Mechanisms of Cellular Alterations Due to Ischemia-Reperfusion Injury in the Heart

  • Rana M. Temsah
  • Thomas Netticadan
  • Naranjan S. Dhalla
Part of the Progress in Experimental Cardiology book series (PREC, volume 6)


Reperfusion of the ischemic heart after a certain period of time has been shown to produce cell injury. There is evidence to show that alterations in mitochondrial metabolism during ischemia results in the accumulation of H+ in the cell and this then leads to the activation of Na+-H+ exchanger, Na+-Ca2+ exchanger and development of intracellular Ca2+-overload upon reperfusion. Changes in mitochondrial metabolism during ischemia and a massive release of catecholamines and their oxidation during reperfusion produce oxyradicals and other oxidants in the myocardium. This oxidative stress causes the depression of sarcolemmal Na+-K+ ATPase and Ca2+-pump ATPase and these changes also contribute towards the occurrence of intracellular Ca2+-overload. Both oxidative stress and intracellular Ca2+-overload produce changes in the sarcoplasmic reticular Ca2+-cycling proteins as well as myofibrillar proteins and these defects then result in contractile dysfunction in the ischemic-reperfused hearts. Ischemic preconditioning and some pharmacological interventions, which attenuate the development of intracellular Ca2+-overload, have been demonstrated to reduce ischemia-reperfusion injury. Thus it appears that intracellular Ca2+-overload plays a critical role in the induction of myocardial cell damage and heart dysfunction due to ischemia-reperfusion.

Key words

Intracellular Ca2+-overload oxidative stress SR Ca2+-cycling proteins cardiac dysfunction sarcolemmal defects ischemia preconditioning 


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Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Rana M. Temsah
    • 1
    • 2
  • Thomas Netticadan
    • 1
    • 2
  • Naranjan S. Dhalla
    • 1
    • 2
  1. 1.Institute of Cardiovascular SciencesSt. Boniface General Hospital Research CentreWinnipegCanada
  2. 2.Department of Physiology, Faculty of MedicineUniversity of ManitobaWinnipegCanada

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