Abstract
Both animal models of experimental myocardial infarction and clinical studies on reperfusion therapy for acute myocardial infarction have provided evidence of impaired tissue perfusion at the microvascular level after initiation of reperfusion despite adequate restoration of epicardial vessel patency. Characteristics of this “no-reflow” phenomenon found in basic science investigations, such as distinct perfusion defects, progressive decrease of resting myocardial flow with ongoing reperfusion and functional vascular alterations are paralleled by clinical observations demonstrating similar features during the course of reperfusion. In experimental animal investigations of coronary occlusion and reperfusion, this no-reflow phenomenon could be characterized as a fundamental mechanism of myocardial ischemia and reperfusion. Major determinants of the amount of no-reflow are the duration of occlusion, infarct size, but also the length of reperfusion, as rapid expansion of perfusion defects occurs during reperfusion. Moreover, no-reflow appears to persist over a period of at least four weeks, a period when major steps of infarct healing take place. The significant association of the degree of compromised tissue perfusion at four weeks and indices of infarct expansion, found in chronic animal models of reperfused myocardial infarction, might be the pathoanatomic correlate for the prognostic significance observed in the clinical setting.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Aiello EA, Jabr RI, Cole WC (1995) Arrhythmia and delayed recovery of cardiac action potential during reperfusion after ischemia. Role of oxygen radical-induced no-reflow phenomenon. Circ Res 77:153–162
Amado LC,Kraitchman DL,Gerber BL, Castillo E, Boston RC,Grayzel J,Lima JA (2004) Reduction of “no-reflow” phenomenon by intra-aortic ballon counterpulsation in a randomized magnetic resonance imaging experimental study. J Am Coll Cardiol 43:1291–1298
Ambrosio G, Becker LC, Grover M, Hutchins GM, Weisman H, Weisfeldt ML (1986) Reduction in experimental infarct size by recombinant human superoxide dismutase: insights into the pathophysiology of reperfusion injury. Circulation 74:1424–1433
Ambrosio G, Tritto I (1999) Reperfusion injury: experimental evidence and clinical implications. Am Heart J 138:69–75
Ambrosio G,Weisman HF, Mannisi JA, Becker LC (1989) Progressive impairment of regional myocardial perfusion after initial restoration of postischemic blood flow. Circulation 80:1846–1861
Asanuma T, Tanabe K, Ochiai K, Yoshitomi H,Nakamura K,Murakami Y, Sano K, Shimada T, Murakami R, MoriokaS, Beppu S (1997) Relationship between progressive microvascular damage and intramyocardial hemorrhage in patients with reperfused anterior myocardial infarction. Circulation 96:448–453
Assali AR, Sdringola S, Ghani M, Denkats AE,Yepes A,Hanna GP,S G,Fujise K, Anderson HV, Smalling RW, Rosales OR (2000) Intracoronary adenosine administered during percutaneous intervention in acute myocardial infarction and reduction in the incidence of “no-reflow” phenomenon. Catheter Cardiovasc Interv 51:27–31
Babbit DG, Virmani R, Forman MB (1989) Intracoronary adenosine administered after reperfusion limits vascular injury after prolonged ischemia in the canine model. Circulation 80:1388–1399
Beauchamp P, Richard V, Tamion F, Lallemand F, Lebreton JP, Vaudry H, Daveau M, Thuillez C (1999) Protective effects of preconditioning in cultured rat endothelial cells Effects on neutrophil adhesion and expression of ICAM-1 after anoxia and reoxygenation. Circulation 100:541–546
Birnbaum Y, Patterson M, Kloner RA (1997) 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 in isolated rat heart. J Mol Cell Cardiol 29:2013–2025
Braunwald E Myocardial reperfusion, limitation of infarct size, reduction of left ventricular dysfunction, and improved survival: Should the paradigm be expanded? Circulation 79:441–444
