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Effects of unipolar stimulation on voltage and calcium distributions in the isolated rabbit heart

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Abstract

Background

The effect of electric stimulation on the polarization of cardiac tissue (virtual electrode effect) is well known; the corresponding response of intracellular calcium concentration ([Ca2+] i ) and its dependence on coupling interval between conditioning stimulus (S1) and test stimulus (S2) has yet to be elucidated.

Objective

Because uncovering the transmembrane potential (V m)–[Ca2+] i relationship during an electric shock is imperative for understanding arrhythmia induction and defibrillation, we aimed to study simultaneous V m and [Ca2+] i responses to strong unipolar stimulation.

Methods

We used a dual-camera optical system to image concurrently V m and [Ca2+] i responses to unipolar stimulation (20 ms ± 20 mA) in Langendorff-perfused rabbit hearts. RH-237 and Rhod-2 fluorescent dyes were used to measure V m and [Ca2+] i , respectively. The S1–S2 interval ranged from 10 to 170 ms to examine stimulation during the action potential.

Results

The [Ca2+] i deflections were less pronounced than changes in V m for all S1–S2 intervals. For cathodal stimulation, [Ca2+] i at the central virtual cathode region increased with prolongation of S1–S2 interval. For anodal stimulation, [Ca2+] i at the central virtual anode area decreased with shortening of the S1–S2 interval. At very short S1–S2 intervals (10–20 ms), when S2 polarization was superimposed on the S1 action potential upstroke, the [Ca2+] i distribution did not follow V m and produced a more complex pattern. After S2 termination [Ca2+] i exhibited three outcomes in a manner similar to V m: non-propagating response, break stimulation, and make stimulation.

Conclusions

Changes in the [Ca2+] i distribution correlate with the behavior of the V m distribution for S1–S2 coupling intervals longer than 20 ms; at shorter intervals S2 creates more heterogeneous [Ca2+] i distribution in comparison with V m. Stimulation in diastole and at very short coupling intervals caused V m–[Ca2+] i uncoupling at the regions of positive polarization (virtual cathode).

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Abbreviations

[Ca2+] i :

intracellular calcium concentration

V m :

transmembrane potential

AP:

action potential

CT:

calcium transient

S1:

conditioning stimulus

S2:

testing stimulus

SR:

sarcoplasmic reticulum

VT:

ventricular tachycardia

VF:

ventricular fibrillation

VC:

virtual cathode

VA:

virtual anode

NCX:

Na+/Ca2+ exchanger

I CaL :

current via the L-type Ca2+ channels

I Na/Ca :

current via Na+/Ca2+ exchanger

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Acknowledgments

This work was supported by the NIH (RO1-HL58241, RO1-HL63267), the American Heart Association (0635037N), and the Vanderbilt Institute for Integrative Biosystems Research and Education. We thank Allison Price and Don Berry for their editorial assistance.

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Authors and Affiliations

  1. Dept. of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA

    Veniamin Y. Sidorov PhD, Marcella C. Woods PhD, Richard A. Gray PhD & John P. Wikswo PhD

  2. Dept. of Physics and Astronomy, Vanderbilt University, VU Station B 351807, Nashville, TN, 37235-1807, USA

    Veniamin Y. Sidorov PhD, Mark R. Holcomb PhD & John P. Wikswo PhD

  3. Vanderbilt Institute for Integrative, Biosystems Research and Education, Vanderbilt University, Nashville, TN, USA

    Veniamin Y. Sidorov PhD, Richard A. Gray PhD & John P. Wikswo PhD

  4. Dept. of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA

    John P. Wikswo PhD

  5. Dept. of Biomedical Engineering, University of Alabama, Birmingham, AL, USA

    Richard A. Gray PhD

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  1. Veniamin Y. Sidorov PhD
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  2. Mark R. Holcomb PhD
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Corresponding author

Correspondence to John P. Wikswo PhD.

Additional information

Returned for 1. Revision: 22 January 2008 1. Revision received: 13 May 2008

Returned for 2. Revision: 20 June 2008 2. Revision received: 2 July 2008

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Sidorov, V.Y., Holcomb, M.R., Woods, M.C. et al. Effects of unipolar stimulation on voltage and calcium distributions in the isolated rabbit heart. Basic Res Cardiol 103, 537–551 (2008). https://doi.org/10.1007/s00395-008-0740-1

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  • DOI: https://doi.org/10.1007/s00395-008-0740-1

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