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Stunning, Hibernation, and Calcium in Myocardial Ischemia and Reperfusion pp 10–55Cite as

Stunning: A Radical Re-view

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Summary

The recovery from trauma, whether ischemia or some other form of tissue injury, is never instantaneous; time is always required for repair and the return of normal metabolism and function. To what extent the delay in recovery of contractile activity (stunning) after a brief period of ischemia represents convalescence from ischemia-induced injury, as opposed to the expression of reperfusion-induced injury, is perhaps not as clear as the proponents of stunning would hope. Definitive evidence for a distinct reperfusion-induced pathology, which compromises the recovery of contractile function from the depressed state induced by ischemia, is elusive. If reperfusion-induced injury accounts for a significant proportion of stunning, then the molecular mechanisms responsible for initiating the event and those responsible for orchestrating the event at the level of the contractile protein are far from clear. Perturbations of calcium homeostasis are frequently cited as responsible for the depressed contractile state, however, some metabolic derangement must precede any pathologically induced ionic disturbance. In this connection, evidence indicates that free-radical-induced oxidant stress, during the early moments of reperfusion, may modify the activity of a number of thiol-regulated proteins that are directly, or indirectly, responsible for controlling the movement of calcium. Sarcolemmal sodium-calcium exchange and the calcium release channel of the sarcoplasmic reticulum may be activated, whereas the sarcolemmal calcium pump and sodium-potassium ATPase, together with the calcium pump of the sarcoplasmic reticulum, may be inhibited. Under the conditions prevailing during ischemia and reperfusion, this would be expected to promote an early intracellular calcium overload. It is difficult to reconcile such a change with the decreased inotropic state that characterizes stunning; however, it seems likely that the calicum overload is transient and that the stunned myocardium rapidly reestablishes normal levels of intracellular calcium. It is still difficult to explain adequately the reduced inotropic state; clearly, the mechanism of stunning is not quite as simple as its definition.

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References

  1. Hearse DJ. Ischemia at the crossroads? Cardiovasc Drugs Ther 1988; 2: 9–15.

    Article  PubMed  CAS  Google Scholar 

  2. Donato L. Concluding remarks: The “stunned” cardiologist. Can J Cardiol 1986; 2 (Suppl A): 260A - 262A.

    Google Scholar 

  3. Hearse DJ. Reperfusion of the ischemic myocardium. J Mol Cell Cardiol 1977; 9: 605–616.

    Article  PubMed  CAS  Google Scholar 

  4. Hearse DJ. Ischemia, reperfusion and the determinants of tissue injury. Cardiovasc Drugs Ther 1990; 4: 767–776.

    Article  PubMed  Google Scholar 

  5. Bolli R. Oxygen-derived free radicals and myocardial re-perfusion injury: An overview. Cardiovasc Drugs Ther 1991; 5: 249–268.

    Article  PubMed  Google Scholar 

  6. Hearse DJ, Bolli R. Reperfusion-induced injury: Manifestation, mechanisms and clinical relevance. Trends Cardiovasc Med 1991, in press.

    Google Scholar 

  7. Hearse DJ. Reperfusion-induced injury: A possible role for oxidant stress and its manipulation. Cardiovasc Drugs Ther 1991; 5: 225–236.

    Article  PubMed  Google Scholar 

  8. Bolli R. Mechanism of myocardial “stunning.” Circulation 1990; 82: 723–738.

    Article  PubMed  CAS  Google Scholar 

  9. Becker LC, Ambrosio G. Myocardial consequences of re-perfusion. Prog Cardiovasc Dis 1987; 30: 23–44.

    Article  PubMed  CAS  Google Scholar 

  10. Opie LH. Reperfusion injury and its pharmacologic modification. Circulation 1989; 80: 1049–1062.

    Article  PubMed  CAS  Google Scholar 

  11. Forman MB, Virmani R. Pathogenesis and modification of myocardial reperfusion injury. In: Gersh BJ, Rahimtoola SH, eds. Acute myocardial infarction. New York, Elsevier, 1990: 349–370.

    Google Scholar 

  12. Braunwald E, Kloner RA. Myocardial reperfusion: A double-edged sword? J Clin Invest 1985; 76: 1713–1719.

    Article  PubMed  CAS  Google Scholar 

  13. Reimer KA, Murry CE, Richard VJ. The role of neutrophils and free radicals in the ischemic-reperfused heart: Why the confusion and controversy? J Mol Cell Cardiol 1989; 21: 1225–1239.

    Article  PubMed  CAS  Google Scholar 

  14. Jennings RB, Reimer KA. Factors involved in salvaging ischemic myocardium: Effect of reperfusion of arterial blood. Circulation 1983; 68 (Suppl I): 125–136.

    Google Scholar 

  15. Tanaka K, Hearse DJ. Reperfusion-induced arrhythmias in the isolated rabbit heart: Characterization of the influence of the duration of regional ischemia and the extracellular potassium concentration. J Mol Cell Cardiol 1988; 20: 201–211.

    Article  PubMed  CAS  Google Scholar 

  16. Manning AS, Heasrse DJ. Reperfusion-induced arrhythmias: Mechanisms and prevention. J Mol Cell Cardiol 1984; 16: 497–518.

    Article  PubMed  CAS  Google Scholar 

  17. Hearse DJ. Free radical and myocardial injury during ischemia and reperfusion: A short-lived phenomenon? In: Rosen M, Palti Y, eds. Lethal arrhythmias resulting from myocardial ischemia and infarction. Boston: Kluwer Academic Press, 1988: 105–115.

    Google Scholar 

  18. Hearse DJ. Free radicals, membrane injury, and electrophysiological disorders. In: Zipes DP, Jalife J, eds. Cardiac electrophysiology from cell to bedside. Philadelphia: WB Saunders, 1990: 442–447.

    Google Scholar 

  19. Braunwald E, Kloner RA. The stunned myocardium: Prolonged, postischemic ventricular dysfunction. Circulation 1982; 66: 1146–1149.

    Article  PubMed  CAS  Google Scholar 

  20. Bolli R. Oxygen-derived free radicals and postischemic myocardial dysfunction (“stunned myocardium”). J Am Coll Cardiol 1988; 12: 239–249.

    Article  CAS  Google Scholar 

  21. Bolli R, Triana JF, Jeroudi MO. Prolonged impairment of coronary vasodilation after reversible ischemia: evidence for microvascular “stunning”. Circ Res 1990; 67: 332–343.

    PubMed  CAS  Google Scholar 

  22. 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: 1322–1334.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  24. 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 

  25. Kloner RA, Ganote CE, Jennings RB. The no reflow phenomenon after temporary occlusion in the dog. J Clin Invest 1974; 54: 1496–1508.

    Article  PubMed  CAS  Google Scholar 

  26. Engler RL, Dahlgren MD, Morris DD, et al. Role of leukocytes in response to acute myocardial ischemia and reflow in dogs. Am J Physiol 1986; 251: H314 - H322.

    PubMed  CAS  Google Scholar 

  27. Guarnieri C, Ferrari R, Visiolo O, et al. Effect of alphatocopherol on hypoxic-perfused and reoxygenated rabbit heart muscle. J Mol Cell Cardiol 1978; 10: 893–906.

