Figure 3.

Five‐dimensional hazard map of drug‐induced arrhythmias. Top: Five‐dimensional data are visualized as a cluster of three‐dimensional subspace distributed in a plane with axes of I _Ks block and I _Na,L block. The coordinate system of subspace consists of the extent of block of I _Kr, I _Na and I _Ca,L. Bottom: In each subspace (in this case, I _Ks block = 0% and I _Na,L block = 0%), the dose‐dependent effect of the drug (bepridil) can be traced as a trajectory. The trajectories were generated by functions, and the numbers on them represent the drug concentrations expressed as multiples of ETPC_unbound. The region of arrhythmia is indicated as brown blocks. The inset shows the concentration–block relations of five ion currents. It demonstrates that virtually no inhibitory effects were observed for I _Ks or I _Na,L in the concentration ranges studied (shaded area). ECG changes at various concentrations are shown to the right with the corresponding activation sequence in the heart.