@entity99 increases circulating @entity1505 and @entity568 and mortality after XXXX @entity5694 .

@entity32 @entity6566 @entity5694 @entity2332 @entity35 @entity20463 @entity1219 @entity568 @entity409 @entity1505 @entity648 @entity651 @entity551 @entity1448 @entity70610 @entity1431 @entity2270 @entity99 @entity493 @entity526
We employed a bile duct ligation (BDL) model of @entity99 to test the hypothesis that this form of preexisting @entity409 alters the kinetics of circulating @entity1505 and @entity568 after @entity526 @entity5694 , thereby augmenting mortality and @entity651 by a @entity1505 :leukotriene (LT) @entity2270 of @entity32 . Male @entity35 were catheterized 13 d after BDL or sham surgery and studied while awake 18 to 24 h later. @entity1448 after BDL was confirmed by baseline serum @entity648 (BDL = 7.34 +/- 0.72 mg/dl, mean +/- SEM, n = 17 versus Sham = 0.25 +/- 0.07, n = 20; p < 0.005) and histopathology. Sham and BDL animals received @entity526 @entity70610 ( @entity70610 , 5 mg/kg i.v.) or 0.9% @entity1219 (NS) ending at t = 0 and were monitored over 24 h for vital signs and hemodynamics. In parallel studies, lipoxygenase inhibition was performed using @entity6566 or the 5-lipoxygenase activating-protein inhibitor @entity20463 . Blood was collected at baseline and at t = 1.5, 3.5, and 24 h for formed elements and for serum endotoxin, @entity1505 , @entity568 , @entity648 , and @entity493 aminotransferase (ALT). Organs were evaluated at 24 h for histopathology, including neutrophil (PMN) densities and wet/dry weight (W/D) ratios. @entity1448 reduced survival after otherwise nonlethal @entity5694 , with seven of 11 BDL + @entity70610 @entity35 dying within 24 h versus no deaths in BDL + NS (n = 6), Sham + @entity70610 (n = 14), or Sham + NS (n = 6) animals (p < 0.01). Despite equivalent serum endotoxin between groups, circulating @entity1505 was 8-fold higher in BDL + @entity70610 than in Sham + @entity70610 @entity35 at 1.5 and 3.5 h (p < 0.001), whereas serum @entity1505 did not differ between BDL + NS and Sham + NS @entity35 . @entity568 likewise was increased differentially by 1.5 h in BDL + @entity70610 animals (11.98 +/- 2.42 ng/ml) versus Sham + @entity70610 @entity35 (3.05 +/- 0.58 ng/ml, p < 0.05). @entity2332 , @entity551 , and @entity1431 were most severe and prolonged in BDL + @entity70610 @entity35 , which also had significantly higher ALT values, W/D ratios, and organ PMN counts. LT inhibition failed to reduce BDL-related differences in serum cytokines or survival after @entity5694 . Thus, @entity1448 augments inflammatory responses to gram-negative @entity5694 , sensitizing the host to enhanced fluid flux in multiple organs and to mortality by a LT-independent mechanism.
