Research on Biomedical Engineering
Research on Biomedical Engineering
Original article

New insight on the relationship between lethal electrical fields versus cardiomyocyte orientation

Fernanda dos Santos Costa Leomil, Pedro Xavier de Oliveira

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Introduction: Cardiovascular diseases represent a major cause of death world-wide and one of their greatest complications is the development of cardiac arrhythmias, in which ventricular fibrillation (VF) stands out as the most severe one. The only therapy that reverses VF is defibrillation. However defibrillatory shock is capable of killing heart cells and it is known that the orientation of the cell major axis with respect to the electrical field (E) direction is a determining factor for cellular excitation and injury, which is leading to the development of new defibrillation protocols. The aim of this work is to fill the gap in information about cell lethality for intermediate cell orientation angles. Methods: Ventricular myocytes were extracted from adult male Wistar rats and the cells were plated in a chamber for perfusion and stimulation with bipolar voltage pulses to determine the stimulation threshold (ET). Then, monopolar stimulus was applied and amplitude was increased until cell lethal injury. This protocol was performed on four experimental groups: cells oriented at 0°, 30°, 60° and 90°, with respect to E direction. Results: 87 cells were analyzed and an increase in amplitude of E associated with 50% lethality (E50) was verified as the direction
of E application and cell major axis orientation departed. Conclusion: Taken the same probability of lethality, our data suggest a nonlinear increase of E amplitude from 0° to 90° similar to that of ET. These in-between data had not yet been shown and are important for service-based future defibrillation protocols.


Defibrillation, Cell electrical stimulation, Probability of cellular lethality.


Bardou AL, Chesnais JM, Birkui PJ, Govaere MC, Auger PM, Von Euw D, Degonde J. Directional variability of stimulation threshold measurements in isolated guinea pig cardiomyocytes: Relationship with orthogonal sequential defibrillating pulses. Pacing Clin Electrophysiol. 1990; 13(12 Pt 1):1590-5. PMid:1704510.

Bassani RA, Lima KA, Gomes PAP, Oliveira PX, Bassani JWM. Combining stimulus direction and waveform for optimization of threshold stimulation of isolated ventricular myocytes. Physiol Meas. 2006; 27(9):851-63. PMid:16868351.

Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, de Ferranti SD, Floyd J, Fornage M, Gillespie C, Isasi CR, Jiménez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Mackey RH, Matsushita K, Mozaffarian D, Mussolino ME, Nasir K, Neumar RW, Palaniappan L, Pandey DK, Thiagarajan RR, Reeves MJ, Ritchey M, Rodriguez CJ, Roth GA, Rosamond WD, Sasson C, Towfighi A, Tsao CW, Turner MB, Virani SS, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P. Heart disease and stroke statistics-2017 update: a report from the American Heart Association. Circulation. 2017; 135(10):e146-603. PMid:28122885.

Cheek ER, Fast VG. Nonlinear changes of transmembrane potential during electrical shocks: role of membrane electroporation. Circ Res. 2004; 94(2):208-14. PMid:14670844.

Coster HG, Zimmermann U. The mechanism of electrical breakdown in the membranes ofValonia utricularis. J Membr Biol. 1975; 22(1):73-90. PMid:1127686.

DeBruin KA, Krassowska W. Modeling Electroporation in a Single Cell. I. Effects of field strength and rest potential. Biophys J. 1999; 77(3):1213-24. PMid:10465736.

Fedorov VV, Nikolski VP, Efimov IR. Effect of electroporation on cardiac electrophysiology. USA: Humana Press; 2008, p. 433-48.

Gomes PAP, Bassani RA, Bassani JWM. Electric field stimulation of cardiac myocytes during postnatal development. IEEE Trans Biomed Eng. 2001; 48(6):630-6. PMid:11396593.

Goulart JT, de Oliveira PX, Bassani JWM, Bassani RA. The influence of cell dimensions on the vulnerability of ventricular myocytes to lethal injury by high-intensity electrical fields. Rev Bras Eng Bioméd. 2012; 28(4):337-45.

Ideker RE, Zhou X, Knisley SB. Correlation among fibrillation, defibrillation, and cardiac pacing. Pacing Clin Electrophysiol. 1995; 18(3 Pt 2):512-25. PMid:7777416.

Ivorra A. Tissue electroporation as a bioelectric phenomenon: Basic concepts. Berlin: Springer; 2010, p. 23-61.

Jones JL, Jones RE, Balasky G. Microlesion formation in myocardial cells by high-intensity electric field stimulation. Am J Physiol. 1987; 253(2 Pt 2):H480-6. PMid:2441612.

Klauke N, Smith G, Cooper JM. Regional electroporation of single cardiac myocytes in a focused electric field. Anal Chem. 2010; 82(2):585-92. PMid:20020746.

Klee M, Plonsey R. Stimulation of spheroidal cells - The role of cell shape. IEEE Trans Biomed Eng. 1976; BME-23(4):347-54. PMid:1278928.

