Short-term Variability of Repolarization Is Superior to Other Repolarization Parameters in the Evaluation of Diverse Antiarrhythmic Interventions in the Chronic Atrioventricular Block Dog
“…In the CAVB dog model, the very strong antiarrhythmic effect of GS967 against TdP [complete (100%) suppression of TdP] resembled that of the I CaL blockers flunarizine and verapamil (Oros et al ., ) and the Na–Ca exchanger inhibitor SEA0400 (Bourgonje et al ., ). However, unlike GS967, all these drugs restored STV to baseline levels and significantly diminished ectopic activity (Bossu et al ., ). Unfortunately, in comparison with GS967 as shown in this study, detailed mapping studies on the effect of flunarizine, verapamil and SEA0400 on intraventricular spatial dispersion of repolarization in the CAVB dog are lacking to date.…”
Section: Discussionmentioning
“…The remodelling processes occurring after creation of AV block, at the structural, mechanical and electrical levels, have been well described in this animal model (Oros et al ., ). The inducibility of TdP arrhythmias upon dofetilide administration persist for more than 20 min (Oros et al ., ), which allows the testing of (pharmacological) antiarrhythmic interventions (Bossu et al ., ).…”
Section: Methodsmentioning
“…Alongside ventricular remodelling, anaesthesia and bradycardia further challenge the repolarisation reserve in the canine CAVB model. [14,21,40] When the ‘final hit’ in the form of an IKr-blocker is infused, the absolute value of STV increases abruptly in the minutes preceding a storm of TdPs (STV arrhythmic ). [13–15,36,41,42] Moreover, STV has been shown to be a superior repolarisation parameter to predict the imminent proarrhythmic outcome, compared with repolarisation prolongation and interventricular dispersion of repolarisation.…”
Section: Ventricular Remodelling In the Chronic Complete Atrioventricmentioning
“…Remarkably, the incidence of monomorphic ventricular tachycardia was also not, significantly, lowered following progesterone pretreatment. Moreover, given the imperfect relationship between QTc duration and proarrhythmia, the authors determined the beat‐to‐beat variability in ventricular repolarization, expressed as QT STV , which is an improved biomarker for TdP arrhythmia . In this endeavor, they showed, for the first time, that progesterone restrains dofetilide‐induced QT STV increase and thus lowered temporal dispersion of repolarization.…”
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“…Indeed, both inhibition of inward (Ca 2+ ) or enhancing outward (K + ) currents shortens action potential duration and thus QTc. I Ca‐L inhibition, for example by verapamil, is a very effective antiarrhythmic strategy, although with the cost of affecting contractility. Pharmacological activation of I Ks by the newly developed compound ML277 was shown to shorten action potential duration in canine and guinea pig ventricular cardiomyocytes .…”
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