Development of a Method for Isolation of Mature Cardiomyocytes from Human Heart Biopsy Specimens.

To increase the yield of living cells and their survival, studies were carried out to optimize the method for isolating cardiomyocytes from biopsy specimens excised from the right atrial appendages. It was found that creatine, blebbistatin, and taurine are necessary components of the buffer solution during cardiomyocyte isolation, and that composition of the solutions is a more important factor than their oxygenation.

Conduction of excitation waves and reentry drift on cardiac tissue with simulated photocontrol-varied excitability.

The development of new approaches to suppressing cardiac arrhythmias requires a deep understanding of spiral wave dynamics. The study of spiral waves is possible in model systems, for example, in a monolayer of cardiomyocytes. A promising way to control cardiac excitability in vitro is the noninvasive photocontrol of cell excitability mediated by light-sensitive azobenzene derivatives, such as azobenzene trimethylammonium bromide (AzoTAB).

Cyclophosphamide arrhythmogenicitytesting using human-induced pluripotent stem cell-derived cardiomyocytes.

Cyclophosphamide (CP) is an anticancer drug, an alkylating agent. Cardiotoxicity of CP is associated with one of its metabolites, acrolein, and clinical cardiotoxicity manifestations are described for cases of taking CP in high doses. Nevertheless, modern arrhythmogenicity prediction assays in vitro include evaluation of beat rhythm and rate as well as suppression of cardiac late markers after acute exposure to CP, but not its metabolites.

Formation of an electrical coupling between differentiating cardiomyocytes.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) serve as an indispensable platform for the study of human cardiovascular disease is human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). While the possibility of reproducing rare pathologies, patient-specific selection of drugs, and other issues concerning single cardiomyocytes have been well studied, little attention has been paid to the properties of the whole syncytium of CMs, in which both the functionality of individual cells and the distribution of electrophysiological connections between them are essential. The aim of this work is to directly study the ability of hiPSC-CMs to form a functional syncytium that can stably conduct an excitation wave.

Muscular Thin Films for Label-Free Mapping of Excitation Propagation in Cardiac Tissue.

Muscular thin films (MTFs), have already found a variety of applications in cardiac tissue engineering and in building of lab-on-a-chip systems. Here we present a novel approach to label-free mapping of excitation waves in the cardiomyocyte cell cultures with the use of MTFs. Neonatal rat ventricular cardiomyocytes were cultured on polydimethylsiloxane (PDMS) thin films and observed by means of off-axis illumination.

The Use of iPSC-Derived Cardiomyocytes and Optical Mapping for Erythromycin Arrhythmogenicity Testing.

Erythromycin is an antibiotic that prolongs the QT-interval and causes Torsade de Pointes (TdP) by blocking the rapid delayed rectifying potassium current (I) without affecting either the slow delayed rectifying potassium current (I) or inward rectifying potassium current (I). Erythromycin exerts this effect in the range of 1.5-100 μM.

Self-organization of conducting pathways explains electrical wave propagation in cardiac tissues with high fraction of non-conducting cells.

Cardiac fibrosis occurs in many forms of heart disease and is considered to be one of the main arrhythmogenic factors. Regions with a high density of fibroblasts are likely to cause blocks of wave propagation that give rise to dangerous cardiac arrhythmias. Therefore, studies of the wave propagation through these regions are very important, yet the precise mechanisms leading to arrhythmia formation in fibrotic cardiac tissue remain poorly understood.

Stilbene derivative as a photosensitive compound to control the excitability of neonatal rat cardiomyocytes.

Substances that can be used as photosensitizers for cardiac tissue are very helpful in modeling various excitation patterns in a cardiac tissue culture and may have prospective use in the temporary and permanent ablation of unwanted excitation sources in the heart.The aim of the present work is to study the effect of stilbene derivative c-TAB (2- {4- [(E) -2- (4-ethoxyphenyl) vinyl] phenoxy} ethyl) trimethylammonium bromide) on the cardiomyocyte layers and voltage-gated ion channels in cardiac cells. C-TAB is a structural analog to AzoTAB, reported previously as a photoswitch for cardiac and neural cells, in which the azobenzene moiety is replaced by a stilbene grouping.

Effect of heptanol and ethanol on excitation wave propagation in a neonatal rat ventricular myocyte monolayer.

In this work, the action of heptanol and ethanol was investigated in a two-dimensional (2D) model of cardiac tissue: the neonatal rat ventricular myocyte monolayer. Heptanol is known in electrophysiology as a gap junction uncoupler but may also inhibit voltage-gated ionic channels. Ethanol is often associated with the occurrence of arrhythmias.

Biocontractile microfluidic channels for peristaltic pumping.

Bio-actuated micro-pumps do not need any external power source and pose no risk of electrical or heat shock for the biological materials in lab-on-chip systems. Several different designs of bio-actuated micro-pumps based on the use of the contractile force of cultured cardiomyocites have been proposed earlier. Here we present a novel type of a bio-actuated micro-pump representing a microfluidic channel with a contractile wall.

Synchronization of excitable cardiac cultures of different origin.

In the present work, we investigated the synchronization of electrical activity in cultured cardiac cells of different origin put in direct contact. In the first set of experiments synchronization was studied in the primary culture cells of neonatal rats taken at different developmental ages, and in the second - in the neonatal rat cardiomyocytes and HL-1 cells. The electrical excitation of cells was recorded using the calcium transient marker Fluor-4.

Photocontrol of Voltage-Gated Ion Channel Activity by Azobenzene Trimethylammonium Bromide in Neonatal Rat Cardiomyocytes.

The ability of azobenzene trimethylammonium bromide (azoTAB) to sensitize cardiac tissue excitability to light was recently reported. The dark, thermally relaxed trans- isomer of azoTAB suppressed spontaneous activity and excitation propagation speed, whereas the cis- isomer had no detectable effect on the electrical properties of cardiomyocyte monolayers. As the membrane potential of cardiac cells is mainly controlled by activity of voltage-gated ion channels, this study examined whether the sensitization effect of azoTAB was exerted primarily via the modulation of voltage-gated ion channel activity.

Conditions for Waveblock Due to Anisotropy in a Model of Human Ventricular Tissue.

Waveblock formation is the main cause of reentry. We have performed a comprehensive numerical modeling study of block formation due to anisotropy in Ten Tusscher and Panfilov (2006) ionic model for human ventricular tissue. We have examined the border between different areas of myocardial fiber alignment and have shown that blockage can occur for a wave traveling from a transverse fiber area to a longitudinal one.

High-frequency instability of wave fronts.

Experimental evidence is presented that a lateral instability of a wave front, as described earlier in a chemically active medium with the Belousov-Zhabotinsky reaction with decreased excitability, can also occur in a medium with any degree of excitability provided that a high-frequency wave train travels through the medium. The interaction of chemical waves with the boundary of the medium can result in the appearance of wave breaks and spiral waves.