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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We have recently demonstrated that injured patients in hemorrhagic shock shed syndecan 1 and that the early use of fresh frozen plasma (FFP) in these patients is correlated with improved clinical outcomes. As the lungs are frequently injured after trauma, we hypothesized that hemorrhagic shock-induced shedding of syndecan 1 exposes the underlying pulmonary vascular endothelium to injury resulting in inflammation and hyperpermeability and that these effects would be mitigated by FFP. In vitro, pulmonary endothelial permeability, endothelial monolayer flux, transendothelial electrical resistance, and leukocyte-endothelial binding were measured in pulmonary endothelial cells after incubation with equal volumes of FFP or lactated Ringer's (LR). ⋯ Fresh frozen plasma resuscitation, compared with LR resuscitation, abrogated these injurious effects. After hemorrhagic shock, FFP resuscitation inhibits endothelial cell hyperpermeability and inflammation and restores pulmonary syndecan 1 expression. Modulation of pulmonary syndecan 1 expression may mechanistically contribute to the beneficial effects FFP.
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Recent studies have demonstrated that volatile anesthetic postconditioning confers myocardial protection against ischemia-reperfusion injury through activation of the reperfusion injury salvage kinase (RISK) pathway. As RISK has been shown to be impaired by ventricular hypertrophy, we investigate whether anesthetic-induced cardiac protection was maintained in rat hearts with ventricular hypertrophy. Transverse aortic constriction operation was performed on male Sprague-Dawley rats to induce left ventricular (LV) hypertrophy, then sham-operated or hypertrophied rat hearts were subjected to 40 min of global ischemia and 2 h of reperfusion. ⋯ Both sevoflurane and ischemic postconditioning significantly improved LV hemodynamics, reduced infarct size, and increased the phosphorylation of Akt, ERK1/2, and their downstream target of GSK3β in the sham-operated rat hearts. In contrast, neither sevoflurane nor ischemic postconditioning improved LV hemodynamic, reduced infarct size, and increased the phosphorylated Akt, ERK1/2, and GSK3β in hypertrophied myocardium. All the results above indicate that ventricular hypertrophy abrogated sevoflurane-induced cardioprotection against ischemia-reperfusion injury by alteration of RISK/GSK3β signals.
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It has been shown that the innate immune system mediates acute lung inflammation triggered by intestinal trauma. Sexual dimorphism modulates the profile of TH1 and TH2 lymphocytes, and accordingly sex hormones may modulate acute lung inflammation by intestinal ischemia/reperfusion (I/R). Studies indicate that female rats are relatively resistant to organ injury caused by hemorrhagic shock and that the gut of female is more resistant than that of the male to deleterious effects of ischemic injury. At the present study, we investigated the effect of estradiol (E(2)) on the lung inflammation after intestinal I/R and its interaction with the nitric oxide (NO) pathway. ⋯ Estradiol treatment is able to reduce lung inflammation due to intestinal I/R, but with the concomitant blockade of NOS activity, this effect is abolished. Nitric oxide probably reduces the vascular deleterious effects of intestinal I/R, and E(2) pretreatment reduces lung inflammation after intestinal I/R and exerts these effects by modulating eNOS protein expression in the lungs.
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Tissue injury, such as burns or inflammation, can lead to the generation of oxidized lipids capable of regulating hemodynamic, pulmonary, immune, and neuronal responses. However, it is not known whether traumatic injury leads to a selective upregulation of transcripts encoding oxidative enzymes capable of generating these mediators. Here, we analyzed microarrays taken from circulating leukocytes of 187 trauma subjects compared with 97 control volunteers for changes in the expression of 105 oxidative enzymes and related receptors. ⋯ In addition, the level of expression of CYP2A7, CYP2B7P1, CYP2C19, CYP2E1, CYP4A11, CYP4F3, CYP8B1, CYP19A1, CYP20A1, CYP51A1, HMOX2, NCF1, NCF2, and NOX1 and the receptors PTGER2 and ESR2 were correlated with clinical trauma indices such as APACHE II, Max Denver Scale, and the Injury Severity Score. Demonstration of a selective alteration in expression of transcripts encoding oxidative enzymes reveals a complex molecular response to major blunt trauma in circulating leukocytes. Furthermore, the association between changes in gene expression and clinical trauma scores suggests an important role in integrating pathophysiologic responses to blunt force trauma.