Research ArticleBioengineering

Electromechanical cardioplasty using a wrapped elasto-conductive epicardial mesh

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Science Translational Medicine  22 Jun 2016:
Vol. 8, Issue 344, pp. 344ra86
DOI: 10.1126/scitranslmed.aad8568
  • Fig. 1. Materials and design strategy of an elasto-conductive epicardial mesh.

    (A) Schematic illustration of the design strategy of an epicardial mesh for electromechanical cardioplasty in accordance with electrophysiological conduction in the cardiac system. Conductive nanowires were homogeneously dispersed in SBS rubber, allowing for electrical signal (e) transfer during the entire cardiac cycle. (B) Scheme of the reaction for LE-AgNW (top). The ligand of AgNW was exchanged from PVP to HAm via NOBF4 treatment. A scanning electron microscopy image of LE-AgNW/SBS nanocomposite is shown. (C) Representative impedance measurement of the initial and ligand-exchanged films as a function of frequency (Freq.) of alternating current. (D) Representative cyclic voltammetry analysis. Current was measured during a potential sweep from −0.8 to 0.8 V. (E) Schematic illustration of the epicardial mesh fabrication. (F) Average stress-strain curves of epicardial sheet, serpentine mesh (epicardial mesh), hyperserpentine mesh, and film. (G) Trajectory of movements of the outer layer of control and post-MI rat heart at end systole (blue) and end diastole (red) measured by two-dimensional (2D) echocardiography. Circumferential strain of the outer layer of the heart was calculated in control hearts (n = 4) and 8-week post-MI hearts (n = 3). (H) Representative relative resistance changes of the epicardial mesh at increasing tensile strains. Cyclic test of the epicardial mesh when applying 15% tensile strain (inset).

  • Fig. 2. Personalized design of the epicardial mesh.

    (A) Panoramic, 2D view of the epicardial mesh composed of an insulated part (I) connecting RV electrode (+), LV electrode (−), and structural supporting parts (S). A scanning electron microscopy image on the right shows the cross section of the mesh electrode to illustrate the conducting (inner) and insulating (outer) layers. The total thickness of the mesh electrode is 100 μm. (B) Manual testing of the elasticity of the epicardial mesh [initial length (L0) = 60 mm, stretched length (L1) = 90 mm, and released length (L0′) = 60 mm)]. (C) Stacked CT images of a rat heart (left) and its 3D heart reconstruction image derived from the 2D layers (right). (D) A photograph of the epicardial mesh encircling the 3D printed heart model from (C).

  • Fig. 3. Theoretical estimation of the mechanical influences of devices on the heart by the computer simulation.

    (A) Biventricular finite element model of a representative rat heart with the fiber orientations of the anisotropic myocardium. (B) Finite element model of the rat heart, wrapped by the gray shell elements representing the epicardial wrapping (mesh or film). (C) Effects of the mesh and the film on the end-diastolic pressure-volume relationship of LV and RV. Each red point indicates pressure-volume value in a simulated heart wrapped by the epicardial mesh. (D) Maximum principal strain distribution without any wrap (left), with the epicardial mesh wrap (middle), and with the film wrap (right). Encircled area indicates RV collapse.

  • Fig. 4. Coupling of the epicardial mesh to the rat heart.

    (A) Photograph of the epicardial mesh implanted in a control heart. (B) Surface ECG (lead II) and intracardiac electrograms recorded from a conventional electrode on the RV and the epicardial mesh encircling the heart. p, p-wave; v, ventricle; a′, atrium. (C) 3D phase attractor of phase consistency of electrograms in (B) recorded from a conventional electrode and the epicardial mesh. (D) From intracardiac electrograms of the conventional electrode (C) and epicardial mesh (Epi), the baselines are extracted using peak analysis software. Average absolute deviation (AVEDEV) was calculated from the baseline. Data are averages ± SEM (n = 3). P value was determined by unpaired Student’s t test.

  • Fig. 5. Hemodynamic and structural effects of electromechanical cardioplasty.

    (A) Effect of the epicardial mesh on diastolic function (LVEDP and τ) in control and 8-week post-MI rats. P values were determined by the linear mixed model between sinus rhythm at baseline and sinus rhythm during device implantation, between right atrial pacing (RAP) and mesh pacing (MeshP), and between all individual cycle lengths. All P values, including overall P value, were statistically insignificant. Data are means ± SEM (n = 5). (B) LV pressure before and after removing the epicardial mesh in a representative 8-week post-MI rat. (C) LV wall stress-pressure loop during one cardiac cycle. Longitudinal wall stress was derived from simultaneous recordings of LV pressure and myocardial strains during RAP and MeshP at the same cycle length of 280 ms. Data are representative of a control and an 8-week post-MI rat.

  • Fig. 6.

