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

Autor: Lukáš Nalos, Dagmar Jarkovská, Jitka Švíglerová, Annabell Süß, Jakub Záleský, Daniel Rajdl, Milada Krejčová, Jitka Kuncová, Josef Rosenberg, Milan Štengl
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Frontiers in Physiology, Vol 12 (2021)
Druh dokumentu: article
ISSN: 1664-042X
DOI: 10.3389/fphys.2021.692921
Popis: 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 three 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 three groups. In TdP-susceptible rabbits, STV was significantly higher compared with arrhythmia-free rabbits but not with 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.
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