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. 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.

journal_name

Circulation

journal_title

Circulation

authors

Hwang GS,Hayashi H,Tang L,Ogawa M,Hernandez H,Tan AY,Li H,Karagueuzian HS,Weiss JN,Lin SF,Chen PS

doi

10.1161/CIRCULATIONAHA.106.630509

subject

Has Abstract

pub_date

2006-12-12 00:00:00

pages

2595-603

issue

24

eissn

0009-7322

issn

1524-4539

pii

CIRCULATIONAHA.106.630509

journal_volume

114

pub_type

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