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Semin Vasc Med 2004; 4(2): 153-159
DOI: 10.1055/s-2004-835373
Copyright © 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001 USA.

Cardiac Saphenous Vein Bypass Graft Disease

G. T. Lau1 , 2 , H. C. Lowe1 , 2 , 3 , L. Kritharides1 , 2 , 3
  • 1Department of Cardiology, Concord Repatriation General Hospital, Hospital Rd, Concord, NSW 2139
  • 2Vascular Biology Laboratory, ANZAC Research Institute, University of Sydney, Concord, NSW 2139
  • 3Centre for Vascular Research, University of New South Wales, Randwick, NSW 2052, Australia
Further Information

Publication History

Publication Date:
11 October 2004 (online)

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Coronary artery bypass grafting is an effective treatment for myocardial ischaemia and is particularly important in patients with multivessel disease and diabetes. However, up to 40% of saphenous vein grafts will occlude within 10 years of surgery. The predominant mechanisms for saphenous vein graft disease are thrombosis, intimal hyperplasia, and accelerated atherosclerosis. The pathology of these changes and the role of key factors such as nitric oxide, cellular proliferation, and the role of hypercholesterolemia and hypertriglyceridaemia, are reviewed. Saphenous vein graft disease is among the first cardiovascular conditions to show significant benefit from gene therapy and promises to show remarkable developments in the near future.

KEYWORDS

Coronary artery bypass grafting - saphenous vein grafts - intimal hyperplasia - hyperlipidaemia

