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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Ischemic conditioning induces a series of cellular modifications that may prevent injury from further hypoxic episodes, but there are few data in sepsis. In this randomized controlled study, we evaluated the effects of ischemic conditioning on the microcirculation, organ function, and survival time in an ovine model of septic shock. Sepsis was induced in 14 anesthetized, mechanically ventilated adult sheep by injecting autologous feces into the abdominal cavity. ⋯ Microcirculatory variables were better preserved in the conditioned than in the control group from 6 h after randomization: the median proportion of perfused vessels was 91 (89-93)% versus 89 (86-90)% (P = 0.024) and there was less heterogeneity. Oliguria, hypotension, and death occurred later in the conditioned than in the control group. In this sepsis model, remote ischemic pre- and post-conditioning therefore decreased organ dysfunction, preserved the microcirculation, and prolonged survival.
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In the United States trauma is the leading cause of mortality among those under the age of 45, claiming approximately 192,000 lives each year. Significant personal disability, lost productivity, and long-term healthcare needs are common and contribute 580 billion dollars in economic impact each year. ⋯ Constituents of the glycocalyx have been used as biomarkers of injury severity and have the potential to be target(s) for therapeutic interventions aimed at immune modulation. In this review, we provide a contemporary understanding of the physiologic structure and function of the glycocalyx and its role in traumatic injury with a particular emphasis on lung injury.
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Mitochondrial function is thought to play a role in sepsis-induced multiple organ failure. However, the temporal and organ-specific alterations in mitochondrial function have yet to be fully elucidated. Many studies show reduced phosphorylating capacity, while others have indicated that mitochondrial respiration is enhanced. ⋯ The present study suggests a diverse and tissue-specific mitochondrial respiratory response to sepsis. The brain displayed an early impaired mitochondrial respiratory efficiency. In the liver the primary finding was a substantial activation of the maximal phosphorylating capacity.
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Dysregulation of the inflammatory response against infection contributes to mortality in sepsis. Inflammation provides critical host defense, but it can cause tissue damage, multiple organ failure, and death. Because the nuclear transcription factor peroxisome proliferator-activated receptor γ (PPARγ) exhibits therapeutic potential, we characterized the role of PPARγ in sepsis. ⋯ Polymorphonuclear leukocytes (PMN) incubated with LPS or Escherichia coli and rosiglitazone increased peritoneal neutrophil extracellular trap (NET)-mediated bacterial killing, an effect reversed by the PPARγ antagonist (GW 9662) treatment. Rosiglitazone also enhanced the release of histones by PMN, a surrogate marker of NET formation, effect abolished by GW 9662. Rosiglitazone modulated the inflammatory response and increased bacterial clearance through PPARγ activation and NET formation, combining immunomodulatory and host-dependent anti-bacterial effects and, therefore, warrants further study as a potential therapeutic agent in sepsis.
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Intestinal ischemia-reperfusion (I/R) occurs in various clinical situations and causes local and remote organ injury, especially in the lungs, leading to significant morbidity and mortality. The maintenance of mitochondrial biogenesis is essential for cell survival and is regulated in part by sirtuin 1 (SIRT1), an energy-sensing enzyme. We hypothesized that SIRT1 activation with SRT1720 would reduce local and remote organ injury after intestinal I/R. ⋯ Lung injury, as measured by histological architecture and myeloperoxidase activity, and lung apoptosis were also improved after the SRT1720 treatment. SRT1720 preserved mitochondrial biogenesis and mass, leading to inhibition of inflammation and oxidative stress, thereby protecting against intestinal I/R-induced injury. Thus, the SIRT1-mediated pathway is a promising target for the treatment of intestinal I/R injury.