NEOFORMATION OF BLOOD-VESSELS IN ASSOCIATION WITH RAT LUNG FIBROSIS INDUCED BY BLEOMYCIN

We have used intratracheal instillation of bleomycin in rats to study the microanatomical changes of blood vessels associated with lung fibr osis. Bleomycin is a toxic cytostatic drug employed in classical model s of lung fibrosis. Wistar rats were submitted to intratracheal inject ion of 1.5 units of bleomycin and sacrificed 2.5 months later, a timin g when marked fibrosis of the lung is observed. We casted the vascular tree of the rat lungs by perfusion with a methacrylate resin. These c asts were studied by scanning electron microscopy. Lung tissue was als o studied by light microscopy and thin section electron microscopy. Th e major vascular modifications observed in the bleomycin-treated rats were: (1) neoformation of an elaborate network of vessels located in t he peribronchial domains of the lung, and (2) distortion of the archit ecture of alveolar capillaries. By light microscopy, it was clear that the newly formed vascular network was located in regions of fibrosis (which in the resin casts were digested away). These neoformed vessels appeared to originate from bronchial arteries. Thin section electron microscopy revealed that endothelial cells of the neoformed vessels we re plump, presented large nuclei, and showed numerous pinocytotic vesi cles that were also observed in subendothelial pericytes. The alveoli of the bleomycin-treated rats were heterogeneous in size and shape in contrast with the homogeneity of alveoli of control animals. The alveo lar capillaries of fibrotic lungs appeared to occupy a larger volume o f the alveolar wall than alveolar capillaries of control rats. Our fin dings indicate that lung fibrosis encompasses marked changes of the va scular system, namely, the neoformation of vessels and the rearrangeme nt of alveolar capillaries. These structural changes suggest that fibr otic transformation of the lung is associated with the local generatio n of angiogenic stimuli. (C) 1994 Wiley-Liss, Inc.