Hemorrhagic shock results in a disruption to systemic homeostasis and can eventually lead to multipleorgan dysfunction syndrome (MODS), which is the cause of 50-80% of deaths in the surgical intensive careunits. Because the development of MODS is poorly understood, current treatment is mainly supportive. It istherefore critical to identify key events and factors that lead to the progression of MODS to identify critical pointsof intervention.The long-range goal of this research is to identify the factors released in response to shock that promotesystemic effects that contribute to the development of (MODS). This proposal focuses on the isolation andidentification of factor(s) that are present in mesenteric (intestinal) lymph and plasma following traumahemorrhagicshock (T/HS) that suppress bone marrow (BM) cell colony formation, activate neutrophils, andincrease red blood cell rigidity. Our central hypothesis is that factors responsible for the BM, PMN and RBCdysfunctions are produced in the gut after T/HS and introduced to the general circulation via the mesentericlymphatics. This is based on in vitro and in vivo data showing that suppression of BM cell colony formation,PMN activation, and RBC rigidification is observed in rats subjected to T/HS but not T/SS and is abolished bymesenteric lymph-duct ligation. Consequently, the primary goal of this project is to identify the biologically activefactors in the lymph and plasma by using a continuum of T/HS lymph/plasma separations where each subseparationis tailored to the characteristics (e.g., protein, lipid, size, charge) of the components present in thesub-fraction that retains toxicity. Identification of these factors will make it possible to study their production,regulation, entry into the lymph and effects on different tissues. This research could help develop newtherapeutic modalities to prevent formation of or limit the damage produced by these factors in order to preventMODS.
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