Document Detail


Neostigmine counteracts spinal clonidine-induced hypotension in sheep.
MedLine Citation:
PMID:  8439026     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Intraspinal clonidine injection produces analgesia free of respiratory depression, but also decreases blood pressure and causes sedation. Spinal neostigmine injection alone increases blood pressure in animals and enhances clonidine-induced analgesia. METHODS: To test whether neostigmine would alter clonidine-induced hypotension, nine chronically prepared sheep received intrathecal injections of saline or neostigmine (150, 300, 1,000 micrograms) followed in 15 min by 200 micrograms clonidine. RESULTS: Clonidine plus saline decreased mean arterial pressure by 12 +/- 3% associated with small, statistically nonsignificant decreases in heart rate, cardiac output, and systemic vascular resistance. Prior injection of neostigmine diminished hypotension 60 min after clonidine injection in a dose-dependent manner. To further define the time course and pharmacology of this interaction, seven other sheep received intrathecal saline, neostigmine (1,000 micrograms), or neostigmine plus methylatropine (1,000 micrograms) 75 min prior to 200 micrograms clonidine. With this longer interval between injections, neostigmine abolished clonidine-induced hypotension, and this protective effect was inhibited by methylatropine. To test whether rostral spread of neostigmine in cerebrospinal fluid would alter its hemodynamic effects, we injected intrathecal neostigmine into the upper cervical site. Intrathecal neostigmine increased mean arterial pressure and heart rate at this site to a degree similar to that in the thoracic area, with no effect on behavioral or arterial blood gas tensions. CONCLUSIONS: These data are consistent with neostigmine's counteraction of clonidine-induced hypotension by a spinal muscarinic mechanism and support investigation of spinal alpha 2-adrenergic-cholinergic combinations for pain therapy.
Authors:
J S Williams; C Tong; J C Eisenach
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Anesthesiology     Volume:  78     ISSN:  0003-3022     ISO Abbreviation:  Anesthesiology     Publication Date:  1993 Feb 
Date Detail:
Created Date:  1993-03-25     Completed Date:  1993-03-25     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  301-7     Citation Subset:  AIM; IM    
Affiliation:
Department of Anesthesia, Wake Forest University Medical Center, Winston-Salem, North Carolina 27157-1009.
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MeSH Terms
Descriptor/Qualifier:
Animals
Clonidine / administration & dosage,  adverse effects,  antagonists & inhibitors*
Female
Hypotension / chemically induced*
Injections, Spinal
Neostigmine / administration & dosage,  pharmacology*
Sheep
Grant Support
ID/Acronym/Agency:
GM35523/GM/NIGMS NIH HHS; T32-DK-07400/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
4205-90-7/Clonidine; 59-99-4/Neostigmine
Comments/Corrections
Comment In:
Anesthesiology. 1994 May;80(5):1180-1   [PMID:  8054061 ]

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