Computational modeling for cardiac safety pharmacology analysis: Contribution of fibroblasts.

Coupling cardiomyocytes and fibroblasts are predicted to decrease proarrhythmic susceptibility under dofetilide, vardenafil and nebivolol block. However, this result is sensitive to parameters which define the electrophysiological function of the fibroblast. Fibroblast membrane capacitance and conductance (C and G) have less of an effect on APD than the fibroblast resting membrane potential (E). This study suggests that in both theoretical models and experimental tissue constructs that represent cardiac tissue, both cardiomyocytes and non-muscle cells should be considered when testing cardiac pharmacological agents.