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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Of the 450,000 burn patients each year, 50% have a positive blood alcohol content, and this predisposes them to worsened clinical outcomes. Despite high prevalence and established consequences, the mechanisms responsible for alcohol-mediated complications of postburn remote organ damage are currently unknown. To this end, mice received a single dose of alcohol (1.12 g/kg) or water by oral gavage and were subjected to a 15% total body surface area burn. ⋯ This retention of water weight despite increased dehydration suggests that intoxication at the time of a burn causes a shift in fluid compartments that may exacerbate end-organ ischemia and damage as evidenced by a 3-fold increase in intestinal bacterial translocation (P < 0.05), a 30% increase (P < 0.05) in liver weight-to-body weight ratio, and an increase in alveolar wall thickness over a burn alone. Furthermore, administration of the bradykinin antagonist HOE140 30 min after intoxication and burn restored fluid balance and alleviated end-organ damage. These findings suggest that alcohol potentiates postburn remote organ damage through shifts in fluid compartments mediated by bradykinin.
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Acute respiratory distress syndrome (ARDS) is a common cause of organ failure with an associated mortality rate of 40%. The initiating event is disruption of alveolar-capillary interface causing leakage of edema into alveoli. ⋯ Electroporation-mediated transfer of Na+,K+ -ATPase/ENaC plasmids improved lung function, reduced fibrin deposits, decreased lung edema, and improved survival in a translational porcine model of ARDS. Gene therapy can attenuate ARDS pathophysiology in a high-fidelity animal model, suggesting a potential new therapy for patients.
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Sepsis is a complex medical condition characterized by a systemic inflammatory response in the setting of infection. We hypothesized that combining antibiotics plus an immunosuppressant would protect against the morbidity and mortality of polymicrobial sepsis in mice better than would antibiotics alone. We used a murine cecal-ligation-and-puncture model in which mice were treated either with imipenem plus cyclophosphamide or imipenem alone. ⋯ In addition, mice treated with cyclophosphamide had higher levels of bacterial colonization in intestinal Peyer's patch lymph nodes at 72 h after the septic insult. Intraperitoneal macrophage phenotypes and phagocytosis activity did not differ between groups. We conclude that the inflammatory response plays a significant role in the mortality of polymicrobial sepsis and that the regulation of this element is both feasible and beneficial in this disease model.
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Acute kidney injury in asphyxiated neonates is common. The renal protective effects of doxycycline, a known matrix metalloproteinase (MMP) inhibitor, have been demonstrated in rat ischemic-reperfusion models of injury. These effects have not been tested in large-animal models designed to reflect true clinical scenarios of neonatal hypoxia-reoxygenation (H-R). ⋯ The H-R piglets had significantly higher urinary N-acetyl-D-glucosaminidase activity, renal tissue lipid hydroperoxides, lactate, and MMP-2 activity, which were attenuated to varied degrees in a dose-related manner in piglets treated with doxycycline (P = 0.08 to P < 0.05). Serum creatinine and histologic features of H-R were not different among groups. Postresuscitation administration of doxycycline improved renal perfusion, attenuated renal injury, and reduced tissue oxidative stress and MMP-2 activity in a clinically translatable newborn swine model of H-R.