The myocardial microcirculation: A key target for salvaging ischemic myocardium?


Clinical management of patients with acute myocardial infarction for the most part involves re-opening of an infarct-related coronary vessel by the use of clot-busting pharmacologic treatment or percutaneous coronary interventions. While blood flow in the epicardial coronary vessel is restored downstream, effects remain largely unexplored; progressive injury at the microvessel level has significant repercussions on restoration of cardiocyte viability and the ventricular blood flow and contractile function relationship. This review focuses on the cardiac microcirculation and the fact that it should be a principle target of future studies to permit improvement of clinical outcomes in patients presenting with evolving myocardial infarction.

Share and Cite:

Kingma, J. (2013) The myocardial microcirculation: A key target for salvaging ischemic myocardium?. World Journal of Cardiovascular Diseases, 3, 8-16. doi: 10.4236/wjcd.2013.35A002.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Reimer, K.A., Lowe, J.E., Rasmussen, M.M. and Jennings, R.B. (1977) The wavefront phenomenon of ischemic cell death: I. Myocardial infarct size vs. duration of coronary occlusion in dogs. Circulation, 56, 786-794. doi:10.1161/01.CIR.56.5.786
[2] Kloner, R.A., Rude, R.E., Carlson, N., Maroko, P.R., De-Boer, L.W.V. and Braunwald, E. (1980) Ultrastructural evidence of microvascular damage and myocardial cell injury after coronary artery occlusion: Which comes first? Circulation, 62, 945-952. doi:10.1161/01.CIR.62.5.945
[3] Matsunari, I., Schricke, U., Bengel, F.M., Haase, H.U., Barthel, P., Schmidt, G., Nekolla, S.G., Schoemig, A. and Schwaiger, M. (2000) Extent of cardiac sympathetic neuronal damage is determined by the area of ischemia in patients with acute coronary syndromes. Circulation, 101, 2579-2585. doi:10.1161/01.CIR.101.22.2579
[4] Braunwald, E. and Kloner, R.A. (1985) Myocardial reperfusion: A double-edged sword? The Journal of Clinical Investigation, 76, 1713-1719. doi:10.1172/JCI112160
[5] Piper, H.M., Garcia-Dorado, D. and Ovize, M. (1998) A fresh look at reperfusion injury. Cardiovascular Research, 38, 291-300. doi:10.1016/S0008-6363(98)00033-9
[6] Yellon, D.M. and Hausenloy, D.J. (2007) Myocardial reperfusion injury. The New England Journal of Medicine, 357, 1121-1135. doi:10.1056/NEJMra071667
[7] Hearse, D.J. (1977) Reperfusion of the ischemic myocardium. Journal of Molecular and Cellular Cardiology, 9, 605-616. doi:10.1016/S0022-2828(77)80357-X
[8] Hausenloy, D.J. and Yellon, D.M. (2013) Myocardial ischemia-reperfusion injury: A neglected therapeutic target. The Journal of Clinical Investigation, 123, 92-100. doi:10.1172/JCI62874
[9] Ito, H., Okamura, A., Iwakura, K., Masuyama, T., Hori, M., Takiuchi, S., Negoro, S., Nakatsuchi, Y., Taniyama, Y., Higashino, Y., Fujii, K. and Minamino, T. (1996) Myocardial perfusion patterns related to thrombolysis in myocardial infarction perfusion grades after coronary angioplasty in patients with acute anterior wall myocardial infarction. Circulation, 93, 1993-1999. doi:10.1161/01.CIR.93.11.1993
[10] Ito, H., Maruyama, A., Iwakura, K., Takiuchi, S., Masuyama, T., Hori, M., Higashino, Y., Fujii, K. and Minamino, T. (1996) Clinical implications of the “no reflow” phenomenon. A predictor of complications and left ventricular remodeling in reperfused anterior wall myocardial infarction. Circulation, 93, 223-228. doi:10.1161/01.CIR.93.2.223
[11] Palade, G.E., Simionescu, M. and Simionescu, N. (1979) Structural aspects of the permeability of the microvascular endothelium. Acta Physiologica Scandinavica, S463, 11-32.
