Damijan Miklavcic

University of Ljubljana · Faculty of Electrical Engineering

Background: Administering gadolinium-based contrast agent before electroporation allows the contrast agent to enter the cells and enables MRI assessment of reversibly electroporated regions. The aim of this study was evaluation of contrast agent entrapment in Chinese hamster ovary (CHO) cells and comparison of these results with those determined b...

Pulsed field ablation (PFA) is an innovative approach in the field of cardiac electrophysiology aimed at treating cardiac arrhythmias. Unlike traditional catheter ablation energies, which use radiofrequency or cryothermal energy to create lesions in the heart, PFA utilizes pulsed electric fields to induce irreversible electroporation, leading to ta...

Background Pulsed field ablation (PFA) is an emerging cardiac ablation modality based on irreversible electroporation with promising preclinical and clinical results. Acute reduction of intracardiac electrograms (bipolar iEGMs) is consistently observed, similar to other ablation modalities, e.g. radiofrequency ablation. We and others have previousl...

Pulsed field ablation (PFA) is a promising new treatment for atrial fibrillation (AF), in which pulmonary vein isolation is achieved by irreversible electroporation. Electroporation causes ATP to leak through the permeabilized membrane. ATP is required both for the healing of the cell membrane and for the functioning of ion pumps, such as sarco/end...

Background Electrochemotherapy (ECT) is a treatment involving the administration of chemotherapeutics drugs followed by the application of 8 square monopolar pulses of 100 μs duration at a repetition frequency of 1 Hz or 5000 Hz. However, there is increasing interest in using alternative types of pulses for ECT. The use of high-frequency short bipo...

Introduction In modern times, bacterial infections have become a growing problem in the medical community due to the emergence of antibiotic-resistant bacteria. In fact, the overuse and improper disposal of antibiotics have led to bacterial resistance and the presence of such bacteria in wastewater. Therefore, it is critical to develop effective st...

Electric pulses used in electroporation-based treatments have been shown to affect the excitability of muscle and neuronal cells. However, understanding the interplay between electroporation and electrophysiological response of excitable cells is complex, since both ion channel gating and electroporation depend on dynamic changes in the transmembra...

Bone metastases can be effectively treated by electrochemotherapy (ECT). Clinical studies report a reduction in pain, preservation of bone stability, and absence of neurologic symptoms after treatment. The transpedicular approach is a promising approach for the treatment of spinal metastases with ECT. The success and safety of treatment can be impr...

Electrochemotherapy treats various types of tumors by combining chemotherapeutic drugs, such as bleomycin or cisplatin, with the delivery of high-voltage pulses resulting in cell membrane electroporation. Conventionally 8 square monopolar pulses of 100 μs duration at a repetition frequency of 1 or 5000 Hz are delivered. Nevertheless, other types of...

Electroporation is used in medicine for drug and gene delivery, and as a nonthermal ablation method in tumor treatment and cardiac ablation. Electroporation involves delivering high-voltage electric pulses to target tissue; however, this can cause effects beyond the intended target tissue like nerve stimulation, muscle contractions and pain, requir...

These authors contributed equally to this work. Abstract: High-Intensity Pulsed Electromagnetic Fields (HI-PEMF) treatment is an emerging noninvasive and contactless alternative to conventional electroporation, since the electric field inside the tissue is induced remotely by an externally applied pulsed magnetic field. Recently, HI-PEMF has been s...

The mechanisms of cell death due to electroporation are still not well understood. Recent studies suggest that cell death due to electroporation is not an immediate all-or-nothing response but rather a dynamic process that occurs over a prolonged period of time. To investigate whether the dynamics of cell death depends on the pulse parameters or ce...

Electroporation is a useful tool for the manipulation with the cell membrane permeability. Underlying physicochemical processes taking place at the molecular level during electroporation are relatively well studied. However, various processes remain unknown, one of them is lipid oxidation, a chain reaction that causes degradation of lipids, and mig...

Introduction Pulsed field ablation is an emerging modality for catheter-based cardiac ablation. The main mechanism of action is irreversible electroporation (IRE), a threshold-based phenomenon in which cells die after exposure to intense pulsed electric fields. Lethal electric field threshold for IRE is a tissue property that determines treatment f...

Traditionally, electroporation-based therapies such as electrochemotherapy (ECT), gene electrotransfer (GET) and irreversible electroporation (IRE) are performed with different but typical pulse durations-100 microseconds and 1-50 milliseconds. However, recent in vitro studies have shown that ECT, GET and IRE can be achieved with virtually any puls...

Electroporation is a biophysical phenomenon involving an increase in cell membrane permeability to molecules after a high-pulsed electric field is applied to the tissue. Currently, electroporation is being developed for non-thermal ablation of cardiac tissue to treat arrhythmias. Cardiomyocytes have been shown to be more affected by electroporation...

italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Objective: The goal of our study was to determine the importance of electric field orientation in an anisotropic muscle tissue for the extent of irreversible electroporation damage by means of an experimentally validated mathematical model. Methods:...

