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

PLoS One. 2020 May 4;15(5):e0232374. doi: 10.1371/journal.pone.0232374. eCollection 2020.

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-to-human 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrial Fibrillation / etiology
  • Atrial Fibrillation / pathology
  • Atrial Fibrillation / physiopathology*
  • Coronary Angiography
  • Disease Models, Animal
  • Electrocardiography
  • Heart Failure / complications*
  • Heart Failure / physiopathology
  • Humans
  • Myocardial Reperfusion Injury / complications*
  • Myocardial Reperfusion Injury / physiopathology
  • Stroke Volume
  • Swine

Grants and funding

This work was supported by the German Centre for Cardiovascular Research (DZHK; 81X2600210, 81X2600204 to SC, SK; 81X3600208, 81X2600249 to SC; 81Z4600241 to SK; 81X2600234, 81X2600232 to SK, RW), by the European Union’s Horizon 2020 research and innovation Programme under grant agreement No 633193 (CATCH ME to SK), by the LMU Munich‘s Institutional Strategy LMUexcellent within the framework of the German Excellence Initiative (to SC, SM), the Förderprogramm für Forschung und Lehre (FöFöLe; 962 to SC), the German Research Council (DFG; SFB1123 and SFB914 to SM; Clinician Scientist Program In Vascular Medicine (PRIME, MA 2186/14-1) to DS and PT), and the Heinrich-and-Lotte-Mühlfenzl Stiftung (to SC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.