CHRONIC INTERSTITIAL PULMONARY FIBROSIS PRODUCED IN HAMSTERS BY ENDOTRACHEAL BLEOMYCIN - LUNG-VOLUMES, VOLUME-PRESSURE RELATIONS, CARBON-MONOXIDE UPTAKE, AND ARTERIAL BLOOD-GAS STUDIES

Abstract

Physiologic studies were carried out in hamsters with interstitial pulmonary fibrosis induced by a single, endotracheal dose of 0.5 units of bleomycin/100 g of body wt. Histologic studies showed that the lesion was maximally severe at 30 days, waned to 90 days and was then stable to 180 days. The volume of air in the lungs at a transpulmonary pressure of 25 cm H2O in anesthetized hamsters was significantly decreased 8, 30, 60, 90 and 180 days after bleomycin treatment, but the decrease was most marked at 30 days. Both quasistatic compliance expressed in ml per cm H2O and volume-corrected chord compliance between transpulmonary pressures of 0 and 5 cm H2O, expressed as a per cent of the volume of air in the lungs at a transpulmonary pressure of 25 cm H2O, were significantly less than corresponding control values at 8, 30 and 60 days, but not at 90 and 180 days. Mean values for the diffusion constant and diffusing capacity for CO by a rebreathing method were 72.0 and 59.6% of control values, respectively, 21 days after bleomycin treatment. Coefficients of correlation between the diffusion constant and inspiratory capacity and between diffusing capacity of the lung for CO and inspiratory capacity were 0.86 and 0.81, respectively; coefficients of correlation between the diffusion constant and volume of air in the lungs at a transpulmonary pressure of 25 cm H2O and between the CO diffusing capacity of the lung and volume of air in the lungs at a transpulmonary pressure of 25 cm H2O were 0.80 and 0.79, respectively. Twelve of 16 awake hamsters studied 21 to 35 days after bleomycin had low arterial PO2 [O2 partial pressure] values with normal PCO2 [CO2 partial pressure] values; mean .+-. SE arterial PO2 of animals treated with bleomycin was 56.5 .+-. 2.8 mm Hg, compared to 71.9 .+-. 1.5 mm Hg in normal animals. Apparently single-dose, bleomycin-induced, chronic interstitial pulmonary fibrosis in hamsters has physiologic characteristics that resemble those of human interstitial pulmonary fibrosis and should prove useful as an animal model of that disease.