[12] Granger, D.N. (1998) Physiology and pathophysiology of the microcirculation. Dialogues in Cardiovascular Medicine, 3, 123-140.
[13] Granger, D.N. and Korthuis, R.J. (1995) Physiologic mechanisms of postischemic tissue injury. Annual Review of Physiology, 57, 311-332. doi:10.1146/
[14] Harrison, D.G. (1997) Cellular and molecular mechanisms of endothelial cell dysfunction. The Journal of Clinical Investigation, 100, 2153-2157. doi:10.1172/JCI119751
[15] Drexler, H. and Hornig, B. (1996) Importance of endothelial function in chronic heart failure. Journal of Cardiovascular Pharmacology, 27, S9-S12. doi:10.1097/00005344-199600002-00003
[16] White, S.K., Hausenloy, D.J. and Moon, J.C. (2012) Imaging the myocardial microcirculation post-myocardial infarction. Current Heart Failure Reports, 9, 282-292. doi:10.1007/s11897-012-0111-y
[17] Camici, P.G. and Crea, F. (2007) Coronary microvascular dysfunction. The New England Journal of Medicine, 356, 830-840. doi:10.1056/NEJMra061889
[18] Chilian, W.M. (1997) Coronary microcirculation in health and disease. Summary of an NHLBI workshop. Circulation, 95, 522-528. doi:10.1161/01.CIR.95.2.522
[19] Krogh, A. (1919) The supply of oxygen to the tissues and the regulation of the capillary circulation. The Journal of Physiology, 52, 457-474.
[20] James, T.N. (1970) The delivery and distribution of coronary collateral circulation. Chest, 58, 183-203. doi:10.1378/chest.58.3.183
[21] De, B.M. and Schaper, W. (1971) Quantitative histology of the canine coronary collateral circulation in localized myocardial ischemia. Life Science, 10, 857-868. doi:10.1016/0024-3205(71)90157-3
[22] Newman, P.E. (1981) The coronary collateral circulation: Determinants and functional significance in ischemic heart disease. American Heart Journal, 102, 431-445. doi:10.1016/0002-8703(81)90318-5
[23] Kersten, J.R., Pagel, P.S., Chilian, W.M. and Warltier, D.C. (1999) Multifactorial basis for coronary collateralization: A complex adaptive response to ischemia. Cardiovascular Research, 43, 44-57. doi:10.1016/S0008-6363(99)00077-2
[24] Kersten, J.R. and Warltier, D.C. (1999) Modulation of the adaptive response to myocardial ischemia by coexisting disease. American Journal of Physiology, 276, H2268-H2270.
