Solute Movement across the Alveolar-Capillary Membrane after Intratracheally Administered Bleomycin in Rats

Publisher Website
Google Scholar
Abstract
The rate of absorption across the alveolar-capillary membrane of inhaled 99mTc-DTPA and the concentration of albumin in the bronchoalveolar lavage (BAL) fluid were characterized in a rat model of bleomycin-induced pulmonary fibrosis. Adult male Lewis rats were studied from 1 h to 120 days after a single intratracheal instillation of bleomycin (0.5 to 0.6 U/100 g body weight). The retention of 99mTc-DTPA in the lungs, expressed as a percentage of the baseline radioactivity, was determined at 15 min (%R15) after delivery of the tracer. The %R15 was 83.7 ± 6.0 for normal untreated rats and 84.3 ± 3.7 for saline-treated animals. The rate of absorption of 99mTc-DTPA began to increase 24 h after bleomycin, reaching a maximum at Day 7, with %R15 = 56.0 ± 6.5 (p < 0.0001). Resolution to control values occurred by Day 34 after bleomycin. At Day 45 after bleomycin, the rate of absorption of 99mTc-DTPA was slower than sham (control), with %R15 = 89.2 ± 1.9 (p < 0.5). However, from Day 63 onwards, removal was not different from control. The concentration of albumin in the BAL fluid began to increase 48 h after bleomycin, was 10-fold greater than control by Day 7 (150 ± 38 versus 16 ± 3 µg/ml), and returned to control values by Day 28. The percentage of neutrophils in the BAL increased at 12 h, reached a plateau of 33 ± 9% between 4 and 7 days, and then returned to control values by Day 14. These data demonstrate that the rate of transfer of both small and large molecular weight molecules across the alveolar-capillary membrane is increased after the intratracheal instillation of bleomycin and that the changes are associated with an influx of inflammatory cells in the lung. The increased rate of removal of aerosolized 99mTc-DTPA can be detected earlier and resolves later than the changes in BAL albumin in the BAL fluid, suggesting that the former might be a more sensitive technique to assess the integrity of the alveolar-capillary membrane.