    Article  PubMed  CAS  Google Scholar 

  28. Guarnieri C, Flamigni F, Caldarera CM. Role of oxygen in the cellular damage induced by re-oxygenation of hypoxie heart. J Mol Cell Cardiol 1980; 12: 797–808.

    Article  PubMed  CAS  Google Scholar 

  29. 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: 641–668.

    Article  PubMed  CAS  Google Scholar 

  30. Hearse DJ, Humphrey SM, Chain EB. Abrupt reoxygenation of the anoxic potassium-arrested perfused rat heart: A study of myocardial enzyme release. J Mol Cell Cardiol 1973; 5: 395–407.

    Article  PubMed  CAS  Google Scholar 

  31. Shattock MJ, Manning, AS, Hearse DJ. Effects of hydrogen peroxide on cardiac function and post-ischemic function recovery in the isolated ‘working’ rat heart. Pharmacology 1982; 24: 118–122.

    Article  PubMed  CAS  Google Scholar 

  32. Shlafer M, Kane P, Wiggins V, et al. Superoxide dismutase plus catalase enhance protective effects of cold cardioplegia in globally ischemic isolated hearts (Abstr). Circulation 1981;64 (Suppl IV):IV148.

    Google Scholar 

  33. Shlafer M, Kane PF, Wiggins VY, et al. Possible role for cytotoxic oxygen metabolites in the pathogenesis of cardiac ischemic injury. Circulation 1982; 66 (Suppl I): I85 - I92.

    PubMed  CAS  Google Scholar 

  34. 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: 830–839.

    PubMed  CAS  Google Scholar 

  35. Stewart JR, Blackwell WH, Crute SL, et al. Prevention of myocardial ischemia/reperfusion injury with oxygen free-radical scavengers. Surg For 1982; 33: 317–320.

    Google Scholar 

  36. 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: 262–272.

    PubMed  CAS  Google Scholar 

  37. Stewart JR, Crute SL, Loughlin V, et al. Prevention of free radical-induced myocardial reperfusion injury with allopurinol. J Thorac Cardiovasc Surg 1985; 90: 68–72.

    PubMed  CAS  Google Scholar 

  38. Stewart JR, Gerhardt EB, Wehr CJ, et al. Free radical scavengers and myocardial preservation during transplantation. Ann Thorac Surg 1986; 42: 390–393.

    Article  PubMed  CAS  Google Scholar 

  39. Chambers DJ, Astras G, Takahashi A, et al. Free radicals and cardioplegia: Organic anti-oxidants as additives to the St Thomas’ Hospital cardioplegia solution. Cardiovasc Res 1989; 23: 351–358.

    Article  PubMed  CAS  Google Scholar 

  40. Chambers DJ, Braimbridge MV, Hearse DJ. Free radicals and cardioplegia: Free radical scavengers improve postischemic function of the rat myocardium. Eur J Cardiothorac Surg 1987; 1: 37–45.

    Article  PubMed  CAS  Google Scholar 

  41. Chambers DJ, Braimbridge MV, Hearse DJ. Free radicals and cardioplegia: The absence of an additive effect with allopurinol pretreatment and the use of antioxidant enzymes in the rat. Eur J Cardiothorac Surg 1987; 1: 80–90.

    Article  PubMed  CAS  Google Scholar 

  42. Chambers DJ, Braimbridge MV, Hearse DJ. Free radicals and cardioplegia: Allopurinol and oxypurinol reduce myocardial injury following ischemic arrest. Ann Thorac Surg 1987; 44: 291–297.

    Article  PubMed  CAS  Google Scholar 

  43. Casale AS, Bulkley GB, Bulkley BH, et al. Oxygen free radical scavengers protect the arrested globally ischemic heart upon reperfusion. Surg For 1983; 34: 313–316.

    Google Scholar 

  44. Gardner TJ, Stewart JR, Casale AS, et al. Reduction of myocardial ischemic injury with oxygen-derived free radical scavengers. Surgery 1983; 94: 423–427.

    PubMed  CAS  Google Scholar 

  45. Menasché P, Grousset C, Gauduel Y, et al. Comparative study of free radical scavengers in cardioplegic solutions. Improved protection with peroxidase. J Thorac Cardiovase Surg 1986; 92: 264–271.

    Google Scholar 

  46. Myers CL, Weiss SJ, Kirsh MM, et al. Effects of supplementing hypothermic crystalloid cardioplegic solution with catalase, superoxide dismutase, allopurinol, or desferrioxamine on functional recovery of globally ischemic and reperfused isolated hearts. J Thorac Cardiovasc Surg 1986; 91: 281–289.

    PubMed  CAS  Google Scholar 

  47. 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: 492–499.

    Article  PubMed  CAS  Google Scholar 

  48. Johnson DL, Horneffer PJ, Dinatale JM, et al. Free radical scavengers improve functional recovery of stunned myocardium in a model of surgical coronary revascularization. Surgery 1987; 102: 334–340.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  50. Jolly SR, Kane WJ, Bailie MB, et al. Canine myocardial reperfusion injury, its reduction by the combined administration of superoxide dismutase and catalase. Circ Res 1984; 54: 277–285.

    PubMed  CAS  Google Scholar 

  51. Hearse DJ. The protection of the ischemic myocardium: Surgical success versus clinical failure. Prog Cardiovasc Dis 1988; 6: 381–402.

    Article  Google Scholar 

  52. Engler R, Gilpin E. Can superoxide dismutase alter myocardial infarct size? Circulation 1989; 79: 1137–1142.

    Article  PubMed  CAS  Google Scholar 

  53. Bolli R, McCay 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 Commun 1990; 9: 169–180.

    Article  CAS  Google Scholar 

  54. 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 

  55. 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 re-perfusion injury. Cire Res 1989; 65: 607–622.

    CAS  Google Scholar 

  56. 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: 4695–4699.

    Article  PubMed  CAS  Google Scholar 

  57. 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 alpha-phenyl N-tert-butyl nitrone. J Clin Invest 1988; 82: 476–485.

    Article  PubMed  CAS  Google Scholar 

  58. Bolli R, Zhu W-X, Hartley CJ, et al. Attenuation of dysfunction in the postischemic ‘stunned’ myocaridum by dimethylthiourea. Circulation 1987; 76: 458–468.

    Article  PubMed  CAS  Google Scholar 

  59. Bolli R, Zhu W-X, Thornby JI, et al. Time course and determinants of recovery of function after reversible ischemia in conscious clogs. Am J Physiol 1988; 254: H102 - H114.

    PubMed  CAS  Google Scholar 

  60. Myers ML, Bolli R. Lekich RF, et al. N-2-mercaptopropionylglycine improves recovery of myocardial function after reversible regional ischemia. J Am Coll Cardiol 1986; 8: 1161–1168.

    Article  PubMed  CAS  Google Scholar 

  61. 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: 915–921.

    Article  PubMed  CAS  Google Scholar 

  62. 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 

  63. Bernard M, Menasché P, Piétri S, et al. Cardioplegic arrest superimposed on evolving myocardial ischemia. Improved recovery after inhibition of hydroxyl radical generation by peroxidase or deferoxamine. A 31P nuclear resonance study. Circulation 1988;78 (Suppl III):I1I164–I1I172.

