Virtual electrode theory explains pacing threshold increase caused by cardiac tissue damage

2004 ◽  
Vol 286 (6) ◽  
pp. H2183-H2194 ◽  
Author(s):  
Aleksandre T. Sambelashvili ◽  
Vladimir P. Nikolski ◽  
Igor R. Efimov

The virtual electrode polarization (VEP) effect is believed to play a key role in electrical stimulation of heart muscle. However, under certain conditions, including clinically, its existence and importance remain unknown. We investigated the influence of acute tissue damage produced by continuous pacing with strong current (40-mA, 4-ms biphasic pulses with 4-Hz frequency for 5 min) on stimulus-generated VEPs and pacing thresholds. A fluorescent optical mapping technique was used to obtain stimulus-induced transmembrane potential distribution around a pacing electrode applied to the ventricular surface of a Langendorff-perfused rabbit heart ( n = 5). Maps and pacing thresholds were recorded before and after tissue damage. Spatial extents of electroporation and cell uncoupling were assessed by propidium iodide ( n = 2) and connexin43 ( n = 3) antibody staining, respectively. On the basis of these data, passive and active three-dimensional bidomain models were built to determine VEP patterns and thresholds for different-sized areas of the damaged region. Electrophysiological results showed that acute tissue damage led to disappearance of the VEP with an associated significant increase in pacing thresholds. Damage was expressed in electroporation and cell uncoupling within a ∼1.0-mm-diameter area around the tip of the electrode. According to computer simulations, cell uncoupling, rather than electroporation, might be the direct cause of VEP elimination and threshold increase, which was nonlinearly dependent on the size of the damaged region. Fiber rotation with depth did not substantially affect the numerical results. The study explains failure to stimulate damaged tissue within the concepts of the VEP theory.

2000 ◽  
Vol 279 (3) ◽  
pp. H1055-H1070 ◽  
Author(s):  
Igor R. Efimov ◽  
Felipe Aguel ◽  
Yuanna Cheng ◽  
Brian Wollenzier ◽  
Natalia Trayanova

We recently suggested that failure of implantable defibrillation therapy may be explained by the virtual electrode-induced phase singularity mechanism. The goal of this study was to identify possible mechanisms of vulnerability and defibrillation by externally applied shocks in vitro. We used bidomain simulations of realistic rabbit heart fibrous geometry to predict the passive polarization throughout the heart induced by external shocks. We also used optical mapping to assess anterior epicardium electrical activity during shocks in Langendorff-perfused rabbit hearts ( n= 7). Monophasic shocks of either polarity (10–260 V, 8 ms, 150 μF) were applied during the T wave from a pair of mesh electrodes. Postshock epicardial virtual electrode polarization was observed after all 162 applied shocks, with positive polarization facing the cathode and negative polarization facing the anode, as predicted by the bidomain simulations. During arrhythmogenesis, a new wave front was induced at the boundary between the two regions near the apex but not at the base. It spread across the negatively polarized area toward the base of the heart and reentered on the other side while simultaneously spreading into the depth of the wall. Thus a scroll wave with a ribbon-shaped filament was formed during external shock-induced arrhythmia. Fluorescent imaging and passive bidomain simulations demonstrated that virtual electrode polarization-induced scroll waves underlie mechanisms of shock-induced vulnerability and failure of external defibrillation.


2006 ◽  
Vol 06 (04) ◽  
pp. 455-475
Author(s):  
TOHRU SUZUKI ◽  
SHUNSUKE SATO ◽  
TOHRU OHE ◽  
RYOJI SUZUKI ◽  
FUMIHIKO KAJIYA

The virtual electrode (VE) has been recognized as an important factor for success or failure of cardiac defibrillation. Many researches have been performed to study characteristics of the VE. However, there are some questions which remain unanswered. In this study, we developed a simulator to solve a three-dimensional bidomain model and performed several simulations to elucidate the basic characteristics of VE in a simplified cardiac tissue with passive membrane when a constant unipolar cathodal stimulus was applied. The results showed that for smaller electrodes, VE has a typical dog-bone shaped virtual cathode (VC) and two egg-shaped virtual anodes (VAs). The distributions both in intra- and extracellular potentials have concentric ellipsoidal isosurfaces, but their ellipticities are subtly different, producing VE. For larger electrodes, VC becomes larger and has a flat-dish shape rather than dog-bone, and VA becomes smaller and also flattens and collapses. The peak values of VE are larger for smaller electrodes, but their time courses show similar tendency among the different sized electrodes. The change of stimulus strength and polarity only affects the magnitude of VE in a linear manner and the distribution pattern is unchanged. These results provide us fundamental knowledge about VE.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1038
Author(s):  
Sonia Trombino ◽  
Federica Curcio ◽  
Roberta Cassano ◽  
Manuela Curcio ◽  
Giuseppe Cirillo ◽  
...  