Background: Contact force has been used to titrate lesion formation for radiofrequency ablation. Pulsed Field Ablation (PFA) is a field-based ablation technology for which limited evidence on the impact of contact force on lesion size is available. Methods: Porcine hearts (n=6) were perfused using a modified Langendorff set-up. A prototype focal...

The exact mechanisms of nucleic acid (NA) delivery with gene electrotransfer (GET) are still unknown, which represents a limitation for its broader use. Further, not knowing the effects that different experimental electrical and biological parameters have on GET additionally hinders GET optimization, resulting in the majority of research being perf...

Electroporation-based treatments such as electrochemotherapy and irreversible electroporation ablation have sparked interest with respect to their use in medicine. Treatment planning involves determining the best possible electrode positions and voltage amplitudes to ensure treatment of the entire clinical target volume (CTV). This process is mainl...

Alteration of cell membrane permeability by exposure of plant tissues to pulsed electric fields (PEF) is associated with physical changes in cellular and subcellular structures. The aim of our study was to investigate the possible non-uniform effect of PEF treatment due to the structural heterogeneity of plant tissues commonly used in industrial PE...

Background: Irreversible electroporation is an energy form utilizing high-voltage pulsed electric field, leading to cellular homeostasis disruption and cell death. Recently, irreversible electroporation has shown promising results for the treatment of cardiac arrhythmias. However, reversible and irreversible effects of pulsed electric field on car...

Background: Contact force has been used to titrate lesion formation for radiofrequency ablation. Pulsed Field Ablation (PFA) is a field-based ablation technology for which limited evidence on the impact of contact force on lesion size is available. Methods : Porcine hearts (n=6) were perfused using a modified Langendorff set-up. A prototype focal P...

Povečano prepustnost celične membrane zaradi izpostavitve celic oz. tkiv električnemu polju imenujemo elektroporacija. Povzroči vrsto sprememb v celici, od strukturnih in kemijskih sprememb v celični membrani, strukturnih sprememb proteinov oz. proteinskih kompleksov, prenosa snovi v celice in iz njih do aktiviranja signalnih poti in popravljalnih...

The increased permeability of a cell membrane due to exposure of cells/tissues to an electric field is called electroporation. Electroporation induces a range of changes in the cell - from structural and chemical changes in the cell membrane, structural changes in proteins or protein complexes, transport of substances in and out of the cell, activa...

Gene electrotransfer (GET) is considered one of the most efficient, safe, reproducible, and cost-effective methods of gene therapy, in which a gene is delivered to the cells in the form of a plasmid DNA vector by a method known as electroporation. To achieve successful electroporation, cells must be exposed to sufficiently high electric fields gene...

A high-intensity pulsed electromagnetic field (HI-PEMF) is a non-invasive and non-contact delivery method and may, as such, have an advantage over gene electrotransfer mediated by conventional electroporation using contact electrodes. Due to the limited number of in vitro studies in the field of gene electrotransfection by HI-PEMF, we designed expe...

Gene electrotransfer (GET) is a widely used method for nucleic acids’ delivery into cells. We explored, evaluated, and demonstrated the potential use of different pulse durations for introducing plasmid DNA (pDNA) into cells in vitro and compared the efficiency and dynamics of transgene expression after GET. We performed experiments on cell suspens...

Background Nanosecond electric pulses showed promising results in electrochemotherapy, but the underlying mechanisms of action are still unexplored. The aim of this work was to correlate cellular cisplatin amount with cell survival of cells electroporated with nanosecond or standardly used 8 × 100 μs pulses and to investigate the effects of electri...

To minimize neuromuscular electrical stimulation during electroporation-based treatments, the replacement of long monophasic pulses with bursts of biphasic high-frequency pulses in the range of microseconds was suggested in order to reduce muscle contraction and pain sensation due to pulse application. This treatment modality appeared under the ter...

Electrochemotherapy (ECT) and irreversible electroporation (IRE) are being investigated for treatment of hepatic tumours. The liver is a highly heterogeneous organ, permeated with a network of macro- and microvasculature, biliary tracts and connective tissue. The success of ECT and IRE depends on sufficient electric field established in whole targe...

Background Pulsed field ablation (PFA) is a novel energy modality for treatment of cardiac arrhythmias. The impact of electrode-tissue proximity on lesion formation by PFA has not been conclusively assessed. The objective of this investigation was to evaluate the effects of electrode-tissue proximity on cardiac lesion formation with a biphasic, bip...

Electroporation or pulsed electric field (PEF) treatment is a method of treating biological cells and tissue that, due to its nonthermal nature, facilitates preservation of natural qualities such as organoleptic properties and nutritional value of food products. The range of processes where benefits of electroporation include preserving quality, in...

Electroporation is used to increase the permeability of the cell membrane through high-voltage electric pulses. Nowadays, it is widely used in different areas, such as medicine, biotechnology, and the food industry. Electroporation induces the formation of hydrophilic pores in the lipid bilayer of cell membranes, to allow the entry or exit of molec...

The success of electroporation-based treatments (i.e., reversible electroporation for electrochemotherapy and gene electrotransfer and irreversible electroporation as a tissue ablation method) depends on complete coverage of the clinical target volume with a sufficiently strong electric field (exceeding the reversible or irreversible electroporatio...