    Google Scholar 

  64. Nejima J, Knight DR, Fallon JT, et al. Superoxide dismutase reduces reperfusion arrhythmias but fails to salvage regional function or myocardium at risk in conscious dogs. Circulation 1989; 79: 143–153.

    Article  PubMed  CAS  Google Scholar 

  65. 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. Cire Res 1989; 64: 86–96.

    CAS  Google Scholar 

  66. Gross GJ, Faber 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 

  67. Przyklenk K, Kloner RA. Superoxide dismutase plus catalase improve contractile function in the canine model of the “stunned myocardium”. Circ Res 1986; 58: 148–156.

    PubMed  CAS  Google Scholar 

  68. Murry CE, Richard VJ, Jennings RB, et al. Free radicals do not cause myocardial stunning after four 5 minute coronary occlusions (Abstr). Circulation 1989;80 (Suppl II): 1I296.

    Google Scholar 

  69. Buchwald A, Klein HH, Lindert S, et al. Effect of intracoronary superoxide dismutase on regional function in stunned myocardium. J Cardiovasc Pharmacol 1989; 13: 258–264.

    Article  PubMed  CAS  Google Scholar 

  70. 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 

  71. 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 an captopril. J Cardiovasc Pharmacol 1991; 17: 185–191.

    Article  PubMed  CAS  Google Scholar 

  72. Ambrosio G, Weisfeldt ML, Jacobus WE, et al. Evidence for reversible oxygen radical-mediated component or re-perfusion injury: Reduction by recombinant human superoxide dismutase administered at the time of reflow. Circulation 1987; 75: 282–291.

    Article  PubMed  CAS  Google Scholar 

  73. Forman MB, Puett DW, Cates CU, et al. Gluthathione redox pathway and reperfusion injury. Effect of N-acetylcysteine on infarct size and ventricular function. Circulation 1988; 78: 202–213.

    Article  PubMed  CAS  Google Scholar 

  74. Qiu Y, Bernier M, Hearse DJ. The influence of N-acetylcysteine on cardiac function and rhythm disorders during ischemia and reperfusion. Cardioscience 1990; 1: 65–74.

    PubMed  CAS  Google Scholar 

  75. Dage RC, Anderson BA, Mao SJ, et al. Probucol reduces myocardial dysfunction during reperfusion after short-term ischemia in rabbit heart. J Cardiovasc Pharmacol 1991; 17: 158–165.

    Article  PubMed  CAS  Google Scholar 

  76. Buchwald A, Klein HH, Lindert S, et al. Effect of alphatocopherol (vitamin E) in a porcine model of stunned myocardium. J Cardiovasc Pharmacol 1989; 14: 46–52.

    Article  PubMed  CAS  Google Scholar 

  77. Ambrosio G, Zweier JL, Jacobus WE, et al. Improvement of postischemic myocardial function and metabolism induced by administration of deferoxamine at the time of reflow: The role of iron in the pathogenesis of reperfusion injury. Circulation 1987; 76: 906–915.

    Article  PubMed  CAS  Google Scholar 

  78. Illes RW, Silverman NA, Krukenkamp IB, et al. Amelioration of postischemic stunning by deferoxamine-blood cardioplegia. Circulation 1989;80 (Suppl III):III30–III35.

    PubMed  CAS  Google Scholar 

  79. 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: 351–360.

    PubMed  CAS  Google Scholar 

  80. Maruyama M, Pieper GN, Kalyanaraman B, et al. Effects of hydroxyethyl starch conjugated deferoxamine on myocardial functional recovery following coronary occlusion and reperfusion in dogs. J Cardiovasc Pharmacol 1991; 17: 166–175.

    Article  PubMed  CAS  Google Scholar 

  81. Bernier M, Hearse DJ, Manning AS. Reperfusion-induced arrhythmias and oxygen-induced free radicals: studies with “anti-free radical interventions” and a free radical generating system in the isolated perfused rat heart. Cire Res 1986; 58: 331–340.

    CAS  Google Scholar 

  82. Euler DE: The effect of free radical scavengers on canine reperfusion arrhythmias (Abstr). Circulation 1989;80 (Suppl II):II30.

    Google Scholar 

  83. van der Kraaij AMM, Mostert LJ, van Eijk HG, et al. Iron-load increases the susceptibility of rat hearts to oxygen reperfusion damage. Protection by the antioxidant (+)-cyanidanol-3 and deferoxamine. Circulation 1988; 78: 442–449.

    Article  PubMed  Google Scholar 

  84. Puett DW, Forman MB, Cates CU, et al. Oxypurinol limits myocardial stunning but does not reduce infarct size after reperfusion. Circulation 1987; 76: 678–686.

    Article  PubMed  CAS  Google Scholar 

  85. Holzgrefe HH, Gibson JK. Beneficial effects of oxypurinol pretreatment in stunned, reperfused canine myocardium. Cardiovasc Res 1989; 23: 340–350.

    Article  PubMed  CAS  Google Scholar 

  86. Werns S. Ventura A, Li GC, et al. Amflutizole, a xanthine oxidase inhibitor, does not attenuate myocardial stunning in the canine heart (Abstr). Circulation 1989; 80 (Suppl II): I1295.

    Google Scholar 

  87. Kloner RA. Do neutrophils mediate the phenomenon of stunned myocardium? J Am Coll Cardiol 1989; 13: 1164–1166.

    Article  PubMed  CAS  Google Scholar 

  88. Lucchesi BR, Werns SW, Fantone JC. The role of the neutrophil and free radicals in ischemic myocardial injury. J Mol Cell Cardiol 1989; 21: 1241–1251.

    Article  PubMed  CAS  Google Scholar 

  89. Fuji H, Kuzuya T, Hoshida S, et al. Free radicals derived from neutrophils mediate reoxygenation-induced myocardial cell injury (Abstr). Circulation 1988;78 (Suppl II): II56.

    Google Scholar 

  90. Engler R, Covell JW. Granulocytes cause reperfusion ventricular dysfunction after 15-minute ischemia in the dog. Circ Res 1987; 61: 20–28.

    PubMed  CAS  Google Scholar 

  91. Westlin W, Mullane KM. Leukocyte depletion attenuates postischemic myocardial dysfunction. FASEB J 1988; 2: A702.

    Google Scholar 

  92. Westlin W, Mullane KM. Alleviation of myocardial stunning by leukocyte and platelet depletion. Circulation 1989; 80: 1828–1836.

    Article  PubMed  CAS  Google Scholar 

  93. 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 

  94. Jeremy RW, Becker LC. Neutrophil depletion does not prevent myocardial dysfunction after brief coronary occlusion. J Am Coll Cardiol 1989; 13: 1155–1163.

    Article  PubMed  CAS  Google Scholar 

  95. O’Neill PG, Charlat ML, Kim H-S, et al. Lipoxygenase inhibitor nafazatrom fails to attenuate postischemic ventricular dysfunction. Cardiovasc Res 1987; 21: 755–760.

