Intrathecal neostigmine prevents intrathecal clonidine from attenuating hypercapnic cerebral vasodilation in rabbits.
We previously demonstrated that lumbar intrathecal alpha(2) agonists attenuate hypercapnia-induced cerebral vasodilation. The combination of intrathecal clonidine and neostigmine is being investigated as pain therapy. The effects of their combination on cerebrovascular reactivity are unknown. We allocated rabbits anesthetized with pentobarbital to two groups: (a) clonidine (normal saline followed 30 min later by clonidine 2 microg/kg, both into the lumbar intrathecal space; n = 6), and (b) neostigmine-pretreatment (neostigmine 2 microg/kg followed 30 min later by clonidine 2 microg/kg, both into the lumbar intrathecal space; n = 6). We then evaluated the hypercapnia-induced changes in pial arteriolar diameter in these two groups using the closed cranial window preparation. The pial arteriolar dilator response to hypercapnia was significantly attenuated in the clonidine group (14% +/- 4%, 4% +/- 4%, 6% +/- 6%, and 5% +/- 7% for before and 30, 60, and 90 min, respectively). Neither normal saline nor neostigmine alone induced any change in the cerebral reactivity to hypercapnia. Pretreatment with neostigmine completely prevented the clonidine-induced attenuation of the hypercapnic cerebral vasodilation attenuated by intrathecal clonidine (16% +/- 7%, 15% +/- 6%, 12% +/- 6%, and 16% +/- 8%, respectively).
Takenaka
Motoyasu
M
Departments of *Anesthesiology and Pain Medicine and †Cardiology, Gifu University Graduate School of Medicine; and ‡Department of Nutrition and Food Science, Gifu Women's University, Gifu City, Japan.
Iida
Hiroki
H
Iida
Mami
M
Sumi
Kazuyuki
K
Kumazawa
Masahiko
M
Tanahashi
Shigeaki
S
Dohi
Shuji
S
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D003000:Clonidine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006935:Hypercapnia / Q000503:physiopathology*; D007278:Injections, Spinal; D008833:Microcirculation / Q000187:drug effects; D009388:Neostigmine / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D002800:Cholinesterase Inhibitors; D009388:Neostigmine; D003000:Clonidine