Article info

PDF

The “no-reflow” phenomenon: basic science and clinical correlates
  1. Correspondence to:
    Robert A Kloner, MD, PhD, The Heart Institute, Good Samaritan Hospital, University of Southern California, 1225 Wilshire Boulevard, Los Angeles, CA 90017-2395, USA;
    RKloner{at}goodsam.org
View Full Text

Citation

Reffelmann T, Kloner RA
The “no-reflow” phenomenon: basic science and clinical correlates

Publication history

  • First published February 1, 2002.
Online issue publication 
February 01, 2002
  • Web only references

      Angiographic assessment of no-reflow

      • Gibson CM, Murphy SA, Rizzo MJ, et al. Relationship between TIMI frame count and clinical outcomes after thrombolytic administration. Thrombolysis in Myocardial Infarction (TIMI) Study Group. Circulation 1999;99:1945-1950.

      • van�t Hof AW, Liem A, Suryapranata H, et al. Angiographic assessment of myocardial reperfusion in patients treated with primary angioplasty for acute myocardial infarction: myocardial blush grade. Zwolle Myocardial Infarction Study Group. Circulation 1998;97:2302-2306.

      Myocardial contrast echocardiography

      • Ito H, Iwakura K. Assessing the relation between coronary reflow and myocardial reflow. Am J Cardiol 1998;81:8G-12G.

      • Lepper W, Hoffmann R, Kamp O, et al. Assessment of myocardial reperfusion by intravenous myocardial contrast echocardiography and coronary flow reserve after primary percutaneous transluminal angioplasty in patients with acute myocardial infarction. Circulation 2000;101:2368-2374.

      • Ito H, Iwakura K, Oh H, et al. Temporal changes in myocardial perfusion patterns in patients with reperfused anterior wall myocardial infarction. Their relation to myocardial viability. Circulation 1995;91:656-662.

      • Sakuma T, Otsuka M, Okimoto T, et al. Optimal time for predicting myocardial viability after successful primary angioplasty in acute myocardial infarction: A study using myocardial contrast echocardiography. Am J Cardiol 2001;87:687-692.

      • Karila-Cohen D, Czitrom D, Brochet E, et al. Decreased no-reflow in patients with anterior myocardial infarction and pre-infarction angina. Eur Heart J 1999;20:1724-1730.

      Magnetic resonance imaging

      • Judd RM, Lugo-Olivieri CH, Arai M, et al. Physiological basis of myocardial contrast enhancement in fast magnetic resonance images of 2-day-old reperfused canine infarcts. Circulation 1995;92:1902-1910.

      • Rochitte CE, Kim RJ, Hillenbrand HB, et al. Microvascular integrity and the time course of myocardial sodium accumulation after acute infarction. Circ Res 2000;87:648-655.

      Scintigraphic techniques

      • Jeremy RW, Links JM, Becker LC. Progressive failure of coronary flow during reperfusion of myocardial infarction: documentation of the no reflow phenomenon with positron emission tomography. J Am Coll Cardiol 1990;16:695-704.

      • Kondo M, Nakano A, Saito D, et al. Assessment of "microvascular no-reflow phenomenon" using technetium-99m macroaggregated albumin scintigraphy in patients with acute myocardial infarction. J Am Coll Cardiol 1998;32:898-903.

      Potential mechanisms of no-reflow

      • Engler RL, Schmid-Schonbein GW, Pavelec RS. Leukocyte capillary plugging in myocardial ischemia and reperfusion in the dog. Am J Pathol 1983;111:98-111.

      • Litt MR, Jeremy RW, Weisman HF, et al. Neutrophil depletion limited to reperfusion reduces myocardial infarct size after 90 minutes of ischemia. Evidence for neutrophil-mediated reperfusion injury. Circulation 1989;80:1816-1827.

      • Kolodgie FD, Virmani R, Frab A. Limitation of no reflow injury by blood-free reperfusion with oxygenated perfluorochemical (Fluosol-DA 20%). J Am Coll Cardiol 1991;18:215-223.

