Increased vulnerability to inducible atrial fibrillation caused by partial cellular uncoupling with heptanol.

We hypothesized that partial cellular uncoupling produced by low concentrations of heptanol increases the vulnerability to inducible atrial fibrillation (AF). The epicardial surface of 12 isolated-perfused canine left atria was optically mapped before and after 1-50 microM heptanol infusion. At baseline, no sustained (>30 s) AF could be induced in any of the 12 tissues. However, after 2 microM heptanol infusion, sustained AF was induced in 9 of 12 tissues (P < 0.001). Heptanol >5 microM caused loss of 1:1 capture during rapid pacing, causing no AF to be induced. AF was initiated by conduction block across the fiber leading to reentry, which broke up after one to two rotations into two to four independent wavelets that sustained the AF. Heptanol at 2 microM had no effect on the cellular action potential duration restitution or on the maximal velocity rate over time of the upstroke. The effects of heptanol were reversible. We conclude that partial cellular uncoupling by heptanol without changing atrial active membrane properties promotes wavebreak, reentry, and AF during rapid pacing.

[1]  J P Wikswo,et al.  Panoramic optical imaging of electrical propagation in isolated heart. , 1999, Journal of biomedical optics.

[2]  M. Fishbein,et al.  Attachment of meandering reentrant wave fronts to anatomic obstacles in the atrium. Role of the obstacle size. , 1997, Circulation research.

[3]  J. Spear,et al.  Effects of Cellular Uncoupling on Conduction in Anisotropic Canine Ventricular Myocardium , 1988, Circulation research.

[4]  A Garfinkel,et al.  Spatiotemporal heterogeneity in the induction of ventricular fibrillation by rapid pacing: importance of cardiac restitution properties. , 1999, Circulation research.

[5]  S. Nattel,et al.  Importance of refractoriness heterogeneity in the enhanced vulnerability to atrial fibrillation induction caused by tachycardia-induced atrial electrical remodeling. , 1998, Circulation.

[6]  Michael D. Lesh,et al.  Cellular Uncoupling Can Unmask Dispersion of Action Potential Duration in Ventricular Myocardium A Computer Modeling Study , 1989, Circulation research.

[7]  M. Allessie,et al.  Structural changes of atrial myocardium due to sustained atrial fibrillation in the goat. , 1997, Circulation.

[8]  T Ikeda,et al.  Meandering and unstable reentrant wave fronts induced by acetylcholine in isolated canine right atrium. , 1997, The American journal of physiology.

[9]  S Nattel,et al.  Ionic remodeling underlying action potential changes in a canine model of atrial fibrillation. , 1997, Circulation research.

[10]  A Garfinkel,et al.  Role of pectinate muscle bundles in the generation and maintenance of intra-atrial reentry: potential implications for the mechanism of conversion between atrial fibrillation and atrial flutter. , 1998, Circulation research.

[11]  A Garfinkel,et al.  Ventricular Fibrillation: How Do We Stop the Waves From Breaking? , 2000, Circulation research.

[12]  R. W. Joyner.  Mechanisms of unidirectional block in cardiac tissues. , 1981, Biophysical journal.

[13]  H. Karagueuzian,et al.  Obstacle-induced transition from ventricular fibrillation to tachycardia in isolated swine right ventricles: insights into the transition dynamics and implications for the critical mass. , 2000, Journal of the American College of Cardiology.

[14]  S Nattel,et al.  Promotion of atrial fibrillation by heart failure in dogs: atrial remodeling of a different sort. , 1999, Circulation.

[15]  R. W. Joyner,et al.  Effects of the Discrete Pattern of Electrical Coupling on Propagation through an Electrical Syncytium , 1982, Circulation research.

[16]  H. Karagueuzian,et al.  Mechanism of procainamide-induced prevention of spontaneous wave break during ventricular fibrillation. Insight into the maintenance of fibrillation wave fronts. , 1999, Circulation.

[17]  P. C. Viswanathan,et al.  Effects of IKr and IKs heterogeneity on action potential duration and its rate dependence: a simulation study. , 1999, Circulation.

[18]  M. Spach.  Changes in the topology of gap junctions as an adaptive structural response of the myocardium. , 1994, Circulation.

[19]  M. Rook,et al.  Mechanism of heptanol-induced uncoupling of cardiac gap junctions: a perforated patch-clamp study. , 1992, The American journal of physiology.

[20]  M. Allessie,et al.  Differential Effects of Heptanol, Potassium, and Tetrodotoxin on Reentrant Ventricular Tachycardia Around a Fixed Obstacle in Anisotropic Myocardium , 1991, Circulation.

[21]  M. Allessie,et al.  Widening of the excitable gap during pharmacological cardioversion of atrial fibrillation in the goat: effects of cibenzoline, hydroquinidine, flecainide, and d-sotalol. , 2000, Circulation.

[22]  B. Lüderitz,et al.  Conduction disturbances and increased atrial vulnerability in Connexin40-deficient mice analyzed by transesophageal stimulation. , 1999, Circulation.

[23]  W. L. Nelson,et al.  Block of sodium current by heptanol in voltage-clamped canine cardiac Purkinje cells. , 1991, Circulation research.

[24]  D. Levy,et al.  Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart Study. , 1994, JAMA.

[25]  M Delmar,et al.  Electrical uncoupling and impulse propagation in isolated sheep Purkinje fibers. , 1989, The American journal of physiology.

[26]  M. Spach,et al.  Relating Extracellular Potentials and Their Derivatives to Anisotropic Propagation at a Microscopic Level in Human Cardiac Muscle: Evidence for Electrical Uncoupling of Side‐to‐Side Fiber Connections with Increasing Age , 1986, Circulation research.

[27]  Yoram Rudy,et al.  A Model Study of the Effects of the Discrete Cellular Structure on Electrical Propagation in Cardiac Tissue , 1987, Circulation research.

[28]  A. Garfinkel,et al.  Chaos and the transition to ventricular fibrillation: a new approach to antiarrhythmic drug evaluation. , 1999, Circulation.

[29]  J P Wikswo,et al.  Quatrefoil Reentry in Myocardinm: An Optical Imaging Study of the Induction Mechanism , 1999, Journal of cardiovascular electrophysiology.

[30]  N. Peters,et al.  Myocardial architecture and ventricular arrhythmogenesis. , 1998, Circulation.

[31]  M. Koller,et al.  Dynamic restitution of action potential duration during electrical alternans and ventricular fibrillation. , 1998, American journal of physiology. Heart and circulatory physiology.