Structure-function correlation of early stages of lung injury induced by intratracheal bleomycin in the rabbit.

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 micrograms/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.(ABSTRACT TRUNCATED AT 250 WORDS)

[1]  C. N. Gillis,et al.  Pulmonary endothelial dysfunction in the presence or absence of interstitial injury induced by intratracheally injected bleomycin in rabbits. , 1983, The American review of respiratory disease.

[2]  J. Lazo,et al.  Lack of metabolism as the biochemical basis of bleomycin-induced pulmonary toxicity. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[3]  D. Prockop,et al.  Prevention of bleomycin-induced pulmonary fibrosis in the hamster by cis-4-hydroxy-l-proline. , 1981, The American review of respiratory disease.

[4]  G. Snider,et al.  Lung statics and connective tissues after penicillamine in bleomycin-treated hamsters. , 1980, Journal of applied physiology: respiratory, environmental and exercise physiology.

[5]  F. J. Miller,et al.  Single-breath diffusing capacity and lung volumes in small laboratory mammals. , 1980, Journal of applied physiology: respiratory, environmental and exercise physiology.

[6]  N. Pride,et al.  Exponential description of the static pressure-volume curve of normal and diseased lungs. , 2015, The American review of respiratory disease.

[7]  G. Snider,et al.  Failure of mechanical properties to parallel changes in lung connective tissue composition in bleomycin-induced pulmonary fibrosis in hamsters. , 2015, The American review of respiratory disease.

[8]  L. Wood,et al.  Mechanisms of increased maximum expiratory flow during HeO2 breathing in dogs. , 1979, Journal of applied physiology: respiratory, environmental and exercise physiology.

[9]  H J Colebatch,et al.  Use of an exponential function for elastic recoil. , 1979, Journal of applied physiology: respiratory, environmental and exercise physiology.

[10]  F. Grover,et al.  Bleomycin-induced diffuse interstitial pulmonary fibrosis in baboons. , 2015, The Journal of clinical investigation.

[11]  J Dosman,et al.  The relations between structural changes in small airways and pulmonary-function tests. , 1978, The New England journal of medicine.

[12]  W. Roberts,et al.  Idiopathic pulmonary fibrosis. Clinical, histologic, radiographic, physiologic, scintigraphic, cytologic, and biochemical aspects. , 1976, Annals of internal medicine.

[13]  K. Yoneda,et al.  Morphologic and biochemical study of pulmonary changes induced by bleomycin in mice. , 1976, Laboratory investigation; a journal of technical methods and pathology.

[14]  R. Davies,et al.  Small airways in fibrosing alveolitis. , 1976, The American review of respiratory disease.

[15]  W. Thurlbeck,et al.  Disease of the small airways in chronic bronchitis. , 2015, The American review of respiratory disease.

[16]  R. Cherniack,et al.  Resistance to airflow in patients with diffuse interstitial lung disease. , 2015, The American review of respiratory disease.

[17]  J. R. Baker,et al.  Bleomycin-induced interstitial pneumonia in dogs , 1971, Thorax.

[18]  W. Thurlbeck,et al.  The number and dimensions of small airways in nonemphysematous lungs. , 1971, The American review of respiratory disease.

[19]  P. Macklem,et al.  Factors determining maximum expiratory flow in dogs. , 1968, Journal of applied physiology.

[20]  J. Scadding,et al.  Diffuse fibrosing alveolitis (diffuse interstitial fibrosis of the lungs) , 1967, Thorax.

[21]  E SALAZAR,et al.  AN ANALYSIS OF PRESSURE-VOLUME CHARACTERISTICS OF THE LUNGS. , 1964, Journal of applied physiology.

[22]  R. Forster,et al.  A standardized breath holding technique for the clinical measurement of the diffusing capacity of the lung for carbon monoxide. , 1957, The Journal of clinical investigation.

[23]  H. W. Chalkley.  Method for the Quantitative Morphologic Analysis of Tissues , 1943 .