Objective: this work focuses on bleomycin electrochemotherapy using new modality of high repetition frequency unipolar nanosecond pulses. Methods: As a tumor model, Lewis lung carcinoma (LLC1) cell line in C57BL mice (n = 42) was used. Electrochemotherapy was performed with intertumoral injection of bleomycin (50 μL of 1500 IU solution) followed...

Gene therapies are revolutionizing medicine by providing a way to cure hitherto incurable diseases. The scientific and technological advances have enabled the first gene therapies to become clinically approved. In addition, with the ongoing COVID-19 pandemic, we are witnessing record speeds in the development and distribution of gene-based vaccines...

The goal of our investigation was to explore the level of membrane permeabilization in plant and animal food matrices (potato, apple, chicken) as resulting from subjecting these matrices to pulsed electric field treatment whereby we employed different assessment methods (electrical impedance spectroscopy, current-voltage measurements, magnetic reso...

Electroporation threshold depends on the membrane composition, with cholesterol being one of its key components already studied in the past, but the results were inconclusive. The aim of our study was to determine behaviour of planar lipid bilayers with varying cholesterol concentrations under electric field. This would give us a better insight int...

Electroporation (EP) is one of the successful physical methods for intracellular drug delivery, which temporarily permeabilizes plasma membrane by exposing cells to electric pulses. Orientation of cells in electric field is important for electroporation and, consequently, for transport of molecules through permeabilized plasma membrane. Uptake of m...

Unintentional metal ion release has been observed with the application of electroporation pulses using metal electrodes, but little research has been conducted evaluating impacts on cell viability. This study focused on the four principal metals found in stainless steel (Fe, Ni, Cr, and Mn), a common electrode material, and analyzed differences in...

Lactic acid bacteria play an important role in functional food and fermentation products for human and animal nutrition, as probiotics, paraprobiotics, postbiotics or high-lactic acid-producing strains in biorefineries. Pulsed electric field (PEF) treatment is gaining recognition in the food industry, but little is known about the effects of PEF tr...

Zdravljenje atrijske fibrilacije (AF) je hitro razvijajoče se področje kardiologije, pri katerem smo priča stalnemu razvoju različnih oblik tehničnih izboljšav in multidisciplinarnega pristopa. Poleg iskanja najprimernejšega ablacijskega načina za učinkovito in varno izoliranje pljučnih ven poskušamo razumeti navidezno kaotičen mehanizem prevajanja...

The aim of the study was to investigate the influence of a pulsed electric field (PEF) on the level of iron ion accumulation in Saccharomyces cerevisiae cells and to select PEF conditions optimal for the highest uptake of this element. Iron ions were accumulated most efficiently when their source was iron (III) nitrate. When the following condition...

Trehalose is a nontoxic disaccharide and a promising cryoprotection agent for medically applicable cells. In this study, the efficiency of combining trehalose with reversible electroporation for cryopreservation of two types of human mesenchymal stromal cells was investigated: adipose-derived stromal cells, and umbilical-cord-derived stromal cells....

Exposure of cells to high voltage electric pulses increases transiently membrane permeability through membrane electroporation. Electroporation can be reversible and is used in gene transfer and enhanced drug delivery but can also lead to cell death. Electroporation resulting in cell death (termed as irreversible electroporation) has been successfu...

Currently, in high-frequency electroporation, much progress has been made but limited to research groups with custom-made laboratory prototype electroporators. According to the review of electroporators and economic evaluations, there is still an area of pulse parameters that needs to be investigated. The development of an asymmetric bipolar pulse...

In Chapter 76, one of the chapter author’s surname has been changed from “Federica Amintrano” to “Federica Amitrano”.

High-Intensity Pulsed Electromagnetic Fields (HI-PEMF) treatment is an emerging noninvasive and contactless alternative to conventional electroporation, since the electric field inside the tissue is induced remotely by external pulsed magnetic field. Recently, HI-PEMF was applied for delivering siRNA molecules to silence enhanced green fluorescent...

Objective: To determine the electric field threshold in our numerical model that best fits the local response to irreversible electroporation (IRE) ablation of hepatic tumors as seen in 6 week follow-up MRI. To numerically evaluate the heat generating effect of IRE and demonstrate the potential of treatment planning to avoid thermal damage and sho...

Basic understanding of the barrier properties of biological membranes can be obtained by studying model systems, such as planar lipid bilayers. Here, we study water pores in planar lipid bilayers in the presence of transmembrane voltage. Planar lipid bilayers were exposed to fast and slow linearly increasing voltage and current signals. We measured...

Background: Pulsed field ablation (PFA) has been identified as an alternative to thermal-based ablation systems for treatment of atrial fibrillation patients. The objective of this Good Laboratory Practice (GLP) study was to characterize the chronic effects and safety of overlapping lesions created by a PFA system at intracardiac locations in a po...

Nanosecond electric pulses have several potential advantages in electroporation-based procedures over the conventional micro- and millisecond pulses including low level of heating, reduced electrochemical reactions and reduced muscle contractions making them alluring for use in biomedicine and food industry. The aim of this study was to evaluate if...