Cardioprotective effect of silicon-built restraint device (ASD), for left ventricular remodeling in rat heart failure model

Abstract

This study aims to evaluate the feasibility and cardio-protective effects of biocompatible silicon-built restraint device (ASD) in the rat's heart failure (HF) model. The performance and compliance characteristics of the ASD device were assessed in vitro by adopting a pneumatic drive and ball burst test. Sprague-Dawley (SD) rats were divided into four groups (n = 6); control, HF, HF + CSD, and HF + ASD groups, respectively. Heart failure was developed by left anterior descending (LAD) coronary artery ligation in all groups except the control group. The ASD and CSD devices were implanted in the heart of HF + ASD and HF + CSD groups, respectively. The ASD's functional and expansion ability was found to be safe and suitable for attenuating ventricular remodeling. ASD-treated rats showed normal heart rhythm, demonstrated by smooth -ST and asymmetrical T-wave. At the same time, hemodynamic parameters of the HF + ASD group improved systolic and diastolic functions, reducing ventricular wall stress, which indicated reverse remodeling. The BNP values were reduced in the HF + ASD group, which confirmed ASD feasibility and reversed remodeling at a molecular level. Furthermore, the HF + ASD group with no fibrosis suggests that ASD has significant curative effects on the heart muscles. In conclusion, ASD was found to be a promising restraint therapy than the previously standard restraint therapies. Stepwise ASD fabrication process (a) 3D computer model of ASD was generated by using Rhinoceros 5.0 software (b) 3D blue wax model of ASD (c) Silicon was prepared by mixing the solutions (as per manufacturer instruction) (d) Blue wax model of ASD was immersed into liquid Silicon (e) ASD model was put into the oven for 3 hours at 50 °C. (f) Blue wax started melting from the ASD model (g) ASD model was built from pure silicon (h) Two access lines were linked to the ASD device, which was connected with an implantable catheter (Port-a-cath), scale bar 100 µm. (Nikon Ldx 2.0).

Stepwise ASD fabrication process (a) 3D computer model of ASD was generated by using Rhinoceros 5.0 software (b) 3D blue wax model of ASD (c) Silicon was prepared by mixing the solutions (as per manufacturer instruction) (d) Blue wax model of ASD was immersed into liquid Silicon (e) ASD model was put into the oven for 3 hours at 50 °C. (f) Blue wax started melting from the ASD model (g) ASD model was built from pure silicon (h) Two access lines were linked to the ASD device, which was connected with an implantable catheter (Port-a-cath), scale bar 100 µm. (Nikon Ldx 2.0).

Fig. 1

Laplace’s law explains the dilated ventricles mechanism and provides a framework for ventricle remodeling. (T) is the dilated heart, directly proportional to left ventricular end-diastolic pressure (LVEDP) (P) and radius chamber radius (R), inversely by wall thickness. Laplace law explains the concept of ASD’s effect on ventricle remodeling. The relationship between transmural pressure (P_tm) and LVEDP is defined by an equation, as shown above in the figure. a By cross-sectional view, the ASD device covered both ventricles from base to apex. b ASD overview of the epicardium. The two tubules are subcutaneously extended, tunneled outside the body, and connected to a medical device for loading and releasing fluid. c View of ASD tubules intercommunicating with each other

Fig. 2

Functional characteristics of ASD device. a Pressure and b flow generated by ASD as a function of drive pressure for an afterload of 120 mmHg and an influx of 6.6 L/min, respectively. Calculations are shown as a solid curve. c Ball burst test of ASD, the pressure is given by pressing the ball at the center of ASD fixed in a circular fixture. ASD undergoes multiaxial expansion by the ball pressure. d Uniaxial circumferential and longitudinal curves were drawn, and a multiaxial curve was also drawn for comparison

Fig. 3

Electrocardiographic exploration of all rats’ groups during various periods. ECG contains a P-wave, followed by the QRS-complex and the T-wave. All measurement was recorded in a millisecond

Fig. 4

a Masson’s trichrome-stained section of rats’ heart in various groups by a photonic microscope (Original magnifications ×4). Showing a segment of the heart fibers encapsulated in collagen (blue) and overlying the myocardium (red). b Quantification of fibrosis of heart tissues obtained from different treatment groups, n = 3, Where, *P < 0.05, **P < 0.01, ***P < 0.001, scale bar 100 µm

Fig. 5

Hemodynamic data are presented as mean ± SEM (n = 6), 1way ANOVA followed by dunnetts’ multiple comparison tests was used for statistical significance of other groups compared to control group. a LVSP b LVEDP c dp/dt_max d −dp/dt_max, ^nsP = no significance;**P < 0.01; ***P < 0.001 vs. Control

Fig. 6

a The BNP results are expressed as mean ± SD; Two-way ANOVA followed by Bonferroni test was used to find statistical analysis compared to the HF group.*P < 0.01; **P < 0.001 vs HF group. b The heart rate of the control and treatment groups, HF, HF + CSD, HF + ASD groups. n = 3