    The effect of electrical stimulation on cardiac electrical and mechanical function and defibrillation function by the epicardial mesh. (A) Representative p-QRS-T complexes during sinus rhythm (baseline) and electrical pacing by the epicardial mesh (MeshP) in control and 8-week post-MI hearts. (B) Effect of MeshP on total ventricular activation time [QRS durations (QRSd)] in control (n = 8) and 8-week post-MI rats (n = 10). P values were determined by paired Student’s t test. (C) Comparison of LVESD and systolic function (% FS) in control (n = 4) and 8-week post-MI (n = 5) animals. *P < 0.005, unpaired Student’s t test; **P < 0.005, paired Student’s t test. (D) Speckle tracking of radial strain in control (n = 5) and 8-week post-MI hearts (n = 6). *P < 0.05 versus respective sinus rhythm, unpaired Student’s t test. Data are means ± SEM. AS, anteroseptal; Ant, anterior; Lat, laterial; Post, posterior; Inf, inferior; Sep, septal. (E) LV contractility index, dP/dtmax, during RAP and MeshP in control (n = 5) and 8-week post-MI rats (n = 5). P values were determined by unpaired Student’s t test. (F) Surface ECG depicting occurrence of a wide-QRS tachycardia, identified as nonsustained ventricular tachycardia from the epicardial mesh recording. (G) Degeneration to ventricular fibrillation (VF) 3 s later and successful termination with a biphasic electrical shock of 2 J delivered through the epicardial mesh. During all assessments, the cycle length of pacing was 280 ms.

  • Fig. 7.

    Biocompatibility of the gold-coated device. (A) Photograph of the Au-coated epicardial mesh. (B) Histology 3 weeks after the implantation of the epicardial mesh and Au-coated epicardial mesh in rat skeletal muscles. Hematoxylin and eosin (H&E) staining and immunohistochemistry for macrophage. The arrows indicate macrophages. (C) Electrical properties. Resistance change under mechanical stretching (left), cyclic resistance behavior under 15% strain (inset), and impedance (right).

Supplementary Materials

  • www.sciencetranslationalmedicine.org/cgi/content/full/8/344/344ra86/DC1

    Materials and Methods

    Fig. S1. Characterization of LE-AgNW and LE-AgNW/SBS nanocomposite.

    Fig. S2. PDMS mold fabrication process for the epicardial mesh.

    Fig. S3. Electrical stimulation by the epicardial mesh.

    Fig. S4. The relation of heart rates to QRS durations, and epicardial mesh pacing at 90% of the baseline cycle lengths.

    Fig. S5. Speckle tracking radial strain.

    Fig. S6. Evaluation of cytotoxicity of the LE-AgNW/SBS film.

    Fig. S7. Feasibility and safety test of the gold-coated epicardial mesh.

    Table S1. Echocardiographic data in controls and 8-week post-MI rats.

    Table S2. Speckle tracking radial strain data in control and 8-week post-MI hearts.

    Table S3. LV contractility index, dP/dtmax, in controls and 8-week post-MI rats.

    Movie S1. Manual testing of the elasticity of the epicardial mesh.

    References (3846)

  • Supplementary Material for:

    Electromechanical cardioplasty using a wrapped elasto-conductive epicardial mesh

    Jinkyung Park, Suji Choi, Ajit H. Janardhan, Se-Yeon Lee, Samarth Raut, Joao Soares, Kwangsoo Shin, Shixuan Yang, Chungkeun Lee, Ki-Woon Kang, Hye Rim Cho, Seok Joo Kim, Pilseon Seo, Wonji Hyun, Sungmook Jung, Hye-Jeong Lee, Nohyun Lee, Seung Hong Choi, Michael Sacks, Nanshu Lu, Mark E. Josephson, Taeghwan Hyeon,* Dae-Hyeong Kim,* Hye Jin Hwang*

    *Corresponding author. Email: hhwang{at}bidmc.harvard.edu (H.J.H.); dkim98{at}snu.ac.kr (D.-H.K.); thyeon{at}snu.ac.kr (T.H.)

    Published 22 June 2016, Sci. Transl. Med. 8, 344ra86 (2016)
    DOI: 10.1126/scitranslmed.aad8568

    This PDF file includes:

    • Materials and Methods
    • Fig. S1. Characterization of LE-AgNW and LE-AgNW/SBS nanocomposite.
    • Fig. S2. PDMS mold fabrication process for the epicardial mesh.
    • Fig. S3. Electrical stimulation by the epicardial mesh.
    • Fig. S4. The relation of heart rates to QRS durations, and epicardial mesh pacing at 90% of the baseline cycle lengths.
    • Fig. S5. Speckle tracking radial strain.
    • Fig. S6. Evaluation of cytotoxicity of the LE-AgNW/SBS film.
    • Fig. S7. Feasibility and safety test of the gold-coated epicardial mesh.
    • Table S1. Echocardiographic data in controls and 8-week post-MI rats.
    • Table S2. Speckle tracking radial strain data in control and 8-week post-MI hearts.
    • Table S3. LV contractility index, dP/dtmax, in controls and 8-week post-MI rats.
    • References (3846)

    [Download PDF]

    Other Supplementary Material for this manuscript includes the following:

    • Movie S1 (.avi format). Manual testing of the elasticity of the epicardial mesh.

    [Download Movies S1]

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