PURPOSE: Interstitial lung fibrosis (ILD) is a devastating progressive disease with a potentially fatal prognosis. The role of vascular remodeling in the pathogenesis of ILD associated pulmonary hypertension has been suggested and needs to be explored. Aims and Objectives: To morphometrically evaluate the vascular remodeling in Bleomycin model of pulmonary fibrosis and correlate with the development of inflammation and fibrosis
METHODS: Male Wistar rats (n=18) were administered intratracheal bleomycin (7 units/kg) and the lung histopathology was examined on Day 7, 14 and 28 and compared to control. The time course of pathological changes in the lung parenchyma, distal airways and pulmonary arterioles was assessed on hematoxylin and eosin stained sections(n=18). The morphometric evaluation of the distal bronchioles ranging from 50µm to 200µm in diameter was done using Nikon 90i fully motorized microscope and image analyzer. An average of 15 bronchioles and their accompanying arterioles were assessed in each case. The pulmonary arterioles were evaluated for muscularization, intimal proliferation. Lung inflammation and fibrosis was semi quantitatively graded using the Ashcroft grading method.
RESULTS: Peribronchiolar neurophilic infiltrate with minimal fibrous thickening (Grade 1) was seen on day 7. On day 14 this progressed to chronic peribronchiolar inflammation with minimal fibrosis (Grade 3) and on day 28, interstitial fibrosis was observed (Grade 5). There was a significant increase in muscularization of the distal arterioles which started on day 7 (16.81µm, p<0.0001), remained constantly elevated till day 14 (16.39 µm, p=0.0003) and further increased till day 28 (19.80µm, p<0.0001) as compared to control (12.64µm).
CONCLUSIONS: This study reveals that there is an onset of vascular remodeling in pulmonary arterioles which occurs concurrently with peribronchiolar inflammation on Day 7 after exposure to bleomycin and this significantly progresses up to Day 28.
CLINICAL IMPLICATIONS: Pulmonary fibrosis and pulmonary arterial hypertension are thought to share pathogenetic mechanisms with a central role of vascular remodeling. In this study we have semiquantitatively assessed pulmonary arteriolar changes by morphometry and correlated with the time course of histopathological changes occurring in bleomycin model of pulmonary fibrosis
DISCLOSURE: The following authors have nothing to disclose: Ritu Kulshrestha, D. Soundarya, A. Dinda, Krishnan Ravi
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