Abstract
Multiscale models of the cardiovascular system can provide new insights into physiological and pathological processes. Models that incorporate molecular-level effects may be particularly useful for clinical applications because they can predict the functional consequences of pharmaceuticals that modulate the properties of molecules and/or the rate at which they undergo reactions. PyMyoVent is a computer model that bridges from molecular to organ-level function and simulates a left ventricle pumping blood through the systemic circulation. Initial work with PyMyoVent focused on the End Systolic Pressure Volume Relationship and ranked potential therapeutic strategies by their impact on contractility. This manuscript extends PyMyoVent by adding baroreflex control of arterial pressure. The reflex algorithm is inspired by the underlying biology. It uses an afferent signal derived from arterial pressure to drive a kinetic model that mimics the net result of neural processing in the medulla and cell-level responses to autonomic drive. The kinetic model outputs control signals that are constrained between limits that represent maximum parasympathetic and maximum sympathetic drive and which modulate heart rate, intracellular Ca2+ dynamics, the molecular-level function of both the thick and the thin myofilaments, and vascular tone. Simulations show that the algorithm can regulate mean arterial pressure at set-points ranging from ∼30 to ∼150 mmHg as well as maintaining arterial pressure when challenged by rapid changes in blood volume or sudden increases in aortic resistance.
Competing Interest Statement
The authors have declared no competing interest.