Circadian Models of Serum Potassium, Sodium, and Calcium Concentrations in Healthy Individuals and Their Application to Cardiac Electrophysiology Simulations at Individual Level

In the article a brief description of the biological basis of the regulation of human biological clocks was presented in order to introduce the role of circadian rhythms in physiology and specifically in the pharmacological translational tools based on the computational physiology models to motivate the need to provide models of circadian fluctuation in plasma cations. The main aim of the study was to develop statistical models of the circadian rhythm of potassium, sodium, and calcium concentrations in plasma. The developed ion models were further tested by assessing their influence on QT duration (cardiac endpoint) as simulated by the biophysically detailed models of human left ventricular cardiomyocyte. The main results are model equations along with an electronic supplement to the article that contains a fully functional implementation of all models.