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Photochemical Tissue Passivation For Prevention Of Vein Graft Intimal Hyperplasia
Harry M. Salinas, MD, Justin Fernandes, MD, Felix Broelsch, MD, Michael C. McCormack, MD, Amanda Meppelink, MD, Michael Watkins, MD, William G. Austen, Jr., MD.
Massachusetts General Hospital, Boston, MA, USA.
Purpose: Vein grafts are frequently used as conduits for coronary bypass, peripheral arterial revascularization, and microsurgical reconstruction of the upper extremities. For coronary revascularization, saphenous vein grafts (SVG) are the most commonly used conduit. However, they have poor long term patency rates compared to arterial grafts due to accelerated atherosclerosis in the venous grafts. Accelerated atherosclerosis begins as intimal hyperplasia (IH), which is a consequence of the intimal injury that results from excessive stretching of the vein graft as it is exposed to arterial pressures. Limiting the stretch of the graft reduces the degree of IH. To date, every modality to prevent stretch has been through the application of external sheaths over the vein graft. Photochemical Tissue Passivation (PTP) is a technology that crosslinks surface proteins by a light activated process. PTP offers a simple approach to stiffen venous conduits, thus limiting excessive stretch and the resulting intimal injury.
Methods: Porcine jugular veins were used to evaluate the effect of PTP on the elasticity of venous tissues. Veins harvested from 5 pigs were divided in half. One segment served as control, the other was treated with 0.1% Rose Bengal and a 532 nm laser. The veins were cut into 0.5x2cm strips (N=33; 16 control, 17 treated). Stress-strain curves were generated for each with a tensiometer and the modulus of elasticity calculated as the slope of the initial linear portion of the curve. Collagenase digestion was performed on treated and untreated rat epigastric vein segments to demonstrate crosslinking. An animal model of IH was then adopted for in-vivo testing. An interposition graft was placed in the femoral artery of Sprague-Dawley rats using a reversed segment of epigastric vein. Animals were euthanized for graft harvest after 4 weeks.
Results: The modulus of elasticity (Young’s modulus) was 587±288 and 1008±555 KPa for untreated and treated samples respectively (p=0.01). Collagenase digestion took 66±8 and 300±0 min for untreated and treated samples respectively (p<0.001). Our in-vivo model showed that after four weeks, intimal thickness was 80±56 and 24±22 µm in untreated and treated grafts (p=0.03). Medial thickness was 216±69 and 141±40 µm in treated and untreated grafts (p=0.04). All grafts were patent.
Conclusion: PTP stiffens venous conduits, increasing the modulus of elasticity by nearly 2-fold. The collagenase digestion assay demonstrated significant collagen cross-linking of venous conduits after treatment with PTP. Our animal model showed 70% reduction in intimal thickness and 35% reduction in medial thickness of treated grafts. Therefore, PTP may improve the long term patency rates of venous grafts used for coronary revascularization and peripheral arterial reconstruction without the need for cumbersome external sheaths.
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