scholarly journals KEY FACTORS TO THE RATE DEPENDENCE OF EARLY AFTERDEPOLARIZATIONS: A SIMULATION STUDY

2021 ◽  
pp. 2150002
Author(s):  
LIAN JIN ◽  
YANQI HUANG ◽  
HONGLEI ZHU ◽  
ZIHUI GENG ◽  
XIAOMEI WU
Keyword(s):  
Cardiac Tissue ◽  
Rate Dependence ◽  
Ion Concentration ◽  
Delayed Rectifier ◽  
Key Factors ◽  
Early Afterdepolarizations ◽  
Simulation Research ◽  
Delayed Rectifier Potassium Current ◽  
Different Types ◽  
Excitation Period

Early afterdepolarizations (EADs) in cardiac myocytes have been reported to be associated with a series of cardiac arrhythmias. The generation of EADs has a high correlation with the excitation period, leading to repolarization dispersion over the cardiac tissue. However, the mechanism of EAD rate dependence has not been thoroughly revealed. In this study, the simulation approach was used to investigate the mechanism underlying EAD rate dependence. The results indicated that the gating variable of the delayed rectifier potassium current ([Formula: see text]-gate) and the intracellular sodium ion concentration ([Na[Formula: see text]][Formula: see text] were key factors contributing to EAD rate dependence. Also, different mathematical models showed different types of EAD rate dependence, which needs to be considered in the future simulation research related to EADs.

scholarly journals Quantitative comparison of cardiac ventricular myocyte electrophysiology and response to drugs in human and nonhuman species

2012 ◽  
Vol 302 (5) ◽  
pp. H1023-H1030 ◽  
Author(s):  
Thomas O'Hara ◽  
Yoram Rudy
Keyword(s):  
Guinea Pig ◽  
Drug Response ◽  
Cellular Level ◽  
Quantitative Comparison ◽  
Rate Dependence ◽  
Delayed Rectifier ◽  
Adrenergic Stimulation ◽  
Early Afterdepolarizations ◽  
Rate Dependent ◽  
Delayed Rectifier Current

Explanations for arrhythmia mechanisms at the cellular level are usually based on experiments in nonhuman myocytes. However, subtle electrophysiological differences between species may lead to different rhythmic or arrhythmic cellular behaviors and drug response given the nonlinear and highly interactive cellular system. Using detailed and quantitatively accurate mathematical models for human, dog, and guinea pig ventricular action potentials (APs), we simulated and compared cell electrophysiology mechanisms and response to drugs. Under basal conditions (absence of β-adrenergic stimulation), Na+/K+-ATPase changes secondary to Na+ accumulation determined AP rate dependence for human and dog but not for guinea pig where slow delayed rectifier current ( IKs) was the major rate-dependent current. AP prolongation with reduction of rapid delayed rectifier current ( IKr) and IKs (due to mutations or drugs) showed strong species dependence in simulations, as in experiments. For humans, AP prolongation was 80% following IKr block. It was 30% for dog and 20% for guinea pig. Under basal conditions, IKs block was of no consequence for human and dog, but for guinea pig, AP prolongation after IKs block was severe. However, with β-adrenergic stimulation, IKs played an important role in all species, particularly in AP shortening at fast rate. Quantitative comparison of AP repolarization, rate-dependence mechanisms, and drug response in human, dog, and guinea pig revealed major species differences (e.g., susceptibility to arrhythmogenic early afterdepolarizations). Extrapolation from animal to human electrophysiology and drug response requires great caution.

Confocal imaging of calcium in intact ventricular muscle provides a new view of excitation-contraction coupling

1996 ◽  
Vol 54 ◽  
pp. 738-739
Author(s):  
W.G. Wier
Keyword(s):  
Local Control ◽  
Cardiac Tissue ◽  
Cell Function ◽  
Isolated Heart ◽  
Cardiac Cells ◽  
Confocal Imaging ◽  
Ion Concentration ◽  
Heart Cell ◽  
Free Calcium ◽  
Heart Cells

A fundamentally new understanding of cardiac excitation-contraction (E-C) coupling is being developed from recent experimental work using confocal microscopy of single isolated heart cells. In particular, the transient change in intracellular free calcium ion concentration ([Ca2+]i transient) that activates muscle contraction is now viewed as resulting from the spatial and temporal summation of small (∼ 8 μm3), subcellular, stereotyped ‘local [Ca2+]i-transients' or, as they have been called, ‘calcium sparks'. This new understanding may be called ‘local control of E-C coupling'. The relevance to normal heart cell function of ‘local control, theory and the recent confocal data on spontaneous Ca2+ ‘sparks', and on electrically evoked local [Ca2+]i-transients has been unknown however, because the previous studies were all conducted on slack, internally perfused, single, enzymatically dissociated cardiac cells, at room temperature, usually with Cs+ replacing K+, and often in the presence of Ca2-channel blockers. The present work was undertaken to establish whether or not the concepts derived from these studies are in fact relevant to normal cardiac tissue under physiological conditions, by attempting to record local [Ca2+]i-transients, sparks (and Ca2+ waves) in intact, multi-cellular cardiac tissue.