Cardiac regeneration aims to reconstruct the heart contractile mass, preventing the organ from a progressive functional deterioration, by delivering pro-regenerative cells, drugs, or growth factors to the site of injury. In recent years, scientific research focused the attention on tissue engineering for the regeneration of cardiac infarct tissue, and biomaterials able to anatomically and physiologically adapt to the heart muscle have been proposed as valuable tools for this purpose, providing the cells with the stimuli necessary to initiate a complete regenerative process. An ideal biomaterial for cardiac tissue regeneration should have a positive influence on the biomechanical, biochemical, and biological properties of tissues and cells; perfectly reflect the morphology and functionality of the native myocardium; and be mechanically stable, with a suitable thickness. Among others, engineered hydrogels, three-dimensional polymeric systems made from synthetic and natural biomaterials, have attracted much interest for cardiac post-infarction therapy. In addition, biocompatible nanosystems, and polymeric nanoparticles in particular, have been explored in preclinical studies as drug delivery and tissue engineering platforms for the treatment of cardiovascular diseases. This review focused on the most employed natural and synthetic biomaterials in cardiac regeneration, paying particular attention to the contribution of Italian research groups in this field, the fabrication techniques, and the current status of the clinical trials.


2017 ◽  
Vol 50 (3) ◽  
pp. 830-839 ◽  
Author(s):  
S. M. Suturin ◽  
V. V. Fedorov ◽  
A. M. Korovin ◽  
N. S. Sokolov ◽  
A. V. Nashchekin ◽  
...  

The development of growth techniques aimed at the fabrication of nanoscale heterostructures with layers of ferroic 3dmetals on semiconductor substrates is very important for their potential usage in magnetic media recording applications. A structural study is presented of single-crystal nickel island ensembles grown epitaxially on top of CaF2/Si insulator-on-semiconductor heteroepitaxial substrates with (111), (110) and (001) fluorite surface orientations. The CaF2buffer layer in the studied multilayer system prevents the formation of nickel silicide, guides the nucleation of nickel islands and serves as an insulating layer in a potential tunneling spin injection device. The present study, employing both direct-space and reciprocal-space techniques, is a continuation of earlier research on ferromagnetic 3dtransition metals grown epitaxially on non-magnetic and magnetically ordered fluorides. It is demonstrated that arrays of stand-alone faceted nickel islands with a face-centered cubic lattice can be grown controllably on CaF2surfaces of (111), (110) and (001) orientations. The proposed two-stage nickel growth technique employs deposition of a thin seeding layer at low temperature followed by formation of the islands at high temperature. The application of an advanced three-dimensional mapping technique exploiting reflection high-energy electron diffraction (RHEED) has proved that the nickel islands tend to inherit the lattice orientation of the underlying fluorite layer, though they exhibit a certain amount of {111} twinning. As shown by scanning electron microscopy, grazing-incidence X-ray diffraction (GIXD) and grazing-incidence small-angle X-ray scattering (GISAXS), the islands are of similar shape, being faceted with {111} and {100} planes. The results obtained are compared with those from earlier studies of Co/CaF2epitaxial nanoparticles, with special attention paid to the peculiarities related to the differences in lattice structure of the deposited metals: the dual-phase hexagonal close-packed/face-centered cubic lattice structure of cobalt as opposed to the single-phase face-centered cubic lattice structure of nickel.


