Mechanical alternancies in cardiomycytes of the myocardial sleeves of the superior vena cava and pulmonary veins as a potential source of ectopic activity of the atria

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Abstract

The myocardium of the right and left atria (RA and LA) continues into the superior vena cava (SVC) and pulmonary veins (PV) and forms myocardial sleeves, which are sources of ectopic activity causing atrial fibrillation. We compared the sarcomere dynamics of single cardiomyocytes from the myocardial sleeves of the SVC and PV and guinea pig atria. SVC cardiomyocytes were characterized by a longer time to peak sarcomere shortening and time to 50% relaxation than cardiomyocytes of other groups. In cardiomyocytes of the SVC, PV and right atrium, there was no correlation between the amplitude of sarcomere shortening and the length of the cardiomyocytes. The sarcomere shortening alternans was found in cardiomyocytes of the SVC and PV. The mechanical alternans and the lack of correlation between the amplitude of the sarcomere shortening and the cell size in the myocardial sleeves of the SVC and PV may point to a mechanical substrate that provokes arrhythmia.

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About the authors

T. A. Myachina

Institute of Immunology and Physiology, Ural branch of Russian Academy of Sciences

Email: cmybp@mail.ru
Russian Federation, Yekaterinburg

X. A. Butova

Institute of Immunology and Physiology, Ural branch of Russian Academy of Sciences

Email: cmybp@mail.ru
Russian Federation, Yekaterinburg

R. A. Simonova

Institute of Immunology and Physiology, Ural branch of Russian Academy of Sciences

Email: cmybp@mail.ru
Russian Federation, Yekaterinburg

A. M. Kochurova

Institute of Immunology and Physiology, Ural branch of Russian Academy of Sciences

Email: cmybp@mail.ru
Russian Federation, Yekaterinburg

G. Kopylova

Institute of Immunology and Physiology, Ural branch of Russian Academy of Sciences

Email: cmybp@mail.ru
Russian Federation, Yekaterinburg

A. D. Khokhlova

Washington University

Email: cmybp@mail.ru

Department of Biomedical Engineering

United States, St. Louis, MO

D. V. Shchepkin

Institute of Immunology and Physiology, Ural branch of Russian Academy of Sciences

Author for correspondence.
Email: cmybp@mail.ru
Russian Federation, Yekaterinburg

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Supplementary files

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2. Fig. 1. Analysis of sarcomere shortening-relaxation parameters of the atria and myocardial venous sleeves: (a) — representative scheme demonstrating the calculation of sarcomere shortening-relaxation parameters; (b) — representative profiles of sarcomere length changes during mechanically unloaded contractions of cardiomyocytes: 1 — sarcomeres of the pulmonary vein (PV) cardiomyocyte; 2 — sarcomeres of the left atrium (LA) cardiomyocyte; 3 — sarcomeres of the superior vena cava (SVC) cardiomyocyte; 4 — sarcomeres of the right atrium (RA) cardiomyocyte. Estimated sarcomere shortening parameters: (c) — end-diastolic sarcomere length (EDSL); (d) — sarcomere shortening amplitude (SLS, in % of the EDSL value); (e) — maximum velocity of reaching the peak of shortening (Vshort). (f) — maximum relaxation velocity (Vrel); (g) — time to peak shortening (TTP); (h) — time to 50% relaxation (TTR50). The data are presented as a box-and-whisker plot (boundaries — Q1-Q3 interval, whiskers — spread between minimum and maximum values ​​in the sample). The number of cardiomyocytes in the sample (n) and the number of animals in the general population (N) are presented on the graph as (n/N). 1-way ANOVA, significance of differences at p < 0.05.

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3. Fig. 2. Analysis of sarcomere shortening alternans: (a, b) — representative records of shortening-relaxation of sarcomeres of the left and right atria (LA, RA) in a steady state; (c, d) — representative records of shortening-relaxation of sarcomeres of the myocardial sleeves (PV, SVC) in a steady state and with the appearance of alternans: 1 — change in sarcomere length in a steady state (without alternans); 2 — changes in sarcomere length with alternating cell activity; MIN, MAX — alternating deviations of sarcomere shortening amplitudes to the smaller (MIN) and larger (MAX) sides from the value recorded before the appearance of alternans. (e) — deviations in the amplitude of shortening of myocardial sleeve sarcomeres in MAX and MIN alternansas in percentages relative to the amplitude values ​​in the pseudo-steady state (before and after alternansas). Data are presented as mean and standard deviation.

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4. Fig. 3. Analysis of morphometric characteristics of atrial and venous cardiomyocytes: (a, b) — representative photographs of cardiomyocytes from the left and right atrium (LA, RA) and (c, d) — myocardial sleeves of the pulmonary and superior vena cava (PV, SVC); (e) — length of atrial and venous cardiomyocytes; (f) — width (diameter) of atrial and venous cardiomyocytes. The scale bar corresponds to 10 μm. Data are presented as a box-and-whisker plot (boundaries are the Q1-Q3 interval, whiskers are the spread between the minimum and maximum values ​​in the sample). 1-way ANOVA, significance of differences at p < 0.05.

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5. Fig. 4. Analysis of the relationship between the morphometric characteristics of cardiomyocytes and the parameters of shortening-relaxation of sarcomeres of the right atrium (RA) and the myocardial sleeve of the superior vena cava (SVC): (a) — correlation of the maximum speed of reaching the peak of sarcomere shortening (Vshort) and the amplitude of sarcomere shortening; (b) — correlation of the amplitude of sarcomere shortening and the length of cardiomyocytes. Strong correlation at r > 0.70.

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6. Fig. 5. SDS-polyacrylamide gels of myosin heavy chain (MHC) isoforms extracted from LA and RA, PV and SVC myocardial arms: 1 — myosin from the left ventricle as a marker for βMHC; 2 — 200 kDa molecular weight marker (Thermo Fisher Scientific, USA); 3, 4, 5, 6 — myosin from LA, PV, SVC and RA, respectively. PAGE stained with SYPRO Ruby (Thermo Fisher Scientific, USA).

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7. Fig. 6. Analysis of the phosphorylation state of sarcomere contractile proteins: (a) example of SDS-PAGE for determination of the phosphorylation state of cMyBP-C, (b) myosin regulatory light chain (RLC), and (c) troponin complex proteins TnT and TnI. 1 — molecular weight marker (Thermo Fisher Scientific, USA); 2 and 6 — myosin from the left atrium (LA); 3 and 7 — myosin from the pulmonary veins PV; 4 and 8 — myosin from the superior vena cava (SVC); 5 and 9 — myosin from the right atrium (RA). Phosphorylation levels of (d) cMyBP-C, (e) RLC, (f) TnT, and (g) TnI. Data on the degree of protein phosphorylation are presented in the form of a “box and whiskers” (boundaries are the Q1-Q3 interval, whiskers are the spread between the minimum and maximum values ​​in the sample). N is the number of animals in each of the analyzed groups.

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