A Model for Mechano-Electrical Feedback Effects on Atrial Flutter Interval Variability

Atrial flutter is a supraventricular arrhythmia, based on a reentrant mechanism mainly confined to the right atrium. Although atrial flutter is considered a regular rhythm, the atrial flutter interval (i.e., the time interval between consecutive atrial activation times) presents a spontaneous beat-to-beat variability, which has been suggested to be related to ventricular contraction and respiration by mechano-electrical feedback. This paper introduces a model to predict atrial activity during atrial flutter, based on the assumption that atrial flutter variability is related to the phase of the reentrant activity in the ventricular and respiratory cycles. Thus, atrial intervals are given as a superimposition of phase-dependent ventricular and respiratory modulations. The model includes a simplified atrioventricular (AV) branch with constant refractoriness and conduction times, which allows the prediction of ventricular activations in a closed-loop with atrial activations. Model predictions are quantitatively compared with real activation series recorded in 12 patients with atrial flutter. The model predicts the time course of both atrial and ventricular time series with a high beat-to-beat agreement, reproducing 96±8% and 86±21% of atrial and ventricular variability, respectively. The model also predicts the existence of phase-locking of atrial flutter intervals during periodic ventricular pacing and such results are observed in patients. These results constitute evidence in favor of mechano-electrical feedback as a major source of cycle length variability during atrial flutter.

[1]  R LANGENDORF,et al.  Concealed A-V conduction; the effect of blocked impulses on the formation and conduction of subsequent impulses. , 1948, American heart journal.

[2]  Deck Ka CHANGES IN THE RESTING POTENTIAL AND THE CABLE PROPERTIES OF PURKINJE FIBERS DURING STRETCH , 1964 .

[3]  K. Deck [CHANGES IN THE RESTING POTENTIAL AND THE CABLE PROPERTIES OF PURKINJE FIBERS DURING STRETCH]. , 1964, Pflugers Archiv fur die gesamte Physiologie des Menschen und der Tiere.

[4]  J J Denier van der Gon,et al.  Mathematical model of A-V conduction in the rat heart. , 1973, Cardiovascular research.

[5]  W Lixfeld,et al.  Effects of respiration on cardiac performance. , 1978, Journal of applied physiology: respiratory, environmental and exercise physiology.

[6]  H A Fozzard,et al.  Effect of stretch on conduction velocity and cable properties of cardiac Purkinje fibers. , 1979, The American journal of physiology.

[7]  M J Lab,et al.  Transient depolarisation and action potential alterations following mechanical changes in isolated myocardium. , 1980, Cardiovascular research.

[8]  W. C. Randall,et al.  Autonomic modulation of A-V nodal conduction in conscious dogs , 1981 .

[9]  M J Lab,et al.  Contraction-excitation feedback in myocardium. Physiological basis and clinical relevance. , 1982, Circulation research.

[10]  Tracy Allen,et al.  On the arithmetic of phase locking: Coupled neurons as a lattice on R2 , 1983 .

[11]  M. Matsuzaki,et al.  Importance of Left Atrial Function in Patients with Myocardial Infarction , 1983, Circulation.

[12]  J. Loeb,et al.  Beat-by-beat modulation of AV conduction. II. Autonomic neural mechanisms. , 1986, The American journal of physiology.

[13]  M. R. Warner,et al.  Beat-by-beat modulation of AV conduction. I. Heart rate and respiratory influences. , 1986, The American journal of physiology.

[14]  J Bélair,et al.  Periodic pulsatile stimulation of a nonlinear oscillator , 1986, Journal of mathematical biology.

[15]  S Nattel,et al.  Prediction of complex atrioventricular conduction rhythms in humans with use of the atrioventricular nodal recovery curve. , 1987, Circulation.

[16]  V. I. Arnold Cardiac arrhythmias and circle mappingsa) , 1991 .

[17]  V. I. Arnold,et al.  Cardiac arrhythmias and circle mappings(a)). , 1991, Chaos.

