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  • Title: Spatiotemporal relationship between intracellular Ca2+ dynamics and wave fragmentation during ventricular fibrillation in isolated blood-perfused pig hearts.
    Author: Warren M, Huizar JF, Shvedko AG, Zaitsev AV.
    Journal: Circ Res; 2007 Oct 26; 101(9):e90-101. PubMed ID: 17932324.
    Abstract:
    Normal "master-slave" relationship between the action potential (AP) and intracellular Ca2+ transient (Ca(i)T) is sometimes altered during ventricular fibrillation (VF). The nature of AP/Ca(i)T dissociation during VF and its role in inducing wavebreaks (WBs) remain unclear. We simultaneously mapped AP (RH237) and Ca(i)T (Rhod-2) during VF in blood-perfused pig hearts. We computed AP and Ca(i)T dominant frequency (DF) and Ca(i)T 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(i)T sequences and CB sites. We used a calcium chelator (BAPTA-AM) to abolish Ca(i)T and test its involvement in WB formation. During VF, the DF difference between AP and Ca(i)T was <10% of the respective values in 95% of pixels, and 80% of all Ca(i)T upstrokes occurred during the initial 25% of the excitation cycle. Aberrant sequences of AP and Ca(i)T occurred almost exclusively near CB sites but could be traced to normal wavefront sequences away from CB sites. Thus, apparent AP/Ca(i)T dissociation was largely attributable to spatial uncertainty of the absolute position of block of each wave. BAPTA-AM reduced Ca(i)T amplitude to 30.5+/-12.9% of control and the DF of AP from 12.2+/-1.6 to 10.4+/-1.3 Hz (P<0.01), but did not significantly alter WB incidence (0.76+/-0.19 versus 0.72+/-0.19 SP/mm2). These results do not support presence of spontaneous, non-voltage-gated Ca(i)Ts during VF and suggest that AP/Ca(i)T dissociation is a consequence rather than a cause of wave fragmentation.
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