DIFFERENCES IN EICOSANOID AND CYTOKINE PRODUCTION BETWEEN INJURY HEMORRHAGE AND BACTEREMIC SHOCK IN THE PIG/

Plasma concentrations of the eicosanoids leukotriene (LT)B-4, LTC4D4E4 , thromboxane (TX)A(2) and prostaglandin (PG)I-2, and tumor necrosis f actor (TNF) were measured during acute bacteremic shock and injury/hem orrhage in two porcine models. As TXA(2) and PGI(2) are rapidly metabo lized, we measured their stable metabolites TXB2 and 6-keto-PGF(1 alph a). Bacteremic shock was induced by a graded infusion of Aeromonas hyd rophila over 4 h. Injury/hemorrhage was produced by a 30 min, 30% tota l blood volume hemorrhage followed by a 30 min shock period and then r einfusion of shed blood. Nociceptive afferent nerve stimulation was ap plied to the brachial plexi to mimic the cardiovascular responses to t issue injury. There was no increase in eicosanoid or TNF levels in the injury/hemorrhage model. In sepsis there was an early peak in TNF (at 60 min) followed by peaks in LTB4 and LTC4D4E4 at 180 min. Both TXB2 and 6-keto-PGF(1 alpha) showed large increases at the end of the study but there was no evidence that they had reached a peak. These results suggest that the very early inflammatory response in bacteremic shock and injury/hemorrhagic shock may be quite different. This may have im plications for any therapies aimed at reducing the incidence of multip le organ failure after either of these physiological insults.