Authors
Abstract
Introduction: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and a significant risk factor for cerebrovascular accident and other morbidities if left untreated. Epidemiological studies show that AF tends to persist over time, creating electrophysiological and anatomical changes called atrial remodeling. It has been shown that these changes result in variations in conduction velocity (CV) in the atrial tissue. Objective: to study the effect of remodeling of gap junctions in the propagation of the action potential by implementing a highly realistic 3D human atrial model. Materials and methods: the changes caused by electrical remodeling were incorporated in an atrial myocyte action potential (AP) model coupled with an anatomically realistic three-dimensional model of dilated human atria. Through simulations of the AP spread in variations of anatomical and electrical remodeling and of gap junctions remodeling, vulnerable windows of reentry generation were measured at the base of the atrium left pulmonary veins. Results: the results obtained indicate that vulnerable window in the gap junctions remodeling moved 38 ms in relation with the expanded model which shows the impact of the dilatation gap junction remodeling. Conclusions: the electrical remodeling produced 70% decrease in action potential duration and decreased conduction velocities between 14.6 and 26 %, which were measured in different regions of the dilated atrium. The focus shot at the base of the left pulmonary veins created a wave which maintains a reentering activity due to the underlying anatomy of the pulmonary veins.
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References
Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, et al. Heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation 2010; 121(7):e46-e215.
Zimerman L, Fenelon G, Martinelli Filho M, Grupi C, Atié J, Lorga Filho A. Diretrizes brasileiras de fibrilação atrial. Arq Bras Cardiol 2009; 92(6 Suppl. 1):1-39.
Fuenmayor A, Fuenmayor A. Tratamiento no farmacológico de la fibrilación auricular. Avances Cardiológicos 2009;29:286-95.
Cox JL, Canavan TE, Schuessler RB, Cain ME, Lindsay BD, Stone C, et al. The surgical treatment of atrial fibrillation. II. Intraoperative electrophysiologic mapping and description of the electrophysiologic basis of atrial flutter and atrial fibrillation. J Thorac Cardiovasc Surg 1991; 101(3):406-26.
Kirchhof C, Chorro F, Scheffer GJ, Brugada J, Konings K, Zetelaki Z, et al. Regional entrainment of atrial fibrillation studied by high-resolution mapping in open-chest dogs. Circulation 1993; 88(2):736-49.
Konings KT, Kirchhof CJ, Smeets JR, Wellens HJ, Penn OC, Allessie MA. High-density mapping of electrically induced atrial fibrillation in humans. Circulation 1994; 89(4):1665-80.
Elvan A, Wylie K, Zipes DP. Pacing-induced chronic atrial fibrillation impairs sinus node function in dogs. Electrophysiological remodeling. Circulation 1996; 94(11):2953-60.
Tieleman RG, De Langen C, Van Gelder IC, de Kam PJ, Grandjean J, Bel KJ, et al. Verapamil reduces tachycardia-induced electrical remodeling of the atria. Circulation 1997; 95(7):1945-53.
Virag N, Jacquemet V, Henriquez CS, Zozor S, Blanc O, Vesin JM, et al. Study of atrial arrhythmias in a computer model based on magnetic resonance images of human atria. Chaos 2002; 12(3):754-763.
Jacquemet V, Virag N, Ihara Z, Dang L, Blanc O, Zozor S, et al. Study of unipolar electrogram morphology in a computer model of atrial fibrillation. J Cardiovasc Electrophysiol 2003; 14(Suppl. 10):S172-9.
Ruiz-Villa C, Tobón C, Heidenreich E, Hornero F. Propagación de potencial de acción en un modelo 3D realista de Aurícula Humana. In: Congreso Anual de la Sociedad Española de Ingeniería Biomédica; 2006. Pamplona.
Ruiz-Villa C, Tobón C, Rodriguez FJ, Heidenreich E. Efecto de la dilatación auricular sobre la vulnerabilidad a reentradas. In: Congreso Anual de la Sociedad española de Ingeniería Biomédica; 2008. Valladolid.
