Short-term Variability of Repolarization Is Superior to Other Repolarization Parameters in the Evaluation of Diverse Antiarrhythmic Interventions in the Chronic Atrioventricular Block Dog

Figures

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  FIGURE 1.. A, Arrhythmogenesis in the CAVB dog model. B, Suppression and prevention experimental setups for antiarrhythmic drug evaluation. Lines define intervals during which arrhythmias were monitored to determine TdP inducibility and AS at corresponding periods. Dots define timepoints at which electrophysiological parameters (ECG intervals, MAPD, and STV) were measured. For the proarrhythmic challenge period, they were measured before incidence of the first ectopic beat or (if possible) TdP episode. In the prevention experiments, in the absence of arrhythmias, these parameters were measured at the end of the proarrhythmic challenge infusion (15 minutes). C, Induction of EADs by a proarrhythmic challenge in isolated canine ventricular cardiomyocytes. EADs occur under conditions of increased action potential duration and STV of repolarization. AS, arrhythmia score; MAPD, monophasic action potential duration; STV, short-term variability of repolarization; X, End of antiarrhythmic drug in suppression experiment; Y, end of antiarrhythmic drug in prevention experiment; EB, ectopic beat; TdP, Torsade de Pointes; EADs, early afterdepolarizations.

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  FIGURE 2.. Temporal dispersion of repolarization (STV) is superior to repolarization (QTc) and its spatial (interventricular ΔMAPD) dispersion parameters in reflecting the magnitude of antiarrhythmic effect in suppression (A) and prevention (B) experiments against TdP arrhythmias. Moderate antiarrhythmic effect by low-dose levcromakalim was accompanied by the reduction of STV but not of other repolarization parameters (QTc and ∆MAPD). Subsequent administration of high-dose levcromakalim exerted stronger antiarrhythmic activity associated with a further STV reduction. Arrhythmias are plotted as percentage (number of TdP observed/number of experiments). Electrophysiological parameters: values are represented as mean ± SD. QTc, QT corrected for heart rate (van de Water formula); STV of repolarization (derived from LV MAPD); ΔMAPD, interventricular dispersion of repolarization (determined as LV−RV MAPD).

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  FIGURE 3.. STV of repolarization strongly indicates the pharmacological antiarrhythmic efficacy in suppression (A) and prevention (B) experiments. STV values (dots), depicted for suppression (after antiarrhythmic drug administration) and prevention (after dofetilide administration) experiments are represented as mean ± SD. AS (bars) is expressed as mean ± SD. TdP inducibility is indicated as number of dogs with TdP/number of experiments. nq: not quantifiable. STV, short-term variability of repolarization (derived from LV MAPD).