Inhibition by leukocyte depletion of neointima formation after balloon angioplasty in a rabbit model of restenosis

Objective: The aim of the current study was to examine neointima formation in balloon injured left subclavian artery of rabbits subjected to two diffe rent methods of leukocyte depletion at the time of injury. Methods: Angiopl asty of the left subclavian artery was performed in leukopenic male New Zea land White rabbits. Depletion of circulating leukocytes was induced by eith er mustine hydrochloride or an antibody against leukocyte common antigen (a nti-LCA) before angioplasty. Left and right subclavian arteries were remove d 28 days after injury for morphological analysis and measurement of neoint imal size. At the same time, leukocytes were isolated from autologous rabbi t blood for Cr-51-labelling for assessment of leukocyte adhesion to injured and non-injured artery segments. Results: Leukopenia decreased neointima f ormation in injured arteries (neointimal area was 0.09+/-0.03 mm(2) in must ine-treated arteries, n=8, vs. 0.56+/-0.07 mm(2) in control arteries, n=7; P<0.001 and 0.07+/-0.01 mm(2) in anti-LCA treated arteries, n=9, vs. 0.22+/ -0.04 mm2 in non immune serum-treated arteries, n=9; P<0.001). Adventitial fibrosis was also significantly (P<0.05) decreased by both leukopenic inter ventions. Neither medial nor adventitial area was modified in any of the gr oups. No differences in leukocyte adhesion were observed between injured an d non-injured arteries in any of the experimental groups at the 28 day time point. Conclusion: These results suggest that leukocytes play a major role in the development of two of the major characteristics of the response to balloon injury, namely formation of neointima and adventitial fibrosis, tha t currently limit the success of clinical angioplasty. Elucidation of the f ine mechanisms involved in leukocyte-mediated injury may lead to the discov ery of novel therapeutic targets for the prevention of restenosis. (C) 2001 Elsevier Science B.V. All rights reserved.