    Article  PubMed  Google Scholar 

  96. Schott RJ, Nan BS, McClanahan TB, et al. F(ab’)2 fragments of anti-mol (904) monoclonal antibodies do not prevent myocardial stunning. Circ Res 1989; 65: 1112–1124.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  98. Bernier M: Hearse DJ. Reperfusion-induced arrhythmias: Mechanisms of protection by glucose and mannitol. Am J Physiol 1988; 254: H862 - H870.

    PubMed  CAS  Google Scholar 

  99. Bernier M, Manning, AS, Hearse DJ. Reperfusion arrhythmias: Dose-related protection by anti-free radical interventions. Am J Physiol 1989; 256: H1344 - H1352.

    PubMed  CAS  Google Scholar 

  100. Kusama Y, Bernier M. Hearse DJ. The exacerbation of reperfusion arrhythmias by sudden oxidant stress. Circ Res 1990; 67: 481–489.

    PubMed  CAS  Google Scholar 

  101. Woodward B, Zakaria MNM. Effect of some free radical scavengers on reperfusion-induced arrhythmias in the isolated rat heart. J Mol Cell Cardiol 1985; 17: 485–493.

    Article  PubMed  CAS  Google Scholar 

  102. 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: 757–760.

    PubMed  CAS  Google Scholar 

  103. Kuzuya T, Hoshida S, Kim Y, et al. Detection of oxygen-derived free radical generation in the canine postischemic heart during late phase of reperfusion. Circ Res 1990; 66: 1160–1165.

    PubMed  CAS  Google Scholar 

  104. Zweier JL, Kuppusamy P. Electron paramagnetic resonance measurements of free radicals in the intact beating heart: A technique for detection and characterization of free radicals in whole biological tissues. Proc Natl Acad Sci USA 1988; 85: 5703–5707.

    Article  PubMed  CAS  Google Scholar 

  105. Kramer JH, Arroyo CM, Dickens BF, et al. Spin-trapping evidence that graded myocardial ischemia alters postischemic superoxide production. Free Rad Biol Med 1987; 3: 153–159.

    Article  PubMed  CAS  Google Scholar 

  106. Zweier JL, Flaherty JT, Weisfeldt ML. Direct measurement of free radical generation following reperfusion of ischemic myocardium. Proc Natl Acad Sci USA 1987; 84: 1404–1407.

    Article  PubMed  CAS  Google Scholar 

  107. Nakazawa H, Ichimori K, Shinozaki Y, et al. Is superoxide demonstration by electron-spin resonance spectroscopy really superoxide ? Am J Physiol 1988; 255: H213 - H215.

    PubMed  CAS  Google Scholar 

  108. Zweier JL, Flaherty JT, Weisfeldt ML. Determination of the window of ischemic duration which results in myocar-dial free radical generation upon reperfusion (Abstr). Cir-culation 1988; 78 (Suppl II): II - 373.

    Google Scholar 

  109. 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: 1–4.

    Article  Google Scholar 

  110. Zweier JL. Measurement of superoxide-derived free radicals in the reperfused heart. Evidence for a free radical mechanism of reperfusion injury. J Biol Chem 1988; 263: 1353–1357.

    PubMed  CAS  Google Scholar 

  111. Reinke LA, Lai EK, DuBose DM, et al. In vivo generation of free radicals in the heart and other organs of rats treated with ethanol or acetaldehyde (Abstr). FASEB J 1988; A1388.

    Google Scholar 

  112. Leiboff RL, Arroyo CM, Schaer GL, et al. Free radical generation in an in vivo model of regional myocardial stunning (Abstr) FASEB J 1988; 3030: A818.

    Google Scholar 

  113. Blasig IE, Ebert B, Hennig C, et al. Inverse relationship between ESR spin trapping of oxyradicals and degree of functional recovery during myocardial reperfusion in isolated working rat heart. Cardiovasc Res 1990; 24: 263–270.

    Article  PubMed  CAS  Google Scholar 

  114. Zweier JL, Rayburn BK, Flaherty JT, et al. Recombinant superoxide dismutase reduces oxygen free radical concentrations in reperfused myocardium. J Clin Invest 1987; 80: 1728–1734.

    Article  PubMed  CAS  Google Scholar 

  115. Pallandi RT, Perry MA, Campbell TJ. Proarrhythmic effects of an oxygen-derived free radical generating system on action potentials recorded from guinea pig ventricular myocardium: A possible cause of reperfusion-induced arrhythmias. Circ Res 1987; 61: 50–54.

    PubMed  CAS  Google Scholar 

  116. Nakaya H, Tohse N, Kanno M. Electrophysiological derangements induced by lipid peroxidation in cardiac tissue. Am J Physiol 1987; 253: H1089 - H1097.

    PubMed  CAS  Google Scholar 

  117. Hearse DJ, Kusama Y, Bernier M. Rapid electrophysiological changes leading to arrhythmias in the aerobic rat heart: Photosensitization studies with rose bengal-derived reactive oxygen intermediates. Circ Res 1989; 65: 146–153.

    PubMed  CAS  Google Scholar 

  118. Barrington PL, Meier CF, Weglicki WB. Abnormal electrical activity induced by free radical generating systems in isolated cardiocytes. J Mol Cell Cardiol 1988; 20: 1163–1178.

    Article  PubMed  CAS  Google Scholar 

  119. 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 

  120. Burton KP, McCord JM, Ghai G. Myocardial alterations due to free-radial generation. Am J Physiol 1984; 246: H776 - H783.

    PubMed  CAS  Google Scholar 

  121. Przyklenk K, Whittaker P, Kloner RA. In vivo infusion of oxygen free radical substrates causes myocardial systolic, but not diastolic dysfunction. Am Heart J 1990; 119: 807–815.

    Article  PubMed  CAS  Google Scholar 

  122. Ytrehus K, Myklebust R, Mjqs OD. Influence of oxygen radicals generated by xanthine oxidase in the isolated per-fused rat heart. Cardiovasc Res 1986; 20: 597–603.

    Article  PubMed  CAS  Google Scholar 

  123. Goldhaber JI, Ji S, Lamp ST, et al. Effect of exogenous free radicals on electromechanical function and metabolism in isolated rabbit and guinea pig ventricle. J Clin Invest 1988; 83: 1800–1809.

    Article  Google Scholar 

  124. Hayashi H, Miyata H, Watanabe H, et al. Effects of hydrogen peroxide on action potentials and intracellular Ca’ concentration of guinea pig heart. Cardiovasc Res 1989; 23: 767–773.

    Article  PubMed  CAS  Google Scholar 

  125. 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: 843–851.

    Article  Google Scholar 

  126. Hearse DJ, Tosaki A. Reperfusion-induced arrhythmias and free radicals: Studies in the rat heart with DMPO. J Cardiovasc Pharmacol 1987; 9: 641–650.

    Article  PubMed  CAS  Google Scholar 

  127. Hearse DJ, Tosaki A. Free radicals and reperfusioninduced arrhythmias: Protection by spin trap agent PBN in the rat heart. Circ Res 1987; 60: 375–383.

    PubMed  CAS  Google Scholar 

  128. Stahl LD, Aversano TR, Becker LC. Selective enhancement of function in stunned myocardium by increased flow. Circulation 1986; 74: 843–851.