[25] Heil, M. and Schaper, W. (2004) Influence of mechanical, cellular, and molecular factors on collateral artery growth (arteriogenesis). Circulation Research, 95, 449-458. doi:10.1161/01.RES.0000141145.78900.44
[26] Kloner, R.A., Ganote, C.E. and Jennings, R.B. (1974) The “no-reflow” phenomenon after temporary coronary occlusion in the dog. The Journal of Clinical Investigation, 54, 1496-1508. doi:10.1172/JCI107898
[27] Schwartz, B.G. and Kloner, R.A. (2012) Coronary no reflow. Journal of Molecular and Cellular Cardiology, 52, 873-882. doi:10.1016/j.yjmcc.2011.06.009
[28] Ito, H., Okamura, A., Iwakura, K., Masuyama, T., Hori, M., Takiuchi, S., Negoro, S., Nakatsuchi, Y., Taniyama, Y., Higashino, Y., Fujii, K. and Minamino, T. (1996) Myocardial perfusion patterns related to thrombolysis in myocardial infarction perfusion grades after coronary angioplasty in patients with acute anterior wall myocardial infarction. Circulation, 93, 1993-1999. doi:10.1161/01.CIR.93.11.1993
[29] Heusch, G., Kleinbongard, P., Bose, D., Levkau, B., Haude, M., Schulz, R. and Erbel, R. (2009) Coronary micro-embolization: from bedside to bench and back to bedside. Circulation, 120, 1822-1836. doi:10.1161/CIRCULATIONAHA.109.888784
[30] Luo, A.K. and Wu, K.C. (2006) Imaging microvascular obstruction and its clinical significance following acute myocardial infarction. Heart Failure Reviews, 11, 305-312. doi:10.1007/s10741-006-0231-0
[31] Hausenloy, D.J., Baxter, G., Bell, R., Botker, H.E., Da-vidson, S.M., Downey, J., Heusch, G., Kitakaze, M., Le-cour, S., Mentzer, R., Mocanu, M.M., Ovize, M., Schulz, R., Shannon, R., Walker, M., Walkinshaw, G. and Yellon, D.M. (2010) Translating novel strategies for cardioprotection: The Hatter Workshop Recommendations. Basic Research in Cardiology, 105, 677-686. doi:10.1007/s00395-010-0121-4
[32] Schwartz, L.L., Kloner, R.A., Arai, A.E., Baines, C.P., Bolli, R., Braunwald, E., Downey, J., Gibbons, R.J., Gottlieb, R.A., Heusch, G., Jennings, R.B., Lefer, D.J., Mentzer, R.M., Murphy, E., Ovize, M., Ping, P., Przyklenk, K., Sack, M.N., Vander Heide, R.S., Vinten-Johansen, J. and Yellon, D.M. (2011) New horizons in cardioprotection: Recommendations from the 2010 National Heart, Lung, and Blood Institute Workshop. Circulation, 124, 1172-1179. doi:10.1161/CIRCULATIONAHA.111.032698
[33] Kloner, R.A. and Jennings, R.B. (2001) Consequences of brief ischemia: Stunning, preconditioning, and their clinical implications: Part 1. Circulation, 104, 2981-2989. doi:10.1161/hc4801.100038
[34] Hausenloy, D.J. and Yellon, D.M. (2009) Myocardial protection: Is primary PCI enough? Nature Clinical Practice Cardiovascular Medicine, 6, 12-13. doi:10.1038/ncpcardio1371
[35] Reimer, K.A., Jennings, R.B., Cobb, F.R., Murdock, R.H., Greenfield, J.C., Becker, L.C., Bulkley, B.H., Hutchins, G.M., Schwartz Jr., R.P., Bailey, K.R. and Passamani, E.R. (1985) Animal models for protecting ischemic myocardium (AMPIM): Results of the NHLBI cooperative study. Comparison of the unconscious and conscious dog models. Circulation Research, 56, 651-665. doi:10.1161/01.RES.56.5.651
[36] Sharma, V., Bell, R.M. and Yellon, D.M. (2012) Targeting reperfusion injury in acute myocardial infarction: A review of reperfusion injury pharmacotherapy. Expert Opinion on Pharmacotherapy, 13, 1153-1175. doi:10.1517/14656566.2012.685163
[37] Bolli, R. (1992) Postischemic myocardial stunning: Pathogenesis, pathophysiology, and clinical relevance. In: Yellon, D.M. and Jennings, R.B., Eds., Myocardial Protection: The Pathophysiology of Reperfusion and Reperfusion Injury, Raven Press, New York, 1992, 105-149.
