Assessing the severity of laparotomy and partial hepatectomy in male rats – a multimodal approach

A total of 136 adult male WistarHan rats were randomly assigned to three groups: Sham-laparotomy (Sham) group [7 days post-surgical survival time (n = 10)]; 50% partial hepatectomy (PH) group; 70% PH group. Both PH groups had three postoperative survival times of 1, 3, or 7 days (n = 21 for each time-point). Postoperative severity assessment was performed daily using a model-specific score sheet, behavioral testing in the Open Field (OF), telemetric data analysis, and analysis of blood and fecal samples. Parameters of surgical and postoperative distress and severity in the animals were analyzed.

Rats were trained to the OF test thrice every alternate training day (D-20, D-18, and D-16). On D-15 (surgery I), a telemetric transmitter (hereafter referred to as transmitter implantation, TI) was surgically implanted subcutaneously in the left flank in 12 animals of each 7-day survival group. All animals in the Sham group were implanted a dummy device. Transmitter implantation was followed by a 12-day recovery phase with no further intervention. To ensure comparability, this test-free recovery period was standardized for all animals, even if they were not telemetrically monitored. Thereafter, retraining was performed on D-2 and -1 in all animals, followed by Sham, 50% PH, or 70% PH (surgery II), on D0. OF tests were performed on POD1, POD3, POD4, and POD7 (depending on survival time). Body weight was measured before individual training, as well as before and after each surgery; in addition, the body weight was measured once daily during postoperative scoring. Postoperative scoring was conducted three times a day from POD1 to POD3 and once a day in the morning from POD4 to POD7. On euthanasia day (POD1, POD3, or POD7) rats were reopened (surgery III) under general anesthesia and analgesia and were euthanized by final blood withdrawal from the inferior vena cava. Organs were removed for subsequent examinations and processed accordingly.

本研究共纳入136只成年雄性WistarHan大鼠，按随机原则分为三组：假剖腹手术（Sham-laparotomy）组[术后存活时长7天，样本量n=10]；50%部分肝切除术（partial hepatectomy, PH）组；70% PH组。两个PH组均设置1、3、7天三个术后存活时间点，每个时间点样本量均为n=21。每日采用针对该模型的专用评分量表开展术后严重程度评估，进行旷场（Open Field, OF）行为学测试、遥测数据分析，并对血液与粪便样本进行检测。对受试大鼠的手术及术后应激与严重程度相关参数进行分析。

大鼠于间隔训练日（D-20、D-18、D-16）接受三次旷场测试训练。于D-15（首次手术，手术I）时，为每个7天存活组中的12只大鼠于左侧腹皮下植入遥测发射器（telemetric transmitter，以下简称发射器植入，TI）；假手术组所有大鼠均植入假装置。发射器植入后设置12天的恢复期，期间无任何额外干预。为保证实验可比性，所有大鼠均标准化采用这一无测试的恢复期，即便未进行遥测监测的个体亦遵循此流程。此后，于D-2与D-1对所有大鼠进行复测训练，随后在D0开展假手术、50% PH或70% PH手术（手术II）。旷场测试分别于术后第1天（POD1）、术后第3天（POD3）、术后第4天（POD4）及术后第7天（POD7，依存活时间而定）进行。分别在单次训练前、每次手术前后称量大鼠体重；此外，术后评分期间每日称量一次体重。术后评分于POD1至POD3每日开展三次，于POD4至POD7每日晨间开展一次。在安乐死当日（POD1、POD3或POD7），大鼠于全身麻醉与镇痛状态下接受二次开腹（手术III），经下腔静脉采血后实施安乐死。摘取器官用于后续检测并按规范流程处理。