Intratracheal aerosolization of endotoxin in the rat: a model of the adult respiratory distress syndrome (ARDS).
A technique is described for the intratracheal aerosolization of endotoxin into the rat. Using a miniaturized nozzle within the tracheal lumen to optimize uniform distribution 0.5 ml of an endotoxin solution (7 mg/kg) was aerosolized and dispersed throughout the lung. Time course studies of pulmonary function and histological changes revealed marked functional and morphological changes by 24 h. Histopathologic changes consisted of widespread pulmonary oedema and a diffuse neutrophilic alveolitis. At the same time, there were significant decreases in tidal volume, minute ventilation and lung compliance. Haematologic changes were also seen, including profound thrombocytopaenia and leukopaenia together with an increased haematocrit, indicating systemic effects in this model. Bronchoalveolar lavage (BAL) at 24 h revealed significant increases in BAL protein, erythrocytes and neutrophils. The functional, cytological and histological changes observed after endotoxin challenge mimic those seen in the Adult Respiratory Distress Syndrome in humans and can thus be used as a model to compare the efficacy of a variety of therapeutic interventions for this syndrome.
Wheeldon
E B
EB
Department of Experimental Pathology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406.
Walker
M E
ME
Murphy
D J
DJ
Turner
C R
CR
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000473:pathology; D002452:Cell Count; D004195:Disease Models, Animal; D004731:Endotoxins / Q000008:administration & dosage*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000473:pathology / Q000662:veterinary*; D014132:Trachea
D000336:Aerosols; D004731:Endotoxins; D008070:Lipopolysaccharides