[18]  Renzo Antolini,et al.  Variations in Human Atrial Flutter Cycle Length Induced by Ventricular Beats: Evidence of a Reentrant Circuit with a Partially Excitable Gap , 1991 .

[19]  D. Cameron,et al.  Effects of posture, Valsalva maneuver and respiration on atrial flutter rate: an effect mediated through cardiac volume. , 1991, Journal of the American College of Cardiology.

[20]  Leon Glass,et al.  Cardiac arrhythmias and circle maps-A classical problem. , 1991, Chaos.

[21]  Solvable models for the quasi-periodic transition to chaos , 1992 .

[22]  E. White,et al.  The effects of increasing cell length on auxotonic contractions; membrane potential and intracellular calcium transients in single guinea‐pig ventricular myocytes , 1993, Experimental physiology.

[23]  G. Nollo,et al.  Evidence of low- and high-frequency oscillations in human AV interval variability: evaluation with spectral analysis. , 1994, The American journal of physiology.

[24]  M. Allessie,et al.  Ventricular beats induce variations in cycle length of rapid (type II) atrial flutter in humans. Evidence of leading circle reentry. , 1994, Circulation.

[25]  L. Kappenberger,et al.  Relation Between Cycle Length, Volume, and Pressure in Type I Atrial Flutter , 1994, Pacing and clinical electrophysiology : PACE.

[26]  Van C. Mow,et al.  Cell Mechanics and Cellular Engineering , 2011, Springer New York.

[27]  Frederick Sachs,et al.  Modeling Mechanical-Electrical Transduction in the Heart , 1994 .

[28]  S Nattel,et al.  Dynamic Behavior of the Atrioventricular Node: , 1994, Journal of cardiovascular electrophysiology.

[29]  L. Tung,et al.  Influence of stretch on excitation threshold of single frog ventricular cells , 1995, Experimental physiology.

[30]  J.M. Smith,et al.  A technique for measurement of the extent of spatial organization of atrial activation during atrial fibrillation in the intact human heart , 1995, IEEE Transactions on Biomedical Engineering.

[31]  M J Lab,et al.  Mechanoelectric feedback in the atrium of the isolated guinea-pig heart. , 1996, Cardiovascular research.

[32]  E. Prystowsky,et al.  Effect of continuous vagal enhancement on concealed conduction and refractoriness within the atrioventricular node. , 1996, The American journal of cardiology.

[33]  M J Lab,et al.  Mechanoelectric feedback and atrial arrhythmias. , 1996, Cardiovascular research.

[34]  M R Franz,et al.  Mechano-electrical feedback in ventricular myocardium. , 1996, Cardiovascular research.

[35]  F Sachs,et al.  Stretch-activated ion channels in the heart. , 1997, Journal of molecular and cellular cardiology.

[36]  M. Allessie,et al.  Effects of atrial dilatation on refractory period and vulnerability to atrial fibrillation in the isolated Langendorff-perfused rabbit heart. , 1997, Circulation.

[37]  E McVeigh,et al.  Model studies of the role of mechano-sensitive currents in the generation of cardiac arrhythmias. , 1998, Journal of theoretical biology.

[38]  Juan Sanchís,et al.  Modificaciones agudas de la longitud de onda del proceso de activación auricular inducidas por la dilatación. Estudio experimental , 1998 .

[39]  P Kohl,et al.  Cellular mechanisms of cardiac mechano-electric feedback in a mathematical model. , 1998, The Canadian journal of cardiology.

[40]  F. Chorro,et al.  [Acute changes in wavelength of the process of auricular activation induced by stretching. Experimental study]. , 1998, Revista espanola de cardiologia.

[41]  Sergio Grinstein,et al.  Topological analysis of NHE1, the ubiquitous Na+/H+exchanger using chymotryptic cleavage. , 1998, American journal of physiology. Cell physiology.

