Trends in Cardiovascular Medicine
Volume 15, Issue 3 , Pages 101-110 , April 2005

Mechanisms of Cell Survival in Myocardial Hibernation

  • Christophe Depre
  • ,
  • Stephen F. Vatner

      Affiliations

    • Corresponding Author InformationAddress correspondence to: Stephen F. Vatner, MD, Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 South Orange Avenue, MSB G-609, Newark, NJ 07103, USA. Tel.: (+1) 973-972-8920; fax: (+1) 973-972-7489

References 

  1. Arai A, Pantely G, Anselone C, et al. Active downregulation of myocardial energy requirements during prolonged moderate ischemia in swine. Circ Res. 1991;69:1458–1469
  2. Ausma J, Thone F, Dispersyn GD, et al. Dedifferentiated cardiomyocytes from chronic hibernating myocardium are ischemia-tolerant. Mol Cell Biochem. 1998;186:159–168
  3. Barnes E, Dutka DP, Khan M, et al. Effect of repeated episodes of reversible myocardial ischemia on myocardial blood flow and function in humans. Am J Physiol. 2002;282:H1603–H1608
  4. Bito V, Heinzel F, Weidemann F, et al. Cellular mechanisms of contractile dysfunction in hibernating myocardium. Circ Res. 2004;94:794–801
  5. Borgers M, Thoné F, Wouters L, et al. Structural correlates of regional myocardial dysfunction in patients with critical coronary artery stenosis. Cardiovasc Pathol. 1993;2:237–245
  6. Brand T, Sharma H, Fleischmann K, et al. Proto-oncogene expression in porcine myocardium subjected to ischemia and reperfusion. Circ Res. 1992;71:1351–1360
  7. Brar B, Stephanou A, Knight R, Latchman D. Activation of protein kinase B/Akt by urocortin is essential for its ability to protect cardiac cells against hypoxia/reoxygenation–induced cell death. J Mol Cell Cardiol. 2002;34:483–492
  8. Buja L, Muntz K, Lipscomb K, Willerson J. Cardiac hypertrophy in chronic ischemic heart disease. Perspect Cardiovasc Res. 1983;8:287–294
  9. Camici P, Wijns W, Borgers M, et al. Pathophysiological mechanisms of chronic reversible left ventricular dysfunction due to coronary artery disease. Circulation. 1997;96:3205–3214
  10. Camici PG, Wijns W, Borgers M, et al. Pathophysiological mechanisms of chronic reversible left ventricular dysfunction due to coronary artery disease (hibernating myocardium). Circulation. 1997;96:3205–3214
  11. Camici PG, Rimoldi OE. Myocardial blood flow in patients with hibernating myocardium. Cardiovasc Res. 2003;57:302–311
  12. Canty JM, Suzuki G, Banas MD, et al. Hibernating myocardium: chronically adapted to ischemia but vulnerable to sudden death. Circ Res. 2004;94:1142–1149
  13. Charpentier A, Bednarek A, Daniel R, et al. Effects of estrogen on global gene expression: identification of novel targets of estrogen action. Cancer Res. 2000;60:5893–5977
  14. Chen C, Chen L, Fallon JT, et al. Functional and structural alterations with 24-hour myocardial hibernation and recovery after reperfusion: a pig model of myocardial hibernation. Circulation. 1996;94:507–516
  15. Chen C, Ma L, Dyckman W, et al. Left ventricular remodeling in myocardial hibernation. Circulation. 1997;96:II46–II50
  16. Conversano A, Walsh J, Geltman E, et al. Delineation of myocardial stunning and hibernation by positron emission tomography in advanced coronary artery disease. Am Heart J. 1996;131:440–450
  17. Cook SA, Matsui T, Li L, Rosenzweig A. Transcriptional effects of chronic Akt activation in the heart. J Biol Chem. 2002;277:22528–22533
  18. de Silva R, Yamamoto Y, Rhodes C, et al. Preoperative prediction of the outcome of coronary revascularization using positron emission tomography. Circulation. 1992;86:1738–1742
