Cardiomyocyte Cultures With Controlled Macroscopic Anisotropy

Bursac, Nenad; Parker, Kevin Kit; Iravanian, Shahriar; Tung, Leslie

doi:10.1161/01.res.0000047530.88338.eb

Cited by 239 publications

(181 citation statements)

References 57 publications

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“…However in the case of propagation the current sources are deeply embedded inside the tissue structure and hence the apparent impedances and current paths in this setting are different from the ones when measuring macroscopic impedances. Experimentally a similar phenomena has been observed by Bursac et al [8], who by means of microabrasion increased the amount of extracellular space and observed a speed up along the fiber structure and a slow down across the fiber structure.…”

Section: Discussionsupporting

confidence: 82%

A model for estimating the anisotropy of the conduction velocity in cardiac tissue based on the tissue morphology

Stinstra

Poelzing

MacLeod

et al. 2007

2007 Computers in Cardiology

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IntroductionIn the quest to better understand the mechanisms underlying cardiac arrhythmias, the use of computer simulations is a common tool. Computer simulations have the advantage of being able to resolve potentials and currents with a finer level of detail than is possible with measurements. However, in order to be useful, simulations need to reproduce observations, in this case from electrophysiology, and hence they must produce results against which to compare with experimental findings.The most common approach to the simulation of the propagation of depolarization fronts inside the myocardium is the use of the "bidomain model" [1]. The bidomain model is based on the notion that the myocardium can be separated into intracellular and extracellular spaces, which are joined to each other by a membrane that acts both as a current source and a pathway allowing current to flow between both spaces. More specifically, the bidomain model assumes that the intracellular space, the extracellular space and the membrane all coexist at each point in space. Hence at each location the myocardium can be characterized by a conductivity tensor for the intracellular space, a conductivity tensor for the extracellular space, and an ionic model that describes the current flowing through the membrane.The two conductivity tensors describing the electrical properties of the tissue represent the homogenized conductivity of either the intracellular or the extracellular space. The most common way of estimating these parameters is to choose them so that simulated cardiac propagation speeds fit experimentally observed values. Although this is a valid way of setting these parameters, it fails to relate them to the underlying tissue structure and composition.In this paper, we describe a model that simulates cardiac propagation based on a more detailed description of the microscopic tissue morphology than that provided by the standard bidomain. One of the reasons for including more details into the model is to be able to simulate pathologies like ischemia based on their physiological origins rather than by assigning parameters to fit experiments. For instance, during an episode of]ischemia the amount of extracellular space changes with time [2] altering the way a depolarization front propagates along the fiber [3].In order to create such a model, we built on the models of Spach et al. [4], who created a 2D model of cardiac tissue that consisted of several hundred realistically shaped myocytes that were coupled by gap junctions. Their model was limited by the fact that it did not include an extracellular space. Two-dimensional models are intrinsically limited because the intracellular and extracellular current paths cannot cross each other, thereby limiting the amount of available extracellular and intracellular pathways.To avoid these limitations of a 2D model, we created a full 3D model of cardiac tissue that included realistically shaped myocytes coupled by gap junctions and embedded in an extracellular matrix. We present here pr...

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Section: Discussionsupporting

confidence: 82%

A model for estimating the anisotropy of the conduction velocity in cardiac tissue based on the tissue morphology

Stinstra

Poelzing

MacLeod

et al. 2007

2007 Computers in Cardiology

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“…Previously, the FPs have been shown to correlate well with the underlying cellular electrophysiology [8], and this arrangement allowed for evaluation of changes in the dominant pacemaker, a surrogate for ectopic activity, and of conduction velocity [9,10]. Mapping of two-dimensional cardiomyocytes cultures has proven an efficient methodology for exploring arrhythmic risk [9][10][11][12][13][14][15][16].…”

