Ventricular divergence correlates with epicardial wavebreaks and predicts ventricular arrhythmia in isolated rabbit hearts during therapeutic hypothermia

• Published in: PloS one 2020-02, Vol.15 (2), p.e0228818-e0228818
• Main Authors: Hsieh, Yu-Cheng, Hsieh, Wan-Hsin, Li, Cheng-Hung, Liao, Ying-Chieh, Lin, Jiunn-Cherng, Weng, Chi-Jen, Lo, Men-Tzung, Tuan, Ta-Chuan, Lin, Shien-Fong, Yeh, Hung-I, Huang, Jin-Long, Haugan, Ketil, Larsen, Bjarne D, Lin, Yenn-Jiang, Lin, Wei-Wen, Wu, Tsu-Juey, Chen, Shih-Ann
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Arrhythmia; Arrhythmias, Cardiac - physiopathology; Biology and Life Sciences; Cardiac arrhythmia; Cardiology; Clinical medicine; Correlation; Data analysis; Divergence; EKG; Electrocardiography; Engineering; Fibrillation; Health aspects; Heart Ventricles - drug effects; Heart Ventricles - physiopathology; Hospitals; Hypothermia; Hypothermia, Induced - adverse effects; Internal medicine; Medicine; Medicine and Health Sciences; Morphology; Oligopeptides - pharmacology; Pericardium - drug effects; Pericardium - physiology; Pericardium - physiopathology; Physical Sciences; Rabbits; Regression analysis; Regression models; Research and Analysis Methods; Statistical analysis; Ventricle; Ventricular fibrillation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0228818

High beat-to-beat morphological variation (divergence) on the ventricular electrogram during programmed ventricular stimulation (PVS) is associated with increased risk of ventricular fibrillation (VF), with unclear mechanisms. We hypothesized that ventricular divergence is associated with epicardial wavebreaks during PVS, and that it predicts VF occurrence. Langendorff-perfused rabbit hearts (n = 10) underwent 30-min therapeutic hypothermia (TH, 30°C), followed by a 20-min treatment with rotigaptide (300 nM), a gap junction modifier. VF inducibility was tested using burst ventricular pacing at the shortest pacing cycle length achieving 1:1 ventricular capture. Pseudo-ECG (p-ECG) and epicardial activation maps were simultaneously recorded for divergence and wavebreaks analysis, respectively. A total of 112 optical and p-ECG recordings (62 at TH, 50 at TH treated with rotigaptide) were analyzed. Adding rotigaptide reduced ventricular divergence, from 0.13±0.10 at TH to 0.09±0.07 (p = 0.018). Similarly, rotigaptide reduced the number of epicardial wavebreaks, from 0.59±0.73 at TH to 0.30±0.49 (p = 0.036). VF inducibility decreased, from 48±31% at TH to 22±32% after rotigaptide infusion (p = 0.032). Linear regression models showed that ventricular divergence correlated with epicardial wavebreaks during TH (p