Carlino M, De Gregorio J, Di Mario C, Anzuini A, Airoldi A, Albiero R, Briguori C, Dharmadhikari A, Sheiban I, Colombo A (1999) Prevention of distal embolization during saphenous vein graft lesion angioplasty: experience with a new temporary occlusion and aspiration system. Circulation 99:3221–3223
Carlson RE, Aisen AM, Buda AJ (1992) Effect of reduction in myocardial edema on myocardial blood flow and ventricular function after coronary reperfusion. Am J Physiol 262:H641–H648
Chambers DE, Parks DA, Patterson G, Roy R, McCord JM, Yoshida S, Parmley LF,Downey JM (1985) Xanthine oxidase as a source of free radical damage in myocardial ischemia. J Mol Cell Cardiol 17:145–152
Choudhury RP, Porto I, Banning AP (2004) Debris trapped by a distal protection device may mimic no-reflow during percutaneous coronary intervention. Circulation 109:803–804
Davies MJ, Woolf N, Robertson WB (1976) Pathology of acute myocardial infarction with particular reference to occlusive coronary thrombi. Br Heart J 38:659–664
Doenst T,Holden JE, Taegtmeyer H, Jeremy RW, Matsumura K, Becker LC (1999) Limitations to the Assessment of Reperfusion Injury With radiolabeled 2-Deoxyglucose Response. Circulation 99:1646–1649
Duilio C, Ambrosio G, Kuppusamy P, DiPaula A, Becker LC, Zweier JL (2001) Neutrophils are primary source of O(2) radicals during reperfusion after prolonged myocardial ischemia. Am J Physiol 280:H2649–2657
Engler RL, Schmid-Schönbein GW, Pavelec RS (1983) Leukocyte capillary plugging in myocardial ischemia and reperfusion in the dog. Am J Pathol 111:98–111
Erbel R, Heusch G (2000) Coronary microembolization. J Am Coll Cardiol 36:22–24
Fishbein MC, Y-Rit J, Lando U, Kanmatsuse K, Mercier JC, Ganz W (1980) The relationship of vascular injury and myocardial hemorrhyge to necrosis after reperfusion. Circulation 62:1274–1279
Galinanes M, Lawson CS, Ferrari R, Limb GA, Derias NW, Hearse DJ (1993) Early and late effects of leukopenic reperfusion on the recovery of cardiac contractile function Studies in the transplanted and isolated blood-perfused rat heart. Circulation 88:673–683
Galiuto L, DeMaria AN, del Balzo U, May-Newman K, Flaim SF, Wolf PL, Kirchengast M, Iliceto S (2000) Ischemia- Reperfusion injury at the microvascular level treatment by endothelin A-selective antagonist and evaluation by myocardial contrast echocardiography. Circulation 102:3111–3116
Genda S, Miura T, Miki T, Ichikawa Y, Shimamoto K (2002) K(ATP) channel opening is an endogenoeus mechanism of protection against the no-reflow phenomenon but its function is compromised by hypercholesterolemia. J Am Coll Cardiol 40:1339–1346
Golino P, Maroko PR, Carew TE (1987) 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 76:173–180
Golino P, Ragni M, Cirillo P, Avvendimento VE, Felicello A, Esposito N, Scognamiglio A, Trimarco B, Iaccarino G, Condorelli M, Chiarello M,Ambrosio G (1996) Effects of tissue factor induced by oxygen free radicals on coronary flow during reperfusion. Nat Med 2:35–41
Golino P, Ragni M, Cirillo P, Scognamiglio A,Ravera A,Buono C,Guarino A, Piro O, Lambiase C, Botticella F, Ezban M, Condorelli M, Chiarello M (2000) Recombinant human,active siteblocked factor VIIa reduces infarct size and no-reflow phenomenon in rabbits. Am J Physiol 278:H1507–1516
Guarnieri C, Flannigan F, Caldarera CM (1980) Role of oxygen in the cellular damage induced by reoxygenation of hypoxic hearts. J Mol Cell Cardiol 12:797–808
Hale SL,Dae MW,Kloner RA (2003) Hypothermia during reperfusion limits ‘no-reflow’ injury in a rabbit myocardial infarct model. Cardiovasc Res 59:715–722
Hale SL, Hammerman H, Kloner RA (1995) Effect of two perfluorocarbon emulsions on reperfusion injury after coronary occlusion in rabbits. Bas Res Cardiol 90:404–409
Hale SL, Leeka JA, Kloner RA (2006) Improved left ventricular function and reduced necrosis after myocardial ischemia/ reperfusion in rabbits treated with ranolazine, an inhibitor of the late sodium channel. J Pharmacol Exp Ther (in press)
