PRESERVATION OF ENDOTHELIAL DEPENDENT RELAXATION

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DESCRIPTION (provided by applicant): Cardiovascular diseases are the leading cause of morbidity and mortality in the United States and are responsible for one out of every five deaths. Coronary artery bypass grafting (CABG) is one of the most effective treatments for advanced coronary artery disease (CAD) and peripheral bypass grafting (PBG) for the treatment of limb salvage in peripheral vascular disease. The most common conduit used to bypass stenotic and occlusive atherosclerotic lesions is the saphenous vein. The saphenous vein (HSV) is harvested from the lower extremity and prepared for use as an arterial conduit. As such, the HSV represents an autologous transplanted "organ" and little attention has been directed at organ preservation of the HSV. The leading cause of HSV failure is the development of intimal hyperplasia, a response to injury. The hypothesis of this investigation is that reducing injury to the HSV during harvest and preparation will preserve endothelial function and the salutary effects of the endothelium (antithrombotic, anti-inflammatory, and growth-inhibitory effects on the smooth muscle). The specific aims of this investigation are to: #1: Optimize techniques to preserve HSV endothelial function during surgical harvest and preparation; and #2: Determine if optimizing endothelial function during preparation reduces the development of intimal hyperplasia. HSV represents a unique opportunity for intervention in that the vein represents an autologous transplant organ. While significant research effort has pursued myocardiac preservation (cardioplegia) during cardiac revascularization, very little attention has been given to preservation of the conduit used for the arterial reconstruction, the HSV. This work will enhance our understanding of the pathogenesis of vein graft failure, improve preservation of the vein graft during harvest and preparation, and modify surgeon behavior in terms of treating the conduit as a transplanted organ that requires careful preservation. The goal of this proposal is to develop approaches to enhance HSV functional cellular viability and demonstrate that these approaches ameliorate intimal hyperplasia. The potential impact of this proposal will enhance our understanding of the role of injury during current graft preparation techniques on the subsequent development of intimal hyperplasia. This proposal will also develop optimal vein preparation techniques that can be readily translated into the clinic. Future directions will determine if optimizing preservation techniques and endothelial function of HSV will improve clinical outcomes following CABG and peripheral bypass procedures. Preventing endothelial injury during harvest represents a simple, straight forward approach to reduce the morbidity, mortality, and costs associated with vein graft failure.