REFERENCES

  • 1 Favaloro R G. Critical analysis of coronary artery bypass graft surgery: a 30-year journey.  J Am Coll Cardiol. 1998;  31(4 suppl B) 1B-63B
    CrossrefPubMedGoogle Scholar
  • 2 Possati G, Gaudino M, Prati F et al.. Long-term results of the radial artery used for myocardial revascularization.  Circulation. 2003;  108(11) 1350-1354
    CrossrefPubMedGoogle Scholar
  • 3 The Bypass Angioplasty Revascularization Investigation (BARI) Investigators . Comparison of coronary bypass surgery with angioplasty in patients with multivessel disease.  N Engl J Med. 1996;  335 217-225
    CrossrefPubMedGoogle Scholar
  • 4 RITA Trial Group. Coronary angioplasty versus coronary artery bypass surgery: the Randomized Intervention Treatment of Angina (RITA) trial.  Lancet. 1993;  341(8845) 573-580
    CrossrefPubMedGoogle Scholar
  • 5 Morris J J, Smith L R, Jones R H et al.. Influence of diabetes and mammary artery grafting on survival after coronary bypass.  Circulation. 1991;  84(5 suppl) III275-III284
    PubMedGoogle Scholar
  • 6 Motwani J G, Topol E J. Aortocoronary saphenous vein graft disease: pathogenesis, predisposition, and prevention.  Circulation. 1998;  97(9) 916-931
    CrossrefPubMedGoogle Scholar
  • 7 Safian R D. Accelerated atherosclerosis in saphenous vein bypass grafts: a spectrum of diffuse plaque instability.  Prog Cardiovasc Dis. 2002;  44(6) 437-448
    PubMedGoogle Scholar
  • 8 Landymore R W, MacAulay M A, Fris J. Effect of aspirin on intimal proliferation and tissue cholesterol in long-term experimental bypass grafts.  Eur J Cardiothorac Surg. 1992;  6(8) 422-426
    CrossrefPubMedGoogle Scholar
  • 9 Batayias G E, Barboriak J J, Korns M E, Pintar K. The spectrum of pathologic changes in aortocoronary saphenous vein grafts.  Circulation. 1977;  56(3 Suppl) II18-II22
    PubMedGoogle Scholar
  • 10 Moor E, Hamsten A, Blomback M, Herzfeld I, Wiman B, Ryden L. Haemostatic factors and inhibitors and coronary artery bypass grafting: preoperative alterations and relations to graft occlusion.  Thromb Haemost. 1994;  72(3) 335-342
    PubMedGoogle Scholar
  • 11 Boisclair M D, Lane D A, Philippou H et al.. Mechanisms of thrombin generation during surgery and cardiopulmonary bypass.  Blood. 1993;  82(11) 3350-3357
    PubMedGoogle Scholar
  • 12 Golledge J, Gosling M, Turner R J, Standfield N J, Powell J T. Arterial flow induces changes in saphenous vein endothelium proteins transduced by cation channels.  Eur J Vasc Endovasc Surg. 2000;  19(5) 545-550
    CrossrefPubMedGoogle Scholar
  • 13 Golledge J, Turner R J, Gosling M, Powell J T. Rapid changes in the coagulant proteins on saphenous vein endothelium in response to arterial flow.  Angiology. 1999;  50(9) 693-701
    PubMedGoogle Scholar
  • 14 Tsui J C, Souza D S, Filbey D, Bomfim V, Dashwood M R. Preserved endothelial integrity and nitric oxide synthase in saphenous vein grafts harvested by a ‘no-touch’ technique.  Br J Surg. 2001;  88(9) 1209-1215
    CrossrefPubMedGoogle Scholar
  • 15 Marx N, Neumann F J, Zohlnhofer D et al.. Enhancement of monocyte procoagulant activity by adhesion on vascular smooth muscle cells and intercellular adhesion molecule-1-transfected Chinese hamster ovary cells.  Circulation. 1998;  98(9) 906-911
    PubMedGoogle Scholar
  • 16 Yamada T, Itoh T, Nakano S, Tokunaga O. Time-dependent thickening of the intima in aortocoronary saphenous vein grafts: clinicopathological analysis of 24 patients.  Heart Vessels. 1995;  10(1) 41-45
    CrossrefPubMedGoogle Scholar
  • 17 Hozumi T, Yoshikawa J, Yoshida K et al.. Use of intravascular ultrasound for in vivo assessment of changes in intimal thickness of angiographically normal saphenous vein grafts one year after aortocoronary bypass surgery.  Heart. 1996;  76(4) 317-320
