This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 101/9/e90    most recent CIRCRESAHA.107.162735v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Warren, M. Articles by Zaitsev, A. V. Search for Related Content PubMed PubMed Citation Articles by Warren, M. Articles by Zaitsev, A. V. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL Related Collections Animal models of human disease Arrythmias-basic studies

(Circulation Research. 2007;101:e90.)
© 2007 American Heart Association, Inc.

UltraRapid Communication

Spatiotemporal Relationship Between Intracellular Ca²⁺ Dynamics and Wave Fragmentation During Ventricular Fibrillation in Isolated Blood-Perfused Pig Hearts

Mark Warren, José F. Huizar, Alexander G. Shvedko, Alexey V. Zaitsev

From the Nora Eccles Harrison Cardiovascular Research and Training Institute (M.W., A.G.S., A.V.Z.), University of Utah, Salt Lake City; and the Institute for Cardiovascular Research (J.F.H.), SUNY Upstate Medical University, Syracuse, NY.

Correspondence to Alexey V. Zaitsev, PhD, Nora Eccles Harrison CVRTI, University of Utah, 95 South 2000 East, Salt Lake City, UT 84112-5000. E-mail zaitsev{at}cvrti.utah.edu

Normal "master–slave" relationship between the action potential (AP) and intracellular Ca²⁺ transient (Ca_iT) is sometimes altered during ventricular fibrillation (VF). The nature of AP/Ca_iT dissociation during VF and its role in inducing wavebreaks (WBs) remain unclear. We simultaneously mapped AP (RH237) and Ca_iT (Rhod-2) during VF in blood-perfused pig hearts. We computed AP and Ca_iT dominant frequency (DF) and Ca_iT delay in each AP cycle. We identified WBs as singularity points in AP phase movies and sites of conduction block (CB) as sites where an AP wavefront failed to propagate. We analyzed spatiotemporal relationship between abnormal AP/Ca_iT sequences and CB sites. We used a calcium chelator (BAPTA-AM) to abolish Ca_iT and test its involvement in WB formation. During VF, the DF difference between AP and Ca_iT was <10% of the respective values in 95% of pixels, and 80% of all Ca_iT upstrokes occurred during the initial 25% of the excitation cycle. Aberrant sequences of AP and Ca_iT occurred almost exclusively near CB sites but could be traced to normal wavefront sequences away from CB sites. Thus, apparent AP/Ca_iT dissociation was largely attributable to spatial uncertainty of the absolute position of block of each wave. BAPTA-AM reduced Ca_iT amplitude to 30.5±12.9% of control and the DF of AP from 12.2±1.6 to 10.4±1.3Hz (P<0.01), but did not significantly alter WB incidence (0.76±0.19 versus 0.72±0.19SP/mm²). These results do not support presence of spontaneous, non–voltage-gated Ca_iTs during VF and suggest that AP/Ca_iT dissociation is a consequence rather than a cause of wave fragmentation.

Key Words: ventricular fibrillation • pig heart • action potential • calcium transient • wavebreak

This article has been cited by other articles:

				M. P. W. Moos, J. D. Mewburn, F. W. K. Kan, S. Ishii, M. Abe, K. Sakimura, K. Noguchi, T. Shimizu, and C. D. Funk Cysteinyl leukotriene 2 receptor-mediated vascular permeability via transendothelial vesicle transport FASEB J, December 1, 2008; 22(12): 4352 - 4362. [Abstract] [Full Text] [PDF]

				L. Tang, G.-S. Hwang, H. Hayashi, J. Song, M. Ogawa, K. Kobayashi, B. Joung, H. S. Karagueuzian, P.-S. Chen, and S.-F. Lin Intracellular calcium dynamics at the core of endocardial stationary spiral waves in Langendorff-perfused rabbit hearts Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H297 - H304. [Abstract] [Full Text] [PDF]

				M. Warren and A. V. Zaitsev Evidence Against the Role of Intracellular Calcium Dynamics in Ventricular Fibrillation Circ. Res., May 9, 2008; 102(9): e103 - e103. [Full Text] [PDF]

				M. Ogawa, S.-F. Lin, J. N. Weiss, and P.-S. Chen Calcium Dynamics and Ventricular Fibrillation Circ. Res., March 14, 2008; 102(5): e52 - e52. [Full Text] [PDF]