Dataset Information

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.

SUBMITTER: Citerni C

PROVIDER: S-EPMC7160334 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Citerni Carlotta C Kirchhoff Jeppe J Olsen Lisbeth Høier LH Sattler Stefan Michael SM Gentilini Fabio F Forni Monica M Zannoni Augusta A Grunnet Morten M Edvardsson Nils N Bentzen Bo Hjorth BH Diness Jonas Goldin JG

Frontiers in veterinary science 20200409

<b>Background:</b> 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. <b>Objective:</b> To gain further insight into the myocardial pathophysiological changes induced by right atrial tachypacing (A-TP) in a large an ...[more]

PMID: 32328502

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Project description:Background and purposeInhibition of the G-protein gated ACh-activated inward rectifier potassium current, IK,ACh may be an effective atrial selective treatment strategy for atrial fibrillation (AF). Therefore, the anti-arrhythmic and electrophysiological properties of a novel putatively potent and highly specific IK,ACh inhibitor, XAF-1407 (3-methyl-1-[5-phenyl-4-[4-(2-pyrrolidin-1-ylethoxymethyl)-1-piperidyl]thieno[2,3-d]pyrimidin-6-yl]azetidin-3-ol), were characterised for the first time in vitro and investigated in horses with persistent AF.Experimental approachThe pharmacological ion channel profile of XAF-1407 was investigated using cell lines expressing relevant ion channels. In addition, eleven horses were implanted with implantable cardioverter defibrillators enabling atrial tachypacing into self-sustained AF. The electrophysiological effects of XAF-1407 were investigated after serial cardioversions over a period of 1 month. Cardioversion success, drug-induced changes of atrial tissue refractoriness, and ventricular electrophysiology were assessed at baseline (day 0) and days 3, 5, 11, 17, and 29 after AF induction.Key resultsXAF-1407 potently and selectively inhibited Kir 3.1/3.4 and Kir 3.4/3.4, underlying the IK,ACh current. XAF-1407 treatment in horses prolonged atrial effective refractory period as well as decreased atrial fibrillatory rate significantly (~20%) and successfully cardioverted AF, although with a decreasing efficacy over time. XAF-1407 shortened atrioventricular-nodal refractoriness, without effect on QRS duration. QTc prolongation (4%) within 15 min of drug infusion was observed, however, without any evidence of ventricular arrhythmia.Conclusion and implicationsXAF-1407 efficiently cardioverted sustained tachypacing-induced AF of short duration in horses without notable side effects. This supports IK,ACh inhibition as a potentially safe treatment of paroxysmal AF in horses, suggesting potential clinical value for other species including humans.

Dataset Information

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

Publications

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

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