  19. Deanfield J, Maseri A, Selwyn A, et al. Myocardial ischaemia during daily life in patients with stable angina: Its relation to symptoms and heart rate changes. Lancet. 1983;2:753–758
  20. Depre C, Vanoverschelde JL, Melin JA, et al. Structural and metabolic correlates of the reversibility of chronic left ventricular ischemic dysfunction in humans. Am J Physiol. 1995;268:H1265–H1275
  21. Depre C, Vanoverschelde JL, Gerber B, et al. Correlation of functional recovery with myocardial blood flow, glucose uptake, and morphologic features in patients with chronic left ventricular ischemic dysfunction undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg. 1997;113:82–87
  22. Depre C, Shipley G, Chen W, et al. Unloaded heart in vivo replicates fetal gene expression of cardiac hypertrophy. Nat Med. 1998;4:1269–1275
  23. Depre C, Taegtmeyer H. Metabolic aspects of programmed cell survival and cell death in the heart. Cardiovasc Res. 2000;45:538–548
  24. Depre C, Tomlinson JE, Kudej RK, et al. Gene program for cardiac cell survival induced by transient ischemia in conscious pig. Proc Natl Acad Sci USA. 2001;98:9336–9341
  25. Depre C, Hase M, Gaussin V, et al. H11 kinase is a novel mediator of myocardial hypertrophy in vivo. Circ Res. 2002;91:1007–1014
  26. Depre C, Kim S-J, John AS, et al. Program of cell survival underlying human and experimental hibernating myocardium. Circ Res. 2004;95:433–440
  27. Diamond G, Forrester J, DeLuz P, et al. Post-extrasystolic potentiation of ischemic myocardium by atrial stimulation. Am Heart J. 1978;95:204–209
  28. Dispersyn GD, Geuens E, Ver Donck L, et al. Adult rabbit cardiomyocytes undergo hibernation-like dedifferentiation when co-cultured with cardiac fibroblasts. Cardiovasc Res. 2001;51:230–240
  29. Elsasser A, Schleper M, Klovekorn WP, et al. Hibernating myocardium: an incomplete adaptation to ischemia. Circulation. 1997;96:2920–2931
  30. Fallavolita JA, Perry BJ, Canty JM. 18F-2-deoxyglucose deposition and regional flow in pigs with chronically dysfunctional myocardium. Evidence for transmural variations in chronic hibernating myocardium. Circulation. 1997;95:1900–1909
  31. Fallavollita JA, Jacob S, Young RF, Canty JM. Regional alterations in SR Ca2+-ATPase, phospholamban, and HSP-70 expression in chronic hibernating myocardium. Am J Physiol Heart Circ Physiol. 1999;277:H1418–H1428
  32. Fath-Ordoubadi F, Beatt KJ, Spyrou N, Camici PG. Efficacy of coronary angioplasty for the treatment of hibernating myocardium. Heart. 1999;82:210–216
  33. Frass O, Sharma H, Knoll R, et al. Enhanced gene expression of calcium regulatory proteins in stunned porcine myocardium. Cardiovasc Res. 1993;27:2037–2043
  34. Gerber B, Melin JA, Bol A, Vanoverschelde JL. Attenuated response of myocardial glucose utilization to insulin stimulation in hibernating myocardium. Circulation. 1995;92:I-313
  35. Gerber BL, Vanoverschelde J-LJ, Bol A, et al. Myocardial blood flow, glucose uptake, and recruitment of inotropic reserve in chronic left ventricular ischemic dysfunction: implications for the pathophysiology of chronic myocardial hibernation. Circulation. 1996;94:651–659
  36. Heusch G. Hibernating myocardium. Physiol Rev. 1998;78:1055–1085
  37. Heusch G, Sipido KR. Myocardial hibernation: a double-edged sword. Circ Res. 2004;94:1005–1007
  38. Heusch G, Schulz R, Rahimtoola SH. Myocardial hibernation: a delicate balance. Am Heart J. 2005;288:984–999
  39. Heyndrickx GR, Millard RW, McRitchie RJ, et al. Regional myocardial functional and electrophysiological alterations after brief coronary artery occlusion in conscious dogs. J Clin Invest. 1975;56:978–985
  40. Holly T, Drincic A, Byun Y, et al. Caspase inhibition reduces myocyte cell death induced by myocardial ischemia and reperfusion in vivo. J Mol Cell Cardiol. 1999;31:1709–1715
