BACKGROUND: The role of intracellular calcium (Ca(i)) in defibrillation and vulnerability is unclear. METHODS AND 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.
BACKGROUND: The role of intracellular calcium (Ca(i)) in defibrillation and vulnerability is unclear. METHODS AND 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: Lianguo Wang; Rachel C Myles; Nicole M De Jesus; Alex K P Ohlendorf; Donald M Bers; Crystal M Ripplinger Journal: Circ Res Date: 2014-02-25 Impact factor: 17.367
Authors: Tetsuji Shinohara; Daehyeok Kim; Boyoung Joung; Mitsunori Maruyama; Kannan Vembaiyan; Thomas G Back; S R Wayne Chen; Peng-Sheng Chen; Shien-Fong Lin Journal: Heart Vessels Date: 2013-07-09 Impact factor: 2.037
Authors: Boyoung Joung; Liang Tang; Mitsunori Maruyama; Seongwook Han; Zhenhui Chen; Marcelle Stucky; Larry R Jones; Michael C Fishbein; James N Weiss; Peng-Sheng Chen; Shien-Fong Lin Journal: Circulation Date: 2009-02-02 Impact factor: 29.690