Hillegass WB, Dean NA, Liao L, Rhinehart RG,Myers PR (2001) Treatment of no-reflow and impaired flow with the nitric oxide donor nitroprusside following percutaneous interventions: initial human clinical experience. J Am Coll Cardiol 37:1335–1343
Homeister JW, Hoff PT, Fletcher DD, Lucchesi BR (1990) Combined adenosine and lidocaine administration limits myocardial reperfusion injury. Circulation 82:595–608
Ichimori K, Nakazawa H, Nioka S, Inubushi T, Chance B (1991) The mechanism underlying heterogeneous pH in ischemic and reperfused myocardium. Jpn Circ J 55:516–523
Ishihara M, Sato H,Tateishi H,Kawagoe T, Shimatani Y, Kurisu S, Kazuko S (1996) Attenuation of the no-reflow phenomenon after coronary angioplasty for acute myocardial infarction with intracoronary papaverine. Am Heart J 132:959–963
Ito BR, Schmid-Schönbein G,Engler RL (1990) Effects of leukocyte activation on myocardial vascular resistance. Blood Cells 16:145–163
Ito H, Iwakura K, Oh H, Masuyama T, Hori M,HigashinoY, Fujii K, Minamino T (1995) Temporal changes in myocardial perfusion patterns in patients with reperfused anterior wall myocardial infarction. Their relation to myocardial viability. Circulation 91:656–662
Ito H,Okamura A, Iwakura K,Masuyam T, Hori M, Takiuchi S, Negoro S, Nakatsuchi Y, Taniyama Y, Higashino Y, Fujii K, Minamino T (1996) Myocardial perfusion patterns related to thrombolysis in myocardial infarction perfusion grades after coronary angioplasty in patients with acute myocardial infarction. Circulation 93:1993–1999
Ito H,Taniyama Y,Iwakura K,Nishikawa N,Masuyama T,Kuzuya M,Higashino Y, Fujii K,Minamino T (1999) Intravenous nicorandil can preserve microvascular integrity and myocardial viability in patients with reperfused anterior wall myocardial infarction. J Am Coll Cardiol 33:654–660
Iwakura K, Ito H, Ikushima M, Kawano S, Okamura A, Asano K, Kuroda T, Tanaka K, Masuyama T, Hori M, Fujii K (2003) Association between hyperglycemia and the no-reflow phenomenon in patients with acute myocardial infarction. J Am Coll Cardiol 41:1–7
Iwakura K, Ito H, Nishikawa N et al. (1999) Early temporal changes in coronary flow velocity patterns in patients with acute myocardial infarction demonstrating the “no-reflow” phenomenon. Am J Cardiol 84:415–419
Jeremy RW, Links JM, Becker LC (1990) Progressive failure of coronary flow during reperfusion of myocardial infarction: documentation of the no reflow phenomenon with positron emission tomography. J Am Coll Cardiol 16:695–704
Johnson WB, Malone SA, Pantely GA, Anselone CG, Bristow JD (1988) No reflow and extent of infarction during maximal vasodilation in the porcine heart. Circulation 78:462–472
Judd RM, Lugo-Olivieri CH, Arai M, Kondo T, Croisille P, Lima JA,Mohan V, Becker LC, Zerhouni EA (1995) Physiological basis of myocardial contrast enhancement in fast magnetic images of 2-day old reperfused infarcts. Circulation 92:1902–1910
Kaeffer N, Richard V, François A, Lallemand F,Henry JP,Thuillez C (1996) Preconditioning prevents chronic reperfusion- induced coronaryendothelial dysfunction in rats. Am J Physiol 271:H842–H849
Kammermeier H (1987) Why do cells need phosphocreatine and a phosphocreatine shuttle? J Mol Cell Cardiol 19:115–118
Kapla BM, Benzuly KH, Kinn JW, Bowers TR, Tilli FV,Grines CL,O’Neill WW, Safian RD (1996) Treatment of no-reflow in degenerated saphenous vein graft interventions: comparison of intracoronary verapamil and nitroglycerin. Cathet Cardiovasc Diagn 39:113–118
Keeley EC, Boura JA, Grines CL (2003) Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 361:13–20
Kim CB, Braunwald E (1993) Potential benefits of late reperfusion of infarcted myocardium: the open artery hypothesis. Circulation 28:837–845
Kloner RA (1993) Does reperfusion injury exist in humans? J Am Coll Cardiol 21:537–545
