Pharmacologic relaxation of vein grafts is beneficial compared with pressure distention caused by upregulation of endothelial nitric oxide synthase and nitric oxide production

Abstract

Pharmacologic preparation of the vein grafts results in upregulation of endothelial nitric oxide synthase and increased nitric oxide production in the vein grafts after arterial implantation. This might provide greater clinical benefit than conventional pressure-distention methods.

In vivo human lower extremity saphenous vein bypass grafts manifest flow mediated vasodilation

“…(7; 8) This damage induces an inflammatory response within the vessel wall and has been shown to decrease the amount and function of endothelial nitric oxide synthase (eNOS) and endothelium-derived nitric oxide (NO), hence impairing normal homeostatic mechanisms of the vessel. (9–12) This injury has been implicated in early vein graft failure and thought to be permissive for the formation of myointimal hyperplasia. (12–14) Moreover, mature vein grafts may require endothelium-dependent vessel homeostasis for maturation and survival.…”

Arterialization of a vein graft promotes cell cycle progression through Akt and p38 mitogen-activated protein kinase pathways: Impact of the preparation procedure

“…A 6 cm segment of the dissected vein was grafted into the carotid artery as an interposition vein graft using an end-to-end anastomotic technique (Figure 1). Before grafting, a piece of the vein from the side randomly assigned to pharmacological relaxation (pharmacological preparation [PP]) was taken as the 'undistended' sample, and the rest was placed in a bath containing a combination of vasodilatatory drugs (alpha-adrenergic antagonist, phenoxybenzamine, at 10 μmol/L; Rho kinase inhibitor, HA-1077 [fasudil], at 50 μmol/L, and a calcium blocker, nicardipine, at 1 μmol/L) for 30 min (14,15). The vein from the other side was first exposed to distention with heparinized saline at a distention pressure of 300 mmHg for 2 min.…”

“…Glycogen synthase kinase 3 beta (GSK3β) is an intermediate in PI3K/Aktdependent proliferation (8,9) and the regulator of beta-catenin levels (12). The conventional preparation procedure, including pressure distention routinely used for overcoming vasospasm, is likely to enhance remodelling of the vein graft (13)(14)(15). This can be realized through Akt, MAPK and beta-catenin cascades, which are known to be activated by mechanical stimuli (9,16).…”

“…This can be realized through Akt, MAPK and beta-catenin cascades, which are known to be activated by mechanical stimuli (9,16). In previous studies (14,15), we have shown that the replacement of pressure distention with effective pharmacological vasodilators (alphaadrenergic antagonist, Rho kinase inhibitor and calcium blocker) prevents vasospasm, preserves endothelial function, and decreases matrix metalloproteinase activation and neointima formation in the vein graft, all of which should be beneficial for graft patency.…”

Strategies to prevent aortic complications in Marfan syndrome

“…Most subsequent studies confirmed a lower aorta dilation rate but only suggested a reduction in mortality (12). Moreover, no benefit was seen in patients with marked aorta dilation (13).…”