Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Rohrer, U.
Atrial Fibrillation and Hypertension – Structural Remodelling in a Porcine Model of Rapid Atrial Pacing
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2016. pp.
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- Autor*innen der Med Uni Graz:
- Rohrer Ursula
- Betreuer*innen:
- Manninger-Wünscher Martin
- Scherr Daniel
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- Abstract:
- Introduction: Atrial fibrillation (AF) is the most common sustained arrhythmia in humans and is associated with an increased risk of stroke, morbidity and death. Arterial hypertension (HT) is found in 60-80% of AF patients, is an independent predictor of new-onset AF and triggers hypertrophic and profibrotic pathways resulting in structural remodelling potentially favouring the progression of the arrhythmia. Due to overlap of multiple possible risk factors and large heterogeneity in patients, risk-factor dependent structural remodelling remains incompletely understood. In a large animal model we combined rapid atrial pacing (RAP) generating atrial fibrillation with DOCA-(desoxycorticosterone acetate)-induced arterial hypertension giving the opportunity to elucidate risk-factor dependent mechanisms favouring the progression of atrial fibrillation. In this study, we aimed to investigate the impact of arterial hypertension on structural remodelling during atrial fibrillation. Material and Methods: 17 landrace pigs were implanted with custom made, telemetrically controllable pacemakers to induce AF. DOCA pellets were subcutaneously implanted in a subgroup of 9 animals (RAP+DOCA), the other 8 animals served as controls (RAP). Pacemakers were activated at a rate of 600/min two weeks before histological samples of both atria were obtained for analysis of cardiomyocyte area (HE staining), atrial fibrosis (Picrosirius-Red staining) and distribution of connexin 43 (Cx43 immunofluorescence for confocal microscopic analysis). Results: Animals in the RAP+DOCA group had significant arterial hypertension and concentric left ventricular hypertrophy. HT was associated with severe structural remodelling. Histologic evaluation showed biatrial cardiomyocyte hypertrophy (cross-section cardiomyocyte area: LA: 243.7±41.8 vs. 174.4±36.0 µm², p<0.01, RA: 271.6 (232,326) vs. 186.8(169,202) µm², p<0.01) as well as interstitial fibrosis (LA: 14.0±2.2 vs. 8.5±1.6 %, p<0.001; RA: 14.4±3.4 vs. 8.3±1.5 %, p<0.001) while distribution of Cx43 remained unchanged (0.37±0.1 vs. 0.39±0.1 ratio between Cx43 located on longitudinal sides and at intercalated disks, n.s.). Conclusion: In this model of secondary hypertension, HT triggers hypertrophic and profibrotic pathways revealing a distinct form of risk factor dependent structural remodelling in atrial fibrillation. These findings will help to understand mechanisms favouring the progression of atrial fibrillation in patients with arterial hypertension.