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Sodium Overload and Mitochondrial Damage in Ischemic/Reperfused Heart

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Myocardial Ischemia and Preconditioning

Part of the book series: Progress in Experimental Cardiology ((PREC,volume 6))

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Summary

Possible mechanisms by which cytosolic sodium overload may lead to the mitochondrial damage followed by ischemia/reperfusion injury were examined in perfused rat hearts. Massive accumulation of myocardial Na+ occurred, but no Ca2+ accumulation was detected during ischemia. This suggests that cytosolic sodium overload in cardiac cells may initiate ionic disturbance in the ischemia/reperfusion injury. Treatment of the pre-ischemic heart with 0.3μM tetrodotoxin, 3μM ethylisopropyl amiloride, 3μM diltiazem, or 100μM propranolol enhanced post-ischemic contractile recovery, which was associated with suppression of cellular Na+ accumulation, restoration of tissue high-energy phosphates, and preservation of the mitochondrial ability to produce ATP in the ischemic/reperfused heart. The improvement of post-ischemic contractile recovery by these agents was closely correlated with the mitochondrial ability to produce ATP at the end of ischemia. Na+ induced impairments of the mitochondrial membrane function such as attenuation of oxidative phosphorylation, swelling, depolarization of the membrane potential, release of cytochrome c in the isolated mitochondria in vitro. The Na+-induced mitochondrial impairments were not canceled under in vitro conditions by the presence of the above agents. The release of cytochrome c from the ischemic heart was observed, which was blocked by treatment of the pre-ischemic heart with these agents. The results suggest that sodium overload may induce deterioration of the mitochondrial function during ischemia and that this mitochondrial damage may determine postischemic contractile dysfunction in perfused rat hearts.

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Authors and Affiliations

  1. Department of Pharmacology, Tokyo University of Pharmacy & Life Science, Hachioji, 1920392, Tokyo, Japan

    Satoshi Takeo Ph.D., Takeshi Iwai & Kouichi Tanonaka

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  1. Satoshi Takeo Ph.D.
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  2. Takeshi Iwai
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  3. Kouichi Tanonaka
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Correspondence to Satoshi Takeo Ph.D. .

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Editors and Affiliations

  1. Institute of Cardiovascular Sciences St. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Naranjan S. Dhalla PhD, MD (Hon), DSc (Hon) (Distinguished Professor and Director) & Anton Lukas PhD (Associate Professor) (Distinguished Professor and Director) &  (Associate Professor)

  2. Aoto Hospital, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan

    Nobuakira Takeda MD, PhD (Associate Professor) (Associate Professor)

  3. Dept. of Pharmaceutical Sciences & Drug Research, Punjabi University, Patiala, India

    Manjeet Singh PhD (Professor & Head) (Professor & Head)

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© 2003 Springer Science+Business Media New York

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Takeo, S., Iwai, T., Tanonaka, K. (2003). Sodium Overload and Mitochondrial Damage in Ischemic/Reperfused Heart. In: Dhalla, N.S., Takeda, N., Singh, M., Lukas, A. (eds) Myocardial Ischemia and Preconditioning. Progress in Experimental Cardiology, vol 6. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0355-2_4

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  • DOI: https://doi.org/10.1007/978-1-4615-0355-2_4

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5036-1

  • Online ISBN: 978-1-4615-0355-2

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