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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Epidermal growth factor (EGF) is a cytoprotective peptide that has healing effects on the intestinal mucosa. We sought to determine whether systemic administration of EGF after the onset of sepsis improved intestinal integrity and decreased mortality. FVB/N mice were subjected to either sham laparotomy or 2 x 23 cecal ligation and puncture (CLP). ⋯ To determine whether improvements in gut homeostasis were associated with a decrease in sepsis-induced mortality, septic mice with or without EGF treatment after CLP were followed 7 days for survival. Mortality decreased from 60% to 30% in mice treated with EGF after the onset of sepsis (P < 0.05). Thus, EGF may be a potential therapeutic agent for the treatment of sepsis in part due to its ability to protect intestinal integrity.
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Time profiles of arterial lactate concentrations have been proposed as markers for both the degree of physiological derangement during shock and effectiveness of clinical resuscitation, but have not been evaluated for use in short-term experimental protocols. We developed two quantitative mixed models of sequential arterial lactate concentrations to evaluate competing low-volume (<4 mL/kg) battlefield resuscitation therapies in a rat model of acute severe hemorrhagic shock: a simple linear additive model and a nonlinear mechanistic model that described lactate profiles in a continuous trajectory with a defined turning point. Data were obtained during a study evaluating a novel hemoglobin polymer (OxyVita) in a cocktail of hypertonic saline and Hextend as an alternative to standard Hextend. ⋯ A cocktail of hypertonic saline and Hextend was superior to standard Hextend in enhancing survival; however, lactate profiles did not differ between treatments. Regardless of resuscitation regimen, animals surviving to at least 60 min posthemorrhage can be discriminated from nonsurvivors by significantly lower peak lactates (a difference of at least 3 mM; P < 0.001), and all survivors exhibited a decline in lactate with resuscitation. Sequential measurements of lactate over relatively short time frames during resuscitation are of value in assessing both response to resuscitation and short-term mortality.
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Enhancing survival to hemorrhage of both civilian and military patients is a major emphasis for trauma research. Previous observations in humans and outbred rats show differential survival to similar levels of hemorrhage. In an initial attempt to determine potential genetic components of such differential outcomes, survival time after a controlled hemorrhage was measured in 15 inbred strains of rats. ⋯ Graded and divergent survival times to hemorrhage in inbred rat strains are remarkable and suggest multiple genetic components for this characteristic. However, this interpretation of differential responses to hemorrhage may be confounded by potential strain-associated differences related to the surgical preparation. Identification of inbred strains divergent in survival time to hemorrhage provides the opportunity for future use of these strains to identify genes associated with this complex response.
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There are few blood biomarkers predictive of mortality in adult respiratory distress syndrome (ARDS), and none that currently serve as therapeutic targets. Here, we ask whether a circulating protein angiopoietin 2 (Ang2) correlates with severity of lung injury and mortality in a surgical intensive care unit cohort with acute lung injury (ALI)/ARDS. Tie 2 is a tyrosine kinase receptor expressed on endothelial cells. ⋯ A patient's convalescent (low Ang2) plasma did not disrupt junctional architecture. Although further studies with larger sample sizes will be needed to confirm these results, high Ang2 in critically ill patients with ALI/ARDS is associated with a poor outcome. These data, coupled with our cell culture experiments, suggest that antagonism of Ang2 may provide a future novel therapeutic target for ARDS.