Skip to main content
SpringerLink
Log in

Moderate ischemic injury and myocardial stunning

  • Chapter
Ischemia-reperfusion in cardiac surgery

Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 142))

Abstract

Reperfusion of acutely ischemic myocardium is associated with a constellation of characteristic structural and functional derangements, which range widely in severity [1]. At one end of the spectrum are transient, completely reversible abnormalities such as reperfusion arrhythmias and postischemic myocardial dysfunction or “myocardial stunning” [2–14]. At the other end are severe, irreversible abnormalities such as cell death (infarction). Thus, myocardial stunning should be considered as a mild, sublethal sequela of ischemia/reperfusion injury.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bolli R. Oxygen-derived free radicals and myocardial reperfusion injury: An overview. Cardiovasc Drugs Ther 1991; 5: 249–68.

    PubMed  Google Scholar 

  2. Weiner JM, Apstein CS, Arthur JH et al. Persistence of myocardial injury following brief periods of coronary occlusion. Cardiovasc Res 1976; 10: 678–86.

    PubMed  CAS  Google Scholar 

  3. Theroux P, Ross J Jr, Franklin D et al. Coronary arterial reperfusion. III. Early and late effects on regional myocardial function and dimensions in conscious dogs. Am J Cardiol 1976; 38: 599–606.

    PubMed  CAS  Google Scholar 

  4. Heyndrickx GR, Baig H, Nellens P et al. Depression of regional blood flow and wall thickening after brief coronary occlusions. Am J Physiol 1978; 234: H653–H659.

    PubMed  CAS  Google Scholar 

  5. Kloner RA, Ellis SG, Lange R et al. Studies of experimental coronary artery reperfusion: effects on infarct size, myocardial function, biochemistry, ultrastructure and microvascular damage. Circulation 1983; 68(Suppl I): I-8-I-15.

    CAS  Google Scholar 

  6. Lavallee M, Cox D, Patrick TA et al. Salvage of myocardial function by coronary artery reperfusion 1, 2, and 3 hours after occlusion in conscious dogs. Circ Res 1983; 53: 235–47.

    PubMed  CAS  Google Scholar 

  7. Bush LR, Buja LM, Samowitz W et al. Recovery of left ventricular segmental function after long-term reperfusion following temporary coronary occlusion in conscious dogs: comparison of 2- and 4-hour occlusions. Circ Res 1983; 53: 248–63.

    PubMed  CAS  Google Scholar 

  8. Ellis SG, Henschke CI, Sandor T et al. Time course of functional and biochemical recovery of myocardium salvaged by reperfusion. J Am Coll Cardiol 1983; 1: 1047–55.

    PubMed  CAS  Google Scholar 

  9. Matsuzaki M, Gallagher KP, Kemper WS et al. Sustained regional dysfunction produced by prolonged coronary stenosis: gradual recovery after reperfusion. Circulation 1983; 68: 170–82.

    PubMed  CAS  Google Scholar 

  10. Bolli R, Zhu WX, Thornby JI et al. Time-course and determinants of recovery of function after reversible ischemia in conscious dogs. Am J Physiol 1988; 254: H102–H114.

    PubMed  CAS  Google Scholar 

  11. Charlat ML, O’Neill PG, Hartley CJ et al. Prolonged abnormalities of left ventricular diastolic wall thinning in the “stunned” myocardium in conscious dogs: Time-course and relation to systolic function. J Am Coll Cardiol 1989; 13: 185–94.

    PubMed  CAS  Google Scholar 

  12. Bolli R, Patel BS, Hartley CJ et al. Nonuniform transmural recovery of contractile function in the “stunned” myocardium Am J Physiol 1989; 257: H375–H385.

    PubMed  CAS  Google Scholar 

  13. Heyndrickx GR, Millard RW, Mc Ritchie RJ et al. Regional myocardial functional and electrophysiological alterations after brief coronary artery occlusion in conscious dogs. J Clin Invest 1975; 56: 978–85.

    PubMed  CAS  Google Scholar 

  14. Braunwald E, Kloner RA. The stunned myocardium: prolonged, postischemic ventricular dysfunction. Circulation 1982; 66: 1146–49.

    PubMed  CAS  Google Scholar 

  15. Bolli R. Mechanism of myocardial “stunning”. Circulation 1990; 82: 723–38.

    PubMed  CAS  Google Scholar 

  16. Jennings RB, Reimer KA. Factors involved in salvaging ischemic myocardium. Effects of reperfusion of arterial blood. Circulation 1983; 68(Supp I): I-25-I-36.

    CAS  Google Scholar 

  17. Nicklas JM, Becker LC, Bulkley BH. Effects of repeated brief coronary occlusion on regional left ventricular function and dimension in dogs. Am J Cardiol 1985; 56: 473–8.

    PubMed  CAS  Google Scholar 

  18. Stahl LD, Aversano TR, Becker LC. Selective enhancement of function of stunned myocardium by increased flow. Circulation 1986; 74: 843–51.

    PubMed  CAS  Google Scholar 

  19. Becker LC, Levine JH, DiPaula AF et al. Reversal of dysfunction in postischemic stunned myocardium by epinephrine and postextrasystolic potentiation. J Am Coll Cardiol 1986; 7: 580–9.

    PubMed  CAS  Google Scholar 

  20. Schroder E, Kieso RA, Laughlin D et al. Altered response of reperfused myocardium to repeated coronary occlusion in dogs. J Am Coll Cardiol 1987; 10: 898–905.

