A Model of Two Nonlinear Coupled Oscillators for the Study of Heartbeat Dynamics

1998 ◽  
Vol 08 (10) ◽  
pp. 1975-1985 ◽  
Author(s):  
Diego di Bernardo ◽  
Maria G. Signorini
Keyword(s):  
Coupled Oscillators ◽  
Heart Rhythm ◽  
Intrinsic Rate ◽  
Cardiac Conduction ◽  
Av Node ◽  
Sa Node ◽  
Nonlinear Coupled Oscillators ◽  
Pace Maker ◽  
Complex Phenomena ◽  
And Function

The cardiac conduction system may be assumed to be a network of self-excitatory pacemakers, with the SinoAtrial (SA) node having the highest intrinsic rate. Subsidiary pacemakers with slower firing frequencies are located in the AtrioVentricular (AV) node and the His-Purkinje system. Under physiological conditions, the SA node is the dominant pace-maker and impulses travel from this node to the ventricle through the AV junction, which is traditionally regarded as a passive conduit. We consider the Av node as an active pace-maker and develop a model of two nonlinear coupled oscillators in order to describe the interaction between the SA and the AV node. These two nonlinear oscillators are based on a modification of the van der Pol osciallator, so that the generated waveforms resemble the action potentials of cells in the SA and the AV node respectively. A bifurcation analysis of this model is performed and the pathophysiological different kinds of heartbeat pathologies (1°, 2° (both Wenckebach and non-Wenckebach) and 3° AV blocks, sinus arrest, atrials bigeminy, etc.). This simple nonlinear model helps to improve the understanding of the complex phenomena involved in heart rhythm generation as well as of heart rate control and function.

scholarly journals The Evolving Roles of Cardiac Macrophages in Homeostasis, Regeneration, and Repair

2021 ◽  
Vol 22 (15) ◽  
pp. 7923
Author(s):  
Santiago Alvarez-Argote ◽  
Caitlin C. O’Meara
Keyword(s):  
Cardiac Injury ◽  
Cardiac Regeneration ◽  
Normal Function ◽  
Cardiac Conduction ◽  
Cell Detection ◽  
Fate Mapping ◽  
The Novel ◽  
Functional Roles ◽  
Macrophage Populations ◽  
And Function

Macrophages were first described as phagocytic immune cells responsible for maintaining tissue homeostasis by the removal of pathogens that disturb normal function. Historically, macrophages have been viewed as terminally differentiated monocyte-derived cells that originated through hematopoiesis and infiltrated multiple tissues in the presence of inflammation or during turnover in normal homeostasis. However, improved cell detection and fate-mapping strategies have elucidated the various lineages of tissue-resident macrophages, which can derive from embryonic origins independent of hematopoiesis and monocyte infiltration. The role of resident macrophages in organs such as the skin, liver, and the lungs have been well characterized, revealing functions well beyond a pure phagocytic and immunological role. In the heart, recent research has begun to decipher the functional roles of various tissue-resident macrophage populations through fate mapping and genetic depletion studies. Several of these studies have elucidated the novel and unexpected roles of cardiac-resident macrophages in homeostasis, including maintaining mitochondrial function, facilitating cardiac conduction, coronary development, and lymphangiogenesis, among others. Additionally, following cardiac injury, cardiac-resident macrophages adopt diverse functions such as the clearance of necrotic and apoptotic cells and debris, a reduction in the inflammatory monocyte infiltration, promotion of angiogenesis, amelioration of inflammation, and hypertrophy in the remaining myocardium, overall limiting damage extension. The present review discusses the origin, development, characterization, and function of cardiac macrophages in homeostasis, cardiac regeneration, and after cardiac injury or stress.

scholarly journals Anisotropic Cardiac Conduction

2020 ◽  
Vol 9 (4) ◽  
pp. 202-210
Author(s):  
Irum Kotadia ◽  
John Whitaker ◽  
Caroline Roney ◽  
Steven Niederer ◽  
Mark O’Neill ◽  
...  
Keyword(s):  
Gap Junction ◽  
Cardiac Tissue ◽  
Diffusion Tensor ◽  
Interstitial Fibrosis ◽  
Cardiac Conduction ◽  
Principal Mechanism ◽  
Disease States ◽  
And Function ◽  
Anisotropic Conduction

