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. 1991 Nov;104(3):691–699. doi: 10.1111/j.1476-5381.1991.tb12490.x

Sequential release of tumour necrosis factor, platelet activating factor and eicosanoids during endotoxin shock in anaesthetized pigs: protective effects of indomethacin.

T Mózes 1, F J Zijlstra 1, J P Heiligers 1, C J Tak 1, S Ben-Efraim 1, I L Bonta 1, P R Saxena 1
PMCID: PMC1908219  PMID: 1797328

Abstract

1. The effects of indomethacin were investigated on haemodynamics, haematological and blood glucose values, and the release of tumour necrosis factor (TNF), platelet activating factor (PAF) and eicosanoids in anaesthetized pigs receiving 5 micrograms kg-1 E. coli lipopolysaccharide (LPS) over 60 min into the superior mesenteric artery. The animals were observed for an additional period of 2 h after the termination of LPS infusion. 2. Eight of the 17 animals infused with LPS and not treated with indomethacin died within 30 min after the beginning of LPS infusion (non-survivors), while the other 9 survived the experimental period of 3 h though in a state of shock (survivors). 3. No alterations were observed in plasma concentrations of PAF and eicosanoids (thromboxane B2 (TXB2), 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) and leukotriene B4 (LTB4] in non-survivors. However, a marked increase was detected in TNF release. A significant, though transient, increase in concentrations of PAF, TNF and eicosanoids occurred in the survivors. The peak in the concentrations of PAF and TXB2 preceded the maximum in TNF values in survivors. 4. Another group of 7 LPS-infused pigs was treated with indomethacin (2 mg kg-1, i.v. bolus 60 min before the start of LPS infusion, followed by a continuous infusion of 3 mg kg-1 h-1). This treatment prevented death and shock despite the high concentrations of circulating TNF and PAF. Concentrations of cyclo-oxygenase enzyme products were reduced, whereas LTB4 release was not affected. The effect of indomethacin on haemodynamic changes occurred earlier than on cyclo-oxygenase products.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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