Human greater saphenous vein (HSV) is the most commonly used conduit for coronary artery bypass grafting (CABG) and the most effective conduit for infrainguinal peripheral vascular bypass grafting (PVBG). However, the rate of vein graft failure remains high (45% at 1-11/2 years) and there is no current therapeutic approach that has yet been shown to reduce vein graft failure in humans. HSV is harvested from the extremity and "prepared" prior to implantation. During this process, surgeons typically manually stretch and distend the HSV, store the conduit in heparinized saline, and mark the vein to prevent twisting or kinking on implantation. These maneuvers cause significant injury to the cellular components of the conduit which leads to intimal hyperplasia and vein graft failure. HSV represents an autologous organ that is transplanted into the arterial circulation. Despite the many advances in organ preservation, the current techniques used to prepare and preserve HSV do not adequately protect the transplanted vein. The hypothesis of this proposal is that injury to the cellular components of HSV during preparation lead to intimal hyperplasia and vein graft failure. The corollary to this hypothesis is that minimizing injury at the time of surgical preparation will impact subsequent vein graft patency. This proposal will develop elegantly simple approaches to prevent injury during graft preparation as well as promote our understanding of the processes that lead to vein graft intimal hyperplasia. The potential impact of this proposal is to develop optimal vein preparation techniques that can be readily translated into the clinic thus reducing the morbidity, mortality, and costs associated with vein graft failure.
Human saphenous vein graft is the most widely used conduit for coronary artery bypass grafting and peripheral vascular bypass grafting procedures. This proposal will identify approaches to ameliorate injuries that occur to the vein graft during surgical preparation and prior to implantation as an autologous transplanted organ and promote our understanding of processes that lead to vein graft intimal hyperplasia. Reducing injury will lead to a reduction in vein graft failure and minimize costly re-operation, myocardial infarction, limb loss, and death.
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|Li, Fan Dong; Sexton, Kevin W; Hocking, Kyle M et al. (2013) Intimal thickness associated with endothelial dysfunction in human vein grafts. J Surg Res 180:e55-62|
|Muto, Akihito; Panitch, Alyssa; Kim, Namho et al. (2012) Inhibition of Mitogen Activated Protein Kinase Activated Protein Kinase II with MMI-0100 reduces intimal hyperplasia ex vivo and in vivo. Vascul Pharmacol 56:47-55|
|Hocking, Kyle M; Brophy, Colleen; Rizvi, Syed Z et al. (2011) Detrimental effects of mechanical stretch on smooth muscle function in saphenous veins. J Vasc Surg 53:454-60|
|Eagle, Susan; Brophy, Colleen M; Komalavilas, Padmini et al. (2011) Surgical skin markers impair human saphenous vein graft smooth muscle and endothelial function. Am Surg 77:922-8|
|Lopes, Luciana B; Brophy, Colleen M; Flynn, Charles R et al. (2010) A novel cell permeant peptide inhibitor of MAPKAP kinase II inhibits intimal hyperplasia in a human saphenous vein organ culture model. J Vasc Surg 52:1596-607|
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