Anisotropy is the property of directional dependence. In cardiac tissue, conduction velocity is anisotropic and its orientation is determined by myocyte direction. Cell shape and size, excitability, myocardial fibrosis, gap junction distribution and function are all considered to contribute to anisotropic conduction. In disease states, anisotropic conduction may be enhanced, and is implicated, in the genesis of pathological arrhythmias. The principal mechanism responsible for enhanced anisotropy in disease remains uncertain. Possible contributors include changes in cellular excitability, changes in gap junction distribution or function and cellular uncoupling through interstitial fibrosis. It has recently been demonstrated that myocyte orientation may be identified using diffusion tensor magnetic resonance imaging in explanted hearts, and multisite pacing protocols have been proposed to estimate myocyte orientation and anisotropic conduction in vivo. These tools have the potential to contribute to the understanding of the role of myocyte disarray and anisotropic conduction in arrhythmic states.

Abstract 395: A Synonymous Coding SNP Alters SCN5A Regulation by miR-24 and Associates With Non-Arrhythmic Death in Heart Failure

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Xiaoming Zhang ◽  
Jin-Young Yoon ◽  
Michael Morley ◽  
Patrick Breheny ◽  
Heather Bloom ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Clinical Signs ◽  
Heart Rhythm ◽  
Coding Sequence ◽  
Reduced Ejection Fraction ◽  
Arrhythmic Death ◽  
And Function ◽  
Myocardial Gene Expression

Mutations disrupting SCN5A coding sequence cause inherited arrhythmias and cardiomyopathy, and SNPs linked to SCN5A splicing, localization and function associate with heart failure-related sudden cardiac death. However, the clinical relevance of SNPs that modulate SCN5A expression levels remains understudied. Recently, we generated a transcriptome-wide map of microRNA (miR) binding sites in human heart and evaluated their interface with polymorphisms. Among >500 common SNPs residing within miR target regions, we identified a synonymous SNP (rs1805126) adjacent to a miR-24 site within SCN5A coding sequence. This SNP is known to reproducibly associate with heart rhythm measurements, but is not considered to be “causal”. Here, we show that miR-24 potently suppresses SCN5A and that rs1805126 modulates this regulation. In further exploring the clinical significance of this, we found that rs1805126 minor allele homozygosity associates with decreased cardiac SCN5A expression and increased mortality in heart failure patients. Unexpectedly, this risk was not linked with arrhythmic sudden cardiac death, but rather, with clinical signs of worsening heart failure (e.g. reduced ejection fraction) and myocardial gene expression changes related to bioenergetics, inflammation and extracellular remodeling. Together, these data attribute a molecular mechanism to this firmly-established GWAS SNP and highlight a novel and surprising link between common variations in SCN5A expression and non-arrhythmic death in heart failure.

Development of the cardiac conduction system

ESC CardioMed ◽  
2018 ◽  
pp. 49-52
Author(s):  
Jan Hendrik van Weerd ◽  
Vincent M. Christoffels
Keyword(s):  
Regulatory Networks ◽  
Atrioventricular Node ◽  
Ventricular Myocardium ◽  
Conduction System ◽  
Cardiac Conduction ◽  
Cardiac Conduction System ◽  
Cellular Mechanisms ◽  
Fibre Network ◽  
Electrical Impulses ◽  
And Function

The contraction of the heart is orchestrated by the components of the cardiac conduction system (CCS), which initiate and propagate the electrical impulses to coordinately activate the cardiac chambers. In the adult heart, the impulse is generated in the sinoatrial node and activates the atrial myocardium. Slow conduction of the impulse through the atrioventricular node allows for emptying of the atria and filling of the ventricles prior to ventricular contraction. Subsequent fast conduction through the atrioventricular bundle, bundle branches, and Purkinje fibre network activates the ventricular myocardium and causes the ventricles to contract. The development and function of the CCS involves complex regulatory networks of transcription factors acting in stage-, tissue-, and dose-dependent manners. Disrupted function or expression of these factors might lead to impaired development or function of the CCS components, associated with heart failure and sudden death. It is therefore crucial to understand the molecular and cellular mechanisms controlling the complex regulation of CCS development. This chapter summarizes current insight in the development and function of the different compartments of the CCS, and discusses the transcriptional networks underlying these processes.

