Evaluation of lung injury in rats and mice

Lung injury is a broad descriptor that can be applied to conditions ranging from mild interstitial edema without cellular injury to massive and fatal destruction of the lung. This review addresses those methods that can be readily applied to rats and mice whose small size limits the techniques that can be practically used to assess injury. The methodologies employed range from nonspecific measurement of edema formation to techniques for calculating values of specific permeability coefficient for the microvascular membrane in lung. Accumulation of pulmonary edema can be easily and quantitatively measured using gravimetric methods and indicates an imbalance in filtration forces or restrictive properties of the microvascular barrier. Lung compliance can be continuously measured, and light and electron microscopy can be used regardless of lung size to detect edema and structural damage. Increases in fluid and/or protein flux due to increased permeability must also be separated from those due to increased filtration pressure for mechanistic interpretation. Although an increase in the initial lung albumin clearance compared with controls matched for size and filtration pressure is a reliable indicator of endothelial dysfunction, calculated alterations in capillary filtration coefficient K(f,c), reflection coefficient sigma, and permeability-surface area product PS are the most accurate indicators of increased permeability. Generally, PS and K(f,c) will increase and sigma will decrease with vascular injury, but derecruitment of microvascular surface area may attenuate the affect on PS and K(f,c) without altering measurements of sigma.