The methodology for endoluminal irreversible electroporation in porcine models

Abstract:
The aim of this study was to describe the methodology of the surgical technique for endoluminal irreversible electroporation in the biliary tract performed within the perihilar region in porcine models. Endoluminal irreversible electroporation of the common bile duct was performed on eight porcine models using an endoluminal device inserted during laparotomy. The endoluminal device consisted of three electrodes 1 cm in length, attached at 120 degrees around the balloon catheter. The procedure was conducted with the following parameters: number of pulses 90, voltage of 1500 V between each couple of electrodes. Cross sectional imaging and histopathological assessment were employed for evaluations of the ablation zone. Models were sacrificed 24 h and 96 h after ablation. The treatment was successful in all porcine models. All animals survived the defined study period. Peri-ablation oedema within the hepatoduodenal ligament and adjacent liver tissue could be measured on post-procedural MRI or CT. Perforation in the site of ablation developed in one model. Histopathological examination showed heavy regressive changes of the ablated tissue. The elastic membranes of the adjacent portal vein were preserved in all models. In our experience, this novel endoluminal modality used within the perihilar region in porcine models is a feasible and well predictable procedure. Further studies should explore the optimal protocol of catheter-based ablation to limit complications. Biliary ablation, magnetic resonance imaging, intraductal ablation, experimental study Therapeutic procedures used in the care of patients with malignant biliary tract stenosis for the last decades have achieved major progress. Cholangiocarcinoma, most frequent in the elderly population, is difficult to treat due to local extension, limited resectability and high rate of local recurrences in up to 75% of cases (Serrablo and Tejedor 2013) and make up from 5% to 30% of malignant hepatic tumours. Therefore, minimally invasive procedures such as brachytherapy, photodynamic therapy, or endoluminal radiofrequency ablation for tumour treatment are options for those who could not undergo radical surgery or those suffering local recurrence. However, even though a promising theoretical basis for these techniques is set, the clinical results are still far from satisfactory. The commonly used local ablative method, intraductal radiofrequency ablation, based on the thermal energy destruction, is limited by the “heat sink” effect of blood vessels larger than 3 mm accompanying the bile duct. This causes insufficient tumour ablation or thermal damage of vessels in the case of more aggressive treatment (Topazian et al. 2013). ACTA VET. BRNO 2019, 88: 201–205; https://doi.org/10.2754/avb201988020201 Address for correspondence: MUDr. Grolich Tomáš, Ph.D. Department of Surgery, Faculty of Medicine University Hospital Brno and Masaryk University Jihlavská 20, Brno 62500 Phone: Tel: +420 532 232 983 E-mail: grolich.tomas @fnbrno.cz http://actavet.vfu.cz/ Possible complications of heat are eliminated within irreversible electroporation (IRE), a non-thermal ablation technique where cells are exposed to very short high voltage pulses. High voltage pulses alter the transmembrane electrochemical potential, resulting in cell membrane instabilities and pore formation (Davalos et al. 2005; Rubinsky et al. 2007). When the energy exceeds the potential gradient between the active electrodes, pores of critical diameter are formed, leading to disintegration of the membrane. Damaged cells lose the ability to maintain a stable internal environment and the process leads to cell death. None or minimal thermal effect of technology is preserving the architecture of the intercellular tissue matrix and reparation of tissues along it is possible. Newly designed and constructed endoluminal catheters with three electrodes for deposition of high voltage pulses were tested in an experimental ex vivo model with thermography measurements (Bernard et al. 2017). The experiments demonstrated the functionality of the system of catheters and the IRE generator, showing that tissue heating is minimal (5 ± 1 °C). But the events that take place in living organisms associated with reparations at the threshold and suprathreshold damage of phospholipid biomembranes by high voltage pulses cannot be estimated solely by ex vivo modelling. The applicability of catheters for ablations in the bile duct and the effect of the ablation method are directly dependent on the reaction of the living organism involved, and in vivo testing should be the first step for the transition to human medicine. The aim of this study was to prove the concept of endoluminal IRE in healthy bile ducts of an in vivo porcine model with prototype catheter. The secondary aims were to set a standard protocol for intraoperative endoluminal IRE ablations and to set a standard preprocedural and post-procedural evaluation of animal models undergoing the endoluminal IRE procedure in the biliary tree. Materials and Methods Experiments were performed under the supervision of the Department of Surgery of the Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences in Brno, Czech Republic, with a prior approval for the use of animal test subjects from the Ethics Committee of the University of Veterinary and Pharmaceutical Sciences in Brno, Czech Republic, according to law on the protection of animals against cruelty (as amended by §17, paragraph 15g, Act no. 246/1992 Coll.). Animal models and general anaesthesia Eight laboratory female piglets (50% Duroc, 25% Pietrain, and 25% Landrace cross-breed; the median weight 37.5 kg, weight range from 36 to 39 kg) were split into two groups of four pigs according to the desired survival time after surgery (24 h vs. 96 h). The whole procedure was carried out under general anaesthesia with deep muscle relaxation, and the animals were intubated and artificially ventilated. The following combinations of substances were applied for general anaesthesia. Premedication was performed by application of tiletamine 2 mg/kg and zolazepam 2 mg/kg (Zoletil 100, Virbac, Czech Republic), ketamine 2 mg/kg (Narketan, Vetoquinol, Czech Republic) and xylazine 2 mg/kg (Sedazine, Fort Dodge, USA) intramuscularly. Lateral ear vein was used for catheterization and propofol at a dose of 1–2 mg/kg (Norofol, FreseniusKabi AG, Germany) was given intravenously following by the intubation of all pigs. General anaesthesia was maintained using inhalation of isoflurane (Aerrane, Baxter, USA) and oxygen-air mixture. During anaesthesia, the heart rate, respiratory rate, saturation of peripheral oxygen and capnography were monitored and recorded. Atracrium (1.5 mg/kg, Tracurium, GlaxoSmithKline, Italy) was injected intravenously for muscle relaxation. Technology and protocol for irreversible electroporation The IRE was performed with an experimental balloon catheter, a prototype developed with the support of the University Hospital Brno start-up grant no. 12/13 and with the institutional support of the Ministry of Health. The balloon catheter was made of a heat-resistant balloon catheter with applied conductor (gold compound), which was conductively connected to a generator with micro conductor (silver compound) (Zemlicka Development and Production of Implants, Omice, Czech Republic) (Plate IV, Fig.1). High-voltage pulse generator, which was designed by Department of Power Electrical and Electronic Engineering, Faculty of Electrical Engineering and Communication, Brno University of Technology, allows manual adjustment of power and ablation time (0-3000 V, up to 100 μs pulses, max amperage 50 A). 202
Author Listing: Tomáš Andrašina;Tomáš Grolich;Michal Crha;Ladislav Stehlík;Tomáš Rohan;Dalibor Cervinka;Veronika Novotna;Vladan Bernard;Iva Svobodová;Vlastimil Válek
Volume: 88
Pages: 201-205
DOI: 10.2754/avb201988020201
Language: English
Journal: Acta Veterinaria Brno