    Article  PubMed  CAS  Google Scholar 

  129. Kitakaze M, Weisfeldt ML, Marban E. Acidosis during early reperfusion prevents myocardial stunning in perfused ferret hearts. J Clin Invest 1988; 82: 920–927.

    Article  PubMed  CAS  Google Scholar 

  130. Hori M, Kitakaze M, Takashima S. AICA-riboside (5amino-4-imidazole carboxamide riboside 100), a novel adenosine potentiator, attenuates myocardial stunning (Abstr). Circulation 1990;82 (Suppl III):1II466.

    Google Scholar 

  131. Pryzklenk K, Kloner RA. Effect of verapamil on postischemic “stunned” myocardium: Importance of the timing of treatment. J Am Coll Cardiol 1988; 11: 614–623.

    Article  Google Scholar 

  132. Ellis SE, Wynne J. Braunwald E, et al. Response of Stunning and Oxidant Stress 49 reperfusion-salvaged myocardium to inotropic stimulation. Am Heart J 1984; 107: 9–13.

    Article  Google Scholar 

  133. Bolli R, Zhu WX, Myers ML, et al. Beta-adrenergic stimulation reverses postischemic myocardial dysfunction without producing subsequent functional deterioriation. Am J Cardiol 1985; 56: 964–968.

    Article  PubMed  CAS  Google Scholar 

  134. Hoffmeister HM, Mauser M, Schaper W. Effect of adenosine and AlCariboside on ATP content and regional contractile function in reperfused canine myocardium. Basic Res Cardiol 1985; 80: 445–458.

    Article  PubMed  CAS  Google Scholar 

  135. Heusch G, Schäfer S, Kröger K. Recruitment of inotropic reserve in “stunned” myocardium by the cardiotonic agent AR-L 57. Basic Res Cardiol 1988; 83: 602–610.

    Article  PubMed  CAS  Google Scholar 

  136. Babbitt DG, Virmani R, Forman MB, Intracoronary adenosine administered after reperfusion limits vascular injury after prolonged ischemia in the canine model. Circulation 1989; 80: 1388–1399.

    Article  PubMed  CAS  Google Scholar 

  137. Ciuffo AA, Ouyang P, Becker LC, et al. Reduction of sympathetic inotropic response after ischemia in dogs: Contributor to stunned myocardium. J Clin Invest 1985; 75: 1504–1509.

    Article  PubMed  CAS  Google Scholar 

  138. Hori M, Kitakaze M, Sato H, et al. Transient acidosis by staged reperfusion prevents myocardial stunning. Circulation 1989;80 (Suppl II):II600.

    Google Scholar 

  139. Taylor AL, Golino P, Pastor P, et al. Differential enhancement of postischemic segmental systolic thickening by diltiazem. J Am Coll Cardiol 1990; 15: 737–747.

    Article  PubMed  CAS  Google Scholar 

  140. Lampling KA, Gross GJ. Improved recovery of myocardial segment function following a short coronary occlusion in dogs by nicorandil, a potential new antianginal agent. J Cardiovasc Pharmacol 1985; 7: 158–166.

    Article  Google Scholar 

  141. Warltier 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): 5120 - S124.

    Google Scholar 

  142. 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: 1176–1183.

    Article  PubMed  CAS  Google Scholar 

  143. Farber NE, Gross GJ. Prostaglandin redirection by thromboxane synthetase inhibition. Attenuation of myocardial stunning in canine heart. Circulation 1990; 81: 369–380.

    Article  PubMed  CAS  Google Scholar 

  144. Grover GJ, Dzwonczyk S, Sleph PG. Ruthenium red improves postischemic contractile function in isolated rat hearts. J Cardiovasc Pharmacol 1990; 16: 783–789.

    Article  PubMed  CAS  Google Scholar 

  145. Boni M. Kitakaze M, Sato H, et al. Transient acidosis by staged reperfusion prevents myocardial stunning (Abstr). Circulation 1989;80 (Suppl II):II600.

    Google Scholar 

  146. Kusuoka H, Porterfield JK, Weisman HF, et al. Pathophysiology and pathogenesis of stunned myocardium: Depressed calcium activation of contraction as a consequence of reperfusion-induced cellular calcium overload in ferret hearts. J Clin Invest 1987; 79: 950–961.

    Article  PubMed  CAS  Google Scholar 

  147. 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):IV17–IV22.

    PubMed  CAS  Google Scholar 

  148. Krause SM, Jacobus WE, Becker LC. Alterations in cardiac sarcoplasmic reticulum calcium transport in the postischemic “stunned” myocardium. Circ Res 1989; 65: 526–530.

    PubMed  CAS  Google Scholar 

  149. Nayler WG, Buckley DJ, Leong J. Calcium antagonists and the “stunned” myocardium. Cardioscience 1990; 1: 61–64.

    PubMed  CAS  Google Scholar 

  150. Kusuoka H, Koretsune Y, Chacko VP, et al. Excitation-contraction coupling in postischemic myocardium. Does failure of activator Ca2+ transients underlie stunning? Cire Res 1990; 66: 1268–1276.

    CAS  Google Scholar 

  151. Tani M, Neely JR. Role of intracellular sodium and calcium overload and depressed recovery of ventricular function of reperfused ischemic rat hearts. Possible involvement of hydrogen-sodium and sodium-calcium exchange. Cire Res 1990; 65: 1045–1056.

    Google Scholar 

  152. Limbruno U, Zucchi R, Ronca-Testoni S, et al. Sarcoplasmie reticulum function in the “stunned” myocardium. J Mol Cell Cardiol 1989; 21: 1063–1072.

    Article  PubMed  CAS  Google Scholar 

  153. Hess ML, Manson NH, Molecular oxygen: Friend and foe. The role of the oxygen free radical system in the calcium paradox, the oxygen paradox and ischemia/reperfusion injury. J Mol Cell Cardiol 1984; 16: 969–985.

    Article  PubMed  CAS  Google Scholar 

  154. Halliwell B, Gutteridge JMC. Free radicals in biology and medicine, 2nd ed. Oxford, Clarendon Press, 1989.

    Google Scholar 

  155. Cumming DVE, Holmberg SRM, Kusama Y, et al. Effects of reactive oxygen species on the structure and function of the calcium-release channel from isolated sheep cardiac sarcoplasmic reticulum (Abstr). J Physiol 1990; 420: 88 P.

    Google Scholar 

  156. Holmberg SRM, Cumming DVE, Kusama Y, et al. Reactive oxygen species modify the structure and function of the cardiac sarcoplasmic reticulum calcium-release channel. Cardioscience 1991; 2: 19–25.

    PubMed  CAS  Google Scholar 

  157. Vandeplassche G, Bernier M, Thoné F, et al. Singlet oxygen and myocardial injury: Ultrastructural, cytochemical and electrocardiographic consequences of photoactivation of rose bengal. J Mol Cell Cardiol 1990; 22: 287–301.

    Article  PubMed  CAS  Google Scholar 

  158. Kusama Y, Bernier M, Hearse DJ. Singlet oxygen-induced arrhythmias: Dose-response and light-response studies for photoactivation of rose bengal in the rat heart. Circulation 1989; 80: 1432–1448.