    PubMed  CAS  Google Scholar 

  21. Stahl LD, Weiss HR, Becker LC. Myocardial oxygen consumption, oxygen supply/demand heterogeneity, and microvascular patency in regionally stunned myocardium. Circulation 1988; 77: 865–72.

    PubMed  CAS  Google Scholar 

  22. Triana JF, Jamaluddin U, Li XY et al. Oxygen free radicals cause myocardial stunning after repetitive ischemia. Circulation 1990; 82: 111–36 (abstr.).

    Google Scholar 

  23. Cohen MV, Downey JM. Myocardial stunning in dogs: Preconditioning effect and influence of coronary collateral flow. Am Heart J 1990; 120: 282–91.

    PubMed  CAS  Google Scholar 

  24. Taegtmeyer H, Roberts AFC, Raine AEG. Energy metabolism in reperfused heart muscle: metabolic correlates to return of function. J Am Coll Cardiol 1985; 6: 864–70.

    PubMed  CAS  Google Scholar 

  25. Kusuoka H., Porterfield JK, Weisman HF et al. Pathophysiology and pathogenesis of stunned myocardium. Depressed Ca2+ activation of contraction as a consequence of reperfusion-induced cellular calcium overload in ferret hearts. J Clin Invest 1987; 79: 950–61.

    PubMed  CAS  Google Scholar 

  26. Steenbergen C, Murphy E, Levy L et al. Elevation in cytosolic free calcium concentration early in myocardial ischemia in perfused rat heart. Circ Res 1987; 60: 700–7.

    PubMed  CAS  Google Scholar 

  27. Porterfield JK, Kusuoka H, Weisman HF et al. Ryanodine prevents the changes in myocardial function and morphology induced by reperfusion after brief periods of ischemia. Clin Res 1987; 35: 315A (abstr.).

    Google Scholar 

  28. Ambrosio G, Jacobus WE., Bergman CA et al. Preserved high energy phosphate metabolic reserve in globally “stunned-hearts despite reduction of basal ATP content and contractility. J Mol Cell Cardiol 1987; 19: 953–64.

    PubMed  CAS  Google Scholar 

  29. Kitakaze M, Weisfeldt ML, Marban E. Acidosis during early reperfusion prevents myocardial stunning in perfused ferret hearts. J Clin Invest 1988; 82: 920–7.

    PubMed  CAS  Google Scholar 

  30. Ambrosio G, Jacobus WE, Mitchell MC et al. Effects of ATP precursors on ATP and free ADP content and functional recovery of postischemic hearts. J Physiol 1989; 256: H560–H566.

    CAS  Google Scholar 

  31. Marban E, Koretsune Y, Corretti M et al. Calcium and its role in myocardial cell injury during ischemia and reperfusion. Circulation 1989; 80(Suppl IV): IV-17-IV-22.

    CAS  Google Scholar 

  32. Kusuoka H, Koretsune Y, Chacko VP et al. Excitation-contraction coupling in postischemic myocardium: Does failure of activator Ca2+’ transients underlie stunning? Circ Res 1990; 66: 1268–76.

    PubMed  CAS  Google Scholar 

  33. Shlafer M, Kane PF, Kirsh MM. Superoxide dismutase plus catalase enhances the efficacy of hypothermic cardioplegia to protect the globally ischemic, reperfused heart. J Thorac Cardiovasc Surg 1982; 83: 830–9.

    PubMed  CAS  Google Scholar 

  34. Shlafer M, Kane PF., Wiggins WY et al. Possible role for cytotoxic oxygen metabolites in the pathogenesis of cardiac ischemic injury. Circulation 1982; 66(Suppl 1): I-85-I-92.

    CAS  Google Scholar 

  35. Casale AS, Bulkley GB, Bulkley BH et al. Oxygen free radical scavengers protect the arrested globally ischemic heart upon reperfusion. Surg Forum 1983; 34: 313–6.

    Google Scholar 

  36. Menasche P, Grousset C, Gauduel Y et al. A comparative study of free radical scavengers in cardioplegic solutions. Improved protection with peroxidase. J Thorac Cardiovasc Surg 1986; 92: 264–71.

    PubMed  CAS  Google Scholar 

  37. Myers CL, Weiss SJ, Kirsh MM et al. Effects of supplementing hypothermic crystalloid cardioplegic solution with catalase, superoxide dismutase, allopurinol, or deferoxamine on functional recovery of globally ischemic and reperfused isolated hearts. J Thorac Cardiovase Surg 1986; 91: 281–9.

    CAS  Google Scholar 

  38. Ambrosio G, Weisfeldt ML, Jacobus WE et al. Evidence for a reversible oxygen radical-mediated component of reperfusion injury: Reduction by recombinant human superoxide dismutase administered at the time of reflow. Circulation 1987; 75: 282–91.

    PubMed  CAS  Google Scholar 

  39. Ytrehus K, Gunnes S., Myklebust R et al. Protection by superoxide dismutase and catalase in the isolated rat heart reperfused after prolonged cardioplegia: A combined study of metabolic, functional and morphometric ultrastructural variables. Cardiovasc Res 1987; 21: 492–9.

    PubMed  CAS  Google Scholar 

  40. Garlick PB, Davies MJ, Hearse DJ et al. Direct detection of free radicals in the reperfused rat heart using electron spin resonance spectroscopy. Circ Res 1987; 61: 757–60.

    PubMed  CAS  Google Scholar 

  41. Kramer JH, Arroyo CM, Dickens BF et al. Spin-trapping evidence that graded myocardial ischemia alters postischemic superoxide production. Free Radical Biol Med 1987; 3: 1539.

