Pathophysiology of Experimental Bovine Endotoxicosis: Endotoxin Induced Synthesis of Prostaglandins and Thromboxane and the Modulatory Effect of Some Non-Steroidal Anti-Inflammatory Drugs

Abstract

Endotoxin-induced synthesis of thromboxane A2 (TXA2), prostacyclin (PGI2) and prostaglandin E2 (PGE2) was studied in 3 cows after intravenous E. coli endotoxin (055:B5–0.025 mg/kg b.w.) administration. Blood sampling and monitoring of clinical signs were performed from 2 h prior to until 6 h after endotoxin challenge. Blood samples were analyzed for stable hydrolysis products of TXA2 (TXB2), PGI2 (6-keto PGF) and PGE2 (bicyclic PGE2), biochemical and haematological parameters. In a similar experimental design the efficacy of the non-steroidal anti-inflammatory drugs (NSAID) flunixin meglumine (FM) and phenylbutazone (PB) in suppressing eicosanoid synthesis and clinical signs in response to endotoxin challenge was investigated. Two groups of cows, each comprising 2 animals, were treated with FM and PB prior to endotoxin challenge. It was observed that plasma concentrations of TXB2, 6-keto PGF and bicyclic PGE2 increased rapidly after endotoxin challenge. Concentrations were significantly elevated for hours and were correlated to the severity of clinical signs of endotoxicosis. Pretreatment with NSAID suppressed mediator production and alleviated clinical signs. The experiments suggest a certain pathophysiological role of TXA2, PGI2 and PGE2 for the early systemic ill-effects of bovine endotoxicosis.

Sammendrag

Endotoksin-induceret syntese af thromboxan A2 (TXA2), prostacyklin (PGI2) og prostaglandin E2 (PGE2) blev undersøgt hos 3 k0er efter intravenøs applikation af E.coli endotoksin (0.55:B5-0.025 mg/kg legemsvægt). Udtagning af blodprøver og registrering af kliniske symptomer blev foretaget fra 2 t før til 6 t efter endotoksinindgift. Blodprøverne blev analyseret for de stabile metabolitter af TXA2 (TXB2), PGI2 (6-keto PGF) og PGE2 (bicyklisk PGE2), biokemiske og hæmatologiske parametre. I en lignende eksperimentel undersøgelse belyses den suppressive effekt af de non-steroide antiinflammatoriske stoffer (NSAID) flunixin meglumin (FM) og fenylbutazon (PB) på eikosanoidsyntese og kliniske symptomer ved eksperimentel endotoksikose. To grupper køer, hver bestående af 2 dyr, blev behandlet med henholdsvis FM og PB inden endotoksinindgift. Forsøgene viste, at plasmakoncentrationerne af de stabile metabolitter steg hurtigt efter endotoksinindgift, var forhøjede i flere timer og korrelerede tidsmæssigt med graden af de kliniske symptomer på endotoksikose. Indgift af FM og PB hæmmede den endotoksininducerede eikosanoidsyntese og svækkede graden af de kliniske symptomer. Resultaterne peger på, at eikosanoiderne TXA2, PGI2 og PGE2 har patofysiologisk betydning for de systemiske manifestationer af bovin eksperimentel endotoksikose.