Dynamical behavior of cardiac conduction system under external disturbances: simulation based on microcontroller technology

2022 ◽  
Author(s):  
Rodrigue Fonkou ◽  
Patrick Louodop ◽  
Pierre Kisito Talla

Abstract The heart rhythm is one of the most interesting aspects of the dynamic behavior of biological systems. Understanding heart rhythms is essential in the dynamic analysis of the heart. Each type of dynamic behaviour can describe normal or pathological physiology. The heart is made up of nodes ranging from SA node (natural pacemaker) to Purkinje fibers. The electric current originates in the sinus node and travels through the heart until it reaches the Purkinje fibers, causing after its passage through each of the nodes a heartbeat thus constituting the electrocardiogram (ECG). Since the origin of the electric current is the sinus node, in this article we study numerically and experimentally by microcontroller the influence of the sinus node on the propagation of electric current through the heart. A study of the sinus node in its autonomous state shows us that in their coupled state, the nodes of the heart qualitatively reproduce the time series of the action potential of this latter, which leads to the recording of the ECG. A study when the sinus node is subjected to periodic pulsed excitation E 1(t) = kP(t), assumed to come from blood pressure, with P(t) the blood pressure, shows that for some selected frequencies, it is found that the nodes of the heart and the ECG exhibit responses having the same shape and the same frequencies as those of the pulsatile blood pressure. This suggests the possibility of using such a conversion and excitation mechanism to replicate the functioning of cardiac conduction system. The chaotic analysis of the sinus node subjected to a sinusoidal type disturbance (E 0sin(ωt)) is also presented, it shows that in its chaotic state, the nodes of the heart, as well as the ECG, provide very high frequency signals. This requires the control of the sinus node (natural pacemaker) in such a situation

1992 ◽  
Vol 2 (2) ◽  
pp. 196-199
Author(s):  
Louis Tsun-cheung Chow ◽  
Wing-Hing Chow

SummaryWe studied the cardiac conduction system in a case of Hurler syndrome. There was dense fibrosis of the supporting matrix of the sinus node and accumulation of mucopolysaccharide in the nodal cells. The bundle branches showed prominent hydropic degeneration, being encased and punctuated by dense fibrous tissue. These changes in the conduction system may predispose to the development of arrhythmias, accounting for the sudden deaths in Hurler syndrome.


2014 ◽  
pp. S9-S18 ◽  
Author(s):  
D. SEDMERA ◽  
R. G. GOURDIE

Purkinje fibers were the first discovered component of the cardiac conduction system. Originally described in sheep in 1839 as pale subendocardial cells, they were found to be present, although with different morphology, in all mammalian and avian hearts. Here we review differences in their appearance and extent in different species, summarize the current state of knowledge of their function, and provide an update on markers for these cells. Special emphasis is given to popular model species and human anatomy.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
L Stuart ◽  
I Y Oh ◽  
Y Wang ◽  
S Nakao ◽  
T Starborg ◽  
...  