Kloner RA, Alker KJ (1984) The effect of streptokinase on intramyocardial hemorrhage, infarct size, and the no-reflow phenomenon during coronary reperfusion. Circulation 70:513–521
Kloner RA, Alker K, Campbell C, Figures G, Eisenhauer A, Hale S (1989) Does tissue-type plasminogen activator have direct beneficial effects on the myocardium independent of its ability to lyse intracoronary thrombi? Circulation 79:1125–1136
Kloner RA, Ganote CE, Jennings RB (1974) The “No-Reflow” phenomenon after temporary coronary occlusion in dogs. J Clin Invest 54:1496–1508
Kloner RA, Giacomelli F, Alker KJ,Hale SL,Matthews R, Bellows S (1991) Influx of neutrophils into the wall of large epicardial coronary arteries in response to ischemia/reperfusion. Circulation 84:1758–1772
Kloner RA, Rude RE, Carlson N, Maroko PR, DeBoer LWV, Braunwald E (1980) Ultrastructural evidence of microvascular damage and myocardial cell injury after coronary artery occlusion: Which comes first? Circulation 62:945–952
Kojima S, SakamotoT, Ishihara M, Kimura K,Mivazaki S,Tei C,Hiraoka H, Sonoda M,Tsuchihashi K,Yamagishi M, Inoue T, Asada Y, Ikeda Y, Shirai M, Ogawa H (2004) The white blood cell count is an independent predictor of no-reflow and mortality following acute myocardial infarction in the coronary interventionalera. Ann Med 36:153–160
Kolodgie FD,Virmani R, Frab A (1991) Limitation of no reflow injury by bloodfree reperfusion with oxygenated perfluorochemical (Fluosol-DA 20%). J Am Coll Cardiol 18:215–223
Komanura K, Kitakaze M, Nishida K, Naka M, Tamai J, Uematzu M, Koretsune Y, Nanto S, Hori M, Inoue M, Kamada T, Kodama K (1994) Progressive decrease in coronary veinflow during reperfusion in acute myocardial infarction: clinical documentation of the no reflow phenomenon after successful thrombolysis. J Am Coll Cardiol 24:370–377
Krug A, de Rochemont WM, Korb G (1966) Blood supply of the myocardium after temporary coronary occlusion. Circ Res 19:57–62
Li XS,Wang QD, Pernow J (1995) Beneficial effects of the endothelin receptor antagonist bosentan on myocardial and endothelial injury following ischaemia/ reperfusion in the rat. Eur J Pharmacol 283:161–168
Lindal S, Sorlie D, Jorgensen L (1988) Endothelial cells of the cardiac microvasculature during and after cold cardioplegic ischaemia. Comparison of endothelial and myocyte damage. Scand J Thorac Cardiovasc Surg 22:257–265
Litt MR, Jeremy RW, Weisman HF, Winkelstein JA, Becker LC (1989) Neutrophil depletion limited to reperfusion reduces myocardial infarct size after 90 minutes of ischemia. Evidence for neutrophil- mediated reperfusion injury. Circulation 80:1816–1827
Majino G, Ames A, Chaing J,Wright RL (1967) No reflow after cerebral ischemia. Lancet 2:569–570
Manciet LH, Poole DC, McDonagh PF, Copeland JG, Mathieu-Costello O (1994) Microvascular compression during myocardial ischemia: mechanistic basis for no-reflow phenomenon. Am J Physiol 266:H1541–H550
Martin SE, Chenoweth DE, Engler RL, Roth DM, Longhurst JC (1988) C5a decreases regional coronary blood flow and myocardial function in pigs: implications for a granulocyte mechanism. Circ Res 63:483–491
Marzilli M, Orsini E,Marraccini P,Testa R (2000) Beneficial effects of intracoronary adenosine as an adjunct to primary angioplasty in acute myocardial infarction. Circulation 101:2154–2159
Matsumura K, Jeremy RW, Schaper J, Becker LC (1998) Progression of myocardial necrosis during reperfusion of ischemic myocardium. Circulation 97:795–804
Morishima I, Sone T, Okumara K, Tsuboi H, Kondo J, Mukawa H, Matsui H, Toki Y, Ito T,Hayakawa T (2000) Angiographic no-reflow as a predictor of adverse long-term outcome in patients treated with percutaneous transluminal coronary angioplasty for first myocardial infarction. J Am Coll Cardiol 36:1202–1209
Nathan CF (1987) Neutrophil activation on biological surfaces: massive secretion of hydrogen peroxide in response to products of macrophages and lymphocytes. J Clin Invest 80:1550–1560
