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Am J Physiol Heart Circ Physiol 295: H1422-H1428, 2008. First published August 1, 2008; doi:10.1152/ajpheart.00001.2008
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Virtual electrodes and the induction of fibrillation in Langendorff-perfused rabbit ventricles: the role of intracellular calcium

Hideki Hayashi,1 Shien-Fong Lin,1,2,3 Boyoung Joung,3 Hrayr S. Karagueuzian,1,2 James N. Weiss,2 and Peng-Sheng Chen1,2,3

1Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, and 2Departments of Medicine (Cardiology) and Physiology, David Geffen School of Medicine at University of California, Los Angeles, California; and 3Krannert Institute of Cardiology, Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana

Submitted 1 January 2008 ; accepted in final form 1 July 2008

A strong premature electrical stimulus (S2) induces both virtual anodes and virtual cathodes. The effects of virtual electrodes on intracellular Ca2+ concentration ([Ca2+]i) transients and ventricular fibrillation thresholds (VFTs) are unclear. We studied 16 isolated, Langendorff-perfused rabbit hearts with simultaneous voltage and [Ca2+]i optical mapping and for vulnerable window determination. After baseline pacing (S1), a monophasic (10 ms anodal or cathodal) or biphasic (5 ms-5 ms) S2 was applied to the left ventricular epicardium. Virtual electrode polarizations and [Ca2+]i varied depending on the S2 polarity. Relative to the level of [Ca2+]i during the S1 beat, the [Ca2+]i level 40 ms after the onset of monophasic S2 increased by 36 ± 8% at virtual anodes and 20 ± 5% at virtual cathodes (P < 0.01), compared with 25 ± 5% at both virtual cathode-anode and anode-cathode sites for biphasic S2. The VFT was significantly higher and the vulnerable window significantly narrower for biphasic S2 than for either anodal or cathodal S2 (n = 7, P < 0.01). Treatment with thapsigargin and ryanodine (n = 6) significantly prolonged the action potential duration compared with control (255 ± 22 vs. 189 ± 6 ms, P < 0.05) and eliminated the difference in VFT between monophasic and biphasic S2, although VFT was lower for both cases. We conclude that virtual anodes caused a greater increase in [Ca2+]i than virtual cathodes. Monophasic S2 is associated with lower VFT than biphasic S2, but this difference was eliminated by the inhibition of the sarcoplasmic reticulum function and the prolongation of the action potential duration. However, the inhibition of the sarcoplasmic reticulum function also reduced VFT, indicating that the [Ca2+]i dynamics modulate, but are not essential, to ventricular vulnerability.

electrical stimulation; mapping



Address for reprint requests and other correspondence: H. Hayashi, Dept. of Cardiovascular and Respiratory Medicine, Shiga Univ. of Medical Science, Otsu, Shiga, 520-2192, Japan (e-mail: hayashih{at}belle.shiga-med.ac.jp)







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