Comparison of three tracers for detecting lung epithelial injury in anesthetized sheep

We compared the ability of three aerosolized tracers to discriminate among control, lung inflation with a positive end expired pressure of 10 cmH2O, lung vascular hypertension and edema without lung injury, and lung edema with lung injury due to intravenous oleic acid. The tracers were 99mTc-diethylenetriaminepentaacetate (99mTc-DTPA, mol wt 492), 99mTc-human serum albumin (99mTc-ALB, mol wt 69,000), and 99mTc-aggregated albumin (99mTc-AGG ALB, mol wt 383,000). 99mTc-DTPA clearance measurements were not able to discriminate lung injury from lung inflation. The 99mTc-AGG ALB clearance rate was unchanged by lung inflation and increased slightly with lung injury. The 99mTc-ALB clearance rate (0.06 +/- 0.02%/min) was unchanged by lung inflation (0.09 +/- 0.02%/min, P greater than 0.05) or 4 h of hypertension without injury (0.09 +/- 0.04%/min, P greater than 0.05). Deposition of 99mTc-ALB within 15 min of the administration of the oleic acid increased the clearance rate to 0.19 +/- 0.06%/min, which correlated well with the postmortem lung water volume (r = 0.92, P less than 0.01). This did not occur when there was a 60-min delay in the deposition of 99mTc-ALB. We conclude that 99mTc-ALB is the best indicator for studying the effects of lung epithelial injury on protein and fluid transport into and out of the air spaces of the lungs in a minimally invasive manner.