scholarly journals Cardiac Organoids to Model and Heal Heart Failure and Cardiomyopathies

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 563
Author(s):  
Magali Seguret ◽  
Eva Vermersch ◽  
Charlène Jouve ◽  
Jean-Sébastien Hulot
Keyword(s):  
Tissue Engineering ◽  
Drug Testing ◽  
Cardiac Tissue ◽  
Cardiac Tissue Engineering ◽  
Cardiac Cells ◽  
Cardiac Functions ◽  
Different Types ◽  
Recent Developments ◽  
Human Cardiac Tissue ◽  
Key Aspects

Cardiac tissue engineering aims at creating contractile structures that can optimally reproduce the features of human cardiac tissue. These constructs are becoming valuable tools to model some of the cardiac functions, to set preclinical platforms for drug testing, or to alternatively be used as therapies for cardiac repair approaches. Most of the recent developments in cardiac tissue engineering have been made possible by important advances regarding the efficient generation of cardiac cells from pluripotent stem cells and the use of novel biomaterials and microfabrication methods. Different combinations of cells, biomaterials, scaffolds, and geometries are however possible, which results in different types of structures with gradual complexities and abilities to mimic the native cardiac tissue. Here, we intend to cover key aspects of tissue engineering applied to cardiology and the consequent development of cardiac organoids. This review presents various facets of the construction of human cardiac 3D constructs, from the choice of the components to their patterning, the final geometry of generated tissues, and the subsequent readouts and applications to model and treat cardiac diseases.

Involvement of monocytes/macrophages as key factors in the development and progression of cardiovascular diseases

2014 ◽  
Vol 458 (2) ◽  
pp. 187-193 ◽  
Author(s):  
María Fernández-Velasco ◽  
Silvia González-Ramos ◽  
Lisardo Boscá
Keyword(s):  
Myocardial Infarction ◽  
Immune System ◽  
Cardiovascular Diseases ◽  
Cardiac Tissue ◽  
Initial Period ◽  
Cardiac Injury ◽  
Key Factors ◽  
Cardiac Damage ◽  
Inflammatory Profile

Emerging evidence points to the involvement of specialized cells of the immune system as key drivers in the pathophysiology of cardiovascular diseases. Monocytes are an essential cell component of the innate immune system that rapidly mobilize from the bone marrow to wounded tissues where they differentiate into macrophages or dendritic cells and trigger an immune response. In the healthy heart a limited, but near-constant, number of resident macrophages have been detected; however, this number significantly increases during cardiac damage. Shortly after initial cardiac injury, e.g. myocardial infarction, a large number of macrophages harbouring a pro-inflammatory profile (M1) are rapidly recruited to the cardiac tissue, where they contribute to cardiac remodelling. After this initial period, resolution takes place in the wound, and the infiltrated macrophages display a predominant deactivation/pro-resolution profile (M2), promoting cardiac repair by mediating pro-fibrotic responses. In the present review we focus on the role of the immune cells, particularly in the monocyte/macrophage population, in the progression of the major cardiac pathologies myocardial infarction and atherosclerosis.

scholarly journals A New Design of Sydney’s Frontport Check-in System

2021 ◽  
Vol 13 (7) ◽  
pp. 3850
Author(s):  
Ting Liu ◽  
Gabriel Lodewijks
Keyword(s):  
Swot Analysis ◽  
Control Measures ◽  
Key Factors ◽  
Scheme Design ◽  
Different Types ◽  
Baggage Handling ◽  
Loading And Unloading ◽  
The Cost ◽  
Main Engine ◽  
Process Method

This paper proposed a scheme design for Sydney’s frontport check-in system, which completes check-in and baggage drop-off at Sydney’s Circular Quay, and transports the baggage to Sydney Kingsford Smith Airport by waterway, and provided a strengths, weaknesses, opportunities and threats (SWOT) analysis of Sydney’s frontport check-in system. Using the process method of quality management, the frontport check-in process was divided into three sub-processes: baggage consignment, baggage packing and transportation, and airport baggage handling. The eight key elements of each sub-process such as input, output, resources, and methods, etc. were discussed, the key factors influencing the cost of baggage transportation were analyzed, and the cost control measures such as adopting economic speed, reducing fuel consumption of the main engine, improving the ship loading rate, and raising loading and unloading efficiency were proposed. At the same time, two different types of baggage transportation ships and other parameters that affect the cost such as the number of berths, ships, lifting machineries, and the yard area were analyzed and calculated through calculation cases. This scheme is a beneficial addition to the existing in-town check-in system.

