Increased intrapulmonary retention of radiolabeled neutrophils in early oxygen toxicity.
Sequential lung injuries, such as oxygen toxicity followed by septicemia, are common during the adult respiratory distress syndrome (ARDS). As these forms of vascular injury may be mediated in part by polymorphonuclear leukocytes (PMN), aberrant interactions between PMN and previously injured pulmonary endothelium are of both theoretical interest and clinical importance. The present study was undertaken to test the hypothesis that early oxygen toxicity at a dose that injuries pulmonary endothelium relatively selectively alters intrapulmonary neutrophil kinetics. Unanesthetized rats breathing 1.0 atmospheres oxygen for 36 h showed ultrastructural endothelial damage but no edema, injury, or neutrophilic inflammation by histologic criteria. However, in these oxygen-toxic animals, whereas initial accumulation of radiolabeled PMN in lungs was normal, washout of PMN was abnormal at 120 min after infusion, at which point the pulmonary retention of radiolabeled PMN in the lungs of oxygen-treated animals was significantly higher than in control animals (139% of control, p less than 0.0096). Features of our methodology, including avoidance of osmotic stress and use of paired control animals, appear to have greatly enhanced the sensitivity of radiolabeled neutrophils for detecting a subtle abnormality of neutrophil-endothelial interactions. Our studies in the oxygen toxicity model provide the first demonstration in vivo of abnormal intrapulmonary neutrophil kinetics in early oxygen toxicity prior to the onset of histologic evidence of lung injury or inflammation.
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D004727:Endothelium / Q000166:cytology / Q000000981:diagnostic imaging / Q000187:drug effects; D004731:Endotoxins / Q000633:toxicity; D004926:Escherichia coli; D007205:Indium Radioisotopes; D008168:Lung / Q000166:cytology / Q000000981:diagnostic imaging / Q000187:drug effects*; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009942:Organometallic Compounds; D010100:Oxygen / Q000633:toxicity*; D015125:Oxyquinoline / Q000031:analogs & derivatives; D011877:Radionuclide Imaging; D051381:Rats; D011919:Rats, Inbred Strains; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors; D014018:Tissue Distribution
D004731:Endotoxins; D007205:Indium Radioisotopes; D009942:Organometallic Compounds; C032950:indium oxine; D015125:Oxyquinoline; D010100:Oxygen