標題: Gap junction modifier rotigaptide decreases the susceptibility to ventricular arrhythmia by enhancing conduction velocity and suppressing discordant alternans during therapeutic hypothermia in isolated rabbit hearts
作者: Hsieh, Yu-Cheng
Lin, Jiunn-Cherng
Hung, Chen-Ying
Li, Cheng-Hung
Lin, Shien-Fong
Yeh, Hung-I
Huang, Jin-Long
Lo, Chu-Pin
Haugan, Ketil
Larsen, Bjarne D.
Wu, Tsu-Juey
分子醫學與生物工程研究所
Institute of Molecular Medicine and Bioengineering
關鍵字: Cardiac alternans;Conduction velocity;Hypothermia;Optical mapping;Gap junction
公開日期: 1-Jan-2016
摘要: BACKGROUND Therapeutic hypothermia (TH) may increase the susceptibility to ventricular arrhythmias by decreasing ventricular conduction velocity (CV) and facilitating arrhythmogenic spatially discordant alternans (SDA). OBJECTIVE The purpose of this study was to test the hypothesis that rotigaptide, a gap junction enhancer, can increase ventricular CV, delay the onset of SDA, and decrease the susceptibility to pacing-induced ventricular fibrillation (PIVF) during TH. METHODS Langendorff-perfused isolated rabbit hearts were subjected to 30-minute moderate hypothermia (33 degrees C) followed by 20-minute treatment with rotigaptide (300 nM, n = 8) or vehicle (n = 5). The same protocol was also performed at severe hypothermia (30 degrees C; n = 8 for rotigaptide, n = 5 for vehicle). Using an optical mapping system, epicardial CV and SDA threshold were evaluated by Si pacing. Ventricular fibrillation inducibility was evaluated by burst pacing for 30 seconds at the shortest pacing cycle length (PCL) that achieved 1:1 ventricular capture. RESULTS Rotigaptide increased ventricular CV during 33 degrees C (PCL 300 ms, from 76 +/- 6 cm/s to 84 +/- 7 cm/s, P =.039) and 30 degrees C (PCL 300 ms, from 62 +/- 6 cm/s to 68 +/- 4 cm/s, P =.008). Rotigaptide decreased action potential duration dispersion at 33 degrees C (P =.01) and 30 degrees C (P =.035). During 30 degrees C, SDA thresholds (P =.042) and incidence of premature ventricular complexes (P =.025) were decreased by rotigaptide. PIVF inducibility was decreased by rotigaptide at 33 degrees C (P =.039) and 30 degrees C (P =.042). Rotigaptide did not change connexin43 expressions and distributions during hypothermia. CONCLUSION Rotigaptide protects the hearts against ventricular arrhythmias by increasing ventricular CV, delaying the onset of SDA, and reducing repolarization heterogeneity during TH. Enhancing cell-to-cell coupling by rotigaptide might be a novel approach to prevent ventricular arrhythmias during TH.
URI: http://dx.doi.org/10.1016/j.hrthm.2015.07.023
http://hdl.handle.net/11536/129504
ISSN: 1547-5271
DOI: 10.1016/j.hrthm.2015.07.023
期刊: HEART RHYTHM
Volume: 13
起始頁: 251
結束頁: 261
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