ISOLATION OF TOXIC FACTORS IN LYMPH AND PLASMA AFTER SHOCK

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

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Abstract

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