Abstract Background and purpose Heart failure (HF) is characterised by generalised dysfunction of the cardiac conduction system (CCS). Ion channel and structural remodelling in the CCS have been widely demonstrated in animal models of cardiovascular disease. As Purkinje fibres (PFs) are minute strands of tissue, little is known about their ultrastructure and remodelling in disease. Furthermore, given the role for microRNAs (miRs) in CCS molecular remodelling, we aimed to develop a tissue specific method for delivering therapeutic transgenes, such as miR sponges. Methods New Zealand rabbits were used for PF ultrastructural studies. HF was induced via pressure and volume overload. Free running PFs were processed for serial block face scanning electron microscopy (SBF-SEM). Manual contrast-based segmentation techniques were used on IMOD software to determine the 3D cellular ultrastructure. To target transgene expression to the CCS, adenoviral plasmids were cloned expressing a GFP reporter gene. GFP transcription was placed under control of the KCNE1 promoter, a K+ channel subunit expressed throughout the CCS, or the HCN4 promoter, a key pacemaker ion channel, to target the sinus node. The strong ubiquitous cytomegalovirus (CMV) promoter was used as a positive control. Adenovirus was produced using via transfection into the 293A cell line for viral packaging and amplification. Results Purkinje cells (PCs) formed a central core within PFs, encapsulated by an extensive collagen matrix. PCs were uninucleated and spindle shaped with an irregular membrane. Gap junctions were abundant and distributed along the lateral surface of cells, and there was a trend towards decreased expression in HF (p=0.0526, n=3 cells analysed per group). Hypertrophy and nuclear membrane breakdown were evident in HF PCs, the latter facilitating mitochondrial entry. Using the CMV-GFP adenoviral construct, abundant GFP expression was conferred in ex vivo sinus node tissue, isolated sinus node myocytes, and neonatal ventricular rat cardiomyocytes (NRCMs). The KCNE1 promoter conferred relatively high GFP expression in NRCMs, greater than that from the HCN4 promoter. In isolated sinus node myocytes, the HCN4 promoter conferred greater transgene expression than in NRCMs. In ex vivo sinus node tissue, only the CMV construct was capable of driving significant GFP expression. Notably, expression was largely confined to the sinus node, with only sparse expression detected in the surrounding atrial muscle. Conclusions SBF-SEM revealed ultrastructure of free running PFs in situ, and uncovered novel structural changes in HF that are likely to be pro-arrhythmic. Preliminary data suggest that 1.2 kb and 0.8 kb fragments of the HCN4 promoter are capable of driving sinus node specific transgene expression. Further tests are warranted to confirm the utility of these promoters to express therapeutic transgenes, such as miR sponges to competitively inhibit miR activity in vitro and in vivo. Acknowledgement/Funding The British Heart Foundation


1997 ◽  
Vol 80 (5) ◽  
pp. 665-672 ◽  
Author(s):  
Tatiana Alyonycheva ◽  
Leona Cohen-Gould ◽  
Christiana Siewert ◽  
Donald A. Fischman ◽  
Takashi Mikawa

2013 ◽  
Vol 2013 ◽  
pp. 1-6
Author(s):  
D. Mandrioli ◽  
F. Ceci ◽  
T. Balbi ◽  
C. Ghimenton ◽  
G. Pierini

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.


2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Paria Parto ◽  
Mina Tadjalli ◽  
S. Reza Ghazi ◽  
Mohammad Ali Salamat

Purkinje fibers or Purkinje cardiomyocytes are part of the whole complex of the cardiac conduction system, which is today classified as specific heart muscle tissue responsible for the generation of the heart impulses. From the point of view of their distribution, structure and ultrastructural composition of the cardiac conduction system in the ostrich heart were studied by light and electron microscopy. These cells were distributed in cardiac conducting system including SA node, AV node, His bundle and branches as well as endocardium, pericardium, myocardium around the coronary arteries, moderator bands, white fibrous sheet in right atrium, and left septal attachment of AV valve. The great part of the Purkinje fiber is composed of clear, structure less sarcoplasm, and the myofibrils tend to be confined to a thin ring around the periphery of the cells. They have one or more large nuclei centrally located within the fiber. Ultrastructurally, they are easily distinguished. The main distinction feature is the lack of electron density and having a light appearance, due to the absence of organized myofibrils. P-cells usually have two nuclei with a mass of short, delicate microfilaments scattered randomly in the cytoplasm; they contain short sarcomeres and myofibrillar insertion plaque. They do not have T-tubules.


Author(s):  
Nataliia Naumova ◽  
Laura Iop

Heart rhythm disturbances caused by different etiologies may affect pediatric and adult patients with life-threatening consequences. When pharmacological therapy is ineffective in treating the disturbances, the implantation of electronic devices to control and/or restore normal heart pacing is a unique clinical management option. Although these artificial devices are life-saving, they display many limitations; not least, they do not have any capability to adapt to somatic growth or respond to neuroautonomic physiological changes. A biological pacemaker could offer a new clinical solution for restoring heart rhythms in the conditions of disorder in the cardiac conduction system. Several experimental approaches, such as cell-based, gene-based approaches, and the combination of both, for the generation of biological pacemakers are currently established and widely studied. Pacemaker bioengineering is also emerging as a technology to regenerate nodal tissues. This review analyzes and summarizes the strategies applied so far for the development of biological pacemakers, and discusses current translational challenges toward the first-in-human clinical application.


