OBJECTIVE: Bacterial translocation from the gut has been invoked as a common inciting event for postinjury multiple organ failure. We previously showed that gut ischemia/reperfusion induces remote organ injury. The purpose of this study was to ascertain if endotoxin has a pivotal mechanistic role in this process. DESIGN: Prospective, randomized study. SETTING: Animal laboratory. SUBJECTS: Sprague-Dawley rats weighing 300 to 350 g. INTERVENTIONS: Anesthetized animals underwent 45 mins of superior mesenteric artery occlusion and 2 hrs of reperfusion; sham laparotomy served as controls. Endotoxin was eliminated with the murine immunoglobulin (Ig) M antibody E5, 3 mg/kg i.v. before the study. MEASUREMENTS AND MAIN RESULTS: Plasma endotoxin was measured by the limulus amebocyte lysate assay. At 2 hrs of reperfusion, circulating neutrophil priming was determined by the difference in superoxide generation with and without the activating stimulus, N-formyl-Met-Leu-Phe. Neutrophil sequestration in the lung was quantitated by myeloperoxidase activity, and by lung endothelial permeability by 125I albumin lung/blood ratio. Endotoxin concentrations were not significantly (significance determined as p < .05) different between the gut ischemia/reperfusion and laparotomy groups (n = > or = 5) during ischemia or reperfusion. Circulating neutrophil priming, neutrophil accumulation in the lung, and lung injury were provoked by gut ischemia/reperfusion, but not altered by endotoxin elimination. CONCLUSION: Gut ischemia/reperfusion primes circulating neutrophils and produces lung injury by a mechanism independent of endotoxin.
OBJECTIVE: Bacterial translocation from the gut has been invoked as a common inciting event for postinjury multiple organ failure. We previously showed that gut ischemia/reperfusion induces remote organ injury. The purpose of this study was to ascertain if endotoxin has a pivotal mechanistic role in this process. DESIGN: Prospective, randomized study. SETTING: Animal laboratory. SUBJECTS:Sprague-Dawley rats weighing 300 to 350 g. INTERVENTIONS: Anesthetized animals underwent 45 mins of superior mesenteric artery occlusion and 2 hrs of reperfusion; sham laparotomy served as controls. Endotoxin was eliminated with the murine immunoglobulin (Ig) M antibody E5, 3 mg/kg i.v. before the study. MEASUREMENTS AND MAIN RESULTS: Plasma endotoxin was measured by the limulus amebocyte lysate assay. At 2 hrs of reperfusion, circulating neutrophil priming was determined by the difference in superoxide generation with and without the activating stimulus, N-formyl-Met-Leu-Phe. Neutrophil sequestration in the lung was quantitated by myeloperoxidase activity, and by lung endothelial permeability by 125I albumin lung/blood ratio. Endotoxin concentrations were not significantly (significance determined as p < .05) different between the gut ischemia/reperfusion and laparotomy groups (n = > or = 5) during ischemia or reperfusion. Circulating neutrophil priming, neutrophil accumulation in the lung, and lung injury were provoked by gut ischemia/reperfusion, but not altered by endotoxin elimination. CONCLUSION: Gut ischemia/reperfusion primes circulating neutrophils and produces lung injury by a mechanism independent of endotoxin.
Authors: Alfred Ayala; Chun-Shiang Chung; Joanne L Lomas; Grace Y Song; Lesley A Doughty; Stephen H Gregory; William G Cioffi; Brian W LeBlanc; Jonathan Reichner; H Hank Simms; Patricia S Grutkoski Journal: Am J Pathol Date: 2002-12 Impact factor: 4.307
Authors: Michael Kuncewitch; Weng-Lang Yang; Asha Jacob; Adam Khader; Matthew Giangola; Jeffrey Nicastro; Gene F Coppa; Ping Wang Journal: J Trauma Acute Care Surg Date: 2015-04 Impact factor: 3.313
Authors: Michael Kuncewitch; Weng Lang Yang; Asha Jacob; Adam Khader; Matthew Giangola; Jeff Nicastro; Gene F Coppa; Ping Wang Journal: Surgery Date: 2015-09-12 Impact factor: 3.982
Authors: Milena Armacki; Anna Katharina Trugenberger; Ann K Ellwanger; Tim Eiseler; Christiane Schwerdt; Lucas Bettac; Dominik Langgartner; Ninel Azoitei; Rebecca Halbgebauer; Rüdiger Groß; Tabea Barth; André Lechel; Benjamin M Walter; Johann M Kraus; Christoph Wiegreffe; Johannes Grimm; Annika Scheffold; Marlon R Schneider; Kenneth Peuker; Sebastian Zeißig; Stefan Britsch; Stefan Rose-John; Sabine Vettorazzi; Eckhart Wolf; Andrea Tannapfel; Konrad Steinestel; Stefan O Reber; Paul Walther; Hans A Kestler; Peter Radermacher; Thomas Fe Barth; Markus Huber-Lang; Alexander Kleger; Thomas Seufferlein Journal: J Clin Invest Date: 2018-10-15 Impact factor: 14.808