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Review
. 2022 Mar;179(5):859-881.
doi: 10.1111/bph.15436. Epub 2021 May 4.

The canine chronic atrioventricular block model in cardiovascular preclinical drug research

Vera Loen  1 , Marc A Vos  1 , Marcel A G van der Heyden  1
Affiliations
Review

The canine chronic atrioventricular block model in cardiovascular preclinical drug research

Vera Loen et al. Br J Pharmacol. 2022 Mar.

Abstract

Ventricular cardiac arrhythmia is a life threating condition arising from abnormal functioning of many factors in concert. Animal models mirroring human electrophysiology are essential to predict and understand the rare pro- and anti-arrhythmic effects of drugs. This is very well accomplished by the canine chronic atrioventricular block (CAVB) model. Here we summarize canine models for cardiovascular research, and describe the development of the CAVB model from its beginning. Understanding of the structural, contractile and electrical remodelling processes following atrioventricular (AV) block provides insight in the many factors contributing to drug-induced arrhythmia. We also review all safety pharmacology studies, efficacy and mechanistic studies on anti-arrhythmic drugs in CAVB dogs. Finally, we compare pros and cons with other in vivo preclinical animal models. In view of the tremendous amount of data obtained over the last 100 years from the CAVB dog model, it can be considered as man's best friend in preclinical drug research. LINKED ARTICLES: This article is part of a themed issue on Preclinical Models for Cardiovascular disease research (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.5/issuetoc.

Keywords: anti-arrhythmics; arrhythmia; chronic AV block dog; history; remodelling; safety pharmacology.

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Conflict of interest statement

M.V. is supported by collaborations with Medtronic and Amgen. V.L. and M.v.d.H. declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Timeline of chronic atrioventricular block (CAVB) dog development and usage in pharmacological research. Inserts: (1) Title page of the landmark Erlanger and Blackman (1910) paper and description of the creation of AV block in dog number 7 on 17th of March 1906. This dog experienced ‘syncopal attacks’ and was found dead in the morning of 15th of April 1906, after 4 weeks of permanent AV block. (2) ECG recording (Einthoven III) of a self‐terminating drug‐induced Torsade de Pointes arrhythmia
FIGURE 2
FIGURE 2
Depiction of cardiac changes in the chronic atrioventricular block (CAVB) dog in time following AV block, compared with the sinus rhythm (SR) animal. See text for further explanation. Bar graphs represent Torsade de Pointes(TdP) inducibility. CO, cardiac output; HR, heart rhythm; HW/BW, heart weight/body weight ratio; LV dP/dt, left ventricular pressure
See this image and copyright information in PMC

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