J.Jpn. Surg. Soc.. 89(1): 6-20, 1988

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Original article

EXPERIMENTAL STUDY ON PATHOPHYSIOLOGY OF ENDOTOXIN SHOCK AS ANALYSED BY THE ALTERATIONS IN THROMBOXANE B₂ AND 6-keto-PGF_1α LEVELS

To evaluate the pathophysiological role of thromboxane A₂ (TXA₂) in endotoxin shock, plasma concentrations of TXA₂ and PGI₂ following E. coli endotoxin (ET) administration were measured in dogs and rats by radioimmunoassay of their stable metabolites TXB₂ and 6-keto-PGF_1α, respectively. Also, the effects of TXA₂ synthetase inhibitor (OKY046) on eicosanoid levels, haemodynamics and survival were assessed. The following results were obtained:
1) Survival rates of the rats given 50mg/kg of ET were 31% at 12 hrs and 17% at 24 hrs. Pretreatment with OKY046 markedly improved the survival rates.
2) Plasma concentrations of TXB₂ were rapidly elevated in untreated control dogs and rats following ET administration, whereas plasma 6-keto-PGF_1α levels were gradually elevatated. TXB₂/6-keto-PGF_1α ratio showed an early elevation at 15 minutes after ET administration. The ratio became lower than base line, thereafter.
3) In contrast to the controls, animals pretreated with OKY046 did not exhibit significant elevations in plasma TXB₂ levels. On the other hand, plasma levels of 6-keto-PGF_1α were not alterd by OKY046 treatment.
4) In the control dogs given ET, the early elevations in pulmonary artery pressure (PAP) and reduction in lung compliance correlated with the early elevation in plasma TXB₂/6-keto-PGF_1α ratio.
5) In OKY046-treated dogs, the early elevation in TXB₂/6-keto-PGF_1α ratio was not seen and PAP increase and lung compliance reduction were prevented.
The results suggest that TXA₂ plays an important pathophysiological role in the development of endotoxin shock.

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