    Article  PubMed  CAS  Google Scholar 

  159. Brigelius R: Mixed disulfides: Biological functions and increase in oxidative stress. In: Sies H, ed. Oxidative stress. London: Academic Press, 1985: 243–272.

    Google Scholar 

  160. Ziegler DM. Role of reversible oxidation-reduction of enzyme thiols-disulfides in metabolic regulation. Ann Rev Biochem 1985; 54: 305–329.

    Article  PubMed  CAS  Google Scholar 

  161. Miller RM, Sies H, Park E-M, et al. Phosphorylase and creatine kinase modification by thiol-disulfide exchange and by xanthine oxidase-initiated S-thiolation. Arch Biochem Biophys 1990; 276: 355–363.

    Article  PubMed  CAS  Google Scholar 

  162. Trimm JL, Salama G, Abramson JJ. Sulfhydryl oxidation induces rapid calcium release from sarcoplasmic reticulum vesicles. J Biol Chem 1986; 261: 16092–16098.

    PubMed  CAS  Google Scholar 

  163. Ceconi C, Curello S, Cargnoni A, et al. The role of glutathione status in the protection against ischaemic and reperfusion damage: Effects of N-acetyl cysteine. J Mol Cell Cardiol 1988; 20: 5–13.

    Article  PubMed  CAS  Google Scholar 

  164. Ferrari R, Ceconi C, Curello S, et al. Oxygen mediated myocardial damage during ischemia and reperfusion: Role of the cellular defences against oxygen toxicity. J Mol Cell Cardiol 1985; 17: 937–945.

    Article  PubMed  CAS  Google Scholar 

  165. Ferrari R, Ceconi C, Curello S, et al. The role of oxygen in myocardial ischemic and reperfusion damage: Effect of alpha-tocopherol. Acta Vitam Enzymol 1985; 7: 61–70.

    CAS  Google Scholar 

  166. Ferrari R, Ceconi C, Curello S, et al. Intracellular effects of myocardial ischemia and reperfusion: Role of calcium and oxygen. Eur Heart J 1986; 7: 3–12.

    PubMed  CAS  Google Scholar 

  167. Ferrari R, Alfieri O, Curello S, et al. Occurrence of oxidative stress during reperfusion of the human heart. Circulation 1990; 81: 201–211.

    Article  PubMed  CAS  Google Scholar 

  168. Ferrari R, Curello S, Cargnoni A, Condorelli E, Comini L, Ghielmi S, Ceconi C. Importance of free radicals generated by endothelial and myocardial cells in ischemia and reperfusion. In: Piper HM, ed. Pathophysiology of severe ischemic myocardial injury. Dordrecht: Kluwer Academic Publishers, 1990: 221–238.

    Chapter  Google Scholar 

  169. Caparrotta L, Prosdocimi M, Gaion RM. Effect of diamide on isolated guinea pig atria. Pharmacol Res Commun 1983; 15: 603–611.

    Article  PubMed  CAS  Google Scholar 

  170. Gailis M, Nguyen M-H. The effect of sulfhydryl reagents on the heart rate and coronary flow of the isolated perfused guinea-pig heart. Arch Intern Pharmacodyn 1975; 218: 19–28.

    CAS  Google Scholar 

  171. Reeves JP, Bailey CA, Hale CC. Redox modification of sodium-calcium exchange activity in cardiac sarcolemmal vesicles. J Biol Chem 1986; 561: 4948–4955.

    Google Scholar 

  172. Salama G, Zaidi NF, Abramson JJ, et al. Reactive disulfide compounds trigger Ca2+ release from sarcoplasmic reticulum (SR) vesicles. (Abstr). Biophys J 1988; 53: 420.

    Google Scholar 

  173. Abramson JJ, Salama G. Critical sulfhydryls regulate calcium release from sarcoplasmic reticulum. J Bioenergetics Biomemb 1989; 21: 283–294.

    Article  CAS  Google Scholar 

  174. Abramson JJ, Cronin JR, Salama G. Oxidation induced by phthalocyanine dyes causes rapid calicum release from sarcoplasmic reticulum vesicles. Arch Biochem Biophys 1988; 263: 245–255.

    Article  PubMed  CAS  Google Scholar 

  175. Abramson JJ, Buck E, Salama G, et al. Mechanism of anthraquinone-induced calcium release from skeletal muscle sarcoplasmic reticulum. J Biol Chem 1988; 263: 18750–18758.

    PubMed  CAS  Google Scholar 

  176. Yamada S, Ikemoto N. Distinction of thiols involved in the specific reaction steps of the Ca2+-ATPase of the sarcoplasmic reticulum. J Biol Chem 1978; 253: 6801–6807.

    PubMed  CAS  Google Scholar 

  177. Yoshida H, Tonomura Y. Chemical modification of the Ca2+-dependent ATPase of sarcoplasmic reticulum from skeletal muscle. I. Binding of N-ethylmaleimide to sarcoplasmic reticulum: Evidence for sulfhydryl groups in the active site of ATPase and for conformational changes induced by adenosine tri-and diphosphate. J Biochem 1976; 79: 649–654.

    PubMed  CAS  Google Scholar 

  178. Scherer NM, Deamer DW. Oxidative stress impairs the function of sarcoplasmic reticulum by oxidation of sulfhydryl groups in the CA2+-ATPase. Arch Biochem, Biophys 1986; 246: 589–601.

    Article  CAS  Google Scholar 

  179. Shi ZQ, Davison AJ, Tibbits GF. Effects of active oxygen generated by DTT/Fe2+ on cardiac Na+/Ca2+ exchange and membrane permeability to Ca2+. J Mol Cell Cardiol 1989; 21: 1009–1016.

    Article  PubMed  CAS  Google Scholar 

  180. Steinberg H, Greenwald, RA, Moak SA, et al. The effect of oxygen adaptation on oxyradical injury to pulmonary endothelium. Am Rev Respir Dis 1983; 128: 94–97.

    PubMed  CAS  Google Scholar 

  181. Pierce GN, Ward R, Philipson KD. Role for sulfur-containing groups in the sodium-calcium exchange of cardiac sarcolemmal vesicles. Memb Biol 1986; 94: 217–225.

    Article  CAS  Google Scholar 

  182. Zaidi NF, Lagenaur CF, Abrahamson JJ, et al. Reactive disulfides trigger Ca2+ release from sarcoplasmic reticulum via an oxidation reaction. J Biol Chem 1989; 264: 21725–21736.

    PubMed  CAS  Google Scholar 

  183. Zaidi NF, Langenaur CF. Disulfide linkage of biotin identifies a 106-kDa Ca2+ release channel in sarcoplasmic reticulum. J Biol Chem 1989; 264: 21737–21747.

    PubMed  CAS  Google Scholar 

  184. Kusama Y, Bernier M, Hearse DJ. Photoactivation of porphyrins: Studies of reactive oxygen intermediates and ar-rhythmogenesis in the aerobic rat heart. Cardiovasc Res 1990; 24: 676–682.

    Article  PubMed  CAS  Google Scholar 

  185. Shattock MJ, Hearse DJ, Matsuura H. Ionic currents underlying oxidant stress-induced arrhythmias. In: Vereecke J, Van Bogaert PP, Verdonck F, eds. Ionic currents and ischemia. Leuven: Leuven University Press, 1990: 165–189.

