A Computational Framework for Analyzing Calcium Signals Reveals Edema-Induced Transitions in Cardiac Calcium-Handling Dynamics

Myocardial edema is associated with cardiac electrical instability, but the cellular mechanisms linking osmotic cell swelling to arrhythmias remain unclear. Hypoosmotic conditions are hypothesized to drive transitions between dynamical regimes (e.g., spiral waves and multiple wavelets), producing distinct calcium oscillatory dynamics that act as markers of the underlying electrophysiological state. This study presents an integrated computational framework combining analysis of optical mapping data with mechanistic mathematical modeling to investigate calcium dynamics in cardiomyocyte monolayers under varying extracellular osmolality conditions. We developed an enhanced signal processing pipeline that reconstructs dynamic baselines from local minima using piecewise linear interpolation, enabling robust detection and characterization of calcium transients in highly heterogeneous and aperiodic signals. The computational workflow incorporated peak detection algorithms adapted for irregular oscillatory patterns, extraction of calcium transient features (amplitude, time to peak, decay durations at 30%, 50%, and 80% of peak amplitude) across spatial regions corresponding to different excitation regimes, and mathematical modeling to investigate the effects of hypoosmotic swelling at a cellular level. The parameters of the Gattoni (2016) rat ventricular cardiomyocyte model were modified to match experimental observations of the calcium transients. Simulation suggests that hypoosmotic swelling increases sarcolemmal calcium pump activity and elevates cytosolic concentrations of calmodulin and troponin, promoting alternans and delayed afterdepolarizations.