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1 Pharmacology, SUNY Upstate Medical University, Syracuse, New York, United States
2 Nora Eccles Harrison Cardiovascular Research and Training Institute, Salt lake, Utah, United States
3 Salt Lake City, Utah, United States; Nora Eccles Harrison Cardiovascular Research and Training Institute, Salt lake, Utah, United States
4 Department of Biomedical Engineering, Nora Eccles Harrison Cardiovascular Research and Training Institute, Salt lake City, Utah, United States
* To whom correspondence should be addressed. E-mail: warren{at}cvrti.utah.edu.
Changes in ventricular fibrillation (VF) organization occurring after the onset of global ischemia are relevant to defibrillation and survival but remain poorly understood. We hypothesized that ischemia-specific dynamic instability of the action potential (AP) causes a loss of spatiotemporal periodicity of propagation and broadening of the ECG frequency spectrum during VF in the ischemic myocardium. We recorded voltage-sensitive fluorescence of Di-4-ANEPPS (anterior LV, 35x35 mm, 64x64 pixels) and the volume-conducted ECG in six blood-perfused hearts during 10 minutes of VF and global ischemia. We used coefficient of variation to estimate variability of AP amplitude, AP duration and diastolic interval (CV-APA, CV-APD, and CV-DI, respectively). We computed excitation median frequency (MedianF), spectral width of the AP and ECG (SpW-AP and SpW-ECG), wavebreak incidence (WBI) and recurrence of propagation direction (RPD). We found three distinct phases of local VF dynamics: "relatively periodic" (<= 1min, high MedianF, moderate AP variability, high WBI, low RPD); "highly periodic" (1-2 min, reduced MedianF, low AP variability, low WBI, high RPD); and "aperiodic" (3-10 min, low MedianF, high AP variability, high WBI, low RPD). In one experiment, a spontaneous conversion from aperiodic to highly periodic phase occurred after 5 min of ischemia. The SpW-ECG was correlated with SpW-AP and metrics of AP variability. We conclude that 1) at least 3 distinct phases of VF dynamics are present in our model; 2) the newly described "aperiodic" phase is related to ischemia-specific dynamic instability of the AP shape which underlies broadening of the ECG spectrum during VF evolution.
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