    Google Scholar 

  186. Shattock MJ, Matsuura H, Hearse W. Functional and electrophysiological effects of oxidant stress on isolated ventricular muscle: A role for oscillatory calcium release from the sarcoplasmic reticulum in arrhythmogenesis? Cardiovasc Res 1991; 25: 645–651.

    Article  PubMed  CAS  Google Scholar 

  187. Matsuura H, Shattock MJ. Membrane potential fluctuations and transient inward currents induced by reactive oxygen intermediates in isolated rabbit ventricular cells. Cire Res 1991; 68: 319–329.

    CAS  Google Scholar 

  188. Shattock MJ, Matsuura H, Hearse DJ. Reperfusion arrhythmias: Role of oxidant stress. In: Duncan DJ, ed. Calcium, oxygen radicals and cellular damage. Cambridge: Cambridge University Press, 1991.

    Google Scholar 

  189. Matsuura H, Shattock MJ: Functional and electrophysiological effects of reative oxygen intermediates on isolated rat ventricular muscle (Abstr). J Mol Cell Cardiol 1989; 21 (Suppl II):S. 129.

    Google Scholar 

  190. Nakata T, Hearse DJ. Species differences in vulnerability to injury by oxidant stress: A possible link with calcium handling? Cardiovasc Res 1990; 24: 857–864.

    Article  PubMed  CAS  Google Scholar 

  191. Matsuura H, Shattcok MJ. Effects of reactive oxygen intermediates on the steady-state membrane currents in isolated single ventricular cells. Am J Physiol 1991, in press.

    Google Scholar 

  192. Matsuura H, Shattock MJ. On the mechanism of the arrhythmogenic action of reactive oxygen intermediates in isolated rabbit ventricular cells (Abstr). Circulation 1989;80 (Suppl II):II118.

    Google Scholar 

  193. Shattock MJ, Matsuura H. Oxidant stress inhibits Na/K pump current in isolated rabbit ventricular myocytes (Abstr). J Mol Cell Cardiol 1990; 22 (Suppl III):S. 51.

    Article  Google Scholar 

  194. Matsuura H, Shattock MJ. Effects of oxidant stress on steady-state background currents in isolated ventricular cells of rabbit heart (Abstr). J Mol Cell Cardiol 1990: 22 (Suppl III):S. 19.

    Article  Google Scholar 

  195. Shattock MJ, Matsuura H, Hearse DJ. Effects of oxidant stress on calcium inward current and sodium pump current in isolated ventricular myocytes (Abstr). Biophys J 1991; 59: 559A.

    Google Scholar 

  196. Hess ML, Okabe E. Ash P, et al. Free radical mediation of the effects of acidosis on calcium transport by cardiac sarcoplasmic reticulum in whole heart homogenates. Cardiovasc Res 1984; 18: 149–157.

    Article  PubMed  CAS  Google Scholar 

  197. Hess ML, Okabe E, Kontos HA. Proton and free oxygen radical interaction with the calcium transport system of cardiac sarcoplasmic reticulum. J Mol Cell Cardiol 1981; 13: 767–772.

    Article  PubMed  CAS  Google Scholar 

  198. Hess ML, Krause S, Kontos HA. Mediation of sarcoplasmic reticulum disruption in the ischemic myocardium: Proposed mechanism by the interaction of hydrogen ions and oxygen free radicals. Adv Exp Biol Med 1983; 161: 377–387.

    CAS  Google Scholar 

  199. Okabe E, Hess ML, Oyama M, et al. Characterization of free radical mediated damage of canine sarcoplasmic reticulum. Arch. Biochem Biophys 1983; 225: 164–177.

    Article  PubMed  CAS  Google Scholar 

  200. Kukreja RC, Weaver AB, Hess ML. Stimulated human neutrophils damage cardiac sarcoplasmic reticulum function by generation of oxidants. Biochim Biophys Acta 1989; 990: 198–205.

    PubMed  CAS  Google Scholar 

  201. Kukreja RC, Okabe E, Schrier G, et al. Oxygen radicals mediate lipid peroxidation and inhibition of calcium ATPase activity of cardiac sarcoplasmic reticulum. Arch Biochem Biophys 1988; 261: 447–475.

    Article  PubMed  CAS  Google Scholar 

  202. Okabe E, Odajima C, Taga R, et al. The effect of oxygen free radicals on calcium loading at steady state in canine sarcoplasmic reticulum. Mol Pharmacol 1988; 34: 388–394.

    PubMed  CAS  Google Scholar 

  203. Bhatnagar A, Srivastava SK, Szabo G. Oxidative stress alters specific membrane currents in isolated cardiac myocytes. Circ Res 1990; 67: 535–549.

    PubMed  CAS  Google Scholar 

  204. Kim M-S, Akera T. O2 free radicals: Cause of ischemiareperfusion injury to cardiac Na+-K‘-ATPase. Am, J Physiol 1987; 252: H252 - H257.

    CAS  Google Scholar 

  205. Kramer JH, Mak IT, Weglicki WB. Differential sensitivity of canine cardiac sarcolemmal and microsomal enzymes to inhibition by free radical-induced lipid peroxidation. Cire Res 1984; 55: 120–124.

    CAS  Google Scholar 

  206. Haddock PS, Hearse DJ, Woodward B. Modification of the activity of bovine sodium/potassium ATPase by reduced and oxidized glutathione and other sulphydryl compounds (Abstr). Br J Pharmacol 1991; 102: 54 P.

    Google Scholar 

  207. Haddock PS, Hearse DJ, Woodward B. Effect of glutathione and other thiols on bovine heart sodium/potassium ATPase activity (Abstr). J Mol Cell Cardiol 1990; 22 (Suppl III):S. 4.

    Article  Google Scholar 

  208. Kukreja RC, Weaver AB, Hess ML. Sarcolemmal sodium-potassium ATPase: Inactivation by neutrophil-derived free radicals and oxidants. Am, J Physiol 1990; 259: H1330 - H1336.

    PubMed  CAS  Google Scholar 

  209. Kaneko M, Beamish RE, Dhalla NS. Depression of sarcolemmal ATP-dependent Ca2+ accumulation and Ca2+ stimulated ATPase activity by oxygen free radicals (Abstr). J Mol Cell Cardiol 1988; 20 (Suppl V):S. 63.

    Google Scholar 

  210. 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 

  211. Kaneko M, Dhalla KS, Singal PK, et al. Inhibition of sarcolemmal ATPase and Ca2+ binding activities by hydrogen peroxide (Abstr). J Mol Cell Cardiol 1988; 20 (Suppl III): S. 12.

    Article  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  213. Kaneko M, Lee S-L, Wolf CM, et al. Reduction of calcium channel antagonist binding sites by oxygen free radicals in the rat heart. J Mol Cell Cardiol 1989; 21: 935–943.

    Article  PubMed  CAS  Google Scholar 

  214. Kaneko M, Singal PK, Dhalla NS. Alterations in heart sarcolemmal Ca2+ Pase and Ca2+ binding activities due to oxygen free radicals. Basic Res Cardiol 1990; 85: 45–54.

