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Updated: Jul 10, 2026
Optocardiography and Electrophysiology Studies of Ex Vivo Langendorff-perfused Hearts
Published on: November 7, 2019
Spatiotemporal relationship between intracellular Ca2+ dynamics and wave fragmentation during ventricular
Mark Warren1, José F Huizar, Alexander G Shvedko
1Nora Eccles Harrison CVRTI, University of Utah, Salt Lake City, UT 84112-5000, USA.
Insights
During ventricular fibrillation (VF), action potential (AP) and intracellular calcium transient (Ca(i)T) dissociation is a consequence, not a cause, of wavebreaks. This study clarifies the spatiotemporal relationship between AP/Ca(i)T dynamics and wave fragmentation during VF.
Area of Science:
- Cardiovascular Physiology
- Cardiac Electrophysiology
- Computational Biology
Background:
- The relationship between action potential (AP) and intracellular calcium transient (Ca(i)T) is crucial for normal heart function.
- Alterations in this relationship are observed during ventricular fibrillation (VF), but their role in wavebreak (WB) formation is unclear.
Purpose of the Study:
- To investigate the spatiotemporal dynamics of AP and Ca(i)T during VF.
- To determine if AP/Ca(i)T dissociation causes or results from wave fragmentation and conduction block (CB).
Main Methods:
- Simultaneous mapping of AP and Ca(i)T using RH237 and Rhod-2 in blood-perfused pig hearts during VF.
- Computation of dominant frequencies (DF) and Ca(i)T delays.
- Identification of WBs and conduction block (CB) sites.
- Pharmacological manipulation using BAPTA-AM to assess Ca(i)T involvement.
Main Results:
- AP/Ca(i)T dissociation was minimal (<10% DF difference) in most areas and primarily observed near CB sites.
- Aberrant AP/Ca(i)T sequences could be traced to normal sequences away from CB sites, suggesting spatial uncertainty.
- Reducing Ca(i)T amplitude with BAPTA-AM did not significantly alter WB incidence, despite reducing AP dominant frequency.
Conclusions:
- AP/Ca(i)T dissociation during VF is largely a consequence of spatial uncertainty related to wave fragmentation and conduction block, not a primary driver.
- The findings do not support the presence of spontaneous, non-voltage-gated Ca(i)Ts contributing to WBs during VF.
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.
