THE ROLE OF GENDER ON GUT AND GUT-INDUCED LUNG INJURY

Univ Of Med/Dent Of Nj-Nj Medical School, Newark NJ

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Abstract

Trauma is the leading cause of death in people under the age of 40 and MODS is the leading cause of[unreadable] death in trauma patients surviving the initial 72 hour injury period. In fact, MODS is the leading cause of[unreadable] death in ICUs today. Although still somewhat controversial, there is recent evidence that the response to[unreadable] injury and sepsis may differ between males and females, with females being more resistant to the adverse[unreadable] consequences of T/HS than males. Thus, understanding the mechanisms by which trauma-hemorrhagic[unreadable] shock (T/HS) leads to MODS, as well as the role of sex hormones in modulating this response, is of major[unreadable] health importance. This Project will follow up on our results indicating that male, but not female, rats[unreadable] develop T/HS-induced lung injury and endothelial cell activation/injury by testing the following two[unreadable] hypotheses. The first hypothesis is that T/HS-induced lung injury and increased endothelial cell[unreadable] permeability is secondary to gut injury and is mediated by factors exiting the gut via the mesenteric[unreadable] lymphatics but not the portal vein. The second hypothesis is that sex hormones modulate gut and hence[unreadable] distant organ injury in a model of T/HS. To test these hypotheses, we will first investigate the potential[unreadable] mechanisms of why the female gut is more resistant than the male gut to T/HS-induced gut injury and does[unreadable] not produce toxic lymph. Next, we will investigate the role of sex hormones as[unreadable] modulators of resistance and susceptibility to T/HS-induced gut and lung injury. We will[unreadable] investigate the hypothesis that estrogen protects against T/HS-induced gut injury by limiting iNOS[unreadable] induction. Lastly, we will investigate the mechanisms by which T/HS mesenteric lymph, alone or in[unreadable] combination with PMNs, increases vascular permeability and how this is influenced by gonadal hormonal[unreadable] manipulation.