Cor Vasa 2011, 53(1-2):84-90

A periadventitial sirolimus-eluting system in the prevention of neointimal hyperplasia in autologous venous grafts

Ivo Skalský^1,*, Ondrej Szárszoi¹, Elena Filová^2,3, Martin Pařízek^2,3, Andriy Lytvynets², Jana Malušková⁴, Alena Lodererová⁴, Jana Olšovská^5,8, Zdeněk Kameník⁵, Eduard Brynda⁶, Zdeněk Plichta⁶, Tomáš Riedel⁶, Věra Lisá², Zuzana Burdíková², Martin Čapek², Ľubica Grausová², Tomáš Suchý⁷, Jan Pirk¹, Lucie Bačáková^2,3

¹ Klinika kardiovaskulární chirurgie, Institut klinické a experimentální medicíny

² Fyziologický ústav, AV ČR

³ Centrum výzkumu chorob srdce a cév

⁴ Pracoviště klinické a transplantační patologie, Institut klinické a experimentální medicíny

⁵ Mikrobiologický ústav, AV ČR

⁶ Ústav makromolekulární chemie, AV ČR

⁷ Ústav struktury a mechaniky hornin, AV ČR

⁸ Výzkumný ústav pivovarský a sladařský, Praha, Česká republika

Aim: Autologous venous grafts such as coronary artery bypass grafts often develop intimal hyperplasia resulting in stenoses and occlusions. The aim of our study was to prevent the development of intimal hyperplasia using a novel perivascular system allowing for long-term release of sirolimus.

Method: The controlled-release system comprises a polyester mesh coated with a sirolimus-eluting copolymer of L lactic acid and ε-caprolactone system designed to be wrapped around an autologous venous graft during its implantation. In vitro sirolimus release and its effects on smooth muscle and endothelial cells were assessed. The sirolimus controlled-release mesh was implanted into the common carotid arteries of rabbits with subsequent assessment of venous graft neointimal hyperplasia at 3 and 6 weeks.

Results: In vitro, the copolymer-coated polyester mesh released sirolimus over a period of 6 weeks. Mesh-eluted sirolimus inhibited the growth of smooth muscle and endothelial cells in seven-day in vitro experiments. After seven days of sirolimus release from the mesh, smooth muscle and endothelial cell counts decreased by 29% and 75%, respectively, with the cells maintaining high viability. Implantation of the sirolimus-release mesh to rabbits resulted in a decrease in intimal thickness by 47% and 56% at 3 and 6 weeks, respectively, compared with the venous intima. After implantation of a sirolimus-free mesh, intimal thickness declined by 35% and 46% at 3 and 6 weeks, respectively.

Conclusion: A sirolimus controlled-release system intended for periadventitial use in autologous venous grafts inhibited the growth of smooth muscle cells in vitro and precluded the development of neointimal hyperplasia in vivo in rabbits. Hence, the perivascular sirolimus-eluting mesh holds promise for preventing the development of stenoses and occlusions in autologous vascular grafts.

Keywords: Jugular veins; Sirolimus; Drug carriers; Autologous transplantation; Restenosis

Published: January 1, 2011  Show citation