[38] Bolli, R. (1992) Myocardial ‘stunning’ in man. Circulation, 86, 1671-1691. doi:10.1161/01.CIR.86.6.1671
[39] Canty Jr., J.M. and Fallavollita, J.A. (2005) Hibernating myocardium. Journal of Nuclear Cardiology, 12, 104-119. doi:10.1016/j.nuclcard.2004.11.003
[40] Tubau, J.F. and Rahimtoola, S.H. (1992) Hibernating myocardium: A historical perspective. Cardiovascular Drugs and Therapy, 6, 267-271. doi:10.1007/BF00051149
[41] Heusch, G. (1998) Hibernating myocardium. Physiological Reviews, 78, 1055-1085.
[42] Heusch, G., Schulz, R. and Rahimtoola, S.H. (2005) Myocardial hibernation: A delicate balance. American Journal of Physiology: Heart and Circulatory Physiology, 288, H984-H999. doi:10.1152/ajpheart.01109.2004
[43] Beltrami, C.A., Finato, N., Rocco, M., Feruglio, G.A., Puricelli, C., Cigola, E., Quaini, F., Sonnenblick, E.H., Olivetti, G. and Anversa, P. (1994) Structural basis of end-stage failure in ischemic cardiomyopathy in humans. Circulation, 89, 151-163. doi:10.1161/01.CIR.89.1.151
[44] Canty Jr., J.M. and Suzuki, G. (2012) Myocardial perfusion and contraction in acute ischemia and chronic ischemic heart disease. Journal of Molecular and Cellular Cardiology, 52, 822-831. doi:10.1016/j.yjmcc.2011.08.019
[45] Kelly, R.F., Cabrera, J.A., Ziemba, E.A., Crampton, M., Anderson, L.B., McFalls, E.O. and Ward, H.B. (2011) Continued depression of maximal oxygen consumption and mitochondrial proteomic expression despite successful coronary artery bypass grafting in a swine model of hibernation. The Journal of Thoracic and Cardiovascular Surgery, 141, 261-268. doi:10.1016/j.jtcvs.2010.08.061
[46] Liem, D.A., Manintveld, O.C., Schoonderwoerd, K., McFalls, E.O., Heinen, A., Verdouw, P.D., Sluiter, W. and Duncker, D.J. (2008) Ischemic preconditioning modulates mitochondrial respiration, irrespective of the employed signal transduction pathway. Translational Research, 151, 17-26. doi:10.1016/j.trsl.2007.09.007
[47] Page, B., Young, R., Iyer, V., Suzuki, G., Lis, M., Korotchkina, L., Patel, M.S., Blumenthal, K.M., Fallavollita, J.A. and Canty Jr., J.M. (2008) Persistent regional downregulation in mitochondrial enzymes and upregulation of stress proteins in swine with chronic hibernating myocardium. Circulation Research, 102, 103-112. doi:10.1161/CIRCRESAHA.107.155895
[48] Hu, Q., Suzuki, G., Young, R.F., Page, B.J., Fallavollita, J.A. and Canty Jr., J.M. (2009) Reductions in mitochondrial O2 consumption and preservation of high-energy phosphate levels after simulated ischemia in chronic hibernating myocardium. American Journal of Physiology: Heart and Circulatory Physiology, 297, H223-H232. doi:10.1152/ajpheart.00992.2008
[49] Gall Jr., S.A., Maier, G.W., Glower, D.D., Gaynor, J.W., Cobb, F.R., Sabiston Jr., D.C. and Rankin, J.S. (1993) Recovery of myocardial function after repetitive episodes of reversible ischemia. American Journal of Physiology: Heart and Circulatory Physiology, 264, H1130-H1138.
[50] Gallagher, K.P., Matsuzaki, M., Koziol, J.A., Kemper, W.S. and Ross Jr., J. (1984) Regional myocardial perfusion and wall thickening during ischemia in conscious dogs. American Journal of Physiology: Heart and Circulatory Physiology, 247, H727-H738.
[51] Heyndrickx, G.R., Baig, H., Nellens, P., Leusen, I., Fishbein, M.C. and Vatner, S.F. (1978) Depression of regional blood flow and wall thickening after brief coronary occlusions. American Journal of Physiology: Heart and Circulatory Physiology, 234, H653-H659.
