Bioelectricity

Plonsey, Robert; Barr, Roger C.

doi:10.1007/978-1-4757-3152-1

Cited by 148 publications

(120 citation statements)

References 0 publications

Supporting

Mentioning

111

Contrasting

Unclassified

Order By: Relevance

“…Electrograms were obtained by assuming an infinite volume conductor and calculating the dipole source density of the membrane potential V m in all voxel points of the ventricular myocardium, using the following equation 36 :…”

Section: Electrogramsmentioning

confidence: 99%

Organization of Ventricular Fibrillation in the Human Heart

Tusscher

Hren

Panfilov

2007

Circulation Research

145

151

View full text Add to dashboard Cite

Abstract-Sudden cardiac death is a major cause of death in the industrialized world, claiming approximately 300 000 victims annually in the United States alone. In most cases, sudden cardiac death is caused by ventricular fibrillation (VF). Experimental studies in large animal hearts have shown that the uncoordinated contractions during VF are caused by large numbers of chaotically wandering reentrant waves of electrical activity. However, recent clinical data on VF in the human heart seem to suggest that human VF may have a markedly different organization. Here, we use a detailed model of the human ventricles, including a detailed description of cell electrophysiology, ventricular anatomy, and fiber direction anisotropy, to study the organization of human VF. We show that characteristics of our simulated VF are qualitatively similar to the clinical data. Furthermore, we find that human VF is driven by only approximately 10 reentrant sources and thus is much more organized than VF in animal hearts of comparable size, where VF is driven by approximately 50 sources. We investigate the influence of anisotropy ratio, tissue excitability, and restitution properties on the number of reentrant sources driving VF. We find that the number of rotors depends strongest on minimum action potential duration, a property that differs significantly between human and large animal hearts. Based on these findings, we suggest that the simpler spatial organization of human VF relative to VF in large animal hearts may be caused by differences in minimum action potential duration. Both the simpler spatial organization of human VF and its suggested cause may have important implications for treating and preventing this dangerous arrhythmia in humans. (Circ Res. 2007;100:e87-e101.)Key Words: ventricular fibrillation Ⅲ computer simulation Ⅲ spatial organization V entricular fibrillation (VF) is the single most common cause of sudden cardiac death, the largest cause of death in the Western world. During VF, the contraction of the ventricles becomes rapid, uncoordinated, and highly ineffective, causing this condition to be lethal within minutes, unless halted by defibrillation. The highly disorganized contractions during VF are caused by a severely disturbed, turbulent conduction of the electrical excitation wave.Experimental studies in animal hearts and tissue 1-6 have shown that the turbulent electrical activity typical of VF is caused by the presence of multiple reentrant waves of electrical excitation. Because of their reentrant behavior and high frequency, these rotors act as self-perpetuating, independent sources of excitation that take over control from the slower sinus node. The number of rotors present during VF is a good quantifier of the complexity and amount of disorganization of the excitation pattern. Results in animal hearts suggest that the number of reentrant sources present during VF increases as a function of heart size. For example, in rabbit hearts, VF can be driven by just 1 or 2 sources, 2,7 whereas in sheep hearts, VF...

show abstract

Section: Electrogramsmentioning

confidence: 99%

Organization of Ventricular Fibrillation in the Human Heart

Tusscher

Hren

Panfilov

2007

Circulation Research

145

151

View full text Add to dashboard Cite

show abstract

“…The driving force for I Na and I K is generated by transmembrane Na + and K + concentration gradients, and its magnitude is the difference between V m and the equilibrium potential, which is computed using the Nernst equation (Plonsey & Barr, 2000). For example, the Na + equilibrium potential, E Na , is found with the following Nernst equation:…”

Section: The Axon Action Potential Modelmentioning

confidence: 99%

Computational biology in the study of cardiac ion channels and cell electrophysiology

Rudy

Silva

2006

Quart. Rev. Biophys.

