OBJECTIVES: To determine the possible role of enteric bacteria-derived endotoxin in the pathogenesis of the lung injury and mortality in rats following hemorrhagic shock and resuscitation. DESIGN: Prospective, randomized study. SETTING: Animal laboratory of an institute for research traumatology. SUBJECTS: Male Sprague-Dawley rats, weighing 450 to 480 g. INTERVENTIONS: Anesthetized rats were subjected to a prolonged hemorrhagic shock (mean arterial pressure of 30 to 35 mm Hg for 180 mins) followed by resuscitation. A murine monoclonal antibody to lipopolysaccharide from Escherichia coli and Salmonella, WN1 222-5, was administered at a total dose of 5 mg/kg i.v., starting at the onset of shock (WN1 group). The control group was treated similarly to the WN1 group but received saline at the same volume as WN1 222-5. MEASUREMENTS AND MAIN RESULTS: The 48-hr mortality rate was significantly reduced by WN1 222-5 treatment (28.6% in the treatment group vs. 78.6% in the control group; p = .0169). The characteristic lung injury in this model was significantly reduced in the WN1 group, as assessed by microscopic histopathologic examination increase in lung wet weight (7.60 +/- 0.47 g/kg in the control group vs. 5.14 +/- 0.31 g/kg in the WN1 group; p = .0002), and pulmonary neutrophilic infiltration (myeloperoxidase activity: 1835 +/- 567 mU/g wet weight in the control group vs. 891 +/- 212 mU/g wet weight in the WN1 group). CONCLUSIONS: These data suggest that a) endotoxin derived from enteric bacteria might play an important role in the pathogenesis of lung injury; and b) antiendotoxin agents, such as WN1 222-5, appear to protect against endogenous bacterial endotoxin-related disorders in severe hemorrhagic shock in rats.
OBJECTIVES: To determine the possible role of enteric bacteria-derived endotoxin in the pathogenesis of the lung injury and mortality in rats following hemorrhagic shock and resuscitation. DESIGN: Prospective, randomized study. SETTING: Animal laboratory of an institute for research traumatology. SUBJECTS: Male Sprague-Dawley rats, weighing 450 to 480 g. INTERVENTIONS: Anesthetized rats were subjected to a prolonged hemorrhagic shock (mean arterial pressure of 30 to 35 mm Hg for 180 mins) followed by resuscitation. A murine monoclonal antibody to lipopolysaccharide from Escherichia coli and Salmonella, WN1 222-5, was administered at a total dose of 5 mg/kg i.v., starting at the onset of shock (WN1 group). The control group was treated similarly to the WN1 group but received saline at the same volume as WN1 222-5. MEASUREMENTS AND MAIN RESULTS: The 48-hr mortality rate was significantly reduced by WN1 222-5 treatment (28.6% in the treatment group vs. 78.6% in the control group; p = .0169). The characteristic lung injury in this model was significantly reduced in the WN1 group, as assessed by microscopic histopathologic examination increase in lung wet weight (7.60 +/- 0.47 g/kg in the control group vs. 5.14 +/- 0.31 g/kg in the WN1 group; p = .0002), and pulmonary neutrophilic infiltration (myeloperoxidase activity: 1835 +/- 567 mU/g wet weight in the control group vs. 891 +/- 212 mU/g wet weight in the WN1 group). CONCLUSIONS: These data suggest that a) endotoxin derived from enteric bacteria might play an important role in the pathogenesis of lung injury; and b) antiendotoxin agents, such as WN1 222-5, appear to protect against endogenous bacterial endotoxin-related disorders in severe hemorrhagic shock in rats.
Authors: Misha D Luyer; Wim A Buurman; M'hamed Hadfoune; T Wolfs; Cornelis van't Veer; Jan A Jacobs; Cornelis H Dejong; Jan Willem M Greve Journal: Ann Surg Date: 2007-05 Impact factor: 12.969
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Authors: Misha D P Luyer; Jan A Jacobs; Anita C E Vreugdenhil; M'hamed Hadfoune; Cornelis H C Dejong; Wim A Buurman; Jan Willem M Greve Journal: Ann Surg Date: 2004-02 Impact factor: 12.969
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