Specificity and sensitivity of noninvasive measurement of pulmonary vascular protein leak

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Abstract
Noninvasive techniques employing external counting of radiolabeled protein have the potential for measuring pulmonary vascular protein permeability, but their specificity and sensitivity remain unclear. The specificity and sensitivity of a double-radioisotope were tested by injecting radiolabeled albumin (131I) and erythrocytes (99mTc) into anesthetized dogs and measuring the counts of each isotope for 150 min after injection with an external gamma probe fixed over the lung. The rate of increase of albumin counts measured by the probe (which reflects the rate at which protein leaks into the extravascular space) was calculated. To assesses permeability the rate of increase in albumin counts was normalized for changes in labeled erythrocyte signal to minimize influence of changes in vascular surface area, thus deriving an albumin leak index. The albumin leak index and gravimetric lung water were measured during hydrostatic edema (acutely elevating left atrial pressure by left atrial balloon inflation: mean pulmonary arterial wedge pressure = 22.6 Torr) and in lung injury edema induced by high- (1.0 g/kg) and low-dose (0.25 g/kg) i.v. thiourea. To test specificity hydrostatic and high-dose thiourea edema were compared. The albumin leak index increased nearly 4-fold from control after thiourea injury (27.2 .+-. 2.3 .times. 10-4 vs. 7.6 .+-. 0.9 .times. 10-4 min) but did not change from control levels after elevating left atrial pressure (8.9 .+-. 1.2 .times. 10-4 min) despite comparable increases in gravimetric lung water. To test sensitivity low-dose thiourea were compared with controls. Following low-dose thiourea, the albumin leak index nearly doubled despite the absence of a measurable increase in lung water. A noninvasive double radioisotope measurement of pulmonary vascular protein leak employing external counting techniques and a simplified method of calculation is specific for lung injury and is also sensitive enough to detect lung injury insufficient to produce detectable pulmonary edema.