Tissue Electroporation as a Bioelectric Phenomenon: Basic Concepts

Electroporation is the phenomenon in which cell membrane permeability to ions and macromolecules is increased by exposing the cell to short (microsecond to millisecond) high electric field pulses. In living tissues, such permeabilization boost can be used in order to enhance the penetration of drugs (electrochemotherapy) or DNA plasmids (electrogenetherapy) or to destroy undesirable cells (irreversible electroporation). The main purpose of the present chapter is to provide an overview of the electrical concepts related to electroporation for those not familiar with electromagnetism. It is explained that electroporation is a dynamic phenomenon that depends on the local transmembrane voltage and it is shown how a voltage difference applied though a pair of electrodes generates an electric field which in turn induces the required transmembrane voltage for electroporation to occur. Quite exhaustive details are given on how electroporation changes the passive electrical properties of living tissues. Furthermore, some remarks are given about the effects of electroporation on other bioelectric phenomena such as cardiac arrhythmias.

[1]  Boris Rubinsky,et al.  In vivo electrical impedance measurements during and after electroporation of rat liver. , 2007, Bioelectrochemistry.

[2]  Boris Rubinsky,et al.  Tumor Ablation with Irreversible Electroporation , 2007, PloS one.

[3]  H. Itoh,et al.  Electroporation of cell membrane visualized under a pulsed-laser fluorescence microscope. , 1988, Biophysical journal.

[4]  L Tung,et al.  Electroporation of Cardiac Cell Membranes with Monophasic or Biphasic Rectangular Pulses , 1991, Pacing and clinical electrophysiology : PACE.

[5]  Tomaz Slivnik,et al.  Sequential finite element model of tissue electropermeabilization , 2005, IEEE Transactions on Biomedical Engineering.

[6]  A. Hodgkin,et al.  THE IONIC BASIS OF ELECTRICAL ACTIVITY IN NERVE AND MUSCLE , 1951 .

[7]  Zap [extreme voltage for fighting diseases] , 2006 .

[8]  Boris Rubinsky,et al.  Irreversible Electroporation in Medicine , 2007, Technology in cancer research & treatment.

[9]  B. Rubinsky,et al.  Optimum Conductivity of Gels for Electric Field Homogenization in Tissue Electroporation Therapies , 2007 .

[10]  Boris Rubinsky,et al.  Irreversible Electroporation Attenuates Neointimal Formation After Angioplasty , 2008, IEEE Transactions on Biomedical Engineering.

[11]  W. Hamilton,et al.  Effects of high electric fields on micro-organisms. 3. Lysis of erythrocytes and protoplasts. , 1968, Biochimica et biophysica acta.

[12]  Seward B Rutkove,et al.  Electrical impedance of muscle during isometric contraction. , 2003, Physiological measurement.

[13]  Junya Suehiro,et al.  Improvement of electric pulse shape for electropermeabilization-assisted dielectrophoretic impedance measurement for high sensitive bacteria detection , 2005 .

[14]  Boris Rubinsky,et al.  The Effect of Irreversible Electroporation on Blood Vessels , 2007, Technology in cancer research & treatment.

[15]  W. Krassowska,et al.  Modeling electroporation in a single cell. , 2007, Biophysical journal.

[16]  Boris Rubinsky,et al.  In vivo results of a new focal tissue ablation technique: irreversible electroporation , 2006, IEEE Transactions on Biomedical Engineering.

[17]  T. Jarm,et al.  An algorithm for synchronization of in vivo electroporation with ECG , 2005, Journal of medical engineering & technology.

[18]  L. J. Fogelson,et al.  Electrophysiologic depression in myocardium by defibrillation-level shocks , 1988, Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[19]  R. Stampflj,et al.  Reversible electrical breakdown of the excitable membrane of a Ranvier node , 1958 .

[20]  Damijan Miklavcic,et al.  The effect of electroporation pulses on functioning of the heart , 2008, Medical & Biological Engineering & Computing.

[21]  W. Krassowska,et al.  Electroporation and Shock-Induced Transmembrane Potential in a Cardiac Fiber During Defibrillation Strength Shocks , 1998, Annals of Biomedical Engineering.

[22]  M. Bier,et al.  Alteration in sensory nerve function following electrical shock. , 1996, Burns : journal of the International Society for Burn Injuries.

[23]  R. Lee,et al.  Surfactant-induced sealing of electropermeabilized skeletal muscle membranes in vivo. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[24]  J Teissié,et al.  Specific electropermeabilization of leucocytes in a blood sample and application to large volumes of cells. , 1990, Biochimica et biophysica acta.