    Google Scholar 

  42. Ambrosio G, Zweier JL, Jacobus WE et al. Improvement of postischemic myocardial function and metabolism induced by administration of desferrioxamine at the time of reflow: the role of iron in the pathogenesis of reperfusion injury. Circulation 1987; 76: 906–15.

    PubMed  CAS  Google Scholar 

  43. Stewart JR, Blackwell WH, Crute SL et al. Inhibition of surgically induced ischemia/reperfusion injury by oxygen free radical scavengers. J Thorac Cardiovasc Surg 1983; 86: 26272.

    Google Scholar 

  44. Johnson DL, Horneffer PJ, Dinatale JM Jr et al. Free radical scavengers improve functional recovery of stunned myocardium in a model of surgical coronary revascularization. Surgery 1987; 102: 334–40.

    PubMed  CAS  Google Scholar 

  45. Gardner TJ. Oxygen radicals in cardiac surgery. Free Radical Biol Med 1988; 4: 45–50.

    CAS  Google Scholar 

  46. Illes RW, Silverman NA, Krukenkamp IB et al. Amelioration of postischemic stunning by deferoxamine-blood cardioplegia. Circulation 1989; 80(Suppl III): III-30-III-35.

    CAS  Google Scholar 

  47. Homans DC, Sublett E, Dai XZ et al. Persistence of regional left ventricular dysfunction after exercise-induced myocardial ischemia. J Clin Invest 1986; 77: 66–73.

    PubMed  CAS  Google Scholar 

  48. O’Neill PG, Charlat ML, Hartley CJ et al. Nonuniform transmural response of the “stunned” myocardium to inotropic stimulation. J Am Coll Cardiol 1987; 9: 145A (abstr.).

    Google Scholar 

  49. Preuss KC, Gross GJ, Brooks HL et al. Time course of recovery of “stunned” myocardium following variable periods of ischemia in conscious and anesthetized dogs. Am Heart J 1987; 114: 696–703.

    PubMed  CAS  Google Scholar 

  50. DeBoer FWV, Ingwall JS, Kloner RA et al. Prolonged derangements of canine myocardial purine metabolism after a brief coronary artery occlusion not associated with anatomic evidence of necrosis. Proc Natl Acad Sci 1980; 77: 5471–5.

    PubMed  CAS  Google Scholar 

  51. Reimer KA, Hill ML, Jennings RB. Prolonged depletion of ATP and of the adenine nucleotide pool due to delayed resynthesis of adenine nucleotides following reversible myocardial ischemic injury in dogs. J Mol Cell Cardiol 1981; 13: 229–39.

    PubMed  CAS  Google Scholar 

  52. Swain JL, Sabina RL, McHale PA et al. Prolonged myocardial nucleotide depletion after brief ischemia in the open-chest dog. Am J Physiol 1982; 242: H818–H826.

    PubMed  CAS  Google Scholar 

  53. Neely JR, Grotyohann LW. Role of glycolytic products in damage to ischemic myocardium: dissociation of adenosine triphosphate levels and recovery of function of reperfused ischemic hearts. Circ Res 1984; 55: 81: 6–24.

    Google Scholar 

  54. Przyklenk K, Kloner RA. Superoxide dismutase plus catalase improve contractile function in the canine model of the “stunned” myocardium. Circ Res 1986; 58: 148–56.

    PubMed  CAS  Google Scholar 

  55. Glower DD, Spratt JA, Newton JR et al. Dissociation between early recovery of regional function and purine nucleotide content in postischemic myocardium in the conscious dog. Cardiovasc Res 1987; 21: 328–36.

    PubMed  CAS  Google Scholar 

  56. Przyklenk K, Kloner RA. Effect of verapamil on postischemic “stunned” myocardium: Importance of the timing of treatment. J Am Coll Cardiol 1988; 11: 614–23.

    PubMed  CAS  Google Scholar 

  57. Guth BD, Martin JF, Heusch G et al. Regional myocardial blood flow, function and metabolism using phosphorus-31 nuclear magnetic resonance spectroscopy during ischemia and reperfusion in dogs. J Am Coll Cardiol 1987; 10: 673–81.

    PubMed  CAS  Google Scholar 

  58. Mercier JC, Lando U, Kanmatsuse K et al. Divergent effects of inotropic stimulation on the ischemic and severely depressed reperfused myocardium. Circulation 1982; 66: 397–400.

    PubMed  CAS  Google Scholar 

  59. Ellis SE, Wynne J, Braunwald E et al. Response of reperfusion-salvaged, stunned myocardium to inotropic-stimulation. Am Heart J 1984; 107: 9–13.

    Google Scholar 

  60. Arnold JMO, Braunwald E, Sandor T et al. Inotropic stimulation of reperfused myocardium with dopamine: effects on infarct size and myocardial function. J Am Coll Cardiol 1985; 6: 1026–4.

    PubMed  CAS  Google Scholar 

  61. Bolli R, Zhu WX, Myers ML et al. Beta-adrenergic stimulation reverses postischemic myocardial dysfunction without producing subsequent functional deterioration. Am J Cardiol 1985: 56: 964–8.

    PubMed  CAS  Google Scholar 

  62. Ito BR, Tate H, Kobayashi M et al. Reversibly injured, postischemic canine myocardium retains normal contractile reserve. Circ Res 1987; 61: 834–6.

    PubMed  CAS  Google Scholar 

  63. Heusch G, Schafer S, Kroger K. Recruitment of inotropic reserve in “stunned” myocardium by the cardiotonic agent AR-L 57. Basic Res Cardiol 1988; 83: 602–10.

