Peak-to-Peak Voltage Mapping Reveals Dynamic Arrhythmogenic Substrate Behavior in Isolated Rabbit Hearts.

Cardiac arrhythmias are associated with structural and electrical remodeling processes that generate heterogeneous arrhythmogenic substrates characterized by low-voltage areas and abnormal conduction. Although electroanatomical voltage mapping is widely used for substrate characterization, epicardial voltage thresholds remain highly dependent on species, chamber, and recording configuration, and have not been systematically established for isolated rabbit hearts. We hypothesized that healthy rabbit epicardial tissue exhibits reproducible chamber-specific voltage distributions and that arrhythmias produce dynamic rhythm-dependent low-voltage areas substrate behavior. Isolated New Zealand White rabbit hearts (n = 9) were perfused using a Langendorff system and mapped using custom epicardial multi-electrode arrays. Unipolar EGMs were acquired from the right atrium (RA), left atrium (LA), and ventricular epicardium (V), while bipolar EGMs were derived from adjacent electrodes. Chamber-specific voltage thresholds were determined from sinus rhythm (SR) recordings using 95th percentile criterion. Voltage dynamics were further investigated during induced atrial tachycardia (AT), ventricular tachycardia (VT), and ventricular fibrillation (VF). Unipolar voltage thresholds were 7.4 mV (RA), 8.9 mV (LA), and 17.4 mV (V), whereas bipolar thresholds were 4.1 mV, 5.7 mV, and 9.5 mV, respectively. Arrhythmias significantly reduced peak-to-peak amplitudes compared with SR (p < 0.05), particularly during VT and VF. Longitudinal voltage mapping revealed both transient rhythm-dependent low-voltage areas and spatially persistent low-voltage areas, suggesting distinct functional substrate behaviors during arrhythmogenesis. These findings establish reference epicardial voltage thresholds for the rabbit heart model and demonstrate the utility of voltage mapping for investigating dynamic arrhythmogenic substrate organization under controlled ex vivo conditions.