Development of the cardiac conduction system

ESC CardioMed ◽  
2018 ◽  
pp. 49-52
Author(s):  
Jan Hendrik van Weerd ◽  
Vincent M. Christoffels
Keyword(s):  
Regulatory Networks ◽  
Atrioventricular Node ◽  
Ventricular Myocardium ◽  
Conduction System ◽  
Cardiac Conduction ◽  
Cardiac Conduction System ◽  
Cellular Mechanisms ◽  
Fibre Network ◽  
Electrical Impulses ◽  
And Function

The contraction of the heart is orchestrated by the components of the cardiac conduction system (CCS), which initiate and propagate the electrical impulses to coordinately activate the cardiac chambers. In the adult heart, the impulse is generated in the sinoatrial node and activates the atrial myocardium. Slow conduction of the impulse through the atrioventricular node allows for emptying of the atria and filling of the ventricles prior to ventricular contraction. Subsequent fast conduction through the atrioventricular bundle, bundle branches, and Purkinje fibre network activates the ventricular myocardium and causes the ventricles to contract. The development and function of the CCS involves complex regulatory networks of transcription factors acting in stage-, tissue-, and dose-dependent manners. Disrupted function or expression of these factors might lead to impaired development or function of the CCS components, associated with heart failure and sudden death. It is therefore crucial to understand the molecular and cellular mechanisms controlling the complex regulation of CCS development. This chapter summarizes current insight in the development and function of the different compartments of the CCS, and discusses the transcriptional networks underlying these processes.

scholarly journals Cardiomyocyte Expression of ZO-1 Is Essential for Normal Atrioventricular Conduction but Does Not Alter Ventricular Function

2020 ◽  
Vol 127 (2) ◽  
pp. 284-297 ◽  
Author(s):  
Jianlin Zhang ◽  
Kevin P. Vincent ◽  
Angela K. Peter ◽  
Matthew Klos ◽  
Hongqiang Cheng ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Optical Mapping ◽  
Physiological Role ◽  
Cardiac Conduction ◽  
Scaffolding Protein ◽  
Surface Ecg ◽  
Associated Proteins ◽  
And Function ◽  
Nodal Tissue ◽  
Intact Heart

Rationale: ZO-1 (Zonula occludens-1), a plasma membrane-associated scaffolding protein regulates signal transduction, transcription, and cellular communication. Global deletion of ZO-1 in the mouse is lethal by embryonic day 11.5. The function of ZO-1 in cardiac myocytes (CM) is largely unknown. Objective: To determine the function of CM ZO-1 in the intact heart, given its binding to other CM proteins that have been shown instrumental in normal cardiac conduction and function. Methods and Results: We generated ZO-1 CM-specific knockout (KO) mice using α-Myosin Heavy Chain-nuclear Cre (ZO-1cKO) and investigated physiological and electrophysiological function by echocardiography, surface ECG and conscious telemetry, intracardiac electrograms and pacing, and optical mapping studies. ZO-1cKO mice were viable, had normal Mendelian ratios, and had a normal lifespan. Ventricular morphometry and function were not significantly different between the ZO-1cKO versus control (CTL) mice, basally in young or aged mice, or even when hearts were subjected to hemodynamic loading. Atrial mass was increased in ZO-1cKO. Electrophysiological and optical mapping studies indicated high-grade atrioventricular (A-V) block in ZO-1cKO comparing to CTL hearts. While ZO-1-associated proteins such as vinculin, connexin 43, N-cadherin, and α-catenin showed no significant change with the loss of ZO-1, Connexin-45 and Coxsackie-adenovirus (CAR) proteins were reduced in atria of ZO-1cKO. Further, with loss of ZO-1, ZO-2 protein was increased significantly in ventricular CM in a presumed compensatory manner but was still not detected in the AV nodal myocytes. Importantly, the expression of the sodium channel protein NaV1.5 was altered in AV nodal cells of the ZO-1cKO versus CTL. Conclusions: ZO-1 protein has a unique physiological role in cardiac nodal tissue. This is in alignment with its known interaction with CAR and Cx45, and a new function in regulating the expression of NaV1.5 in AV node. Uniquely, ZO-1 is dispensable for function of the working myocardium.

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