    PubMed  CAS  Google Scholar 

  64. Hoffmeister HM, Mauser M, Schaper W. Effect of adenosine and AICAriboside on ATP content and regional contractile function in reperfused canine myocardium. Basic Res Cardiol 1985; 80: 445–58.

    PubMed  CAS  Google Scholar 

  65. Greenfield RA, Swain JL Disruption of myofibrillar energy use: dual mechanisms that may contribute to postischemic dysfunction in stunned myocardium. Circ Res 1987; 60: 283–9.

    PubMed  CAS  Google Scholar 

  66. Ciuffo M, Ouyang P, Becker LC et al. Reduction of sympathetic inotropic response after ischemia in dogs: contributor to stunned myocardium. J Clin Invest 1985; 75: 1504–9.

    PubMed  CAS  Google Scholar 

  67. Heusch G, Frehen D, Kroger K et al. Integrity of sympathetic neurotransmission in stunned myocardium. J Appl Cardiol 1988; 3: 259–72.

    Google Scholar 

  68. O’Neill PG, Charlat ML, Michael LH et al. Influence of neutrophil depletion on myocardial function and flow after reversible ischemia. Am J Physiol 1989; 256: H341–H351.

    PubMed  Google Scholar 

  69. Bolli R, Triana JF, Jeroudi MO: Postischemic mechanical and vascular dysfunction (myocardial “stunning” and microvascular “stunning”) and the effects of calcium channel blockers on ischemia/reperfusion injury. Clin Cardiol 1989; 12: III-16-III-25.

    CAS  Google Scholar 

  70. Bolli R, Triana JF, Jeroudi MO. Prolonged impairment of coronary vasodilation after reversible ischemia: Evidence for microvascular “stunning”. Circ Res 1990; 67: 332–43.

    PubMed  CAS  Google Scholar 

  71. Zhao M, Zhang H, Robinson TF et al. Profound structural alterations of the extracellular collagen matrix in postischemic dysfunctional (“stunned”) but viable myocardium. J Am Coll Cardiol 1987; 10: 1322–34.

    PubMed  CAS  Google Scholar 

  72. Charney RH, Takahashi S, Zhao M et al. Collagen loss in the stunned myocardium. Circulation 1989; 80(Suppl II): 11–99 (abstr.).

    Google Scholar 

  73. Whittaker P, Przyklenk K, Boughner DR et al. Collagen damage in two different models of stunned myocardium. J Mol Cell Cardiol 1989; 21 (Suppl II): S163 (abstr.).

    Google Scholar 

  74. Guarnieri T: Direct measurement of [Ca2+]i, in early and late reperfused myocardium. Circulation 1989; 80(Suppl II): 11–241 (abstr.).

    Google Scholar 

  75. Kitakaze M, Weisman HF, Marban E. Contractile dysfunction and ATP depletion after transient calcium overload in perfused ferret hearts. Circulation 1988; 77: 685–95.

    PubMed  CAS  Google Scholar 

  76. Hori M, Kitakaze M, Sato H et al. Transient acidosis by staged reperfusion prevents myocardial stunning. Circulation 1989; 80(Suppl II): 11–600 (abstr).

    Google Scholar 

  77. Marban E, Kitakaze M, Kusoka H et al. Intracellular free calcium concentration measured with 19F NMR spectroscopy in intact ferret hearts. Proc Natl Acad Sci USA 1987; 84: 6005–9.

    PubMed  CAS  Google Scholar 

  78. Lee H-C, Smith N, Mohabir R et al. Cytosolic calcium transients from the beating mammalian heart. Proc Natl Acad Sci USA 1987; 84: 7793–7.

    PubMed  CAS  Google Scholar 

  79. Marban E, Kitakaze M, Koretsune Y et al. Quantification of [Ca2+]i, in perfused hearts: Critical evaluation of the 5F-BAPTA and nuclear magnetic resonance method as applied to the study of ischemia and reperfusion. Circ Res 1990; 66: 1255–67.

    PubMed  CAS  Google Scholar 

  80. Krause SM, Hess ML. Characterization of cardiac sarcoplasmic reticulum dysfunction during short-term normothermic global ischemia. Circ Res 1985; 55: 176–84.

    Google Scholar 

  81. Lazdunski M, Frelin C., Vigue P. The sodium/hydrogen exchange system in cardiac cells: Its biochemical and pharmacological properties and its role in regulating internal concentrations of sodium and internal pH. J Mol Cell Cardiol 1985; 17: 1029–42.

    PubMed  CAS  Google Scholar 

  82. Murphy JG, Smith TW, Marsh JD. Mechanisms of reoxygenation-induced calcium overload in cultured chick embryo heart cells. Am J Physiol 1988; 254: H1133–H1141.

    PubMed  CAS  Google Scholar 

  83. Tani M, Neely JR. Role of intracellular Na-in Ca2+ overload and depressed recovery of ventricular function of reperfused ischemic rat hearts. Possible involvement of H+-Na+ and Na“ -Ca2+ exchange. Circ Res 1989; 65: 1045–56.

    PubMed  CAS  Google Scholar 

  84. Grinwald PM. Calcium uptake during postischemic reperfusion in the isolated rat heart: influence of extracellular sodium. J Mol Cell Cardiol 1982; 14: 359–65.

    PubMed  CAS  Google Scholar 

  85. Renlund DG, Gerstenblith G, Lakatta EG et al. Perfusate sodium during ischemia modifies postischemic functional and metabolic recovery in the rabbit heart. J Mol Cell Cardiol 1984; 16: 795–801.