Tyrosine-protein kinase Src regulates Kv1.5 channel activity and membrane expression through interaction with the N-terminus of the channel

2020 ◽  
Author(s):  
Taylore Dodd ◽  
Tingzhong Wang ◽  
Shetuan Zhang
Keyword(s):  
Protein Kinase ◽  
Cell Voltage ◽  
Underlying Mechanism ◽  
Delayed Rectifier ◽  
Binding Motif ◽  
Membrane Expression ◽  
Binding Motifs ◽  
Delayed Rectifier Potassium Current ◽  
N Terminus ◽  
Tyrosine Protein Kinase

Kv1.5 is a voltage-gated potassium channel that generates the ultra-rapid delayed rectifier potassium current (IKur) important in the repolarization of the atrial action potential. Malfunction of the Kv1.5 channel often results in atrial fibrillation (AFib). A reduction in Kv1.5 current (IKv1.5) occurs upon activation of the endogenous tyrosine-protein kinase Src. The Src SH3 domain binds to proline-rich motifs located within the N-terminus of Kv1.5. Disruption of these binding motifs has been involved in the development of familial AFib. The mechanism underlying the reduction of IKv1.5 upon Src activation has not yet been established and the relationship between Kv1.5 and Src is poorly understood. Therefore, the present study aims to further elucidate the mechanism behind IKv1.5  reduction. The hypothesis that Src regulates Kv1.5 activity by altering the density of mature membrane-localized channels was tested using whole-cell voltage clamp and Western blot analysis. We demonstrate that Src tonically inhibits Kv1.5 activity and decreases the density of mature membrane-localized channels. Kv1.5 channels possessing mutations within the Src binding motifs were also investigated and it was determined that each binding motif contributes to the Kv1.5-Src relationship, however, the binding of Src to an individual motif is sufficiently effective. Our findings indicate that Src regulates Kv1.5 through an interaction with the N-terminal binding motifs and suggests that the inhibition of forward trafficking may be involved in the underlying mechanism. (Supported by the Heart and Stroke foundation of Canada and The Canadian Institutes of Health Research).

The combination of different open innovations: a longitudinal case study

2019 ◽  
Vol 13 (2) ◽  
pp. 342-362
Author(s):  
Xiaodong Yuan ◽  
Xiaotao Li
Keyword(s):  
New Product Development ◽  
Open Innovation ◽  
Point Of View ◽  
Longitudinal Case Study ◽  
Key Factors ◽  
Content Type ◽  
Strategic Direction ◽  
Different Types ◽  
Innovation Capacity

Purpose The purpose of this paper is to explore how an organization can combine different types of open innovations and what are the key factors that may influence the combination of different open innovations. Design/methodology/approach The basic methodology of this paper is the longitudinal inductive analysis within the conceptual framework of the open innovation proposed by Dahlander and Gann (2010). In this case study of Xiaomi Tech Inc., the open innovation combination is investigated through examining 25 new products created between August 2010 and December 2016 in terms of four general types: acquiring, sourcing, selling and revealing open innovation. Findings In practice, the combination of different types of open innovations can be realized. A firm may combine different open innovations at three levels: a single product level, a related product cluster level and a company level. In addition, different open innovations can be combined in diverse modes. The purpose of combining different types of open innovations is to overcome the disadvantages of each type and to exploit the advantages of all different types. Many factors may affect a firm’s option of how to combine open innovations. At different development stages, a firm may make and implement corresponding strategic direction based on its innovation capacity and internal resource. For a given strategy, the firm needs to create profits and manage intellectual property in the implementation of open innovations. These factors are interacted each other, rather than isolated. Originality/value The findings of this paper are helpful for better understanding how and why an organization can combine different types of open innovations. From a managerial point of view, an organization may combine different types of open innovations to leverage advantages and avoid disadvantages of each certain type of open innovation. An appropriate combination of different open innovations can effectively improve new product development.

scholarly journals Analysis of rail yard and terminal performances

2014 ◽  
Vol 8 (2) ◽  
pp. 178-200 ◽  
Author(s):  
Marin Marinov ◽  
Leonardo Di Giovanni ◽  
Giulia Bellisai ◽  
Julian Clevermann ◽  
Anastasia Mastellou ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Critical Points ◽  
Network Performance ◽  
Logical Consequence ◽  
Time Frame ◽  
Key Factors ◽  
Railway Network ◽  
Rail Infrastructure ◽  
Different Types ◽  
Junction Points

One of the latest trends in the transport field is the increasing interest for the rejuvenation of the railway. It is considered to be a logical consequence of the gradual switch towards a more sustainable future in transports. Terminals and stations are considered to be the junction points between the various lines that constitute the railway network and can simply be described as points of arrival, departure and interchange of passengers or commodities. The most commonly used indicators that measure the level of their performance are time and cost. This study aims at exploring possible improvements that could be implemented to the infrastructure and the operation of terminals and stations in order to increase the efficiency level. Firstly, drawing upon grounded theory about rail infrastructure and terminals, a description is conducted, followed by a comparative analysis of the different types of existing terminals and stations. Secondly, the suggested improvements are presented in accordance with their time frame completion. The main contribution of this study is to illustrate the high significance of terminals, stations and yards, acknowledging them as crucial parts of the railway network, because as characterized and demonstrated in this study, their performance are key factors to the whole network performance, making the identification of their critical points and respective possible solutions, the final objective of this paper. In addition to this, emphasis is given to the need of improving and developing the existing terminal infrastructure and operations.

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