[52] Vatner, S.F. (1980) Correlation between acute reductions in myocardial blood flow and function in conscious dogs. Circulation Research, 47, 201-207. doi:10.1161/01.RES.47.2.201
[53] Heusch, G. (2008) Heart rate in the pathophysiology of coronary blood flow and myocardial ischaemia: Benefit from selective bradycardic agents. British Journal of Pharmacology, 153, 1589-1601. doi:10.1038/sj.bjp.0707673
[54] Ross Jr., J. (1991) Myocardial perfusion-contraction matching. Implications for coronary heart disease and hibernation. Circulation, 83, 1076-1083. doi:10.1161/01.CIR.83.3.1076
[55] Kingma, J.G., Simard, D. and Rouleau, J.R. (2011) Modulation of nitric oxide affects myocardial perfusion-contraction matching in anesthetised dogs with recurrent noflow ischemia. Experimental Physiology, 96, 1293-1301. doi:10.1113/expphysiol.2011.060244
[56] DeFily, D.V. (1998) Control of microvascular resistance in physiological conditions and reperfusion. Journal of Molecular and Cellular Cardiology, 30, 2547-2554. doi:10.1006/jmcc.1998.0826
[57] Chilian, W.M. (1991) Microvascular pressures and resistances in the left ventricular subepicardium and subendocardium. Circulation Research, 69, 561-570. doi:10.1161/01.RES.69.3.561
[58] Krug, A., Du Mesnil, D.R. and Korb, G. (1966) Blood supply of the myocardium after temporary coronary occlusion. Circulation Research, 19, 57-62. doi:10.1161/01.RES.19.1.57
[59] Staat, P., Rioufol, G., Piot, C., Cottin, Y., Cung, T.T., L’Huillier, I., Aupetit, J.F., Bonnefoy, E., Finet, G., Andre-Fouet, X. and Ovize, M. (2005) Postconditioning the human heart. Circulation, 112, 2143-2148. doi:10.1161/CIRCULATIONAHA.105.558122
[60] Guo, A.Q., Sheng, L., Lei, X. and Shu, W. (2013) Pharmacological and physical prevention and treatment of no-reflow after primary percutaneous coronary intervention in ST-segment elevation myocardial infarction. Journal of International Medical Research, 41, 537-547. doi:10.1177/0300060513479859
[61] Niccoli, G., Burzotta, F., Galiuto, L. and Crea, F. (2009) Myocardial no-reflow in humans. Cardiology, 54, 281-292. doi:10.1016/j.jacc.2009.03.054
[62] Reffelmann, T., Hale, S.L., Li, G. and Kloner, R.A. (2002) Relationship between no reflow and infarct size as influenced by the duration of ischemia and reperfusion. American Journal of Physiology: Heart and Circulatory Physiology, 282, H766-H772.
[63] Reffelmann, T. and Kloner, R.A. (2002) Microvascular reperfusion injury: Rapid expansion of anatomic no reflow during reperfusion in the rabbit. American Journal of Physiology: Heart and Circulatory Physiology, 283, H1099-H1107.
