The investigators hypothesize that following shock from either hemorrhage or thermal injury; there is a release of mediators from the gastrointestinal tract, which interact with mesenteric lymphatic system to cause the release of cytotoxic mediators from the mesenteric lymph nodes. The materials from the lymph nodes activate of pulmonary endothelium resulting in the adherence of leukocytes to the pulmonary microvasculature, and pulmonary vascular injury. In their first specific aim the investigators will characterize the action of shock lymph on endothelial cells and neutrophils and identify the humoral factors present in the mesenteric lymph after injury. The second specific aim they will determine the role of adherence molecule expression on the shock induced lung injury. The final specific aim will determine mechanisms by which mesenteric lymph from blood or burned rats, produces the lung injury. They will determine how diversion of the lymphatic drainage from the gut will prevent the pulmonary changes (deposition of cells in the lung, expression of adherence molecules and cytokines) associated with hypovolemic and burn shock. They will inject lymph into the animals and evaluate changes in the lung. This work will help to determine why disruption of gut barrier function will lead to lung injury. It will also more clearly define the role of the gut inducing lung injury and in the development of the systemic inflammatory response syndrome and multiple organ failure (MOF).

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM059841-03
Application #
6386594
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Somers, Scott D
Project Start
1999-09-01
Project End
2003-08-31
Budget Start
2001-09-01
Budget End
2002-08-31
Support Year
3
Fiscal Year
2001
Total Cost
$435,897
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Surgery
Type
Schools of Medicine
DUNS #
605799469
City
Newark
State
NJ
Country
United States
Zip Code
07107
Qin, Xiaofa; Deitch, Edwin A (2015) Dissolution of lipids from mucus: a possible mechanism for prompt disruption of gut barrier function by alcohol. Toxicol Lett 232:356-62
Fishman, Jordan E; Sheth, Sharvil U; Levy, Gal et al. (2014) Intraluminal nonbacterial intestinal components control gut and lung injury after trauma hemorrhagic shock. Ann Surg 260:1112-20
Deitch, Edwin A; Condon, Michael; Feketeova, Eleonora et al. (2014) Trauma-hemorrhagic shock induces a CD36-dependent RBC endothelial-adhesive phenotype. Crit Care Med 42:e200-10
Sambol, Justin; Deitch, Edwin A; Takimoto, Koichi et al. (2013) Cellular basis of burn-induced cardiac dysfunction and prevention by mesenteric lymph duct ligation. J Surg Res 183:678-85
Tiesi, Gregory; Reino, Diego; Mason, Leonard et al. (2013) Early trauma-hemorrhage-induced splenic and thymic apoptosis is gut-mediated and toll-like receptor 4-dependent. Shock 39:507-13
Fishman, Jordan E; Levy, Gal; Alli, Vamsi et al. (2013) Oxidative modification of the intestinal mucus layer is a critical but unrecognized component of trauma hemorrhagic shock-induced gut barrier failure. Am J Physiol Gastrointest Liver Physiol 304:G57-63
Levy, Gal; Fishman, Jordan E; Xu, Dazhong et al. (2013) Parasympathetic stimulation via the vagus nerve prevents systemic organ dysfunction by abrogating gut injury and lymph toxicity in trauma and hemorrhagic shock. Shock 39:39-44
Levy, Gal; Fishman, Jordan E; Xu, Da-zhong et al. (2012) Vagal nerve stimulation modulates gut injury and lung permeability in trauma-hemorrhagic shock. J Trauma Acute Care Surg 73:338-42; discussion 342
Qin, Xiaofa; Dong, Wei; Sharpe, Susan M et al. (2012) Role of lipase-generated free fatty acids in converting mesenteric lymph from a noncytotoxic to a cytotoxic fluid. Am J Physiol Gastrointest Liver Physiol 303:G969-78
Reino, Diego C; Palange, David; Feketeova, Elenora et al. (2012) Activation of toll-like receptor 4 is necessary for trauma hemorrhagic shock-induced gut injury and polymorphonuclear neutrophil priming. Shock 38:107-14

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