Martin Manninger1, David Zweiker2, Arne van Hunnik3, Alessio Alogna4, Anton J Prassl5, Julia Schipke6, Stef Zeemering3, Birgit Zirngast7, Patrick Schönleitner3, Michael Schwarzl8, Viktoria Herbst2, Eva Thon-Gutschi2, Stefan Huber7, Ursula Rohrer2, Jakob Ebner2, Helmut Brussee2, Burkert M Pieske3, Frank R Heinzel3, Sander Verheule3, Gudrun Antoons3, Andreas Lueger2, Christian Mühlfeld6, Gernot Plank5, Ulrich Schotten3, Heiner Post9, Daniel Scherr10. 1. Division of Cardiology, Department of Medicine, Medical University of Graz, Graz, Austria. Electronic address: martin.manninger-wuenscher@medunigraz.at. 2. Division of Cardiology, Department of Medicine, Medical University of Graz, Graz, Austria. 3. Department of Physiology, Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, The Netherlands. 4. Department of Cardiology, Charité University Medicine, Campus Virchow-Klinikum, Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany. 5. Institute of Biophysics, Medical University of Graz, Graz, Austria. 6. Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany. 7. Department of Cardiothoracic Surgery, Medical University of Graz, Graz, Austria. 8. Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf, Hamburg, Germany; DZHK (German Centre for Cardiovascular Research), Partner site Hamburg/Kiel/Lübeck, Berlin, Germany. 9. Department of Cardiology, Charité University Medicine, Campus Virchow-Klinikum, Berlin, Germany; Department of Cardiology, Contilia Heart and Vessel Centre, St. Marien-Hospital Mülheim, Mülheim, Germany. 10. Division of Cardiology, Department of Medicine, Medical University of Graz, Graz, Austria; Department of Cardiology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
Abstract
BACKGROUND: Arterial hypertension (HT) contributes to progression of atrial fibrillation (AF) via unknown mechanisms. OBJECTIVE: We aimed to characterize electrical and structural changes accounting for increased AF stability in a large animal model of rapid atrial pacing (RAP)-induced AF combined with desoxycorticosterone acetate (DOCA)-induced HT. METHODS: Eighteen pigs were instrumented with right atrial endocardial pacemaker leads and custom-made pacemakers to induce AF by continuous RAP (600 beats/min). DOCA pellets were subcutaneously implanted in a subgroup of 9 animals (AF+HT group); the other 9 animals served as controls (AF group). Final experiments included electrophysiology studies, endocardial electroanatomic mapping, and high-density mapping with epicardial multielectrode arrays. In addition, 3-dimensional computational modeling was performed. RESULTS: DOCA implantation led to secondary HT (median [interquartile range] aortic pressure 109.9 [100-137] mm Hg in AF+HT vs 82.2 [79-96] mm Hg in AF; P < .05), increased AF stability (55.6% vs 12.5% of animals with AF episodes lasting >1 hour; P < .05), concentric left ventricular hypertrophy, atrial dilatation (119 ± 31 cm2 in AF+HT vs 78 ± 23 cm2 in AF; P < .05), and fibrosis. Collagen accumulation in the AF+HT group was mainly found in non-intermyocyte areas (1.62 ± 0.38 cm3 in AF+HT vs 0.96 ± 0.3 cm3 in AF; P < .05). Left and right atrial effective refractory periods, action potential durations, endo- and epicardial conduction velocities, and measures of AF complexity were comparable between the 2 groups. A 3-dimensional computational model confirmed an increase in AF stability observed in the in vivo experiments associated with increased atrial size. CONCLUSION: In this model of secondary HT, higher AF stability after 2 weeks of RAP is mainly driven by atrial dilatation.
BACKGROUND: Arterial hypertension (HT) contributes to progression of atrial fibrillation (AF) via unknown mechanisms. OBJECTIVE: We aimed to characterize electrical and structural changes accounting for increased AF stability in a large animal model of rapid atrial pacing (RAP)-induced AF combined with desoxycorticosterone acetate (DOCA)-induced HT. METHODS: Eighteen pigs were instrumented with right atrial endocardial pacemaker leads and custom-made pacemakers to induce AF by continuous RAP (600 beats/min). DOCA pellets were subcutaneously implanted in a subgroup of 9 animals (AF+HT group); the other 9 animals served as controls (AF group). Final experiments included electrophysiology studies, endocardial electroanatomic mapping, and high-density mapping with epicardial multielectrode arrays. In addition, 3-dimensional computational modeling was performed. RESULTS:DOCA implantation led to secondary HT (median [interquartile range] aortic pressure 109.9 [100-137] mm Hg in AF+HT vs 82.2 [79-96] mm Hg in AF; P < .05), increased AF stability (55.6% vs 12.5% of animals with AF episodes lasting >1 hour; P < .05), concentric left ventricular hypertrophy, atrial dilatation (119 ± 31 cm2 in AF+HT vs 78 ± 23 cm2 in AF; P < .05), and fibrosis. Collagen accumulation in the AF+HT group was mainly found in non-intermyocyte areas (1.62 ± 0.38 cm3 in AF+HT vs 0.96 ± 0.3 cm3 in AF; P < .05). Left and right atrial effective refractory periods, action potential durations, endo- and epicardial conduction velocities, and measures of AF complexity were comparable between the 2 groups. A 3-dimensional computational model confirmed an increase in AF stability observed in the in vivo experiments associated with increased atrial size. CONCLUSION: In this model of secondary HT, higher AF stability after 2 weeks of RAP is mainly driven by atrial dilatation.
Authors: Martin Manninger; David Zweiker; Martin Dobrovnik; Arne van Hunnik; Ursula Rohrer; Birgit Zirngast; Viktoria Herbst; Heinrich Maechler; Ulrich Schotten; Andreas Zirlik; Daniel Scherr Journal: Sci Rep Date: 2020-07-17 Impact factor: 4.379
Authors: Ge Jin; Martin Manninger; Gabriel Adelsmayr; Michael Schwarzl; Alessio Alogna; Patrick Schönleitner; David Zweiker; Florian Blaschke; Mohammad Sherif; Snjezana Radulovic; Paulina Wakula; Sylvia Schauer; Gerald Höfler; Ursula Reiter; Gert Reiter; Heiner Post; Daniel Scherr; Karoly Acsai; Gudrun Antoons; Burkert Pieske; Frank R Heinzel Journal: ESC Heart Fail Date: 2020-11-29