skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Explore Research Products in the PAR
It may take a few hours for recently added research products to appear in PAR search results.


Title: Experimental studies of spiral wave teleportation in a light sensitive Belousov–Zhabotinsky system
Cardiac arrythmias are a form of heart disease that contributes toward making heart disease a significant cause of death globally. Irregular rhythms associated with cardiac arrythmias are thought to arise due to singularities in the heart tissue that generate reentrant waves in the underlying excitable medium. A normal approach to removing such singularities is to apply a high voltage electric shock, which effectively resets the phase of the cardiac cells. A concern with the use of this defibrillation technique is that the high-energy shock can cause lasting damage to the heart tissue. Various theoretical works have investigated lower-energy alternatives to defibrillation. In this work, we demonstrate the effectiveness of a low-energy defibrillation method in an experimental 2D Belousov–Zhabotinsky (BZ) system. When implemented as a 2D spatial reaction, the BZ reaction serves as an effective analog of general excitable media and supports regular and reentrant wave activity. The defibrillation technique employed involves targeted low-energy perturbations that can be used to “teleport” and/or annihilate singularities present in the excitable BZ medium.  more » « less
Award ID(s):
2102137
PAR ID:
10599936
Author(s) / Creator(s):
; ; ; ;
Publisher / Repository:
AIP
Date Published:
Journal Name:
Chaos: An Interdisciplinary Journal of Nonlinear Science
Volume:
34
Issue:
9
ISSN:
1054-1500
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; ; ; (, Scientific Reports)
    null (Ed.)
    Abstract Intercellular electrical coupling is an essential means of communication between cells. It is important to obtain quantitative knowledge of such coupling between cardiomyocytes and non-excitable cells when, for example, pathological electrical coupling between myofibroblasts and cardiomyocytes yields increased arrhythmia risk or during the integration of donor (e.g., cardiac progenitor) cells with native cardiomyocytes in cell-therapy approaches. Currently, there is no direct method for assessing heterocellular coupling within multicellular tissue. Here we demonstrate experimentally and computationally a new contactless assay for electrical coupling, OptoGap, based on selective illumination of inexcitable cells that express optogenetic actuators and optical sensing of the response of coupled excitable cells (e.g., cardiomyocytes) that are light-insensitive. Cell–cell coupling is quantified by the energy required to elicit an action potential via junctional current from the light-stimulated cell(s). The proposed technique is experimentally validated against the standard indirect approach, GapFRAP, using light-sensitive cardiac fibroblasts and non-transformed cardiomyocytes in a two-dimensional setting. Its potential applicability to the complex three-dimensional setting of the native heart is corroborated by computational modelling and proper calibration. Lastly, the sensitivity of OptoGap to intrinsic cell-scale excitability is robustly characterized via computational analysis. 
    more » « less
  2. ; (, PLOS One)
    Loppini, Alessandro (Ed.)
    Cardiac myocytes synchronize through electrical signaling to contract heart muscles, facilitated by gap junctions (GJs) located in the intercalated disc (ID). GJs provide low-resistance pathways for electrical impulse propagation between myocytes, considered the primary mechanism for electrical communication in the heart. However, research indicates that conduction can persist without GJs. Ephaptic coupling (EpC), which depends on electrical fields in the narrow ID between adjacent myocytes, offers an alternative mechanism for cardiac conduction when GJs are impaired. Research suggests that EpC can enhance conduction velocity (CV) and reduce the likelihood of conduction block (CB), particularly when GJs are impaired, demonstrating the anti-arrhythmic potential of EpC. Reduced GJ communication increases the susceptibility of heart to arrhythmias due to ectopic or triggered activity, highlighting the pro-arrhythmic effect of GJ uncoupling. However, the interplay between GJs and EpC, and their roles in the initiation, dynamics, and termination of arrhythmias, remain unclear. Reentry, characterized by a loop of electrical activity, is a common mechanism underlying arrhythmogenesis in the heart. This study aims to explore the interplay between EpC and GJs on reentry initiation and its underlying dynamics. Specifically, we employed a two-dimensional (2D) discrete bidomain model that integrates EpC to simulate ephaptic conduction during reentry. We quantitatively assessed the outcomes of reentry initiation and the resulting dynamics across different levels of EpC, GJs, and initial perturbations. The results show that sufficiently strong EpC (i.e., sufficiently narrow clefts) tends to suppress reentry initiation, resulting in absent or non-sustained reentrant activity, while also introducing transient instability and heterogeneity into the cardiac dynamics. In contrast, relatively weak EpC (wide clefts) support sustained reentry with a stable rotor. Furthermore, we found that sufficiently strong EpC can lower the maximal dominant frequency observed during reentrant activity. Overall, this suggests that strong EpC exerts an anti-arrhythmic effect. 