[64] Galiuto, L. and Iliceto, S. (1998) Myocardial contrast echocardiography in the evaluation of viable myocardium after acute myocardial infarction. American Journal of Cardiology, 81, 29G-32G. doi:10.1016/S0002-9149(98)00050-2
[65] Galiuto, L., DeMaria, A.N., May-Newman, K., Del, B.U., Ohmori, K., Bhargava, V., Flaim, S.F. and Iliceto, S. (1998) Evaluation of dynamic changes in microvascular flow during ischemia-reperfusion by myocardial contrast echocardiography. Cardiology, 32, 1096-1101. doi:10.1016/S0735-1097(98)00349-0
[66] Ambrosio, G., Weisman, H.F., Mannisi, J.A. and Becker, L.C. (1989) Progressive impairment of regional myocardial perfusion after initial restoration of postischemic blood flow. Circulation, 80, 1846-1861. doi:10.1161/01.CIR.80.6.1846
[67] Golino, P., Maroko, P.R. and Carew, T.E. (1987) The effect of acute hypercholesterolemia on myocardial infarct size and the no-reflow phenomenon during coronary occlusion-reperfusion. Circulation, 75, 292-298. doi:10.1161/01.CIR.75.1.292
[68] Matsumura, K., Jeremy, R.W., Schaper, J. and Becker, L.C. (1998) Progression of myocardial necrosis during reperfusion of ischemic myocardium. Circulation, 97, 795-804. doi:10.1161/01.CIR.97.8.795
[69] Rezkalla, S.H., Dharmashankar, K.C., Abdalrahman, I.B. and Kloner, R.A. (2010) No-reflow phenomenon following percutaneous coronary intervention for acute myocardial infarction: Incidence, outcome, and effect of pharmacologic therapy. Journal of Interventional Cardiology, 23, 429-436. doi:10.1111/j.1540-8183.2010.00561.x
[70] Murry, C.E., Jennings, R.B. and Reimer, K.A. (1986) Preconditioning with ischemia: A delay of lethal cell injury in ischemic myocardium. Circulation, 74, 1124-1136. doi:10.1161/01.CIR.74.5.1124
[71] Ovize, M., Baxter, G.F., Di, L.F., Ferdinandy, P., Garcia-Dorado, D., Hausenloy, D.J., Heusch, G., Vinten-Johansen, J., Yellon, D.M. and Schulz, R. (2010) Post-conditioning and protection from reperfusion injury: Where do we stand? Position paper from the Working Group of Cellular Biology of the Heart of the European Society of Cardiology. Cardiovascular Research, 87, 406-423. doi:10.1093/cvr/cvq129
[72] Yellon, D.M. and Downey, J.M. (2003) Preconditioning the myocardium: From cellular physiology to clinical cardiology. Physiological Reviews, 83, 1113-1151.
[73] Downey, J.M., Davis, A.M. and Cohen, M.V. (2007) Signaling pathways in ischemic preconditioning. Heart Failure Reviews, 12, 181-188. doi:10.1007/s10741-007-9025-2
[74] Hausenloy, D.J. and Yellon, D.M. (2009) Preconditioning and postconditioning: Underlying mechanisms and clinical application. Atherosclerosis, 204, 334-341. doi:10.1016/j.atherosclerosis.2008.10.029
[75] Lu, Y.Z., Wu, C.C., Huang, Y.C., Huang, C.Y., Yang, C.Y., Lee, T.C., Chen, C.F. and Yu, L.C. (2012) Neutrophil priming by hypoxic preconditioning protects against epithelial barrier damage and enteric bacterial translocation in intestinal ischemia/reperfusion. Laboratory Investigation, 92, 783-796. doi:10.1038/labinvest.2012.11
[76] Ko, J.K. and Cho, C.H. (2011) Adaptive cytoprotection and the brain-gut axis. Digestion, 83, 19-24. doi:10.1159/000323400
[77] Meng, R., Asmaro, K., Meng, L., Liu, Y., Ma, C., Xi, C., Li, G., Ren, C., Luo, Y., Ling, F., Jia, J., Hua, Y., Wang, X., Ding, Y., Lo, E.H. and Ji, X. (2012) Upper limb ischemic preconditioning prevents recurrent stroke in intracranial arterial stenosis. Neurology, 79, 1853-1861. doi:10.1212/WNL.0b013e318271f76a
[78] Koch, S., Sacco, R.L. and Perez-Pinzon, M.A. (2012) Preconditioning the brain: Moving on to the next frontier of neurotherapeutics. Stroke, 43, 1455-1457. doi:10.1161/STROKEAHA.111.646919
[79] Lynch III, C. (1999) Anesthetic preconditioning: Not just for the heart? Anesthesiology, 91, 606-608. doi:10.1097/00000542-199909000-00007
[80] Minguet, G., Joris, J. and Lamy, M. (2007) Preconditioning and protection against ischaemia-reperfusion in non-cardiac organs: A place for volatile anaesthetics? European Journal of Anaesthesiology, 24, 733-745. doi:10.1017/S0265021507000531
[81] Ma, X.J., Zhang, X.H., Li, C.M. and Luo, M. (2006) Effect of postconditioning on coronary blood flow velocity and endothelial function in patients with acute myocardial infarction. Scandinavian Cardiovascular Journal, 40, 327-333. doi:10.1080/14017430601047864
[82] Laskey, W.K., Yoon, S., Calzada, N. and Ricciardi, M.J. (2008) Concordant improvements in coronary flow reserve and ST-segment resolution during percutaneous coronary intervention for acute myocardial infarction: A benefit of postconditioning. Catheterization and Cardiovascular Interventions, 72, 212-220.
