Lack of effect of the antimigraine drugs, sumatriptan, ergotamine and dihydroergotamine on arteriovenous anastomotic shunting in the dura mater of the pig.
1. In anaesthetized animals, the antimigraine drugs, sumatriptan, ergotamine and dihydroergotamine, reduce carotid arteriovenous anastomotic shunting. Within the carotid vascular bed arteriovenous anastomoses are located, amongst other places in the dura mater, which is a putative site of the pain during a migraine attack. 2. In this investigation, we have localized and measured the arteriovenous shunting within the carotid vascular bed of the pig by using simultaneous intracarotid injections of radiolabelled microspheres of three different sizes (10, 15 and 50 microns), which provides an index of blood flow via arteriovenous anastomoses larger than approximately 14, 27 and 90 microns diameter, respectively. The effects of sumatriptan (0.3 mg kg-1), ergotamine (0.02 mg kg-1), dihydroergotamine (0.1 mg kg-1) and saline were studied by repeating the injections of 15 and 50 microns spheres after the treatments. 3. There was no difference in shunting or entrapment between the 10 and 15 microns microsphere, indicating the absence of arteriovenous anastomoses with a diameter between 14 and 27 microns. 4. Arteriovenous anastomoses with a diameter between 27 and 90 microns, as indicated by the difference in blood flow measured by 15 and 50 microns spheres, were located in the dura mater, ears, skin, fat and, to a lesser extent, in the skeletal muscles and eyes. 5. Sumatriptan, ergotamine and dihydroergotamine reduced the overall flow in the smaller arteriovenous anastomoses (diameter between 27 and 90 microns), and even more in larger shunts (wider than 90 microns). 6. Locally, blood flow in the smaller arteriovenous shunts was reduced in the skin and fat, but not in the dura mater, ears, eyes and muscles.It is not possible to determine in which tissues blood flow in the larger arteriovenous anastomoses was reduced.7. Tissue blood flow measured with 15 gm microspheres remained unchanged after the three antimigraine drugs, implying a lack of effect on capillary flow.8. It is concluded that in the anaesthetized pigs the only evident effect of these antimigraine drugs on carotid haemodynamics is a decrease in blood flow in both smaller and larger arteriovenous anastomoses;the smaller arteriovenous anastomoses were affected in the skin and fat, but not in other tissues.
den Boer
M O
MO
Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The Netherlands.
Somers
J A
JA
Saxena
P R
PR
D000818:Animals; D001163:Arteriovenous Anastomosis / Q000187:drug effects*; D004087:Dihydroergotamine / Q000494:pharmacology; D004388:Dura Mater / Q000098:blood supply* / Q000187:drug effects; D004878:Ergotamine / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D008863:Microspheres; D008881:Migraine Disorders / Q000188:drug therapy; D012039:Regional Blood Flow / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D018170:Sumatriptan; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D007211:Indoles; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; D004087:Dihydroergotamine; D018170:Sumatriptan; D004878:Ergotamine