    Article  PubMed  CAS  Google Scholar 

  215. Dixon IMC, Kaneko M, Hata T, et al. Alterations in cardiac membrane calcium transport during oxidative stress. Mol Cell Biochem. 1990; 99: 125–133.

    Article  PubMed  CAS  Google Scholar 

  216. Lehninger AL, Vercesi A, Bababunmi EA. Regulation of Ca2+release from mitochondria by the oxidation-reduction state of pyridine nucleotides. Proc Natl Acad Sci USA 1978; 75: 1690–1694.

    Article  PubMed  CAS  Google Scholar 

  217. Richter C. Frei B. Ca2+ movements induced by hydroperoxides in mitochondria. In: Sies H, ed. Oxidant stress. London: Academic Press, 1985: 221–241.

    Google Scholar 

  218. Richter C, Frei B. Ca2+ release from mitochondria induced by prooxidants. Free Rad Biol Med 1988; 4: 365–375.

    Article  PubMed  CAS  Google Scholar 

  219. Sies H. Oxidative stress: Introductory remarks. In: Sies H, ed. Oxidative stress. London: Academic Press, 1985.

    Google Scholar 

  220. Sies H. Oxidative stress. London: Academic Press, 1985.

    Google Scholar 

  221. Crompton M, Costi A. A heart mitochondrial calcium-dependent pore of possible relevance to re-perfusioninduced injury. Biochem J 1990; 266: 33–39.

    PubMed  CAS  Google Scholar 

  222. Crompton M. The role of calcium in the function and dysfunction of heart mitochondria. In: Langer GA, ed. Calcium and the heart. New York: Raven Press, 1990: 167–198.

    Google Scholar 

  223. Crompton M, Costi A, Hayat L. Evidence for the presence of a reversible Ca2+-dependent pore activated by oxidative stress in heart mitochondria. Biochem J 1987; 245: 915–918.

    PubMed  CAS  Google Scholar 

  224. Reed NJ. Nitrosoureas. In: Sies H, ed. Oxidative stress. London: Academic Press, 1985: 115–130.

    Google Scholar 

  225. Burton KP, Morris AC, Massey KD, et al. Free radicals alter ionic calcium levels and membrane phospholipids in cultured rat ventricular myocytes. J Mol Cell Cardiol 1990; 22: 1035–1047.

    Article  PubMed  CAS  Google Scholar 

  226. Jennings RB, Sommers HM, Smyth GA, et al. Myocardial necrosis induced by temporary occlusion of a coronary artery in the dog. Arch Pathol 1960; 70: 68–78.

    PubMed  CAS  Google Scholar 

  227. Steenbergen C, Murphy E, Watts JA, et al. Correlation between cytosolic free calcium, contracture, ATP, and irreversible ischemic injury in perfused rat heart. Cire Res 1990; 66: 135–146.

    CAS  Google Scholar 

  228. Carrozza JP, Bentivegna LA, Grossman W, et al. Abnormal calcium handling during ischemia and reperfusion precedes myocardial stunning. Circulation 1990; 82 (Suppl III): 465.

    Google Scholar 

  229. Nishimura M, Matsuda H, Kaneko M, et al. Hyperkalemic reperfusion attenuates myocardial stunning by reducing calcium overload: Real-time analysis of intracellular calcium concentration in perfused rat hearts loaded with indo-1. Circulation 1990; 82 (Suppl III): 571.

    Google Scholar 

  230. Marban E, Kitakaze M, Koretsune Y, et al. Quantification of [Ca2+]i in perfused hearts: Critical evaluation of the 5FBAPTA and nuclear magnetic resonance method as applied to the study of ischemia and reperfusion. Cire Res 1990; 66: 1255–1267.

    CAS  Google Scholar 

  231. 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 

  232. Tani M, Neely JR. Role of intracellular Na+ in Ca’ overload and depressed recovery of ventricular function of reperfused ischemic rat hearts. Possible involvement of 1+-Na+ and Na+-Ca2+ exchange. Circ Res 1989; 65: 1045–1956.

    PubMed  CAS  Google Scholar 

  233. Berlin JR, Cannell MB, Lederer W. Cellular origins of the transient inward current in cardiac myocytes. Role of fluctuations and waves of elevated intracellular calcium. Circ Res 1989; 65: 115–126.

    PubMed  CAS  Google Scholar 

  234. Capogrossi MC, Lakatta EG. Frequency modulation and synchronization of spontaneous oscillations in cardiac cells. Am J Physiol 1985; 248: H412 - H418.

    PubMed  CAS  Google Scholar 

  235. Kort AA, Lakatta EG. Calcium-dependent mechanical oscillations occur spontaneously in unstimulated mammalian cardiac tissues. Circ Res 1984; 54: 396–404.

    PubMed  CAS  Google Scholar 

  236. Hearse DJ, Stewart DA, Chain EB. Diabetes and the survival and recovery of the anoxic myocardium. J Mol Cell Cardiol 1975; 7: 397–415.

    Article  PubMed  CAS  Google Scholar 

  237. Kuroda H, Ishiguro S, Mori T. Optimal calcium concentration in the initial reperfusate for post-ischemic myocardial performance (calcium concentration during reperfusion). J Mol Cell Cardiol 1986; 18: 625–633.

    Article  PubMed  CAS  Google Scholar 

  238. Du Toit E, Owen P, Opie LH. Attenuated reperfusion stunning with a calcium channel antagonist or internal calcium blocker in the isolated perfused rat heart (Abstr). J Mol Cell Cardiol 1990; 22: 558.

    Google Scholar 

  239. Kitakaze M, Weisman HF, Marban E. Contractile dysfunction and ATP depletion after transient calcium overload in perfused ferret hearts. Circulation 1988; 77: 685–695.

    Article  PubMed  CAS  Google Scholar 

  240. Ito BR, Tate H, Kobayashi M, et al. Reversibly injured, postischemic canine myocardium retains normal contractile reserve. Circ Res 1987; 61: 834–846.

    PubMed  CAS  Google Scholar 

  241. Lederer WJ, Niggli E, Hadley RW. Sodium-calcium exchange in excitable cells: Fuzzy space. Science 1990; 248: 283.

    Article  PubMed  CAS  Google Scholar 

  242. Williford DJ, Sharma VK, Korth M, et al. Spatial heterogeneity of intracellular calcium concentration in nonbeating guinea pig ventricular myocytes. Circ Res 1990; 66: 234–241.

    Google Scholar 

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  1. David J. Hearse
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Editors and Affiliations

  1. University of Cape Town, Cape Town, South Africa

    Lionel H. Opie MD, DPhil. (Professor of Medicine, Visiting Professor) (Professor of Medicine, Visiting Professor)

  2. Division of Cardiology, Stanford University Medical Center, Stanford, California, USA

    Lionel H. Opie MD, DPhil. (Professor of Medicine, Visiting Professor) (Professor of Medicine, Visiting Professor)

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Hearse, D.J. (1992). Stunning: A Radical Re-view. In: Opie, L.H. (eds) Stunning, Hibernation, and Calcium in Myocardial Ischemia and Reperfusion. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1517-9_3

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