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 cerebral 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-hydroxytryptamine1 agonist (sumatriptan).


METHODS
ICP was raised by inflation of two balloons covering both parieto-occipital 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 content difference (CavO2), and jugular venous pH (vpH) were performed 5, 20, 40, 60, and 75 min after start of the infusion. ICP, mean arterial pressure, and EEG were recorded continuously. Direct effects of sumatriptan were also compared in cortical arteries and veins in vitro.


RESULTS
Significant decreases in ICP were obtained in groups A, B, and C while group D exhibited a progressive increase in ICP. Significant reductions in CBF, increase in CavO2, and slowing of EEG were observed in groups B, C, and D. Sumatriptan caused moderate constriction of the arteries and a more pronounced dilatation of veins in vitro.


CONCLUSIONS
The results indicate that a low dose of sumatriptan has the potential to reduce a raised ICP. High doses of sumatriptan cause a further increase of ICP possibly by dilatation of intracerebral veins.
Nilsson
F
F
Department of Anaesthesia and Intensive Care, Malmö University Hospital, Sweden.
Nilsson
T
T
Edvinsson
L
L
Rosén
I
I
Björkman
S
S
Messeter
K
K
Nordström
C H
CH
D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects / Q000503:physiopathology; D002550:Cerebral Veins / Q000187:drug effects / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D066298:In Vitro Techniques; D011559:Pseudotumor Cerebri / Q000188:drug therapy* / Q000503:physiopathology; D018170:Sumatriptan / Q000627:therapeutic use*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*
D014662:Vasoconstrictor Agents; D018170:Sumatriptan