Background: Vein grafting is the final solution for occlusive vascular diseases. However, clinically the 10-year-patent rate is less than 60%. Intimal hyperplasia and subsequent accelerated atherosclerosis are major causes of vein graft failure. Methods: The inferior vena cava from the donor mouse was implanted into the right carotid artery of the recipient mouse, which was anaesthetized by sodium pentobarbital (60mg/kg body weight). Vein grafts were harvested at 1, 3, 7, 14 and 28 days after operation, and were fixed by 10% formalin for histology (H&E) and immunohistochemistry (eNOS and iNOS) study. Fresh vein grafts were also harvested at 28 days for vascular reactivity study using myograph technique. Circulating leukocytes were depleted by injection of anti-CD45/LCA antibody at the end of the 2nd week after surgery to investigate the influence of chronic inflammation and circulating leukocyte on neointima remodeling. Results: In the vein grafts, neointima was present at 1 week after operation, and was very thick by 4 weeks. The endothelium was denuded within 3 days after surgery. In days 1-3 there was intense inflammation, which resolved when endothelial cells re-grew reaching confluence 2 weeks after surgery (stained for anti-eNOS). There was positive staining for iNOS in neointima and endothelium at 2 and 4 weeks, associated with leukocyte adhesion. Vein grafts contracted and possessed endothelial-dependent relaxation, although much smaller than normal carotid artery. Relaxation to a nitric oxide donor was also reduced. Depletion of circulating leukocytes to 30% of normal level, with recovery to 70% within one week, had no effect on vein graft vasomotor function at 4 weeks. Conclusion: Injuries including surgical trauma and endothelial damage initiated an acute inflammation accompanied by a rapid formation of neointima. The intense inflammatory process produces a very thick neointima with abnormal expression of iNOS. The neointima is capable of contraction and relaxation though these processes are severely disrupted compared to normal artery. The remodeling process was not significantly affected by depletion of circulating leukocytes during the first few days.
Life Sciences 2007 (2007) Proc Life Sciences, PC380
Poster Communications: The role of nitric oxide and vascular function in vein graft failure
J. Wu1, R. M. Wadsworth1, S. Kennedy2
1. Institute of Pharmacy & Biomedical Sciences , University of Strathclyde, Glasgow, United Kingdom. 2. Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
View other abstracts by:
Where applicable, experiments conform with Society ethical requirements.