Effects of dihydroergotamine and sumatriptan on isolated human cerebral and peripheral arteries and veins.
BACKGROUND
Pharmacological cerebral vasoconstriction has recently been suggested as treatment for patients with increased intracranial pressure (ICP) after severe traumatic brain lesions. Hypothetically, a moderate constriction of precapillary resistance vessels might be advantageous since it decreases intracapillary blood pressure, and a contraction of cerebral veins might effectively reduce intracranial blood volume and ICP. This report examines the in vitro effects of two vasoconstrictors, dihydroergotamine (DHE) and sumatriptan, which may be considered for treatment of increased ICP.


METHODS
The reactivity of isolated small human cerebral subcutaneous and omental arteries and veins were studied during exposure to different concentrations of DHE and sumatriptan.


RESULTS
Both sumatriptan and DHE induced concentration-dependent contractions in human cerebral arteries and veins and 50% of maximum contractions were obtained at significantly lower concentrations of DHE than of sumatriptan. The maximum contraction of cerebral arteries was significantly higher with sumatriptan than with DHE. Both drugs caused contractions of subcutaneous arteries at concentrations of 10(-7)-10(-6)M, which is within the therapeutic concentration range of sumatriptan, while no effect was obtained in omental vessels.


CONCLUSIONS
Both DHE and sumatriptan cause contraction of isolated human cortical arteries and veins at very low concentrations. The differences observed between the two drugs may be explained by the fact that DHE is an alpha-adrenergic as well as a 5-HT agonist while sumatriptan acts specifically on 5-HT receptors. The study supports the hypothesis underlying the use of DHE for the treatment of increased ICP in patients with severe traumatic brain lesions.
Nilsson
F
F
Department of Anaesthesia and Intensive Care, and Experimental Research, Malmö University Hospital, Sweden.
Nilsson
T
T
Edvinsson
L
L
Björkman
S
S
Nordström
C H
CH
D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology; D002550:Cerebral Veins / Q000187:drug effects* / Q000502:physiology; D004087:Dihydroergotamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007427:Intracranial Pressure / Q000187:drug effects; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D017366:Serotonin Receptor Agonists; D014662:Vasoconstrictor Agents; D004087:Dihydroergotamine; D018170:Sumatriptan