Submitted on January 2, 2008
Revised on June 11, 2008
Accepted on July 1, 2008
Virtual Electrodes and the Induction of Fibrillation in Langendorff-Perfused Rabbit Ventricles: The Role of Intracellular Calcium
Hideki Hayashi1*, Shien-Fong Lin2, Boyoung Joung3, Hrayr Karagueuzian4, James N. Weiss5, and Peng-Sheng Chen3
1 Shiga University of Medical Science
2 Indiana University School of Medicine
3 Krannert Institute of Cardiology
4 ucla
5 University of California School of Medicine
* To whom correspondence should be addressed. E-mail: hayashih{at}belle.shiga-med.ac.jp.
A strong premature electrical stimulus (S2) induces both virtual anodes and virtual cathodes. The effects of virtual electrodes on intracellular calcium (Cai) transients and ventricular fibrillation thresholds (VFTs) are unclear. We studied 16 isolated, Langendorff-perfused rabbit hearts with simultaneous voltage and Cai 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 Cai varied depending on the S2 polarity. Relative to the level of Cai during the S1 beat, the Cai 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 to 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 APD compared to control (255±22 ms 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 Cai than virtual cathodes. Monophasic S2 is associated with lower VFT than biphasic S2, but this difference was eliminated by inhibition of SR function and prolongation of APD. However, inhibition of SR function also reduced VFT, indicating that the Cai dynamics modulate, but are not essential, to ventricular vulnerability.
