title: Site of hemodynamic effects of intrathecal alpha 2-adrenergic agonists.
abstract: Intrathecally administered alpha 2-adrenergic agonists produce analgesia in humans but may also produce hypotension and bradycardia. To further characterize hemodynamic depression produced by intrathecally administered alpha 2-adrenergic agonists, clonidine (100-1,500 micrograms) was injected into the cervical, thoracic, or lumbar intrathecal space of conscious sheep. Only thoracic intrathecal clonidine injection (100 or 300 micrograms) decreased blood pressure, whereas these doses did not affect blood pressure when injected at other sites. A greater clonidine dose (1,500 micrograms) increased blood pressure to a similar degree at all sites. Hypotension after thoracic intrathecal clonidine injection was inhibited by pretreatment with the alpha 2-adrenergic antagonist idazoxan (1 mg, intrathecally) or the depleter of acetylcholine stores hemicholinium-3 (2 mg, intrathecally), suggesting an action at alpha 2-adrenoceptors on cholinergic preganglionic sympathetic neurons. ST-91, a polar clonidine analog, did not decrease blood pressure after thoracic intrathecal injection. Intrathecal injection of the muscarinic receptor agonist carbamylcholine increased blood pressure. These data describe a complex action of intrathecal alpha 2-adrenergic agonists on hemodynamic parameters that is dependent on site of injection, drug dose, and drug lipophilicity; that can be explained by anatomic factors; and that may possibly be exploited to minimize hemodynamic depression from these agents.
authors.affiliation: Department of Anesthesia, Wake Forest University Medical Center, Winston-Salem, North Carolina 27103.
authors.forename: J C
authors.initials: JC
authors.lastname: Eisenach
authors.forename: C Y
authors.initials: CY
authors.lastname: Tong
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D003000:Clonidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004146:Dioxanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D019329:Idazoxan; D007278:Injections, Spinal; D012756:Sheep
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; C011266:ST 91; D002217:Carbachol; D003000:Clonidine; D019329:Idazoxan