Knisley SB, Grant AO. Asymmetrical electrically induced injury of rabbit ventricular myocytes. J Mol Cell Cardiol. 1995; 27(5):1111-22. PMid:7473769.

Knisley SB, Hill BC, Ideker RE. Virtual electrode effects in myocardial fibers. Biophys J. 1994; 66(3 Pt 1):719-28. PMid:8011903.

Kotnik T, Pucihar G, Reberšek M, Miklavčič D, Mir LM. Role of pulse shape in cell membrane electropermeabilization. Biochim Biophys Acta - Biomembr. 2003; 1614(2):193-200.

Krauthamer V, Jones JL. Calcium dynamics in cultured heart cells exposed to defibrillator-type electric shocks. Life Sci. 1997; 60(2):1977-85.

Miklavcic D, Pucihar G, Macek Lebar A, Krmelj J, Towhidi L. The pulse intensity-duration dependency for cell membrane electroporation. In: Pakhomov AG, Miklavicic D, Markov MS, editors. Advanced electroporation techniques in biology and medicine. Boca Raton: CRC Press, 2010. p. 246-59.

Neunlist M, Tung L. Dose-dependent reduction of cardiac transmembrane potential by high-intensity electrical shocks. Am J Physiol Circ Physiol. 1997; 273(6 Pt 2):H2817-25. PMid:9435619.

Nikolski V, Efimov I. Electroporation of the heart. Europace. 2005; 7:S146-54.

Oliveira PX, Bassani RA, Bassani JWM. Lethal effect of electric fields on isolated ventricular myocytes. IEEE Trans Biomed Eng. 2008; 55(11):2635-42. PMid:18990634.

Penna LB, Bassani RA. Increased spontaneous activity and reduced inotropic response to catecholamines in ventricular myocytes from footshock-stressed rats. Stress. 2010; 13(1):73-82. PMid:19697264.

Prado LN, Goulart JT, Zoccoler M, Oliveira PX. Ventricular myocyte injury by high-intensity electric field: Effect of pulse duration. Gen Physiol Biophys. 2016; 35(2):121-30. PMid:26830130.

Roth BJ. A mathematical model of make and break electrical stimulation of cardiac tissue by a unipolar anode or cathode. IEEE Trans Biomed Eng. 1995; 42(12):1174-84. PMid:8550059.

Spaeth CS, Boydston EA, Figard LR, Zuzek A, Bittner GD. A model for sealing plasmalemmal damage in neurons and other eukaryotic cells. J Neurosci. 2010; 30(47):15790-800. PMid:21106818.

Steinhardt RA, Bi G, Alderton JM. Cell membrane resealing by a vesicular mechanism similar to neurotransmitter release. Science. 1994; 263(5145):390-3. PMid:7904084.

Togo T, Alderton JM, Bi GQ, Steinhardt RA. The mechanism of facilitated cell membrane resealing. J Cell Sci. 1999; 112(Pt 5):719-31. PMid:9973606.

Tsong TY. Electroporation of cell membranes. Biophys J. 1991; 60(2):297-306. PMid:1912274.

Tung L, Sliz N, Mulligan MR. Influence of electrical axis of stimulation on excitation of cardiac muscle cells. Circ Res. 1991; 69(3):722-30. PMid:1873867.

Tung L. Detrimental effects of electrical fields on cardiac muscle. Proc IEEE. 1996; 84(3):366-78.

Viana MA, Bassani RA, Petrucci O, Marques DA, Bassani JWM, Viana MA, Bassani RA, Petrucci O, Marques DA, Bassani JWM. System for open-chest, multidirectional electrical defibrillation. Res Biomed Eng. 2016; 32(1):74-84.

Weaver JC. Molecular basis for cell membrane electroporationa. Ann N Y Acad Sci. 1994; 720(1):141-52. PMid:8010633.

Weisz MT. Physical principles of defibrillators. Anaesth Intensive Care Med. 2009; 10(8):367-9.

Yabe S, Smith WM, Daubert JP, Wolf PD, Rollins DL, Ideker RE. Conduction disturbances caused by high current density electric fields. Circ Res. 1990; 66(5):1190-203. PMID:2335021.

Zipes DP, Camm AJ, Borggrefe M, Buxton AE, Chaitman B, Fromer M, Gregoratos G, Klein G, Moss AJ, Myerburg RJ, Priori SG, Quinones MA, Roden DM, Silka MJ, Tracy C, Smith SC Jr, Jacobs AK, Adams CD, Antman EM, Anderson JL, Hunt SA, Halperin JL, Nishimura R, Ornato JP, Page RL, Riegel B, Priori SG, Blanc JJ, Budaj A, Camm AJ, Dean V, Deckers JW, Despres C, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Tamargo JL, Zamorano JL. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death). J Am Coll Cardiol. 2006; 48(5):e247-346. PMid:16949478.

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