Human In Silico Drug Trials Demonstrate Higher Accuracy than Animal Models in Predicting Clinical Pro-Arrhythmic Cardiotoxicity
E Passini, OJ Britton, HR Lu, J Rohrbacher… - Frontiers in …, 2017 - frontiersin.org
Early prediction of cardiotoxicity is critical for drug development. Current animal models
raise ethical and translational questions, and have limited accuracy in clinical risk prediction …
raise ethical and translational questions, and have limited accuracy in clinical risk prediction …
[HTML][HTML] Quantitative systems toxicology
P Bloomingdale, C Housand, JF Apgar… - Current opinion in …, 2017 - Elsevier
The overarching goal of modern drug development is to optimize therapeutic benefits while
minimizing adverse effects. However, inadequate efficacy and safety concerns remain to be …
minimizing adverse effects. However, inadequate efficacy and safety concerns remain to be …
Basic research approaches to evaluate cardiac arrhythmia in heart failure and beyond
Patients with heart failure often develop cardiac arrhythmias. The mechanisms and
interrelations linking heart failure and arrhythmias are not fully understood. Historically …
interrelations linking heart failure and arrhythmias are not fully understood. Historically …
Fibrotic remodeling during persistent atrial fibrillation: In silico investigation of the role of calcium for human atrial myofibroblast electrophysiology
During atrial fibrillation, cardiac tissue undergoes different remodeling processes at different
scales from the molecular level to the tissue level. One central player that contributes to both …
scales from the molecular level to the tissue level. One central player that contributes to both …
Population-based mechanistic modeling allows for quantitative predictions of drug responses across cell types
Quantitative mismatches between human physiology and experimental models can be
problematic for the development of effective therapeutics. When the effects of drugs on …
problematic for the development of effective therapeutics. When the effects of drugs on …
Abnormal calcium homeostasis in heart failure with preserved ejection fraction is related to both reduced contractile function and incomplete relaxation: an …
Heart failure with preserved ejection fraction (HFpEF) accounts for about 50% of heart failure
cases. It has features of incomplete relaxation and increased stiffness of the left ventricle …
cases. It has features of incomplete relaxation and increased stiffness of the left ventricle …
Heterogeneous effects of fibroblast-myocyte coupling in different regions of the human atria under conditions of atrial fibrillation
Background: Atrial fibrillation (AF), the most common cardiac arrhythmia, is characterized by
alteration of the action potential (AP) propagation. Under persistent AF, myocytes undergo …
alteration of the action potential (AP) propagation. Under persistent AF, myocytes undergo …
Investigational treatments for COVID-19 may increase ventricular arrhythmia risk through drug interactions
M Varshneya, I Irurzun-Arana, C Campana, R Dariolli… - Biophysical …, 2021 - cell.com
Several drugs proposed for the treatment of COVID-19 have reported cases of cardiac
adverse events such as ventricular arrhythmias. To properly weigh risks against potential …
adverse events such as ventricular arrhythmias. To properly weigh risks against potential …
Reduced response to IKr blockade and altered hERG1a/1b stoichiometry in human heart failure
Abstract Heart failure (HF) claims 250,000 lives per year in the US, and nearly half of these
deaths are sudden and presumably due to ventricular tachyarrhythmias. QT interval and …
deaths are sudden and presumably due to ventricular tachyarrhythmias. QT interval and …
[HTML][HTML] Computational assessment of the functional role of sinoatrial node exit pathways in the human heart
Aim The human right atrium and sinoatrial node (SAN) anatomy is complex. Optical mapping
experiments suggest that the SAN is functionally insulated from atrial tissue except at …
experiments suggest that the SAN is functionally insulated from atrial tissue except at …