239

181

View full text Add to dashboard Cite

The cardiac cell is a complex biological system where various processes interact to generate electrical excitation (the action potential, AP) and contraction. During AP generation, membrane ion channels interact nonlinearly with dynamically changing ionic concentrations and varying transmembrane voltage, and are subject to regulatory processes. In recent years, a large body of knowledge has accumulated on the molecular structure of cardiac ion channels, their function, and their modification by genetic mutations that are associated with cardiac arrhythmias and sudden death. However, ion channels are typically studied in isolation (in expression systems or isolated membrane patches), away from the physiological environment of the cell where they interact to generate the AP. A major challenge remains the integration of ion-channel properties into the functioning, complex and highly interactive cell system, with the objective to relate molecular-level processes and their modification by disease to whole-cell function and clinical phenotype. In this article we describe how computational biology can be used to achieve such integration. We explain how mathematical (Markov) models of ion-channel kinetics are incorporated into integrated models of cardiac cells to compute the AP. We provide examples of mathematical (computer) simulations of physiological and pathological phenomena, including AP adaptation to changes in heart rate, genetic mutations in SCN5A and HERG genes that are associated with fatal cardiac arrhythmias, and effects of the CaMKII regulatory pathway and β-adrenergic cascade on the cell electrophysiological function. Prologue'Things should be made as simple as possible, but not any simpler.' Albert EinsteinCardiac muscle can generate propagating electrical impulses (action potentials), a property that classifies it as an excitable tissue similar to skeletal muscle and nerve. At the single-cell level, the electrical action potential (AP) triggers mechanical contraction by inducing a transient rise of intracellular calcium which, in turn, carries the contraction message to the contractile proteins of the cell. This process that couples electrical excitation to mechanical function is termed excitation-contraction coupling. APs are generated by individual cells and are conducted from cell to cell through intercellular gap junctions, forming waves of excitation that activate and synchronize the blood pumping action of the heart. Similar to nerve and skeletal muscle, AP initiation and conduction in cardiac ventricular tissue rely mostly on a single membrane process, namely the flow of sodium ions through sodium-specific ion channels. However, unlike the short-duration APs of skeletal muscle and nerve, the cardiac ventricular AP is characterized by long plateau and repolarization phases that prevent premature arrhythmogenic excitation and provide control of mechanical contraction. In NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript contrast to the 'single-current mechanism' of...

show abstract

“…23 The resulting discretized problem can be expressed as follows for each time instant in the cardiac cycle:…”

Section: Appendixmentioning

confidence: 99%

Imaging Dispersion of Myocardial Repolarization, II

et al. 2001

View full text Add to dashboard Cite

Background-Dispersion of myocardial repolarization supports the development and maintenance of life-threatening arrhythmias. Current noninvasive approaches for detecting substrates with increased dispersion based on ECG measures (eg, QT dispersion) have shown limited success and inconsistencies. The companion article shows that, in contrast, epicardial potentials and derived measures reflect local dispersion of repolarization. Here, using a recently developed ECG imaging method, we evaluate the feasibility of noninvasive reconstruction of such epicardial measures from body-surface ECG data. Methods and Results-Epicardial potentials were recorded with a 224-electrode sock from an open-chest dog during control, regional warming, cooling, and simultaneous adjacent warming and cooling to induce localized changes in myocardial repolarization and regions of increased dispersion. Body-surface potentials were generated from these epicardial potentials in a human torso model. Realistic geometric errors and measurement noise were added to the torso data, which were then used to noninvasively reconstruct epicardial measures of repolarization dispersion (activation recovery intervals [ARIs] and QRST integrals). Repolarization properties were accurately depicted by ECG imaging, including (1) shortened ARIs and increased QRST integrals over the warmed region, (2) prolonged ARIs and decreased QRST integrals over the cooled region, and (3) high gradients of ARIs and QRST integrals over the adjacent warmed and cooled regions. Conclusions-ECG imaging can reconstruct repolarization properties accurately and localize areas of increased dispersion of repolarization in the heart noninvasively. Its clinical significance lies in the possibility of noninvasive risk stratification and in guidance and evaluation of therapy.

show abstract

Bioelectricity

Cited by 148 publications

References 0 publications

Organization of Ventricular Fibrillation in the Human Heart

Organization of Ventricular Fibrillation in the Human Heart

Computational biology in the study of cardiac ion channels and cell electrophysiology

Imaging Dispersion of Myocardial Repolarization, II

Contact Info

Product

Resources

About