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Atrial remodeling and the substrate for atrial fibrillation in rat hearts with elevated afterload
Shang-Jin Kim1, Stéphanie C M Choisy, Palash Barman
1Cardiovascular Research Laboratories, School of Physiology & Pharmacology, University of Bristol, Bristol, UK.
Insights
Elevated afterload, even without hypertension, causes atrial remodeling and increases atrial fibrillation (AF) risk. This study reveals fibrosis and conduction issues linked to connexin43 changes in a rat model.
Area of Science:
- Cardiology
- Electrophysiology
- Cardiac Remodeling
Background:
- Arterial hypertension and left ventricular hypertrophy are known risk factors for atrial fibrillation (AF).
- The direct relationship between elevated afterload and the development of AF is not fully understood.
- Investigating atrial remodeling and arrhythmia substrates in response to elevated afterload is crucial.
Purpose of the Study:
- To investigate atrial remodeling and the substrate for arrhythmia in a surgical model of elevated afterload in rats.
- To determine the impact of increased afterload on atrial electrophysiology and structure.
- To elucidate the mechanisms linking elevated afterload to AF.
Main Methods:
- Surgical induction of partial stenosis of the ascending aorta (AoB) in male Wistar rats to create elevated afterload.
- Sham operation served as the control group.
- Electrophysiological recordings (unipolar electrograms) and histological/immunocytochemical analyses of left atrial tissue at 8, 14, and 20 weeks post-surgery.
Main Results:
- AoB rats exhibited significant left atrial hypertrophy and fibrosis at 14 and 20 weeks.
- Pacing-induced AF incidence and duration were increased in AoB rats at 20 weeks.
- Conduction velocity was reduced, with increased inhomogeneity, and connexin43 expression was decreased in AoB hearts.
Conclusions:
- Elevated afterload, independent of systemic hypertension, induces AF and left atrial remodeling in a small-animal model.
- Fibrosis, altered connexin43 expression, and conduction abnormalities contribute to the arrhythmogenic substrate.
- This model provides insights into the mechanisms underlying AF development due to increased cardiac afterload.
Background:
Although arterial hypertension and left ventricular hypertrophy are considered good epidemiological indicators of the risk of atrial fibrillation (AF) in patients, the link between elevated afterload and AF remains unclear. We investigated atrial remodeling and the substrate for arrhythmia in a surgical model of elevated afterload in rats.
Methods And Results:
Male Wistar rats (aged 3-4 weeks) were anesthetized and subjected to either partial stenosis of the ascending aorta (AoB) or sham operation (Sham). Experiments were performed on excised hearts 8, 14, and 20 weeks after surgery. Unipolar electrograms were recorded from the left atrial epicardial surface of perfused hearts using a 5×5 electrode array. Cryosections of left atrial tissue were retained for histological and immunocytochemical analyses. Compared to Sham, AoB hearts showed marked left atrial hypertrophy and fibrosis at 14 and 20 weeks postsurgery. The incidence and duration of pacing-induced AF was increased in hearts from AoB rats at 20 weeks postsurgery. The substrate for arrhythmia was associated with reduced vectorial conduction velocity and greater inhomogeneity in conduction but without changes in effective refractory period. Left atrial expression of the gap junction protein, connexin43, was markedly reduced in AoB compared with Sham hearts.
Conclusions:
Using a small-animal model, we demonstrate that elevated afterload in the absence of systemic hypertension results in increased inducibility of AF and left atrial remodeling involving fibrosis, altered atrial connexin43 expression, and marked conduction abnormalities.
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