    PubMed  CAS  Google Scholar 

  86. McCord JM. Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med 1985; 312: 159–63.

    PubMed  CAS  Google Scholar 

  87. Opie LH. Reperfusion injury and its pharmacologic modification. Circulation 1989; 80: 1049–62.

    PubMed  CAS  Google Scholar 

  88. Taylor AL, Golino P, Eckels R et al. Differential enhancement of postischemic segmental systolic thickening by diltiazem. J Am Coll Cardiol 1990; 15: 737–47.

    PubMed  CAS  Google Scholar 

  89. Lamping KA, Gross GJ. Improved recovery of myocardial segment function following a short coronary occlusion in dogs by nicorandil, a potential new antianginal agent, and nifedipine. J Cardiovasc Pharmacol 1985; 7: 158–66.

    PubMed  CAS  Google Scholar 

  90. Waritier DC, Gross GJ, Brooks HL et al. Improvement of postischemic, contractile function by the calcium channel blocking agent nitrendipine in conscious dogs. J Cardiovasc Pharmacol 1988; 12(Suppl 4): S120–S124.

    Google Scholar 

  91. Dunlap E. Millard RW. Amlodipine, a new long-acting calcium channel blocking agent, improves recovery of -stunned“ myocardium. The Pharmacologist 1989; 31: 145 (abstr.).

    Google Scholar 

  92. Przyklenk K, Ghafari GB, Eitzman DT et al. Nifedipine administered after reperfusion ablates systolic contractile dysfunction of postischemic “stunned” myocardium. J Am Coll Cardiol 1989; 13: 1176–83.

    PubMed  CAS  Google Scholar 

  93. Bann M, Ehring T, Heusch G. Nisoldipine improves the functional recovery of stunned myocardium only when given before ischemia. Circulation 1991; 84(Suppl II): 656.

    Google Scholar 

  94. Krause SM, Jacobus WE, Becker LC. Alterations in cardiac sarcoplasmic reticulum calcium transport in the postischemic “stunned” myocardium. Circ Res 1989; 65: 526–30.

    PubMed  CAS  Google Scholar 

  95. Zhu WX, Myers ML, Hartley CJ et al. Validation of a single crystal for measurement of transmural and epicardial thickening. Am J Physiol 1986; 251: H1045–H1055.

    PubMed  CAS  Google Scholar 

  96. Myers ML, Bolli R. Lekich RF et al. Enhancement of recovery of myocardial function by oxygen free-radical scavengers after reversible regional ischemia. Circulation 1985; 72: 915–21.

    PubMed  CAS  Google Scholar 

  97. Gross GJ, Farber NE, Hardman HF et al. Beneficial actions of superoxide dismutase and catalase in stunned myocardium of dogs. Am J Physiol 1986; 250: H372–H377.

    PubMed  CAS  Google Scholar 

  98. Murry, CE, Richard VJ, Jennings RB et al. Free radicals do not cause myocardial stunning after four 5 minute coronary occlusions. Circulation 1989; 80(Suppl II): 11–296 (abstr.).

    Google Scholar 

  99. Koerner JE, Anderson BA, Dage RC. Protection against postischemic myocardial dysfunction in anesthetized rabbits with scavengers of oxygen-derived free radicals: Superoxide dismutase plus catalase, N-2-mercaptopropionyl glycine and captopril. J Cardiovasc Pharmacol 1991; 17: 185–91.

    PubMed  CAS  Google Scholar 

  100. Jeroudi MO, Triana FJ, Patel BS et al. Effect of superoxide dismutase and catalase, given separately, on myocardial “stunning”. Am J Physiol 1990; 259: H889–H901.

    PubMed  CAS  Google Scholar 

  101. Buchwald A, Klein HH, Lindert S et al. Effect of intracoronary superoxide dismutase on regional function in stunned myocardium. J Cardiovasc Pharmacol 1989; 13: 258–64.

    PubMed  CAS  Google Scholar 

  102. Halliwell B, Gutteridge JMC. Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J 1984; 219: 1–14.

    PubMed  CAS  Google Scholar 

  103. Fox RB. Prevention of granulocyte-mediated oxidant lung injury in rats by a hydroxyl radical scavenger, dimethyithiourea. J Clin Invest 1984; 74: 1456.

    PubMed  CAS  Google Scholar 

  104. Bolli R, Zhu WX, Hartley CJ et al. Attenuation of dysfunction in the postischemic “stunned” myocardium by dimethyithiourea. Circulation 1987; 76: 458–68.

    PubMed  CAS  Google Scholar 

  105. Bolli R, Jeroudi MO, Patel BS et al. Marked reduction of free radical generation and contractile dysfunction by antioxidant therapy begun at the time of reperfusion: evidence that myocardial “stunning” is a manifestation of reperfusion injury. Circ Res 1989; 65: 607–22.

    PubMed  CAS  Google Scholar 

  106. Myers ML, Bolli R, Lekich RF et al. N-2-mercaptopropionylglycine improves recovery of myocardial function following reversible regional ischemia. J Am Coll Cardiol 1986; 8: 1161–8.

    PubMed  CAS  Google Scholar 

  107. Bolli R, Patel BS, Zhu WX et al. The iron chelator desferrioxamine attenuates postischemic ventricular dysfunction. Am J Physiol 1987; 253: H1372–H1380.

    PubMed  CAS  Google Scholar 

  108. Farber NE, Vercellotti GM, Jacob HS et al. Evidence for a role of iron-catalyzed oxidants in functional and metabolic stunning in the canine heart. Circ Res 1988; 63: 351–60.

