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bioRxiv · 10.1101/2023.08.25.554690

Preserving endothelial integrity in human saphenous veins during preparation for coronary bypass surgery

Sedovy, M. W.·Leng, X.·Iqbal, F.·Renton, M. C.·Leaf, M.·Roberts, K.·Malek, A.·Arnold, W. S.·Wyatt, D. A.·Choate, C. W.·Rowe, J. F.·Baker, J. W.·Johnstone, S. R.·Joseph, M.
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Abstract

ObjectiveWhile multiple factors influence coronary artery bypass graft success rates, preserving saphenous vein endothelium during surgery may improve patency. Standard methods of saphenous vein graft preparation in heparinized saline (saline) solutions result in endothelial loss and damage. Here we investigated the impact of preparing saphenous graft vessels in heparinized patient blood (blood) vs saline on cellular health and survival. MethodsSaphenous vein tissues from a total of 23 patients undergoing coronary artery bypass graft surgery were split into 2 treatment groups, 1) standard preparation using saline and 2) preparation using blood. Immediately following surgery, excess tissue was fixed for analysis. Level of endothelial coverage, oxidative stress marker 4-hydroxynonenal (4HNE), and oxidative stress protective marker nuclear factor erythroid 2-related factor 2 (NRF2) expression were evaluated. ResultsIn saline patient veins, histological analysis revealed a broken or absent luminal layer, suggesting a loss of endothelial cell (EC) coverage. Luminal cell coverage was notably preserved in blood-treated samples. Immunofluorescent staining of endothelial markers vascular endothelial cadherin (VE-cadherin) and endothelial nitric oxide (eNOS) identified a significant improvement in endothelial coverage in the blood group compared to saline. Although in both treatment groups EC expressed 4HNE indicating a similar level of oxidative stress, EC stored in blood solutions expressed higher levels of the protective transcription NRF2. ConclusionsOur data indicate that maintaining and preparing saphenous vein tissues in solutions containing heparinized blood helps preserve the endothelium and promotes vein graft health. This has the potential to improve long-term outcomes in patients. Central MessageDuring coronary artery bypass grafting, preparation of saphenous veins with heparinized saline damages the endothelium and increases oxidative stress. Heparinized blood preparation limits this endothelial loss and damage. Perspectives StatementSaphenous vein grafts are prone to failure through neointimal hyperplasia or thrombosis. Endothelial damage and loss are thought to be major contributing factors to graft failure. Here we find that preparation and preservation of saphenous vein grafts with patients own heparinized blood is sufficient to ensure endothelial preservation and protect vessels from oxidative stress compared with heparinized saline. These changes may increase long-term graft patency rates.

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Sedovy, M. W., Leng, X., Iqbal, F., Renton, M. C., Leaf, M., Roberts, K., Malek, A., Arnold, W. S., Wyatt, D. A., Choate, C. W., Rowe, J. F., Baker, J. W., Johnstone, S. R., Joseph, M.. 2023-08-27. Preserving endothelial integrity in human saphenous veins during preparation for coronary bypass surgery. https://doi.org/10.1101/2023.08.25.554690

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