Why the study?
Inter-species differences in excitation-contraction coupling mechanisms limit translation of animal findings to human cardiac physiology and undermine drug safety and efficacy assessments.
A novel computational translation tool enables quantitative mapping of cardiac electrophysiological responses from animal models to human physiology, potentially improving drug efficacy and safety assessment.
May facilitate cross-species myocyte mapping; leaves open utility for human drug safety assessment.
Animal experimentation is key in the evaluation of cardiac efficacy and safety of novel therapeutic compounds. However, inter-species differences in the mechanisms regulating excitation-contraction coupling can limit the translation of experimental findings from animal models to human physiology, and undermine the assessment of drugs’ efficacy and safety. Here, we built a suite of translators for quantitatively mapping electrophysiological responses in ventricular myocytes across species. We trained these statistical operators using a broad dataset obtained by simulating populations of our biophysically detailed computational models of action potential and Ca 2+ transient in mouse, rabbit, and human. We then tested our translators against experimental data describing the response to stimuli, such as ion channel block, change in beating rate, and β-adrenergic challenge. We demonstrate that this approach is well suited to predicting the effects of perturbations across different species or experimental conditions, and suggest its integration into mechanistic studies and drug development pipelines.
No takes yet. Share an insight, caveat, or question.
Morotti et al. (2020) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: