STRUCTURE-FUNCTION CORRELATION OF EARLY STAGES OF LUNG INJURY INDUCED BY INTRATRACHEAL BLEOMYCIN IN THE RABBIT

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Abstract
After measurement of lung volume, pressure-volume relationship of the lungs, flow-volume relationship, and single-breath diffusing capacity, the effect of endotracheal injection of bleomycin (10 .mu.g/kg) on structural and functional changes was assessed in 21 rabbits and compared with 8 rabbits who received endotracheal injection of saline. Lung function was reassessed in the control rabbits at 1, 3, and 5 wk, and they were then killed. The bleomycin-treated rabbits were divided into 3 groups and retested at 1 (n = 7), 3 (n = 6), and 5 (n = 8) wk. Each group of animals was killed after the functional assessment, and after fixation the lungs were examined morphometrically. The degree of fibrosis in the bleomycin-treated animals was small even at 5 wk. Volume densities of pulmonary structures, alveolar wall thickness, airway diameters, airway inflammation scores, and fibrosis scores were determined and their correlation with the functional measurements was assessed. Lung volume subdivisions, pressure-volume characteristics, and diffusing capacity for carbon monoxide were significantly reduced, and the resistance of the upstream segment of airways was significantly increased after the bleomycin injection. Changes in lung volume correlated significantly with the volume densities of free alveolar cells, nonparenchymal tissue, and alveolar wall thickness. The exponent K, derived by fitting an exponential function to the pressure-volume data, which is indicative of lung elastic behavior, did not correlate with any morphometric index of interstitial disease. The diffusing capacity for CO was significantly correlated with the volume densities of alveolar wall, nonparenchymal tissue, and alveolar wall thickness, but these correlations became nonsignificant when the diffusing capacity was corrected for alveolar volume. It is concluded that the cellular stage of bleomycin lung toxicity in rabbits results in small, stiff lungs with impaired diffusing capacity. It seems unlikely that these tests would offer a clear distinction between the cellular and fibrotic stages of idiopathic pulmonary fibrosis in humans.