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 previously demonstrated survival benefit to induced hypothermia in a porcine model of controlled hemorrhagic shock simulating an associated delay to definitive care. In the current study, we wished to evaluate the effects of environmental hypothermia in a porcine model of hemorrhagic shock with the addition of polytrauma. Sixteen pigs were randomized to normothermic (39°C, n = 7) or hypothermic (34°C, n = 9) groups. ⋯ Markers of organ injury were elevated in the hypothermia group at 24 h after injury but were identical between groups at the end of the experimental protocol (48 h after injury). There were no noted differences in neurologic function between the two groups. Environmental hypothermia in a model of polytrauma and hemorrhagic shock was not associated with worse outcomes.
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The objectives of this study were to determine whether type 2 diabetic mice would exhibit a more severe renal impact of hemorrhagic shock (HS) based on a recently described model of acute kidney injury and to determine the impact of HS on renal responses to hypoxia. We induced HS or sham procedure in type 2 diabetic and obese db/db mice. Creatininemia, glomerular filtration rate, urine output, histologic injury score, and kidney inductible molecule 1 mRNA were used to investigate the renal impact of HS. ⋯ Furthermore, endothelial nitric oxide synthase was highly overexpressed in diabetic shocked mice when compared with nondiabetic shocked mice. Renal impact of HS in type 2 diabetic mice is more intense than in nondiabetic ones. Preexisting hypoxia during diabetes could result in a renal preconditioning that modifies endothelial and tissular responses to acute kidney injury.
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The present study attempts to evaluate the role of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling in intestinal ischemia/reperfusion (I/R)-induced intestinal injury and whether immediate ischemic postconditioning ameliorates intestinal injury via attenuation of intestinal mucosal apoptosis subsequent to inhibiting JAK/STAT signaling activation. Anesthetized adult male Sprague-Dawley rats were subjected to superior mesenteric artery occlusion consisting of 60 min of ischemia and 2 h of reperfusion; sham laparotomy served as controls. Animals received either subcutaneous administration of JAK2 inhibitor (AG490, 8 mg/kg) or STAT inhibitor (rapamycin, 0.4 mg/kg) 30 min before ischemia. ⋯ Both ischemic postconditioning and pretreatment with AG490 or rapamycin significantly attenuated all the above changes. These results indicate that JAK/STAT pathway activation plays a critical role in I/R-induced intestinal injury, which is associated with increased oxidative stress, neutrophil accumulation, intestinal mucosal apoptosis, and microcirculation disturbance. Ischemic postconditioning mediates attenuation of intestinal I/R injury, and cell apoptosis may be attributable to the JAK/STAT signaling inhibition.
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The aim of this study was to evaluate microdialysis of the rectus abdominis muscle (RAM) for early detection of subclinical organ dysfunction in a porcine model of critical intra-abdominal hypertension (IAH). Microdialysis catheters for analyses of lactate, pyruvate, and glycerol levels were placed in cervical muscles (control), gastric and jejunal wall, liver, kidney, and RAM of 30 anesthetized mechanically ventilated pigs. Catheters for venous lactate and interleukin 6 samples were placed in the jugular, portal, and femoral vein. ⋯ Venous lactate was increased compared with baseline and shams in the femoral vein of the IAH30 group only. Intra-abdominal pressure-induced ischemic metabolic changes are detected more rapidly and pronounced by microdialysis of the RAM when compared with intra-abdominal organs. Thus, the RAM represents an important and easily accessible site for the early detection of subclinical organ dysfunction during critical IAH.
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Aspiration of hydrochloric acid (HCl)-containing gastric juice leads to acute lung injury (ALI) and hypoxemic respiratory failure due to an exuberant inflammatory response associated with pulmonary edema from increased vascular and epithelial permeability. The aim of this study was to determine the role and signaling mechanisms of tumor necrosis factor α (TNF-α) in experimental ALI from HCl aspiration using a combination of genetic animal models and pharmacologic inhibition strategies. To this end, HCl was instilled intratracheally to mice, followed by respiratory system elastance measurement, bronchoalveolar lavage, and lung tissue harvesting 24 h after injection. ⋯ Hydrochloric acid induced a 6-fold increase in apoptotic, caspase 3-positive cells in lung sections from wild-type mice, which was abrogated in mice lacking TNF-α receptor I. In immunoblotting and immunohistochemistry studies, HCl stimulated signaling via p44/42 and c-Jun N-terminal kinase, which was blocked in TNF-α receptor I knockout mice. In conclusion, ALI induced by HCl requires TNF-α receptor I function and associates with activation of downstream proinflammatory signaling pathways p44/42 and c-Jun N-terminal kinase.