[83] Laude, K., Beauchamp, P., Thuillez, C. and Richard, V. (2002) Endothelial protective effects of preconditioning. Cardiovascular Research, 55, 466-473. doi:10.1016/S0008-6363(02)00277-8
[84] Reffelmann, T. and Kloner, R.A. (2002) Is microvascular protection by cariporide and ischemic preconditioning causally linked to myocardial salvage? American Journal of Physiology: Heart and Circulatory Physiology, 284, H1134-H1141.
[85] Zhao, Z.Q., Corvera, J.S., Halkos, M.E., Kerendi, F., Wang, N.P., Guyton, R.A. and Vinten-Johansen, J. (2003) Inhibition of myocardial injury by ischemic postconditioning during reperfusion: Comparison with ischemic preconditioning. American Journal of Physiology: Heart and Circulatory Physiology, 285, H579-H588.
[86] Kaeffer, N., Richard, V., Francois, A., Lallemand, F., Henry, J.P. and Thuillez, C. (1996) Preconditioning prevents chronic reperfusion-induced coronary endothelial dysfunction in rats. American Journal of Physiology, 271, H842-H849.
[87] Richard, V., Kaeffer, N., Tron, C. and Thuillez, C. (1994) Ischemic preconditioning protects against coronary endothelial dysfunction induced by ischemia and reperfusion. Circulation, 89, 1254-1261. doi:10.1161/01.CIR.89.3.1254
[88] Skyschally, A., Walter, B. and Heusch, G. (2012) Coronary microembolization during early reperfusion: Infarct extension, but protection by ischaemic postconditioning. European Heart Journal. doi:10.1093/eurheartj/ehs434
[89] Whittaker, P. and Przyklenk, K. (1994) Reduction of infarct size in vivo with ischemic preconditioning: Mathematical evidence for protection via non-ischemic tissue. Basic Research in Cardiology, 89, 6-15. doi:10.1007/BF00788673
[90] Freixa, X., Bellera, N., Ortiz-Perez, J.T., Jimenez, M., Pare, C., Bosch, X., De Caralt, T.M., Betriu, A. and Masotti, M. (2012) Ischaemic postconditioning revisited: Lack of effects on infarct size following primary percutaneous coronary intervention. European Heart Journal, 33, 103-112. doi:10.1093/eurheartj/ehr297
[91] Sorensson, P., Saleh, N., Bouvier, F., Bohm, F., Settergren, M., Caidahl, K., Tornvall, P., Arheden, H., Ryden, L. and Pernow, J. (2010) Effect of postconditioning on infarct size in patients with ST elevation myocardial infarction. Heart, 96, 1710-1715. doi:10.1136/hrt.2010.199430
[92] Herrmann, J., Kaski, J.C. and Lerman, A. (2012) Coronary microvascular dysfunction in the clinical setting: From mystery to reality. European Heart Journal, 33, 2771-2781. doi:10.1093/eurheartj/ehs246
[93] Dwivedi, G., Janardhanan, R., Hayat, S.A., Lim, T.K., Greaves, K. and Senior, R. (2010) Relationship between myocardial perfusion with myocardial contrast echocardiography and function early after acute myocardial infarction for the prediction of late recovery of function. International Journal of Cardiology, 140, 169-174. doi:10.1016/j.ijcard.2008.11.052
