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Three distinct phases of VF during global ischemia in the isolated blood-perfused pig heart

¹Institute for Cardiovascular Research and ²Department of Pharmacology, State University of New York Upstate Medical University, Syracuse, New York; and ³Nora Eccles Harrison Cardiovascular Research and Training Institute and ⁴Department of Biomedical Engineering, University of Utah, Salt Lake City, Utah

Submitted 31 January 2007 ; accepted in final form 1 June 2007

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 electrocardiogram (ECG) frequency spectrum during VF in the ischemic myocardium. We recorded voltage-sensitive fluorescence of di-4-ANEPPS (anterior left ventricle, 35 x 35 mm, 64 x 64 pixels) and the volume-conducted ECG in six blood-perfused hearts during 10 min of VF and global ischemia. We used coefficient of variation (CV) to estimate variability of AP amplitude, AP duration, and diastolic interval (CV-APA, CV-APD, and CV-DI, respectively). We computed excitation median frequency (Median_F), spectral width of the AP and ECG (SpW-AP and SpW-ECG, respectively), wavebreak incidence (WBI), and recurrence of propagation direction (RPD). We found three distinct phases of local VF dynamics: "relatively periodic" (1 min, high Median_F, moderate AP variability, high WBI, low RPD), "highly periodic" (1–2 min, reduced Median_F, low AP variability, low WBI, high RPD), and "aperiodic" (3–10 min, low Median_F, high AP variability, high WBI, low RPD). In one experiment, spontaneous conversion from the aperiodic to the highly periodic phase occurred after 5 min of ischemia. The SpW-ECG was correlated with SpW-AP, CV-APD, and CV-APA. We conclude that 1) at least three distinct phases of VF dynamics are present in our model, and 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.

ventricular fibrillation; action potential; electrocardiogram

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