Simulated Electromechanical Heterogeneity in Human Left Ventricle
- Forschungsthema:Simulated Electromechanical Heterogeneity in Human Left Ventricle
- Typ:Diplomarbeit
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Beschreibung
Nowadays, heart diseases are the most
common diseases in the western world. Many people suffer from different
heart diseases and die of them. Recent studies have shown that in most
cases sudden cardiac death is caused by cardiac arrhythmias, mainly
ventricular tachycardia (VT) degenerating into ventricular fibrillation
(VF) or immediately occurring VF. On the other hand, the basis of
cellular physiology and also electromechanical coupling in the heart
failure is still largely unknown.
In the last decades, human heart used
to be considered homogeneous across the ventricle wall, but recent
studies have established three distinct cell types in the ventricular
myocardium: subepicardial (Epi), midmyocardial (M) and subendocardial
(Endo) cells. They differ from each other with respect to the
morphology of action potential (AP), the AP duration (APD), and the
frequency dependence of APD shortening. The ionic bases were proposed
later in different species. Recent research of calcium activity in
canine left ventricle has proved that the heterogeneity in ventricle
exists not only in electrophysiology but also in mechanical functions.
Due to the limitation of experiments
on heart, especially on failed heart, computational modeling plays an
important role in understanding the physiology and mechanics in the
heart. The first human ventricular model was presented by Priebe and
Beuckelmann. It was mainly based on the Luo-Rudy phase II ventricular
myocyte model for guinea pig and developed using parameter variation.
Ten Tusscher et al. subsequently presented a human ventricular model in
which parameters are based on more recent whole-cell current data in
isolated human ventricular myocytes. In 2005 a new model was developed
by Iyer et al. to present the epicardial cell in human left ventricle,
which used continuous-time Markov chain models to describe
transmembrane ion channels and intracellular ion handling and was based
on recent experimental data. Theses models describe the properties of
various ion channels and handling of intracellular ion concentration,
and can represent the action potential properties and the cellular
properties.
Though much attention has been
focused on the mathematical description of the cell model of human
ventricular myocyte, the heterogeneity in the ventricular wall has not
gained much attention. Ten Tusscher et al. have developed a model to
present different APs in different layers of human ventricle, but only
transient outward current and the slow component of the delayed
rectifier current were concerned. Seemann et al. have developed a model
to reconstruct the heterogeneity in human ventricular myocardium, in
which the parameters and conductance of Ito, IKs, IK1 and INaCa were
adjusted according to the recent experimental data.
This diploma thesis was focused on
the electromechanical heterogeneity in human left ventricular myocytes.
The Iyer et al. model was used and modified to reconstruct the
inhomogeneous transmembrane electrophysiology and intracellular calcium
activities. The modified model was able to simulate the heterogeneous
densities or properties of late sodium current (late INa), transient
outward current (Ito), slow component of delayed rectifier current
(IKs), inwardly rectifier current (IK1) and sodium-calcium exchange
current (I), as well as calcium release (Irel) and uptake (Iup)
currents of sarcoplasmic reticulum in calcium handling. With these
modifications, the difference in APs, calcium transients and tension
development of Epi, M and Endo cell in human left ventricle can be
reconstructed. Cordeiro et al. have published the heterogeneous AP and
calcium activity in canine left ventricle. The tendency
of the regional difference in AP, calcium transient, as well as
mechanical function, in this simulation work showed good agreement to
their experiment. This work can explain how heterogeneous transmembrane
ion currents and intracellular calcium handling lead to an
inhomogeneous electrophysiology of human left ventricular myocytes but
a more homogenized contraction of the ventricular wall. Heterogeneity
is such an important characteristic of human left ventricle, that it
might determine the electromechanical properties of ventricle,
furthermore, its abnormality might be the crucial basis of some kind of
heart failing. Myocytes with mishandling of calcium are the central
cause of both contractile dysfunction and arrhythmias in
pathophysiological conditions. This simulation could contribute to the
simulation of calcium handling in failing heart and the research of
human cardiac diseases in the future.