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; Watkins, Anthony C.; Barlos, Dimitrios; Xu, Da-Zhong; Lu, Quan; Abungu, Billy; Caputo, Frank; Feinman, Rena; Deitch, Edwin A.

doi:10.1097/sla.0b013e3180caa3af

Cited by 60 publications

(54 citation statements)

References 36 publications

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“…The results from our study show that melatonin preserved the intestinal epithelial and mucosal architecture and reduced inflammatory cell infiltration in the small intestine after HS. Among the organs damaged by HS, the lung is especially vulnerable to neutrophil accumulation, which can result in acute respiratory distress syndrome [18,19]. Treatment with melatonin significantly reduces lung injury induced by bleomycin in mice [20].…”

Section: Discussionmentioning

confidence: 99%

Melatonin Ameliorates Hemorrhagic Shock-Induced Organ Damage in Rats

Yang¹,

Subeq²,

Lee³

et al. 2011

Journal of Surgical Research

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Section: Discussionmentioning

confidence: 99%

Melatonin Ameliorates Hemorrhagic Shock-Induced Organ Damage in Rats

Yang¹,

Subeq²,

Lee³

et al. 2011

Journal of Surgical Research

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“…Separate aliquots of lymph were collected prior to the induction of T/HS, during the 90 minute shock (sham-shock) period as well as during the first 3 hours after the end of the shock or sham-shock period (post-shock lymph). This 3 hour post-shock lymph collection period was based on our previous studies documenting that the in vivo biologic activity of T/HS lymph is maximal during the first 3 hour post-shock period and is relatively rapidly lost thereafter (15). After the lymph was collected, it was processed, aliquoted and stored at −80°C until tested.…”

Section: Methodsmentioning

confidence: 99%

A Sphingosine-1 Phosphate Agonist (FTY720) Limits Trauma/Hemorrhagic Shock–Induced Multiple Organ Dysfunction Syndrome

Bonitz

Son

Chandler

et al. 2014

Shock

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BACKGROUND Trauma/hemorrhagic shock is one of the major consequences of battlefield injury as well as civilian trauma. FTY720 (sphingosine-1 phosphate agonist) has the capability to decrease the activity of the innate and adaptive immune systems and, at the same time, maintain endothelial cell barrier function and vascular homeostasis during stress. For this reason, we hypothesize that FTY720, as part of resuscitation therapy, would limit T/HS induced multiple organ dysfunction syndrome (MODS) in a rodent trauma-hemorrhagic shock (T/HS) model. METHODS Rats subjected to trauma/sham-shock (T/SS) or T/HS (30 mm Hg × 90 min), were administered FTY720 (1 mg/kg) post-T/HS during volume resuscitation. Lung injury (permeability to Evans Blue dye), PMN priming (respiratory burst activity), and RBC rigidity were measured. In addition, lymph duct cannulated rats were used to quantify the effect of FTY720 on gut injury (permeability and morphology) and the biologic activity of T/HS vs. T/SS lymph on PMN-RB and RBC deformability. RESULTS T/HS-induced increased lung permeability, PMN priming and RBC rigidity were all abrogated by FTY720. The systemic protective effect of FTY720 was only partially at the gut level, since FTY720 did not prevent T/HS-induced gut injury (morphology or permeability,) however, it did abrogate T/HS lymph-induced increased respiratory burst and RBC rigidity. CONCLUSION FTY720 limited T/HS-induced MODS (lung injury, red cell injury, and neutrophil priming) as well as T/HS lymph bioactivity, although it did not limit gut injury.

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“…Once in the circulation, these factors would come into contact with circulating RBC and other blood components. This hypothesis is based on our previous studies in this T/HS model indicating that factors released from the stressed gut and carried in the intestinal lymph to the systemic circulation initiate a systemic response resulting in acute lung injury, neutrophil activation, bone marrow dysfunction, and impaired RBC deformability (7,16). This hypothesis was first tested by determining whether ligation of the main lymphatic duct exiting the gut would prevent T/HS-induced increases in RBC adhesion to the endothelium and/or CD36 expression, since lymph duct ligation (LDL) prevents intestinal lymph from reaching the systemic circulation.…”

Section: T/hs-induced Rbc Changes Are Triggered By Factors Contained mentioning

confidence: 99%

Trauma-Hemorrhagic Shock Induces a CD36-Dependent RBC Endothelial-Adhesive Phenotype

Deitch

Condon

Feketeova

et al. 2014

Critical Care Medicine

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1) Trauma-hemorrhagic shock induces rapid RBC adhesion to endothelial cells in patients and animals. 2) Increased RBC CD36 expression characterizes the RBC-adhesive phenotype. 3) The RBC phenotypic and functional changes were induced by gut-derived humoral factors. These novel findings may explain the microvascular dysfunction occurring after trauma-hemorrhagic shock, sepsis, and other stress states.

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

Abstract: 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.

Cited by 60 publications

References 36 publications

Melatonin Ameliorates Hemorrhagic Shock-Induced Organ Damage in Rats

Melatonin Ameliorates Hemorrhagic Shock-Induced Organ Damage in Rats

A Sphingosine-1 Phosphate Agonist (FTY720) Limits Trauma/Hemorrhagic Shock–Induced Multiple Organ Dysfunction Syndrome

Trauma-Hemorrhagic Shock Induces a CD36-Dependent RBC Endothelial-Adhesive Phenotype

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