[25]  I. G. Abidor,et al.  Studies of cell pellets: II. Osmotic properties, electroporation, and related phenomena: membrane interactions. , 1994, Biophysical journal.

[26]  K. Schoenbach,et al.  Intracellular effect of ultrashort electrical pulses , 2001, Bioelectromagnetics.

[27]  Damijan Miklavcic,et al.  Real time electroporation control for accurate and safe in vivo non-viral gene therapy. , 2007, Bioelectrochemistry.

[28]  M. Okino,et al.  Optimal Electric Conditions in Electrical Impulse Chemotherapy , 1992, Japanese journal of cancer research : Gann.

[29]  W. Hamilton,et al.  Effects of high electric fields on microorganisms: I. Killing of bacteria and yeasts , 1967 .

[30]  K. Schoenbach,et al.  The effect of pulsed electric fields on biological cells: experiments and applications , 1997 .

[31]  B. Rubinsky,et al.  Intravascular irreversible electroporation: Theoretical and experimental feasibility study , 2008, 2008 30th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[32]  L. Chernomordik,et al.  Voltage-induced nonconductive pre-pores and metastable single pores in unmodified planar lipid bilayer. , 2001, Biophysical journal.

[33]  H. Nishikawa,et al.  The variation of action potential and impedance in human skeletal muscle during voluntary contraction. , 1994, The Tohoku journal of experimental medicine.

[34]  Damijan Miklavčič,et al.  Variability of the Minimal Transmembrane Voltage Resulting in Detectable Membrane Electroporation , 2008, Electromagnetic biology and medicine.

[35]  R. W. Lau,et al.  The dielectric properties of biological tissues: II. Measurements in the frequency range 10 Hz to 20 GHz. , 1996, Physics in medicine and biology.

[36]  U. Zimmermann,et al.  Release and uptake of haemoglobin and ions in red blood cells induced by dielectric breakdown. , 1975, Biochimica et biophysica acta.

[37]  Nonlinear Changes of Transmembrane Potential During Electrical Shocks: Role of Membrane Electroporation , 2004, Circulation research.

[38]  A. Kuznetsov,et al.  Numerical modeling of in vivo plate electroporation thermal dose assessment. , 2006, Journal of Biomechanical Engineering.

[39]  M. Prausnitz,et al.  Quantitative study of electroporation-mediated molecular uptake and cell viability. , 2001, Biophysical journal.

[40]  Damijan Miklavčič,et al.  Electrochemotherapy – An easy, highly effective and safe treatment of cutaneous and subcutaneous metastases: Results of ESOPE (European Standard Operating Procedures of Electrochemotherapy) study , 2006 .

[41]  J Teissié,et al.  An experimental evaluation of the critical potential difference inducing cell membrane electropermeabilization. , 1993, Biophysical journal.

[42]  M. Sugimachi,et al.  Electroporation in a Model of Cardiac Defibrillation , 2001, Journal of cardiovascular electrophysiology.

[43]  Ulrich Zimmermann,et al.  Dielectric Breakdown of Cell Membranes , 1974 .

[44]  R. O. Price,et al.  Plasma membrane voltage changes during nanosecond pulsed electric field exposure. , 2006, Biophysical journal.

[45]  C.S. Henriquez,et al.  Three-dimensional finite element solution for biopotentials: erythrocyte in an applied field , 1988, IEEE Transactions on Biomedical Engineering.

[46]  K. Schoenbach,et al.  Self-Consistent Analyses For Potential Conduction Block In Nerves By An Ultra-Short, High-Intensity Electric Pulse , 2007, 2007 IEEE 34th International Conference on Plasma Science (ICOPS).

[47]  W. Krassowska Effects of Electroporation on Transmembrane Potential Induced by Defibrillation Shocks , 1995, Pacing and clinical electrophysiology : PACE.

[48]  H. Fricke,et al.  A Mathematical Treatment of the Electric Conductivity and Capacity of Disperse Systems ii. The Capacity of a Suspension of Conducting Spheroids Surrounded by a Non-Conducting Membrane for a Current of Low Frequency , 1925 .

[49]  P. Leder,et al.  Enhancer-dependent expression of human kappa immunoglobulin genes introduced into mouse pre-B lymphocytes by electroporation. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[50]  Boris Rubinsky,et al.  Theoretical analysis of the thermal effects during in vivo tissue electroporation. , 2003, Bioelectrochemistry.

[51]  Cardiac Sensitivity to Electrical Stimulation , 1998 .

