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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL070715-09A1
Application #
8630185
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Reid, Diane M
Project Start
2002-04-01
Project End
2017-12-18
Budget Start
2013-12-19
Budget End
2014-12-18
Support Year
9
Fiscal Year
2014
Total Cost
$352,125
Indirect Cost
$127,125
Name
Vanderbilt University Medical Center
Department
Surgery
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Boire, Timothy C; Balikov, Daniel A; Lee, Yunki et al. (2016) Biomaterial-Based Approaches to Address Vein Graft and Hemodialysis Access Failures. Macromol Rapid Commun 37:1860-1880
Hocking, Kyle M; Luo, Weifeng; Li, Fan Dong et al. (2016) Brilliant blue FCF is a nontoxic dye for saphenous vein graft marking that abrogates response to injury. J Vasc Surg 64:210-8
Wise, Eric S; Hocking, Kyle M; Luo, Weifeng et al. (2016) Traditional graft preparation decreases physiologic responses, diminishes viscoelasticity, and reduces cellular viability of the conduit: A porcine saphenous vein model. Vasc Med :
Hocking, Kyle M; Putumbaka, Gowthami; Wise, Eric S et al. (2016) Papaverine Prevents Vasospasm by Regulation of Myosin Light Chain Phosphorylation and Actin Polymerization in Human Saphenous Vein. PLoS One 11:e0154460
Wise, Eric S; Hocking, Kyle M; Eagle, Susan et al. (2015) Preservation solution impacts physiologic function and cellular viability of human saphenous vein graft. Surgery 158:537-46
Wise, Eric S; Hocking, Kyle M; Feldman, Daniel et al. (2015) An Optimized Preparation Technique for Saphenous Vein Graft. Am Surg 81:E274-6
Osgood, Michael J; Hocking, Kyle M; Voskresensky, Igor V et al. (2014) Surgical vein graft preparation promotes cellular dysfunction, oxidative stress, and intimal hyperplasia in human saphenous vein. J Vasc Surg 60:202-11
Li, Fan Dong; Eagle, Susan; Brophy, Colleen et al. (2014) Pressure control during preparation of saphenous veins. JAMA Surg 149:655-62
Voskresensky, Igor V; Wise, Eric S; Hocking, Kyle M et al. (2014) Brilliant blue FCF as an alternative dye for saphenous vein graft marking: effect on conduit function. JAMA Surg 149:1176-81
Harskamp, Ralf E; Alexander, John H; Schulte, Phillip J et al. (2014) Vein graft preservation solutions, patency, and outcomes after coronary artery bypass graft surgery: follow-up from the PREVENT IV randomized clinical trial. JAMA Surg 149:798-805

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