Normal 123I-MIBG uptake areas may be associated with hyperinnervation and arrhythmia risk in phenol model rabbit hearts
Normal 123I-MIBG uptake areas may be associated with hyperinnervation and arrhythmia risk in phenol model rabbit hearts
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苯酚模型兔心脏中正常的 123I-MIBG 摄取面积可能与过度神经支配和心律失常风险相关
DOI：
10.1111/pace.13174
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Ikari Yuji
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文献类型：
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作者：
Amino Mari;Yoshioka Koichiro;Tanaka Sachie;Kawabe Noboru;Kurosawa Hiroyuki;Uchida Keisuke;Oshikiri Shinobu;Hashida Tadashi;Kanda Shigetaka;Inokuchi Sadaki;Ikari Yuji
背景碘-123 间碘苄基胍 (123I-MIBG) 可用于检测心脏的交感神经支配，并且与致命性心律失常密切相关。然而，这种成像通常针对最高摄取区域进行校准，因此无法识别过度神经支配的区域。我们假设去神经心脏中正常的 123 I-MIBG 摄取区域将表现出神经萌芽并与心律失常发生的可能性相关。方法在麻醉下准备 20 只用苯酚或假手术治疗的新西兰白兔。使用苯酚 4 周后，使用放射自显影和免疫染色对交感神经支配进行量化，并进行电生理学研究。结果 123I-MIBG 显示，与最低摄取区域内相邻区域之间的同位素摄取相比，MIBG 减弱和丰富的区域之间的边界区域的同位素摄取存在最大局部差异。在免疫染色中，在 MIBG 减弱区域观察到生长相关蛋白 43 信号的异质性和表达减少；然而，在 MIBG 丰富的区域发现了丰富的信号。在 MIBG 丰富区域的部分观察到酪氨酸羟化酶信号的上调。在电生理学研究中，通过去甲肾上腺素输注，苯酚应用区域的激活恢复间隔（ARI）离散度增加。星状刺激加剧了应用苯酚和未应用苯酚区域的 ARI 分散，并与室性心动过速和心室颤动的诱发性增加有关。 结论 去神经兔心脏的非去神经区域存在过度神经支配，表明异质神经重塑发生在看似正常 123 I-MIBG 摄取的区域，并导致电不稳定。
BackgroundIodine‐123 metaiodobenzylguanidine (123I‐MIBG) is useful for detecting sympathetic innervation in the heart, and has been closely associated with fatal arrhythmias. However, such imaging is typically calibrated to the area of highest uptake and thus is unable to identify areas of hyperinnervation. We hypothesized that normal123I‐MIBG uptake regions in the denervated heart would demonstrate nerve sprouting and correlate with the potential for arrhythmogenesis.MethodsTwenty New Zealand white rabbits treated with phenol or sham were prepared under anesthesia. Sympathetic innervation was quantified using autoradiography and immunostaining 4 weeks after phenol application, and electrophysiological study was performed.Results123I‐MIBG revealed maximal local differences in isotope uptake in the border zone between areas with attenuated and abundant MIBG compared with that seen between adjacent regions within the lowest uptake areas. On immunostaining, heterogeneous and decreased expressions of growth‐associated protein 43 signal were observed in the MIBG‐attenuated areas; however, abundant signals were recognized in the MIBG‐abundant areas. Upregulation of the tyrosine hydroxylase signal was observed at the part of the MIBG‐abundant area. In electrophysiological study, the dispersion of activation recovery interval (ARI) was increased in the phenol‐applied areas by norepinephrine infusion. Stellate stimulation exacerbated the ARI dispersion in both the phenol‐applied and nonapplied areas, and was associated with increased inducibility of ventricular tachycardia and ventricular fibrillation.ConclusionsThe presence of hyperinnervation in the nondenervated regions of denervated rabbit hearts suggests that heterogeneous neural remodeling occurs in regions with seemingly normal123I‐MIBG uptake and contributes to electrical instability.