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. 1991 Sep;139(3):581–587.

Inhibition of vein graft intimal proliferative lesions in the rat by heparin.

G M Hirsch 1, M J Karnovsky 1
PMCID: PMC1886235  PMID: 1887863

Abstract

The authors investigated the effect of heparin on the development of myointimal proliferative lesions in a rat vein graft model. Intimal thickening in this model was most pronounced in the anastomotic regions, and was composed principally of vascular smooth muscle cells, as identified by immunocytochemistry with anti-muscle actin antibody, HHF-35. Medial thickening was less cellular, and evenly distributed throughout the grafts. Continuous, intravenous infusion of whole heparin at 0.3 mg/kg/hr effectively inhibited the development of myointimal proliferative lesions, although with no effect on medial thickening. The authors suggest that heparin, through its antiproliferative activity for vascular smooth muscle cells, may have a potentially important pharmacologic role in preventing vein graft failure, which most commonly results from the development of myointimal proliferative lesions.

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Selected References

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  1. Abbott W. M., Megerman J., Hasson J. E., L'Italien G., Warnock D. F. Effect of compliance mismatch on vascular graft patency. J Vasc Surg. 1987 Feb;5(2):376–382. [PubMed] [Google Scholar]
  2. Atkinson J. B., Forman M. B., Vaughn W. K., Robinowitz M., McAllister H. A., Virmani R. Morphologic changes in long-term saphenous vein bypass grafts. Chest. 1985 Sep;88(3):341–348. doi: 10.1378/chest.88.3.341. [DOI] [PubMed] [Google Scholar]
  3. Berguer R., Higgins R. F., Reddy D. J. Intimal hyperplasia. An experimental study. Arch Surg. 1980 Mar;115(3):332–335. doi: 10.1001/archsurg.1980.01380030078019. [DOI] [PubMed] [Google Scholar]
  4. Bulkley B. H., Hutchins G. M. Pathology of coronary artery bypass graft surgery. Arch Pathol Lab Med. 1978 Jun;102(6):273–280. [PubMed] [Google Scholar]
  5. Carson S. N., Esquivel C. O., French S. W. Experimental carotid stenosis due to fibrous intimal hyperplasia. Surg Gynecol Obstet. 1981 Dec;153(6):883–888. [PubMed] [Google Scholar]
  6. Castellot J. J., Jr, Hoover R. L., Harper P. A., Karnovsky M. J. Heparin and glomerular epithelial cell-secreted heparin-like species inhibit mesangial-cell proliferation. Am J Pathol. 1985 Sep;120(3):427–435. [PMC free article] [PubMed] [Google Scholar]
  7. Castellot J. J., Jr, Wright T. C., Karnovsky M. J. Regulation of vascular smooth muscle cell growth by heparin and heparan sulfates. Semin Thromb Hemost. 1987 Oct;13(4):489–503. doi: 10.1055/s-2007-1003525. [DOI] [PubMed] [Google Scholar]
  8. Clowes A. W., Clowes M. M. Kinetics of cellular proliferation after arterial injury. II. Inhibition of smooth muscle growth by heparin. Lab Invest. 1985 Jun;52(6):611–616. [PubMed] [Google Scholar]
  9. Clowes A. W., Karnowsky M. J. Suppression by heparin of smooth muscle cell proliferation in injured arteries. Nature. 1977 Feb 17;265(5595):625–626. doi: 10.1038/265625a0. [DOI] [PubMed] [Google Scholar]
  10. Ernst C. B., Rutkow I. M., Cleveland R. J., Folse J. R., Johnson G., Jr, Stanley J. C. Vascular surgery in the United States. Report of the Joint Society for Vascular Surgery--International Society for Cardiovascular Surgery Committee on Vascular Surgical Manpower. J Vasc Surg. 1987 Dec;6(6):611–621. [PubMed] [Google Scholar]
