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Regional increase in ROS within stretched region exacerbates arrhythmias in rat trabeculae with nonuniform contraction

  • Muscle physiology
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Abstract

In diseased hearts, impaired muscle within the hearts is passively stretched by contractions of the more viable neighboring muscle during the contraction phase. We investigated whether in the myocardium with nonuniform contraction such passive stretch regionally generates ROS within the stretched region and exacerbates arrhythmias. In trabeculae from rat hearts, force, intracellular Ca2+, and membrane potential were measured. To assess regional ROS generation, the slope of the change in the 2′,7′-dichlorofluorescein fluorescence (DCFslope) was calculated at the each pixel position along the long axis of trabeculae using DCF fluorescence images. Ca2+ waves and arrhythmias were induced by electrical stimulation. A H2O2 (1 mmol/L) jet regionally increased the DCFslope within the jet-exposed region. A blebbistatin (10 μmol/L) jet caused passive stretch of the muscle within the jet-exposed region during the contraction phase and increased the DCFslope within the stretched region, the velocity of Ca2+ waves, and the number of beats after electrical stimulation (0.2 μmol/L isoproterenol), while 3 μmol/L diphenyleneiodonium (DPI), NADPH oxidase inhibitor, decreased them. A jet of a solution containing 0.2 mmol/L H2O2 in addition to 10 µmol/L blebbistatin also increased them. A H2O2 jet within the region where Ca2+ waves propagated increased their velocity. In the myocardium with nonuniform contraction, passive stretch of the muscle by contractions of the neighboring muscle regionally increases ROS within the stretched region, and the regional ROS exacerbates arrhythmias by activating the propagation of Ca2+ waves.

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Conflict of interest

The authors declare that they have no conflict of interest.

Funding

This work was supported by Grant-in-Aid for Scientific Research (C) from Japan Society for the Promotion of Science (M. Miura, No. 26460288; C Shindoh No. 16K08485).

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Authors and Affiliations

  1. Department of Clinical Physiology, Health Science, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan

    Masahito Miura, Yuhto Taguchi, Tetsuya Handoh, Taiki Hasegawa, Yui Takahashi, Natsuki Morita, Ayana Matsumoto, Haruka Sato & Chiyohiko Shindoh

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  1. Masahito Miura
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Miura, M., Taguchi, Y., Handoh, T. et al. Regional increase in ROS within stretched region exacerbates arrhythmias in rat trabeculae with nonuniform contraction. Pflugers Arch - Eur J Physiol 470, 1349–1357 (2018). https://doi.org/10.1007/s00424-018-2152-x

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