Journal
BRITISH JOURNAL OF PHARMACOLOGY
Volume 179, Issue 5, Pages 859-881Publisher
WILEY
DOI: 10.1111/bph.15436
Keywords
anti‐ arrhythmics; arrhythmia; chronic AV block dog; history; remodelling; safety pharmacology
Categories
Funding
- Netherlands Cardio Vascular Research Initiative (CVON): the Dutch Heart Foundation
- Dutch Federation of University Medical Centres
- Netherlands Organization for Health Research and Development
- Royal Netherlands Academy of Sciences [CVON-PREDICT2 2018-30]
- Medtronic
- Amgen
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The article highlights the importance of ventricular cardiac arrhythmia and animal models in predicting drug effects, focusing on the chronic atrioventricular block (CAVB) model in dogs and summarizing its role and development in cardiovascular research. Data obtained from CAVB dogs are crucial for understanding the mechanisms of arrhythmias and drug efficacy.
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.
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