Pulmonary inflammatory cell response to sustained endotoxin administration

We have developed a model of human sepsis in sheep. Twenty-four hours after continuous infusion of Escherichia coli endotoxin (lipopolysaccharide) (10 ng · kg^-1 · min^-1) was begun, pulmonary transvascular fluid flux was almost five times the baseline values, cardiac output was nearly doubled, and mean arterial pressure was reduced by ~20 mmHg. At this time, the animals were killed and their lungs were fixed by endotracheal installation of 2.5% glutaraldehyde at 25 cmH₂O pressure. Morphometry was performed by point counting, and data were expressed as relative volume density. Pulmonary edema and congestion were observed in sheep receiving lipopolysaccharide, whereas sham controls appeared normal. There was an increase in interstitial volume density. There was a significant increase (P < 0.01) in volume density of the pulmonary intravasculature (180%), interstitial macrophages (270%), and mast cells (240%). The volume densities of intravascular and interstitial polymorphonuclear neutrophils also showed a small insignificant increase.