Department of Otorhinolaryngology - Head and Neck Surgery, Vienna General Hospital, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
MED-EL Medical Electronics Gesellschaft m.b.H., Innsbruck, Austria.
Hear Res. 2022 Dec;426:108644. doi: 10.1016/j.heares.2022.108644. Epub 2022 Oct 31.
Various animal models have been established and applied in hearing research. In the exploration of novel cochlear implant developments, mainly rodents have been used. Despite their important contribution to the understanding of auditory function, translation of experimental observations from rodents to humans is limited due to the size differences and genetic variability. Large animal models with better representation of the human cochlea are sparse. For this reason, we evaluated domestic piglets and Aachen minipigs for the suitability as a cochlear implantation animal model with commercially available cochlear implants.
Four domestic piglets (two male and two female) and six Aachen minipigs were implanted with either MED-EL Flex24 or Flex20 cochlear implants respectively, after a step-by-step surgical approach was trained with pig cadavers. Electrophysiological measurements were performed before, during and after implantation for as long as 56 days after surgery. Auditory brainstem responses, electrocochleography as well as electrically and acoustically evoked compound action potentials were recorded. Selected cochleae were further analyzed histologically or with micro-CT imaging.
A surgical approach was established using a retroauricular single incision. Baseline auditory thresholds were 27 ± 3 dB sound pressure level (SPL; auditory brainstem click responses, mean ± standard error of the mean) and ranged between 30 and 80 dB SPL in frequency-specific responses (0.5 - 32 kHz). Follow-up measurements revealed deafness within the first two weeks after surgery, but some animals partially recovered to a hearing threshold of 80 dB SPL in certain frequencies as well as in click responses. Electrically evoked compound action potential thresholds increased within the first week after surgery, which led to lower stimulation responses or increase of necessary charge input. Immune reactions and consecutive scalar fibrosis following implantation were confirmed with histological analysis of implanted cochleae and may result in increased impedances. A three-dimensional minipig micro-CT segmentation revealed cochlear volumetric data similar to human inner ear dimensions.
This study underlines the feasibility of cochlear implantation with clinically used cochlear implants in a large animal model with representative inner ear dimensions comparable to humans. To bridge the gap between small animal models and humans in translational research and to account for the structural and size differences, we recommend the minipig as a valuable animal model for hearing research. First insights into the induced trauma in minipigs after cochlear implant surgery and a partial hearing recovery present important data of the cochlear health changes in large animal cochleae.
各种动物模型已被建立并应用于听力研究。在探索新型人工耳蜗开发的过程中，主要使用啮齿动物。尽管它们对听觉功能的理解做出了重要贡献，但由于大小差异和遗传可变性，将实验观察结果从啮齿动物转化为人类是有限的。具有更好的人耳蜗代表性的大型动物模型稀缺。出于这个原因，我们评估了家猪和亚琛米尼猪作为适合使用市售人工耳蜗植入物的耳蜗植入动物模型的适用性。
使用 MED-EL Flex24 或 Flex20 人工耳蜗分别对四只家猪（两只雄性和两只雌性）和六只亚琛米尼猪进行了植入，在此之前，使用猪尸体进行了逐步手术方法的培训。在手术前后进行了电生理测量，最长可达术后 56 天。记录了听觉脑干反应、电 Cochleography 以及电和声学诱发复合动作电位。进一步对选定的耳蜗进行了组织学或微 CT 成像分析。
使用耳后单切口建立了手术方法。基线听觉阈值为 27±3dB 声压级（听觉脑干点击反应，平均值±均数标准误差），在特定频率（0.5-32kHz）的频率特异性反应中范围为 30-80dB SPL。后续测量显示手术后前两周内失聪，但一些动物在某些频率和点击反应中部分恢复到 80dB SPL 的听力阈值。手术后第一周内，电诱发复合动作电位阈值增加，导致刺激反应降低或所需电荷输入增加。植入耳蜗的组织学分析证实了植入后的免疫反应和随后的标量纤维化，这可能导致阻抗增加。三维米尼猪微 CT 分割显示耳蜗容积数据与人内耳尺寸相似。
这项研究强调了使用具有代表性的内耳尺寸的大型动物模型进行临床使用的人工耳蜗植入的可行性，该模型与人内耳尺寸相似。为了缩小小型动物模型和人类在转化研究中的差距，并考虑到结构和大小差异，我们建议将迷你猪作为听力研究的有价值的动物模型。迷你猪在人工耳蜗手术后的听力恢复和听力恢复方面的初步研究提供了大型动物耳蜗内耳蜗健康变化的重要数据。
