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. 2025 Sep;25(9):1344-1351.
doi: 10.1007/s12012-025-10033-3. Epub 2025 Jun 24.

Arrhythmia Inducibility in the CAVB Dog Model, A Critical Analysis on Underlying Factors

Joanne J A van Bavel  1 , Henriëtte D M Beekman  1 , Marien J C Houtman  1 , Marc A Vos  1 , Marcel A G van der Heyden  2
Affiliations

Arrhythmia Inducibility in the CAVB Dog Model, A Critical Analysis on Underlying Factors

Joanne J A van Bavel et al. Cardiovasc Toxicol. 2025 Sep.

Abstract

The dog with chronic atrioventricular block (CAVB) combines a number of risk factors associated with Torsade de Pointes (TdP) arrhythmias. Nevertheless, approximately 33% of the animals are resistant to dofetilide-induced TdP arrhythmia. Of a group of 78 experimentally identical CAVB dogs, we compared TdP inducible vs. non-inducible animals for a set of basic, and cardiac electrical and mechanical parameters. Body weight, but not sex or age, is associated with TdP inducibility. Of the cardiac parameters, longer ventricular repolarization duration and increased contractility at baseline are associated with dofetilide-induced TdP arrhythmias. Differences in cardiac parameters disappeared upon dofetilide infusion. We discuss that prolonged repolarization and increased contractility may be early indications of calcium-mediated early after depolarization that may develop into TdP arrhythmias.

Keywords: AV block dog model; Arrhythmia predisposition; Remodeling; Torsade de pointes.

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Conflict of interest statement

Declarations. Conflict of Interest: Marcel AG van der Heyden is Associate Editor of Cardiovascular Toxicology. Ethical Approval: Full experimental details including notifications on ARRIVE guidelines can be found in the associated publications, as referred to in the methods section. An earlier version of this manuscript was published in the thesis entitled ‘’Drug and device testing in a preclinical model sensitive to cardiac arrhythmias’’ by JJA van Bavel.

Figures

Fig. 1
Fig. 1
Arrhythmia inducibility per general characteristic of chronic AV block dogs. A Sex (female n = 34, male n = 27), B age, C time of dofetilide experiment (morning n = 43 and afternoon n = 18), D body weight during dofetilide experiment, E body weight of female and males, F body weight at heart isolation timepoint, G heart weight/body weight (HW/BW), H lung weight/body weight, and I liver weight/body weight at heart isolation timepoint. I = inducible, and NI = non-inducible. Mean ± SD, two-way ANOVA and unpaired students t-test, * refers to p < 0.05
Fig. 2
Fig. 2
Parameters at baseline indicating arrhythmia outcome. A QT interval and B LVdP/dtmax at baseline for inducible (I) and non-inducible (NI) dogs. C Arrhythmia score reflecting the average of the three highest scored arrhythmic events after dofetilide. Mean ± SD, unpaired students t-test, * refers to p < 0.05
Fig. 3
Fig. 3
Patch clamp measurements during baseline including A action potential duration at 90% repolarization (APD90) and B short term variability (STV) of the APD90 of isolated left and right ventricular cardiomyocytes from inducible (I, n = 14 for APD90 and n = 13 for STV) and non-inducible (NI, n = 12 for APD90 and n = 11 for STV) chronic atrioventricular block dogs. Mean ± SD, unpaired Student’s t-test
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