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

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.

<strong></strong>Therapeutic Approach for Global Myocardial Injury Using Bone Marrow-Derived Mesenchymal Stem Cells by Cardiac Support Device in Rats

“…ASD has a similar advantage as a cell sheet, but it can also spread the stem cells or drugs all over the ventricles and deliver cells continuously [38]. Our previous study has confirmed the delivery of lidocaine by ASD was beneficial to reversing calcium chloride-induced ventricular fibrillation [19]. Similarly, ASD delivery of nitroglycerine has improved cardiac function and has a protective effect on the ischemic injury of the heart [39].…”

“…Active hydraulic ventricular attaching support system (ASD) is a net cover made of silicon, a biocompatible material with a heart-shaped configuration consisting of flexible interconnected hollow tubules; it is surgically fixed to the outer wall of the heart and covers both ventricles of the heart providing physical support [18]. ASD is manufactured as a previously described method [19,20]. Briefly, the 3D printed wax model of ASD was made at first, and covered it with silicone evenly, then heated it at 100 • C for one hour to melt the wax and obtained the pure silicone ASD (Fig.…”

Cardioprotective effect of silicone built restraint device (ASD), for left ventricle remodeling in rat heart failure models

“…HF model was then induced in all groups except the control group by left anterior descending (LAD) coronary artery ligation 41 . The method and process of ligation was performed as described by Sufia et.al and Naveed et.al with minor modifications 19,20 After confirmation of HF in the rats, ASD was then implanted in the ASD+HF group. After steady-state baseline measurement, the ASD device was placed around the heart and sutured to the atrioventricular (AV) groove using prolene sutures (4-0) to cover both ventricles.…”

“…The ASD portacath was channeled subcutaneously through the second intercostal space into the left anterior chest wall and extended outside the body through a 1cm opening made in the skin at spinotrapezius. The sternum and portacath incision was then closed in layers 19,20 Saline was instilled in 20 ml increments into ASD tubules and electrocardiogram was monitored. AMVR was observed as the maximum pressure applied by the ASD to the epicardium through a constant volume of saline inside the ASD tubules.…”

“…The objective was to fill the ASD device tubules with a characteristic fluid and observe its restraint property. Furthermore, through this system pharmacological and biological agents can be delivered to the heart locally 19,20 In this study, we have addressed the following important questions. Firstly, whether silicon built restraint device is feasible to attenuate ventricle remodeling in rats model of HF or not?…”