Abstract
According to ICH S7B Guidelines evolving drug candidates need to be evaluated for effects on cardiac repolarization. An important model is the evaluation of action potential duration prolongation in vitro. The use of sinus arrhythmia pacing protocols (mimicking sinus arrhythmia in vivo) generates a cyclic structure from the repolarization duration. We use Poincare Plot derived metrics to quantify (i) central AP duration, (ii) dynamical range of AP duration and (iii) principal shape of APD trajectories expressing repolarization variability. A proof of concept study (N=3) was performed evaluating the effect of the reference drug moxifloxacin using Purkinje fibers and papillary muscles with standard micro electrode techniques. Poincare shape metrics under moxifloxacin treatment resulted in distinctly different responses between the tissue types. We conclude that the proposed method has potential for an improved quantification of repolarization variability.
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