  41. Huang WP, Klionsky DJ. Autophagy in yeast: a review of the molecular machinery. Cell Struct Funct Dec. 2002;27(6):409–420
  42. Jonassen AK, Sack MN, Mjos OD, Yellon DM. Myocardial protection by insulin at reperfusion requires early administration and is mediated via Akt and p70s6 kinase cell-survival signaling. Circ Res. 2001;89:1191–1198
  43. Kalra DK, Zhu X, Ramchandani MK, et al. Increased myocardial gene expression of tumor necrosis factor-α and nitric oxide synthase-2: a potential mechanism for depressed myocardial function in hibernating myocardium in humans. Circulation. 2002;105:1537–1540
  44. Kang P, Izumo S. Apoptosis and heart failure: a critical review of the literature. Circ Res. 2000;86:1107–1113
  45. Kappe G, Verschuure P, Philipsen R, et al. Characterization of two novel human small heat shock proteins: protein kinase–related HspB8 and testis-specific HspB9. Biochim Biophys Acta. 2001;1520:1–6
  46. Kim S, Peppas A, Hong S, et al. Persistent stunning induces myocardial hibernation and protection. Circ Res. 2003;92:1233–1239
  47. Kloner RA, Bolli R, Marban E, et al. Medical and cellular implications of stunning, hibernation, and preconditioning. An NHLBI workshop. Circulation. 1998;97:1848–1867
  48. Knoll R, Arras M, Zimmermann R, et al. Changes in gene expression following short coronary occlusions studied in porcine hearts with run-on assays. Cardiovasc Res. 1994;28:1062–1069
  49. Kudej R, Ghaleh B, Sato N, et al. Ineffective perfusion-contraction matching in conscious, chronically instrumented pigs with an extended period of coronary stenosis. Circ Res. 1998;82:1199–1205
  50. Kudej R, Kim S, Shen Y, et al. Nitric oxide, an important regulator of perfusion-contraction matching in conscious pigs. Am J Physiol. 2000;279:H451–H456
  51. Kudej R, White L, Kudej A, et al. Brief increase in carbohydrate oxidation after reperfusion reverses myocardial stunning in conscious pigs. Circulation. 2002;106:2836–2841
  52. Lai T, Fallon JT, Liu J, et al. Reversibility and pathohistological basis of left ventricular remodeling in hibernating myocardium. Cardiovasc Pathol. 2000;9:323–335
  53. Lee W, Chen J, Ting C, et al. Insulin-like growth factor 1 improves cardiovascular function and suppresses apoptosis of cardiomyocytes in dilated cardiomyopathy. Endocrinology. 1999;140:4831–4840
  54. Li Q, Li B, Wang X, et al. Overexpression of insulin-like growth factor-1 in mice protects from myocyte death after infarction, attenuating ventricular dilation, wall stress and cardiac hypertrophy. J Clin Invest. 1997;100:1991–1999
  55. Liedtke AJ, Renstrom B, Hacker TA, Nellis SH. Effects of moderate repetitive ischemia on myocardial substrate utilization. Am J Physiol. 1995;269:H246–H253
  56. Liedtke AJ, Renstrom B, Nellis SH, et al. Mechanical and metabolic functions in pig hearts after 4 days of chronic coronary stenosis. J Am Col Cardiol. 1995;26:815–825
  57. Luss H, Boknik P, Heusch G, et al. Expression of calcium regulatory proteins in short-term hibernation and stunning in the in-situ porcine heart. Cardiovasc Res. 1998;37:606–617
  58. Luss H, Schafers M, Neumann J, et al. Biochemical mechanisms of hibernation and stunning in the human heart. Cardiovasc Res. 2002;56:411–421
  59. Maes A, Flameng W, Borgers M, et al. Regional myocardial blood flow, glucose utilization and contractile function before and after revascularization and ultrastructural findings in patients with chronic coronary artery disease. Eur J Nucl Med. 1995;22:1299–1305
  60. Maki M, Luotolahti M, Nuutila P, et al. Glucose uptake in the chronically dysfunctional but viable myocardium. Circulation. 1996;93:1658–1666
