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

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

Format: Article
Diterbitkan: Frontiers Media S.A. 2021-06-01

Deskripsi

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.