      • Hale SL, Hammerman H, Kloner RA. Effect of two perfluorocarbon emulsions on reperfusion injury after coronary artery occlusion in rabbits. Basic Res Cardiol 1995;90:404-409

      • Li XS, Wang QD, Pernow J. Beneficial effects of the endothelin receptor antagonist bosentan on myocardial and endothelial injury following ischaemia/reperfusion in the rat. Eur J Pharmacol 1995;283:161-168.

      • Hale S, Kloner RA. Ischemic preconditioning in the rabbit: effect on regional myocardial blood flow. Coronary Artery Dis 1992;3:133-140.

      • Bauer B, Simkhovich BZ, Kloner RA, et al. Does preconditioning protect the coronary vasculature from subsequent ischemia/reperfusion injury? Circulation 1993;88:659-672.

      • Kloner RA, Giacomelli F, Alker KJ, et al. Influx of neutrophils into the wall of large epicardial coronary arteries in response to ischemia/reperfusion. Circulation 1991;84:1758-1772.

      • Manciet LH, Poole DC, McDonagh PF, et al. Microvascular compression during myocardial ischemia: mechanistic basis for no-reflow phenomenon. Am J Physiol 1994;266:H1541-H550.

      • Carlson RE, Aisen AM, Buda AJ. Effect of reduction in myocardial edema on myocardial blood flow and ventricular function after coronary reperfusion. Am J Physiol 1992;262:H641-H648

      • Willerson JT, Watson JT, Hutton I, et al. The influence of hypertonic mannitol on regional myocardial blood flow during acute and chronic myocardial ischemia in anesthetized and awake intact dogs. J Clin Invest 1975;55:892-902.

      • Siminiak T, Flores NA, Sheridan DJ. Neutrophil interactions with endothelium and platelets: possible role in the development of cardiovascular injury. Eur Heart J 1995;16:160-170.

      • Beauchamp P, Richard V, Tamion F, et al. Protective effects of preconditioning in cultured rat endothelial cells: Effects on neutrophil adhesion and expression of ICAM-1 after anoxia and reoxygenation. Circulation 1999;100:541-546.

      • Ohnishi M, Yamada K, Morooka S, et al. Inhibition of P-selectin attenuates neutrophil-mediated myocardial dysfunction in isolated rat heart. Eur J Pharmacol 1999;366:271-279.

      • Birnbaum Y, Patterson M, Kloner RA. The effect of CY1503, a sialyl Lewisx analog blocker of the selectin adhesion molecules, on infarct size and "no-reflow" in the rabbit model of acute myocardial infarction/reperfusion. J Mol Cell Cardiol 1997;29:2013-2025.

      • Golino P, Maroko PR, Carew TE. Efficacy of platelet depletion in counteracting the detrimental effect of acute hypercholesterolemia on infarct size and the no-reflow phenomenon in rabbits undergoing coronary artery occlusion-reperfusion. Circulation 1987;76:173-180.

      • Galiuto L, DeMaria AN, del Balzo U, et al.. Ischemia-reperfusion injury at the microvascular level treatment by endothelin A-selective antagonist and evaluation by myocardial contrast echocardiography. Circulation 2000;102:3111-3116.

      • Ambrosio G, Becker LC, Hutchins GM, et al. Reduction in experimental infarct size by recombinant human superoxide dismutase: insights into the pathophysiology of reperfusion injury. Circulation 1986;74:1424-1433.

      • Villari B, Ambrosio G, Golino P, et al. The effects of calcium channel antagonist treatment and oxygen radical scavenging on infarct size and the no-reflow phenomenon in reperfused hearts. Am Heart J 1993;125:11-23

      • Ambrosio G, Tritto I. Reperfusion injury: experimental evidence and clinical implications. Am Heart J 1999;138:S69-75.

      • Kloner RA. Does reperfusion injury exist in humans? J Am Coll Cardiol 1993;21:537-545.

      • Kloner RA, Alker KJ. The effect of streptokinase on intramyocardial hemorrhage, infarct size, and the no-reflow phenomenon during coronary reperfusion. Circulation 1984;70:513-521.

