Severity assessment and refinement in animal models of kidney ischemia–reperfusion injury, liver-resection, and transplantation in rats and pigs

需要剖腹手术的手术模式通常用于生物医学研究领域，根据欧盟指令2010/63第15条，在其中进行的手术被定义为中等手术。然而，在不同的模式下，痛苦、痛苦和痛苦的程度有相当大的差异，这引起了公众的关注和伦理问题。本研究的目的是在大鼠和猪的单肾切除合并缺血再灌注损伤、肝切除和肝移植的经典模型上，评估第一个资助期的外科手术结果的稳健性(可转移性和普适性)。另一个目的是评估开放式测试中的行为参数以及生化参数，例如粪便皮质酮代谢物(FCM)是否适合不同手术模式和物种。此外，我们打算进行改进，确定不同的止痛方案是否会影响先前发现的稳健性。除了临床观察外，我们计划结合炎症和应激标志物获得客观的生理数据，以及来自评分系统和行为数据的观察数据，以便将它们与第一个资助期的结果进行比较。由于这些结果和合作工作组的发现，我们将通过遥测和家庭笼子监测、PET-CT和近红外(NIR)热像仪测量每个动物模型的心率、体温和运动活动。此外，我们将比较不同的止痛药和常用的止痛药，并就外科手术中止痛药的使用提出建议，以求在立法层面上加以完善。正如在第一个资助期内建立的那样，我们将使用遥测数据和评分系统(Morton DB 1985)以及行为测试结果来量化动物在实验过程中经历的疼痛、痛苦和痛苦的程度。我们假设，当转移到其他外科手术程序和物种时，开放领域测试参数和FCM是可靠的标记。此外，我们预计，优化的止痛方案将有助于降低体重减轻的程度和FCMS的浓度。

Surgical models that require laparotomy are commonly used in the field of biomedical research and procedures performed in them are defined as moderate according to Article 15 of the EU-Directive 2010/63. However, there is considerable variability with respect to the degree of pain, distress and suffering in different models, which raises public concerns and ethical questions. The aim of the present study is to assess the robustness (transferability and generalizability) of first funding period’s findings pertaining to surgical procedures using classic models of uninephrectomy with ischemia–reperfusion injury, liver resection and liver transplantation in both rats and pigs. Another aim is to evaluate whether behavioural parameters in the open-field test as well as biochemical parameters, e.g. faecal corticosterone metabolites (FCMs) are suitable markers for different surgical models and species. Furthermore, we intend to apply refinement and determine whether different analgesia regimens influence the robustness of the previous findings.In addition to clinical observations, we plan to obtain objective physiological data in combination with inflammatory and stress markers, as well as observational data from scoring systems and behavioural data in order to compare them with the findings of the first funding period. Due to those results and the findings of the collaborating working groups, we will measure for each animal model, heart rate, body temperature, and locomotor activity via telemetry as well as home-cage monitoring, PET-CT and near-infrared (NIR) thermography. Additionally, we will compare different analgesic agents with commonly used analgesic drugs and provide recommendations for the use of analgesia in surgical procedures for refinement also on legislative level. As established within the first funding period, we will use the telemetric data in conjunction with scoring systems (Morton DB 1985) as well as behavioural test results to quantify the degree of pain, distress, and suffering experienced by the animals during experimental procedures. We hypothesize that open-field test parameters and FCMs are robust markers when transferred to other surgical procedures and species. In addition, we expect that optimization of analgesia regimens will help reduce the extent of body weight loss and the concentration of FCMs.