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Verification of the production of peptide leukotrienes (LT) in traumatic shock

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:7023606

Both lipoxygenase inhibition and leukotriene receptor antagonism have been demonstrated to provide significant protection in traumatic shock. Despite these findings, leukotrienes have not been found in circulating blood in Noble-Collip drum induced traumatic shock using radioimmunoassay techniques. Anesthetized rats subjected to Noble-Collip drum trauma developed a shock state characterized by a significant reduction in mean arterial blood pressure, a 4.5 fold increase in plasma cathepsin D activity, a 3-fold increase in myocardial depressant factor activity and a mean survival time of 1.9 +/- 0.3 hours. Plasma and bile samples were analyzed by reverse phase high pressure liquid chromatography to determine LT production in this shock model. No detectable peptide leukotrienes or their metabolites were found in plasma. The major peptide leukotriene from bile eluted between LTC/sub 4/ and LTD/sub 4/ and corresponds to a metabolite of LTE/sub 4/, N-acetyl-LTE/sub 4/. This metabolite increased from 6 +/- 3 to 41 +/- 4 units in traumatic shock when compared to sham trauma (p < 0.01). Infusion of exogenous LTC/sub 4/, LTD/sub 4/ and LTE/sub 4/ (10 ..mu..g/kg/h) also resulted in the metabolism of > 90% of the parent LT to this metabolite in bile. Therefore, plasma LTs accumulate in the bile following trauma in rats. Moreover, LTC/sub 4/, LTD/sub 4/ and LTE/sub 4/ apparently are rapidly metabolized to N-acetyl LTE/sub 4/. These findings further support a role for leukotrienes in the pathogenesis of traumatic shock in rats.

Research Organization:
Thomas Jefferson Univ., Philadelphia, PA
OSTI ID:
7023606
Report Number(s):
CONF-8604222-
Journal Information:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:4; ISSN FEPRA
Country of Publication:
United States
Language:
English