Characterization of a porcine model of atrial arrhythmogenicity in the context of ischaemic heart failure

Clauss, Sebastian; Schuettler, Dominik; Bleyer, Christina; Vlcek, Julia; Shakarami, Mehdi; Tomsits, Philipp; Schneider, Sarah; Maderspacher, Florian; Chataut, Kavi; Trebo, Anna; Wang, Christine; Kleeberger, Jan; Xia, Ruibing; Baloch, Elisabeth; Hildebrand, Bianca; Massberg, Steffen; Wakili, Reza und Kääb, Stefan (2020): Characterization of a porcine model of atrial arrhythmogenicity in the context of ischaemic heart failure.
In: PLOS One 15(5), e0232374

Abstract

Atrial fibrillation (AF) is a major healthcare challenge contributing to high morbidity and mortality. Treatment options are still limited, mainly due to insufficient understanding of the underlying pathophysiology. Further research and the development of reliable animal models resembling the human disease phenotype is therefore necessary to develop novel, innovative and ideally causal therapies. Since ischaemic heart failure (IHF) is a major cause for AF in patients we investigated AF in the context of IHF in a close-tohuman porcine ischaemia-reperfusion model. Myocardial infarction (AMI) was induced in propofol/fentanyl/ midazolam-anaesthetized pigs by occluding the left anterior descending artery for 90 minutes to model ischaemia with reperfusion. After 30 days ejection fraction (EF) was significantly reduced and haemodynamic parameters (pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP), left ventricular enddiastolic pressure (LVEDP)) were significantly elevated compared to age/weight matched control pigs without AMI, demonstrating an IHF phenotype. Electrophysiological properties (sinus node recovery time (SNRT), atrial/AV nodal refractory periods (AERP, AVERP)) did not differ between groups. Atrial burst pacing at 1200 bpm, however, revealed a significantly higher inducibility of atrial arrhythmia episodes including AF in IHF pigs (3/15 vs. 10/16, p = 0.029). Histological analysis showed pronounced left atrial and left ventricular fibrosis demonstrating a structural substrate underlying the increased arrhythmogenicity. Consequently, selective ventricular infarction via LAD occlusion causes haemodynamic alterations inducing structural atrial remodeling which results in increased atrial fibrosis as the arrhythmogenic atrial substrate in pigs with IHF.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1932-6203
• Sprache: Englisch