The Journal of surgical research
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There have been many studies on anti-lipopolysaccharide (LPS) agents and LPS-neutralizing agents; however, there have been no reports on the changes in clinical status and mediators that occur when these agents are used. Polymyxin (PMX) (treatment using a column containing polymyxin B-immobilized fiber) removed circulating endotoxin, and reduced various cytokines within 120 min, even in patients with high levels of plasma cytokines. Our purpose was examine the mechanisms of PMX treatment by which plasma cytokines are reduced by endotoxin neutralization with polymyxin B, even during therapy for sepsis and/or endotoxin shock. ⋯ These findings may indicate one of the mechanisms operating in the clinical changes that occur after circulating endotoxin removal, and are likely to have therapeutic value, even for patients with high proinflammatory cytokine levels.
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The acute respiratory distress syndrome (ARDS) occurs in patients with clearly identifiable risk factors, and its treatment remains merely supportive. We postulated that patients at risk for ARDS can be protected against lung injury by a prophylactic treatment strategy that targets neutrophil-derived proteases. We hypothesized that a chemically modified tetracycline 3 (COL-3), a potent inhibitor of neutrophil matrix metalloproteinases (MMPs) and neutrophil elastase (NE) with minimal toxicity, would prevent ARDS in our porcine endotoxin-induced ARDS model. ⋯ A single prophylactic treatment with COL-3 prevented lung injury in our model of endotoxin-induced ARDS. The proposed mechanism of COL-3 is a synergistic inhibition of the terminal neutrophil effectors MMPs and NE. Similar to the universal practice of prophylaxis against gastric stress ulceration and deep venous thromboses in trauma patients, chemically modified tetracyclines may likewise be administered to prevent acute lung injury in critically injured patients at risk of developing ARDS.
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Recent evidence suggests that hyperlactatemia in shock may reflect accelerated aerobic glycolysis linked to activity of the Na(+), K(+)-ATPase rather than hypoxia. Epinephrine stimulates glycolysis in resting muscle largely by stimulating Na(+), K(+)-ATPase activity. This study evaluates the effects of hemorrhagic shock, with and without combined alpha- and beta-adrenergic receptor blockade, on lactate production, glycogenolysis, Na(+)-K(+) pump activity, and high-energy phosphates in rat skeletal muscle. ⋯ Neither hypoxia nor defective oxidative metabolism appeared responsible for increased glycolysis during hemorrhagic shock. Adrenergic blockade concurrently reduced plasma lactate, muscle levels of lactate and glucose 6-phosphate, and muscle Na(+)-K(+) pump activity during shock. Rapid skeletal muscle aerobic glycolysis in response to increased plasma epinephrine levels may be an important contributor to increased glycolysis in muscle and increased plasma lactate during hemorrhagic shock.
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Tissue culture techniques enable in vitro expansion of keratinocytes that can be used to treat burns and chronic wounds. These keratinocytes are commonly grafted onto the wounds as differentiated sheets of mature epithelium. Less is however known about the effects of transplanting the cells as suspensions. This study evaluated epidermal regeneration in fluid-treated skin wounds treated with suspensions of cultured and noncultured autologous keratinocytes. ⋯ Our study demonstrates successful transplantation of keratinocyte suspensions and their dose-dependent acceleration of wound repair. Selection of proliferative cells during culture and higher colony-forming efficiency may explain the greater effects observed with cultured keratinocytes.
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Positive end-expiratory pressure (PEEP) reduces ventilator-induced lung injury (VILI), presumably by mechanically stabilizing alveoli and decreasing intrapulmonary shear. Although there is indirect support for this concept in the literature, direct evidence is lacking. In a surfactant depletion model of acute lung injury we observed unstable alveolar mechanics referred to as repeated alveolar collapse and expansion (RACE) as measured by changes in alveolar area from inspiration to expiration (I - E(Delta)). We tested the hypothesis that over a range of tidal volumes PEEP would prevent RACE by mechanically stabilizing alveoli. ⋯ RACE occurs in our surfactant deactivation model of acute lung injury. PEEP mechanically stabilizes alveoli and prevents RACE over a range of tidal volumes. This is the first study to visually document the existence of RACE and the mechanical stabilizing effects of PEEP at the alveolar level. The ability of PEEP to stabilize alveoli and reduce shear during mechanical ventilation has important implications for therapeutic strategies directed at VILI and acute respiratory distress syndrome.