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Prevention of Vein Intimal Hyperplasia with Photochemical Tissue Passivation in a Porcine Model
Saiqa I. Khan, MD, Harry M. Salinas, MD, Amanda Meppelink, BS, Michael C. McCormack, MBA, Mark A. Randolph, MAS, Robert W. Redmond, PhD, William G. Austen, Jr., MD.
Massachusetts General Hospital - Harvard Medical School, Boston, MA, USA.
Veins are frequently used in microsurgical reconstruction of extremities, coronary bypass procedures, peripheral arterial revascularization, and vascular access for hemodialysis. Autologous veins are the conduit of choice for arterial reconstruction due to availability, superior patency rates, ease of use, and decreased infection risk compared to synthetic grafts. Despite widespread employment of autologous vein grafts, their effectiveness is limited by poor long-term patency rates compared to arterial grafts. Poor long-term outcomes are due to luminal narrowing caused by intimal hyperplasia (IH), medial thickening, and subsequent superimposed accelerated atherosclerosis. IH is a consequence of intimal injury that ensues after exposure of a vein to arterial pressures. Studies have shown that limiting the distension of the graft reduces the degree of IH, increasing patency rates.
Photochemical Tissue Passivation (PTP) is a novel technology that crosslinks surface proteins (i.e. collagen) by a light-activated process. Cross-linking stiffens the venous conduit, making its compliance and elasticity similar to that of an artery. We hypothesize that PTP of porcine vein grafts will limit distension thereby reducing IH.
Porcine saphenous veins were used to evaluate the effect of PTP on vessel compliance. Veins were harvested from Yorkshire pigs and cut into three centimeter sections, which were randomly assigned to control or treated groups. Stress-strain curves were generated for each section and the modulus of elasticity was calculated as the slope of the initial portion of the curve. A porcine model of vein interposition grafts was used to test the effects of PTP on IH. Reversed saphenous vein interposition grafts were placed in bilateral carotid arteries of Yorkshire pigs (n=6). Each pig was internally controlled, as one graft was PTP-treated and the other graft was left untreated. At four weeks, graft diameter and patency were assessed, followed by harvest for histological analysis.
The initial slopes or moduli of elasticity (Young’s modulus) of untreated and treated veins were 213.38±61.2 and 699.91±76.5 (p=0.0002), respectively. After four weeks, IH area was 4.0±1.6 mm2 in untreated and 1.3±0.7 mm2 (p=0.03) in treated grafts. Medial area was 9.2±1.8 and 5.1±1.8 mm2 (p=0.02) in untreated and treated grafts, respectively. IH thickness was 0.78±0.2 and 0.41±0.2 mm (p=0.002) in untreated and treated grafts, respectively. Medial thickness was 1.15±0.2 mm in untreated grafts and 0.83±0.2 mm (p=0.02) in treated grafts. Treated grafts appeared less dilated and tortuous than untreated grafts (Figure 1). All grafts were patent.
PTP improves vein graft compliance by 3-fold. Treated grafts demonstrated a reduction in IH area by 68%, and decreased medial area by 44%. In this model, PTP effectively reduced vein graft IH. This therapy may lead to improved long-term patency rates of venous grafts used for extremity microsurgical reconstruction, coronary revascularization, peripheral arterial reconstruction, and vascular access for hemodialysis. The next step is to investigate the affect of PTP on long-term patency.
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