Effects of unipolar stimulation on voltage and calcium distributions in the isolated rabbit heart.
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 ([Ca(2+)](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))-[Ca(2+)](i) relationship during an electric shock is imperative for understanding arrhythmia induction and defibrillation, we aimed to study simultaneous V(m) and [Ca(2+)](i) responses to strong unipolar stimulation.


METHODS
We used a dual-camera optical system to image concurrently V (m) and [Ca(2+)](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 [Ca(2+)](i), respectively. The S1-S2 interval ranged from 10 to 170 ms to examine stimulation during the action potential.


RESULTS
The [Ca(2+)](i) deflections were less pronounced than changes in V(m) for all S1-S2 intervals. For cathodal stimulation, [Ca(2+)](i) at the central virtual cathode region increased with prolongation of S1-S2 interval. For anodal stimulation, [Ca(2+)](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 [Ca(2+)](i) distribution did not follow V(m) and produced a more complex pattern. After S2 termination [Ca(2+)](i) exhibited three outcomes in a manner similar to V(m): non-propagating response, break stimulation, and make stimulation.


CONCLUSIONS
Changes in the [Ca(2+)](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 [Ca(2+)](i) distribution in comparison with V(m). Stimulation in diastole and at very short coupling intervals caused V(m)-[Ca(2+)](i) uncoupling at the regions of positive polarization (virtual cathode).
Sidorov
Veniamin Y
VY
Dept. of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
Holcomb
Mark R
MR
Woods
Marcella C
MC
Gray
Richard A
RA
Wikswo
John P
JP
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004558:Electric Stimulation; D022062:Electrophysiologic Techniques, Cardiac / Q000379:methods*; D005260:Female; D005456:Fluorescent Dyes; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011817:Rabbits; D016277:Ventricular Function, Left / Q000502:physiology
D005456:Fluorescent Dyes; D002118:Calcium