ISSN 1671-5411 CN 11-5329/R
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Please cite this article as: LIU Y, ZHU XY, SONG ZL, QIN M, XU CH, LIU X. Right atrial mechanism contributes to atrial fibrillation in a canine model of pulmonary arterial hypertension. J Geriatr Cardiol 2022; 19(0): 1−10. DOI: 10.11909/j.issn.1671-5411.2022.12.011
Citation: Please cite this article as: LIU Y, ZHU XY, SONG ZL, QIN M, XU CH, LIU X. Right atrial mechanism contributes to atrial fibrillation in a canine model of pulmonary arterial hypertension. J Geriatr Cardiol 2022; 19(0): 1−10. DOI: 10.11909/j.issn.1671-5411.2022.12.011

Right atrial mechanism contributes to atrial fibrillation in a canine model of pulmonary arterial hypertension

doi: 10.11909/j.issn.1671-5411.2022.12.011
*The authors contributed equally to this manuscript
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  •  OBJECTIVES To investigate proarrhythmic substrates of atrial fibrillation (AF) in a canine model of dehydromonophylline (DMCT)-induced pulmonary arterial hypertension (PAH). METHODS All cannines (n = 12) underwent baseline echocardiographic and hemodynamic examinations, 7 of which were injected with DMCT (3.0 mg/kg) to induce PAH via jugular vein cannulation. The control beagles (n = 5) were given the same dose of normal saline. Then, both groups were monitored by insertable cardiac monitors. Hemodynamic, echocardiographic, electrophysiological and histological examinations were performed 8 weeks later. RESULTS In PAH group, two died after the injection (mortality 28.6%). Thus, 10 beagles (PAH group: 5, control group: 5) underwent all the examinations. The pulmonary artery pressure increased significantly while the right atrium (RA) and right ventricle expanded slightly. Spontaneous AF episodes were recorded in all PAH canines 1 week after the injection. The AF burden increased rapidly from 1 week (7.6% ± 1.8%) and remained high after 2-3 weeks (32.0% ± 4.9% at 8 weeks). Compared with the control group, the PAH group had abbreviated effective refractory periods (ERPs), increased atrial ERP dispersion, and slower conduction velocities. Notably, AF susceptibility and atrial remodeling in RA was more significant those in LA, such as increased WOV (39.0 ± 6.5 vs. 28.0 ± 5.7 ms, P = 0.022), enlarged low voltage regions (7.66% ± 0.46% vs. 4.40% ± 0.55%, P < 0.0001) and fibrosis (8.22% ± 0.61% vs. 4.93% ± 0.60%, P < 0.0001). CONCLUSIONS  DMCT-induced canine PAH model increased the incidence of spontaneous and induced AF. The electrophysiological and structural remodeling of the RA facilitated the AF genesis.
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  • [1]
    Dimopoulos K, Inuzuka R, Goletto S, et al. Improved survival among patients with Eisenmenger syndrome receiving advanced therapy for pulmonary arterial hypertension. Circulation 2010; 121: 20−5. doi: 10.1161/CIRCULATIONAHA.109.883876
    Diller GP, Kempny A, Inuzuka R, et al. Survival prospects of treatment naive patients with Eisenmenger: a systematic review of the literature and report of own experience. Heart 2014; 100: 1366−72. doi: 10.1136/heartjnl-2014-305690
    Diller GP, Dimopoulos K, Broberg CS, et al. Presentation, survival prospects, and predictors of death in Eisenmenger syndrome: a combined retrospective and case-control study. Eur Heart J 2006; 27: 1737−42. doi: 10.1093/eurheartj/ehl116
    Hoeper MM, Huscher D, Ghofrani HA, et al. Elderly patients diagnosed with idiopathic pulmonary arterial hypertension: results from the COMPERA registry. Int J Cardiol 2013; 168: 871−80. doi: 10.1016/j.ijcard.2012.10.026
    Hyduk A, Croft JB, Ayala C, Zheng K, Zheng ZJ, Mensah GA. Pulmonary hypertension surveillance-United States, 1980-2002. MMWR Surveill Summ 2005; 54: 1−28.
