Restitution characteristics of His bundle and working myocardium in isolated rabbit hearts

The Purkinje system (PS) and the His bundle have been recently implicated as an important driver of the rapid activation rate after 1–2 minutes of ventricular fibrillation (VF). It is unknown whether activations during VF propagate through the His-Purkinje system to other portions of the the working myocardium (WM). Little is known about restitution characteristic differences between the His bundle and working myocardium at short cycle lengths. In this study, rabbit hearts (n = 9) were isolated, Langendorff-perfused, and electromechanically uncoupled with blebbistatin (10 μM). Pacing pulses were delivered directly to the His bundle. By using standard glass microelectrodes, action potentials duration (APD) from the His bundle and WM were obtained simultaneously over a wide range of stimulation cycle lengths (CL). The global F-test indicated that the two restitution curves of the His bundle and the WM are statistically significantly different (P<0.05). Also, the APD of the His bundle was significantly shorter than that of WM throughout the whole pacing course (P<0.001). The CL at which alternans developed in the His bundle vs. the WM were shorter for the His bundle (134.2±13.1ms vs. 148.3±13.3ms, P<0.01) and 2:1 block developed at a shorter CL in the His bundle than in WM (130.0±10.0 vs. 145.6±14.2ms, P<0.01). The His bundle APD was significantly shorter than that of WM under both slow and rapid pacing rates, which suggest that there may be an excitable gap during VF and that the His bundle may conduct wavefronts from one bundle branch to the other at short cycle lengths and during VF.

[1]  M. Rosen,et al.  Regional differences in electrophysiological properties of epicardium, midmyocardium, and endocardium. In vitro and in vivo correlations. , 1996, Circulation.

[2]  R. Ideker,et al.  Long-Duration Ventricular Fibrillation Exhibits 2 Distinct Organized States , 2013, Circulation. Arrhythmia and electrophysiology.

[3]  R. W. Joyner,et al.  Unidirectional block between isolated rabbit ventricular cells coupled by a variable resistance. , 1991, Biophysical journal.

[4]  P D Wolf,et al.  Regional capture of fibrillating ventricular myocardium. Evidence of an excitable gap. , 1995, Circulation research.

[5]  D. Bers,et al.  Formation of Spatially Discordant Alternans Due to Fluctuations and Diffusion of Calcium , 2013, PloS one.

[6]  J. C. Bailey,et al.  Action potential duration alternans in dog Purkinje and ventricular muscle fibers. Further evidence in support of two different mechanisms. , 1989, Circulation.

[7]  R. Ideker,et al.  The Importance of Purkinje Activation in Long Duration Ventricular Fibrillation , 2014, Journal of the American Heart Association.

[8]  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.

[9]  C. Ripplinger,et al.  Cardiac myocyte alternans in intact heart: Influence of cell-cell coupling and β-adrenergic stimulation. , 2015, Journal of molecular and cellular cardiology.

[10]  Jian Huang,et al.  Restitution Properties During Ventricular Fibrillation in the In Situ Swine Heart , 2004, Circulation.

[11]  Jian Huang,et al.  Chemical ablation of the Purkinje system causes early termination and activation rate slowing of long-duration ventricular fibrillation in dogs. , 2008, American journal of physiology. Heart and circulatory physiology.

[12]  V. Fast,et al.  Paradoxical Improvement of Impulse Conduction in Cardiac Tissue by Partial Cellular Uncoupling , 1997, Science.

[13]  Raymond E. Ideker,et al.  Activation Patterns of Purkinje Fibers During Long-Duration Ventricular Fibrillation in an Isolated Canine Heart Model , 2007, Circulation.

[14]  Y Rudy,et al.  Ionic mechanisms of propagation in cardiac tissue. Roles of the sodium and L-type calcium currents during reduced excitability and decreased gap junction coupling. , 1997, Circulation research.

[15]  Youhua Zhang,et al.  AV Nodal Dual Pathway Electrophysiology and Wenckebach Periodicity , 2011, Journal of cardiovascular electrophysiology.

[16]  Robert F Gilmour,et al.  Contribution of IKr to Rate-Dependent Action Potential Dynamics in Canine Endocardium , 2004, Circulation research.

[17]  Godfrey L. Smith,et al.  Effect of activation sequence on transmural patterns of repolarization and action potential duration in rabbit ventricular myocardium. , 2010, American journal of physiology. Heart and circulatory physiology.

[18]  Youhua Zhang.  His electrogram alternans (Zhang’s phenomenon) and a new model of dual pathway atrioventricular node conduction , 2015, Journal of Interventional Cardiac Electrophysiology.

[19]  James Winter,et al.  The mechanical uncoupler blebbistatin is associated with significant electrophysiological effects in the isolated rabbit heart , 2013, Experimental physiology.

[20]  A. Rowan.  Guide for the Care and Use of Laboratory Animals , 1979 .

[21]  Joshua I. Goldhaber,et al.  Action Potential Duration Restitution and Alternans in Rabbit Ventricular Myocytes: The Key Role of Intracellular Calcium Cycling , 2005, Circulation research.

[22]  Zhongju Lu,et al.  Xenografted Adult Human Mesenchymal Stem Cells Provide a Platform for Sustained Biological Pacemaker Function in Canine Heart , 2007, Circulation.

[23]  R B Robinson,et al.  Electrical restitution process in dispersed canine cardiac Purkinje and ventricular cells. , 1987, The American journal of physiology.

[24]  E. Entcheva,et al.  Cardiac cellular coupling and the spread of early instabilities in intracellular Ca2+. , 2012, Biophysical journal.

[25]  J. Boineau,et al.  Microfibrosis Produces Electrical Load Variations Due to Loss of Side‐to‐Side Cell Connections; A Major Mechanism of Structural Heart Disease Arrhythmias , 1997, Pacing and clinical electrophysiology : PACE.

[26]  I. Efimov,et al.  Application of blebbistatin as an excitation-contraction uncoupler for electrophysiologic study of rat and rabbit hearts. , 2007, Heart rhythm.

[27]  Nathan Angel,et al.  His Bundle Activates Faster than Ventricular Myocardium during Prolonged Ventricular Fibrillation , 2014, PloS one.