EFFECTS OF DIHYDROERGOTAMINE AND SUMATRIPTAN ON ISOLATED HUMAN CEREBRAL AND PERIPHERAL ARTERIES AND VEINS

Background: Pharmacological cerebral vasoconstriction has recently bee n suggested as treatment for patients with increased intracranial pres sure (ICP) after severe traumatic brain lesions. Hypothetically, a mod erate constriction of precapillary resistance vessels might be advanta geous since it decreases intracapillary blood pressure, and a contract ion of cerebral veins might effectively reduce intracranial blood volu me and ICP. This report examines the in vitro effects of two vasoconst rictors, dihydroergotamine (DHE) and sumatriptan, which may be conside red for treatment of increased ICP. Methods: The reactivity of isolate d small human cerebral, subcutaneous and omental arteries and veins we re studied during exposure to different concentrations of DHE and suma triptan. Results: Both sumatriptan and DHE induced concentration-depen dent contractions in human cerebral arteries and veins and 50% of maxi mum contractions were obtained at significantly lower concentrations o f DHE than of sumatriptan. The maximum contraction of cerebral arterie s 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 sum atriptan, while no effect was obtained in omental vessels. Conclusions : Both DHE and sumatriptan cause contraction of isolated human cortica l arteries and veins at very low concentrations. The differences obser ved between the two drugs may be explained by the fact that DHE is an or-adrenergic as well as a 5-HT agonist while sumatriptan acts specifi cally on 5-HT receptors. The study supports the hypothesis underlying the use of DHE for the treatment of increased ICP in patients with sev ere traumatic brain lesions.