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Defects in Mitochondrial Oxidative Phosphorylation in Hearts Subjected to Ischemia-Reperfusion Injury

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Cardiac Energy Metabolism in Health and Disease

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 11))

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Abstract

Although several studies have shown impairment of mitochondrial respiratory and oxidative phosphorylation activities in the ischemic-reperfused (I/R) hearts, the mechanisms of these alterations are not fully understood. Recently, we have shown that the I/R-induced changes in mitochondrial function were attenuated by an oxyradical scavenging system or antioxidants such as N-acetyl-l-cysteine and N-(2-mercaptopropionyl)-glycine. On the other hand, perfusion of hearts with an oxyradical generating system or H2O2, a well known oxidant, simulated the I/R induced mitochondrial dysfunction. Furthermore, intracellular Ca2+-overload induced by perfusing the Ca2+-depleted hearts with Ca2+-containing medium produced changes in mitochondrial respiratory and oxidative phosphorylation activities similar to those seen due to I/R injury. Mitochondrial dysfunction was also observed upon incubating these organelles with high concentrations of Ca2+. These observations support the view that mitochondrial dysfunction with respect to energy production due to I/R injury, occurs as a result of oxidative stress and intracellular Ca2+-overload. It is also evident that mitochondrial alterations in the I/R hearts lead to the depletion of high-energy phosphate stores and thus may play a critical role in the development of cardiac dysfunction.

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Acknowledgements

The infrastructure support for this project was provided by the St. Boniface Hospital Research Foundation.

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Authors and Affiliations

  1. Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, University of Manitoba, 369 Tache Avenue, Winnipeg, MB, Canada, R2H 2A6

    Vijayan Elimban & Naranjan S. Dhalla

  2. Asper Clinical Research Institute, St. Boniface Hospital Research Centre, 369 Tache Avenue, Winnipeg, MB, Canada, R2H 2A6

    Paramjit S. Tappia

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  1. Vijayan Elimban
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  2. Paramjit S. Tappia
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  3. Naranjan S. Dhalla
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Correspondence to Naranjan S. Dhalla .

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Editors and Affiliations

  1. Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada

    Gary D. Lopaschuk

  2. University of Manitoba, Institute of Cardiovascular Sciences, St. Boniface Hospital Research, Winnipeg, Manitoba, Canada

    Naranjan S. Dhalla

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Elimban, V., Tappia, P.S., Dhalla, N.S. (2014). Defects in Mitochondrial Oxidative Phosphorylation in Hearts Subjected to Ischemia-Reperfusion Injury. In: Lopaschuk, G., Dhalla, N. (eds) Cardiac Energy Metabolism in Health and Disease. Advances in Biochemistry in Health and Disease, vol 11. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1227-8_12

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