals were randomized into four groups receiving sumatriptan: 0.01 mg . kg(-1) (A), 0.03 mg . kg(-1) (B), 0. 1 mg . kg(-1) (C), and 0.5 mg . kg(-1) (D) intravenously over 10 min. Measurements of cerebral blood flow (CBF), arterio-venous oxygen conte nt difference (CavO(2)), and jugular venous pH (vpH) were performed 5, 20, 40, 60, and 75 min after start of the infusion. ICP, mean arteria l pressure, and EEG were recorded continuously. Direct effects of suma triptan were also compared in cortical arteries and veins in vitro. Re sults: Significant decreases in ICP were obtained in groups A, B, and C while group D exhibited a progressive increase in ICP. Significant r eductions in CBF, increase in CavO(2), and slowing of EEG were observe d in groups B, C, and D. Sumatriptan caused moderate constriction of t he arteries and a more pronounced dilatation of veins in vitro. Conclu sion: The results indicate that a low dose of sumatriptan has the pote ntial to reduce a raised ICP. High doses of sumatriptan cause a furthe r increase of ICP possibly by dilatation of intracerebral veins.