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

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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.