We present a pilot study on the long term effects of irreversible electroporation (IRE) on a large blood vessel. The study was motivated by the anticipated use of IRE for treatment of cancer tumors abutting large blood vessels. A sequence of 10 direct current IRE pulses of 3800 V/cm, 100µs each, at a frequency of 10 pulses per second, were applied directly to the carotid artery in six rats. Measuring tissue conductivity during the procedure showed, as predicted, an increase in conductivity during the application of the pulse, which suggests that this measurement can be used to control the application of IRE. All the animals survived the procedure and showed no side effects. Histology performed 28 days after the procedure showed that the connective matrix of the blood vessels remained intact and the number of vascular smooth muscle cells (VSMC) in the arterial wall decreased with no evidence of aneurysm, thrombus formation or necrosis. Average VSMC density was significantly lower following IRE ablation compared with control (24 ± 11 vs. 139 ± 14, P<0.001), with no apparent damage to extra cellular matrix components and structure. In addition to the relevance of this study to treatment of cancer near large blood vessels these findings tentatively suggest that IRE has possible applications to treatment of pathological processes in which it is desired to reduce the proliferation of VSMC population, such as restenosis and for attenuating atherosclerotic processes in clinical important locations such as coronary, carotid and renal arteries. IntroductionIrreversible electroporation (IRE) is a modality in which microsecond electrical pulses are applied across the cell to generate a destabilizing electric potential across cell outer membrane and cause formation of permanent nanoscale defects in the lipid bilayer. The permanent permeabilization of cell membrane leads to changes in cell homeostasis and cell death (1-3). A recent theoretical study has found that irreversible electroporation could ablate substantial volumes of tissue without thermal effects (4). Subsequent studies have demonstrated the ability of irreversible ablation pulses to completely ablate cancer cells, as a function of the electrical fields (5). The validity of the theoretical study was demonstrated in vivo in the rat liver (6). The first long term IRE in vivo study was performed in the pig liver. Among the many findings with clinical relevance the study has shown the ability of irreversible electroporation to ablate tissue to the margin of a large blood vessel, while the vessel remained patent after the treatment (7). This finding is of major importance in the treatment of cancer, where tumors near large blood vessels are often either untreatable or the treatment fails. The difficulty with surgical treatment of tumors near large blood vessels is evident. In minimally ablation thermal treatment of tumors, the thermal effect of blood flow in the large blood vessels has an opposing effect to the applied thermal treatment, either cold or heat, and residu...

Aims To estimate the prevalence, incidence, mortality, and risk factors for atrial fibrillation (AF) in 195 countries and territories from 1990 to 2017. Methods and Results Following the methodologies used in the Global Burden of Disease study 2017, the prevalence, incidence, and mortality of AF were analyzed by age, sex, year, socio-demographic index (SDI), and location. The percentage contributions of major risk factors to age-standardised AF deaths were measured by population attributable fractions. In 2017, there were 37.57 million [95% uncertainty interval (UI) 32.55 to 42.59] prevalent cases and 3.05 million (95% UI 2.61 to 3.51) incident cases of AF globally, contributing to 287,241 (95% UI 276,355 to 304,759) deaths. The age-standardised rates of prevalent cases, incident cases, and deaths of AF in 2017 and their temporal trends from 1990 to 2017 varied significantly by SDI quintile and location. High systolic blood pressure was the leading risk factor for AF age-standardised deaths [34.3% (95% UI 27.4 to 41.5)] in 2017, followed by high body-mass index [20.7% (95% UI 11.5 to 32.2)] and alcohol use [9.4% (95% UI 7.0 to 12.2)]. Conclusion Our study has systematically and globally assessed the temporal trends of AF, which remains a major public heath challenge. Although AF mainly occurred in developed countries, the unfavorable trend in countries with lower SDI also deserves particular attention. More effective prevention and treatment strategies aimed at counteracting the increase in AF burden should be established in some countries.

