Marta Gomez, Jesus Carro, Esther Pueyo, Alba Perez, Aida Olivan, Violeta Monasterio
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引用次数: 0
Abstract
Objective: The pathophysiological role of the small conductance calcium-activated potassium (SK) channels in human ventricular myocytes remains unclear. Experimental studies have reported upregulation of in pathological states, potentially contributing to ventricular arrhythmias. In heart failure (HF) patients, the upregulation of SK channels could be an adaptive physiological response to shorten the action potential duration (APD) under conditions of reduced repolarization reserve. In this work, we aimed at uncovering the contribution of SK channels to ventricular repolarization in failing myocytes.
Methods: We extended an in silico electrophysiological model of human ventricular failing myocytes by including a representation of the SK channel activity. To calibrate the maximal SK current conductance (G SK), we simulated action potentials (APs) at different pacing frequencies and matched the changes in AP duration induced by SK channel inhibition or activation to available experimental data.
Results: The optimal value obtained for GSK was 4.288 μ S/ μF in mid-myocardial cells, and 6.4 μS/ μF for endocardial and epicardial cells. The simulated SK block-induced effects were consistent with experimental evidence. 1-D simulations of a transmural ventricular fiber indicated that SK channel block may prolong the QT interval and increase the transmural dispersion of repolarization, potentially increasing the risk of arrhythmia in HF.
Conclusion: Our results highlight the importance of considering the SK channels to improve the characterization of HF-induced ventricular remodeling. Simulations across various scenarios in 0-D and 1-D scales suggest that pharmacological SK channel inhibition could lead to adverse effects in failing ventricles.
期刊介绍：
IEEE Journal of Biomedical and Health Informatics publishes original papers presenting recent advances where information and communication technologies intersect with health, healthcare, life sciences, and biomedicine. Topics include acquisition, transmission, storage, retrieval, management, and analysis of biomedical and health information. The journal covers applications of information technologies in healthcare, patient monitoring, preventive care, early disease diagnosis, therapy discovery, and personalized treatment protocols. It explores electronic medical and health records, clinical information systems, decision support systems, medical and biological imaging informatics, wearable systems, body area/sensor networks, and more. Integration-related topics like interoperability, evidence-based medicine, and secure patient data are also addressed.
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