A detailed Sensitivity Analysis of the Human Ventricular Cell Model in one-dimensional and two-dimensional tissue using GPU computing.

Ventricular Arrhythmia is the leading cause of sudden cardiac death in the world. One goal of the CiPA initiative, sponsored by the FDA, is the in-silico quantification of the proarrhythmic effects of drugs. CiPA has selected the human ventricular model developed by O’Hara et al. (OVVR) as the most complete model to be used. So far, single-cell dynamics has been the focus of the study due to the computational complexity of the OVVR model (61 differential equations per cell to simulate 12 ionic currents). However, single-cell results do not translate to the 2D tissue behavior, where the coupling between cells induces emergent behavior like reentrant spiral waves. We present the first sensitivity analysis of the OVVR model in tissue computed using our WebGL library (Abubu.js) for simulation of 1D tissue faster than real-time, and of 2D tissue in near-realtime, without the need for a supercomputer. We quantify the dynamics in 1D by calculating action potential duration (APD) and conduction velocity (CV) restitution curves as we vary the parameter of the model. Surprisingly, we found a marginal effect on the APD restitution or the CV restitution for most currents. We conclude with a study of spiral-wave dynamics for the relevant parameters in 2D.