Cardiac electrophysiology

ESC CardioMed ◽  
2018 ◽  
pp. 115-120
Author(s):  
Marek Malik

Cardiac electrophysiology involves voltage gradients across myocardial cells and their changes during heartbeat cycles. These processes are maintained by ion exchanges across cellular membranes. Their character and dynamics vary for different types of myocytes as well as different layers and strata of cardiac walls. Electrical changes of the cellular membranes of a cell influence neighbouring cells. Electrical excitation that precedes cardiac contraction is propagated throughout the heart in this way, forming the so-called depolarization waveform. The processes of cellular electrical recovery during which the cellular membranes are recharged for the next cardiac cycle do not follow the same path and sequence as the excitation waveform. These recovery processes do not depend on cell-to-cell signal transmission but even during electrical recovery, neighbouring cells influence each other by means of the so-called electrotonic interactions. Abnormalities in electrical excitation due to anatomical blocks and/or functional barriers as well as heterogeneity of the electrical recovery across myocardium may lead to self-perpetuating excitation processes that are the basis of tachyarrhythmias.

2015 ◽  
Vol 1 (1) ◽  
pp. 413-417
Author(s):  
Eike M. Wülfers ◽  
Zhasur Zhamoliddinov ◽  
Olaf Dössel ◽  
Gunnar Seemann

AbstractUsing OpenCL, we developed a cross-platform software to compute electrical excitation conduction in cardiac tissue. OpenCL allowed the software to run parallelized and on different computing devices (e.g., CPUs and GPUs). We used the macroscopic mono-domain model for excitation conduction and an atrial myocyte model by Courtemanche et al. for ionic currents. On a CPU with 12 HyperThreading-enabled Intel Xeon 2.7 GHz cores, we achieved a speed-up of simulations by a factor of 1.6 against existing software that uses OpenMPI. On two high-end AMD FirePro D700 GPUs the OpenCL software ran 2.4 times faster than the OpenMPI implementation. The more nodes the discretized simulation domain contained, the higher speed-ups were achieved.


1989 ◽  
Vol 9 (1) ◽  
pp. 109-115
Author(s):  
J C Ruiz ◽  
K H Choi ◽  
D D von Hoff ◽  
I B Roninson ◽  
G M Wahl

Gene amplification in human tumor cells is frequently mediated by extrachromosomal elements (e.g., double minute chromosomes [DMs]). Recent experiments have shown that DMs can be formed from smaller, submicroscopic circular precursors referred to as episomes (S. M. Carroll, M. L. DeRose, P. Gaudray, C. M. Moore, D. R. Needham-Vandevanter, D. D. Von Hoff and G. M. Wahl, Mol. Biol. 8:1525-1533, 1988). To investigate whether episomes are generally involved as intermediates in gene amplification, we determined whether they mediate the amplification of the mdr1 gene, which when overexpressed engenders cross resistance to multiple lipophilic drugs. A variety of methods including electrophoresis of undigested DNAs in high-voltage gradients, NotI digestion, and production of double-strand breaks by gamma irradiation were used to distinguish between mdr1 sequences amplified on submicroscopic circular molecules and those amplified within DMs or chromosomal DNA. The gamma-irradiation procedure provides a new method for detecting and determining the size of circular molecules from 50 kilobases (kb) to greater than 1,000 kb. These methods revealed that some of the amplified mdr1 genes in vinblastine-resistant KB-V1 cells are contained in supercoiled circular molecules of approximately 600 and approximately 750 kb. Analysis of the replication of these molecules by a Meselson-Stahl density shift experiment demonstrated that they replicate approximately once in a cell cycle. The data lend further support to a model for gene amplification in which DMs are generally formed from smaller, autonomously replicating precursors.