    PubMedGoogle Scholar
  • 18 Willard J E, Netto D, Demian S E et al.. Intravascular ultrasound imaging of saphenous vein grafts in vitro: comparison with histologic and quantitative angiographic findings.  J Am Coll Cardiol. 1992;  19(4) 759-764
    PubMedGoogle Scholar
  • 19 Marin M L, Veith F J, Panetta T F et al.. Saphenous vein biopsy: a predictor of vein graft failure.  J Vasc Surg. 1993;  18(3) 407-414
    PubMedGoogle Scholar
  • 20 Campbell G R, Campbell J H. The phenotypes of smooth muscle expressed in human atheroma.  Ann N Y Acad Sci. 1990;  598 143-158
    PubMedGoogle Scholar
  • 21 Amano J, Suzuki A, Sunamori M, Tsukada T, Numano F. Cytokinetic study of aortocoronary bypass vein grafts in place for less than six months.  Am J Cardiol. 1991;  67(15) 1234-1236
    CrossrefPubMedGoogle Scholar
  • 22 Mehta D, George S J, Jeremy J Y et al.. External stenting reduces long-term medial and neointimal thickening and platelet derived growth factor expression in a pig model of arteriovenous bypass grafting.  Nat Med. 1998;  4(2) 235-239
    PubMedGoogle Scholar
  • 23 Tanner F C, Boehm M, Akyurek L M et al.. Differential effects of the cyclin-dependent kinase inhibitors p27(Kip1), p21(Cip1), and p16(Ink4) on vascular smooth muscle cell proliferation.  Circulation. 2000;  101(17) 2022-2025
    PubMedGoogle Scholar
  • 24 Crook M F, Akyurek L M. Gene transfer strategies to inhibit neointima formation.  Trends Cardiovasc Med. 2003;  13(3) 102-106
    CrossrefPubMedGoogle Scholar
  • 25 Tanner F C, Meier P, Greutert H, Champion C, Nabel E G, Luscher T F. Nitric oxide modulates expression of cell cycle regulatory proteins: a cytostatic strategy for inhibition of human vascular smooth muscle cell proliferation.  Circulation. 2000;  101(16) 1982-1989
    PubMedGoogle Scholar
  • 26 Salvemini D, Radziszewski W, Korbut R, Vane J. The use of oxyhaemoglobin to explore the events underlying inhibition of platelet aggregation induced by NO or NO-donors.  Br J Pharmacol. 1990;  101(4) 991-995
    PubMedGoogle Scholar
  • 27 Lefer A M. Role of selectins in myocardial ischemia-reperfusion injury.  Ann Thorac Surg. 1995;  60(3) 773-777
    CrossrefPubMedGoogle Scholar
  • 28 Lefer A M, Tsao P S, Lefer D J, Ma X L. Role of endothelial dysfunction in the pathogenesis of reperfusion injury after myocardial ischemia.  FASEB J. 1991;  5(7) 2029-2034
    PubMedGoogle Scholar
  • 29 Sarkar R, Meinberg E G, Stanley J C, Gordon D, Webb R C. Nitric oxide reversibly inhibits the migration of cultured vascular smooth muscle cells.  Circ Res. 1996;  78(2) 225-230
    PubMedGoogle Scholar
  • 30 Best P J, Hasdai D, Sangiorgi G et al.. Apoptosis. Basic concepts and implications in coronary artery disease.  Arterioscler Thromb Vasc Biol. 1999;  19(1) 14-22
    PubMedGoogle Scholar
  • 31 Guo J P, Murohara T, Buerke M, Scalia R, Lefer A M. Direct measurement of nitric oxide release from vascular endothelial cells.  J Appl Physiol. 1996;  81(2) 774-779
    PubMedGoogle Scholar
  • 32 Dignan R J, Dyke C M, Abd-Elfattah A S et al.. Coronary artery endothelial cell and smooth muscle dysfunction after global myocardial ischemia.  Ann Thorac Surg. 1992;  53(2) 311-317
    PubMedGoogle Scholar
  • 33 Nakanishi K, Zhao Z Q, Vinten-Johansen J, Lewis J C, McGee D S, Hammon Jr J W. Coronary artery endothelial dysfunction after global ischemia, blood cardioplegia, and reperfusion.  Ann Thorac Surg. 1994;  58(1) 191-199
    PubMedGoogle Scholar
