Mechanoelectric effects in healthy cardiac function and under Left Bundle Branch Block pathology. (April 2023)

• Record Type: Journal Article
• Authors: Petras, Argyrios; Gsell, Matthias A.F.; Augustin, Christoph M.; Rodriguez-Padilla, Jairo; Jung, Alexander; Strocchi, Marina; Prinzen, Frits W.; Niederer, Steven A.; Plank, Gernot; Vigmond, Edward J.
• Is Part Of: Computers in biology and medicine. Volume 156(2023)
• Publication Date: 2023-04
• Subjects: Computational model -- Cardiac electromechanics -- Mechanoelectric feedback -- Stretch activated channels -- Canine heart; Medicine -- Data processing -- Periodicals; Biology -- Data processing -- Periodicals; 610.285
• DOI: 10.1016/j.compbiomed.2023.106696
• Languages: English
• ISSNs: 0010-4825

Abstract

Abstract: Mechanoelectric feedback (MEF) in the heart operates through several mechanisms which serve to regulate cardiac function. Stretch activated channels (SACs) in the myocyte membrane open in response to cell lengthening, while tension generation depends on stretch, shortening velocity, and calcium concentration. How all of these mechanisms interact and their effect on cardiac output is still not fully understood. We sought to gauge the acute importance of the different MEF mechanisms on heart function. An electromechanical computer model of a dog heart was constructed, using a biventricular geometry of 500K tetrahedral elements. To describe cellular behavior, we used a detailed ionic model to which a SAC model and an active tension model, dependent on stretch and shortening velocity and with calcium sensitivity, were added. Ventricular inflow and outflow were connected to the CircAdapt model of cardiovascular circulation. Pressure–volume loops and activation times were used for model validation. Simulations showed that SACs did not affect acute mechanical response, although if their trigger level was decreased sufficiently, they could cause premature excitations. The stretch dependence of tension had a modest effect in reducing the maximum stretch, and stroke volume, while shortening velocity had a much bigger effect on both. MEF served to reduce the heterogeneity in stretch while increasing tension heterogeneity. In the context of left bundle branch block, a decreased SAC trigger level could restore cardiac output by reducing the maximal stretch when compared to cardiac resynchronization therapy. MEF is an important aspect of cardiac function and could potentially mitigate activation problems. Highlights: The role of mechanoelectric feedback mechanisms in the cardiac function is explored. An in-silico study using a biventricular canine cardiac geometry is conducted. The study uses 3D-0D fluid-electromechanical framework implemented in CARP. Length and velocity dependence in the active tension enhances the cardiac contraction. Stretch activated channels introduce tension heterogeneities and regularize stretch.