[52]  H. Calkins,et al.  Sequential Change in Action Potential of Rabbit Epicardium During and Following Radiofrequency Ablation , 1999, Journal of cardiovascular electrophysiology.

[53]  T. Tsong,et al.  Voltage-induced conductance in human erythrocyte membranes. , 1979, Biochimica et biophysica acta.

[54]  L. Marcu,et al.  Electrode microchamber for noninvasive perturbation of mammalian cells with nanosecond pulsed electric fields , 2005, IEEE Transactions on NanoBioscience.

[55]  S. J. Trout,et al.  Regional variation in electrically‐evoked contractions of rabbit isolated pulmonary artery , 2002, British journal of pharmacology.

[56]  L. Mir,et al.  Electrochemotherapy potentiation of antitumour effect of bleomycin by local electric pulses. , 1991, European journal of cancer.

[57]  G. T. Martin,et al.  Kinetics of the temperature rise within human stratum corneum during electroporation and pulsed high-voltage iontophoresis. , 2002, Bioelectrochemistry.

[58]  L. Mir,et al.  Use of conductive gels for electric field homogenization increases the antitumor efficacy of electroporation therapies , 2008, Physics in medicine and biology.

[59]  R. Barr,et al.  Electric Fields in Tumors Exposed to External Voltage Sources: Implication for Electric Field-Mediated Drug and Gene Delivery , 2006, Annals of Biomedical Engineering.

[60]  Antoni Ivorra,et al.  Bioimpedance Monitoring for physicians: an overview , 2003 .

[61]  T. Clausen,et al.  Role of Na,K pumps in restoring contractility following loss of cell membrane integrity in rat skeletal muscle. , 2005, Acta physiologica Scandinavica.

[62]  C. Collins,et al.  Standard operating procedures of the electrochemotherapy: Instructions for the use of bleomycin or cisplatin administered either systemically or locally and electric pulses delivered by the CliniporatorTM by means of invasive or non-invasive electrodes , 2006 .

[63]  Boris Rubinsky,et al.  Irreversible Electroporation: Implications for Prostate Ablation , 2007, Technology in cancer research & treatment.

[64]  J. G. Webster,et al.  Changes in electrical resistivity of swine liver after occlusion and postmortem , 2006, Medical and Biological Engineering and Computing.

[65]  I. Efimov,et al.  Electroporation of the heart. , 2005, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[66]  Mojca Pavlin,et al.  Effect of cell electroporation on the conductivity of a cell suspension. , 2005, Biophysical journal.

[67]  J. Weaver,et al.  Changes in the passive electrical properties of human stratum corneum due to electroporation. , 1995, Biochimica et biophysica acta.

[68]  W. Hamilton,et al.  Effects of high electric fields on microorganisms: II. Mechanism of action of the lethal effect , 1967 .

[69]  Torben Skovsgaard,et al.  Vascular reactions to in vivo electroporation: characterization and consequences for drug and gene delivery. , 2002, Biochimica et biophysica acta.

[70]  B. Simpson,et al.  Application of high hydrostatic pressure to control enzyme related fresh seafood texture deterioration , 1996 .

[71]  J. Weaver,et al.  The Spatially Distributed Dynamic Transmembrane Voltage of Cells and Organelles due to 10 ns Pulses: Meshed Transport Networks , 2006, IEEE Transactions on Plasma Science.

[72]  D Miklavcic,et al.  A validated model of in vivo electric field distribution in tissues for electrochemotherapy and for DNA electrotransfer for gene therapy. , 2000, Biochimica et biophysica acta.

[73]  U. Pliquett,et al.  Mechanism for the conductivity changes caused by membrane electroporation of CHO cell-pellets , 2004 .

[74]  Determination of intracellular conductivity from electrical breakdown measurements. , 1985, Biochimica et biophysica acta.

[75]  Jon F Edd,et al.  Mathematical Modeling of Irreversible Electroporation for Treatment Planning , 2007, Technology in cancer research & treatment.

[76]  Juergen F Kolb,et al.  Long‐lasting plasma membrane permeabilization in mammalian cells by nanosecond pulsed electric field (nsPEF) , 2007, Bioelectromagnetics.

[77]  Damijan Miklavcic,et al.  The course of tissue permeabilization studied on a mathematical model of a subcutaneous tumor in small animals , 2005, IEEE Transactions on Biomedical Engineering.

[78]  Enhancement of cancer chemotherapy in vitro by intense ultrawideband electric field pulses , 2006 .

[79]  R. Benz,et al.  Pulse-length dependence of the electrical breakdown in lipid bilayer membranes. , 1980, Biochimica et biophysica acta.

