title: Effects of unipolar stimulation on voltage and calcium distributions in the isolated rabbit heart.
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 ([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).
authors.affiliation: Dept. of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
authors.forename: Veniamin Y
authors.initials: VY
authors.lastname: Sidorov
authors.forename: Mark R
authors.initials: MR
authors.lastname: Holcomb
authors.forename: Marcella C
authors.initials: MC
authors.lastname: Woods
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gray
authors.forename: John P
authors.initials: JP
authors.lastname: Wikswo
mesh_terms: 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
chemical_list: D005456:Fluorescent Dyes; D002118:Calcium