This Article Full Text Full Text (PDF) All Versions of this Article: 114/24/2595    most recent CIRCULATIONAHA.106.630509v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hwang, G.-S. Articles by Chen, P.-S. Search for Related Content PubMed PubMed Citation Articles by Hwang, G.-S. Articles by Chen, P.-S. Related Collections Arrythmias-basic studies Ablation/ICD/surgery

(Circulation. 2006;114:2595-2603.)
© 2006 American Heart Association, Inc.

Arrhythmia/Electrophysiology

Intracellular Calcium and Vulnerability to Fibrillation and Defibrillation in Langendorff-Perfused Rabbit Ventricles

Gyo-Seung Hwang, MD, PhD; Hideki Hayashi, MD, PhD; Liang Tang, PhD; Masahiro Ogawa, MD, PhD; Heidy Hernandez; Alex Y. Tan, MD; Hongmei Li, MD; Hrayr S. Karagueuzian, PhD; James N. Weiss, MD; Shien-Fong Lin, PhD; Peng-Sheng Chen, MD

From the Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, and the Departments of Medicine (Cardiology) and Physiology (J.N.W.), David Geffen School of Medicine at UCLA, Los Angeles, Calif.

Correspondence to Peng-Sheng Chen, MD, Room 5537, Cedars-Sinai Medical Center, Los Angeles, CA 90048. E-mail chenp{at}cshs.org

Received March 29, 2006; revision received October 9, 2006; accepted October 13, 2006.

Background— The role of intracellular calcium (Ca_i) in defibrillation and vulnerability is unclear.

Methods and Results— We simultaneously mapped epicardial membrane potential and Ca_i during shock on T-wave episodes (n=104) and attempted defibrillation episodes (n=173) in 17 Langendorff-perfused rabbit ventricles. Unsuccessful and type B successful defibrillation shocks were followed by heterogeneous distribution of Ca_i, including regions of low Ca_i surrounded by elevated Ca_i ("Ca_i sinkholes") 31±12 ms after shock. The first postshock activation then originated from the Ca_i sinkhole 53±14 ms after the shock. No sinkholes were present in type A successful defibrillation. A Ca_i sinkhole also was present 39±32 ms after a shock on T that induced ventricular fibrillation, followed 22±15 ms later by propagated wave fronts that arose from the same site. This wave propagated to form a spiral wave and initiated ventricular fibrillation. Thapsigargin and ryanodine significantly decreased the upper limit of vulnerability and defibrillation threshold. We studied an additional 7 rabbits after left ventricular endocardial cryoablation, resulting in a thin layer of surviving epicardium. Ca_i sinkholes occurred 31±12 ms after the shock, followed in 19±7 ms by first postshock activation in 63 episodes of unsuccessful defibrillation. At the Ca_i sinkhole, the rise of Ca_i preceded the rise of epicardial membrane potential in 5 episodes.

Conclusions— There is a heterogeneous postshock distribution of Ca_i. The first postshock activation always occurs from a Ca_i sinkhole. The Ca_i prefluorescence at the first postshock early site suggests that reverse excitation-contraction coupling might be responsible for the initiation of postshock activations that lead to ventricular fibrillation.

---

 

CLINICAL PERSPECTIVE

This article has been cited by other articles:

				M. R. Holcomb, M. C. Woods, I. Uzelac, J. P. Wikswo, J. M. Gilligan, and V. Y. Sidorov The Potential of Dual Camera Systems for Multimodal Imaging of Cardiac Electrophysiology and Metabolism Experimental Biology and Medicine, November 1, 2009; 234(11): 1355 - 1373. [Abstract] [Full Text] [PDF]

				M. Attin and W. T. Clusin Basic Concepts of Optical Mapping Techniques in Cardiac Electrophysiology Biol Res Nurs, October 1, 2009; 11(2): 195 - 207. [Abstract] [PDF]

				B. Joung, L. Tang, M. Maruyama, S. Han, Z. Chen, M. Stucky, L. R. Jones, M. C. Fishbein, J. N. Weiss, P.-S. Chen, et al. Intracellular Calcium Dynamics and Acceleration of Sinus Rhythm by {beta}-Adrenergic Stimulation Circulation, February 17, 2009; 119(6): 788 - 796. [Abstract] [Full Text] [PDF]

				H. Hayashi, S.-F. Lin, B. Joung, H. S. Karagueuzian, J. N. Weiss, and P.-S. Chen Virtual electrodes and the induction of fibrillation in Langendorff-perfused rabbit ventricles: the role of intracellular calcium Am J Physiol Heart Circ Physiol, October 1, 2008; 295(4): H1422 - H1428. [Abstract] [Full Text] [PDF]

				G.-S. Hwang, L. Tang, B. Joung, N. Morita, H. Hayashi, H. S. Karagueuzian, J. N. Weiss, S.-F. Lin, and P.-S. Chen Superiority of Biphasic Over Monophasic Defibrillation Shocks Is Attributable to Less Intracellular Calcium Transient Heterogeneity J. Am. Coll. Cardiol., September 2, 2008; 52(10): 828 - 835. [Abstract] [Full Text] [PDF]

				J. P. Daubert and S.-S. Sheu Mystery of Biphasic Defibrillation Waveform Efficacy: Is it Calcium? J. Am. Coll. Cardiol., September 2, 2008; 52(10): 836 - 838. [Full Text] [PDF]

				J. F. Huizar, M. D. Warren, A. G. Shvedko, J. Kalifa, J. Moreno, S. Mironov, J. Jalife, and A. V. Zaitsev Three distinct phases of VF during global ischemia in the isolated blood-perfused pig heart Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1617 - H1628. [Abstract] [Full Text] [PDF]