    PubMed  CAS  Google Scholar 

  109. Dage RC, Anderson BA, Mao SJT et al. Probucol reduces myocardial dysfunction during reperfusion after short-term ischemia in rabbit heart. J Cardiovasc Pharmacol 1991: 17: 158–65.

    PubMed  CAS  Google Scholar 

  110. Schrier GM, Hess ML. Quantitative identification of superoxide anion as a negative isotropic species. Am J Physiol 1988; 24: H138–H143.

    Google Scholar 

  111. DiGuiseppi J, Fridovich I. Oxygen toxicity in streptococcus sanguis: The relative importance of superoxide and hydroxyl radicals. J Biol Chem 1982; 257: 4046–51.

    PubMed  CAS  Google Scholar 

  112. Triana JF, Unisa A, Bolli R. Antioxidant enzymes attenuate myocardial “stunning” in the conscious dog. FASEB J 1990; 4: A622 (abstr.).

    Google Scholar 

  113. Sekili S, Li XY, Zughaib M a al. Evidence for a major pathogenetic role of hydroxyl radical in myocardial “stunning” in the conscious dog. Circulation 1991; 84(Supp II): 656.

    Google Scholar 

  114. Zweier JL, Flaherty JT, Weisfeldt ML. Direct measurement of free radical generation following reperfusion of ischemic myocardium. Proc Natl Acad Sci USA 1987; 84: 14047.

    Google Scholar 

  115. Baker JE, Felix CC., Olinger GN et al. Myocardial ischemia and reperfusion: Direct evidence for free radical generation by electron spin resonance spectroscopy. Proc Natl Acad Sci USA 1988; 85: 2786–9.

    PubMed  CAS  Google Scholar 

  116. Zweier JL. Measurement of superoxide-derived free radicals in the reperfused heart. J Biol Chem 1988; 263: 1353–7.

    CAS  Google Scholar 

  117. Bolli R. Mc Cay PB. Use of spin traps in intact animals undergoing myocardial ischemia/reperfusion: A new approach to assessing the role of oxygen radicals in myocardial “stunning”. Free Rad Res Comms 1990: 9: 169–80.

    CAS  Google Scholar 

  118. Bolli R, Patel BS, Jeroudi MO et al. Demonstration of free radical generation in “stunned” myocardium of intact dogs with the use of the spin trap a-phenyl N-tert-butyl nitrone. J Clin Invest 1988; 82: 476–85.

    PubMed  CAS  Google Scholar 

  119. Bolli R, Jeroudi MO, Patel BS et al. Direct evidence that oxygen-derived free radicals contribute to postischemic myocardial dysfunction in the intact dog. Proc Natl Acad Sci USA 1989; 86: 4695–9.

    PubMed  CAS  Google Scholar 

  120. Bolli R, Patel BS, Jeroudi MO et al. Iron-mediated radical reactions upon reperfusion contribute to myocardial “stunning”. Am J Physiol 1990; 259: H1901–H1911.

    PubMed  CAS  Google Scholar 

  121. Zughayb M, Sekili S., Li XY et al. Detection of free radical generation in the “stunned” myocardium in the conscious dog using spin trapping techniques. FASEB J 1991: 5: A704.

    Google Scholar 

  122. Leiboff RL, Arroyo CM, Schaer GL et al. Free radical generation in an in vivo model of regional myocardial stunning. FASEB J 1988; 2: A818 (abstr.).

    Google Scholar 

  123. Bolli R, Kaur H, Li XY et al. Demonstration of hydroyl radical generation in -stunned“ myocardium of intact dogs using aromatic hydroxylation of phenylalanine. FASEB J 1991; 5: A704.

    Google Scholar 

  124. Burton KP, Mc Cord JM., Ghai G. Myocardial alterations due to free-radical generation. Am J Physiol 1984; 246: H776–H783.

    PubMed  CAS  Google Scholar 

  125. Blaustein AS, Schine L, Brooks WW et al. Influence of exogenously generated oxidant species on myocardial function. Am J Physiol 1986; 250: H595–H599.

    PubMed  CAS  Google Scholar 

  126. Shattock MJ, Manning AS., Hearse DJ. Effects of hydrogen peroxide on cardiac function and postischemic functional recovery in the isolated “working” rat heart. Pharmacology 1982: 24: 118–22.

    PubMed  CAS  Google Scholar 

  127. Ytrehus K., Myklebust R, Mjos OD. Influence of oxygen radicals generated by xanthine oxidase in the isolated perfused rat heart. Cardiovasc Res 1986; 20: 597–603.

    PubMed  CAS  Google Scholar 

  128. Miki S, Ashraf M, Salka S et al. Myocardial dysfunction and ultrastructural alterations mediated by oxygen metabolites. J Mol Cell Cardiol 1988; 20: 1009–24.

    PubMed  CAS  Google Scholar 

  129. Jackson CV, Mickelson JK, Pope TK et al. 0 2 free radical-mediated myocardial and vascular dysfunction. Am J Physiol 1986; 251: H1225–H1231.

    PubMed  CAS  Google Scholar 

  130. Goldhaber JI, Ji S, Lamp ST et al. Effects of exogenous free radicals on electromechanical function and metabolism in isolated rabbit and guinea pig ventricle: Implications for ischemia and reperfusion injury. J Clin Invest 1988; 83: 1800–9.

    Google Scholar 

  131. Davies KJA. Protein damage and degradation by oxygen radicals. 1. General aspects. J Biol Chem 1987; 262: 9895–901.

    CAS  Google Scholar 

  132. Thompson JA, Hess ML. The oxygen free radical system: A fundamental mechanism in the production of myocardial necrosis. Prog Cardiovasc Dis 1986; 28: 449–62.

