Development of the cardiac conduction system

Cellular Mechanisms ◽

Fibre Network ◽

Electrical Impulses ◽

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.

Sudden Unexpected Death Associated with Arrhythmogenic Cardiomyopathy: Study of the Cardiac Conduction System

Diagnostics ◽

10.3390/diagnostics11081323 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1323

Author(s):

Giulia Ottaviani ◽

Graziella Alfonsi ◽

Simone G. Ramos ◽

L. Maximilian Buja

Keyword(s):

Fibromuscular Dysplasia ◽

Ventricular Myocardium ◽

Conduction System ◽

Cardiac Conduction ◽

Future Research ◽

Arrhythmogenic Cardiomyopathy ◽

Unexpected Death ◽

The Past ◽

The Right

A retrospective study was conducted on pathologically diagnosed arrhythmogenic cardiomyopathy (ACM) from consecutive cases over the past 34 years (n = 1109). The anatomo-pathological analyses were performed on 23 hearts diagnosed as ACM (2.07%) from a series of 1109 suspected cases, while histopathological data of cardiac conduction system (CCS) were available for 15 out of 23 cases. The CCS was removed in two blocks, containing the following structures: Sino-atrial node (SAN), atrio-ventricular junction (AVJ) including the atrio-ventricular node (AVN), the His bundle (HB), the bifurcation (BIF), the left bundle branch (LBB) and the right bundle branch (RBB). The ACM cases consisted of 20 (86.96%) sudden unexpected cardiac death (SUCD) and 3 (13.04%) native explanted hearts; 16 (69.56%) were males and 7 (30.44%) were females, ranging in age from 5 to 65 (mean age ± SD, 36.13 ± 16.06) years. The following anomalies of the CCS, displayed as percentages of the 15 ACM SUCD cases in which the CCS has been fully analyzed, have been detected: Hypoplasia of SAN (80%) and/or AVJ (86.67%) due to fatty-fibrous involvement, AVJ dispersion and/or septation (46.67%), central fibrous body (CFB) hypoplasia (33.33%), fibromuscular dysplasia of SAN (20%) and/or AVN (26.67%) arteries, hemorrhage and infarct-like lesions of CCS (13.33%), islands of conduction tissue in CFB (13.33%), Mahaim fibers (13.33%), LBB block by fibrosis (13.33%), AVN tongue (13.33%), HB duplicity (6.67%%), CFB cartilaginous meta-hyperplasia (6.67%), and right sided HB (6.67%). Arrhythmias are the hallmark of ACM, not only from the fatty-fibrous disruption of the ventricular myocardium that accounts for reentrant ventricular tachycardia, but also from the fatty-fibrous involvement of CCS itself. Future research should focus on application of these knowledge on CCS anomalies to be added to diagnostic criteria or at least to be useful to detect the patients with higher sudden death risks.

The formation and function of the cardiac conduction system

Development ◽

10.1242/dev.124883 ◽

2016 ◽

Vol 143 (2) ◽

pp. 197-210 ◽

Cited By ~ 85

Author(s):

Jan Hendrik van Weerd ◽

Vincent M. Christoffels

Keyword(s):

Conduction System ◽

Cardiac Conduction ◽

SEM, TEM, and IHC Analysis of the Sinus Node and Its Implications for the Cardiac Conduction System

Anatomy Research International ◽

10.1155/2013/961459 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6

Author(s):

D. Mandrioli ◽

F. Ceci ◽

T. Balbi ◽

C. Ghimenton ◽

G. Pierini

Keyword(s):

Electron Microscopy ◽

Sinus Node ◽

Atrioventricular Node ◽

Definite Description ◽

Conduction System ◽

Cardiac Conduction ◽

Ordered Structure ◽

Healthy Individuals ◽

Optical And Electron Microscopy

More than 100 years after the discovery of the sinus node (SN) by Keith and Flack, the function and structure of the SN have not been completely established yet. The anatomic architecture of the SN has often been described as devoid of an organized structure; the origin of the sinus impulse is still a matter of debate, and a definite description of the long postulated internodal specialized tract conducting the impulse from the SN to the atrioventricular node (AVN) is still missing. In our previously published study, we proposed a morphologically ordered structure for the SN. As a confirmation of what was presented then, we have added the results of additional observations regarding the structural particularities of the SN. We investigated the morphology of the sinus node in the human hearts of healthy individuals using histochemical, immunohistochemical, optical, and electron microscopy (SEM, TEM). Our results confirmed that the SN presents a previously unseen highly organized architecture.

P5693Desmin is essential for the structure and function of the cardiac conduction system; implications for arrhythmogenesis

European Heart Journal ◽

10.1093/eurheartj/ehy566.p5693 ◽

2018 ◽

Vol 39 (suppl_1) ◽

Author(s):

N Athanasiadis ◽

M Mavroidis ◽

P Rigas ◽

I Kostavasili ◽

I Kloukina ◽

...

