Document Detail

The potential role of thromboxane and prostacyclin in endotoxic and septic shock.
MedLine Citation:
PMID:  6440569     Owner:  NLM     Status:  MEDLINE    
The potential role of thromboxane (TxA2), a platelet aggregator and vasoconstrictor, and prostacyclin (PGI2) a platelet anti-aggregator and vasodilator, in endotoxic and septic shock was investigated. Early endotoxic shock in the rat is associated with marked elevations of plasma TxB2 (the stable metabolite of TxA2) and lesser increases in plasma 6-keto-PGF1 alpha (the stable metabolite of PGI2). Selective inhibition of TxA2 synthesis by several different chemical classes of Tx synthetase inhibitors was beneficial in endotoxic shock. In contrast, shock induced by acute intra-abdominal sepsis in the rat was characterized by high levels of plasma 6-keto-PGF1 alpha, which exceeded plasma TxA2 six- to eight fold at most time intervals studied. Tx synthetase inhibitors were not protective in this model of acute sepsis, but treatment with fatty acid cyclo-oxygenase inhibitors, an antibiotic (gentamicin), or reduction in arachidonic acid metabolism by essential fatty acid (EFA) deficiency significantly prolonged survival time. An important aspect of the latter study is that decreased arachidonic acid metabolism was an effective adjunct to antibiotic therapy. Conjoint administration of gentamicin in EFA-deficient rats or with indomethacin synergistically improved long-term survival, a result that was not evident with single treatment interventions. In addition to experimental studies, plasma TxB2 levels were measured during clinical sepsis. These studies demonstrated that plasma TxB2 levels were elevated tenfold in patients dying of septic shock compared with septic survivors or nonseptic controls. These composite experimental and clinical observations suggest that arachidonic acid metabolites play a role in the pathogenesis of endotoxic and septic shock.
J A Cook; W C Wise; R R Butler; H D Reines; W Rambo; P V Halushka
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of emergency medicine     Volume:  2     ISSN:  0735-6757     ISO Abbreviation:  Am J Emerg Med     Publication Date:  1984 Jan 
Date Detail:
Created Date:  1985-03-21     Completed Date:  1985-03-21     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8309942     Medline TA:  Am J Emerg Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  28-37     Citation Subset:  IM    
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MeSH Terms
Arachidonic Acids / blood
Aspirin / therapeutic use
Cyclooxygenase Inhibitors
Epoprostenol / analysis,  metabolism*
Fatty Acids / deficiency
Gentamicins / therapeutic use
Ibuprofen / therapeutic use
Imidazoles / therapeutic use
Methacrylates / therapeutic use
Peritonitis / metabolism
Rats, Inbred Strains
Shock, Septic / drug therapy,  metabolism*
Thromboxane-A Synthase / antagonists & inhibitors
Thromboxanes / analysis,  metabolism*
Grant Support
Reg. No./Substance:
0/Arachidonic Acids; 0/Cyclooxygenase Inhibitors; 0/Fatty Acids; 0/Gentamicins; 0/Imidazoles; 0/Methacrylates; 0/Thromboxanes; 15687-27-1/Ibuprofen; 288-32-4/imidazole; 35121-78-9/Epoprostenol; 50-78-2/Aspirin; 75987-08-5/2-methyl-3-(4-(3-pyridinylmethyl)phenyl)-2-propenoic acid; 78218-09-4/dazoxiben; EC Synthase

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