**5. Reperfusion injury**

Approximately 12% of patients experience thrombosis of saphenous vein grafts within 30 days of surgery [24]. It has been shown that this acute thrombosis is likely a combination of multiple factors including ischemia and hemostasis during coronary procedures which favors throm‐ bogenesis [25]. The ischemic period in which the vein has been harvested but not yet reimplanted into the myocardium, marks the beginning of the cascade to possible thrombosis. Upon re-establishment of blood flow through the vein it has been shown that neutrophils in the oxygenated blood are attracted to the areas of endothelial injury [26]. This ischemiareperfusion results in a reduction in both basal and stimulated nitric oxide release, yet attenuates the vaso-relaxation responses to the agonist stimulators of endothelial nitric oxide acetylcholine and bradykinin. Together this impairs the release of nitric oxide and down regulates nitric oxide production after an ischemic event.

After the saphenous vein is harvested, the initial injury causes a decrease in nitric oxide due to the traumatic endothelial cell injury from manipulation and distention. Following the ischemic period and after implantation, nitric oxide synthesis will increase due to the reper‐ fusion. Re-implantation causes release of multiple growth factors, and cytokines that cause the migration and proliferation of vascular smooth muscle cells and formation of extracellular matrix into the intimal compartment of the vein graft. Once neutrophils are adherent they initiate further endothelial damage and activation of the coagulation cascade which can lead to thrombosis [1]. The release of nitric oxide at this time can limit neointimal hyperplasia by inhibiting this proliferation and promoting apoptosis [27].
