Anti‐arrhythmic investigations in large animal models of atrial fibrillation

Abstract

Atrial fibrillation (AF) constitutes an increasing health problem in the aging population. Animal models reflecting human phenotypes are needed to understand the mechanisms of AF, as well as to test new pharmacological interventions. In recent years, a number of large animal models, primarily pigs, goats, dog and horses have been used in AF research. These animals can to a certain extent recapitulate the human pathophysiological characteristics and serve as valuable tools in investigating new pharmacological interventions for treating AF. This review focuses on anti‐arrhythmic investigations in large animals. Initially, spontaneous AF in small and large mammals is discussed. This is followed by a short presentation of frequently used methods for inducing short‐ and long‐term AF. The major focus of the review is on anti‐arrhythmic compounds either frequently used in the human clinic (ranolazine, flecainide, vernakalant and amiodarone) or being promising new AF medicine candidates (IK,Ach, ISK,Ca and IK2P blockers). 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

Peptide Inhibitors of Kv1.5: An Option for the Treatment of Atrial Fibrillation

“…Despite AF being quite common in humans, spontaneously occurring AF has only been reported in relatively few animal species, such as cats, dogs, pigs, goats, sheep, cattle, horses, camelids and monkeys. In horses and cattle, the prevalence of spontaneous AF is the highest (about 2.5%), whereas in the other animals spontaneous AF cases rarely occur as an isolated problem without other cardiac diseases [143]. For this reason, AF has to be induced in the animal model through raterelated electrical remodeling or with atrial-structural remodeling [144] using models such as rapid atrial tachypacing, heart failure-associated AF and vagal tone-induced AF [143].…”

“…In horses and cattle, the prevalence of spontaneous AF is the highest (about 2.5%), whereas in the other animals spontaneous AF cases rarely occur as an isolated problem without other cardiac diseases [143]. For this reason, AF has to be induced in the animal model through raterelated electrical remodeling or with atrial-structural remodeling [144] using models such as rapid atrial tachypacing, heart failure-associated AF and vagal tone-induced AF [143]. In the following section, we will focus on experiments in which the effects of drugs targeting I Kur have been studied in animal models.…”

“…In the following section, we will focus on experiments in which the effects of drugs targeting I Kur have been studied in animal models. However, we refer readers to two reviews by Shuttler et al (2020) [145] and Saljic et al (2021) [143], where they discussed extensively the animals models for AF studies.…”

“…It has been tested in several animal models, including goats [154], pigs [155] and dogs [156]. However, nowadays, it is considered as a multichannel blocker rather than an I Kur specific blocker [143].…”

Increased fibroblast accumulation in the equine heart following persistent atrial fibrillation

“…Over the last couple of years, the horse has gained increasing interest as a large animal model of arrhythmias [18] , [19] , [20] , [21] , [22] . In contrast to other animal models usually used in AF research, such as rodents, pigs, dogs and goats, horses are frequently reported to develop AF spontaneously, just like humans [23] , [24] , [25] , [26] . Furthermore, spontaneous pulmonary vein firings were recorded in a horse recently, indicating that AF triggering processes might resemble the ones in humans, which supports the horse as a highly suitable and interesting animal for AF research [27] .…”