Document Detail


Failure of drugs that selectively inhibit thromboxane synthesis to modify endotoxin shock in conscious rats.
MedLine Citation:
PMID:  6375795     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effects of two thromboxane synthetase inhibitors ( dazoxiben and UK 38485) were investigated on the cardiovascular and metabolic effects of Escherichia coli endotoxin infusion in the conscious, unrestrained rat. Infusion of E. coli endotoxin (41.7 ng kg-1 min-1) for 4 h produced a fall in mean arterial pressure, an increase in heart rate, a transient hyperglycaemia (at 1 h) followed by hypoglycaemia (evident at 6 h), an elevation in plasma lactate and a profound thrombocytopenia. The above changes were accompanied by a marked elevation in plasma thromboxane B2 concentrations (e.g. endotoxin-treated 935 +/- 150 pg ml-1 at 1 h compared with pre-endotoxin values of 125 +/- 30 pg ml-1). The administration of either dazoxiben (30 mg kg-1 i.v., given 30 min before starting the endotoxin infusion) or UK 38485 (15 mg kg-1 given 30 min before, and again 4 h after, starting the endotoxin infusion) prevented the rise in plasma thromboxane B2 concentrations. Neither dazoxiben nor UK 38485 prevented the metabolic, cardiovascular or thrombocytopenic effects of endotoxin and did not modify mortality. These results suggest that, although large amounts of thromboxane are generated in response to endotoxin, they do not play an important role in the major pathophysiological consequences of acute endotoxaemia.
Authors:
B L Furman; K McKechnie; J R Parratt
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  82     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  1984 May 
Date Detail:
Created Date:  1984-08-02     Completed Date:  1984-08-02     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  289-94     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Glucose / metabolism
Blood Pressure / drug effects
Escherichia coli
Heart Rate / drug effects
Imidazoles / pharmacology
Lactates / blood
Lactic Acid
Male
Platelet Count
Rats
Rats, Inbred Strains
Shock, Septic / metabolism*
Thromboxane B2 / blood
Thromboxanes / biosynthesis*
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Imidazoles; 0/Lactates; 0/Thromboxanes; 50-21-5/Lactic Acid; 54397-85-2/Thromboxane B2; 76894-77-4/dazmegrel; 78218-09-4/dazoxiben
Comments/Corrections

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