Development ◽  
1995 ◽  
Vol 121 (5) ◽  
pp. 1423-1431 ◽  
Author(s):  
R.G. Gourdie ◽  
T. Mima ◽  
R.P. Thompson ◽  
T. Mikawa

The rhythmic contraction of the vertebrate heart is dependent on organized propagation of electrical excitation through the cardiac conduction system. Because both muscle- and neuron-specific genes are co-expressed in cells forming myocardial conduction tissues, two origins, myogenic and neural, have been suggested for this specialized tissue. Using replication-defective retroviruses, encoding recombinant beta-galactosidase (beta-gal), we have analyzed cell lineage for Purkinje fibers (i.e., the peripheral elements of the conduction system) in the chick heart. Functioning myocyte progenitors were virally tagged at embryonic day 3 of incubation (E3). Clonal beta-gal+ populations of cells, derived from myocytes infected at E3 were examined at 14 (E14) and 18 (E18) days of embryonic incubation. Here, we report that a subset of clonally related myocytes differentiates into conductile Purkinje fibers, invariably in close spatial association with forming coronary arterial blood vessels. These beta-gal+ myogenic clones, containing both working myocytes and Purkinje fibers, did not incorporate cells contributing to tissues of the central conduction system (e.g. atrioventricular ring and bundles). In quantitative analyses, we found that whereas the number of beta-gal+ myocyte nuclei per clone more than doubled between E14 and E18, the number of beta-gal+ Purkinje fiber nuclei remained constant.(ABSTRACT TRUNCATED AT 250 WORDS)


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Hayashi ◽  
N Fujino ◽  
H Furusho ◽  
S Usui ◽  
K Sakata ◽  
...  

Abstract Background The genetic bases of cardiac conduction-system disease (CCSD) range from ion channelopathies to mutations in many other genes. Genome-wide association studies have shown common variants in SCN10A influence cardiac conduction. However, it has not yet to be determined whether vulnerability to CCSD is associated with rare coding sequence variation in the SCN10A gene. Purpose We sought to determine the clinical impact of rare variants in SCN10A in patients with CCSD and classified the variants according to the 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines. Methods We performed screening for rare variants (minor allele frequency ≤0.001) in SCN10A in CCSD patients with an onset at a young age under 65 or those who had a family history of pacemaker implantation (PMI) (n=40; 18 female; mean age, 41±18 years). We transiently expressed engineered variants in ND 7/23 cells, and conducted whole-cell voltage clamp experiments to clarify the functional properties of the Nav1.8 current. Results We identified nine rare variants in SCN10A in 7 patients. Two patients were carriers of two rare variants in SCN10A and 5 were carriers of one rare variant in SCN10A. Four patients were affected with sinus node dysfunction, 1 were atrioventricular block, and 2 were both dysfunctions. We performed electrophysiological study for 8 of 9 rare variants. It demonstrated that 2 rare variants showed gain-of-function, and 3 rare variants showed loss-of-function. We finally determined 5 likely pathogenic variants in SCN10A in 5 patients (12.5%) according to the ACMG standards and guidelines. All 5 patients underwent a pacemaker implantation at an average age of 43±16. Conclusions These results demonstrate that SCN10A variants play a pivotal role in enhanced susceptibility of CCSD. We suggest the importance for screening SCN10A variants in clinical settings. Funding Acknowledgement Type of funding source: None


2019 ◽  
Vol 8 (3) ◽  
pp. 96-103 ◽  
Author(s):  
I. V. Plotnikova ◽  
L. I. Svintsova ◽  
O. Yu. Dzhaffarova

This review discusses the role of autoimmune mechanisms in the development of heart rhythm disturbances and conduction disorders of various origins. The search was performed using PubMed, Medline and Google Scholar. Specific cardiovascular diseases (dilated cardiomyopathy, myocarditis, conduction disorders) developing in childhood and adolescence are associated with an increase in titer to intracellular proteins specific to myocardiocytes and cells of the cardiac conduction system. Candidate autoantibodies markers for autoimmune response have been selected. The rationale for analyzing the immune status of heart rhythm disturbances in children and adolescents has been provided.


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