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Chapter 3
Oral Heparin Prevents Neointimal Growth Following Vascular Injury: Implications for Potential Clinical Use 1
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Frederick G. P. Welt , T. Cooper Woods , and Elazer R. Edelman
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Division of Health Sciences and Technology, Harvard-MIT, 77 Massachusetts Avenue, Cambridge, MA 02139 Department of Genomics, Emisphere Technologies, Inc., 765 Old Saw Mill River Road, Tarrytown, NY 10591 Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115
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Background: Heparin is the archetypical modulator of vascular repair following arterial injury in animal models. In these models, heparin delivered either as a continuous intravenous infusion or via frequent subcutaneous dosing, inhibits neointimal hyperplasia after either balloon injury or stent implantation. However, use of subcutaneous heparin following human percutaneous intervention has failed to prevent restenosis. It may be that these failures arise from a need for more frequent dosing regimens in man. Recently, the drug delivery agent Sodium N-caprylate (SNAC) has been found to facilitate gastric absorption of heparin raising the possibility of convenient frequent dosing. Methods and Results: To investigate the effects of orally delivered heparin on neointimal hyperplasia following varying forms of arterial injury, New Zealand White rabbits underwent iliac artery balloon dilatation. In half of the animals, endovascular stents were implanted and heparin delivered through different methods. Arteries were harvested at 14 days and neointimal area was assessed using computer-aided morphometry. Following balloon injury, both intravenous (0.3 mg/kg/hr) and
© 2003 American Chemical Society
Dinh and Liu; Advances in Controlled Drug Delivery ACS Symposium Series; American Chemical Society: Washington, DC, 2003.
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34 oral heparin (90 mg/kg BID) inhibited neointimal growth (0.11±0.02 and 0.09±0.07 mm respectively vs. control 0.16±0.06 mm , p