1989 ◽  
Vol 9 (1) ◽  
pp. 109-115 ◽  
Author(s):  
J C Ruiz ◽  
K H Choi ◽  
D D von Hoff ◽  
I B Roninson ◽  
G M Wahl

Gene amplification in human tumor cells is frequently mediated by extrachromosomal elements (e.g., double minute chromosomes [DMs]). Recent experiments have shown that DMs can be formed from smaller, submicroscopic circular precursors referred to as episomes (S. M. Carroll, M. L. DeRose, P. Gaudray, C. M. Moore, D. R. Needham-Vandevanter, D. D. Von Hoff and G. M. Wahl, Mol. Biol. 8:1525-1533, 1988). To investigate whether episomes are generally involved as intermediates in gene amplification, we determined whether they mediate the amplification of the mdr1 gene, which when overexpressed engenders cross resistance to multiple lipophilic drugs. A variety of methods including electrophoresis of undigested DNAs in high-voltage gradients, NotI digestion, and production of double-strand breaks by gamma irradiation were used to distinguish between mdr1 sequences amplified on submicroscopic circular molecules and those amplified within DMs or chromosomal DNA. The gamma-irradiation procedure provides a new method for detecting and determining the size of circular molecules from 50 kilobases (kb) to greater than 1,000 kb. These methods revealed that some of the amplified mdr1 genes in vinblastine-resistant KB-V1 cells are contained in supercoiled circular molecules of approximately 600 and approximately 750 kb. Analysis of the replication of these molecules by a Meselson-Stahl density shift experiment demonstrated that they replicate approximately once in a cell cycle. The data lend further support to a model for gene amplification in which DMs are generally formed from smaller, autonomously replicating precursors.


Author(s):  
Shigeo Wada ◽  
Masatsugu Soga ◽  
Yoshihiro Ujihara ◽  
Masanori Nakamura ◽  
Kenichiro Koshiyama ◽  
...  

The responses of a tissue to an applied mechanical load are the results of overall responses of cells. Deformation of cells embedded in the tissue is immediately transmitted to internal cytoskeletons that interact extensively and intimately with cellular membranes. Cytoskeletons have been shown to dynamically respond to changes in external mechanical environments such as stretch, which results in various outcomes such as change in cell stiffness, alteration of cell adhesivity to substrates or generation of processes. Taking into account a fact that cytoskeletons are concerned deeply with such cellular remodeling, it is necessary to investigate cytoskeletal deformations when cells are subjected to deformation for gaining mechanical insight into the mechanism of cellular remodeling.


2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Francesca Rusconi ◽  
Michele Miragoli ◽  
Elisa Di Pasquale ◽  
Marcella Rocchetti ◽  
Paola Ceriotti ◽  
...  

Voltage dependent L-Type calcium-channels (LTCCs) are located on the cardiomyocyte membrane and regulate cardiac contraction and rhythmicity. In human pathologies, such as heart failure (HF), decreased inward calcium current (I Ca ) is frequently observed. Here, we generated a mimetic peptide (MP) that targets LTCCs and restores impaired intracellular calcium homeostasis through a novel mechanism. Effective delivery of MP, fused with a cell penetrating peptide, was found to correct Ca2+ alterations in a mouse model of HF, in human cardiomyocytes derived from induced pluripotent stem-cells. These data provide a proof-of-concept supporting a therapeutic role for MP to treat human diseases related to LTCC abnormalities. Category: heart failure biology


Author(s):  
C Herndon ◽  
H C Astley ◽  
T Owerkowicz ◽  
F H Fenton

Abstract Effective cardiac contraction during each heartbeat relies on the coordination of an electrical wave of excitation propagating across the heart. Dynamically induced heterogeneous wave propagation may fracture and initiate reentry-based cardiac arrhythmias, during which fast rotating electrical waves lead to repeated self-excitation that compromises cardiac function and potentially results in sudden cardiac death. Species which function effectively over a large range of heart temperatures must balance the many interacting, temperature-sensitive biochemical processes to maintain normal wave propagation at all temperatures. To investigate how these species avoid dangerous states across temperatures, we optically mapped the electrical activity across the surfaces of alligator (Alligator mississippiensis) hearts at 23 °C and 38 °C over a range of physiological heart rates and compare them with that of rabbits (Oryctolagus cuniculus). We find that unlike rabbits, alligators show minimal changes in wave parameters (action potential duration and conduction velocity) which complement each other to retain similar electrophysiological wavelengths across temperatures and pacing frequencies. The cardiac electrophysiology of rabbits accommodates the high heart rates necessary to sustain an active and endothermic metabolism at the cost of increased risk of cardiac arrhythmia and critical vulnerability to temperature changes, whereas that of alligators allows for effective function over a range of heart temperatures without risk of cardiac electrical arrhythmias such as fibrillation, but is restricted to low heart rates.


