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Gut ischemia/reperfusion produces lung injury 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.
Insights
Gut ischemia/reperfusion primes neutrophils and causes lung injury through a mechanism independent of endotoxin. This study investigated the role of endotoxin in post-injury organ failure.
Area of Science:
- Gastroenterology
- Immunology
- Critical Care Medicine
Background:
- Bacterial translocation from the gut is implicated in post-injury multiple organ failure.
- Previous research demonstrated that gut ischemia/reperfusion can induce remote organ injury.
Purpose of the Study:
- To determine if endotoxin plays a critical role in the mechanism of gut ischemia/reperfusion-induced remote organ injury.
Main Methods:
- Prospective, randomized animal study using Sprague-Dawley rats.
- Animals underwent superior mesenteric artery occlusion and reperfusion, with endotoxin elimination using the IgM antibody E5.
- Measurements included plasma endotoxin levels, circulating neutrophil priming, lung neutrophil sequestration, and lung endothelial permeability.
Main Results:
- Gut ischemia/reperfusion induced circulating neutrophil priming, lung neutrophil sequestration, and lung injury.
- No significant difference in plasma endotoxin levels was observed between groups.
- Eliminating endotoxin did not alter the observed neutrophil priming or lung injury.
Conclusions:
- Gut ischemia/reperfusion primes circulating neutrophils.
- Lung injury following gut ischemia/reperfusion occurs via a mechanism independent of endotoxin.