Experiments described in this proposal are based on the hypothesis that major traumatic injury and related stressors may induce gut dysfunction that contributes to multisystem organ failure (MOF). This Trauma Research Center brings together a multidisciplinary team of basic and clinical scientists who have joined their respective areas of expertise and knowledge with the goal of determining, in relevant animal models, factors in gut dysfunction following traumatic stress. The major objectives to achieve this goal are: 1) To determine the pathological mechanisms that contribute to gut stasis following traumatic stress and develop strategies to restore normal gut propulsion; 2) To identify at the cellular level the perturbations within the gut mucosa that allow the transmigration of enteric bacteria and endotoxin following traumatic stress and develop ways to prevent this process; 3) to characterize the role of eicosanoids, oxygen-derived free radicals, and nitric oxide in regulating the normal and stressed splanchnic circulation and organ function, and 4) To determine if immunosuppression or anergy in the intestine, resulting from radiation-induced injury to the GI tract, can be prevented or alleviated through nutritional means. To achieve these objectives, rats and opossums will be exposed to major clinical elements of traumatic stress (hemorrhage with reinfusion, oral food deprivation, total parenteral nutrition, morphine analgesia, inflammation, infection, endotoxemia, and irradiation), with appropriate controls and safeguards for their welfare. Intestinal and biliary motility, bacterial translocation, splanchnic circulation and eicosanoid biosynthesis, and gut wall immunity will be studied with appropriate methodologies. The role of inflammatory mediators (cytokines, oxygen-derived free radicals) and nitric oxide will be examined at the cellular and molecular levels using intact animals and in vitro, tissue preparations. The results of these studies should provide a clear answer as to whether gut wall function is altered under these experimental conditions of traumatic stress. If such is the case, then early restoration of gut function may emerge as a strategy for the prevention of this highly lethal syndrome.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center (P50)
Project #
5P50GM038529-08
Application #
2179380
Study Section
Special Emphasis Panel (SRC (05))
Project Start
1988-05-01
Project End
1998-06-30
Budget Start
1995-07-01
Budget End
1996-06-30
Support Year
8
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Surgery
Type
Schools of Medicine
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225
Galvagno Jr, Samuel M; Fox, Erin E; Appana, Savitri N et al. (2017) Outcomes after concomitant traumatic brain injury and hemorrhagic shock: A secondary analysis from the Pragmatic, Randomized Optimal Platelets and Plasma Ratios trial. J Trauma Acute Care Surg 83:668-674
Moore, Frederick A; Moore, Ernest E; Billiar, Timothy R et al. (2017) The role of NIGMS P50 sponsored team science in our understanding of multiple organ failure. J Trauma Acute Care Surg 83:520-531
Galvagno Jr, Samuel M; Fox, Erin E; Appana, Savitri N et al. (2017) Outcomes Following Concomitant Traumatic Brain Injury and Hemorrhagic Shock: A Secondary Analysis from the PROPPR Trial. J Trauma Acute Care Surg :
Deng, Xiyun; Cao, Yanna; Huby, Maria P et al. (2016) Adiponectin in Fresh Frozen Plasma Contributes to Restoration of Vascular Barrier Function After Hemorrhagic Shock. Shock 45:50-54
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Hobson, Charles; Singhania, Girish; Bihorac, Azra (2015) Acute Kidney Injury in the Surgical Patient. Crit Care Clin 31:705-23
Adams, Sasha D; Cotton, Bryan A; Wade, Charles E et al. (2013) Do not resuscitate status, not age, affects outcomes after injury: an evaluation of 15,227 consecutive trauma patients. J Trauma Acute Care Surg 74:1327-30
Radwan, Zayde A; Bai, Yu; Matijevic, Nena et al. (2013) An emergency department thawed plasma protocol for severely injured patients. JAMA Surg 148:170-5
Dial, Elizabeth J; Tran, Duy M; Hyman, Ari et al. (2013) Endotoxin-induced changes in phospholipid dynamics of the stomach. J Surg Res 180:140-6

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