期刊
CIRCULATION-CARDIOVASCULAR INTERVENTIONS
卷 3, 期 2, 页码 157-U96出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCINTERVENTIONS.109.864660
关键词
drugs; microspheres; muscle; smooth; vein bypass; atherosclerosis
资金
- British Heart Foundation
- Higher Education Funding Council for England
- NIHR Bristol Biomedical Research Unit in Cardiovascular Medicine
Background-Neointima formation and atherosclerosis compromise long-term graft patency in aortocoronary and peripheral vein bypass grafts. We investigated the short-and long-term effects of periadventitial application of a sustained-release formulation of rapamycin on experimental pig vein grafts with similar dimensions and kinetics to human saphenous vein bypass grafts. Methods and Results-Periadventitial application of rapamycin-eluting polyvinyl alcohol microspheres (60 mu g . cm(-2)) to porcine saphenous vein-to-carotid artery interposition grafts inhibited vein graft positive and vascular smooth muscle cell proliferation in 1-week grafts. It also decreased neointima formation and wall thickening in 4-week vein grafts compared with controls. The inhibition of vein graft thickening was not sustained; however, a catch-up phenomenon was observed, and there was no therapeutic benefit evident in 12-week grafts. Increasing the dose of rapamycin to 120 mu g . cm(-2) was associated with significant local toxicity manifest by high rates of graft rupture (25%), inhibition of adventitial neoangiogenesis, and a paradoxical acceleration of vein graft disease as evidenced by increased vascular smooth muscle cell proliferation. Conclusions-Local toxicity and poor long-term efficacy limits the clinical applicability of locally applied, sustained rapamycin release in vein graft disease. (Circ Cardiovasc Interv. 2010;3:157-165.)
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