Egami Naoya, Kakigi Akinobu, Takeda Taizo, Yamasoba Tatsuya
Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
Hear Res. 2016 Feb;332:151-159. doi: 10.1016/j.heares.2015.12.017. Epub 2015 Dec 21.
We investigated the influence of vasopressin type 2 receptor antagonist (OPC-41061; Tolvaptan) on experimentally induced endolymphatic hydrops (EH) in guinea pigs. In the first series, the endolymphatic sac (ES) of the left ear of all animals was electrocauterized. Four weeks after surgery, the animals were allocated to four groups: three systemic applications groups (saline, OPC 10 and 100 mg/kg) and a local round window (RW) OPC 1 mg/body application group. We examined the histopathology of the temporal bones and assessed volumetric changes of the endolymphatic space in the cochlea and saccule. In the second series, we investigated the effects of systemic and topical applications of OPC on plasma vasopressin (p-VP) concentrations and plasma osmolality (p-OSM). In the first series, we found that EH was reduced in the OPC 10 mg/kg systemic and OPC RW application groups. In contrast, EH increased in the OPC 100 mg/kg systemic application group. In the second series, neither p-VP levels nor p-OSM were significantly different among the non-OPC, OPC 10 mg/kg systemic, and OPC RW application groups. However, in the OPC 100 mg/kg systemic application group, the p-VP level was significantly higher than that in other groups, and p-OSM was higher than that in the non-OPC group. The systemic application of a low dose of OPC and topical application of OPC resulted in reduced EH in the face of minimal systemic effects (p-VP and p-OSM). These findings suggest that OPC-41061 may be one useful treatment option for EH.
我们研究了2型血管加压素受体拮抗剂（OPC - 41061；托伐普坦）对豚鼠实验性诱导的内淋巴积水（EH）的影响。在第一组实验中，对所有动物左耳的内淋巴囊（ES）进行电灼。术后四周，将动物分为四组：三个全身给药组（生理盐水、OPC 10和100 mg/kg）和一个局部圆窗（RW）OPC 1 mg/只给药组。我们检查了颞骨的组织病理学，并评估了耳蜗和球囊内淋巴间隙的容积变化。在第二组实验中，我们研究了OPC全身给药和局部给药对血浆血管加压素（p - VP）浓度和血浆渗透压（p - OSM）的影响。在第一组实验中，我们发现OPC 10 mg/kg全身给药组和OPC RW给药组的EH有所减轻。相比之下，OPC 100 mg/kg全身给药组的EH有所加重。在第二组实验中，非OPC组、OPC 10 mg/kg全身给药组和OPC RW给药组之间的p - VP水平和p - OSM均无显著差异。然而，在OPC 100 mg/kg全身给药组中，p - VP水平显著高于其他组，且p - OSM高于非OPC组。低剂量OPC的全身给药和OPC的局部给药在全身影响（p - VP和p - OSM）最小的情况下导致EH减轻。这些发现表明，OPC - 41061可能是EH的一种有效治疗选择。