  • 34 Kown M H, Yamaguchi A, Jahncke C L et al.. L-arginine polymers inhibit the development of vein graft neointimal hyperplasia.  J Thorac Cardiovasc Surg. 2001;  121(5) 971-980
    CrossrefPubMedGoogle Scholar
  • 35 Asahara T, Bauters C, Pastore C et al.. Local delivery of vascular endothelial growth factor accelerates reendothelialization and attenuates intimal hyperplasia in balloon-injured rat carotid artery.  Circulation. 1995;  91(11) 2793-2801
    PubMedGoogle Scholar
  • 36 Grotendorst G R, Soma Y, Takehara K, Charette M. EGF and TGF-alpha are potent chemoattractants for endothelial cells and EGF-like peptides are present at sites of tissue regeneration.  J Cell Physiol. 1989;  139(3) 617-623
    CrossrefPubMedGoogle Scholar
  • 37 Kalmes A, Daum G, Clowes A W. EGFR transactivation in the regulation of SMC function.  Ann N Y Acad Sci. 2001;  947 42-54
    PubMedGoogle Scholar
  • 38 Lindner V, Reidy M A. Platelet-derived growth factor ligand and receptor expression by large vessel endothelium in vivo.  Am J Pathol. 1995;  146(6) 1488-1497
    PubMedGoogle Scholar
  • 39 Banai S, Wolf Y, Golomb G et al.. PDGF-receptor tyrosine kinase blocker AG1295 selectively attenuates smooth muscle cell growth in vitro and reduces neointimal formation after balloon angioplasty in swine.  Circulation. 1998;  97 1960-1969
    PubMedGoogle Scholar
  • 40 Lindner V, Lappi D A, Baird A, Majack R A, Reidy M A. Role of basic fibroblast growth factor in vascular lesion formation.  Circ Res. 1991;  68(1) 106-113
    PubMedGoogle Scholar
  • 41 Lowe H C, Chesterman C N, Hopkins A P, Juergens C P, Khachigian L M. Acute local release of fibroblast growth factor-2 but not transforming growth factor-beta1 following coronary stenting.  Thromb Haemost. 2001;  85(3) 574-576
    PubMedGoogle Scholar
  • 42 Lindner V. Role of basic fibroblast growth factor and platelet-derived growth factor (B-chain) in neointima formation after arterial injury.  Z Kardiol. 1995;  (84 Suppl 4) 137-144
    PubMedGoogle Scholar
  • 43 Lindner V, Reidy M A. Expression of basic fibroblast growth factor and its receptor by smooth muscle cells and endothelium in injured rat arteries. An en face study.  Circ Res. 1993;  73(3) 589-595
    PubMedGoogle Scholar
  • 44 Lindner V, Reidy M A. Proliferation of smooth muscle cells after vascular injury is inhibited by an antibody against basic fibroblast growth factor.  Proc Natl Acad Sci USA. 1991;  88(9) 3739-3743
    PubMedGoogle Scholar
  • 45 Neschis D G, Safford S D, Hanna A K, Fox J C, Golden M A. Antisense basic fibroblast growth factor gene transfer reduces early intimal thickening in a rabbit femoral artery balloon injury model.  J Vasc Surg. 1998;  27(1) 126-134
    PubMedGoogle Scholar
  • 46 Khachigian L M, Collins T. Inducible expression of Egr-1-dependent genes. A paradigm of transcriptional activation in vascular endothelium.  Circ Res. 1997;  81(4) 457-461
    PubMedGoogle Scholar
  • 47 Santiago F S, Lowe H C, Kavurma M M et al.. New DNA enzyme targeting Egr-1 mRNA inhibits vascular smooth muscle proliferation and regrowth after injury.  Nat Med. 1999;  5(12) 1438
    PubMedGoogle Scholar
  • 48 Lowe H C, Fahmy R G, Kavurma M M, Baker A, Chesterman C N, Khachigian L M. Catalytic oligodeoxynucleotides define a key regulatory role for early growth response factor-1 in the porcine model of coronary in-stent restenosis.  Circ Res. 2001;  89(8) 670-677
    PubMedGoogle Scholar
  • 49 Bjorkerud S. Effects of transforming growth factor-beta 1 on human arterial smooth muscle cells in vitro.  Arterioscler Thromb. 1991;  11(4) 892-902
    PubMedGoogle Scholar
  • 50 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;  88(3) 341-348
    PubMedGoogle Scholar
