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.
Highlights
Atrial fibrillation (AF) is the most common sustained arrhythmia and has shown an increase in incidence, prevalence and AF-associated mortality over the last decades [1]
Ventricular myocardial infarction was induced by balloon occlusion of the left anterior descending artery (LAD) distal to the first diagonal branch at day 0 (d0)
Selective ventricular infarction without atrial involvement was verified macroscopically after 30 days of reperfusion when the hearts were removed (d30). 6 pigs died during balloon occlusion due to ventricular fibrillation and 6 pigs died within 30 days of reperfusion due to heart failure related complications (sudden cardiac death (SCD)) and were not included in our analysis
Summary
Atrial fibrillation (AF) is the most common sustained arrhythmia and has shown an increase in incidence, prevalence and AF-associated mortality over the last decades [1]. -called remodeling processes contribute solitary or combined to the development of AF: (I) electrical remodeling which includes changes in calcium handling, ion currents or electrical conduction, (II) structural remodeling including atrial enlargement and fibrosis and (III) autonomic remodeling with changes in autonomic nerve density and innervation patterns [3]. Since these alterations create a vulnerable atrial substrate any trigger such as a premature atrial capture beat can initiate AF [5]. The likelihood of AF maintenance is higher in patients with dilated, i.e. structurally remodeled atria, AF can occur in structurally healthy atria demonstrating the heterogeneity of the disease [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