[80]  Boris Rubinsky,et al.  A novel nonthermal energy source for surgical epicardial atrial ablation: irreversible electroporation. , 2007, The heart surgery forum.

[81]  R. W. Lau,et al.  The dielectric properties of biological tissues: III. Parametric models for the dielectric spectrum of tissues. , 1996, Physics in medicine and biology.

[82]  E Gersing,et al.  Monitoring Temperature‐Induced Changes in Tissue during Hyperthermia by Impedance Methods a , 1999, Annals of the New York Academy of Sciences.

[83]  B. Rubinsky,et al.  Electric field modulation in tissue electroporation with electrolytic and non-electrolytic additives. , 2007, Bioelectrochemistry.

[84]  L Tung,et al.  Electroporation and recovery of cardiac cell membrane with rectangular voltage pulses. , 1992, The American journal of physiology.

[85]  E. Neumann,et al.  Electroporation of subcutaneous mouse tumors by rectangular and trapezium high voltage pulses. , 2004, Bioelectrochemistry.

[86]  L. Chernomordik,et al.  Reversible electrical breakdown of lipid bilayers: formation and evolution of pores. , 1988, Biochimica et biophysica acta.

[87]  B. Persson,et al.  Transfection of HeLa-cells with pEGFP plasmid by impedance power-assisted electroporation. , 2005, Biotechnology and bioengineering.

[88]  B. Rubinsky,et al.  Electrical impedance measurements during electroporation of rat liver and muscle , 2007 .

[89]  W M Smith,et al.  Prolongation and shortening of action potentials by electrical shocks in frog ventricular muscle. , 1994, The American journal of physiology.

[90]  T. Tsong,et al.  Formation and resealing of pores of controlled sizes in human erythrocyte membrane , 1977, Nature.

[91]  D Miklavcic,et al.  The importance of electric field distribution for effective in vivo electroporation of tissues. , 1998, Biophysical journal.

[92]  Damijan Miklavcic,et al.  Feasibility of Employing Model-Based Optimization of Pulse Amplitude and Electrode Distance for Effective Tumor Electropermeabilization , 2007, IEEE Transactions on Biomedical Engineering.

[93]  Damijan Miklavčič,et al.  Electroporation for Electrochemotherapy and Gene Therapy , 2004 .

[94]  Mojca Pavlin,et al.  Dependence of induced transmembrane potential on cell density, arrangement, and cell position inside a cell system , 2002, IEEE Transactions on Biomedical Engineering.

[95]  Joachim Wegener,et al.  Recovery of adherent cells after in situ electroporation monitored electrically. , 2002, BioTechniques.

[96]  J. Crowley,et al.  Electrical breakdown of bimolecular lipid membranes as an electromechanical instability. , 1973, Biophysical journal.

[97]  L. Mir,et al.  [Electrochemotherapy, a new antitumor treatment: first clinical trial]. , 1991, Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie.

[98]  Martin A Gundersen,et al.  Nanosecond electric pulse-induced calcium entry into chromaffin cells. , 2008, Bioelectrochemistry.

[99]  Sverre Grimnes,et al.  Bioimpedance and Bioelectricity Basics , 2000 .

[100]  C Gabriel,et al.  The dielectric properties of biological tissues: I. Literature survey. , 1996, Physics in medicine and biology.

[101]  W. Russell,et al.  Ethical and Scientific Considerations Regarding Animal Testing and Research , 2011, PloS one.

[102]  M. R. Tarasevich,et al.  246 - Electric breakdown of bilayer lipid membranes I. The main experimental facts and their qualitative discussion , 1979 .

[103]  K. Sugibayashi,et al.  Electric field analysis on the improved skin concentration of benzoate by electroporation. , 2001, International journal of pharmaceutics.

[104]  Deepak Dhar,et al.  Electric field of a six-needle array electrode used in drug and DNA delivery in vivo: analytical versus numerical solution , 2003, IEEE Transactions on Biomedical Engineering.

[105]  I R Efimov,et al.  The role of electroporation in defibrillation. , 2000, Circulation research.

[106]  H. Itoh,et al.  Time courses of cell electroporation as revealed by submicrosecond imaging of transmembrane potential. , 1993, Biophysical journal.

[107]  E. Neumann,et al.  Gene transfer into mouse lyoma cells by electroporation in high electric fields. , 1982, The EMBO journal.

[108]  M J Jaroszeski,et al.  Novel electrode designs for electrochemotherapy. , 1997, Biochimica et biophysica acta.

[109]  J. Patrick Reilly,et al.  Applied Bioelectricity: From Electrical Stimulation to Electropathology , 1998 .