    Rajdev A, Garan H, Biviano A. Arrhythmias in pulmonary arterial hypertension. Prog Cardiovasc Dis 2012; 55: 180−6. doi: 10.1016/j.pcad.2012.06.002
    Tongers J, Schwerdtfeger B, Klein G, et al. Incidence and clinical relevance of supraventricular tachyarrhythmias in pulmonary hypertension. Am Heart J 2007; 153: 127−32. doi: 10.1016/j.ahj.2006.09.008
    Hiram R, Naud P, Xiong F, et al. Right Atrial Mechanisms of Atrial Fibrillation in a Rat Model of Right Heart Disease. J Am Coll Cardiol 2019; 74: 1332−47. doi: 10.1016/j.jacc.2019.06.066
    Mattocks AR, Jukes R, Brown J. Simple procedures for preparing putative toxic metabolites of pyrrolizidine alkaloids. Toxicon 1989; 27: 561−7. doi: 10.1016/0041-0101(89)90117-7
    Medi C, Kalman JM, Ling LH, et al. Atrial electrical and structural remodeling associated with longstanding pulmonary hypertension and right ventricular hypertrophy in humans. J Cardiovasc Electrophysiol 2012; 23: 614−20. doi: 10.1111/j.1540-8167.2011.02255.x
    Mercurio V, Peloquin G, Bourji KI, et al. Pulmonary arterial hypertension and atrial arrhythmias: incidence, risk factors, and clinical impact. Pulm Circ 2018; 8: 2045894018769874.
    Huxtable RJ. Activation and pulmonary toxicity of pyrrolizidine alkaloids. Pharmacol Ther 1990; 47: 371−89.
    Sivak JA, Raina A, Forfia PR. Assessment of the physiologic contribution of right atrial function to total right heart function in patients with and without pulmonary arterial hypertension. Pulm Circ 2016; 6: 322−8. doi: 10.1086/687767
    Medi C, Kalman JM, Spence SJ, et al. Atrial electrical and structural changes associated with longstanding hypertension in humans: implications for the substrate for atrial fibrillation. J Cardiovasc Electrophysiol 2011; 22: 1317−24. doi: 10.1111/j.1540-8167.2011.02125.x
    John B, Stiles MK, Kuklik P, et al. Electrical remodelling of the left and right atria due to rheumatic mitral stenosis. Eur Heart J 2008; 29: 2234−43. doi: 10.1093/eurheartj/ehn329
    Roh SY, Choi JI, Lee JY, et al. Catheter ablation of atrial fibrillation in patients with chronic lung disease. Circ Arrhythm Electrophysiol 2011; 4: 815−22. doi: 10.1161/CIRCEP.110.960435
    Chen D, Zhou D, Qian J, et al. Atorvastatin prevents dehydromonocrotaline-induced pulmonary hypertension in beagles. Exp Lung Res 2012; 38: 333−43. doi: 10.3109/01902148.2012.702852
    Ghodsi F, Will JA. Changes in pulmonary structure and function induced by monocrotaline intoxication. Am J Physiol 1981; 240: H149−55.
    Valdivia E, Lalich JJ, Hayashi Y, Sonnad J. Alterations in pulmonary alveoli after a single injection of monocrotaline. Arch Pathol 1967; 84: 64−76.
    Chesney CF, Allen JR, Hsu IC. Right ventricular hypertrophy in monocrotaline pyrrole treated rats. Exp Mol Pathol 1974; 20: 257−68. doi: 10.1016/0014-4800(74)90058-6
    Yagmur J, Yetkin O, Cansel M, et al. Assessment of atrial electromechanical delay and influential factors in patients with obstructive sleep apnea. Sleep Breath 2012; 16: 83−8. doi: 10.1007/s11325-010-0477-6
    Hohl M, Linz B, Bohm M, Linz D. Obstructive sleep apnea and atrial arrhythmogenesis. Curr Cardiol Rev 2014; 10: 362−8. doi: 10.2174/1573403X1004140707125137
    Riaz S, Bhatti H, Sampat PJ, Dhamoon A. The Converging Pathologies of Obstructive Sleep Apnea and Atrial Arrhythmias. Cureus 2020; 12: e9388.
