Multiscale Modelling of β-Adrenergic Stimulation in Cardiac Electromechanical Function

β-adrenergic receptor stimulation (β-ARS) is a physiological mechanism that regulates cardiovascular function under stress conditions or physical exercise. Triggered during the so-called “fight-or-flight” response, the activation of the β-adrenergic receptors located on the cardiomyocyte membrane initiates a phosphorylation cascade of multiple ion channel targets that regulate both cellular excitability and recovery and of different proteins involved in intracellular calcium handling. As a result, β-ARS impacts both the electrophysiological and the mechanical response of the cardiomyocyte. β-ARS also plays a crucial role in several cardiac pathologies, greatly modifying cardiac output and potentially causing arrhythmogenic events. Mathematical patient-specific models are nowadays envisioned as an important tool for the personalised study of cardiac disease, the design of tailored treatments, or to inform risk assessment. Despite that, only a reduced number of computational studies of heart disease have incorporated β-ARS modelling. In this review, we describe the main existing multiscale frameworks to equip cellular models of cardiac electrophysiology with a β-ARS response. We also outline various applications of these multiscale frameworks in the study of cardiac pathology. We end with a discussion of the main current limitations and the future steps that need to be taken to adapt these models to a clinical environment and to incorporate them in organ-level simulations.