NaV1.5 or KCa2 channel blockade does not increase arrhythmia risk in hypokalemic rabbit hearts, unlike KV11.1 inhibition with dofetilide

Fig. 1. Timeline for experiment. Note that the arrhythmia quantification period during hypokalemia is placed 2.5 min after changing the solution to hypokalemic conditions in contrast to drug treatment where unpaced quantification was performed after 9 min. This is done to assess the immediate effect of hypokalemia.

Fig. 2. Effects on ventricular APD90. Top: The effects of DMSO (black), dofetilide (red), AP14145 (green), AP30663 (blue), and flecainide (orange) on ventricular APD90 measured at 3 different heart rates (200, 120 and 92 BPM), during normo- and hypokalemia. Data are presented as mean ± SEM, n = 5–8, details on sample sizes see Table 2. Bottom: Mono phasic action potential recordings from the 5 different groups (TMC, dofetilide, AP14145, AP30663 and flecainide) during baseline (black), drug (grey) and drug + hypokalemia (red) paced at 92 BPM. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 3. Effects on ventricular action potential triangulation. The effects of DMSO (black), dofetilide (red), AP14145 (green), AP30663 (blue), and flecainide (orange) on ventricular action potential triangulation (APD30-PAD90) measured at 3 different heart rates (200, 120 and 92 BPM), during normo- and hypokalemia. Data are presented as mean ± SEM, n = 5–8, details on sample sizes see Table 4. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 4. Effects of drugs on short-term variability of ventricular APD90. The effects of DMSO (black), dofetilide (red), AP14145 (green), AP30663 (blue), and flecainide (orange) on short-term variability (STV) of ventricular APD90 Data are presented as mean ± SEM, n = 5–8, details on sample sizes see Table 5. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 5. Effect of drugs on ventricular arrhythmia. Left: Number of animals with one or more VF episodes during normo- or hypokalemia. Right: Arrhythmia scores for the different treatment groups during normo- or hypokalemia (data are presented as mean ± SEM). Bottom: Examples of different arrhythmia.