Periadventitial rapamycin-eluting microbeads promote vein graft disease in long-term pig vein-into-artery interposition grafts

T Rajathurai, SIA Rizvi, H Lin, G Angelini, AC Newby, GJ Murphy

Research output: Contribution to journalArticle (Academic Journal)peer-review

24 Citations (Scopus)

Abstract

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 microg . 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 microg . 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.
Translated title of the contributionPeriadventitial rapamycin-eluting microbeads promote vein graft disease in long-term pig vein-into-artery interposition grafts
Original languageEnglish
Pages (from-to)157 - 165
Number of pages11
JournalCirculation: Cardiovascular Interventions
Volume3(2)
Publication statusPublished - Apr 2010

Bibliographical note

Publisher: Circ Cardiovasc Interv

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