Wang K, Ho SY, Gibson DG, Anderson RH. Architecture of atrial musculature in humans. Br Heart J 1995; 73(6):559-65.
Cohen GI, White M, Sochowski RA, Klein AL, Bridge PD, Stewart WJ, et al. Reference values for normal adult transesophageal echocardiographic measurements. J Am Soc Echocardiogr 1995; 8(3):221-30.
Feld GK, Mollerus M, Birgersdotter-Green U, Fujimura O, Bahnson TD, Boyce K, et al. Conduction velocity in the tricuspid valve-inferior vena cava isthmus is slower in patients with type I atrial flutter compared to those without a history of atrial flutter. J Cardiovasc Electrophysiol 1997; 8(12):1338-48.
Hansson A, Holm M, Blomstrom P, Johansson R, Luhrs C, Brandt J, et al. Right atrial free wall conduction velocity and degree of anisotropy in patients with stable sinus rhythm studied during open heart surgery. Eur Heart J 1998; 19(2):293-300.
Ho SY, Sanchez-Quintana D, Anderson RH. Can anatomy define electric pathways? In: International Workshop on Computer Simulation and Experimental Assessment of Electrical Cardiac Function; 1998. Lausanne, Switzerland.
Allessie M, Ausma J, Schotten U. Electrical, contractile and structural remodeling during atrial fibrillation. Cardiovasc Res 2002; 54(2):230-46.
Nygren A, Fiset C, Firek L, Clark JW, Lindblad DS, Clark RB, et al. Mathematical model of an adult human atrial cell: the role of K+ currents in repolarization. Circ Res 1998; 82(1):63-81.
Bosch RF, Zeng X, Grammer JB, Popovic K, Mewis C, Kuhlkamp V. Ionic mechanisms of electrical remodeling in human atrial fibrillation. Cardiovasc Res 1999; 44(1):121-31.
Workman AJ, Kane KA, Rankin AC. The contribution of ionic currents to changes in refractoriness of human atrial myocytes associated with chronic atrial fibrillation. Cardiovasc Res 2001; 52(2):226-35.
Takeuchi S, Akita T, Takagishi Y, Watanabe E, Sasano C, Honjo H, et al. Disorganization of gap junction distribution in dilated atria of patients with chronic atrial fibrillation. Circ J 2006; 70(5):575-82.
Jongsma HJ, Wilders R. Gap junctions in cardiovascular disease. Circ Res 2000; 86(12):1193-7.
Kostin S, Rieger M, Dammer S, Hein S, Richter M, Klovekorn WP, et al. Gap junction remodeling and altered connexin 43 expression in the failing human heart. Mol Cell Biochem 2003; 242(1-2):135-44.
Spach MS, Heidlage JF, Dolber PC, Barr RC. Electrophysiological effects of remodeling cardiac gap junctions and cell size: experimental and model studies of normal cardiac growth. Circ Res 2000; 86(3):302-11.
Boyett MR, Honjo H, Kodama I. The sinoatrial node, a heterogeneous pacemaker structure. Cardiovasc Res 2000; 47(4):658-87.
Wilders R. Computer modelling of the sinoatrial node. Med Biol Eng Comput 2007; 45(2):189-207.
Seemann G, Bustamante PC, Ponto S, Wilhelms M, Scholz EP, Do, et al. Atrial fibrillation-based electrical remodeling in a computer model of the human atrium. In: Computing in Cardiology, 2010; 2010 26-29 Sept. 2010; 2010. p. 417-420.
Kharche S, Zhang H. Simulating the effects of atrial fibrillation induced electrical remodeling: A comprehensive simulation study. In: Engineering in Medicine and Biology Society, 2008. EMBS 2008. 30th Annual International Conference of the IEEE; 2008. p. 593-5.