BackgroundNon thermal Irreversible electroporation (NTIRE) is a new tissue ablation method that induces selective damage only to the cell membrane while sparing all other tissue components. Our group has recently showed that NTIRE attenuated neointimal formation in rodent model. The goal of this study was to determine optimal values of NTIRE for vascular smooth muscle cell (VSMC) ablation.Methods and Results33 Sprague-Dawley rats were used to compare NTIRE protocols. Each animal had NTIRE applied to its left common carotid artery using a custom-made electrodes. The right carotid artery was used as control. Electric pulses of 100 microseconds were used. Eight IRE protocols were compared: 1–4) 10 pulses at a frequency of 10 Hz with electric fields of 3500, 1750, 875 and 437.5 V/cm and 5–8) 45 and 90 pulses at a frequency of 1 Hz with electric fields of 1750 and 875 V/cm. Animals were euthanized after one week. Histological analysis included VSMC counting and morphometry of 152 sections. Selective slides were stained with elastic Van Gieson and Masson trichrome to evaluate extra-cellular structures. The most efficient protocols were 10 pulses of 3500 V/cm at a frequency of 10 Hz and 90 pulses of 1750 V/cm at a frequency of 1 Hz, with ablation efficiency of 89±16% and 94±9% respectively. Extra-cellular structures were not damaged and the endothelial layer recovered completely.ConclusionsNTIRE is a promising, efficient and simple novel technology for VMSC ablation. It enables ablation within seconds without causing damage to extra-cellular structures, thus preserving the arterial scaffold and enabling endothelial regeneration. This study provides scientific information for future anti-restenosis experiments utilizing NTIRE.

Aims The aim of this study was to estimate the burden and risk factors for ischaemic heart disease (IHD) in 195 countries and territories from 1990 to 2017. Methods and results Data from the Global Burden of Disease Study 2017 were used. Prevalence, incidence, deaths, years lived with disability (YLDs), and years of life lost (YLLs) were metrics used to measure IHD burden. Population attributable fraction was used to estimate the proportion of IHD deaths attributable to potentially modifiable risk factors. Globally, in 2017, 126.5 million [95% uncertainty interval (UI) 118.6 to 134.7] people lived with IHD and 10.6 million (95% UI 9.6 to 11.8) new IHD cases occurred, resulting in 8.9 million (95% UI 8.8 to 9.1) deaths, 5.3 million (95% UI 3.7 to 7.2) YLDs, and 165.0 million (95% UI 162.2 to 168.6) YLLs. Between 1990 and 2017, despite the decrease in age-standardized rates, the global numbers of these burden metrics of IHD have significantly increased. The burden of IHD in 2017 and its temporal trends from 1990 to 2017 varied widely by geographic location. Among all potentially modifiable risk factors, age-standardized IHD deaths worldwide were primarily attributable to dietary risks, high systolic blood pressure, high LDL cholesterol, high fasting plasma glucose, tobacco use, and high body mass index in 2017. Conclusion Our results suggested that IHD remains a major public health challenge worldwide. More effective and targeted strategies aimed at implementing cost-effective interventions and addressing modifiable risk factors are urgently needed, particularly in geographies with high or increasing burden.

Tissue scaffolding is a key component for tissue engineering, and the extracellular matrix (ECM) is nature's ideal scaffold material. A conceptually different method is reported here for producing tissue scaffolds by decellularization of living tissues using nonthermal irreversible electroporation (NTIRE) pulsed electrical fields to cause nanoscale irreversible damage to the cell membrane in the targeted tissue while sparing the ECM and utilizing the body's host response for decellularization. This study demonstrates that the method preserves the native tissue ECM and produces a scaffold that is functional and facilitates recellularization. A two-dimensional transient finite element solution of the Laplace and heat conduction equations was used to ensure that the electrical parameters used would not cause any thermal damage to the tissue scaffold. By performing NTIRE in vivo on the carotid artery, it is shown that in 3 days post NTIRE the immune system decellularizes the irreversible electroporated tissue and leaves behind a functional scaffold. In 7 days, there is evidence of endothelial regrowth, indicating that the artery scaffold maintained its function throughout the procedure and normal recellularization is taking place.

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Acute changes in LA pressure after MitraClip procedure are associated with clinical improvement as measured by 6MWT. Continuous LA pressure monitoring may be a useful tool for procedural guidance during transcatheter mitral repair.

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