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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Comparative Study
The impact of resuscitated fecal peritonitis on the expression of the hepatic bile salt transporters in a porcine model.
Sepsis is often associated with cholestatic liver dysfunction caused by changes in the expression profile of hepatic bile salt transporters. However, in rodent endotoxin models, the role of ischemic hepatitis caused by liver hypoperfusion cannot be delineated. We hypothesized that hepatocytes change their expression pattern of bile salt transporters during early severe sepsis despite adequate resuscitation. ⋯ Bile salt export pump and MRP2 staining were downregulated in septic pigs. During early porcine fluid-resuscitated sepsis, hepatic basolateral influx (Na-taurocholate cotransporting polypeptide) and canalicular efflux (bile salt export pump) of bile salts were downregulated without hemodynamic signs of hepatic hypoperfusion or biochemical signs of cholestasis. In parallel, the basolateral escape transport (MRP4) was markedly upregulated, possibly as an early adaptive response to counteract hepatocellular accumulation of toxic bile acids.
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Immature myeloid cells have been implicated as a source of postburn inflammation, and the appearance of these cells correlates with enhanced upregulation of hematopoiesis. The role of proliferative cells in postburn immune changes has not been directly tested. Gemcitabine, a ribonucleotide reductase inhibitor, has been shown to deplete proliferative immature myeloid cells in tumor models while sparing mature cells, leading to restored lymphocyte function and tumor regression. ⋯ Treatment of burn mice with gemcitabine ameliorated burn-induced susceptibility to LPS and infiltration of polymorphonuclear leukocytes into the liver and lung. Finally, gemcitabine treatment blocked the protective effect of burn injury upon P. aeruginosa infection. Our report shows that proliferative cells are major drivers of postburn immune changes and provides evidence that implicates immature myeloid cells in these processes.
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Lung recruitment maneuvers (RMs), used to reopen atelectatic lung units and to improve oxygenation during mechanical ventilation, may result in hemodynamic impairment. We hypothesize that pulmonary arterial hypertension aggravates the consequences of RMs in the splanchnic circulation. Twelve anesthetized pigs underwent laparotomy and prolonged postoperative ventilation. ⋯ The corresponding recovery to at least 90% of baseline regional blood flow and organ perfusion lasted 1 to 5 min. Importantly, the decreases in regional blood flows and organ perfusion and the time to recovery of these flows did not differ from the controls. In conclusion, lipopolysaccharide-induced pulmonary arterial hypertension does not aggravate the RM-induced significant but short-lasting decreases in systemic, regional, and organ blood flows.
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Comparative Study
Peritoneal negative pressure therapy prevents multiple organ injury in a chronic porcine sepsis and ischemia/reperfusion model.
Sepsis and hemorrhage can result in injury to multiple organs and is associated with an extremely high rate of mortality. We hypothesized that peritoneal negative pressure therapy (NPT) would reduce systemic inflammation and organ damage. Pigs (n = 12) were anesthetized and surgically instrumented for hemodynamic monitoring. ⋯ Our data suggest NPT efficacy is partially due to an attenuation of peritoneal inflammation by the removal of ascites. However, the exact mechanism needs further elucidation. The clinical implication of this study is that sepsis/trauma can result in an inflammatory ascites that may perpetuate organ injury; removal of the ascites can break the cycle and reduce organ damage.
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Today, there is no continuous monitoring of the bronchial epithelial lining fluid. This study used microdialysis as a method of continuous monitoring of early lung cytokine response secondary to intestinal ischemia-reperfusion in pigs. The authors aimed to examine bronchial microdialysis for continuous monitoring of IL-1β, TNF-α, IL-8, and fluorescein isothiocyanate Dextran 4,000 Da (FD-4). ⋯ During reperfusion, PaO2/FiO2 ratio decreased in the ischemia group. Histology was normal in both groups. Bronchial microdialysis detects altered levels of cytokines in the epithelial lining fluid and can be used for continuous monitoring of the immediate local lung cytokine response secondary to intestinal ischemia-reperfusion.