2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Katsuhisa Matsuura ◽  
Tatsuya Shimizu ◽  
Nobuhisa Hagiwara ◽  
Teruo Okano

We have developed an original scaffold-free tissue engineering approach, “cell sheet engineering”, and this technology has been already applied to regenerative medicine of various organs including heart. As the bioengineered three-dimensional cardiac tissue is expected to not only function for repairing the broad injured heart but also to be the practicable heart tissue models, we have developed the cell sheet-based perfusable bioengineered three-dimensional cardiac tissue. Recently we have also developed the unique suspension cultivation system for the high-efficient cardiac differentiation of human iPS cells. Fourteen-day culture with the serial treatments of suitable growth factors and a small compound in this stirring system with the suitable dissolved oxygen concentration produced robust embryoid bodies that showed the spontaneous beating and were mainly composed of cardiomyocytes (~80%). When these differentiated cells were cultured on temperature-responsive culture dishes after the enzymatic dissociation, the spontaneous and synchronous beating was observed accompanied with the intracellular calcium influx all over the area even after cell were detached from culture dishes as cell sheets by lowering the culture temperature. The cardiac cell sheets were mainly composed of cardiomyocytes (~80%) and partially mural cells (~20%). Furthermore, extracellular action potential propagation was observed between cell sheets when two cardiac cell sheets were partially overlaid, and this propagation was inhibited by the treatment with some anti-arrhythmic drugs. When the triple layered cardiac tissue was transplanted onto the subcutaneous tissue of nude rats, the spontaneous pulsation was observed over 2 months and engrafted cardiomyocytes were vascularized with the host tissue-derived endothelial cells. These findings suggest that cardiac cell sheets formed by hiPSC-derived cardiomyocytes might have sufficient properties for the creation of thickened cardiac tissue. Now we are developing the vascularized thickened human cardiac tissue by the repeated layering of cardiac cell sheets on the artificial vascular bed in vitro.


2019 ◽  
Vol 25 (3) ◽  
pp. 496-514 ◽  
Author(s):  
Nataraj Poomathi ◽  
Sunpreet Singh ◽  
Chander Prakash ◽  
Rajkumar V. Patil ◽  
P.T. Perumal ◽  
...  

Purpose Bioprinting is a promising technology, which has gained a recent attention, for application in all aspects of human life and has specific advantages in different areas of medicines, especially in ophthalmology. The three-dimensional (3D) printing tools have been widely used in different applications, from surgical planning procedures to 3D models for certain highly delicate organs (such as: eye and heart). The purpose of this paper is to review the dedicated research efforts that so far have been made to highlight applications of 3D printing in the field of ophthalmology. Design/methodology/approach In this paper, the state-of-the-art review has been summarized for bioprinters, biomaterials and methodologies adopted to cure eye diseases. This paper starts with fundamental discussions and gradually leads toward the summary and future trends by covering almost all the research insights. For better understanding of the readers, various tables and figures have also been incorporated. Findings The usages of bioprinted surgical models have shown to be helpful in shortening the time of operation and decreasing the risk of donor, and hence, it could boost certain surgical effects. This demonstrates the wide use of bioprinting to design more precise biological research models for research in broader range of applications such as in generating blood vessels and cardiac tissue. Although bioprinting has not created a significant impact in ophthalmology, in recent times, these technologies could be helpful in treating several ocular disorders in the near future. Originality/value This review work emphasizes the understanding of 3D printing technologies, in the light of which these can be applied in ophthalmology to achieve successful treatment of eye diseases.


2019 ◽  
Vol 25 (4) ◽  
pp. 243-252 ◽  
Author(s):  
Bai Yang ◽  
Cecillia Lui ◽  
Enoch Yeung ◽  
Hiroshi Matsushita ◽  
Anjana Jeyaram ◽  
...  

Author(s):  
S.D. Rykunov ◽  
E.D. Rykunova ◽  
A.I. Boyko ◽  
M.N. Ustinin

A new method of analyzing magnetic encephalography data, the virtual electrode method, was developed. According to magnetic encephalography data, a functional tomogram is constructed — the spatial distribution of field sources on a discrete grid. A functional tomogram displays on the head space the information contained in the multichannel time series of an encephalogram. This is achieved by solving the inverse problem for all elementary oscillations extracted using the Fourier transform. Each oscillation frequency corresponds to a three-dimensional grid node in which the source is located. The user sets the location, size and shape of the brain area for a detailed study of the frequency structure of a functional tomogram - a virtual electrode. The set of oscillations that fall into a given region represents the partial spectrum of this region. The time series of the encephalogram measured by the virtual electrode is restored using this spectrum. The method was applied to the analysis of magnetic encephalography data in two variations - a virtual electrode of a large radius and a point virtual electrode.


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