Role of Mn-SOD Induction in the Second Window Phenomenon of Preconditioning of Ischemic Hearts

  • Tsunehiko Kuzuya
  • Masashi Nishida
  • Shiro Hoshida
  • Nobushige Yamashita
  • Michihiko Tada
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 194)


Recently, growing numbers of evidence suggest that the myocardium undergoes adaptation after sub-lethal cellular stresses including ischemia, heat stress and exposure to cytokines.1-4 The second window, or late phase, of ischemic preconditioning, is one of the adaptation phenomena after non-lethal ischemia, which specifically observed 24 hr after ischemic preconditioning. The mechanism of the acquisition of tolerance to ischemia-reperfusion in the myocardium is still the matter of discussion. However, de novo synthesis of rescue proteins, such as heat shock proteins and antioxidants, are strongly implicated in molecular mechanism of the cellular protection. In this review, we will focus on the aspect of oxygen radical metabolism in the heart at ischemia-reperfusion and outline our recent findings on the role of manganese superoxide dismutase, an intrinsic oxygen radical scavenger localized in mitochondria, in the protection of myocardium from ischemia-reperfusion.


Leave Anterior Descend Cardiac Myocytes Hypoxic Precondition Prolonged Hypoxia Creatine Kinase Release 
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  1. 1.
    Brown JM, White CW, Terada LS et al. Interleukin 1 pretreatment decreases ischemia/reperfusion injury. Proc Natl Acad Sci USA 1990;87: 5026–5030.PubMedCrossRefGoogle Scholar
  2. 2.
    Eddy LJ, Goeddei DV, Wong GHW. Tumor necrosis factor-a pretreatment is protective in a rat model of myocardial ischemia-reperfusion injury. Biochem Biophys Res Commun 1992;184: 1056–1059.PubMedCrossRefGoogle Scholar
  3. 3.
    Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 1986;74: 1124–1136.PubMedCrossRefGoogle Scholar
  4. 4.
    Yellon DM, Pasini E, Cargnoni A et al. The protective role of heat stress in the ischaemic and reperfused rabbit myocardium. J Mol Cell Cardiol 1992;24: 895–907.PubMedCrossRefGoogle Scholar
  5. 5.
    Garlick PB, Davies MJ, Hearse DJ et al. Direct detection of free radicals in the reperfused rat heart using electron spin resonance. Circ Res 1987;61: 757–760.PubMedCrossRefGoogle Scholar
  6. 6.
    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.PubMedCrossRefGoogle Scholar
  7. 7.
    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.PubMedCrossRefGoogle Scholar
  8. 8.
    Opie LH. Reperfusion injury and its pharmacologic modification. Circulation 1989;80: 1049–1062.PubMedCrossRefGoogle Scholar
  9. 9.
    Hoshida S, Kuzuya T, Fuji H et al. Sublethal ischemia alters myocardial antioxidant activity in canine heart. Am J Physiol. 1993;264: H33–H39.PubMedGoogle Scholar
  10. 10.
    Kuzuya T, Hoshida S, Yamashita N et al. Delayed effects of sublethal ischemia on the acquisition of tolerance to ischemia. Circ Res 1993;72: 1293–1299.PubMedCrossRefGoogle Scholar
  11. 11.
    Yamashita N, Nishida M, Hoshida S et al. Induction of manganese superoxide dismutase in rat cardiac myocytes increases tolerance to hypoxia 24 hours after preconditioning. J Clin Invest 1994;94: 2193–2199.PubMedCrossRefGoogle Scholar
  12. 12.
    Hutter MM, Sievers RE, Barbosa V et al. Heat-shock protein induction in rat hearts. A direct correlation between the amount of heat-shock protein induced and the degree of myocardial protection. Circulation 1994;89: 355–360.PubMedCrossRefGoogle Scholar
  13. 13.
    Yamashita N, Nishida M, Hoshida S et al. al-adrenergic stimulation induced tolerance of cardiac myocytes to hypoxia through induction and activation of manganese superoxide dismutase. Am J Physiol 1996(In Press).Google Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Tsunehiko Kuzuya
  • Masashi Nishida
  • Shiro Hoshida
  • Nobushige Yamashita
  • Michihiko Tada

There are no affiliations available

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