Combining wet and dry research: experience with model development for cardiac mechano-electric structure-function studies

Quinn, T. Alexander; Kohl, Peter

doi:10.1093/cvr/cvt003

Cited by 66 publications

(46 citation statements)

References 146 publications

(159 reference statements)

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“…This is in contrast with experience, as the left ventricular wall can thicken up to 40% of its diastolic value [35]. To obtain such a large deformation, different mechanisms must take place.…”

Section: Linking Micro To Macromentioning

confidence: 86%

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Thermodynamically consistent orthotropic activation model capturing ventricular systolic wall thickening in cardiac electromechanics

Rossi

Lassila

Ruiz–Baier

et al. 2014

European Journal of Mechanics - A/Solids

102

175

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The complex phenomena underlying mechanical contraction of cardiac cells and their influence in the dynamics of ventricular contraction are extremely important in understanding the overall function of the heart. In this paper we generalize previous contributions on the active strain formulation and propose a new model for the excitation-contraction coupling process. We derive an evolution equation for the active fiber contraction based on configurational forces, which is thermodynamically consistent. Geometrically, we link microscopic and macroscopic deformations giving rise to an orthotropic contraction mechanism that is able to represent physiologically correct thickening of the ventricular wall. A series of numerical tests highlights the importance of considering orthotropic mechanical activation in the heart and illustrates the main features of the proposed model.

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Section: Linking Micro To Macromentioning

confidence: 86%

“…Our hypothesis is that wall thickening is due to rearrangement of cardiomyocytes in each layer. models of cardiac function are not able to explain ventricular wall thickening, being the role of collagen sheetlets at the micro and macro levels still poorly understood [35]. Nevertheless, it is known (see e.g.…”

Section: Dislocation Approachmentioning

confidence: 99%

Thermodynamically consistent orthotropic activation model capturing ventricular systolic wall thickening in cardiac electromechanics

Rossi

Lassila

Ruiz–Baier

et al. 2014

European Journal of Mechanics - A/Solids

102

175

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“…Computational modeling of cardiac electromechanics affords an opportunity to conduct such a mechanistic investigation (30,38) and to reveal the role of individual HF remodeling aspects in prolonging EMD in dyssynchronous HF. In this study, we used MRI-based electromechanical models of dyssynchronous canine nonfailing and HF hearts to determine the individual and combined contributions of the major HF remodeling aspects, i.e., altered ventricular structure, slowed conduction, deranged Ca 2ϩ handling, and decreased stiffness, in extending EMD.…”

mentioning

confidence: 99%

Mechanistic insight into prolonged electromechanical delay in dyssynchronous heart failure: a computational study

