Sunday Symposium

​"Roles of cardiac potassium channels in repolarization and arrhythmia" 
Potassium channels form a very diverse class of ion channels that generate K⁺ currents crucial for modulation of membrane potential in almost all living cells. In the heart, these channels are responsible for the repolarizing currents controlling the action potential frequency and duration. K⁺ channels form a so-called repolarization reserve that allows maintaining the stability of heart beating in all conditions. Mutations in genes encoding cardiac K⁺ currents have been associated with a number of idiopathic ventricular and supraventricular arrhythmias such as long and short QT syndromes and atrial fibrillation.
After a short review of the different class of K⁺ channels expressed in cardiac cells, some example of their implications in inherited arrhythmic disorders will be discussed.
 

"Applications requiring high-resolution electrical and mechanical heart models" 
Limited compute power has mostly restricted electrophysiological heart models to spatial discretizations that are much coarser than heart cells.  Here, we remove the compute limitation by running on Lawrence Livermore National Laboratory’s Sequoia, a 96-rack Blue Gene Q computer with a peak speed of 20 PFLOPS.  A two ventricle model of the human heart with a spatial discretization of 0.1 mm, roughly the long dimension of a heart cell, can be simulated in just over 3 seconds, more than three orders of magnitude faster than previous benchmarks.  In mechanics, spatial resolution has been constrained primarily by theoretical and algorithm limitations.  We present a new approach in which deformation of the ventricles is solved using an iterative solver for an ill-conditioned system of equations derived from an implicit numerical method. For the first time, ventricular geometries with trabeculae and papillary muscles can be simulated, and the dispersion of transmural strains predicted across the ventricular wall is similar to real measures.

​"Neural circulation control during exercise: impact of aging and heart failure"
Group III/IV muscle afferents play a significant role in regulating the cardiovascular and hemodynamic response to physical activities. Specifically, these sensory neurons modulate various autonomic responses to exercise and thereby assure adequate muscle blood flow and oxygen delivery. Although aging has no effect on the contribution of group III/IV muscle afferents in regulating arterial blood pressure during exercise (i.e. the so-called exercise pressor reflex), the mechanisms accounting for this response are altered in the elderly. While young individuals predominantly rely on alterations in cardiac output to change arterial blood pressure, the role of the heart decreases with age and peripheral vasomotor activation becomes a more prominent mechanism in determining the exercise pressor reflex in the elderly. Additionally, although group III/IV muscle afferents play a clear role in increasing leg vascular conductance during locomotor exercise in the young, it seems that these afferents may actually compromise exercise-induced peripheral hemodynamics in older individuals. Heart failure further impairs the neural control of the circulation. Specifically, although group III/IV muscle afferents remain an important determinant for central hemodynamics in patients with heart failure, it also appears that these sensory neurons cause excessive sympatho-excitation impairing limb blood flow which likely contributes to the exercise intolerance in this population. This presentation will highlight key human findings documenting the influence of group III/IV muscle afferents in the circulatory response to physical activities and focus on the impact of healthy aging and heart failure on this regulatory mechanism.