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Effect of Cooling on Force-Frequency Relationship, Rest Potentiation, and Frequency-Dependent Acceleration of Relaxation in the Guinea Pig Myocardium

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Abstract

While deep hypothermia is well known to lead to cardiac malfunction up to circulatory arrest, mild hypothermia can prevent hypoxic damage to the heart. Importantly, a large body of research on deep hypothermia was carried out on rats and mice whose myocardium is significantly different from the human. In the present work, we investigated the effect of deep hypothermia on rhythmoinotropic phenomena in the guinea pig (GP) whose myocardium is more alike the human. The force––frequency relationship (FFR), effect of post-rest potentiation, and frequency-dependent acceleration of relaxation (FDAR) were studied in GP right ventricular papillary muscles (PM) within a range of 0.1–3.0 Hz at temperatures of 30, 20 and 10°C. It was shown that a positive FFR, mediated mainly by the inward Ca2+ current through the L-type Ca2+ channel, persists when cooling to 10°C, suggesting that this mechanism retains its activity even under deep hypothermia. The effect of post-rest potentiation persists down to 20°C, while further cooling replaces potentiation by depression. This may indicate that at 10°C, the functioning of the sarcoplasmic reticulum is impaired, as manifested in the rest-induced inversion of the post-rest potentiation effect. The effect of frequency-dependent acceleration of the kinetics of muscular contraction also persists down to 20°C, supporting the suggestion that this effect in the GP myocardium relies on the sarcoplasmic reticulum. Thus, we found that among the studied frequency-dependent effects, there are those affected by deep hypothermia (post-rest potentiation effect, FDAR) and those resistant to this exposure (FFR), which may reflect the differences in thermal sensitivity of the underlying mechanisms of Ca2 + transport.

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Funding

This work was implemented within a Governmental assignment to the Institute of Cell Biophysics (Russian Academy of Sciences) “A study of the features and mechanisms of the functioning of the myocardium in model animals exposed to hypothermia”.

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Authors and Affiliations

  1. Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Russia

    A. S. Averin

  2. G.K. Scriabin Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, Pushchino, Russia

    N. M. Zakharova

  3. M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Russia

    S. V. Tarlachkov

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  1. A. S. Averin
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  2. N. M. Zakharova
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  3. S. V. Tarlachkov
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Experimental design, data collection, writing a manuscript (A.S.A.); editing a manuscript (N.M.Z.); data treatment (S.V.T.).

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Correspondence to A. S. Averin.

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Translated by A. Polyanovsky

Russian Text © The Author(s), 2021, published in Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, 2021, Vol. 57, No. 4, pp. 289–299https://doi.org/10.31857/S0044452921040021.

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Averin, A.S., Zakharova, N.M. & Tarlachkov, S.V. Effect of Cooling on Force-Frequency Relationship, Rest Potentiation, and Frequency-Dependent Acceleration of Relaxation in the Guinea Pig Myocardium. J Evol Biochem Phys 57, 761–771 (2021). https://doi.org/10.1134/S0022093021040025

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