High Intensity Electric Pulses Research Articles

Self-consistent analyses for potential conduction block in nerves by an ultrashort high-intensity electric pulse

Simulation studies are presented that probe the possibility of using high-field (> 100 kV/cm) , short-duration ( approximately 50 ns) electrical pulses for nonthermal and reversible cessation of biological electrical signaling pathways. This would have obvious applications in neurophysiology, clinical research, neuromuscular stimulation therapies, and even nonlethal bioweapons development. The concept is based on the creation of a sufficiently high density of pores on the nerve membrane by an electric pulse. This modulates membrane conductance and presents an effective "electrical short" to an incident voltage wave traveling across a nerve. Net blocking of action potential propagation can then result. A continuum approach based on the Smoluchowski equation is used to treat electroporation. This is self-consistently coupled with a distributed circuit representation of the nerve dynamics. Our results indicate that poration at a single neural segment would be sufficient to produce an observable, yet reversible, effect.

Lethality mechanisms in Escherichia coli induced by intense sub-microsecond electrical pulses

In this letter, the authors present the inactivation kinetics of cells of Escherichia coli and its mutants following treatment with high-intensity electrical pulses of 700 and 32ns durations. Their experimental results suggest that bacterial inactivation by 700ns pulses is consistent with a mechanism of reversible electroporation, whereas inactivation by 32ns pulses may occur as a result of damage to intracellular components. They believe that their results represent a first step towards elucidating the mechanism of lethality of submicrosecond pulses of different durations in prokaryotes.

Statistical analysis of patellar resurfacing in Caucasian and Japanese subjects

Although tissue ablation by irreversible electroporation (IRE) has been characterized as nonthermal, the application of frequent repetitive high-intensity electric pulses has the potential of substantially heating the targeted tissue and causing thermal damage. This study evaluates the risk of possible thermal damage by measuring temperature development and distribution during IRE of porcine kidney tissue.The animal procedures were conducted following an approved Institutional Animal Ethics Committee protocol. IRE ablation was performed in 8 porcine kidneys. Of them, 4 kidneys were treated with a 3-needle configuration and the remaining 4 with a 4-needle configuration. All IRE ablations consisted of 70 pulses with a length 90 µs. The pulse frequency was set at 90 pulses/min, and the pulse intensity at 1,500 V/cm with a spacing of 15 mm between the needles. The temperature was measured internally using 4 fiber-optic temperature probes and at the surface using a thermal camera.For the 3-needle configuration, a peak temperature of 57°C (mean = 49±10°C, n = 3) was measured in the core of the ablation zone and 40°C (mean = 36±3°C, n = 3) at 1 cm outside of the ablation zone, from a baseline temperature of 33±1°C. For the 4-needle configuration, a peak temperature of 79°C (mean = 62±16°C, n = 3) was measured in the core of the ablation zone and 42°C (mean = 39±3°C, n = 3) at 1 cm outside of the ablation zone, from a baseline of 35±1°C. The thermal camera recorded the peak surface temperatures in the center of the ablation zone, reaching 31°C and 35°C for the 3- and 4-needle configuration IRE (baseline 22°C).The application of repetitive high-intensity electric pulses during IRE ablation in porcine kidney causes a lethal rise in temperature within the ablation zone. Temperature monitoring should be considered when performing IRE ablation near vital structures.

Simulations of transient membrane behavior in cells subjected to a high-intensity ultrashort electric pulse

A molecular dynamics (MD) scheme is combined with a distributed circuit model for a self-consistent analysis of the transient membrane response for cells subjected to an ultrashort (nanosecond) high-intensity (approximately 0.01-V/nm spatially averaged field) voltage pulse. The dynamical, stochastic, many-body aspects are treated at the molecular level by resorting to a course-grained representation of the membrane lipid molecules. Coupling the Smoluchowski equation to the distributed electrical model for current flow provides the time-dependent transmembrane fields for the MD simulations. A good match between the simulation results and available experimental data is obtained. Predictions include pore formation times of about 5-6 ns. It is also shown that the pore formation process would tend to begin from the anodic side of an electrically stressed membrane. Furthermore, the present simulations demonstrate that ions could facilitate pore formation. This could be of practical importance and have direct relevance to the recent observations of calcium release from the endoplasmic reticulum in cells subjected to such ultrashort, high-intensity pulses.