  61. Martin J, Metsril R, Hilal-Dandan R, et al. Small heat shock proteins and protection against ischemic injury in cardiac myocytes. Circulation. 1997;96:4343–4348
  62. Matsui T, Tao J, Del Monte F, et al. Akt activation preserves cardiac function and prevents injury after transient cardiac ischemia in vivo. Circulation. 2001;104:330–335
  63. Matsuzaki M, Gallagher K, Kemper W, et al. Sustained regional dysfunction produced by prolonged coronary stenosis: Gradual recovery after reperfusion. Circulation. 1983;68:170–182
  64. McNulty PH, Luba MC. Transient ischemia induces regional myocardial glycogen synthase activation and glycogen synthesis in vivo. Am J Physiol. 1995;268:H364–H370
  65. Mehrhof FB, Muller F-U, Bergmann MW, et al. In cardiomyocyte hypoxia, insulin-like growth factor-I–induced antiapoptotic signaling requires phosphatidylinositol-3-OH-kinase–dependent and mitogen-activated protein kinase–dependent activation of the transcription factor cAMP response element–binding protein. Circulation. 2001;104:2088–2094
  66. Melendez A, Talloczy Z, Seaman M, et al. Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science. 2003;301:1387–1391
  67. Mercadier J, Lompre A, Wisnewsky C, et al. Myosin isoenzymic changes in several models of rat cardiac hypertrophy. Circ Res. 1981;49:525–532
  68. Narula J, Haider N, Virmani R, et al. Apoptosis in myocytes in end-stage heart failure. N Engl J Med. 1996;335:1182–1189
  69. Ohsumi Y. Molecular dissection of autophagy: two ubiquitin-like systems. Nat Rev Mol Cell Biol Mar. 2001;2:211–216
  70. Olivetti G, Abbi R, Quaini F, et al. Apoptosis in human failing heart. N Engl J Med. 1997;336:1131–1141
  71. Otto GP, Wu MY, Kazgan N, et al. Macroautophagy is required for multicellular development of the social amoeba Dictyostelium discoideum. J Biol Chem. 2003;278:17636–17645
  72. Palojoki E, Saraste A, Eriksson A, et al. Cardiomyocyte apoptosis and ventricular remodeling after myocardial infarction in rats. Am J Physiol. 2001;280:H2726–H2731
  73. Pantely G, Malone S, Rhen W, et al. Regeneration of myocardial phosphocreatine in pigs despite continued moderate ischemia. Circ Res. 1990;67:1481–1493
  74. Radford N, Fina M, Benjamin I, et al. Cardioprotective effects of 70-kDa heat shock protein in transgenic mice. Proc Natl Acad Sci USA. 1996;93:2339–2342
  75. Rahimtoola SH. A perspective on the three large multicenter randomized clinical trials of coronary bypass surgery for chronic stable angina. Circulation. 1985;72:V123–V135
  76. Rahimtoola S. The hibernating myocardium. Am Heart J. 1989;117:211–221
  77. Ross JJ. Myocardial perfusion-contraction matching. Implications for coronary heart disease and hibernation. Circulation. 1991;83:1076–1083
  78. Schulz R, Guth B, Pieper K, et al. Recruitment of an inotropic reserve in moderately ischemic myocardium at the expense of metabolic recovery. A model of short-term hibernation. Circ Res. 1992;70:1282–1295
  79. Schulz R, Rose J, Martin C, et al. Development of short-term myocardial hibernation. Its limitation by the severity of ischemia and inotropic stimulation. Circulation. 1993;88
  80. Schwartz K, Boheler KR, De La Bastie D, et al. Switches in cardiac muscle gene expression as a result of pressure and volume overload. Am J Physiol. 1992;262:R364–R369
  81. Schwartz ER, Schaper J, vom Dahl J, et al. Myocyte degeneration and cell death in hibernating human myocardium. J Am Coll Cardiol. 1996;27:1577–1585
  82. Shan K, Bick RJ, Poindexter BJ, et al. Altered adrenergic receptor density in myocardial hibernation in humans: a possible mechanism of depressed myocardial function. Circulation. 2000;102:2599–2606