Keyword(s):

Structure And Function ◽

Conduction System ◽

Cardiac Conduction ◽

Development and Function of the Cardiac Conduction System in Health and Disease

Journal of Cardiovascular Development and Disease ◽

10.3390/jcdd4020007 ◽

2017 ◽

Vol 4 (2) ◽

pp. 7 ◽

Cited By ~ 12

Author(s):

◽

Keyword(s):

Conduction System ◽

Cardiac Conduction ◽

Health And Disease ◽

Simulation of Heartbeat Dynamics: A Nonlinear Model

International Journal of Bifurcation and Chaos ◽

10.1142/s0218127498001418 ◽

1998 ◽

Vol 08 (08) ◽

pp. 1725-1731 ◽

Cited By ~ 11

Author(s):

Maria G. Signorini ◽

Diego di Bernardo

Keyword(s):

Mathematical Modeling ◽

Simple Structure ◽

Nonlinear Differential Equations ◽

Atrioventricular Node ◽

Nonlinear Oscillators ◽

Conduction System ◽

Cardiac Conduction ◽

Real Situation ◽

Cardiac Dynamics

The mathematical modeling of biological systems has proven to be a valuable tool by allowing experiments which would otherwise be unfeasible in a real situation. In this work we propose a system of nonlinear differential equations describing the macroscopic behavior of the cardiac conduction system. The model describes the interactoin between the SinoAtrial and AtrioVentricular node. Its very simple structure consists of two nonlinear oscillators resistively coupled. The numerical analysis detects different kinds of bifurcations whose pathophysiological meanings are discussed. Moreover, the model is able to classify different pathologies, such as several classes of arrhythmic events, as well as to suggest hypothesis on the mechanisms that induce them. These results also show that the mechanisms generating the heartbeat obey complex laws. The model provides a wuite complete description of different pathological phenomena and its simplicity can be exploited for further studies on the control of cardiac dynamics.

Measurement of cAMP in the cardiac conduction system of rats.

Journal of Histochemistry & Cytochemistry ◽

10.1177/43.6.7769230 ◽

1995 ◽

Vol 43 (6) ◽

pp. 601-605 ◽

Cited By ~ 4

Author(s):

A Sugiyama ◽

S McKnite ◽

P Wiegn ◽

K G Lurie

Keyword(s):

Atrioventricular Node ◽

Conduction System ◽

Cardiac Conduction ◽

Camp Production ◽

Adrenergic Stimulation ◽

Beta Adrenergic ◽

His Bundle ◽

Freeze Dried ◽

Camp Levels

To characterize differences in regional cAMP production in the cardiac conduction system, 18 rats were anesthetized with pentobarbital (65 mg/kg IP) and randomized into a control (n = 9) and a stimulated group (n = 9). The stimulated group received aminophylline (20 mg/kg SC) and isoproterenol (16 micrograms/kg SC). The concentration of cAMP in freeze-dried, micro dissected pieces (1-3 micrograms) of cardiac tissue was measured using a new microanalytical method. The cAMP contents in right atrium, atrioventricular node, His bundle, and left ventricle (fmol/microgram dry weight, mean +/- SE) were 38.9 +/- 2.5, 39.0 +/- 4.3, 46.4 +/- 6.1, and 41.4 +/- 3.3 in controls and 72.9 +/- 6.7, 86.1 +/- 2.9, 115.0 +/- 11.5, and 79.5 +/- 7.3 in the stimulated group, respectively. Basal cAMP levels were similar throughout the heart, whereas isoproterenol increased cAMP levels in all regions (p < 0.01). Furthermore, cAMP levels in His bundle, after isoproterenol, were higher than in any other region (p < 0.05). These results demonstrate that: (a) cAMP can be measured in discrete portions of the cardiac conduction system; (b) there are significant regional differences of beta-adrenergic control in the cardiac conduction system; and (c) cAMP production after beta-adrenergic stimulation was lower than expected in the AV nodal region, based on previously described beta-adrenoceptor density measurements.

Tbx3-Mediated Regulation of Cardiac Conduction System Development and Function: Potential Contributions of Alternative RNA Processing

Pediatric Cardiology ◽

10.1007/s00246-019-02166-4 ◽

2019 ◽

Vol 40 (7) ◽

pp. 1388-1400

Author(s):

Brian P. Delisle ◽

Yao Yu ◽

Pavan Puvvula ◽

Allison R. Hall ◽

Chad Huff ◽

...

Keyword(s):

Rna Processing ◽

System Development ◽

Conduction System ◽

Cardiac Conduction ◽

And Function ◽

Function Potential

Abstract 1462: Lineage Analysis of Mesp1 Expressing Cells in Cardiac Conduction System

Circulation ◽

10.1161/circ.118.suppl_18.s_330-a ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Reza Rafie ◽

Amir R Hajrasouliha ◽

Sina Tavakoli ◽

Kamal Kotak ◽

Mohammad Pashmforoush

Keyword(s):

Sinoatrial Node ◽

Atrioventricular Node ◽

Conduction System ◽

Cardiac Conduction ◽

Transgenic Mouse Line ◽

His Bundle ◽

Reporter Mice ◽

A Minor ◽

Lineage Analysis

Mesp1 is the earliest transcription factor detected in cardiac precursor cells considered to play a key role in their early specification. The lineage analysis, using Mesp1- Cre transgenic mouse line, has shown that there is a minor contribution of Mesp1 non-expressing cells to the formation of ventricular conduction system. The purpose of the present study is to evaluate the contribution of Mesp1 -expressing and non-expressing cells to the development of sinoatrial node, atrioventricular node and His bundle in embryonic, neonatal and adult heart. In this study, the contribution of Mesp1 -expressing cells was evaluated by a lineage analysis using the cross of Mesp1 -Cre and ROSA26R reporter mice. Different components of the cardiac conduction system were identified by a combination of histological (hematoxylin/eosin), acetylcholinesterase, and immunofluorescent stainings for specific markers (HCN4 and connexin40). Sinoatrial and atrioventricular nodes as well as His bundle are derived almost exclusively from Mesp1- expressing cells as evident by β-gal activity. The contribution of Mesp1 non-expressing cells becomes prominent, though still less than Mesp1 -expressing cells, in the distal components of cardiac conduction system (i.e. bundle branches). This pattern was consistent in embryonic and neonatal stages as well as adult hearts. Unlike the distal components of cardiac conduction system, which is composed of a mixed population of Mesp1 -expressing and non-expressing cells, sinoatrial node, atrioventricular node and His bundle are derived almost exclusively from Mesp1 -expressing cells.