Key result
In-silico modeling of human atrial cardiomyocytes demonstrated that advancing age reduces sensitivity to dofetilide, with action potential duration increasing by 6% in older models versus 15% in adult models at 5 nM.
Why the study?
Experimental data on action potentials and transmembrane currents across different ages in healthy human cardiomyocytes are deeply lacking, and mammalian data are incomplete and contradictory.
Does Dofetilide affect action potential duration differently in aging human atrial cardiomyocytes?
Does Dofetilide affect action potential duration differently in aging human atrial cardiomyocytes?
In-silico modeling suggests that the efficacy of dofetilide in prolonging action potential duration in human atrial cardiomyocytes decreases with advancing age.
Electrophysiology of cardiomyocytes changes with aging. Agerelated ionic remodeling in cardiomyocytes may increase the incidence and prevalence of atrial fibrillation (AF) in the elderly and affect the efficiency of antiarrhythmic drugs. There is the deep lack of experimental data on an action potential and transmembrane currents recorded in the healthy human cardiomyocytes of different age. Experimental data in mammals is also incomplete and often contradicting depending on the experimental conditions. In this in-silico study, we used a population of ionic models of human atrial cardiomyocytes to transfer data on the age- related ionic remodeling in atrial cardiomyocytes from canines and mice to predict possible consequences for human cardiomyocyte activity. Based on experimental data, we analyzes two hypotheses on the aging effect on the ionic currents using two age-related sets of varied model parameters and evaluated corresponding changes in action potential morphology with aging. Using the two populations of aging models, we analyzed the agedependent sensitivity of atrial cardiomyocytes to Dofetilide which is one of the antiarrhythmic drugs widely used in patients with atrial fibrillation.
No takes yet. Share an insight, caveat, or question.
Nesterova et al. (2020) studied Aging atrial cardiomyocytes. Dofetilide vs. Baseline (no drug) across different age groups was evaluated on Action potential duration (APD90) change. In-silico modeling of human atrial cardiomyocytes demonstrated that advancing age reduces sensitivity to dofetilide, with action potential duration increasing by 6% in older models versus 15% in adult models at 5 nM.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: