Pulmonary inflammatory cell response to sustained endotoxin administration

Abstract

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 approximately 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.

Effects of ventilation strategy on distribution of lung inflammatory cell activity

“…In previous studies, the current endotoxin dose allowed for survival of awake animals for 24 h [35,36]. Thus, in terms of lung injury, the initial 2 h of endotoxin exposure represent early events, as attested by very low lung injury scores obtained by histological analysis.…”

Mitigation of endotoxin-induced acute lung injury in ventilated rabbits by surfactant and inhaled nitric oxide

“…This can be considered an ªearlyº intervention aimed at preventing further deterioration of lung function. In contrast to other ALI models [31,32,33,34,35] with either endotoxin priming or sustained endotoxin infusion for many hours or days, or intratracheal instillation of endotoxin, the method we applied in the present study (a low dose of endotoxin for priming and a major dose for challenge 12 h apart), consistently induced ALI with respiratory failure in the subsequent 12±14 h, facilitating comparison of the various therapies. The low priming dose of endotoxin potentiat-235 ed endogenous NO production, as reflected by elevated urinary nitrite/nitrate levels, without causing septic shock.…”

Assessment of Lung Inflammation With18F-FDG PET During Acute Lung Injury

“…Moreover, in endotoxin models of ALI, the increase in macrophage counts is similar to [45, 46] or higher than [47] that of neutrophils. In other models of ALI, macrophage depletion has been found to protect the lung from dysfunction and injury [48–54].…”