    PubMed  CAS  Google Scholar 

  133. Romaschin AD, Rebeyka I, Wilson GJ et al. Conjugated dienes in ischemic and reperfused myocardium: an in vivo chemical signature of oxygen free radical mediated injury. J Mol Cell Cardiol 1987; 19: 289–302.

    PubMed  CAS  Google Scholar 

  134. Weisel RD, Mickle DAG, Finkle CD et al. Myocardial free-radical injury after cardioplegia. Circulation 1989; 80(Suppl III): III-14-III-18.

    CAS  Google Scholar 

  135. Rowe GT, Manson NH, Caplan M et al. Hydrogen peroxide and hydroxyl radical mediation of activated leukocyte depression of cardiac sarcoplasmic reticulum: participation of the cyclooxygenase pathway. Circ Res 1983; 53: 584–91.

    PubMed  CAS  Google Scholar 

  136. Kaneko M, Beamish RE, Dhalla NS. Depression of heart sarcolemmal Ca2+-pump activity by oxygen free radicals. Am J Physiol 1989; 256: H368–H374.

    PubMed  CAS  Google Scholar 

  137. Kaneko M, Elimban V, Dhalla NS. Mechanism for depression of heart sarcolemmal Ca2+ pump by oxygen free radicals. Am J Physiol 1989; 257: H804–H811.

    PubMed  CAS  Google Scholar 

  138. Kramer JH, Mak IT, Weglicki WB. Differential sensitivity of canine cardiac sarcolemmal and microsomal enzymes to inhibition by free radical-induced lipid peroxidation. Circ Res 1984; 55: 120–4.

    PubMed  CAS  Google Scholar 

  139. Kim M-S, Akera T. O2 free radicals: cause of ischemia-reperfusion injury to cardiac Na+-K+-ATPase. Am J Physiol 1987; 252: H252–H257.

    PubMed  CAS  Google Scholar 

  140. Charlat ML, O’Neill PG, Egan JM et al. Evidence for a pathogenetic role of xanthine oxidase in the “stunned” myocardium. Am J Physiol 1987; 252: H566–H577.

    PubMed  CAS  Google Scholar 

  141. Holzgrefe HH, Gibson JK. Enhanced function recovery in the stunned canine myocardium by pretreatment with oxypurinol. J Am Coll Cardiol 1988; 11: 208A (abstr.).

    Google Scholar 

  142. Puen DW, Forman MB, Cates CU et al. Oxypurinol limits myocardial stunning but does not reduce infarct size after reperfusion. Circulation 1987; 76: 678–86.

    Google Scholar 

  143. Jarasch ED, Bruder G, Heid HW. Significance of xanthine oxidase in capillary endothelial cells. Acta Physiol Scand 1986; 548(Suppl): 39–46.

    CAS  Google Scholar 

  144. Eddy W, Stewart JR, Jones HP et al. Free radical-producing enzyme, xanthine oxidase, is undetectable in human hearts. Am J Physiol 1987; 253: H709–H711.

    PubMed  CAS  Google Scholar 

  145. Muxfeldt M. Schaper W. The activity of xanthine oxidase in hearts of pigs, guinea pigs, rats, and humans. Basic Res Cardiol 1987; 82: 486–92.

    PubMed  CAS  Google Scholar 

  146. Huizer T, de Jong JW, Nelson JA et al. Urate production by human heart. J Mol Cell Cardiol 1989; 21: 691–95.

    PubMed  CAS  Google Scholar 

  147. Grum CM, Gallagher KP, Kirsh MM et al. Absence of detectable xanthine oxidase in human myocardium. J Mol Cell Cardiol 1989; 21: 263–7

    PubMed  CAS  Google Scholar 

  148. Lucchesi BR, Mullane KM. Leukocytes and ischemia-induced myocardial injury. Ann Rev Pharmacol Toxicol 1986; 26: 201–24.

    CAS  Google Scholar 

  149. Engler R. Granulocytes and oxidative injury in myocardial ischemia and reperfusion. Federation Proc 1987; 46: 2395–6.

    Google Scholar 

  150. Shea MJ, Simpson PJ, Werns SW et al. Effect of neutrophil depletion on recovery of “stunned” myocardium. Clin Res 1987; 35: 327A (abstr.).

    Google Scholar 

  151. Jeremy RW, Becker LC. Neutrophil depletion does not prevent myocardial dysfunction after brief coronary occlusion: J Am Coll Cardiol 1989; 13: 1155–63.

    PubMed  CAS  Google Scholar 

  152. O’Neill PG, Charlat ML, Kim H-S et al. Lipoxygenase inhibitor nafazatrom fails to attenuate postischemic ventricular dysfunction. Cardiovasc Res 1987; 21: 755–60.

    PubMed  Google Scholar 

  153. Schott RJ, Nao BS, McClanahan TB et al. F(ab’)2 Fragments of anti-mol (904) monoclonal antibodies do not prevent myocardial stunning. Circ Res 1989; 65: 1112–24.

    PubMed  CAS  Google Scholar 

  154. Kerber RE, Shasby DM, Seabold J et al. Does reduction of leukocyte accumulation in reperfused myocardium affect stunning? Circulation 1989; 80(Supp II): 11–401 (abstr.).

    Google Scholar 

  155. Go LO, Murry CE., Richard VJ et al. Myocardial neutrophil accumulation during reper-fusion after reversible or irreversible ischemic injury. Am J Physiol 1988: 255: H1188–H1198.

