AUTHOR=Nalos Lukáš , Jarkovská Dagmar , Švíglerová Jitka , Süß Annabell , Záleský Jakub , Rajdl Daniel , Krejčová Milada , Kuncová Jitka , Rosenberg Josef , Štengl Milan 

TITLE=TdP Incidence in Methoxamine-Sensitized Rabbit Model Is Reduced With Age but Not Influenced by Hypercholesterolemia

JOURNAL=Frontiers in Physiology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2021.692921

DOI=10.3389/fphys.2021.692921

ISSN=1664-042X

ABSTRACT=Metabolic syndrome is associated with hypercholesterolemia, cardiac remodeling and increased susceptibility to ventricular arrhythmias. Effects of diet-induced hypercholesterolemia on susceptibility to Torsades de Pointes arrhythmias (TdP) together with potential indicators of arrhythmic risk were investigated in 3 experimental groups of Carlsson´s rabbit model:  1) young rabbits (YC, young control, age 12-16 weeks), older rabbits (AC, adult control, age 20-24 weeks) and older age-matched cholesterol-fed rabbits (CH, cholesterol, age 20-24 weeks).  TdP was induced by α-adrenergic stimulation by methoxamine and IKr block in 83% of YC rabbits, 18% of AC rabbits and 21% of CH rabbits. High incidence of TdP was associated with high incidence of single (SEB) and multiple ectopic beats (MEB), but the QTc prolongation and short-term variability (STV) were similar in all 3 groups. In TdP-susceptible rabbits, STV was significantly higher compared to arrhythmia-free rabbits but not to rabbits with other than TdP arrhythmias (SEB, MEB). Amplitude-aware permutation entropy analysis of baseline ECG could identify arrhythmia-resistant animals with high sensitivity and specificity. The data indicate that the TdP susceptibility in methoxamine-sensitized rabbits is affected by the age of rabbits but probably not by hypercholesterolemia. Entropy analysis could potentially stratify the arrhythmic risk and identify the low risk individuals.