  • 51 Newby A C. Molecular and cell biology of native coronary and vein-graft atherosclerosis: regulation of plaque stability and vessel-wall remodelling by growth factors and cell-extracellular matrix interactions.  Coron Artery Dis. 1997;  8(3-4) 213-224
    PubMedGoogle Scholar
  • 52 Hong M K, Mintz G S, Hong M K et al.. Intravascular ultrasound assessment of the presence of vascular remodeling in diseased human saphenous vein bypass grafts.  Am J Cardiol. 1999;  84(9) 992-998
    CrossrefPubMedGoogle Scholar
  • 53 Shuhaiber J H, Evans A N, Massad M G, Geha A S. Mechanisms and future directions for prevention of vein graft failure in coronary bypass surgery.  Eur J Cardiothorac Surg. 2002;  22(3) 387-396
    CrossrefPubMedGoogle Scholar
  • 54 Porter K E, Loftus I M, Peterson M, Bell P R, London N J, Thompson M M. Marimastat inhibits neointimal thickening in a model of human vein graft stenosis.  Br J Surg. 1998;  85(10) 1373-1377
    CrossrefPubMedGoogle Scholar
  • 55 Elices M J, Osborn L, Takada Y et al.. VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site.  Cell. 1990;  60(4) 577-584
    CrossrefPubMedGoogle Scholar
  • 56 Bevilacqua M P. Endothelial-leukocyte adhesion molecules.  Annu Rev Immunol. 1993;  11 767-804
    CrossrefPubMedGoogle Scholar
  • 57 Kukielka G L, Hawkins H K, Michael L et al.. Regulation of intercellular adhesion molecule-1 (ICAM-1) in ischemic and reperfused canine myocardium.  J Clin Invest. 1993;  92(3) 1504-1516
    PubMedGoogle Scholar
  • 58 Solymoss B C, Nadeau P, Millette D, Campeau L. Late thrombosis of saphenous vein coronary bypass grafts related to risk factors.  Circulation. 1988;  78(3 Pt 2) I140-I143
    PubMedGoogle Scholar
  • 59 Campeau L, Enjalbert M, Lesperance J et al.. The relation of risk factors to the development of atherosclerosis in saphenous-vein bypass grafts and the progression of disease in the native circulation. A study 10 years after aortocoronary bypass surgery.  N Engl J Med. 1984;  311(21) 1329-1332
    CrossrefPubMedGoogle Scholar
  • 60 Neitzel G F, Barboriak J J, Pintar K, Qureshi I. Atherosclerosis in aortocoronary bypass grafts. Morphologic study and risk factor analysis 6 to 12 years after surgery.  Arteriosclerosis. 1986;  6(6) 594-600
    PubMedGoogle Scholar
  • 61 Cashin-Hemphill L, Mack W J, Pogoda J M, Sanmarco M E, Azen S P, Blankenhorn D H. Beneficial effects of colestipol-niacin on coronary atherosclerosis. A 4-year follow-up.  JAMA. 1990;  264 3013-3017
    CrossrefPubMedGoogle Scholar
  • 62 Campeau L, Hunninghake D B, Knatterud G L et al.. Aggressive cholesterol lowering delays saphenous vein graft atherosclerosis in women, the elderly, and patients with associated risk factors. NHLBI post coronary artery bypass graft clinical trial. Post CABG Trial Investigators.  Circulation. 1999;  99(25) 3241-3247
    PubMedGoogle Scholar
  • 63 Linden T, Bondjers G, Karlsson T, Wiklund O. Serum triglycerides and HDL cholesterol-major predictors of long-term survival after coronary surgery.  Eur Heart J. 1994;  15(6) 747-752
    PubMedGoogle Scholar
  • 64 Cataldo G, Braga M, Pirotta N, Lavezzari M, Rovelli F, Marubini E. Factors influencing 1-year patency of coronary artery saphenous vein grafts. Studio Indobufene nel Bypass Aortocoronarico (SINBA).  Circulation. 1993;  88(5 Pt 2) II93-II98
    PubMedGoogle Scholar
  • 65 Grundy S M, Vega G L. Two different views of the relationship of hypertriglyceridemia to coronary heart disease. Implications for treatment.  Arch Intern Med. 1992;  152(1) 28-34
    CrossrefPubMedGoogle Scholar
  • 66 Grundy S M, Benjamin I J, Burke G L et al.. Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association.  Circulation. 1999;  100(10) 1134-1146