Modeling Studies of Cell Response to Ultrashort, High-Intensity Electric Fields—Implications for Intracellular Manipulation

The dynamics of electroporation in biological cells subjected to nanosecond, high-intensity pulses are studied based on a coupled scheme involving both the current continuity and Smoluchowski equations. A new distributed network model, that includes dynamic conductivities of cell membranes and substructures, is introduced for evaluations of transmembrane potential. It is shown that subcellular structures could be affected through nanosecond pulses, and that, despite the high field intensity, the processes remain nonthermal. As an example of selectivity, differences in cell responses between normal and malignant (Farage) tonsillar B-cells are compared and discussed. It is shown that ultrashort, high-intensity electric pulses could damage cancer cells. Finally, the model predicts that it is possible to target the inner mitochondrial membrane (i.e., selectivity at the organelle level), in keeping with recent experimental observations.

Energy-landscape-model analysis for irreversibility and its pulse-width dependence in cells subjected to a high-intensity ultrashort electric pulse.

We provide a simple, but physical analysis for cell irreversibility and apoptosis in response to an ultrashort (nanosecond), high-intensity electric pulse. Our approach is based on an energy landscape model for determining the temporal evolution of the configurational probability function p(q). The primary focus is on obtaining qualitative predictions of a pulse width dependence to apoptotic cell irreversibility that has been observed experimentally. The analysis couples a distributed electrical model for current flow with the Smoluchowski equation to provide self-consistent, time-dependent transmembrane voltages. The model captures the essence of the experimentally observed pulse-width dependence, and provides a possible physical picture that depends only on the electrical trigger. A number of interesting features are predicted.

Mechanism for membrane electroporation irreversibility under high-intensity, ultrashort electrical pulse conditions.

An improved electroporation model is used to address membrane irreversibility under ultrashort electric pulse conditions. It is shown that membranes can survive a strong electric pulse and recover provided the pore distribution has a relatively large spread. If, however, the population consists predominantly of larger radii pores, then irreversibility can result. Physically, such a distribution could arise if pores at adjacent sites coalesce. The requirement of close proximity among the pore sites is more easily satisfied in smaller organelles than in outer cell membranes. Model predictions are in keeping with recent observations of cell damage to intracellular organelles (e.g., mitochondria), without irreversible shock at the outer membranes, by a nanosecond, high-intensity electric pulse. This mechanism also explains the greater damage from multiple electric shocks.

Effects of high hydrostatic pressure or high intensity electrical field pulse pre-treatment on dehydration characteristics of red paprika

The effects of various pre-treatments (hot water blanching, skin treatments, high pressure and high intensity electric field pulse treatment) on the dehydration characteristics of red paprika ( Capsicum annuum L.) were evaluated and compared with untreated samples. Hot water blanching (100°C, 3 min) prior to dehydration (fluidised bed dryer at 60°C, 6 h and 1 m/s) resulted in the permeabilisation of 88% of the cell membranes in paprika, which in turn resulted in a higher mass and heat transfer. Skin treatments (such as lye peeling and acid treatment), as practised conventionally, increased dehydration rates but affected only the skin permeability. The application of high hydrostatic pressure (HHP, 400 MPa for 10 min at 25°C) or high intensity electric field pulses (HELP, 2.4 kV/cm, pulse width 300 μs, 10 pulses, pulse frequency 1 Hz) pre-treatments resulted in cell disintegration indexes of 0.58 and 0.61, respectively. Cell permeabilisation of these physical treatments resulted in higher drying rates, as well as higher mass and heat transfer coefficients, as compared to conventional pre-treatments.

Processing concepts based on high intensity electric field pulses

Emerging non-thermal food processing techniques are receiving considerable attention. This is because of their potential for quality and safety improvement of our food supply, for the ability to enhance conventional processing operations or to create alternative ones, as well as modify existing or non-conventional raw materials, food constituents or processed foods. High intensity electric field pulse technology is one of the most advanced emerging non-thermal processing methods and is currently undergoing intensive scientific and developmental evaluation. The objectives of this review are to summarize and identify the key advantages of this emerging technology and to convert it into optimum use. Those attempts are a combination of research on a kinetic basis and on a cellular level and the subsequent transfer of the knowledge gained into pilot scale.

Resistivity of red blood cells against high-intensity, short-duration electric field pulses induced by chelating agents.

The interaction of human red blood cells (RBCs) with diethylenetriamine-pentaacetic acid (DTPA) or its Gd-complex (Magnevist, a widely used clinical magnetic resonance contrast agent containing free DTPA ligands) led to the following, obviously interrelated phenomena. (i) Both compounds protected erythrocytes against electrohemolysis in isotonic solutions caused by a high-intensity DC electric field pulse. (ii) The inhibition of electrohemolysis was observed only when cells were electropulsed in low-conductivity solutions. (iii) The uptake of Gd-DTPA by electropulsed RBCs was relatively low. (iv) (Gd-) DTPA reduced markedly deformability of erythrocytes, as revealed by the electrodeformation experiments using high-frequency electric fields. Taken together, the results indicate that (Gd-) DTPA produce stiffer erythrocytes that are more resistant to electric field exposure. The observed effects of the chelating agents on the mechanical properties and the electropermeabilization of RBCs must have an origin in molecular changes of the bilayer or membrane-coupled cytoskeleton, which, in turn, appear to result from an alteration of the ionic equilibrium (e.g., Ca(2+) sequestration) in the vicinity of the cell membrane.

