Takeda Taizo, Takeda Setsuko, Uehara Natsumi, Yanagisawa Shungaku, Furukawa Tatsuya, Nibu Ken-Ichi, Kakigi Akinobu
*Department of Otolaryngology, Nishinomiya Municipal Central Hospital †Nishinomiya ‡Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kobe University, Japan.
Otol Neurotol. 2017 Apr;38(4):599-605. doi: 10.1097/MAO.0000000000001333.
The correlation between the isosorbide-induced decompression effect on the endolymphatic space and plasma osmolality (p-OSM) or plasma arginine vasopressin (p-AVP) was investigated on comparing two different dosages of isosorbide (2.8 and 1.4 g/kg) to elucidate why the decompression effect is delayed with a large dose of isosorbide.
Two experiments were performed using 80 guinea pigs. Experiment 1 was designed to morphologically investigate the sequential influence of the oral intake of 1.4- and 2.8-g/kg doses of isosorbide on the endolymphatic volume. The animals used were 50 guinea pigs (control: 10, experimental: 40). All animals underwent surgical obliteration of the endolymphatic sac of the left ear. One month after the surgery, control animals were sacrificed 3 hours after the intake of distilled water, and experimental animals were sacrificed 3 and 6 hours after the isosorbide intake. All of the left temporal bone served for the quantitative assessment of changes in the endolymphatic space, and the cross-sectional area of the scala media was measured from the mid-modiolar sections of the cochlea.Experiment 2 was designed to investigate changes in p-OSM and p-AVP levels 3 hours after the oral intake of isosorbide. Animals used were 15 guinea pigs (control: 5, experimental: 10). The control group received the oral administration of distilled water (4 ml/kg), and the experimental animals were subdivided into two groups consisting of 10 animals each by the dosage of isosorbide (1.4 or 2.8 g/kg). All animals were sacrificed for the measurement of p-OSM and p-AVP concentrations 3 hours after the intake of water or 70% isosorbide solution.
Morphologically, an isosorbide-induced decompression effect was noted in animals with both 1.4- and 2.8-g/kg doses of isosorbide. According to the regression analysis, however, the volumetric decrease of the endolymphatic space was more evident in cases with the small dose (1.4 g/kg) 3 hours after the intake (analysis of covariance [ANCOVA], p < 0.001). Six hours after, the decompression effect was significantly greater in cases with the large dose (2.8 g/kg) (ANCOVA, p < 0.001).Isosorbide intake caused a rise in p-OSM levels dose-dependently. The Cochran-Cox test revealed that the differences in the mean values among control and isosorbide groups were significant (p < 0.01). Regarding the p-AVP level, a significant increase was evident in cases with the large dose (2.8 g/kg) (p < 0.01, Cochran-Cox test), and not in cases with the small dose (1.4 g/kg).
An isosorbide-induced decompression effect of the endolymphatic space was evident in spite of two different dosages of isosorbide (2.8 and 1.4 g/kg). Three hours after the isosorbide intake, however, the decompression effect was more marked in the group with the small dose (1.4 g/kg). Since significant rises in p-OSM and p-AVP were evident in the group with the large dose, this early rise of p-AVP due to dehydration seems to be the major reason for the delayed decompression effect in cases with a large isosorbide intake.
通过比较两种不同剂量的异山梨醇（2.8和1.4 g/kg），研究异山梨醇对内淋巴间隙的减压作用与血浆渗透压（p-OSM）或血浆精氨酸加压素（p-AVP）之间的相关性，以阐明大剂量异山梨醇减压作用延迟的原因。
使用80只豚鼠进行了两项实验。实验1旨在从形态学上研究口服1.4 g/kg和2.8 g/kg剂量异山梨醇对内淋巴体积的顺序影响。所用动物为50只豚鼠（对照组：10只，实验组：40只）。所有动物均接受左耳内淋巴囊手术闭塞。手术后1个月，对照组动物在摄入蒸馏水3小时后处死，实验组动物在摄入异山梨醇3小时和6小时后处死。所有左侧颞骨用于对内淋巴间隙变化进行定量评估，并从耳蜗的中轴切面测量中阶的横截面积。实验2旨在研究口服异山梨醇3小时后p-OSM和p-AVP水平的变化。所用动物为15只豚鼠（对照组：5只，实验组：10只）。对照组口服蒸馏水（4 ml/kg），实验组动物按异山梨醇剂量（1.4或2.8 g/kg）分为两组，每组10只。所有动物在摄入水或70%异山梨醇溶液3小时后处死，用于测量p-OSM和p-AVP浓度。
在形态学上，1.4 g/kg和2.8 g/kg剂量的异山梨醇组动物均出现了异山梨醇诱导的减压作用。然而，根据回归分析，摄入后3小时小剂量（1.4 g/kg）组内淋巴间隙的体积减小更为明显（协方差分析[ANCOVA]，p<0.001）。6小时后，大剂量（2.8 g/kg）组的减压作用明显更大（ANCOVA，p<0.001）。异山梨醇摄入导致p-OSM水平呈剂量依赖性升高。 Cochr an-Cox检验显示，对照组和异山梨醇组之间的平均值差异具有显著性（p<0.01）。关于p-AVP水平，大剂量（2.8 g/kg）组有明显升高（p<0.01， Cochr an-Cox检验），小剂量（1.4 g/kg）组则无明显升高。
尽管异山梨醇有两种不同剂量（2.8和1.4 g/kg），但其对内淋巴间隙的减压作用是明显的。然而，在摄入异山梨醇3小时后，小剂量（1.4 g/kg）组的减压作用更为显著。由于大剂量组中p-OSM和p-AVP明显升高，这种因脱水导致的p-AVP早期升高似乎是大剂量异山梨醇摄入时减压作用延迟的主要原因。
