采用主动液压心室附着支撑系统经心外膜给予利多卡因治疗心室颤动的新方法:大鼠实验研究。

A novel approach to devise the therapy for ventricular fibrillation by epicardial delivery of lidocaine using active hydraulic ventricular attaching support system: An experimental study in rats.

机构信息

Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu Province, 211198, China.

Shanghai Jiao Tong University, School of Pharmacy, 800 Dongchuan Road, Shanghai, 200240, China.

出版信息

J Biomed Mater Res B Appl Biomater. 2019 Jul;107(5):1722-1731. doi: 10.1002/jbm.b.34265. Epub 2018 Oct 27.

Abstract

Active hydraulic ventricular attaching support system (ASD) placed around the heart is not only a novel, nontransplant surgical device used for epicardial administration of drugs like lidocaine, but also a promising treatment option for ventricular fibrillation (VF) and arrhythmias. We hypothesize that lidocaine in 5 mg/kg dose released by ASD significantly improves the VF in the rat model. Sprague-Dawley (SD) rats were selected and were divided into four groups, intravenous injection (IV), epicardial infusion (EI), ASD, and control. ASD group was further divided into four subgroups for different lidocaine doses (i) ASD+A group (10 mg/kg), (ii) ASD+B group (5 mg/kg), (iii) ASD+C group (1 mg/kg), and (iv) ASD+D group (0.1 mg/kg). VF was induced with calcium chloride injection and was confirmed by electrocardiogram (ECG) in all the groups. VF was treated with different doses of lidocaine using different modes of administration. Data were analyzed using the SPSS 19.0 Chi-square tests and one-way analysis of variance (ANOVA). The Kaplan-Meier curve for OS was compared to the Logrank test based on the survival time. P < 0.05 was considered as statistically significant. ASD + B group (5 mg/kg) showed significantly reduced sgroup. The time of first sinus rhythm recovered (15.96 ± 21.77 min) and ▵T-SOD in plasma (-42.02 ± 26.99 U/mL) was significantly different than that of control, IV, and EI groups. ▵T-SOD in plasma for all ASD-treated groups was smaller than the control and IV groups. This study proves that ASD with 5 mg/kg lidocaine dose appears as a promising therapeutic platform for treating VF in rats. Furthermore, ASD may also have potential for treating VF or other cardiovascular disease with different therapeutic agents. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1722-1731, 2019.

摘要

主动液压心室附着支撑系统 (ASD) 环绕心脏放置,不仅是一种用于心外膜给予利多卡因等药物的新型非移植手术设备,也是治疗室颤 (VF) 和心律失常的有前途的治疗选择。我们假设 ASD 释放的 5mg/kg 剂量的利多卡因可显著改善大鼠模型中的 VF。选择 Sprague-Dawley (SD) 大鼠并将其分为四组,即静脉注射 (IV)、心外膜输注 (EI)、ASD 和对照组。ASD 组进一步分为四个亚组,用于不同的利多卡因剂量:(i) ASD+A 组 (10mg/kg)、(ii) ASD+B 组 (5mg/kg)、(iii) ASD+C 组 (1mg/kg) 和 (iv) ASD+D 组 (0.1mg/kg)。所有组均用氯化钙注射诱导 VF,并通过心电图 (ECG) 确认。用不同的给药方式给予不同剂量的利多卡因治疗 VF。数据使用 SPSS 19.0 卡方检验和单因素方差分析 (ANOVA) 进行分析。根据生存时间比较 OS 的 Kaplan-Meier 曲线和 Logrank 检验。P<0.05 被认为具有统计学意义。ASD+B 组 (5mg/kg) 显示出明显降低的 VF 发作持续时间和 ▵T-SOD 在血浆中的浓度 (-42.02±26.99U/mL),与对照组、IV 组和 EI 组相比差异显著。所有 ASD 治疗组的 ▵T-SOD 在血浆中的浓度均小于对照组和 IV 组。本研究证明,ASD 联合 5mg/kg 利多卡因剂量似乎是治疗大鼠 VF 的一种很有前途的治疗平台。此外,ASD 还可能具有治疗 VF 或其他心血管疾病的潜力,使用不同的治疗剂。©2018Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:1722-1731, 2019.

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