    more » « less
  3. ; ; (, Frontiers in Cardiovascular Medicine)
    Cardiovascular disease is the leading cause of death worldwide and bears an immense economic burden. Late-stage heart failure often requires total heart transplantation; however, due to donor shortages and lifelong immunosuppression, alternative cardiac regenerative therapies are in high demand. Human pluripotent stem cells (hPSCs), including human embryonic and induced pluripotent stem cells, have emerged as a viable source of human cardiomyocytes for transplantation. Recent developments in several mammalian models of cardiac injury have provided strong evidence of the therapeutic potential of hPSC-derived cardiomyocytes (hPSC-CM), showing their ability to electromechanically integrate with host cardiac tissue and promote functional recovery. In this review, we will discuss recent developments in hPSC-CM differentiation and transplantation strategies for delivery to the heart. We will highlight the mechanisms through which hPSC-CMs contribute to heart repair, review major challenges in successful transplantation of hPSC-CMs, and present solutions that are being explored to address these limitations. We end with a discussion of the clinical use of hPSC-CMs, including hurdles to clinical translation, current clinical trials, and future perspectives on hPSC-CM transplantation. 
    more » « less
  4. ; ; ; ; ; ; ; (, Metabolites)
    Metabolic acidosis (MA) is a highly prevalent disorder in a significant proportion of the population, resulting from imbalance in blood pH homeostasis. The heart, being an organ with very low regenerative capacity and high metabolic activity, is vulnerable to chronic, although low-grade, MA. To systematically characterize the effect of low-grade MA on the heart, we treated male and female mice with NH4Cl supplementation for 2 weeks and analyzed their blood chemistry and transcriptomic signature of the heart tissue. The reduction of pH and plasma bicarbonate levels without an associated change in anion gap indicated a physiological manifestation of low-grade MA with minimal respiratory compensation. On transcriptomic analysis, we observed changes in cardiac-specific genes with significant gender-based differences due to MA. We found many genes contributing to dilated cardiomyopathy to be altered in males, more than in females, while cardiac contractility and Na/K/ATPase-Src signaling were affected in the opposite way. Our model presents a systems-level understanding of how the cardiovascular tissue is affected by MA. As low-grade MA is a common ailment with many dietary and pharmaceutical interventions, our work presents avenues to limit chronic cardiac damage and disease manifestation, as well as highlighting the sex differences in MA-induced cardiovascular damage. 
    more » « less
  5. ; ; ; ; ; ; ; ; ; ; et al (, Annals of Biomedical Engineering)
    Abstract Genetic mutations to the Lamin A/C gene (LMNA) can cause heart disease, but the mechanisms making cardiac tissues uniquely vulnerable to the mutations remain largely unknown. Further, patients withLMNAmutations have highly variable presentation of heart disease progression and type.In vitropatient-specific experiments could provide a powerful platform for studying this phenomenon, but the use of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) introduces heterogeneity in maturity and function thus complicating the interpretation of the results of any single experiment. We hypothesized that integrating single cell RNA sequencing (scRNA-seq) with analysis of the tissue architecture and contractile function would elucidate some of the probable mechanisms. To test this, we investigated five iPSC-CM lines, three controls and two patients with a (c.357-2A>G) mutation. The patient iPSC-CM tissues had significantly weaker stress generation potential than control iPSC-CM tissues demonstrating the viability of ourin vitroapproach. Through scRNA-seq, differentially expressed genes between control and patient lines were identified. Some of these genes, linked to quantitative structural and functional changes, were cardiac specific, explaining the targeted nature of the disease progression seen in patients. The results of this work demonstrate the utility of combiningin vitrotools in exploring heart disease mechanics. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email