Neumann FJ,Blasini R, Schmitt C,Alt E, Dirschinger J, Gawaz M, Kastrati A, Schömig A (1998) 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 98:2695–2701
Ohnishi M,Yamada K,Morooka S, Tojo SJ (1999) Inhibition of P-selectin attenuates neutrophil-mediated myocardial dysfunction. Eur J Pharmacol 366:271–279
O’Neill W, Timmis GC, Bourdillon PD, Lai P, Ganshadarhan V, Walton J Jr, Ramos R, Laufer N, Gordon S, Schork MA et al. (1986) A prospective randomized clinical trial of intracoronary streptokinase versus coronary angioplasty for acute myocardial infarction. N Engl J Med 314:812–818
Piana RN, Paik GY,Moscucci M, Cohen DJ,Gibson CM,Kugelmass AD,Carozza JP,Kuntz RE, Baim DS (1994) Incidence and treatment of ‘no-reflow’ after percutaneous coronary intervention. Circulation 89:2524–2518
Pitarys CJ, Virmani R, Vildibill HD, Jackson EK, Forman MB (1991) Reduction of myocardial reperfusion injury by intravenous adenosine administered during the early reperfusion period. Circulation 83:237–247
Przyklenk K,Kloner RA (1989) “Reperfusion injury” by oxygen-derived free radicals? Effect of superoxide dismutase plus catalase, given at the time of reperfusion, on myocardial infarct size, contractile function, coronary microvasculature, and regional myocardial blood flow. Circ Res 64:86–96
Ragosta M,Camarano G,Kaul S,Powers ER, Sarembock IJ, Gimple LW (1994). Microvascular integrity indicates myocellular viability in patients with recent myocardial infarction. New insights using myocardial contrast echocardiography. Circulation 89:2562–2569
Reffelmann T, Hale SL, Dow JS, Kloner RA (2003) No-reflow phenomenon persists long-term after ischemia/reperfusion in the rat and predicts infarct expansion. Circulation 108:2911–2917
Reffelmann T,Hale SL, Li G, Kloner RA (2002) Relationship between no-reflow and infarct size as influenced by the duration of ischemia and reperfusion in the rabbit. Am J Physiol 283:H766–H772
Reffelmann T, Kloner RA (2002) Microvascular reperfusion injury: Rapid expansion of anatomic no reflow during reperfusion in the rabbit. Am J Physiol 283:H1099- H1107
Reffelmann T, Kloner RA (2003) Is microvascular protection by Cariporide and ischemic preconditioning causally linked to myocardial salvage? Am J Physiol 284:H1134–H1141
Reffelmann T,Kloner RA (2003) Effects of sildenafil on myocardial infarct size, microvascular function, and acute ischemic left ventricular dilation. Cardiovasc Res 98:275–284
Reffelmann T,Kloner RA (2004) Effects of adenosine and verapamil on anatomic no reflow in a rabbit model of coronary artery occlusion and reperfusion. J Cardiovasc Pharmacol 43:580–588
Reffelmann T, Kloner RA (2002) The “no-reflow” phenomenon: Basic science and clinical correlates. Heart 87:162–168
Rentrop KP, Blanke H, Karsch KR,Wiegand V, Kostering H, Oster H, Leitz K (1979) Acute myocardial infarction: intracoronary application of nitroglycerin and streptokinase. Clin Cardiol 18:354–363
Reynolds JM, McDonagh PF (1989) Early in reperfusion, leukocytes alter perfused coronary capillarity and vascular resistance. Am J Physiol 256:H982–H989
Rezkalla SH, Kloner RA (2002) No-reflow phenomenon. Circulation 105:656–662
Richard V, Kaeffer N, Tron C, Thuillez C (1994) Ischemic preconditioning protects against coronary endothelial dysfunction induced by ischemia and reperfusion. Circulation 89:1254–1261
Rochitte CE, Lima JA, Bluemke DA, Reeder SB, McVeigh ER, Furuta T, Becker LC, Melin JA (1998) Magnitude and time course of microvascular obstruction and tissue injury after acute myocardial infarction. Circulation 98:1006–1014
Sage MD, Gavin JB (1986) Microvascular function at the margins of early experimental myocardial infarcts in isolated rabbit hearts. Heart Vessels 2:81–86
Schmiedl A, Richter J, Schnabel PA (2002) Different preservation of myocardial capillary endothelial cells and cardiomyocytes during and after cardioplegic ischemia (25 degrees C) of canine hearts Pathol Res Pract 198:281–290