Electropulsation as an alternative method for protein extraction from yeast

The application of series of high intensity electric pulses to a yeast suspension provoked a considerable release of some cytoplasmic proteins, glutathione reductase, 3-phosphoglycerate kinase and alcohol dehydrogenase. A maximal yield was achieved 3–8 h after pulsation. The electro-induced protein efflux was accelerated by pretreatment with the reducing agent dithiothreitol and showed a strong dependence on the growth phase and the presence of monovalent ions in the post-pulse incubation medium. The results obtained for two strains of Saccharomyces cerevisiae, PV3 (diploid) and Y47 (wild haploid), showed that electropulsation can be used for the effective extraction of cytoplasmic proteins with a preserved functional activity.

Electropulsation as an alternative method for protein extraction from yeast.

The application of series of high intensity electric pulses to a yeast suspension provoked a considerable release of some cytoplasmic proteins, glutathione reductase, 3-phosphoglycerate kinase and alcohol dehydrogenase. A maximal yield was achieved 3-8 h after pulsation. The electro-induced protein efflux was accelerated by pretreatment with the reducing agent dithiothreitol and showed a strong dependence on the growth phase and the presence of monovalent ions in the post-pulse incubation medium. The results obtained for two strains of Saccharomyces cerevisiae, PV3 (diploid) and Y47 (wild haploid), showed that electropulsation can be used for the effective extraction of cytoplasmic proteins with a preserved functional activity.

Kinetics of electroinduced pores as a probe of membrane modification produced by ionizing radiation

In this work, we have attempted to demonstrate that the study of erythrocyte electroporation can be used to characterize modifications induced at the membrane level by the exposure of living cells to ionizing radiation. Wistar rats were contaminated by chronic ingestion of tritiated water (HTO) in a range of absorbed doses between 0 and 49 cGy. Erythrocyte suspensions were subjected to single electrical pulses and, by modelling the time evolution of light absorption at 610 nm, kinetic parameters describing the electroporated suspension were calculated. A significant increase in the apparent haemolysis rate was observed for the irradiated erythrocytes when subjected to long, high-intensity electrical pulses. In milder electropulsation conditions, when the reversible electroporation process was favoured, the irradiated erythrocytes showed a significant increase in both the radius pore resealing rate and the maximum area of the electroporated surface (for a dose of 49 cGy) compared with the control. The results indicate that the modifications of the parameters due to the effects of irradiation on the erythrocytes reflect an increase in the membrane fluidity without disturbing the association between the cytoskeleton and membrane proteins.

Long-term adaptation in cat auditory-nerve fiber responses.

Driven responses of cat auditory-nerve fibers to long-duration characteristic-frequency (CF) tones could decrease substantially over time periods ranging from seconds to minutes. In extreme cases, the discharge rate could fall before the pre-stimulation spontaneous rate (SR). Reductions in response were characterized by two processes, each of which followed a decaying exponential function. long-term adaptation affects the discharge rate in the first several seconds following stimulus onset. The average amount in high-SR fibers was 42.5% for tones at 20-40 dB SL, and the mean time constant was 3.65 s. Long-term adaptation increased significantly with sensation level (SL, or level above threshold), decreased with SR, and was not significantly correlated with CF or fiber response threshold. Time constants did not depend on CF, SR, or SL. Very-long-term adaptation refers to further, smaller reductions in the discharge rate that accumulate over a period of minutes. Fiber responses formed two groups. The larger group adapted with a mean time constant of 45.22 s for CF tones at 20-40 dB SL, and the smaller group did not adapt over very long terms. Considerable variability in amounts of long-term and very-long-term effects do not arise from cochlear mechanics or middle ear muscle activity. No long-term effects were observed in responses of fibers directly stimulated by high-intensity electrical pulses present at rates up to 500/s through a cochlear implant. This suggests that the effects do not arise from fundamental differences in spike-generating properties of spiral ganglion cells. The data suggest that long-term adaptation may occur either when neurotransmitter utilization at inner hair cell synapses exceeds the rate at which it is replenished from global stores or uptake mechanisms, or which metabolic resources influencing neurotransmitter release become depleted. The neural data are related to perceptual findings in human listeners, in which unusually large amounts of tone decay may be observed at high frequencies, and they indicate that the perceptual effects originate peripherally.