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
Cheung-Flynn, Joyce; Song, Jun; Voskresensky, Igor et al. (2017) Limiting Injury During Saphenous Vein Graft Preparation For Coronary Arterial Bypass Prevents Metabolic Decompensation. Sci Rep 7:14179
Komalavilas, Padmini; Luo, Weifeng; Guth, Christy M et al. (2017) Vascular surgical stretch injury leads to activation of P2X7 receptors and impaired endothelial function. PLoS One 12:e0188069
Luo, Weifeng; Feldman, Daniel; McCallister, Reid et al. (2017) P2X7R antagonism after subfailure overstretch injury of blood vessels reverses vasomotor dysfunction and prevents apoptosis. Purinergic Signal 13:579-590
Guth, Christy M; Luo, Weifung; Jolayemi, Olukemi et al. (2017) Adenosine triphosphate as a molecular mediator of the vascular response to injury. J Surg Res 216:80-86
Wise, Eric S; Hocking, Kyle M; Evans, Brian C et al. (2017) Unregulated saphenous vein graft distension decreases tissue viscoelasticity. Perfusion 32:489-494
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; 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 21:413-421
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
Osgood, Michael J; Sexton, Kevin; Voskresensky, Igor et al. (2016) Use of Brilliant Blue FCF during vein graft preparation inhibits intimal hyperplasia. J Vasc Surg 64:471-478
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

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