Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Coronary collateral circulation

Bruce D Klugherz, MD
Daniel M Kolansky, MD
Section Editor
Bernard J Gersh, MB, ChB, DPhil, FRCP, MACC
Deputy Editor
Gordon M Saperia, MD, FACC


Anastomotic channels, known as collateral vessels, can develop in the heart as an adaptation to ischemia [1,2]. They serve as conduits that bridge severe stenoses or connect a territory supplied by one epicardial coronary artery with that of another [3]. Collaterals therefore provide an alternative source of blood supply to myocardium jeopardized by occlusive coronary artery disease, and they can help to preserve myocardial function in the setting of a chronic total coronary occlusion [4].

Two classes of collateral vessels have been recognized:

Capillary size collaterals, in which smooth muscle cells are absent, may be observed throughout the myocardium, although they have a predilection for the subendocardium.

Larger, muscular collaterals, which develop from pre-existing arterioles, are typically located epicardially [5].


The clinical and pathophysiologic determinants of collateral recruitment are poorly understood. Although primarily thought to be initiated by ischemia, appreciable collateral perfusion is present in some patients who do not have coronary disease [6].

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: May 17, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Fujita M, Sasayama S, Ohno A, et al. Importance of angina for development of collateral circulation. Br Heart J 1987; 57:139.
  2. Tayebjee MH, Lip GY, MacFadyen RJ. Collateralization and the response to obstruction of epicardial coronary arteries. QJM 2004; 97:259.
  3. Levin DC. Pathways and functional significance of the coronary collateral circulation. Circulation 1974; 50:831.
  4. Werner GS, Ferrari M, Betge S, et al. Collateral function in chronic total coronary occlusions is related to regional myocardial function and duration of occlusion. Circulation 2001; 104:2784.
  5. Schaper W. Collateral vessel growth in the human heart. Role of fibroblast growth factor-2. Circulation 1996; 94:600.
  6. Wustmann K, Zbinden S, Windecker S, et al. Is there functional collateral flow during vascular occlusion in angiographically normal coronary arteries? Circulation 2003; 107:2213.
  7. Piek JJ, van Liebergen RA, Koch KT, et al. Clinical, angiographic and hemodynamic predictors of recruitable collateral flow assessed during balloon angioplasty coronary occlusion. J Am Coll Cardiol 1997; 29:275.
  8. Senti S, Fleisch M, Billinger M, et al. Long-term physical exercise and quantitatively assessed human coronary collateral circulation. J Am Coll Cardiol 1998; 32:49.
  9. Pohl T, Seiler C, Billinger M, et al. Frequency distribution of collateral flow and factors influencing collateral channel development. Functional collateral channel measurement in 450 patients with coronary artery disease. J Am Coll Cardiol 2001; 38:1872.
  10. Kurotobi T, Sato H, Kinjo K, et al. Reduced collateral circulation to the infarct-related artery in elderly patients with acute myocardial infarction. J Am Coll Cardiol 2004; 44:28.
  11. Duran J, Olavarría PS, Mola M, et al. Genetic association study of coronary collateral circulation in patients with coronary artery disease using 22 single nucleotide polymorphisms corresponding to 10 genes involved in postischemic neovascularization. BMC Cardiovasc Disord 2015; 15:37.
  12. Fujita M, Ikemoto M, Kishishita M, et al. Elevated basic fibroblast growth factor in pericardial fluid of patients with unstable angina. Circulation 1996; 94:610.
  13. Shweiki D, Itin A, Neufeld G, et al. Patterns of expression of vascular endothelial growth factor (VEGF) and VEGF receptors in mice suggest a role in hormonally regulated angiogenesis. J Clin Invest 1993; 91:2235.
  14. Kersten JR, Pagel PS, Warltier DC. Protamine inhibits coronary collateral development in a canine model of repetitive coronary occlusion. Am J Physiol 1995; 268:H720.
  15. Fleisch M, Billinger M, Eberli FR, et al. Physiologically assessed coronary collateral flow and intracoronary growth factor concentrations in patients with 1- to 3-vessel coronary artery disease. Circulation 1999; 100:1945.
  16. Hojo Y, Ikeda U, Zhu Y, et al. Expression of vascular endothelial growth factor in patients with acute myocardial infarction. J Am Coll Cardiol 2000; 35:968.
  17. Takeshita S, Isshiki T, Ochiai M, et al. Endothelium-dependent relaxation of collateral microvessels after intramuscular gene transfer of vascular endothelial growth factor in a rat model of hindlimb ischemia. Circulation 1998; 98:1261.
  18. Matsunaga T, Warltier DC, Weihrauch DW, et al. Ischemia-induced coronary collateral growth is dependent on vascular endothelial growth factor and nitric oxide. Circulation 2000; 102:3098.