  11. Guyton J. R., Rosenberg R. D., Clowes A. W., Karnovsky M. J. Inhibition of rat arterial smooth muscle cell proliferation by heparin. In vivo studies with anticoagulant and nonanticoagulant heparin. Circ Res. 1980 May;46(5):625–634. doi: 10.1161/01.res.46.5.625. [DOI] [PubMed] [Google Scholar]
  12. Imparato A. M., Bracco A., Kim G. E., Zeff R. Intimal and neointimal fibrous proliferation causing failure of arterial reconstructions. Surgery. 1972 Dec;72(6):1007–1017. [PubMed] [Google Scholar]
  13. Kern W. H., Dermer G. B., Lindesmith G. G. The intimal proliferation in aortic-coronary saphenous vein grafts. Light and electron microscopic studies. Am Heart J. 1972 Dec;84(6):771–777. doi: 10.1016/0002-8703(72)90070-1. [DOI] [PubMed] [Google Scholar]
  14. Kohler T. R., Kirkman T., Clowes A. W. Effect of heparin on adaptation of vein grafts to arterial circulation. Arteriosclerosis. 1989 Jul-Aug;9(4):523–528. doi: 10.1161/01.atv.9.4.523. [DOI] [PubMed] [Google Scholar]
  15. Loop F. D., Wilcox B. R., Cunningham J. N., Jr, Fosburg R. G., Geha A. S., Laks H., Mark J. B., Badhwar K., Williams G. W. Thoracic surgery manpower: the fourth manpower study of thoracic surgery: 1985 report of the Ad Hoc Committee on Manpower of The American Association for Thoracic Surgery and The Society of Thoracic Surgeons. Ann Thorac Surg. 1987 Nov;44(5):450–461. doi: 10.1016/s0003-4975(10)62101-7. [DOI] [PubMed] [Google Scholar]
  16. Owens G. K., Schwartz S. M. Alterations in vascular smooth muscle mass in the spontaneously hypertensive rat. Role of cellular hypertrophy, hyperploidy, and hyperplasia. Circ Res. 1982 Sep;51(3):280–289. doi: 10.1161/01.res.51.3.280. [DOI] [PubMed] [Google Scholar]
  17. Somogyi P., Takagi H. A note on the use of picric acid-paraformaldehyde-glutaraldehyde fixative for correlated light and electron microscopic immunocytochemistry. Neuroscience. 1982 Jul;7(7):1779–1783. doi: 10.1016/0306-4522(82)90035-5. [DOI] [PubMed] [Google Scholar]
  18. Szilagyi D. E., Elliott J. P., Hageman J. H., Smith R. F., Dall'olmo C. A. Biologic fate of autogenous vein implants as arterial substitutes: clinical, angiographic and histopathologic observations in femoro-popliteal operations for atherosclerosis. Ann Surg. 1973 Sep;178(3):232–246. doi: 10.1097/00000658-197309000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Vlodaver Z., Edwards J. E. Pathologic changes in aortic-coronary arterial saphenous vein grafts. Circulation. 1971 Oct;44(4):719–728. doi: 10.1161/01.cir.44.4.719. [DOI] [PubMed] [Google Scholar]
  20. Whittemore A. D., Clowes A. W., Couch N. P., Mannick J. A. Secondary femoropopliteal reconstruction. Ann Surg. 1981 Jan;193(1):35–42. doi: 10.1097/00000658-198101000-00006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Wright T. C., Jr, Johnstone T. V., Castellot J. J., Karnovsky M. J. Inhibition of rat cervical epithelial cell growth by heparin and its reversal by EGF. J Cell Physiol. 1985 Dec;125(3):499–506. doi: 10.1002/jcp.1041250320. [DOI] [PubMed] [Google Scholar]
  22. Zwolak R. M., Adams M. C., Clowes A. W. Kinetics of vein graft hyperplasia: association with tangential stress. J Vasc Surg. 1987 Jan;5(1):126–136. [PubMed] [Google Scholar]

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