The goal of this study was to collect a comprehensive set of data that related lethal effects of electric fields to the duration of the pulse. Electric pulses of different strengths and durations were applied to a suspension of HEp-2 cells (epidermoid carcinoma of the human larynx) using a six-needle electrode array connected through an autoswitcher to a square wave generator. Pulse durations varied from 50 μs to 16 ms and the ranges of electric field were adjusted for each duration to capture cell viabilities between 0% and 100%. After pulsation, cells were incubated for 44 h at 37 ×C, and their viability was measured spectrophotometrically using an XTT assay. For each pulse duration (d), viability data were used to determine the electric field that killed half of the cells (E50). When plotted on logarithmic axes, E50 vs. d was a straight line, leading to a hyperbolic relationship: E50=const/d. This relationship suggests that the total charge delivered by the pulse is the decisive factor in killing HEp-2 cells.© 2003 Biomedical Engineering Society.

We present an analytical solution for the electrical potential and field established by a six-needle array electroporation electrode, which is used in vivo for cancer treatment and DNA delivery. The analytical solution closely matches the numerical solution obtained with the finite element method: the mean error is less than 0.6 %.

Recently, a new type of cancer treatment has been introduced that combines pulsed electric fields (PEF) with anticancer drugs. The proposed mode of action is that PEF create transient pores in the membranes which allow entry of drugs into the cells. This method increases cytotoxicity of some anticancer drugs like bleomycin (BLM) by 2-3 orders of magnitude, which, in turn, reduces systemic drug dosage without decreasing efficacy. In the present study, magnetic resonance imaging (MRI) was used to determine changes in apparent water self-diffusion coefficients (ADC) and spin-lattice (T(1)) and spin-spin (T(2)) relaxation times that occur in an animal laryngeal tumor (HEp-2 cells) model with BLM delivered by PEF. A Bruker 14 Tesla (600 MHz) wide-bore spectrometer with micro-imaging capability was used to generate all the data. Mice carrying approximately 8 mm tumors were treated with several combinations of drug and PEF. All measurements were made on tumor samples excised from mice 24 and 48 hours after treatment with (i) saline, intratumor injection (i.t.), (ii) BLM, i.t., (iii) saline with PEF, and (iv) BLM, i.t., followed by PEF. Although T(1) does not differ between the controls (i, ii, and iii) and full treatment (iv) 6.72 +/- 0.20 s vs. 6.31 +/- 1.7 s, T(2) for (iv) at 24 hours is significantly different from the controls 52.4 +/- 0.91 ms vs. 46.5 +/- 1.54 ms. T(2) differences between treatment and controls disappear at 48 hours. ADC increases significantly from 24 to 48 hours (7.31 +/- 0.16 x 10(-6) to 8.28 +/- 0.28 x 10(-6) cm(2)/sec, p = 0.05). Longer T(2) values may reflect early apoptosis and tumor death when the tumor is structurally less dense. Higher ADC's, associated with the periphery of the tumors and the central region, may indicate loose structural organization and necrosis resulting from the combination treatment.

The present study examined the use of electroporation (pulsed electric field application) to temporarily permeabilize vascular cell membranes and thereby deliver drugs directly into cells of the vessel wall to treat focal cardiovascular diseases (e.g., postangioplasty restenosis). A unique intravascular porous balloon electroporation catheter has been designed specifically to enhance drug uptake directly into the arterial wall. The effect of heparin on neointimal growth following balloon‐induced injury of the carotid arteries of rats was used as a measure of effective drug delivery. Histomorphometrical analysis of arteries showed that neointimal growth and lumen loss were significantly inhibited by heparin in combination with electroporation, but not by heparin delivered without electroporation. We conclude that the application of electroporation technology may be a viable approach to intramural drug delivery of potential therapeutic compounds for the treatment of neointimal growth and negative remodeling during postangioplasty restenosis.

Current methods of local drug delivery frequently fail to achieve a prolonged therapeutically effective tissue drug level without producing vascular trauma. A novel double-balloon catheter system, incorporating electroporation technology, has been designed and tested to deliver heparin into rabbit carotid arteries in an overstretch balloon injury model in vivo. Following arterial injury, fluoresceinated heparin was delivered into the volume between the two inflated balloons, and the artery was subjected to an electrical pulse. Catheter deployment and endovascular electrical pulsing were well-tolerated in all animals (N = 21) without adverse hemodynamic and histological changes. Periodic arterial blood samples revealed no abnormalities in the clotting profile or any gross morphological changes in the blood cells up to 8 hr after treatment. Much stronger heparin fluorescence was detected throughout the vessel layers for at least 12 hr in the pulsed samples compared to the control. Histochemical staining of the tissue showed intracellular localization of heparin. Endovascular electroporation may provide better retention and higher therapeutic efficacy than can be achieved by conventional systemic delivery of heparin at clinically safe concentrations.