ACTA VETERINARIA BRNO

ACTA VET BRNO

影响因子:0.6 是否综述期刊:否 是否OA:是 是否预警:不在预警名单内 发行时间:1969 ISSN:0001-7213 发刊频率:Quarterly 收录数据库:SCIE/Scopus收录 出版国家/地区:CZECH REPUBLIC 出版社:University of Veterinary and Pharmaceutical Sciences

期刊介绍

ACTA VETERINARIA BRNO is a scientific journal of the University of Veterinary and Pharmaceutical Sciences in Brno, Czech Republic.The scientific journal Acta Veterinaria Brno is dedicated to the publication of original research findings and clinical observations in veterinary and biomedical sciences. Original scientific research articles reporting new and substantial contribution to veterinary science and original methods that have not been submitted for publication elsewhere are considered for publication. A written statement to this effect should accompany the manuscript, along with approval for publication by the author´s head of department. The authors bear full responsibility for the contents of their contribution. Book reviews are published, too.

《布尔诺兽医学报》(Acta Veterinaria Brno)是捷克共和国布尔诺兽医和制药科学大学的科学期刊,专门发表兽医和生物医学科学的原创研究成果和临床观察。报告对兽医科学有新的和实质性贡献的原始科学研究文章以及尚未在其他地方提交发表的原始方法将被考虑发表。手稿应附有一份书面声明,沿着附有作者所在部门负责人的出版批准。作者对其稿件内容承担全部责任。书评也出版了。

年发文量 53
国人发稿量 -
国人发文占比 0%
自引率 33.3%
平均录取率 容易
平均审稿周期 较慢,18-36周
版面费 -
偏重研究方向 农林科学-兽医学
期刊官网 http://actavet.vfu.cz/
投稿链接 http://actavet.vfu.cz/submissions.html

质量指标占比

研究类文章占比 OA被引用占比 撤稿占比 出版后修正文章占比
94.34% 100.00% 0.00% 0.00%

相关指数

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期刊预警不是论文评价,更不是否定预警期刊发表的每项成果。《国际期刊预警名单(试行)》旨在提醒科研人员审慎选择成果发表平台、提示出版机构强化期刊质量管理。

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WOS期刊SCI分区是指SCI官方(Web of Science)为每个学科内的期刊按照IF数值排 序,将期刊按照四等分的方法划分的Q1-Q4等级,Q1代表质量最高,即常说的1区期刊。
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分区表升级版(试行)的优势:一是论文层级的主题体系既能体现学科交叉特点,又可以精准揭示期刊载文的多学科性;二是采用“期刊超越指数”替代影响因子指标,解决了影响因子数学性质缺陷对评价结果的干扰。整体而言,分区表升级版(试行)突破了期刊评价中学科体系构建、评价指标选择等瓶颈问题,能够更为全面地揭示学术期刊的影响力,为科研评价“去四唯”提供解决思路。相关研究成果经过国际同行的认可,已经发表在科学计量学领域国际重要期刊。

《2019年中国科学院文献情报中心期刊分区表升级版(试行)》首次将社会科学引文数据库(SSCI)期刊纳入到分区评估中。升级版分区表(试行)设置了包括自然科学和社会科学在内的18个大类学科。基础版和升级版(试行)将过渡共存三年时间,推测在此期间各大高校和科研院所仍可能会以基础版为考核参考标准。 提示:中科院分区官方微信公众号“fenqubiao”仅提供基础版数据查询,暂无升级版数据,请注意区分。

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