Section: Resultsmentioning

confidence: 99%

A possible mechanism of halocarbon-induced cardiac sensitization arrhythmias

Jing

Jesús

Iravanian

et al. 2006

Journal of Molecular and Cellular Cardiology

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Cardiac sensitization is the term used for malignant ventricular arrhythmias associated with exposure to inhaled halocarbons in the presence of catecholamines. We investigated the electrophysiological changes associated with cardiomyocyte exposure to epinephrine and a halocarbon known to be associated with cardiac sensitization (halon 1301, CF 3 Br). Cardiomyocytes (CMs) were isolated from neonatal rats and grown on multielectrode arrays (MEAs). Upon exposure to epinephrine, the CM inter-spike interval (ISI) was decreased 14% at 10 µg/L (P<0.05) and 27% at 100 µg/L (P<0.05) as compared to baseline. Halon alone (50 mg/L) mildly prolonged the field potential (FP) duration (7%). CMs exposed to combinations of epinephrine (100 µg/L) and halon (50 mg/L) for 15 min showed a blunted increase in the ISI (35±12%) and a 38% decrease in conduction velocity (P<0.05) when compared to epinephrine alone. There was no change in field potential properties, but dephosphorylated connexin 43 (Cx43) was increased 60±16% with the combination as compared to epinephrine alone (P<0.05). Treatment with okadaic acid, a phosphatase inhibitor, prevented the Cx43 dephosphorylation and the reduction in conduction velocity upon exposure to halon and epinephrine. Moreover, the electrophysiological changes induced by epinephrine and halon were indistinguishable from those seen with the gap junction inhibitor heptanol. In conclusion, the combination of a halocarbon and epinephrine results in a unique electrophysiological signature including slow conduction that may explain, in part, the basis for cardiac sensitization. The slowing of conduction is most likely related to changes in the phosphorylation state of Cx43.

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“…Micorstructured surfaces were prepared using the method previously described for cultivation of cardiomyocytes by Bursac et al [22]. Polyvinyl carbonate cover slips (22mm × 22mm) were abraded using lapping paper with various abrasion grain sizes from McMaster-Carr (aluminum oxide 30, 40, 60, 80μm) and Ultratech USA (silicone carbide 1, 3, 5, 9, 12μm).…”

Section: Microabraded Surfacesmentioning

confidence: 99%

Interactive effects of surface topography and pulsatile electrical field stimulation on orientation and elongation of fibroblasts and cardiomyocytes

Au¹,

Cheng²,

Chowdhury³

et al. 2007

Biomaterials

177

166

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In contractile tissues such as myocardium, functional properties are directly related to the cellular orientation and elongation. Thus, tissue engineering of functional cardiac patches critically depends on our understanding of the interaction between multiple guidance cues such as topographical, adhesive or electrical. The main objective of this study was to determine the interactive effects of contact guidance and electrical field stimulation on elongation and orientation of fibroblasts and cardiomyocytes, major cell populations of the myocardium. Polyvinyl surfaces were abraded using lapping paper with grain size 1 to 80μm, resulting in V-shaped abrasions with the average abrasion peak-to-peak width in the range from 3 to 13μm, and the average depth in the range from 140nm to 700nm (AFM). The surfaces with abrasions 13μm wide and 700nm deep, exhibited the strongest effect on neonatal rat cardiomyocyte elongation and orientation as well as statistically significant effect on orientation of fibroblasts, thus they were utilized for electrical field stimulation. Electrical field stimulation was performed using a regime of relevance for heart tissue in vivo as well as for cardiac tissue engineering. Stimulation (square pulses, 1ms duration, 1Hz, 2.3V/cm or 4.6V/cm) was initiated 24hr after cell seeding and maintained for additional 72hr. The cover slips were positioned between the carbon rod electrodes so that the abrasions were either parallel or perpendicular to the field lines. Non-abraded surfaces were utilized as controls. Field stimulation did not affect cell viability (live/dead staining). The presence of a well developed contractile apparatus in neonatal rat cardiomyocytes (staining for cardiac Troponin I and actin filaments) was identified in the groups cultivated on abraded surfaces in the presence of field stimulation. Overall we observed that i) fibroblast and cardiomyocyte elongation on non-abraded surfaces was significantly enhanced by electrical field stimulation ii) electrical field stimulation promoted orientation of fibroblasts in the direction perpendicular to the field lines when the abrasions were also placed perpendicular to the field lines and iii) topographical cues were a significantly stronger determinant of cardiomyocyte orientation than the electrical field stimulation. The orientation and elongation response of cardiomyocytes was completely abolished by inhibition of actin polymerization (Cytochalasin D) and only partially by inhibition of phosphatidyl-inositol 3 kinase (PI3K) pathway (LY294002).

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Cardiomyocyte Cultures With Controlled Macroscopic Anisotropy

Cited by 239 publications

References 57 publications

A model for estimating the anisotropy of the conduction velocity in cardiac tissue based on the tissue morphology

A model for estimating the anisotropy of the conduction velocity in cardiac tissue based on the tissue morphology

A possible mechanism of halocarbon-induced cardiac sensitization arrhythmias

Interactive effects of surface topography and pulsatile electrical field stimulation on orientation and elongation of fibroblasts and cardiomyocytes

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