  19. Foreman BW, Dai XZ, Bache RJ. Vasoconstriction of canine coronary collateral vessels with vasopressin limits blood flow to collateral-dependent myocardium during exercise. Circ Res 1991; 69:657.
  20. Bache RJ, Schwartz JS. Myocardial blood flow during exercise after gradual coronary occlusion in the dog. Am J Physiol 1983; 245:H131.
  21. Sambuceti G, Parodi O, Giorgetti A, et al. Microvascular dysfunction in collateral-dependent myocardium. J Am Coll Cardiol 1995; 26:615.
  22. Kinn JW, Altman JD, Chang MW, Bache RJ. Vasomotor responses of newly developed coronary collateral vessels. Am J Physiol 1996; 271:H490.
  23. Hautamaa PV, Dai XZ, Homans DC, Bache RJ. Vasomotor activity of moderately well-developed canine coronary collateral circulation. Am J Physiol 1989; 256:H890.
  24. Rapps JA, Myers PR, Zhong Q, Parker JL. Development of endothelium-dependent relaxation in canine coronary collateral arteries. Circulation 1998; 98:1675.
  25. Frank MW, Harris KR, Ahlin KA, Klocke FJ. Endothelium-derived relaxing factor (nitric oxide) has a tonic vasodilating action on coronary collateral vessels. J Am Coll Cardiol 1996; 27:658.
  26. Feldman RD, Christy JP, Paul ST, Harrison DG. Beta-adrenergic receptors on canine coronary collateral vessels: characterization and function. Am J Physiol 1989; 257:H1634.
  27. Harrison DG, Chilian WM, Marcus ML. Absence of functioning alpha-adrenergic receptors in mature canine coronary collaterals. Circ Res 1986; 59:133.
  28. Traverse JH, Altman JD, Kinn J, et al. Effect of beta-adrenergic receptor blockade on blood flow to collateral-dependent myocardium during exercise. Circulation 1995; 91:1560.
  29. Traverse JH, Kinn JW, Klassen C, et al. Nitric oxide inhibition impairs blood flow during exercise in hearts with a collateral-dependent myocardial region. J Am Coll Cardiol 1998; 31:67.
  30. Kinn JW, Bache RJ. Effect of platelet activation on coronary collateral blood flow. Circulation 1998; 98:1431.
  31. Werner GS, Emig U, Mutschke O, et al. Regression of collateral function after recanalization of chronic total coronary occlusions: a serial assessment by intracoronary pressure and Doppler recordings. Circulation 2003; 108:2877.
  32. Lee JH, Kim CY, Kim N, et al. Coronary Collaterals Function and Clinical Outcome Between Patients With Acute and Chronic Total Occlusion. JACC Cardiovasc Interv 2017; 10:585.
  33. Möbius-Winkler S, Uhlemann M, Adams V, et al. Coronary Collateral Growth Induced by Physical Exercise: Results of the Impact of Intensive Exercise Training on Coronary Collateral Circulation in Patients With Stable Coronary Artery Disease (EXCITE) Trial. Circulation 2016; 133:1438.
  34. Gensini GG, Bruto da Costa BC. The coronary collateral circulation in living man. Am J Cardiol 1969; 24:393.
  35. Rockstroh J, Brown BG. Coronary collateral size, flow capacity, and growth: estimates from the angiogram in patients with obstructive coronary disease. Circulation 2002; 105:168.
  36. Rentrop KP, Cohen M, Blanke H, Phillips RA. Changes in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects. J Am Coll Cardiol 1985; 5:587.
  37. Seiler C, Fleisch M, Garachemani A, Meier B. Coronary collateral quantitation in patients with coronary artery disease using intravascular flow velocity or pressure measurements. J Am Coll Cardiol 1998; 32:1272.
  38. Billinger M, Raeber L, Seiler C, et al. Coronary collateral perfusion in patients with coronary artery disease: effect of metoprolol. Eur Heart J 2004; 25:565.
  39. Sezer M, Nisanci Y, Umman B, et al. Pressure-derived collateral flow index: a strong predictor of late left ventricular remodeling after thrombolysis for acute myocardial infarction. Coron Artery Dis 2006; 17:139.
  40. Mills JD, Fischer D, Villanueva FS. Coronary collateral development during chronic ischemia: serial assessment using harmonic myocardial contrast echocardiography. J Am Coll Cardiol 2000; 36:618.
  41. Vernon SM, Camarano G, Kaul S, et al. Myocardial contrast echocardiography demonstrates that collateral flow can preserve myocardial function beyond a chronically occluded coronary artery. Am J Cardiol 1996; 78:958.
  42. Sabia PJ, Powers ER, Ragosta M, et al. An association between collateral blood flow and myocardial viability in patients with recent myocardial infarction. N Engl J Med 1992; 327:1825.
  43. Christian TF, O'Connor MK, Schwartz RS, et al. Technetium-99m MIBI to assess coronary collateral flow during acute myocardial infarction in two closed-chest animal models. J Nucl Med 1997; 38:1840.
  44. Matsuo H, Watanabe S, Kadosaki T, et al. Validation of collateral fractional flow reserve by myocardial perfusion imaging. Circulation 2002; 105:1060.
