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

Abstract

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" (<or=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.