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

大鼠和猪肾缺血再灌注损伤、肝切除和移植动物模型的严重程度评估和完善

• 批准号: 329784982
• 负责人: Professor Dr. René H. Tolba
• 金额: --
• 依托单位: Institut für Versuchstierkunde sowie Zentrallaboratorium für Versuchstiere
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/329784982?language=en
• 关键词: Severity; assessment; refinement; animal; models

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.

需要剖腹手术的手术模型通常用于生物医学研究领域，根据欧盟指令2010/63第15条，在这些模型中进行的手术被定义为中度。然而，在不同的模型中，疼痛、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道德问题。本研究的目的是评估第一期资助期研究结果的稳健性（可转移性和可推广性），这些研究结果与外科手术有关，使用经典模型进行大鼠和猪的非肾切除伴缺血再灌注损伤、肝切除和肝移植。另一个目的是评估野外试验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型和物种。此外，我们打算进行细化并确定不同的镇痛方案是否会影响先前研究结果的稳健性。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，以及评分系统和行为数据的观察数据，以便将其与第一个资助期的结果进行比较。根据这些结果和合作工作组的发现，我们将通过遥测以及家庭笼监测、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，我们将比较不同的镇痛剂和常用的镇痛药物，并为外科手术中镇痛的使用提供建议，以完善立法层面。在第一个资助期内，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所经历的疼痛、痛苦和痛苦的程度。我们假设，当转移到其他外科手术和物种时，开放场测试参数和fcm是稳健的标记。此外，我们期望优化镇痛方案有助于降低体重减轻程度和fcm浓度。