Published Online
on November 20, 2006

A more recent version of this article appeared on December 12, 2006

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Submitted on March 29, 2006
Revised on October 9, 2006
Accepted on October 13, 2006

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, and 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.

^* To whom correspondence should be addressed. E-mail: chenp{at}cshs.org.

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.

Key words: arrhythmia • cardioversion • electrical stimulation • electrocardiography • electrophysiology

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