Intravenous injection of trauma-hemorrhagic shock mesenteric lymph causes lung injury that is dependent upon activation of the inducible nitric oxide synthase pathway

• Published in: Annals of surgery 2007-11, Vol.246 (5), p.822-830
• Main Authors: SENTHIL, Maheswari, WATKINS, Anthony, BARLOS, Dimitrios, ZHONG XU, QI LU, ABUNGU, Billy, CAPUTO, Frank, FEINMAN, Rena, DEITCH, Edwin A
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Disease Models, Animal; General aspects; Injections, Intravenous; Lymph - physiology; Male; Medical sciences; Mesentery; Mice; Mice, Knockout; Nitric Oxide - physiology; Nitric Oxide Synthase Type II - physiology; Rats; Rats, Sprague-Dawley; Respiratory Distress Syndrome, Adult - etiology; Respiratory Distress Syndrome, Adult - metabolism; Respiratory Distress Syndrome, Adult - pathology; Shock, Hemorrhagic - complications; Shock, Hemorrhagic - metabolism
• ISSN: 0003-4932; 1528-1140
• DOI: 10.1097/SLA.0b013e3180caa3af

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. 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. 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. 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. 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.