Photochemical Tissue Passivation of Arteriovenous Grafts Prevents Long-term Development of Intimal Hyperplasia in a Swine Model

Background: The autologous vein remains the standard conduit for lower extremity and coronary artery bypass grafting despite a 30%-50% 5-y failure rate, primarily attributable to intimal hyperplasia (IH) that develops in the midterm period (3-24 mo) of graft maturation. Our group discovered that externally strengthening vein grafts by cross-linking the adventitial collagen with photochemical tissue passivation (PTP) mitigates IH in an arte- riovenous model at 4 wk. We now investigate whether this effect is retained in the midterm period follow-up. Methods: Six Hanford miniature pigs received bilateral carotid artery interposition vein grafts. In each animal, the external surface of one graft was treated with PTP before grafting, whereas the opposite side served as the untreated control. The grafts were har- vested after 3 mo. Ultrasound evaluation of all vein grafts was performed at the time of grafting and harvest. The grafts were also evaluated histomorphometrically and immu- nohistologically for markers of IH. Results: All vein grafts were patent at 3 mo except one graft in the PTP-treated group because of early technical failure. The control vein grafts had significantly greater IH than PTP-treated grafts at 3 mo, as evidenced by the intimal area (2.6 ? 1.0 mm2 versus 1.4 ? 1.5 mm2, respectively, P ¼ 0.045) and medial area (5.1 ? 1.9 mm2 versus 2.7 ? 2.4 mm2, respectively, P ¼ 0.048). The control grafts had an increased presence and proliferation of mural myofibroblasts with greater smooth muscle actin and proliferating cell nuclear antigen staining. Conclusions: PTP treatment to the external surface of the vein grafts decreases IH at 3 mo after arteriovenous grafting and may prevent future graft failure.