  45. Pearlman JD, Laham RJ, Simons M, et al. Extent of myocardial collateralization: determination with three-dimensional elastic-subtraction spiral CT. Acad Radiol 1997; 4:680.
  46. Jerosch-Herold M, Wilke N. MR first pass imaging: quantitative assessment of transmural perfusion and collateral flow. Int J Card Imaging 1997; 13:205.
  47. Akutsu Y, Hara T, Michihata T, et al. Functional role of coronary collaterals with exercise in infarct-related myocardium. Int J Cardiol 1995; 51:47.
  48. Sand NP, Rehling M, Bagger JP, et al. Functional significance of recruitable collaterals during temporary coronary occlusion evaluated by 99mTc-sestamibi single-photon emission computerized tomography. J Am Coll Cardiol 2000; 35:624.
  49. Cheirif J, Narkiewicz-Jodko JB, Hawkins HK, et al. Myocardial contrast echocardiography: relation of collateral perfusion to extent of injury and severity of contractile dysfunction in a canine model of coronary thrombosis and reperfusion. J Am Coll Cardiol 1995; 26:537.
  50. Habib GB, Heibig J, Forman SA, et al. Influence of coronary collateral vessels on myocardial infarct size in humans. Results of phase I thrombolysis in myocardial infarction (TIMI) trial. The TIMI Investigators. Circulation 1991; 83:739.
  51. Blanke H, Cohen M, Karsch KR, et al. Prevalence and significance of residual flow to the infarct zone during the acute phase of myocardial infarction. J Am Coll Cardiol 1985; 5:827.
  52. Nicolau JC, Pinto MA, Nogueira PR, et al. The role of antegrade and collateral flow in relation to left ventricular function post-thrombolysis. Int J Cardiol 1997; 61:47.
  53. Lee CW, Park SW, Cho GY, et al. Pressure-derived fractional collateral blood flow: a primary determinant of left ventricular recovery after reperfused acute myocardial infarction. J Am Coll Cardiol 2000; 35:949.
  54. Rentrop KP, Feit F, Sherman W, et al. Late thrombolytic therapy preserves left ventricular function in patients with collateralized total coronary occlusion: primary end point findings of the Second Mount Sinai-New York University Reperfusion Trial. J Am Coll Cardiol 1989; 14:58.
  55. Hirai T, Fujita M, Nakajima H, et al. Importance of collateral circulation for prevention of left ventricular aneurysm formation in acute myocardial infarction. Circulation 1989; 79:791.
  56. Elsman P, van 't Hof AW, de Boer MJ, et al. Role of collateral circulation in the acute phase of ST-segment-elevation myocardial infarction treated with primary coronary intervention. Eur Heart J 2004; 25:854.
  57. Pérez-Castellano N, García EJ, Abeytua M, et al. Influence of collateral circulation on in-hospital death from anterior acute myocardial infarction. J Am Coll Cardiol 1998; 31:512.
  58. Nicolau JC, Nogueira PR, Pinto MA, et al. Early infarct artery collateral flow does not improve long-term survival following thrombolytic therapy for acute myocardial infarction. Am J Cardiol 1999; 83:21.
  59. Antoniucci D, Valenti R, Moschi G, et al. Relation between preintervention angiographic evidence of coronary collateral circulation and clinical and angiographic outcomes after primary angioplasty or stenting for acute myocardial infarction. Am J Cardiol 2002; 89:121.
  60. Desch S, de Waha S, Eitel I, et al. Effect of coronary collaterals on long-term prognosis in patients undergoing primary angioplasty for acute ST-elevation myocardial infarction. Am J Cardiol 2010; 106:605.
  61. Meier P, Gloekler S, Zbinden R, et al. Beneficial effect of recruitable collaterals: a 10-year follow-up study in patients with stable coronary artery disease undergoing quantitative collateral measurements. Circulation 2007; 116:975.
  62. Abaci A, Oğuzhan A, Kahraman S, et al. Effect of diabetes mellitus on formation of coronary collateral vessels. Circulation 1999; 99:2239.
  63. Waltenberger J, Lange J, Kranz A. Vascular endothelial growth factor-A-induced chemotaxis of monocytes is attenuated in patients with diabetes mellitus: A potential predictor for the individual capacity to develop collaterals. Circulation 2000; 102:185.
  64. Marfella R, Esposito K, Nappo F, et al. Expression of angiogenic factors during acute coronary syndromes in human type 2 diabetes. Diabetes 2004; 53:2383.
  65. Tanaka T, Fujita M, Nakae I, et al. Improvement of exercise capacity by sarpogrelate as a result of augmented collateral circulation in patients with effort angina. J Am Coll Cardiol 1998; 32:1982.
  66. Fabre JE, Rivard A, Magner M, et al. Tissue inhibition of angiotensin-converting enzyme activity stimulates angiogenesis in vivo. Circulation 1999; 99:3043.
  67. Zbinden S, Brunner N, Wustmann K, et al. Effect of statin treatment on coronary collateral flow in patients with coronary artery disease. Heart 2004; 90:448.
  68. Meier P, Zbinden R, Togni M, et al. Coronary collateral function long after drug-eluting stent implantation. J Am Coll Cardiol 2007; 49:15.