Annals of Surgery

Skip Navigation LinksHome > November 2007 - Volume 246 - Issue 5 > Intravenous Injection of Trauma-Hemorrhagic Shock Mesenteric...
Annals of Surgery:
doi: 10.1097/SLA.0b013e3180caa3af
Original Articles

Intravenous Injection of Trauma-Hemorrhagic Shock Mesenteric Lymph Causes Lung Injury That Is Dependent Upon Activation of the Inducible Nitric Oxide Synthase Pathway

Senthil, Maheswari MD; Watkins, Anthony MD; Barlos, Dimitrios MD; Xu, Da-Zhong MD, PhD; Lu, Qi MD; Abungu, Billy BSc; Caputo, Frank MD; Feinman, Rena PhD; Deitch, Edwin A. MD

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Objective: To test the hypothesis that gut-derived factors carried in trauma-hemorrhagic shock (T/HS) lymph is sufficient to induce lung injury. Additionally, because our previous studies showed that T/HS-induced nitric oxide production was associated with lung injury, we examined whether T/HS lymph-induced lung injury occurs via an inducible nitric oxide synthase (iNOS)-dependent pathway.

Background: We have previously shown that T/HS-induced lung injury is mediated by gut-derived humoral factors carried in the mesenteric lymph. However, it remains unclear whether T/HS lymph itself is sufficient to induce lung injury, or requires the activation of other factors during the T/HS period to exert its effect.

Methods: Mesenteric lymph collected from T/HS or trauma-sham shock (T/SS) animals was injected intravenously into male rats at a rate of 1 mL/h for 3 hours. At the end of infusion, lung injury was assessed by lung permeability and lung histology. The effect of iNOS inhibition on T/HS lymph-induced lung injury was studied and this was further confirmed in iNOS knockout mice. Finally, iNOS immunohistochemistry was performed to identify the cells of origin of iNOS.

Results: The injection of T/HS lymph, but not sham shock lymph, caused lung injury. This was associated with increased plasma nitrite/nitrate levels as well as induction of iNOS protein in the lung, liver, and gut. Treatment with the selective iNOS inhibitor aminoguanidine prevented T/HS lymph-induced lung injury. iNOS knockout mice, but not their wild-type controls, were resistant to T/HS lymph-induced lung injury. By immunohistochemistry, neutrophils and macrophages, rather than parenchymal cells, were the source of T/HS lymph-induced lung iNOS.

Conclusions: These results indicate that T/HS lymph is sufficient to induce acute lung injury and that lymph-induced lung injury occurs via an iNOS-dependent pathway.

© 2007 Lippincott Williams & Wilkins, Inc.


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