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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Na(+)/H(+) exchange (NHE) is involved in the myocardial injury that occurs during ischemia and reperfusion. The goal of the present study was to investigate the role of NHE in hypovolemic circulatory shock by using a potent NHE-1 selective inhibitor BIIB513. Acute rapid hemorrhage was induced in 14 pigs by bleeding (30 mL/kg over 30 min). ⋯ NHE blockade also attenuated the metabolic acidosis, improved tissue oxygen delivery, and improved cardiac function from resuscitation. The circulating levels of creatine phosphokinase (CPK) and cardiac troponin-I were significantly lower in the BIIB513 treatment group. These results suggest that NHE activation plays an important pathophysiological role in hypovolemic circulatory shock, and NHE-1 blockade is a powerful intervention to improve cardiovascular outcomes of resuscitation from prolonged hypovolemic circulatory shock.
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These studies evaluated the effects treatment with glucan phosphate, a soluble polysaccharide immunomodulator, on the inflammatory response induced by burn injury and on resistance to Pseudomonas aeruginosa burn wound infection. Mice were exposed to 35% total body surface area burns and were resuscitated with lactated Ringer's (LR) solution alone or LR supplemented with glucan phosphate (40 mg/kg). Glucan phosphate treatment attenuated burn-induced expression of interleukin (IL)-1beta, IL-6, and IL-10 mRNAs in spleen, lung, and heart. ⋯ Glucan phosphate treatment significantly improved survival in mice exposed to P. aeruginosa burn wound infection. The improved survival correlated with lower bacterial burden in the burn wound, attenuated production of proinflammatory cytokines, and enhanced production of Th1 cytokines. These studies show that glucan phosphate treatment attenuates burn-induced inflammation and increases resistance to P. aeruginosa burn wound infection in an experimental model of burn injury.
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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.