Systems Approach to Understanding Electromechanical Activity in the Human Heart

Abstract

Abstract-The National Heart, Lung, and Blood Institute (NHLBI) convened a workshop of cardiologists, cardiac electrophysiologists, cell biophysicists, and computational modelers on August 20 and 21, 2007, in Washington, DC, to advise the NHLBI on new research directions needed to develop integrative approaches to elucidate human cardiac function. The workshop strove to identify limitations in the use of data from nonhuman animal species for elucidation of human electromechanical function/activity and to identify what specific information on ion channel kinetics, calcium handling, and dynamic changes in the intracellular/extracellular milieu is needed from human cardiac tissues to develop more robust computational models of human cardiac electromechanical activity. This article summarizes the workshop discussions and recommendations on the following topics: (1) limitations of animal models and differences from human electrophysiology, (2) modeling ion channel structure/function in the context of whole-cell electrophysiology, (3) excitation-contraction coupling and regulatory pathways, (4) whole-heart simulations of human electromechanical activity, and (5) what human data are currently needed and how to obtain them. The recommendations can be found on the NHLBI Web site at

Short-term disruption in regional left ventricular electrical conduction patterns increases interstitial matrix metalloproteinase activity

“…Electrical activation of myocytes initiates a number of ionic processes, which then culminate in mechanical contraction (13,16). Therefore, changes in the electrical activation pattern of the myocardium can alter the intracellular milieu of myocytes as well as the mechanical functioning of the affected myocardium (16).…”

“…Electrical activation of myocytes initiates a number of ionic processes, which then culminate in mechanical contraction (13,16). Therefore, changes in the electrical activation pattern of the myocardium can alter the intracellular milieu of myocytes as well as the mechanical functioning of the affected myocardium (16). Since a number of intracellular ions, e.g., Ca 2ϩ , play crucial roles as mediators/ activators in signaling cascades, and mechanical stretch can induce stretch-activated receptors, abnormalities in electrical activation may alter intracellular signaling pathways.…”

Volumetric Modeling Electromechanics of the Heart

“…Third, we have simplified the effect of mechanoelectrical feedback by only considering the effect of heart deformation to the position of electrical source. The realistic mechanoelectrical feedback simulation can only be achieved through models include the contribution of stretch-activated channels (SACs) [3,12]. However, this kind of models usually contain a lot of parameters and are much more complex than phenomenal models used in the paper.…”

“…Experimental and clinical research has demonstrated that mechanical activity of the heart affects cardiac electrophysiology [3]. Mechanical activity affects cardiac electrophysiology mainly in two ways: firstly, the position of electrical source inside the myocardium will be changed while the geometry of the heart changes; secondly, stretch-activated ion channels in the cell membrane will be activated when the heart deforms [3,12]. In the paper, we only consider the effect of heart motion to the electrical source position.…”

Introduction to the Series on Computational Approaches to Cardiac Arrhythmias

“…During the last 20 years, such methods have made it conceivable to generate geometrically accurate numeric models that incorporate precise information about local cellular electrical activity, as well as highly sophisticated electrode and optical mapping systems that allow detailed analyses of the dynamics of cardiac electric wave propagation in 1, 2, and 3 dimensions in the normal and the disease heart. [10][11][12][13] Computational approaches have been used for many years as valuable tools to aid in research aiming at understanding…”