Biomechanics and Mechanobiology of Saphenous Vein Grafts

Abstract

Within several weeks of use as coronary artery bypass grafts (CABG), saphenous veins (SV) exhibit significant intimal hyperplasia (IH). IH predisposes vessels to thrombosis and atherosclerosis, the two major modes of vein graft failure. The fact that SV do not develop significant IH in their native venous environment coupled with the rapidity with which they develop IH following grafting into the arterial circulation suggests that factors associated with the isolation and preparation of SV and/or differences between the venous and arterial environments contribute to disease progression. There is strong evidence suggesting that mechanical trauma associated with traditional techniques of SV preparation can significantly damage the vessel and might potentially reduce graft patency though modern surgical techniques reduces these injuries. In contrast, it seems possible that modern surgical technique, specifically endoscopic vein harvest, might introduce other mechanical trauma that could subtly injure the vein and perhaps contribute to the reduced patency observed in veins harvested using endoscopic techniques. Aspects of the arterial mechanical environment influence remodeling of SV grafted into the arterial circulation. Increased pressure likely leads to thickening of the medial wall but its role in IH is less clear. Changes in fluid flow, including increased average wall shear stress, may reduce IH while disturbed flow likely increase IH. Nonmechanical stimuli, such as exposure to arterial levels of oxygen, may also have a significant but not widely recognized role in IH. Several potentially promising approaches to alter the mechanical environment to improve graft patency are including extravascular supports or altered graft geometries are covered.

The Role of Immunomodulation in Vein Graft Remodeling and Failure

“…This change in shear stress declines the production of growth inhibitors that protect the vascular wall from vasoactive substances derived from platelets-promoting thrombosis [16]. Moreover, reduced shear stress increases the production of different mitogens that promote VSMC proliferation-leading to IH [17]. Distension of the graft upregulates the expression of endothelial adhesion molecules (ICAM-1, VCAM-1, PECAM, P-Selectin) and inflammatory markers (interleukin (IL)-1, MCP-1, and TNFα via the activation of the NF-κB pathway), triggering the influx of immune cells-ultimately promoting atherosclerosis [18,19].…”

Atorvastatina Reduz o Acúmulo de Células Musculares Lisas Vasculares para Inibir a Hiperplasia Intimal pela Inibição de Via p38 MAPK em um Modelo de Enxerto de Veia em Ratos

“…A proliferação, migração e secreção de células endoteliais e de CMLVs são cruciais à HI, causa principal da reestenose. 20 Em um estudo prévio, demonstramos que a p38 MAPK é fosforilada em um modelo de enxerto venoso arterializado em ratos, seguido pela ativação da resposta imune inata (inflamação), e um inibidor de p38 MAPK seria capaz de reduzir a proliferação celular induzida por arterialização e diminuir a resposta inflamatória precoce que segue a injúria vascular. 19 Portanto, testamos a expressão de α-SMA, PCNA, p38 MAPK e fosforilação de p38 MAPK após o tratamento com estatina e os resultados mostraram que a atorvastatina não reduziu o nível de p38 MAPK significativamente (p > 0,05).…”

Effects of Braiding Parameters on Tissue Engineered Vascular Graft Development

“…Coronary and peripheral bypass procedures commonly utilize autologous vascular grafts, which have demonstrated 10 year patencies of 60-90% depending on the procedure and the vessel used. [1][2][3] However, about one-third of patients lack suitable autologous vessels due to pre-existing conditions or previous operations. [4,5] Tissue engineered vascular grafts (TEVGs) offer a unique solution, allowing fabrication of off-the-shelf vascular conduits that can develop into functional blood vessels within the body.…”