Document Detail


Endotoxin disrupts beta-adrenergic signal transduction in the heart.
MedLine Citation:
PMID:  8304831     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Nonsurvivors of septic shock demonstrate impaired myocardial function refractory to the administration of beta-agonists. METHODS: Using the isolated rat heart preparation, the integrity of the beta-adrenergic transduction pathway was tested (rate pressure product, rate of contraction, rate of relaxation, and cyclic adenosine monophosphate content) using isoproterenol hydrochloride (beta-receptor agonist) or colforsin (forskolin) (adenylyl cyclase activator) stimulation following intracoronary endotoxin infusion. RESULTS: Basal rate pressure product, rate of contraction, rate of relaxation, and cyclic adenosine monophosphate concentrations were unaffected by endotoxin infusion. Endotoxin impaired, increases in rate pressure product, rates of contraction and relaxation, and cyclic adenosine monophosphate to isoproterenol (P < .05), but the response to colforsin was unaffected by endotoxin. CONCLUSIONS: Endotoxin disrupts the myocardial response to direct beta-receptor stimulation but not to adenylyl cyclase stimulation in the isolated rat heart. CLINICAL RELEVANCE: Alteration of the proximal beta-adrenoreceptor complex by endotoxin suggests that therapy of the failing heart during refractory septic shock may be directed to intact sites distal in the beta-adrenergic pathway.
Authors:
D D Bensard; A Banerjee; R C McIntyre; R L Berens; A H Harken
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Archives of surgery (Chicago, Ill. : 1960)     Volume:  129     ISSN:  0004-0010     ISO Abbreviation:  Arch Surg     Publication Date:  1994 Feb 
Date Detail:
Created Date:  1994-03-10     Completed Date:  1994-03-10     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9716528     Medline TA:  Arch Surg     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  198-204; discussion 204-5     Citation Subset:  AIM; IM    
Affiliation:
Department of Surgery, University of Colorado Health Sciences Center, Denver.
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MeSH Terms
Descriptor/Qualifier:
Adenylate Cyclase / drug effects
Animals
Cardiac Output / drug effects
Cyclic AMP / metabolism
Endotoxins / adverse effects*
Forskolin / pharmacology*
Heart / drug effects*
Heart Rate / drug effects
Isoproterenol / pharmacology*
Lipopolysaccharides / adverse effects*
Male
Myocardial Contraction / drug effects
Rats
Rats, Sprague-Dawley
Receptors, Adrenergic, beta / drug effects*
Salmonella typhimurium*
Signal Transduction / drug effects*
Ventricular Pressure / drug effects
Grant Support
ID/Acronym/Agency:
HL 44186/HL/NHLBI NIH HHS; R29-H43696//PHS HHS
Chemical
Reg. No./Substance:
0/Endotoxins; 0/Lipopolysaccharides; 0/Receptors, Adrenergic, beta; 60-92-4/Cyclic AMP; 66428-89-5/Forskolin; 7683-59-2/Isoproterenol; EC 4.6.1.1/Adenylate Cyclase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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