2022 ◽  
Vol 12 ◽  
Author(s):  
Nik Nur Syazana Nik Mohamed Kamal ◽  
Wan Nazatul Shima Shahidan

Periodontitis is a chronic inflammatory condition that causes tooth loss by destroying the supporting components of the teeth. In most cases, it is difficult to diagnose early and results in severe phases of the disease. Given their endogenous origins, exosomes, which are rich in peptides, lipids, and nucleic acids, have emerged as a cell-free therapeutic approach with low immunogenicity and increased safety. Because the constituents of exosomes can be reprogrammed depending on disease states, exosomes are increasingly being evaluated to act as potential diagnostic biomarkers for dental disease, including periodontitis. Exosomes also have been demonstrated to be involved in inflammatory signal transmission and periodontitis progression in vitro, indicating that they could be used as therapeutic targets for periodontal regeneration. Nevertheless, a review on the involvement of salivary exosomes in periodontitis in impacting the successful diagnosis and treatment of periodontitis is still lacking in the literature. Thus, this review is intended to scrutinize recent advancements of salivary exosomes in periodontitis treatment. We summarize recent research reports on the emerging roles and characteristics of salivary exosomes, emphasizing the different expressions and changed biological roles of exosomes in periodontitis.


1989 ◽  
Vol 257 (4) ◽  
pp. H1263-H1274
Author(s):  
M. Malik ◽  
A. J. Camm

Wenckebach periodicity is characterized by progressive lengthening of conduction intervals and by progressive shortening of the intervals between conducted excitations. Although different hypotheses have been suggested to explain the mechanisms of Wenckebach periods, no serious proposition explaining both components of the phenomenon has yet been reported. A computer model simulating detailed mechanisms of excitation transmission and electrotonic interactions between neighboring cardiac cells has been employed to investigate the conduction properties of a one-dimensional cable composed of simulated cells. When introducing gradual prolongation of the recovery phase for the elements in the center of the cable and when incorporating physiologically realistic shapes of premature action potential curves into the simulation experiments, the model was able to reproduce all aspects of Wenckebach periodicity. Systematic evaluation with simulation experiments showed that a shorter duration of premature action potentials (i.e., of action potentials resulting from excitation of a cell before it has been fully repolarized) produced shortening of intervals between conducted excitations during a Wenckebach period.


2022 ◽  
Vol 12 ◽  
Author(s):  
Karoline Horgmo Jæger ◽  
Aslak Tveito

The bidomain model is considered to be the gold standard for numerical simulation of the electrophysiology of cardiac tissue. The model provides important insights into the conduction properties of the electrochemical wave traversing the cardiac muscle in every heartbeat. However, in normal resolution, the model represents the average over a large number of cardiomyocytes, and more accurate models based on representations of all individual cells have therefore been introduced in order to gain insight into the conduction properties close to the myocytes. The more accurate model considered here is referred to as the EMI model since both the extracellular space (E), the cell membrane (M) and the intracellular space (I) are explicitly represented in the model. Here, we show that the bidomain model can be derived from the cell-based EMI model and we thus reveal the close relation between the two models, and obtain an indication of the error introduced in the approximation. Also, we present numerical simulations comparing the results of the two models and thereby highlight both similarities and differences between the models. We observe that the deviations between the solutions of the models become larger for larger cell sizes. Furthermore, we observe that the bidomain model provides solutions that are very similar to the EMI model when conductive properties of the tissue are in the normal range, but large deviations are present when the resistance between cardiomyocytes is increased.


Author(s):  
R.J. Barrnett

This subject, is like observing the panorama of a mountain range, magnificent towering peaks, but it doesn't take much duration of observation to recognize that they are still in the process of formation. The mountains consist of approaches, materials and methods and the rocky substance of information has accumulated to such a degree that I find myself concentrating on the foothills in the foreground in order to keep up with the advance; the edifices behind form a wonderous, substantive background. It's a short history for such an accumulation and much of it has been moved by the members of the societies that make up this International Federation. My panel of speakers are here to provide what we hope is an interesting scientific fare, based on the fact that there is a continuum of biological organization from biochemical molecules through macromolecular assemblies and cellular membranes to the cell itself. Indeed, this fact explains the whole range of towering peaks that have emerged progressively during the past 25 years.


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