    Higashimoto Y, Yamagata Y, Taya S, et al. Systemic inflammation in chronic obstructive pulmonary disease and asthma: Similarities and differences. Respirology 2008; 13: 128−33.
    Lau DH, Linz D, Sanders P. New Findings in Atrial Fibrillation Mechanisms. Card Electrophysiol Clin 2019; 11: 563−71. doi: 10.1016/j.ccep.2019.08.007
    Zhang M, Hill MC, Kadow ZA, et al. Long-range Pitx2c enhancer-promoter interactions prevent predisposition to atrial fibrillation. Proc Natl Acad Sci USA 2019; 116: 22692−8. doi: 10.1073/pnas.1907418116
    Pang PD, Alsina KM, Cao S, Koushik AB, Wehrens XHT, Cooper TA. CRISPR -Mediated Expression of the Fetal Scn5a Isoform in Adult Mice Causes Conduction Defects and Arrhythmias. J Am Heart Assoc 2018; 7: e010393. doi: 10.1161/JAHA.118.010393
    Benito B, Gay-Jordi G, Serrano-Mollar A, et al. Cardiac arrhythmogenic remodeling in a rat model of long-term intensive exercise training. Circulation 2011; 123: 13−22. doi: 10.1161/CIRCULATIONAHA.110.938282
    Iwasaki YK, Kato T, Xiong F, et al. Atrial fibrillation promotion with long-term repetitive obstructive sleep apnea in a rat model. J Am Coll Cardiol 2014; 64: 2013−23. doi: 10.1016/j.jacc.2014.05.077
    Liu M, Li W, Wang H, et al. CTRP9 Ameliorates Atrial Inflammation, Fibrosis, and Vulnerability to Atrial Fibrillation in Post-Myocardial Infarction Rats. J Am Heart Assoc 2019; 8: e013133. doi: 10.1161/JAHA.119.013133
    Yu G, Yu Y, Li YN, Shu R. Effect of periodontitis on susceptibility to atrial fibrillation in an animal model. J Electrocardiol 2010; 43: 359−66. doi: 10.1016/j.jelectrocard.2009.12.002
    Chen PS, Chen LS, Fishbein MC, Lin SF, Nattel S. Role of the autonomic nervous system in atrial fibrillation: pathophysiology and therapy. Circ Res 2014; 114: 1500−15. doi: 10.1161/CIRCRESAHA.114.303772
    Satoh T, Zipes DP. Unequal atrial stretch in dogs increases dispersion of refractoriness conducive to developing atrial fibrillation. J Cardiovasc Electrophysiol 1996; 7: 833−42. doi: 10.1111/j.1540-8167.1996.tb00596.x
    Shi Y, Ducharme A, Li D, Gaspo R, Nattel S, Tardif JC. Remodeling of atrial dimensions and emptying function in canine models of atrial fibrillation. Cardiovasc Res 2001; 52: 217−25. doi: 10.1016/S0008-6363(01)00377-7
    Eckstein J, Maesen B, Linz D, et al. Time course and mechanisms of endo-epicardial electrical dissociation during atrial fibrillation in the goat. Cardiovasc Res 2011; 89: 816−24. doi: 10.1093/cvr/cvq336
    Verheule S, Tuyls E, van Hunnik A, Kuiper M, Schotten U, Allessie M. Fibrillatory conduction in the atrial free walls of goats in persistent and permanent atrial fibrillation. Circ Arrhythm Electrophysiol 2010; 3: 590−9. doi: 10.1161/CIRCEP.109.931634
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