Schmiedl A, Schnabel PA, Kausch Blecken von Schmeling H, Marten K, Richter J (2001) Swelling of capillary endothelial cells and cardiomyocytes in the ischaemic myocardium of artificially arrested canine hearts. J Electron Microsc 50:349–357
Siminiak T, Flores NA, Sheridan DJ (1995) Neutrophil interactions with endothelium and platelets: possible role in the development of cardiovascular injury. Eur Heart J 16:160–170
Staat P, Rioufol G, Piot C,Cottin Y,Cung TT, L’Huillier I, Aupetit JF, Bonnefoy E, Finet G, Andre-Fouet X, Ovize M (2005) Postconditioning the human heart. Circulation 112:2143–2148
Stein BC, Moses J, Teirstein PS (2000) Balloon occlusion and transluminal aspiration of saphenous vein grafts to prevent distal embolization. Catheter Cardiovasc Interv 51:69–73
Summer WK, Janninson RI (1971) The no reflow phenomenon in renal ischemia. Lab Invest 25:635–643
Swinburn JM, Lahiri A, Senior R (2001) Intravenous myocardial contrast echocardiography predicts recovery of dyssynergic myocardium early after myocardial infarction. J Am Coll Cardiol 38:19–25
Taniyama Y, Ito H, Iwakura K, Masuyama T, Hori M, Takiuchi S, Nishikawa N, Higashino Y, Fujii K, Minamino T (1997) Beneficial effect of intracoronary verapamil on microvascular and myocardial salvage in patients with acute myocardial infarction. J Am Coll Cardiol 30:1193–1199
Topol EJ,Yadav JS (2000) Recognition of the importance of embolization in atherosclerotic vascular disease. Circulation 101:570–580
Tranum-Jensen J, Janse MJ, Fiolet JWT, Krieger WJG,D’Alnoncourt CN,Durrer D (1981) Tissue osmolality, cell swelling, and reperfusion in acute regional myocardial ischemia in the isolated porcine heart.Circ Res 49:364–381
Villanueva FS, Glasheen WP, Sklenar J, Kaul S (1993) Characterization of spatial patterns of flow within the reperfused myocardium by myocardial contrast echocardiography. Implication in determining myocardial salvage. Circulation 88:2596–2606
Villari B,Ambrosio G, Golino P, Ragni M, Focaccio A, Tritto I, Salvatore M, Chiarello M (1993) 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 125:11–23
Watt JA, Hawes EM, Jenkins SH, Williams TC (1990) Effects of nisoldipine on the no-reflow phenomenon in globally ischemic rat hearts. J Cardiovasc Pharmacol 16:487–494
Weiss SJ, Klein R, Slivka A, Wei M (1982) Chlorination of taurine by human neutrophils: evidence for hypochloous acid generation. J Clin Invest 70:598–607
Willerson JT, Watson JT, Hutton I, Fixler DE, Curry GC, Templeton GH (1975) The influence of hypertonic mannitol on regional myocardial blood flow during acute and chronic myocardial ischemia in anaesthetized and awake intact dogs. J Clin Invest 55:892–902
Willms-Kretschmer K,Majno G (1969) Ischemia of the skin. Electron microscopic study of vascular injury. Am J Pathol 54:327–343
Wu KC,Kim RJ, Bluemke DA,Rochitte CE, Zerhouni EA, Becker LC, Lima JA (1998) Quantification and time course of microvascular obstruction by contrast- enhanced echocardiography and magnetic resonance imaging following acute myocardial infarction and reperfusion. J Am Coll Cadiol 32:1756–1764
Wu KC, Zerhouni EA, Judd RM et al. (1998) Prognostic significance of microvascular obstruction by magnetic resonance imaging in patients with acute myocardial infarction. Ciculation 97:765–772
Zhao ZQ, Corvera JS, Halkos ME, Kerendi F,Wang NP, Guyton RA,Vinten- Johansen J (2003) Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol 285:H579–H588
Zhao ZQ, Vinten-Johansen J (2006) Postconditioning: reduction of reperfusion- induced injury. Cardiovasc Res 70:200–211
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Reffelmann, T., Kloner, R.A. The no-reflow phenomenon: A basic mechanism of myocardial ischemia and reperfusion. Basic Res Cardiol 101, 359–372 (2006). https://doi.org/10.1007/s00395-006-0615-2
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00395-006-0615-2