title: Cardiac response to low-energy field pacing challenges the standard theory of defibrillation.
abstract: BACKGROUND
  The electric response of myocardial tissue to periodic field stimuli has attracted significant attention as the basis for low-energy antifibrillation pacing, potentially more effective than traditional single high-energy shocks. In conventional models, an electric field produces a highly nonuniform response of the myocardial wall, with discrete excitations, or hot spots (HS), occurring at cathodal tissue surfaces or large coronary vessels. We test this prediction using novel 3-dimensional tomographic optical imaging.
  
  
  RESULTS
  Experiments were performed in isolated coronary perfused pig ventricular wall preparations stained with near-infrared voltage-sensitive fluorescent dye DI-4-ANBDQBS. The 3-dimensional coordinates of HS were determined using alternating transillumination. To relate HS formation with myocardial structures, we used ultradeep confocal imaging (interrogation depths, >4 mm). The peak HS distribution is located deep inside the heart wall, and the depth is not significantly affected by field polarity. We did not observe the strong colocalization of HS with major coronary vessels anticipated from theory. Yet, we observed considerable lateral displacement of HS with field polarity reversal. Models that de-emphasized lateral intracellular coupling and accounted for resistive heterogeneity in the extracellular space showed similar HS distributions to the experimental observations.
  
  
  CONCLUSIONS
  The HS distributions within the myocardial wall and the significant lateral displacements with field polarity reversal are inconsistent with standard theories of defibrillation. Extended theories based on enhanced descriptions of cellular scale electric mechanisms may be necessary. The considerable lateral displacement of HS with field polarity reversal supports the hypothesis of biphasic stimuli in low-energy antifibrillation pacing being advantageous.
authors.affiliation: From the Department of Pharmacology, State University of New York Upstate Medical University, Syracuse (B.J.C., A.M.P.); and Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand (M.L.T.).
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Caldwell
authors.affiliation: From the Department of Pharmacology, State University of New York Upstate Medical University, Syracuse (B.J.C., A.M.P.); and Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand (M.L.T.). m.trew@auckland.ac.nz.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Trew
authors.affiliation: From the Department of Pharmacology, State University of New York Upstate Medical University, Syracuse (B.J.C., A.M.P.); and Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand (M.L.T.).
authors.forename: Arkady M
authors.initials: AM
authors.lastname: Pertsov
mesh_terms: D015081:2-Naphthylamine / Q000031:analogs & derivatives; D000200:Action Potentials; D000818:Animals; D002304:Cardiac Pacing, Artificial / Q000379:methods*; D004554:Electric Countershock / Q000379:methods*; D005456:Fluorescent Dyes; D006321:Heart / Q000502:physiology*; D007090:Image Interpretation, Computer-Assisted; D021621:Imaging, Three-Dimensional; D018613:Microscopy, Confocal; D023421:Models, Animal; D011806:Quinolinium Compounds; D013552:Swine; D013997:Time Factors; D056969:Voltage-Sensitive Dye Imaging
chemical_list: C553754:1-(4-sulfanatobutyl)-4-(beta-(2-(di-n-butylamino)-6-naphthyl)butadienyl)quinolinium betaine; D005456:Fluorescent Dyes; D011806:Quinolinium Compounds; D015081:2-Naphthylamine
keywords: computer models; electrical stimulation; optical imaging