利伐斯的明单次和重复给药对实验猪胃电活动的影响。

The effect of single and repeated doses of rivastigmine on gastric myoelectric activity in experimental pigs.

机构信息

Biomedical Research Centre, University Hospital, Hradec Kralove, Czech Republic.

Animal Laboratory, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic.

出版信息

PLoS One. 2023 Jun 1;18(6):e0286386. doi: 10.1371/journal.pone.0286386. eCollection 2023.

DOI:10.1371/journal.pone.0286386

PMID:37262057

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10234519/

Abstract

BACKGROUND

Rivastigmine is a pseudo-irreversible cholinesterase inhibitor used for therapy of Alzheimer's disease and non-Alzheimer dementia syndromes. In humans, rivastigmine can cause significant gastrointestinal side effects that can limit its clinical use. The aim of this study was to assess the impact of rivastigmine on gastric motor function by means of electrogastrography (EGG) in experimental pigs.

METHODS

Six experimental adult female pigs (Sus scrofa f. domestica, hybrids of Czech White and Landrace breeds; 3-month-old; mean weight 30.7 ± 1.2 kg) were enrolled into the study twice and created two experimental groups. In group A, a single intragastric dose of 6 mg rivastigmine hydrogen tartate was administered in the morning to fasting pigs before EGG recording. In group B, rivastigmine was administered to overnight fasting animals in a dietary bolus in the morning for 7 days (6 mg per day). On day 8, an intragastric dose of 12 mg rivastigmine was given in the morning to fasting pigs before EGG. EGG recording was accomplished by means of an EGG standalone system. Recordings from both groups were evaluated in dominant frequency and EGG power (areas of amplitudes).

RESULTS

In total, 1,980 one-minute EGG intervals were evaluated. In group A, basal EGG power (median 1290.5; interquartile range 736.5-2330 μV2) was significantly higher in comparison with the power of intervals T6 (882; 577-1375; p = 0.001) and T10 (992.5; 385-2859; p = 0.032). In group B, the dominant frequency increased significantly from basal values (1.97 ± 1.57 cycles per minute) to intervals T9 (3.26 ± 2.16; p < 0.001) and T10 (2.14 ± 1.16; p = 0.012), respectively. In group B, basal EGG power (median 1030.5; interquartile range 549-5093) was significantly higher in comparison with the power of intervals T7 (692.5; 434-1476; p = 0.002) and T8 (799; 435-1463 μV2; p = 0.004).

CONCLUSIONS

Both single as well as repeated intragastric administration of rivastigmine hydrogen tartrate caused a significant decrease of EGG power (areas of amplitudes) in experimental pigs. EGG power may serve as an indirect indicator of gastric motor competence. These findings might provide a possible explanation of rivastigmine-associated dyspepsia in humans.

摘要

背景

利伐斯的明是一种拟不可逆的胆碱酯酶抑制剂，用于治疗阿尔茨海默病和非阿尔茨海默痴呆综合征。在人类中，利伐斯的明会引起明显的胃肠道副作用，这可能会限制其临床应用。本研究的目的是通过胃电图（EGG）评估利伐斯的明对实验猪胃动力功能的影响。

方法

将 6 只实验成年雌性猪（Sus scrofa f. domestica，捷克白和长白品种的杂种；3 月龄；平均体重 30.7±1.2kg）分为两组，每组 3 只，进行两次实验。在 A 组中，在禁食的猪中于早晨单次给予 6mg 利伐斯的明氢酒石酸盐，然后进行 EGG 记录。在 B 组中，将利伐斯的明以膳食丸的形式给予禁食的猪，每天 6mg，共 7 天。第 8 天，在禁食的猪中于早晨给予 12mg 利伐斯的明氢酒石酸盐，然后进行 EGG 记录。通过 EGG 独立系统完成 EGG 记录。评估两组的主导频率和 EGG 功率（振幅面积）。

结果

共评估了 1980 个 1 分钟的 EGG 间隔。在 A 组中，基础 EGG 功率（中位数 1290.5；四分位距 736.5-2330μV2）明显高于 T6 间隔（882；577-1375；p=0.001）和 T10 间隔（992.5；385-2859；p=0.032）的功率。在 B 组中，主导频率从基础值（1.97±1.57 次/分钟）显著增加到 T9 间隔（3.26±2.16；p<0.001）和 T10 间隔（2.14±1.16；p=0.012）。在 B 组中，基础 EGG 功率（中位数 1030.5；四分位距 549-5093）明显高于 T7 间隔（692.5；434-1476；p=0.002）和 T8 间隔（799；435-1463μV2；p=0.004）的功率。