    CrossrefPubMedGoogle Scholar
  • 67 Haffner S M. Insulin resistance, inflammation, and the prediabetic state.  Am J Cardiol. 2003;  92(4A) 18J-26J
    PubMedGoogle Scholar
  • 68 Vaya A, Mira Y, Ferrando F et al.. Hyperlipidaemia and venous thromboembolism in patients lacking thrombophilic risk factors.  Br J Haematol. 2002;  118(1) 255-259
    CrossrefPubMedGoogle Scholar
  • 69 Puccetti L, Bruni F, Pasqui A L et al.. Dyslipidemias and fibrinolysis.  Ital Heart J. 2002;  3(10) 579-586
    PubMedGoogle Scholar
  • 70 Griffin J H, Fernandez J A, Deguchi H. Plasma lipoproteins, hemostasis and thrombosis.  Thromb Haemost. 2001;  86(1) 386-394
    PubMedGoogle Scholar
  • 71 Griffin J H, Kojima K, Banka C L, Curtiss L K, Fernandez J A. High-density lipoprotein enhancement of anticoagulant activities of plasma protein S and activated protein C.  J Clin Invest. 1999;  103(2) 219-227
    CrossrefPubMedGoogle Scholar
  • 72 Schaefer E J, McNamara J R, Shah P K et al.. Elevated remnant-like particle cholesterol and triglyceride levels in diabetic men and women in the Framingham Offspring Study.  Diabetes Care. 2002;  25(6) 989-994
    PubMedGoogle Scholar
  • 73 Mompeo B, Ortega F. Immunohistochemical and ultrastructural study of microvessels in diabetic veins.  Ultrastruct Pathol. 1999;  23(1) 25-31
    PubMedGoogle Scholar
  • 74 Wengerter K R, Veith F J, Gupta S K, Ascer E, Rivers S P. Influence of vein size (diameter) on infrapopliteal reversed vein graft patency.  J Vasc Surg. 1990;  11(4) 525-531
    PubMedGoogle Scholar
  • 75 Milazzo D, Biasucci L M, Luciani N et al.. Elevated levels of C-reactive protein before coronary artery bypass grafting predict recurrence of ischemic events.  Am J Cardiol. 1999;  84 459-461
    CrossrefPubMedGoogle Scholar
  • 76 Cameron A A, Davis K B, Rogers W J. Recurrence of angina after coronary artery bypass surgery: predictors and prognosis (CASS Registry). Coronary Artery Surgery Study.  J Am Coll Cardiol. 1995;  26(4) 895-899
    CrossrefPubMedGoogle Scholar
  • 77 Eritsland J, Arnesen H, Seljeflot I et al.. Influence of serum lipoprotein(a) and homocyst(e)ine levels on graft patency after coronary artery bypass grafting.  Am J Cardiol. 1994;  74(11) 1099-1102
    CrossrefPubMedGoogle Scholar
  • 78 Mann M J, Whittemore A D, Donaldson M C et al.. Ex-vivo gene therapy of human vascular bypass grafts with E2F decoy: the PREVENT single-centre, randomised, controlled trial.  Lancet. 1999;  354(9189) 1493-1498
    CrossrefPubMedGoogle Scholar
  • 79 Ehsan A, Mann M J, Dell'Acqua G, Dzau V J. Long-term stabilization of vein graft wall architecture and prolonged resistance to experimental atherosclerosis after E2F decoy oligonucleotide gene therapy.  J Thorac Cardiovasc Surg. 2001;  121(4) 714-722
    CrossrefPubMedGoogle Scholar
  • 80 Shigematsu K, Yasuhara H, Shigematsu H. Topical application of antiangiogenic agent AGM-1470 suppresses anastomotic intimal hyperplasia after ePTFE grafting in a rabbit model.  Surgery. 2001;  129(2) 220-230
    CrossrefPubMedGoogle Scholar
  • 81 Kolodgie F D, Gold H K, Burke A P et al.. Intraplaque hemorrhage and progression of coronary atheroma.  N Engl J Med. 2003;  349(24) 2316-2325
    CrossrefPubMedGoogle Scholar
  • 82 Dzau V J. Predicting the future of human gene therapy for cardiovascular diseases: what will the management of coronary artery disease be like in 2005 and 2010?.  Am J Cardiol. 2003;  92(9B) 32N-35N
    PubMedGoogle Scholar

 Professor
Leonard Kritharides

Department of Cardiology, 3 West, Concord Repatriation General Hospital

Hospital Road, Concord, NSW 2139, Australia