اشترك بالحزمة الذهبية واحصل على وصول غير محدود شمرا أكاديميا
تسجيل مستخدم جديدAn in silico study of electrophysiological parameters that affect the spiral-wave frequency in mathematical models for cardiac tissue
80
0
0.0
(
0
)
اسأل ChatGPT حول البحث
ﻻ يوجد ملخص باللغة العربية
Spiral waves of excitation in cardiac tissue are associated with life-threatening cardiac arrhythmias. It is, therefore, important to study the electrophysiological factors that affect the dynamics of these spiral waves. By using an electrophysiologically detailed mathematical model of a myocyte (cardiac cell), we study the effects of cellular parameters, such as membrane-ion-channel conductances, on the properties of the action-potential (AP) of a myocyte. We then investigate how changes in these properties, specifically the upstroke velocity and the AP duration (APD), affect the frequency $omega$ of a spiral wave in the mathematical model that we use for human-ventricular tissue. We find that an increase (decrease) in this upstroke-velocity or a decrease (increase) in the AP duration increases (decreases) $omega$. We also study how other intercellular factors, such as the fibroblast-myocyte coupling, diffusive coupling strength, and the effective number of neighboring myocytes, modulate $omega$. Finally, we demonstrate how a spiral wave can drift to a region with a high density of fibroblasts. Our results provide a natural explanation for the anchoring of spiral waves in highly fibrotic regions in fibrotic hearts.
قيم البحث
اقرأ أيضاً
We conduct a systematic,direct-numerical-simulation study,in mathematical models for ventricular tissue,of the dependence of spiral-and scroll-wave dynamics on $G_{Kr}$, the maximal conductance of the delayed rectifier Potassium current($I_{Kr}$) cha
nnel,and the parameter $gamma_{Cao}$,which determines the magnitude and shape of the current $I_{CaL}$ for the L-type calcium-current channel,in both square and anatomically realistic,whole-ventricle simulation domains using canine and human models. We use ventricular geometry with fiber-orientation details and employ a physiologically realistic model for a canine ventricular myocyte. We restrict ourselves to an HRD-model parameter regime, which does not produce spiral- and scroll-wave instabilities because of other,well-studied causes like a very sharp action-potential-duration-restitution (APDR) curve or early after depolarizations(EADs) at the single-cell level. We find that spiral- or scroll-wave dynamics are affected predominantly by a simultaneous change in $I_{CaL}$ and $I_{Kr}$,rather than by a change in any one of these currents;other currents do not have such a large effect on these wave dynamics in this parameter regime of the HRD model.We obtain stability diagrams in the $G_{Kr} -gamma_{Cao}$ plane.In the 3D domain,the geometry of the domain supports the confinement of the scroll waves and makes them more stable compared to their spiral-wave counterparts in 2D domain. We have also carried out a comparison of our HRD results with their counterparts for the human-ventricular TP06 model and have found important differences. In both these models,to make a transition,(from broken-wave to stable-scroll states or vice versa) we must simultaneously increase $I_{Kr}$ and decrease $I_{CaL}$;a modification of only one of these currents is not enough to effect this transition.
Complex spatiotemporal patterns of action potential duration have been shown to occur in many mammalian hearts due to a period-doubling bifurcation that develops with increasing frequency of stimulation. Here, through high-resolution optical mapping
and numerical simulations, we quantify voltage length scales in canine ventricles via spatiotemporal correlation analysis as a function of stimulation frequency and during fibrillation. We show that i) length scales can vary from 40 to 20 cm during one to one responses, ii) a critical decay length for the onset of the period-doubling bifurcation is present and decreases to less than 3 cm before the transition to fibrillation occurs, iii) fibrillation is characterized by a decay length of about 1 cm. On this evidence, we provide a novel theoretical description of cardiac decay lengths introducing an experimental-based conduction velocity dispersion relation that fits the measured wavelengths with a fractional diffusion exponent of 1.5. We show that an accurate phenomenological mathematical model of the cardiac action potential, fine-tuned upon classical restitution protocols, can provide the correct decay lengths during periodic stimulations but that a domain size scaling via the fractional diffusion exponent of 1.5 is necessary to reproduce experimental fibrillation dynamics. Our study supports the need of generalized reaction-diffusion approaches in characterizing the multiscale features of action potential propagation in cardiac tissue. We propose such an approach as the underlying common basis of synchronization in excitable biological media.
Ventricular tachycardia (VT) and ventricular fibrillation (VF) are lethal rhythm disorders, which are associated with the occurrence of abnormal electrical scroll waves in the heart. Given the technical limitations of imaging and probing, the in situ
visualization of these waves inside cardiac tissue remains a challenge. Therefore, we must, perforce, rely on in-silico simulations of scroll waves in mathematical models for cardiac tissue to develop an understanding of the dynamics of these waves in mammalian hearts. We use direct numerical simulations of the Hund-Rudy-Dynamic (HRD) model, for canine ventricular tissue, to examine the interplay between electrical scroll-waves and conduction and ionic inhomogeneities, in anatomically realistic canine ventricular geometries with muscle-fiber architecture. We find that millimeter-sized, distributed, conduction inhomogeneities cause a substantial decrease in the scroll wavelength, thereby increasing the probability for wave breaks; by contrast, single, localized, medium-sized ($simeq $ cm) conduction inhomogeneities, exhibit the potential to suppress wave breaks or enable the self-organization of wave fragments into stable, intact scrolls. We show that ionic inhomogeneities, both distributed or localised, suppress scroll-wave break up. The dynamics of a stable rotating wave is not affected significantly by such inhomogeneities, except at high concentrations of distributed inhomogeneities, which can cause a partial break up of scroll waves. Our results indicate that inhomogeneities in the canine ventricular tissue are less arrhythmogenic than inhomogeneities in porcine ventricular tissue, for which an earlier in silico study has shown that the inhomogeneity-induced suppression of scroll waves is a rare occurrence.
The temperature effect on the cardiac ryanodine receptor (RyR) function has been studied within the electron-conformational (EC) model. It is shown that simple EC model with the Arrhenius like temperature dependence of internal and external frictions
and a specific thermosensitivity of the tunnelling open - close transitions can provide both qualitative and quantitative description of the temperature effects for isolated RyRs. The potential of the model was illustrated by explaining the experimental data on the temperature dependence of sheeps isolated cardiac RyR gating and conductance (R. Sitsapesan et al., J Physiol 434, 469 (1991)).
We propose a novel numerical method able to determine efficiently and effectively the relationship of complementarity between portions of proteins surfaces. This innovative and general procedure, based on the representation of the molecular iso-elect
ron density surface in terms of 2D Zernike polynomials, allows the rapid and quantitative assessment of the geometrical shape complementarity between interacting proteins, that was unfeasible with previous methods. We first tested the method with a large dataset of known protein complexes obtaining an overall area under the ROC curve of 0.76 in the blind recognition of binding sites and then applied it to investigate the features of the interaction between the Spike protein of SARS-Cov-2 and human cellular receptors. Our results indicate that SARS-CoV-2 uses a dual strategy: its spike protein could also interact with sialic acid receptors of the cells in the upper airways, in addition to the known interaction with Angiotensin-converting enzyme 2.
سجل دخول لتتمكن من نشر تعليقات
التعليقات
جاري جلب التعليقات
سجل دخول لتتمكن من متابعة معايير البحث التي قمت باختيارها
