Controlling transplant vasculopathy in cryopreserved vein grafts with polyethylene glycol and glutathione during transport

Background: the biological characteristics of cryopreserved allografts are poorly understood, although many factors are known to influence their outcome. This study examines the development of transplant vasculopathy in both fresh and cryopreserved vein allografts and specifically assesses the efficacy of a transport solution containing 10% polyethylene glycol and 10 μM glutathione (PEG/GSH). Methods: jugular veins were harvested from control donor rabbits and transplanted as interposition carotid bypass grafts in 30 New Zealand White (NZW) rabbits. Ten received the fresh jugular veins (fresh). Ten animals received jugular veins which had been harvested, transported in a physiological solution, cryopreserved and stored in a standard fashion (cryopreserved). Ten animals received jugular veins which had been harvested, transported in the same solution with the addition of PEG/GSH, cryopreserved and stored in a standard fashion (PEG/GSH). Cryopreserved jugular veins were stored for 6 weeks before transplantation. All animals were sacrificed 28 days postoperatively. Vein grafts were perfusion-fixed and wall dimensions were determined by planimetry. Results: all transplanted grafts were patent at harvest. The control cryopreserved vein grafts showed a 54% increase in mean intimal thickness (63 ± 10 μm vs. 41 ± 3 μm; p < 0.05) but no change in mean medial thickness (125 ± 9 μm vs. 119 ± 13 μm; p = N.S.) compared to the fresh allograft. Transport of the grafts in PEG/GSH solution resulted in the abolition of the increase in intimal thickness (41 ± 4 μm; p < 0.01) associated with cryopreservation without a change in medial thickness (140 ± 15 μm; p = N.S.) compared to the cryopreserved allograft. Conclusion: cryopreserved vein grafts develop significant intimal hyperplasia compared to freshly transplanted grafts. The use of PEG/GSH in the transport solution significantly reduces this transplant graft intimal hyperplasia to that which develops in fresh grafts and may lead to improvements in the clinical use of cryopreserved veins.