Phase resetting in human stem cell derived cardiomyocytes explains complex cardiac arrhythmias.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41637430.
- Also identified by DOI 10.1371/journal.pcbi.1013935 and PMC identifier 12900431.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Phase resetting of cardiac oscillators underlies some complex arrhythmias. Here we use optogenetic stimulation to construct phase response curves (PRC) for spheroids of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM) and a computational cardiomyocyte model to identify ionic mechanisms shaping the PRC. The clinical utility of the human PRCs is demonstrated by adding a patient-based conduction delay to the same equations to explain complex multi-day Holter ECG dynamics and cardiac arrhythmias. Periodic stimulation of these patient-based models and the computational model of human iPSC-CM reveal similar bifurcation patterns and entrainment zones. Cell therapy by injecting iPSC-CM into diseased hearts can induce ectopic foci-based engraftment arrhythmias. The PRC analysis offers a potential strategy to entrain these foci in a parameter space that avoids such arrhythmias.
Medical subject headings
- Myocytes, Cardiac
- Arrhythmias, Cardiac
- Induced Pluripotent Stem Cells
- Models, Cardiovascular