Molecular engineering of vein bypass grafts

Regulation of intimal hyperplasia in rabbit vein grafts by local modulation of the inhibitor of apoptosis protein (IAP) survivin. Rabbit jugular vein carotid interposition grafts were treated at implantation with adenoviral vectors encoding a dominant-negative form of survivin (AdT34), wild-type survivin (AdWT), or an irrelevant gene (AdGFP). Panel A, Representative histology (I, Intima; M, media, A, adventitia) at 4 weeks. Panel B, morphologic analysis at 4 weeks. A significant (41%) reduction in wall thickness was observed in AdT34 treated grafts, and a corresponding increase (37%) was observed in AdWT treated grafts that overexpressed survivin.¹⁰

Device used for intraoperative, pressure-mediated transfection of vein grafts with ODN (edifoligide) in the PREVENT clinical trials. Top panel, Assembled device with vial for administering test article is shown. Bottom panel, Intraoperative photograph demonstrates treatment of a vein graft before implantation in PREVENT III.⁴⁶

Changes in lumen diameter and wall thickness in lower extremity vein grafts over time, assessed by ultrasound studies.⁴⁴ A, Data demonstrate serial lumen diameter measurement of a defined region (index segment) of vein grafts in 90 subjects. B, Data show changes in wall stiffness assessed by graft pulse wave velocity in 83 subjects. Results are presented as mean ± standard deviation.

Relationship of preoperative high sensitivity C-reactive protein (CRP) level to adverse events during follow-up in 91 patients undergoing lower extremity vein bypass surgery.⁴⁵