Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Mesenteric ischemia/reperfusion (IR) damages the gastrointestinal epithelia and impairs gut function. Ischemic preconditioning (IPC) has been shown to protect organs against IR injury. We hypothesized that IPC protects the gut from IR injury. ⋯ Our results suggest that early and late IPC improves intestinal dysfunction, decreases inflammation, and provides mucosal protection in the intestine after IR. Our results show that IR-induced gut dysfunction can be improved by IPC. Both phases of IPC can potentially be useful in the clinical setting of surgical patient care.
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Decreased lymphocyte proliferation, lymphopenia, immunodepression, and opportunistic infections are common after major trauma. Early alimentation in these patients corrects lymphopenia, enhances immunity, and reduces the incidence of infections, but the underlying mechanisms are poorly understood. Tryptophan is essential for the production and function of rapidly proliferating cells such as lymphocytes. ⋯ Although patients with poor outcomes (i.e., BS, ARDS, MOF, and death) had significantly lower tryptophan levels and greater lymphopenia on several days after injury, the sample size was too small to draw any definitive conclusions. These data indicate that decreased plasma tryptophan levels and lymphopenia typically occur after major trauma. A concomitant increase in kynurenine suggests that the observed tryptophan deficiency is caused, in part, by IDO-mediated tryptophan degradation.
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Comparative Study
Ringer's ethyl pyruvate in hemorrhagic shock and resuscitation does not improve early hemodynamics or tissue energetics.
Reactive oxygen species (ROS) have been implicated in the pathogenesis of hemorrhagic shock. Ethyl pyruvate, a derivative of pyruvate and a proposed oxygen radical scavenger, is attractive as a possible resuscitation fluid. We investigated whether resuscitation with lactated Ringer's (LR) containing ethyl pyruvate (REP) had any hemodynamic or tissue energetic benefits compared with LR alone for hemorrhagic shock. ⋯ The clinical significance of these findings are unclear. There is no short-term hemodynamic or tissue energetic advantage to using REP as a resuscitation fluid when compared with LR. Long-term outcome studies are needed to further evaluate any potential benefits of use of REP in hemorrhagic shock.
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Thermal injury induces immune dysfunction and alters numerous physiological parameters. Studies have proposed that genetics influence the outcome after traumatic injury and/or sepsis, however, the contribution of genetics to the immune-inflammatory response postburn has not been investigated. In this study, mice of three distinct genetic backgrounds (C57BL/6NCrlBR, BALB/cAnNCrlBR, and 129S6/SvEvTac) were subjected to thermal injury or a sham procedure, and 3 days later, blood and splenic immune cells (splenocytes and macrophages) were isolated for analysis. ⋯ However, significant postburn weight loss was observed in the BALB/cNCrlBR and 129S6/SvEvTac strains, but not in the C57BL/6NCrlBR strain. In summary, these findings support the concept that the immune-inflammatory response postburn is influenced by genetic make-up. Further elucidation of the influence of genetics under such conditions is likely to contribute to the improvement in existing, and development of new, therapeutic regimes for burn patients.
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Numerous clinical trials using anti-inflammatory agents for patients with acute respiratory distress syndrome (ARDS) have failed despite efficacy in acute animal models. This underscores the necessity of developing a clinically relevant model of ARDS. Initially, we attempted to induce lung injury in pigs by fecal peritonitis only. ⋯ The addition of a second "hit" (SMA occlusion, I/R) to a FC sepsis model resulted in severe lung injury that developed within a 3-day period. To our knowledge, this is the first large animal experiment that definitively and consistently causes insidious onset ARDS in pigs. By closely paralleling the clinical development of pulmonary injury, this model should prove invaluable in the study of human ARDS.