title: Intracellular calcium and vulnerability to fibrillation and defibrillation in Langendorff-perfused rabbit ventricles.
abstract: BACKGROUND
  The role of intracellular calcium (Ca(i)) in defibrillation and vulnerability is unclear.
  
  
  RESULTS
  We simultaneously mapped epicardial membrane potential and Ca(i) during shock on T-wave episodes (n=104) and attempted defibrillation episodes (n=173) in 17 Langendorff-perfused rabbit ventricles. Unsuccessful and type B successful defibrillation shocks were followed by heterogeneous distribution of Ca(i), including regions of low Ca(i) surrounded by elevated Ca(i) ("Ca(i) sinkholes") 31+/-12 ms after shock. The first postshock activation then originated from the Ca(i) sinkhole 53+/-14 ms after the shock. No sinkholes were present in type A successful defibrillation. A Ca(i) sinkhole also was present 39+/-32 ms after a shock on T that induced ventricular fibrillation, followed 22+/-15 ms later by propagated wave fronts that arose from the same site. This wave propagated to form a spiral wave and initiated ventricular fibrillation. Thapsigargin and ryanodine significantly decreased the upper limit of vulnerability and defibrillation threshold. We studied an additional 7 rabbits after left ventricular endocardial cryoablation, resulting in a thin layer of surviving epicardium. Ca(i) sinkholes occurred 31+/-12 ms after the shock, followed in 19+/-7 ms by first postshock activation in 63 episodes of unsuccessful defibrillation. At the Ca(i) sinkhole, the rise of Ca(i) preceded the rise of epicardial membrane potential in 5 episodes.
  
  
  CONCLUSIONS
  There is a heterogeneous postshock distribution of Ca(i). The first postshock activation always occurs from a Ca(i) sinkhole. The Ca(i) prefluorescence at the first postshock early site suggests that reverse excitation-contraction coupling might be responsible for the initiation of postshock activations that lead to ventricular fibrillation.
authors.affiliation: Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Gyo-Seung
authors.initials: GS
authors.lastname: Hwang
authors.forename: Hideki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Liang
authors.initials: L
authors.lastname: Tang
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ogawa
authors.forename: Heidy
authors.initials: H
authors.lastname: Hernandez
authors.forename: Alex Y
authors.initials: AY
authors.lastname: Tan
authors.forename: Hongmei
authors.initials: H
authors.lastname: Li
authors.forename: Hrayr S
authors.initials: HS
authors.lastname: Karagueuzian
authors.forename: James N
authors.initials: JN
authors.lastname: Weiss
authors.forename: Shien-Fong
authors.initials: SF
authors.lastname: Lin
authors.forename: Peng-Sheng
authors.initials: PS
authors.lastname: Chen
mesh_terms: D000200:Action Potentials; D000818:Animals; D018780:Body Surface Potential Mapping; D002118:Calcium / Q000378:metabolism*; D004554:Electric Countershock; D006352:Heart Ventricles; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D011817:Rabbits; D012433:Ryanodine / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014693:Ventricular Fibrillation / Q000209:etiology* / Q000503:physiopathology
chemical_list: D012433:Ryanodine; D019284:Thapsigargin; D002118:Calcium