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J Thorac Cardiovasc Surg 2001;121:971-980
© 2001 The American Association for Thoracic Surgery
Cardiopulmonary Support and Physiology |
From the Department of Cardiothoracic Surgery,a Stanford University School of Medicine, Stanford, Calif; and Cellgate,b Sunnyvale, Calif.
Supported by the Roche Laboratories Surgical Scientist Scholarship from the American Society of Transplant Surgeons and the Ralph and Marian Falk Foundation for Cardiovascular Research.
Received for publication July 5, 2000. Revisions requested Sept 12, 2000; revisions received Oct 5, 2000. Accepted for publication Oct 26, 2000. Address for reprints: Robert C. Robbins, MD, Falk Research Building, 2nd Floor, Stanford University Medical School, Stanford, CA 94305-5247 (E-mail: robbins{at}leland.stanford.edu).
Objective: We sought to determine whether L-arginine polymer treatment of vein grafts enhances vascular production of nitric oxide and inhibits the development of neointimal hyperplasia.
Methods: External jugular veins of New Zealand White rabbits (n = 42) were harvested; treated intraluminally for 15 minutes with phosphate-buffered saline solution or L-arginine polymer 5, 7, or 9 at either 10 or 100 µmol/L; and then grafted into the contralateral carotid artery. Rabbits were killed after 28 days, and 5-µm sections of vessels were stained with hematoxylin and scored for intima/media ratio by using computerized morphometric analysis. Separate veins were treated in a similar fashion with biotinylated polymers and phosphate-buffered saline solution to assess for translocation efficiencies. Finally, vein segments pretreated with either phosphate-buffered saline solution or L-arginine polymers were cultured in Dulbecco's modified Eagle's medium containing lipopolysaccharide (100 µg/mL) and interferon 
(200 U/mL) for 48 hours before measuring nitric oxide levels by means of the Griess reaction.
Results: Biotinylated L-arginine polymers demonstrated a dose- and length-dependent uptake into intimal and medial cells of treated vessels. Nitric oxide levels were significantly higher in vein segments treated with 100 µmol/L of L-arginine polymer 9 compared with control segments. Finally, the intima/media ratio also reflected both length- and concentration-dependent inhibition of neointimal hyperplasia.
Conclusions: Arginine polymers of sufficient length and concentration were effective in increasing nitric oxide levels and reducing neointimal hyperplasia in this vein graft model.
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