      • Kloner RA, Alker K, Campbell C, et al. Does tissue-type plasminogen activator have direct beneficial effects on the myocardium independent of its ability to lyse intracoronary thrombi? Circulation 1989;79:1125-1136.

      Coronary microembolization

      • Yao SK, Ober JC, McNatt J, et al. ADP plays an important role in mediating platelet aggregation and cyclic flow variations in vivo in stenosed and endothelium-injured canine coronary arteries. Circ Res 1992;70:39-48.

      • Erbel R, Heusch G. Coronary microembolization. J Am Coll Cardiol 2000;36:22-24.

      • Mutin M, Canavy I, Blann A, et al. Direct evidence of endothelial injury in acute myocardial infarction and unstable angina by demonstration of circulating endothelial cells. Blood 1999;93:2951-2958.

      • Mak KH, Challapalli R, Eisenberg MJ, et al., for the EPIC Investigators. Effect of platelet glycoprotein IIb/IIIa receptor inhibition on distal embolization during percutaneous revascularization of aortocoronary saphenous vein grafts. Am J Cardiol 1997;80:985-988.

      • Carlino M, De Gregorio J, Di Mario C, et al. Prevention of distal embolization during saphenous vein graft lesion angioplasty. Experience with a new temporary occlusion and aspiration system. Circulation 1999;99:3221-3223.

      • Koch KC, vom Dahl J, Kleinhans E, et al. Influence of platelet GPIIb/IIIa receptor antagonist on myocardial hypoperfusion during rotational atherectomy as assessed by myocardial Tc-99 sestamibi scintigraphy. J Am Coll Cardiol 1999;33:998-1004.

      • Topol EJ, Leya F, Pinkerton CA, et al., for the CAVEAT Study Group. A comparison of directional atherectomy with coronary angioplasty in patients with coronary artery disease. N Engl J Med 1993;329:221-227.

      • Holmes DR, Topol EJ, Califf RM, et al., for the CAVEAT-II Investigators. A multicenter, randomized trial of coronary angioplasty versus directional atherectomy for patients with saphenous vein bypass graft lesions. Circulation 1995;91:1966-1974.

      Treatment strategies

      • Pitarys CJ, Virmani R, Vildibill HD, et al. Reduction of myocardial reperfusion injury by intravenous adenosine administered during the early reperfusion period. Circulation 1991;83:237-247.

      • Homeister JW, Hoff PT, Fletcher DD, et al. Combined adenosine and lidocaine administration limits myocardial reperfusion injury. Circulation 1990;82:595-608.

      • Marzilli M, Orsini E, Marraccini P, et al. Beneficial effects of intracoronary adenosine as an adjunct to primary angioplasty in acute myocardial infarction. Circulation 2000;101:2154-2159.

      • Flaherty JT, Pitt B, Gruber JW, et al. Recombinant human superoxide dismutase (h-SOD) fails to improve recovery of ventricular function in patients undergoing coronary angioplasty for acute myocardial infarction. Circulation 1994;89:1982-1991.

      • Ishihara M, Sato H, Tateishi H, et al. Attenuation of the no-reflow phenomenon after coronary angioplasty for acute myocardial infarction with intracoronary papaverine. Am Heart J 1996;132:959-963.

      • Hillegass WB, Dean NA, Liao L, et al. Treatment of no-reflow and impaired flow with the nitric oxide donor nitroprusside following percutaneous interventions: initial human clinical experience. J Am Coll Cardiol 2001; 37:1335-1343.

      • Neumann FJ, Blasini R, Schmitt C, et al. Effect of glycoprotein IIb/IIIa receptor blockade on recovery of coronary flow and left ventricular function after the placement of coronary-artery stents in acute myocardial infarction. Circulation 1998;98:2695-2701.

      • Gibson CM, Cohen DJ, Cohen EA, et al., for the ESPRIT study group. Effect of Eptifibatide on coronary flow reserve following coronary stent implantation (an ESPPRIT substudy). Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy. Am J Cardiol 2001;87:1293-1295.

    Request permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.