    PubMed  CAS  Google Scholar 

  156. Juneau CF., Ito BR, del Balzo U et al. Severe neutrophil depletion by leukocyte filters or cytotoxic drugs does not improve the recovery of contractile function in stunned myocardium. Circulation 1991; 85(Suppl II): 11–655.

    Google Scholar 

  157. Westlin W., Mullane KM. Does captopril attenuate reperfusion-induced myocardial dysfunction by scavenging free radicals? Circulation 1988; 77(Suppl I): I-30-I-39.

    CAS  Google Scholar 

  158. Ferrari R, Alfieri O, Curello S et al. Occurrence of oxidative stress during reperfusion of the human heart. Circulation 1990; 81: 201–11.

    PubMed  CAS  Google Scholar 

  159. Asinger RW, Peterson DA., Elsperger KJ et al. Long-term recovery of LV wall thickening after 1 hour of ischemia is not affected when superoxide dismutase and catalase are administered during the first 45 minutes of reperfusion. J Am Coll Cardiol 1988; 2: 163A (abstr.).

    Google Scholar 

  160. Nejima J, Knight DR., Fallon JT et al. Superoxide dismutase reduces reperfusion arrhythmias but fails to salvage regional myocardial function or myocardium at risk in conscious dogs. Circulation 1989; 78: 143–53.

    Google Scholar 

  161. Przyklenk K, Kloner RA. “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 1989; 64: 86–96.

    PubMed  CAS  Google Scholar 

  162. Patel BS, Jeroudi MO, O’Neill PG et al. Effect of human recombinant superoxide dismutase on canine myocardial infarction. Am J Physiol 1990; 258: H369–H380.

    PubMed  CAS  Google Scholar 

  163. Forman MB, Puett DW, Cates CU et al. Glutathione redox pathway and reperfusion injury. Effect of N-acetylcysteine on infarct size and ventricular function. Circulation 1988; 78: 202–13.

    PubMed  CAS  Google Scholar 

  164. Klein HH, Pich S, Schuff-Werner P et al. Trolox, a water-soluble vitamin E analogue, accelerates functional recovery but does not reducc infarct size in regionally ischemic, reperfused porcine hearts. Am Heart J (in press).

    Google Scholar 

  165. Homans DC, Sublett E, Asinger R et al. SOD + catalase does not attenuate regional left ventricular dysfunction following exercise induced ischemia. J Am Coll Cardiol 1988; 78: 11–76 (abstr.).

    Google Scholar 

  166. Hearse DJ., Humphrey SM, Bullock GR. The oxygen paradox and the calcium paradox: two facets of the same problem? J Mol Cell Cardiol 1978; 10: 641–68.

    PubMed  CAS  Google Scholar 

  167. Reeves JP. Bailey CA. Hale CC. Redox modification of sodium-calcium exchange activity in cardiac sarcolemmal vesicles. J Biol Chem 1986; 261: 4948–4955.

    PubMed  CAS  Google Scholar 

  168. Bolli R, Hartley CJ, Rabinovitz RS. Clinical relevance of myocardial “stunning”. Cardiovase Drugs Ther 1991; 5: 877–90.

    CAS  Google Scholar 

  169. Mathias P, Kent NZ, Blevins RD et al. Coronary vasospasm as a cause of stunned myocardium. Am Heart J 1987; 113: 383–5.

    PubMed  CAS  Google Scholar 

  170. Fine DG., Clements IP, Callahan MJ. Myocardial stunning in hypertrophic cardiomyopathy: Recovery predicted by single photon emission computed tomographic thallium-201 scintigraphy. J Am Coll Cardiol 1989; 13: 1415–8.

    PubMed  CAS  Google Scholar 

  171. Luu M, Stevenson LW, Brunken RC et al. Delayed recovery of revascularized myocardium after referral for cardiac transplantation. Am Heart J 1990; 119: 668–70.

    PubMed  CAS  Google Scholar 

  172. Homan DC, Laxson DD, Sublett E et al. Cumulative deterioration of myocardial function after repeated episodes of exercise-induced ischemia. Am Physiol Soc 1989; 256: H1463–H1471.

    Google Scholar 

  173. Cohn PF. Silent myocardial ischemia: classification, prevalence, and prognosis. Am J Med 1985; 79(Suppl 3A): 2–12.

    PubMed  CAS  Google Scholar 

  174. Bolli R. Oxygen-derived free radicals and postischemic myocardial dysfunction (“stunned myocardium”). J Am Coll Cardiol 1988; 12: 239–49.

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. Marcel E. Zughaib
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul B. McCay
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohamed O. Jeroudi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Craig Hartley
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jian-Zhong Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Selim Sekili
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiao-Ying Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Roberto Bolli
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Institute of Physiology, Heinrich-Heine-University, Düsseldorf, Germany

    Hans Michael Piper

  2. Department of Thoracic and Cardiovascular Surgery, Heinrich-Heine-University, Düsseldorf, Germany

    Claus J. Preusse

Rights and permissions

Reprints and permissions

Copyright information

© 1993 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Zughaib, M.E. et al. (1993). Moderate ischemic injury and myocardial stunning. In: Piper, H.M., Preusse, C.J. (eds) Ischemia-reperfusion in cardiac surgery. Developments in Cardiovascular Medicine, vol 142. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-1713-5_1

Download citation

  • DOI: https://doi.org/10.1007/978-94-011-1713-5_1

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-4750-0

  • Online ISBN: 978-94-011-1713-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation