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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The development of sepsis and multiple organ failure are important determinants of the outcome in critically ill patients. Hepatosplanchnic hypoperfusion and resulting intestinal and hepatic cell damage have been implicated as central events in the development of sepsis and multiple organ failure. Our aim was to study (1) the relation between intramucosal perfusion and intestinal and hepatic cell damage in an early phase of sepsis and (2) the correlation of these parameters with mortality. ⋯ At intensive care unit admission, nonsurvivors had significantly higher I-FABP and L-FABP values than survivors (I-FABP: 325 vs. 76 pg/mL, P < 0.04; L-FABP: 104 vs. 31 ng/mL, P < 0.04). Patients with abdominal sepsis was especially responsible for high-admission I-FABP and L-FABP levels in nonsurvivors (I-FABP: 405 vs. 85 pg/mL, P < 0.04; L-FABP: 121 vs. 59 ng/mL, P < 0.04). This study shows that splanchnic hypoperfusion correlates with intestinal mucosal damage, and that elevated plasma levels of I-FABP and L-FABP are associated with a poor outcome in critically ill patients with abdominal sepsis.
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Microcirculatory dysfunction contributes significantly to tissue hypoxia and multiple organ failure in sepsis. Ischemia of the gut and intestinal hypoxia are especially relevant for the evolution of sepsis because the mucosal barrier function may be impaired, leading to translocation of bacteria and toxins. Because sympathetic blockade enhances intestinal perfusion under physiologic conditions, we hypothesized that thoracic epidural anesthesia (TEA) may attenuate microcirculatory perturbations during sepsis. ⋯ Notably, TEA did not impair systemic hemodynamic variables beyond the changes caused by sepsis itself. Therefore, sympathetic blockade may represent a therapeutic option to treat impaired microcirculation in the gut mucosa resulting from sepsis. Additional studies are warranted to assess the microcirculatory effects of sympathetic blockade on other splanchnic organs in systemic inflammation.
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Severe sepsis and septic shock are major causes of morbidity and mortality among children in pediatric intensive care units (PICUs) worldwide. Activated protein C (PC) is a critical endogenous regulator of coagulation and inflammation in patients with sepsis. However, the role of PC in pediatric sepsis is still obscure. ⋯ Also, there was no correlation between plasma PC activity and D-dimer levels (r = -0.07; P = 0.6). Importantly, the odds of dying were significantly higher in patients whose level of PC activity was less than 25% (odds ratio = 5.6; P = 0.02). Pediatric patients with septic shock demonstrate very low levels of PC activity, and this may be associated with an increased risk of death.
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Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a nuclear receptor that regulates diverse biological functions including inflammation. The PPARgamma ligands have been reported to exert cardioprotective effects and attenuate myocardial reperfusion injury. Here, we examined the molecular mechanisms of their anti-inflammatory effects. ⋯ The cardioprotection afforded by ciglitazone was attenuated by the PPAR-gamma antagonist GW-9662. In contrast, GW-9662 did not affect the beneficial effects afforded by 15d-PGJ2. Thus, our data suggest that treatment with these chemically unrelated PPAR-gamma ligands results in diverse anti-inflammatory mechanisms.
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Neutrophil infiltration is a crucial step in the development of organ dysfunction after trauma. We have previously shown that keratinocyte-derived chemokine (KC), a chemoattractant for neutrophils, is up-regulated after trauma-hemorrhage. To determine the role of KC after trauma-hemorrhage, the effect of a KC-neutralizing antibody on the posttraumatic inflammatory response was examined. ⋯ Administration of the anti-KC antibody before trauma-hemorrhage prevented increases in KC plasma levels, which was accompanied by amelioration of neutrophil infiltration and edema formation in lung and liver after trauma-hemorrhage. No effect on other cytokines in plasma or Kupffer cell release was observed. These results suggest that KC plays a pivotal role in neutrophil infiltration and organ damage after trauma-hemorrhage and resuscitation.