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Membrane polarization at the excitation threshold induced by external electric fields in cardiomyocytes of rats at different developmental stages

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Abstract

External electric fields (E), used for cardiac pacing and defibrillation/cardioversion, induce a spatially variable change in cardiomyocyte transmembrane potential (ΔVm) that depends on cell geometry and E orientation. This study investigates E-induced ΔVm in cardiomyocytes from rats at different ages, which show marked size/geometry variation. Using a tridimensional numerical electromagnetic model recently proposed (NM3D), it was possible: (a) to evaluate the suitability of the simpler, prolate spheroid analytical model (PSAM) to calculate amplitude and location of ΔVm maximum (ΔVmax) for E = 1 V.cm−1; and (b) to estimate the ΔVmax required for excitation (ΔVT) from experimentally determined threshold E values (ET). Ventricular myocytes were isolated from neonatal, weaning, adult, and aging Wistar rats. NM3D was constructed as the extruded 2D microscopy cell image, while measured minor and major cell dimensions were used for PSAM. Acceptable ΔVm estimates can be obtained with PSAM from paralelepidal cells for small θ. ET, but not ΔVT, was higher for neonate cells. ΔVT was significantly greater in the cell from older animals, which indicate lower responsiveness to E associated with aging, rather than with altered cell geometry/dimensions. ΔVT might be used as a non-invasive indicator of cell excitability as it is little affected by cell geometry/size.

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Acknowledgements

The authors are indebted to Ms. Elizângela S. Oliveira and Mr. Renato S. Moura (CEB/UNICAMP) for the technical support, and to Dr. Lynn M. Johnson (Cornell Univerity Statistical Consulting Unit) for the statistical support.

Funding

São Paulo Research Foundation (FAPESP, Proc. 2008/54795–6 and 2013/05441–5), Brazilian National Council for Scientific and Technological Development (CNPq, Proc. 302996/2011–7, 30408/2022-0 and 203312/2014–7), Brazilian Ministry of Health and Funding Authority for Studies and Projects (Finep: 0441/12 - 01.13.0214.00), and Coordination for the Improvement of Higher Education Personnel (CAPES; scholarship to HFMM and AAA).

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Author notes

  1. Hugo F. M. Milan and Ahmad A. Almazloum contributed equally to this work.

Authors and Affiliations

  1. Department of Electronics and Biomedical Engineering, School of Electrical and Computer Engineering, University of Campinas (UNICAMP), Cidade Universitária Zeferino Vaz, Av. Albert Einstein 400, Campinas, SP, 13083-852, Brazil

    Hugo F. M. Milan, Ahmad A. Almazloum, Rosana A. Bassani & José W. M. Bassani

  2. LabNECC, Center for Biomedical Engineering (CEB), University of Campinas (UNICAMP), R. Alexander Fleming 163, Cidade Universitária Zeferino Vaz, Campinas, SP, 13083-881, Brazil

    Rosana A. Bassani & José W. M. Bassani

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Contributions

JWMB, RAB, and HFMM were responsible for the conception of the study. HFMM and AAA performed the experiments, the calculations, and the statistical analysis. All authors participated in the interpretation and revision of the results. HFMM, AAA, and RAB elaborated the first version of the manuscript, which was revised and approved by all authors.

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Correspondence to Hugo F. M. Milan.

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Protocols of animal care and use were approved by the institutional Committee of Ethics in Animal Use (CEUA/IB/UNICAMP; process numbers 2941-1D, 2942-1D, 3009-1A, 3281-1 K and 4093-1G).

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Highlights

• Cardiac stimulation with electric fields (E) is used to treat arrhythmias.

• During development and aging, the size and shape of cardiac cells change, which may alter their electrical response to E.

• Experiments and computer simulation were used to predict membrane polarization by E.

• The lowest E intensity required for excitation depends on cell geometry and was greater in neonates.

• The membrane depolarization required for excitation was greater in cells from old rats only.

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Milan, H.F.M., Almazloum, A.A., Bassani, R.A. et al. Membrane polarization at the excitation threshold induced by external electric fields in cardiomyocytes of rats at different developmental stages. Med Biol Eng Comput 61, 2637–2647 (2023). https://doi.org/10.1007/s11517-023-02868-1

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