Constantino

Lardo³

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Constantino J, Hu Y, Lardo AC, Trayanova NA. Mechanistic insight into prolonged electromechanical delay in dyssynchronous heart failure: a computational study. Am J Physiol Heart Circ Physiol 305: H1265-H1273, 2013. First published August 9, 2013 doi:10.1152/ajpheart.00426.2013.-In addition to the left bundle branch block type of electrical activation, there are further remodeling aspects associated with dyssynchronous heart failure (HF) that affect the electromechanical behavior of the heart. Among the most important are altered ventricular structure (both geometry and fiber/sheet orientation), abnormal Ca 2ϩ handling, slowed conduction, and reduced wall stiffness. In dyssynchronous HF, the electromechanical delay (EMD), the time interval between local myocyte depolarization and myofiber shortening onset, is prolonged. However, the contributions of the four major HF remodeling aspects in extending EMD in the dyssynchronous failing heart remain unknown. The goal of this study was to determine the individual and combined contributions of HF-induced remodeling aspects to EMD prolongation. We used MRI-based models of dyssynchronous nonfailing and HF canine electromechanics and constructed additional models in which varying combinations of the four remodeling aspects were represented. A left bundle branch block electrical activation sequence was simulated in all models. The simulation results revealed that deranged Ca 2ϩ handling is the primary culprit in extending EMD in dyssynchronous HF, with the other aspects of remodeling contributing insignificantly. Mechanistically, we found that abnormal Ca 2ϩ handling in dyssynchronous HF slows myofiber shortening velocity at the early-activated septum and depresses both myofiber shortening and stretch rate at the late-activated lateral wall. These changes in myofiber dynamics delay the onset of myofiber shortening, thus giving rise to prolonged EMD in dyssynchronous HF. cardiac electromechanics; electromechanical modeling; dyssynchronous heart failure HEART FAILURE (HF) is a major cause of morbidity and mortality, contributing significantly to healthcare expenditures. A subset of HF patients exhibit contractile dyssynchrony due to electrical intraventricular delay of the left bundle branch block (LBBB) type. In addition to this altered electrical activation pattern, other detrimental remodeling aspects of HF also contribute to electromechanical dysfunction of the heart and to the dyssynchrony between its electrical and mechanical behavior. Among these are remodeled ventricular structure and fiber/ sheet architecture (14), slowed electrical conduction (2), deranged Ca 2ϩ handling (40), and reduced stiffness of the failing myocardium (18).The electromechanical delay (EMD), the time interval between the local myocyte depolarization and the onset of myofiber shortening, and its three-dimensional (3-D) distribution are manifestations of the intricate relationship between the electrical and mechanical activity of the heart. Computational (12) and experimental (3, 27, 35) studie...

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“…209–211 Interestingly, the vast majority of observed acute electrophysiological responses of the heart to stretch can be successfully reproduced simply by invoking SAC NS . 212 …”

Section: Mechanistic Projection Between Levels Of Investigationmentioning

confidence: 99%

Cardiac Mechano-Gated Ion Channels and Arrhythmias

Peyronnet

Nerbonne

Kohl

2016

Circulation Research

Self Cite

180

167

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Mechanical forces will have been omnipresent since the origin of life, and living organisms have evolved mechanisms to sense, interpret and respond to mechanical stimuli. The cardiovascular system in general, and the heart in particular, are exposed to constantly changing mechanical signals, including stretch, compression, bending, and shear. The heart adjusts its performance to the mechanical environment, modifying electrical, mechanical, metabolic, and structural properties over a range of time scales. Many of the underlying regulatory processes are encoded intra-cardially, and are thus maintained even in heart transplant recipients. Although mechano-sensitivity of heart rhythm has been described in the medical literature for over a century, its molecular mechanisms are incompletely understood. Thanks to modern biophysical and molecular technologies, the roles of mechanical forces in cardiac biology are being explored in more detail, and detailed mechanisms of mechano-transduction have started to emerge. Mechano-gated ion channels are cardiac mechano-receptors. They give rise to mechano-electric feedback, thought to contribute to normal function, disease development, and, potentially, therapeutic interventions. In this review, we focus on acute mechanical effects on cardiac electrophysiology, explore molecular candidates underlying observed responses, and discuss their pharmaceutical regulation. From this, we identify open research questions and highlight emerging technologies that may help in addressing them. Cardiac electrophysiology is acutely affected by the heart’s mechanical environment. Mechano-electric feedback affects excitability, conduction, and electrical load, and remains an underestimated player in arrhythmogenesis. The utility of therapeutic interventions targeting acute mechano-electrical transduction is an open field worthy of further study.

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Combining wet and dry research: experience with model development for cardiac mechano-electric structure-function studies

Cited by 66 publications

References 146 publications

Thermodynamically consistent orthotropic activation model capturing ventricular systolic wall thickening in cardiac electromechanics

Thermodynamically consistent orthotropic activation model capturing ventricular systolic wall thickening in cardiac electromechanics

Mechanistic insight into prolonged electromechanical delay in dyssynchronous heart failure: a computational study

Cardiac Mechano-Gated Ion Channels and Arrhythmias

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