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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Ventilation of an unprotected airway may result in stomach inflation. The purpose of this study was to evaluate the effect of clinically realistic stomach inflation on cardiopulmonary function during hemorrhagic shock in a porcine model. ⋯ During hemorrhagic shock stomach inflation caused an abdominal compartment syndrome and thereby impaired cardiopulmonary function and aerobic metabolism, and increased mortality. Subsequent stomach evacuation partly reversed adverse stomach-inflation triggered effects.
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Intestinal barrier dysfunction is thought to contribute to the development of multiple organ dysfunction syndrome in sepsis. Although there are similarities in clinical course following sepsis, there are significant differences in the host response depending on the initiating organism and time course of the disease, and pathways of gut injury vary widely in different preclinical models of sepsis. The purpose of this study was to determine whether the timecourse and mechanisms of intestinal barrier dysfunction are similar in disparate mouse models of sepsis with similar mortalities. ⋯ Mice with pneumonia had an increase in intestinal permeability similar in timecourse and magnitude to that seen in CLP. Similar changes in tight junction proteins were seen in both models of sepsis although mice subjected to pneumonia also had a marked decrease in ZO-1 not seen in CLP. These results indicate that two disparate, clinically relevant models of sepsis induce a significant increase in intestinal permeability mediated through a common pathway involving alterations in claudin 2, claudin 5, JAM-A, and occludin although model-specific differences in ZO-1 were also identified.
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It has been shown that microcirculation is hypersensitized to endothelin1 (ET-1) following endotoxin (lipopolysaccharide [LPS]) treatment leading to an increased vasopressor response. This may be related in part to decreased activation of endothelial nitric oxide synthase (eNOS) by ET-1. eNOS can also be uncoupled to produce superoxide (O2). This aberrant eNOS activity could further contribute to the hyperconstriction and injury caused by ET-1 following LPS. ⋯ DCF experiments confirmed intracellular ROS while Mitosox suggested a non-mitochondrial source. ET-1 treatment following a chronic LPS stress significantly monomerized the eNOS homodimer that was inhibited by sepiapterin loading. The two concomitant phenomena of decreased NO production and increased ROS formation seem to be multifactorial in nature with ROS production dependent upon pterin availability.
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Decreased Monocyte Hla-Dr Expression in Patients After Non-Shockable Out-of-Hospital Cardiac Arrest.
Out-of-hospital cardiac arrest (OHCA) constitutes a major health care problem with the development in immediate survivors of a post-cardiac arrest syndrome including systemic inflammatory response as observed in sepsis. As a decreased monocyte HLA-DR expression (mHLA-DR) has been repeatedly described in septic patients in association with an increased risk of death and nosocomial infections, we tested whether this immune alteration could also be observed after OHCA. Fifty-five non-shockable OHCA patients sampled at Day 0 (D0: within 4 h after OHCA), D1 (the next day), and D3: (after 2 additional days) were included. ⋯ In conclusion, this preliminary pilot study describes the occurrence of OHCA-induced immune alterations as illustrated by a decreased mHLA-DR and CD4+ lymphopenia. Furthermore, we show for the first time the differential overtime evolution in mHLA-DR between survivors and non-survivors without association with usual prognostic markers and multiple organ failure. These initial results should now be confirmed in a larger cohort of OHCA patients.
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Intestinal ischemia can quickly escalate to bowel necrosis and perforation. Transplantation of stem cells presents a novel treatment modality for this problem. We hypothesized that: human adipose-derived stromal cells (hASCs) would increase survival and mesenteric perfusion to a greater degree compared with differentiated cellular controls following ischemic intestinal injury, and improved outcomes with hASC therapy would be associated with preservation of intestinal histological and tight junction architecture, and lower levels of systemic inflammation following intestinal injury. ⋯ Human adipose-derived stromal cells improved survival and mesenteric perfusion and attenuated the mucosal damage associated with intestinal I/R injury. hASCs should be considered as a plausible cell source for novel cellular treatment plans following intestinal ischemia.