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Electrophysiological insights into the relationship between calcium dynamics and cardiomyocyte beating function in chronic hemodialysis treatment

  • Original Article
  • Artificial Kidney / Dialysis
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Abstract

For patients in which the Ca2+ concentration of dialysis fluid is lower than that in plasma, chronic hemodialysis treatment often leads to cardiac beating dysfunction. By applying these conditions to an electrophysiological mathematical model, we evaluated the impact of body fluid Ca2+ dynamics during treatment on cardiomyocyte beating and, moreover, explored measures that may prevent cardiomyocyte beating dysfunction. First, Ca2+ concentrations in both plasma and interstitial fluid were decreased with treatment time, which induced both a slight decline in beating rhythm on a sinoatrial nodal cell and a wane in contraction force on a ventricular cell. These simulated results were in agreement with clinical observations. Next, a relationship between the intracellular Ca2+ concentration and ion current dynamics of ion transporters were examined to elucidate the mechanism underlying cardiomyocyte beating dysfunction. The inward current of the Na/Ca exchanger (NCX) increased with a decrease in Ca2+ concentration in interstitial fluid and induced a reduction in intracellular Ca2+ concentration during treatment. Furthermore, the decline in intracellular Ca2+ concentration reduced the contraction force. These findings implied that ion transport through the NCX is a dominant factor that induces cardiomyocyte beating dysfunction during hemodialysis. Finally, the replenishment of Ca2+ or application of an NCX inhibitor during treatment suppressed the decrease in intracellular Ca2+ concentration and contributed to the stabilization of cardiomyocyte beating function. In summary, the clinical implementation of hepatically cleared NCX inhibitor may be a suitable approach to improving the quality of life for patients on chronic hemodialysis.

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Acknowledgments

This research was supported by JSAO Grant MERA 2015 and JSPS KAKENHI Grant Number JP18K12131. We thank Prof. DM. Bers and Prof. D. Sato in the University of California at Davis, and our colleagues from the committee for application of new technologies to blood purification therapy in Japanese Society of Dialysis Therapy who provided insight and expertise that greatly assisted the research.

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Authors and Affiliations

  1. Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka-city, Fukuoka, 819-0395, Japan

    Hiroyuki Hamada, Taizo Hanai & Masahiro Okamoto

  2. Department of Systems Life Sciences, Graduate School of Systems Life Sciences, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka-city, Fukuoka, 819-0395, Japan

    Hiroyuki Hamada, Taizo Hanai & Masahiro Okamoto

  3. Clinical Engineering Research Center, Faculty of Medicine, Oita University, 1-1 Idai-gaoka, Hasama-machi, Yufu-city, Oita, 879-5593, Japan

    Tadashi Tomo

  4. Research Planning Division, Social medical corporation Kawashima Hospital, 1-1-39 Kitasako, Tokushima-city, Tokushima, 770-0011, Japan

    Sung-Teh Kim

  5. Department of Chemical Science and Technology, Faculty of Bioscience and Applied Chemistry, Hosei University, 1-7-2 Kajio-cho, Koganei-city, Tokyo, 184-8584, Japan

    Akihiro C. Yamashita

Authors
  1. Hiroyuki Hamada
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  2. Tadashi Tomo
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  4. Taizo Hanai
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Correspondence to Akihiro C. Yamashita.

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Conflict of interest

Akihiro C. Yamashita has received research funding from Nipro Co., Osaka, Japan, and from Asahi-Kasei Medical Co., Tokyo, Japan, and has advisory role for Nikkiso Co., Tokyo, Japan, and for Asahi-Kasei Medical Co., Tokyo, Japan. Other authors declare that they have no conflict of interest.

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Hamada, H., Tomo, T., Kim, ST. et al. Electrophysiological insights into the relationship between calcium dynamics and cardiomyocyte beating function in chronic hemodialysis treatment. J Artif Organs 24, 58–64 (2021). https://doi.org/10.1007/s10047-020-01207-7

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  • DOI: https://doi.org/10.1007/s10047-020-01207-7

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