The Journal of surgical research
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Acute traumatic injury is a complex disease that has remained a leading cause of death, which affects all ages in our society. Direct mechanical insult to tissues may result in physiological and immunologic disturbances brought about by blood loss, coagulopathy, as well as ischemia and reperfusion insults. This inappropriate response leads to an abnormal release of endogenous mediators of inflammation that synergistically contribute to the incidence of morbidity and mortality. ⋯ The enigmatic immunopathology of the human immunologic response after severe trauma, however, has never more been apparent and there grows a need for a clinically relevant animal model, which mimics this immune physiology to enhance the care of the most severely injured. This has necessitated preclinical studies in a more closely related model system, the nonhuman primate. In this review article, we summarize animal models of trauma that have provided insight into the clinical response and understanding of cellular mechanisms involved in the onset and progression of ischemia-reperfusion injury as well as describe future treatment options using immunomodulation-based strategies.
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Thrombelastography (TEG) is a viscoelastic hemostatic assay. We have observed that end-stage renal disease (ESRD) and trauma-induced coagulopathy (TIC) produce distinctive TEG tracings. We hypothesized that rigorously definable TEG patterns could discriminate between healthy controls and patients with ESRD and TIC. ⋯ ESRD and TIC demonstrate distinct TEG patterns. The coagulopathy of ESRD is typified by a prolonged enzymatic phase of clot formation, with normal-to-elevated final clot strength. Conversely, TIC is typified by prolonged clot formation and weakened clot strength. Our taxonomic categorization constitutes a rigorous system for the algorithmic interpretation of TEG based on cluster analysis. This will form the basis for clinical decision support software for viscoelastic hemostatic assays.
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Release of neutrophil extracellular traps (NETs) has been identified as an important aspect of innate immunity. We examined whether sepsis had any influence on ex vivo generation of NETs by neutrophils. ⋯ The ex vivo generation of NETs is downregulated in neutrophils isolated from patients with sepsis. However, it is unclear whether in vivo NET formation is also impaired during sepsis, so further investigation is necessary.
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Mortality in sepsis is most often attributed to the development of multiple organ failure. In sepsis, inflammation-mediated endothelial activation, defined as a proinflammatory and procoagulant state of the endothelial cells, has been associated with severity of disease. Thus, the objective of this study was to test the hypothesis that adenosine monophosphate-activated protein kinase (AMPK) activation limits inflammation and endothelium activation to protect against organ injury in sepsis. 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), which is an adenosine monophosphate analog, has been used to upregulate activity of AMPK. Compound C is a cell-permeable pyrrazolopyrimidine compound that inhibits AMPK activity. ⋯ In this model, activation of AMPK was protective, and AICAR minimized organ injury by decreasing inflammatory cytokines and endothelial activation. These data suggest that AMPK signaling influences sepsis or LPS-induced endothelial activation and organ injury.
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Postoperative cognitive dysfunction is increasingly recognized as an important clinical syndrome. Inhalation anesthetics are commonly used during surgery, and it has been proposed that inhalation anesthetics impair cognitive function. However, there are few clinical interventions and treatments available to prevent this disorder. GTS-21, a selective agonist of alpha 7 nicotinic acetylcholine receptor, has been indicated to exert neuroprotective effects in the experimental animal models of neurodegenerative diseases. Therefore, we hypothesized that pretreatment with GTS-21 attenuates isoflurane-induced cognitive decline in aged rats. ⋯ The study demonstrated that pretreatment with α7 nicotinic acetylcholine receptor agonist GTS-21 attenuates isoflurane-induced learning and memory impairment in aged rats.