Refinement of Surgical Procedure and Husbandry Practices of Bile Duct Ligation in Mice Model of Cholestatic Disease
DOI:
https://doi.org/10.48165/jlas.2022.5.1.4Keywords:
essential components, replacementAbstract
Refinement of procedure plays a pivotal role on improving the well-being of laboratory animals that enables successful outcomes of experiments by obtaining reliable data. In general, identical practices reduce variability among mice and there may be several factors that can confound results which becomes inevitable within the context of long-term experiments. We explored several refinements pertaining to surgical techniques and husbandry practices of ongoing studies with the objectives of reducing early mortality during post-operative period (72h) and ensuring animal welfare as higher priority by providing better alternative husbandry practices until the termination of experiments. The entire refinement process was systematically implemented in mice where surgical intervention of bile duct ligation (BDL) was carried out and allowed to develop liver fibrosis as part of therapeutic requirement then treated with new chemical entities (NCE’s) along with standard of care (SOC) upto 14 days. Survival surgery involving large number of mice in different groups was approved by the ethical committee. The notable refinements implemented such as suture patterns along with tissue adhesive to prevent wound dehiscence; replacement of corncob by adopting paper based bedding with nesting pads as enrichments; provision of Individually Ventilated Cages (IVC) with top inlet air supply for uniform flow in order to minimize hypothermia. Other contributing factors which included the use of improved surgical platform with thermo-controlled integral monitoring systems; Provision of infra-red light source immediately after surgery and until recovery; use of food supplement (Diet Gel) along with regular rodent diet; clinical scoring of mice during post-operative care and its management. However, there was no interference on fibrotic disease progression as well as experimental results because these refinements were implemented in a coordinated manner as part of ongoing process. Collectively, refinements of surgical as well as husbandry practices have improved the likelihood of mice and reduced incidences of mortality from 35% to 4% of four subsequent studies conducted at different intervals in mice.
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