[42]  F. Ravelli Atrial flutter cycle length oscillations and role of the autonomic nervous system. , 1998, Circulation.

[43]  Eric A Sobie,et al.  Stretch-induced changes in arrhythmogenesis and excitability in experimentally based heart cell models. , 1998, American journal of physiology. Heart and circulatory physiology.

[44]  M. Weckström,et al.  Mechanisms of stretch-induced changes in [Ca2+]i in rat atrial myocytes: role of increased troponin C affinity and stretch-activated ion channels. , 1998, Circulation research.

[45]  E. White,et al.  The role of calcium in the response of cardiac muscle to stretch. , 1999, Progress in biophysics and molecular biology.

[46]  J E Saffitz,et al.  Pulsatile Stretch Remodels Cell-to-Cell Communication in Cultured Myocytes , 2000, Circulation research.

[47]  A. Waldo Treatment of atrial flutter , 2000, Heart.

[48]  M R Franz,et al.  Gadolinium decreases stretch-induced vulnerability to atrial fibrillation. , 2000, Circulation.

[49]  M J Lab,et al.  Mechano-electric feedback in right atrium after left ventricular infarction in rats. , 2000, Journal of molecular and cellular cardiology.

[50]  F. Chorro Atrial-AV Nodal Electrophysiology: A View from the Millennium , 2001 .

[51]  U. Schotten,et al.  Verapamil Prevents Stretch‐Induced Shortening of Atrial Effective Refractory Period in Langendorff‐Perfused Rabbit Heart , 2001, Journal of cardiovascular electrophysiology.

[52]  Leon Glass,et al.  A mathematical model of human atrioventricular nodal function incorporating concealed conduction , 2002, Bulletin of mathematical biology.

[53]  M. Franz,et al.  Mechano-electrical feedback underlying arrhythmias: the atrial fibrillation case. , 2003, Progress in biophysics and molecular biology.

[54]  Peter Kohl,et al.  Cardiac mechano-electric feedback: past, present, and prospect. , 2003, Progress in biophysics and molecular biology.

[55]  M. Allessie,et al.  Effects of Acute Atrial Dilation on Heterogeneity in Conduction in the Isolated Rabbit Heart , 2003, Journal of cardiovascular electrophysiology.

[56]  Leslie Tung,et al.  Stretch-induced excitation and action potential changes of single cardiac cells. , 2003, Progress in biophysics and molecular biology.

[57]  M. Lab,et al.  Feedback interaction of mechanical and electrical events in the isolated mammalian ventricular myocardium (cat papillary muscle) , 2004, Pflügers Archiv.

[58]  齋藤 紀子 Autonomic neural mechanisms of nonnutritive-sucking-related tachycardia , 2004 .

[59]  Mark McGuinness,et al.  Arnold tongues in human cardiorespiratory systems. , 2004, Chaos.

[60]  K. A. Deck,et al.  Änderungen des Ruhepotentials und der Kabeleigenschaften von Purkinje-Fäden bei der Dehnung , 1964, Pflüger's Archiv für die gesamte Physiologie des Menschen und der Tiere.

[61]  F. Sachs,et al.  Mechanical transduction by membrane ion channels: a mini review , 2004, Molecular and Cellular Biochemistry.

[62]  Andrew D McCulloch,et al.  An ionic model of stretch-activated and stretch-modulated currents in rabbit ventricular myocytes. , 2005, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[63]  K. Murphy,et al.  Dietary Fish Oil Protects Against Stretch‐Induced Vulnerability to Atrial Fibrillation in a Rabbit Model , 2005, Journal of cardiovascular electrophysiology.

[64]  Leon Glass,et al.  Effects of antiarrhythmic drug therapy on atrioventricular nodal function during atrial fibrillation in humans. , 2005, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[65]  T. Arts,et al.  Mechanoelectric feedback leads to conduction slowing and block in acutely dilated atria: a modeling study of cardiac electromechanics. , 2007, American journal of physiology. Heart and circulatory physiology.