Chronic intermittent hypoxia augments bleomycin induced lung fibrosis in rats (LB794)

Abstract

Rationale: Obstructive sleep apnea (OSA) is common among patients with idiopatic pulmonary fibrosis (IPF), where it has been linked with increased mortality. Chronic intemittent hypoxia (CIH) _ its hallmark feature_ may be one culprit. We tested the effects of CIH exposure on lung collagen, gas exchange and lung function following intratracheal bleomycin instillation in rats. Methods: Four groups (n=4/group) of Sprague Dawley rats were instilled with bleomycin (1.5 U/kg) (BLEO) or saline (SAL). Five days after instillation, rats were subjected to CIH (10% FiO2, 30 episodes/h, 10h/day) vs. normoxia (NORM) for 30 days. Total collagen in the right lung, pO2 and pCO2 in the exhaled air, and lung function by body plethysmography were compared between groups. Results: CIH resulted in: 1) significant increase in total collagen in bleomycin injured lungs compared to BLEO/NORM or the SAL controls (Figure 1); 2) significant exhaled O2 abnormalities in both SAL and BLEO treated groups compared to the respective NORM groups (Figure 2); 3) a trend of reduced FEV0.1/FVC ratio in CIH treated groups in both the BLEO and SAL compared to the NORM group (0.78±0.10 vs. 0.71±0.14 and 0.67±0.17 vs. 0.61±0.15). Conclusions: CIH aggravates lung fibrosis and gas exchange abnormalities following bleomycin. These findings underscore the potential of OSA to exacerbate IPF. Grant Funding Source: UW-Madison Department of Medicine Pilot Funding