Cardiomyocyte lethality by multidirectional stimuli


Multidirectional defibrillation protocols have shown better efficiency than monodirectional; still, no testing was performed to assess cell lethality. We investigated lethality of multidirectional defibrillator-like shocks on isolated cardiomyocytes. Cells were isolated from adult male Wistar rats and plated into a perfusion chamber. Electrical field stimulation threshold (ET) was obtained, and cells were paced with suprathreshold bipolar electrical field (E) pulses. Either one monodirectional high-intensity electrical field (HEF) pulse aligned at 0° (group Mono0) or 60° (group Mono60) to cell major axis or a multidirectional sequence of three HEF pulses aligned at 0°, 60°, and 120° each was applied. If cell recovered from shock, pacing was resumed, and a higher amplitude HEF, proportional to ET, was applied. The sequence was repeated until cell death. Lethality curves were built by means of survival analysis from sub-lethal and lethal E. Non-linear fit was performed, and E values corresponding to 50% probability of lethality (E50) were compared. Multidirectional groups presented lethality curves similar to Mono0. Mono60 displayed the highest E50. The novel data endorse the idea of multidirectional stimuli being safer because their effects on lethality of individual cells were equal to a single monodirectional stimulus, while their defibrillatory threshold is lower.

Monodirectional and multidirectional lethality protocol comparison on isolated rat cardiomyocytes. The heart image is a derivative of “3D Heart in zBrush” ( by Laloxl, used under CC BY 3.0 ( extracted from original video.

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The authors would like to acknowledge the team of the R&D staff at CEB/UNICAMP for the technical support.


This work was supported by CNPq (National Council for Scientific and Technological Development, scholarship to MSc José Américo Nabuco Leva Ferreira de Freitas), FAPESP (Foundation for Research of the State of São Paulo (Proc. No. 2014/18.798-1)), and CAPES (Coordination of Improvement of Higher Education Personnel, scholarships to MSc Fernanda dos Santos Costa Leomil, MSc Marcelo Zoccoler, and MSc Priscila Correia Antoneli).

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Correspondence to Marcelo Zoccoler.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the institutional Committee of Ethics in Animal Use (CEUA/IB/UNICAMP, protocol numbers 4093-1(I) and 4093-1(K)).

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The authors declare that they have no conflict of interest.

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de Freitas, J.A.N.L.F., dos Santos Costa Leomil, F., Zoccoler, M. et al. Cardiomyocyte lethality by multidirectional stimuli. Med Biol Eng Comput 56, 2177–2184 (2018).

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  • Isolated ventricular myocytes
  • Defibrillation
  • Electrical field stimulation