Use of Telemetry and Plethysmography to Assess Respiratory Function in Conscious Rats with Bleomycin-Induced Lung Fibrosis

Introduction: IPF is characterised by irreversible lung function decline. This study assessed lung function in a repetitive bleomycin challenge model to better diagnose fibrosis in conscious rats. Respiratory parameters were determined using Intra-Pleural Pressure/Head-out Plethysmography and Whole Body Plethysmography. Method: Male telemetered rats were administered bleomycin on 5 occasions and treated with nintendanib (60 mg/kg, BID) or vehicle. Respiratory assessments were performed during Week 1 and 4. Lungs were scored for fibrosis. Results: Bleomycin-challenged animals developed fibrosis; fibrosis was reduced in nintedanib-treated animals. In the acute phase, bleomycin significantly changed respiratory rate, tidal volume, apnoea time and compliance; these parameters were improved with nintedanib treatment (Table). There were no significant differences in respiratory parameters in the established fibrosis phase. Acute phase respiratory rates and apnoea times were positively correlated with the extent of lung fibrosis on Day 29 (P Conclusion: Lung function assessment in concious rats detected early damage but did not diagnose the extent of fibrosis once established. These data will now be analysed using Attractor Reconstruction to determine whether fibrosis is better identified by novel parameters generated from the complete waveform.