Electrophysiological insights into the relationship between calcium dynamics and cardiomyocyte beating function in chron
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ORIGINAL ARTICLE Artificial Kidney / Dialysis
Electrophysiological insights into the relationship between calcium dynamics and cardiomyocyte beating function in chronic hemodialysis treatment Hiroyuki Hamada1,2 · Tadashi Tomo3 · Sung‑Teh Kim4 · Taizo Hanai1,2 · Masahiro Okamoto1,2 · Akihiro C. Yamashita5 Received: 26 February 2020 / Accepted: 24 August 2020 © The Japanese Society for Artificial Organs 2020
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, C a2+ 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 C a2+ 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 C a2+ or application of an NCX inhibitor during treatment suppressed the 2+ decrease in intracellular Ca 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. Keywords Renal replacement therapy · Cardiac beating · Excitation–contraction coupling · Calcium dynamics · Mathematical analysis
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10047-020-01207-7) contains supplementary material, which is available to authorized users. * Akihiro C. Yamashita [email protected] Hiroyuki Hamada [email protected]‑u.ac.jp 1
2
Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi‑ku, Fukuoka‑city, Fukuoka 819‑0395, Japan Department of Systems Life Sciences, Graduate School of Systems Life Sciences, Kyushu University, 744 Motooka, Nishi‑ku, Fukuoka‑city, Fukuoka 819‑0395, Japan
3
Clinical Engineering Research Center, Faculty of Medicine, Oita University, 1‑1 Idai‑gaoka, Hasama‑machi, Yufu‑city, Oita 879‑5593, Japan
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