A novel computational model of beta-adrenergic receptor signaling demonstrated that sympathetically remodeled ventricular substrates host faster (4.5 Hz vs. 3.7 Hz) and more stable VTs.
Does spatial variation in β-adrenergic receptor signaling affect ventricular tachycardia rotor dynamics in a computational model?
A novel computational model demonstrates that spatial gradients of sympathetic stimulation can break VT rotors into wavelets, providing insights into the mechanisms of sympathetically modulated arrhythmias.
Absolute Event Rate: 4.5% vs 3.7%
Abstract Ventricular tachycardia (VT) dynamics in myocardial infarction and heart failure patients could be influenced by heterogeneous sprouting of sympathetic nerves or alteration of β‐adrenergic receptors to disrupt normal β‐adrenergic receptor signalling (BARS). Because sympathetic remodelling is challenging to control experimentally, we created and validated a novel ionic model incorporating the macroscopic effects of BARS on intracellular Ca 2+ dynamics and handling for tissue‐scale simulations. Using our model we created ventricular sheets with varying spatial densities and gradients to study VT behaviour, represented as a rotor. We demonstrated that our BARS model reduces action potential durations (APDs) by 16% due to drastic changes in K + and Ca 2+ regulation, consistent with experimental data from animal and human studies. We also demonstrated that the ventricular substrate with spatial BARS density for µM (ISO) could host faster (4.5 Hz vs . 3.7 Hz) and more stable (5.6 mm 2 vs . 14 mm 2 ) VTs than non‐BARS substrates. We also showed that VTs hosted in substrates with spatial BARS gradients ( could splinter into multiple slow and disorganized wavelets, indicative of fibrillation. Our model and simulation findings may help predict and enhance the effectiveness of neuromodulatory interventions for sympathetically modulated VTs. image Key points A novel human ventricular model is used for tissue‐scale simulation of sympathetic activity Sympathetically remodelled substrates may have fast and stable rotors Spatial gradients of sympathetic stimulation could break rotors into wavelets Simulations may help inform interventions for sympathetically modulated arrhythmias
Zhang et al. (Sat,) conducted a other in Ventricular tachycardia. Beta-adrenergic receptor signalling (BARS) model vs. Non-BARS substrates was evaluated on Ventricular tachycardia speed. A novel computational model of beta-adrenergic receptor signaling demonstrated that sympathetically remodeled ventricular substrates host faster (4.5 Hz vs. 3.7 Hz) and more stable VTs.