The goals of this Human Core are to provide human samples collected in a standardized manner to Projectmembers of the Center and to begin translational studies in trauma patients based upon the data generatedin our rat model. The central hypothesis of the Center Grant is that acute trauma and hemorrhagic shockinducedorgan dysfunction (acute lung injury, bone marrow failure, neutrophil activation, red blood celldysfunction and endothelial cell activation) is to a large extent secondary to the development of gut injury.This hypothesis is based on the concept that splanchnic ischemia leads to gut injury/inflammation and thesubsequent production of toxic factors that are carried through the mesenteric lymph to the systemiccirculation and that these gut-derived factors are responsible for post-traumatic organ dysfunction. Asecondary hypothesis is that these early post-traumatic events are modulated by gender and sexhormones. This unified gut-lymph hypothesis has been developed through the use of animal models. Ourrodent work has been invaluable in shaping our understanding of these events and has allowed us togenerate relevant clinically-testable hypotheses and thus initiate translational human studies with the twingoals of validating the clinical relevance of our animal results and clarifying the mechanisms of acute posttraumaticorgan failure in trauma patient populations. In addition, the potential role of gender and sexhormone status as modulators of organ dysfunction will also begin to be elucidated through thesetranslational studies. To accomplish these goals we propose the following specific aims:
Aim 1 : To create aHuman registry to match human samples with known demographic and outcome information, Aim 2: Tostandardized the collection and processing of human samples and serve as a repository for human samplesand Aim 3: To begin prospective targeted translational studies based upon the data generated by the animalstudies utilized in the Center Grant. Accomplishing these aims will add crucial human data to ourunderstanding of the role of gut ischemia and gender on the development of early posttraumatic multipleorgan failure.
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