  83. Shen YT, Vatner SF. Mechanism of impaired myocardial function during progressive coronary stenosis in conscious pigs: hibernation versus stunning?. Circ Res. 1995;76:479–488
  84. Shen Y, Kudej R, Bishop S, Vatner S. Inotropic reserve and histological appearance of hibernating myocardium in conscious pigs with ameroid-induced coronary stenosis. Basic Res Cardiol. 1996;91:479–485
  85. Shivalkar B, Maes A, Borgers M, et al. Only hibernating myocardium invariably shows early recovery after coronary revascularization. Circulation. 1996;94:308–315
  86. Smith C, Luo J, Hunter J, et al. The transmembrane domain of the large subunit of HSV-2 ribonucleotide reductase (ICP10) is required for the transformation-related signaling pathways that involve ras activation. Virology. 1994;200:598–612
  87. Smith C, Yu Y, Kulka M, Aurelian L. A novel human gene similar to the protein kinase (PK) coding domain of the large subunit of herpes simplex virus type 2 ribonucleotide reductase (ICP10) codes for a serine–threonine PK and is expressed in melanoma cells. J Biol Chem. 2000;275:25690–25699
  88. Stromhaug PE, Klionsky DJ. Approaching the molecular mechanism of autophagy. Traffic. 2001;2:524–531
  89. Sun K, Czernin J, Krivokapich J, et al. Effects of dobutamine stimulation on myocardial blood flow, glucose metabolism, and wall motion in normal and dysfunctional myocardium. Circulation. 1996;94:3146–3154
  90. Suzuki G, Lee T, Fallavollita J, Canty J. Adenoviral gene transfer of FGF-5 to hibernating myocardium improves function and stimulates myocytes to hypertrophy and reenter the cell cycle. Circ Res. 2005;96:767–775
  91. Tamaki N, Kawamoto M, Takahashi N, et al. Positron emission tomography using fluorine-18 deoxyglucose in evaluation of coronary artery bypass grafting. J Am Col Cardiol. 1989;64:860–865
  92. Thomas S, Fallavollita J, Lee T, et al. Absence of troponin I degradation or altered sarcoplasmic reticulum uptake protein expression after reversible ischemia in swine. Circ Res. 1999;85:446–456
  93. Trost S, Omens J, Karlon W, et al. Protection against myocardial dysfunction after a brief ischemic period in transgenic mice expressing inducible heat shock protein 70. J Clin Invest. 1998;101:855–862
  94. Uren NG, Melin JA, De Bruyne B, et al. Relation between myocardial blood flow and the severity of coronary-artery stenosis. N Engl J Med. 1994;330:1782–1788
  95. Vanoverschelde J, Wijns W, Depre C, et al. Mechanisms of chronic regional postischemic dysfunction in humans. New insights from the study of noninfarcted collateral-dependent myocardium. Circulation. 1993;87:1513–1523
  96. Vanoverschelde JL, Wijns W, Borgers M, et al. Chronic myocardial hibernation in humans. From bedside to bench. Circulation. 1997;95:1961–1971
  97. Vanoverschelde J, Depre C, Gerber B, et al. Time course of functional recovery after coronary artery bypass graft surgery in patients with chronic left ventricular ischemic dysfunction. Am J Cardiol. 2000;85:1432–1439
  98. Wang L, Zajac A, Hedhli N, Depre C. Increased expression of H11 kinase stimulates glycogen synthesis in the heart. Mol Cell Biochem. 2004;265:71–78
  99. Wijns W, Vatner SF, Camici PG. Hibernating myocardium. N Engl J Med. 1998;339:173–181
  100. Williams R, Benjamin I. Protective responses in the ischemic myocardium. J Clin Invest. 2000;106:813–818
  101. Yan L, Kim SJ, Ge H, et al. Autophagy, a survival mechanism in chronically ischemic myocardium. Circulation. 2004;110:II-298

PII: S1050-1738(05)00040-X

doi: 10.1016/j.tcm.2005.04.006

Trends in Cardiovascular Medicine
Volume 15, Issue 3 , Pages 101-110 , April 2005