The canine chronic atrioventricular block model in cardiovascular preclinical drug research

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.