[94] Hayat, S.A. and Senior, R. (2008) Myocardial contrast echocardiography in ST elevation myocardial infarction: Ready for prime time? European Heart Journal, 29, 299-314. doi:10.1093/eurheartj/ehm621
[95] Bolognese, L., Carrabba, N., Parodi, G., Santoro, G.M., Buonamici, P., Cerisano, G. and Antoniucci, D. (2004) Impact of microvascular dysfunction on left ventricular remodeling and long-term clinical outcome after primary coronary angioplasty for acute myocardial infarction. Circulation, 109, 1121-1126. doi:10.1161/01.CIR.0000118496.44135.A7
[96] Dwivedi, G., Janardhanan, R., Hayat, S.A., Swinburn, J.M. and Senior, R. (2007) Prognostic value of myocardial viability detected by myocardial contrast echocardiography early after acute myocardial infarction. Cardiology, 50, 327-334. doi:10.1016/j.jacc.2007.03.036
[97] Posa, A., Pavo, N., Hemetsberger, R., Csonka, C., Csont, T., Ferdinandy, P., Petrasi, Z., Varga, C., Pavo, I.J., Laszlo Jr., F., Huber, K. and Gyongyosi, M. (2010) Protective effect of ischaemic preconditioning on ischaemia/reperfusion-induced microvascular obstruction determined by on-line measurements of coronary pressure and blood flow in pigs. Thrombosis and Haemostasis, 103, 450-460. doi:10.1160/TH09-03-0165
[98] Hoffman, J.I. (1995) Heterogeneity of myocardial blood flow. Basic Research in Cardiology, 90, 103-111. doi:10.1007/BF00789440
[99] Hoffman, J.I.E. (1987) A critical view of coronary reserve. Circulation, 75, 1-6.
[100] Austin, R.E.J., Aldea, G.S., Coggins, D.L., Flynn, A.E. and Hoffman, J.I.E. (1990) Profound spatial heterogeneity of coronary reserve. Discordance between patterns of resting and maximal myocardial blood flow. Circulation Research, 67, 319-331. doi:10.1161/01.RES.67.2.319
[101] Bassingthwaighte, J.B., King, R.B. and Roger, S.A. (1989) Fractal nature of regional myocardial blood flow heterogeneity. Circulation Research, 65, 578-590. doi:10.1161/01.RES.65.3.578
[102] Kingma Jr., J.G., Simard, D. and Rouleau, J.R. (2005) Comparison of neutron activated and radiolabeled microsphere methods for measurement of transmural myocardial blood flow in dogs. Journal of Thrombosis and Thrombolysis, 19, 201-208. doi:10.1007/s11239-005-1201-4
[103] Alhaddad, I.A., Kloner, R.A., Hakim, I., Garno, J.L. and Brown Jr., E.J. (1996) Benefits of late coronary artery reperfusion on infarct expansion progressively diminish over time: relation to viable islets of myocytes within the scar. American Heart Journal, 131, 451-457. doi:10.1016/S0002-8703(96)90522-0
[104] Fearon, W.F., Aarnoudse, W., Pijls, N.H., De, B.B., Balsam, L.B., Cooke, D.T., Robbins, R.C., Fitzgerald, P.J., Yeung, A.C. and Yock, P.G. (2004) Microvascular resistance is not influenced by epicardial coronary artery stenosis severity: Experimental validation. Circulation, 109, 2269-2272. doi:10.1161/01.CIR.0000128669.99355.CB

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.