Multiscale simulations of cardiac growth based on sarcomere biophysics.

Abstract

Multiscale models of the cardiovascular system can provide new insights into physiological and pathological processes. PyMyoVent is a computer model that bridges from molecular to organ-level function and which simulates a left ventricle pumping blood through the systemic circulation. The code is being developed as a testbed for a long-term project that seeks to use computer models to optimize care for patients with cardiac disease. Recently, PyMyoVent was extended to provide baroreflex control of arterial pressure. This allowed the model to regulate arterial pressure when sarcomere-level function was perturbed via myotropes and/or genetic modifications. This abstract describes a new growth module for PyMyoVent that allows the ventricle to dilate/constrict (eccentric growth) or thicken/thin (concentric growth) in response to physiological signals. Eccentric growth is mimicked by adding/removing sarcomeres in series around the ventricular circumference. Concentric growth involves the addition/removal of sarcomeres in parallel. Initial calculations have tested different potential growth signals. The best results to date have been obtained by controlling eccentric growth with passive intracellular stress and concentric growth via the intracellular ATP concentration. Simulations based on these feedback laws reproduce ventricular growth patterns induced by clinical conditions including: aortic valve stenonsis, mitral valve regurgitation, depressed sarcomere-level contractility, and ventricular constriction induced by mechanical unloading via ventricular assist devices. The long-term goal is to extend the modeling framework to develop computer models that clinicans can use to develop personalized therapeutic plans for patients with different forms of cardiovascular disease.