The goals of this Human Core are to provide human samples collected in a standardized manner to Project members of the Center and to begin translational studies in trauma patients based upon the data generated in our rat model. The central hypothesis of the Center Grant is that acute trauma and hemorrhagic shockinduced organ dysfunction (acute lung injury, bone marrow failure, neutrophil activation, red blood cell dysfunction 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 the subsequent production of toxic factors that are carried through the mesenteric lymph to the systemic circulation and that these gut-derived factors are responsible for post-traumatic organ dysfunction. A secondary hypothesis is that these early post-traumatic events are modulated by gender and sex hormones. This unified gut-lymph hypothesis has been developed through the use of animal models. Our rodent work has been invaluable in shaping our understanding of these events and has allowed us to generate relevant clinically-testable hypotheses and thus initiate translational human studies with the twin goals of validating the clinical relevance of our animal results and clarifying the mechanisms of acute posttraumatic organ failure in trauma patient populations. In addition, the potential role of gender and sex hormone status as modulators of organ dysfunction will also begin to be elucidated through these translational studies. To accomplish these goals we propose the following specific aims:
Aim 1 : To create a Human registry to match human samples with known demographic and outcome information, Aim 2: To standardized the collection and processing of human samples and serve as a repository for human samples and Aim 3: To begin prospective targeted translational studies based upon the data generated by the animal studies utilized in the Center Grant. Accomplishing these aims will add crucial human data to our understanding of the role of gut ischemia and gender on the development of early posttraumatic multiple organ failure.
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