Characterization of Atrial and Ventricular Structural Remodeling in a Porcine Model of Atrial Fibrillation Induced by Atrial Tachypacing

Abstract

Background: Atrial fibrillation (AF) is characterized by electrical and structural remodeling. Irregular and/or fast atrio-ventricular (AV) conduction during AF can result in AV dyssynchrony, tachymyopathy, pressure and volume overload with subsequent dilatation, valve regurgitation, and ventricular dysfunction with progression to heart failure. Objective: To gain further insight into the myocardial pathophysiological changes induced by right atrial tachypacing (A-TP) in a large animal model. Methods: A total of 28 Landrace pigs were randomized as 14 into AF-induced A-TP group and 14 pigs to control group. AF pigs were tachypaced for 43 ± 4 days until in sustained AF. Functional remodeling was investigated by echocardiography (after cardioversion to sinus rhythm). Structural remodeling was quantified by histological preparations with picrosirius red and immunohistochemical stainings. Results: A-TP resulted in decreased left ventricular ejection fraction (LVEF) accompanied by increased end-diastolic and end-systolic left atrium (LA) volume and area. In addition, A-TP was associated with mitral valve (MV) regurgitation, diastolic dysfunction and increased atrial and ventricular fibrotic extracellular matrix (ECM). Conclusions: A-TP induced AF with concomitant LV systolic and diastolic dysfunction, increased LA volume and area, and atrial and ventricular fibrosis.

Increased fibroblast accumulation in the equine heart following persistent atrial fibrillation

“…A few studies have previously investigated the alterations in vasculature during AF. Pigs subjected to atrial tachypacing and kept in AF for approximately six weeks had an increase in capillary density in RA and the same tendency was observed in LA [46] . Data from human studies are however pointing towards another direction either showing no change or even a reduction in capillary number [47] , [48] , [49] , [50] , [51] .…”

Anti‐arrhythmic investigations in large animal models of atrial fibrillation

“…The goat model of rapid atrial tachypacing has later been used to test the effect of anti‐arrhythmic drugs and to investigate how the properties of these drugs change upon atrial electrical remodelling. The rapid atrial tachypacing model has further been developed and is today commonly used in various other large animals, including horses (Hesselkilde et al, 2019), pigs (Citerni et al, 2020) and dogs (Morillo et al, 1995). ECG examples of both tachypacing‐induced AF and persistent AF in various animals and humans are shown in Figure 1.…”

Model Systems for Addressing Mechanism of Arrhythmogenesis in Cardiac Repair

“…A commonly used model of AF is atrial tachypacing. Although it is employed in dogs [30], sheep [31], pigs [32], and rabbits [33], its usage has not been extended over to smaller animals due to their significantly higher heart rates [34]. Tachypacing may also be used on the ventricles to study HF-induced arrhythmogenesis [35].…”