Cardiac Electrophysiological Dynamics From the Cellular Level to the Organ Level

Cardiac alternans describes contraction of the ventricles in a strong-weak-strong-weak sequence at a constant pacing frequency. Clinically, alternans manifests as alternation of the T-wave on the ECG and predisposes individuals to arrhythmia and sudden cardiac death. In this review, we focus on the fundamental dynamical mechanisms of alternans and show how alternans at the cellular level underlies alternans in the tissue and on the ECG. A clear picture of dynamical mechanisms underlying alternans is important to allow development of effective anti-arrhythmic strategies.

[1]  Alan Garfinkel,et al.  Spatially discordant alternans in cardiac tissue: role of calcium cycling. , 2005, Circulation research.

[2]  R. Gilmour,et al.  Memory models for the electrical properties of local cardiac systems. , 1997, Journal of theoretical biology.

[3]  H M Hastings,et al.  Mechanisms for Discordant Alternans , 2001, Journal of cardiovascular electrophysiology.

[4]  D. Bers,et al.  Potentiation of fractional sarcoplasmic reticulum calcium release by total and free intra-sarcoplasmic reticulum calcium concentration. , 2000, Biophysical journal.

[5]  J. Nolasco,et al.  A graphic method for the study of alternation in cardiac action potentials. , 1968, Journal of applied physiology.

[6]  A Garfinkel,et al.  Model of intracellular calcium cycling in ventricular myocytes. , 2003, Biophysical journal.

[7]  R J Cohen,et al.  Electrical alternans and cardiac electrical instability. , 1988, Circulation.

[8]  Daisuke Sato,et al.  Acceleration of cardiac tissue simulation with graphic processing units , 2009, Medical & Biological Engineering & Computing.

[9]  A. Fabiato,et al.  Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum. , 1983, The American journal of physiology.

[10]  Alain Karma,et al.  Coupled dynamics of voltage and calcium in paced cardiac cells. , 2005, Physical review. E, Statistical, nonlinear, and soft matter physics.

[11]  Alan Garfinkel,et al.  Spark-Induced Sparks As a Mechanism of Intracellular Calcium Alternans in Cardiac Myocytes , 2010, Circulation research.

[12]  D. Rosenbaum,et al.  Repolarization alternans: implications for the mechanism and prevention of sudden cardiac death. , 2003, Cardiovascular research.

[13]  Blas Echebarria,et al.  Instability and spatiotemporal dynamics of alternans in paced cardiac tissue. , 2001, Physical review letters.

[14]  W Yuan,et al.  Fractional SR Ca release is regulated by trigger Ca and SR Ca content in cardiac myocytes. , 1995, The American journal of physiology.

[15]  D. Adam,et al.  Fluctuations in T-wave morphology and susceptibility to ventricular fibrillation. , 1984, Journal of electrocardiology.

[16]  D. Adam,et al.  Period multupling-evidence for nonlinear behaviour of the canine heart , 1984, Nature.

[17]  A. Garfinkel,et al.  Mechanisms of Discordant Alternans and Induction of Reentry in Simulated Cardiac Tissue , 2000, Circulation.

[18]  D. Bers Cardiac excitation–contraction coupling , 2002, Nature.

[19]  Dmitry Terentyev,et al.  Calsequestrin determines the functional size and stability of cardiac intracellular calcium stores: Mechanism for hereditary arrhythmia , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Shien-Fong Lin,et al.  Spatial Heterogeneity of Calcium Transient Alternans During the Early Phase of Myocardial Ischemia in the Blood-Perfused Rabbit Heart , 2001, Circulation.

[21]  M J Lab,et al.  Electrophysiological alternans and restitution during acute regional ischaemia in myocardium of anaesthetized pig. , 1988, The Journal of physiology.

[22]  Daniel J. Gauthier,et al.  Prevalence of Rate-Dependent Behaviors in Cardiac Muscle , 1999 .

[23]  F Van de Werf,et al.  Low efficiency of Ca2+ entry through the Na(+)-Ca2+ exchanger as trigger for Ca2+ release from the sarcoplasmic reticulum. A comparison between L-type Ca2+ current and reverse-mode Na(+)-Ca2+ exchange. , 1997, Circulation research.

[24]  Blas Echebarria,et al.  Amplitude equation approach to spatiotemporal dynamics of cardiac alternans. , 2006, Physical review. E, Statistical, nonlinear, and soft matter physics.

[25]  D. Rosenbaum,et al.  Mechanism linking T-wave alternans to the genesis of cardiac fibrillation. , 1999, Circulation.

[26]  Alessio Gizzi,et al.  Effects of Pacing Site and Stimulation History on Alternans Dynamics and the Development of Complex Spatiotemporal Patterns in Cardiac Tissue , 2013, Front. Physiol..

[27]  D. Bers,et al.  Can the sodium-calcium exchanger initiate or suppress calcium sparks in cardiac myocytes? , 2012, Biophysical journal.

[28]  A Garfinkel,et al.  Intracellular Ca(2+) dynamics and the stability of ventricular tachycardia. , 1999, Biophysical journal.

[29]  Alain Karma,et al.  Turing instability mediated by voltage and calcium diffusion in paced cardiac cells. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[30]  A. Garfinkel,et al.  Inferring the cellular origin of voltage and calcium alternans from the spatial scales of phase reversal during discordant alternans. , 2007, Biophysical journal.

[31]  R. Gilmour,et al.  Memory and complex dynamics in cardiac Purkinje fibers. , 1997, The American journal of physiology.

[32]  J. Ruskin,et al.  Electrical alternans and vulnerability to ventricular arrhythmias. , 1994, The New England journal of medicine.

[33]  Sandor Györke,et al.  The role of calsequestrin, triadin, and junctin in conferring cardiac ryanodine receptor responsiveness to luminal calcium. , 2004, Biophysical journal.

[34]  Donald M Bers,et al.  Cardiac Alternans Do Not Rely on Diastolic Sarcoplasmic Reticulum Calcium Content Fluctuations , 2006, Circulation research.

[35]  Colleen E. Clancy,et al.  In silico Prediction of Sex-Based Differences in Human Susceptibility to Cardiac Ventricular Tachyarrhythmias , 2012, Front. Physio..

[36]  Colleen E Clancy,et al.  L-type Ca2+ channel mutations and T-wave alternans: a model study. , 2007, American journal of physiology. Heart and circulatory physiology.

[37]  Daniel J Gauthier,et al.  Experimental control of cardiac muscle alternans. , 2002, Physical review letters.

[38]  Natalia A Trayanova,et al.  Rate-dependent action potential alternans in human heart failure implicates abnormal intracellular calcium handling. , 2009, Heart rhythm.

[39]  A. Garfinkel,et al.  From Pulsus to Pulseless: The Saga of Cardiac Alternans , 2006, Circulation research.

[40]  J. Restrepo,et al.  Unidirectional pinning and hysteresis of spatially discordant alternans in cardiac tissue. , 2011, Physical review letters.