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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Sivelestat sodium hydrate is a selective inhibitor of neutrophil elastase, which is effective in acute lung injury associated with systemic inflammatory response syndrome. However, the effectiveness of sivelestat in sepsis has not been fully examined. In the present study, the effect of sivelestat on severe sepsis in a rat cecal ligation and puncture (CLP) model was investigated. ⋯ The lungs from sivelestat-treated rats exhibited less severe pathological changes and decreased the numbers of HMGB1, IL-8, and CD68-positive cells (P < 0.001). Sivelestat significantly improved survival rate of rats with clinically relevant sepsis, possibly by attenuating sepsis-induced systemic inflammatory response and lung injury. This may explain the implicated health benefits of sivelestat in reducing morbidity and mortality from sepsis.
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Although the use of supplemental oxygen to resuscitate asphyxiated neonates remains controversial, the effects of hypoxia and reoxygenation (room air versus pure oxygen) on the hypothalamo-pituitary-adrenal axis are unknown. We aimed to evaluate the effect of hypoxia and reoxygenation with either 21% or 100% oxygen on plasma cortisol before and after an adrenocorticotrophin (ACTH) challenge in newborn piglets. Thirty-five piglets (aged 1-3 days, weighing 1.5-2.4 kg) were instrumented to measure heart rate, MAP, and cardiac output. ⋯ The response to ACTH was delayed in H-R groups, with the maximum increase at 120 min post-ACTH administration (versus 30-60 min post-ACTH for sham-operated piglets). Plasma cortisol levels increased significantly post-ACTH administration in 21% H-R and sham-operated piglets (115% +/-50% and 126% +/- 25% at 120 min, respectively, P < 0.05 vs. pre-ACTH baselines) but not in 100% H-R piglets (51% +/-14%), which had a lower expression of steroidogenic factor 1 than the other groups. Although the clinical significance of high cortisol levels and cortisol response to ACTH in H-R newborn piglets is uncertain, a preserved cortisol response may support using room air in neonatal resuscitation.
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Pharmacological protection from myocardial reperfusion injury, despite plenty of approaches, has still not been realized in humans. We studied the putative infarct size (IS)-sparing capacity of poly(ADP-ribose)polymerase inhibitor, INO-1001, and focused on cardiac functional recovery during reperfusion. Male farm-bred Landrace pigs were subjected to 1-h left anterior descending coronary artery occlusion followed by 3 h of reperfusion (control). ⋯ Ischemic preconditioning reduced myocardial damage reflected by a smaller IS and lower plasma markers of myocardial injury. INO-1001 did not reduce IS but significantly improved functional recovery (increased stroke volume, cardiac index, and mixed venous oxygen saturation) during reperfusion compared with vehicle-treated control and ischemic preconditioning. Although we could not confirm the IS-sparing capacities of poly(ADP-ribose)polymerase inhibitor, INO-1001, the drug holds the potential of hemodynamic improvement during reperfusion.
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Hypertonic sodium pyruvate (HSP), as well as ethyl pyruvate solutions, has been proposed as resuscitative fluids in the treatment of hemorrhagic shock (HS) because of their anti-inflammatory and antioxidant properties. The effectiveness of one pyruvate preparation over the other in the treatment of HS has not been evaluated. The authors aimed to compare two pyruvate solutions for resuscitation and their mechanisms of action in rats during HS. ⋯ In comparison with Ringer's ethyl pyruvate, HSP administration after hemorrhage reduced liver injury, which was associated with increased levels of serum and tissue inflammatory cytokines, inflammatory mediators such as NOS and cyclooxygenase 2, lipid peroxidation, and higher hepatocellular adenosine triphosphate. Cellular apoptotic events related to the activation of caspase-3 and poly(ADP-ribose)polymerase cleavage were also decreased by sodium pyruvate. Resuscitation with small-volume HSP offers significant protection against inflammatory and oxidative stress and in preventing liver injury compared with large-volume Ringer's ethyl pyruvate.