Abdominal multiorgan procurement from slaughterhouse pigs: a bespoke model in organ donation after circulatory death for ex vivo organ perfusion compliant with the 3 Rs (Reduction, Replacement & Refinement)

Abstract

Background: Advances in organ preservation, reconditioning and assessment have been driven by the increasing necessity to utilise organs from extended criteria donors, particularly donors after circulatory death. Research efforts in this area have aided translation of machine perfusion technology into clinical practice. Pigs are anatomically and physiologically similar to humans and are an excellent model. However, conducting large animal experimental research is challenging and typically limited by ethical and economic constraints. Here we describe a reproducible, cost-effective multi-organ abdominal procurement model of porcine organs from the slaughterhouse. Methods: Domestic pigs are electrically stunned and exsanguinated following the standard abattoir process. Via a longitudinal midline incision, the thoracoabdominal viscera are removed en bloc by incising along the anterior vertebral plane. The abdominal organs are isolated, perfused and separated preserving their respective vasculature, allowing individual organ use for specific experiments. Results:The warm ischaemic time is kept between 15-30 minutes. Using this highly protocolized procurement technique we have procured 12 livers, 162 kidneys and 12 pancreata for research, the majority of which have been utilized for ex situ perfusion experiments. Conclusions:We have described a reliable and reproducible procedure for abdominal multi-organ procurement from slaughterhouse pigs.

Kidney Normothermic Machine Perfusion Can Be Used as a Preservation Technique and a Model of Reperfusion to Deliver Novel Therapies and Assess Inflammation and Immune Activation

“…We acknowledge that the use of a slaughterhouse model presents more variability in comparison to an animal house model, where the environment is more controlled. However, we have refined this method of retrieval over a number of years and previously described the strengths and limitations ( 50 ). We have shown acceptable reproducibility in preclinical dose–response studies where kidneys underwent normothermic perfusion as a basis for a clinical trial ( 17 ) and have also demonstrated that this method of multiple organ procurement is adequate for comparing different preservation methods in pig pancreases ( 51 ).…”

From waste to wealth: Repurposing slaughterhouse waste for xenotransplantation

“…This method is advantageous because it reduces cold ischemia times, provides an opportunity for quality assessment, and decreases organ degradation (Tembo and Nonga, 2015). The development of ex vivo organ perfusion systems has been extensively researched using multiorgan procurement techniques, which can maintain organ viability comparable to levels observed in organs donated from circulatory death models (Dengu et al, 2022). Slaughterhouse porcine organs, in particular, have been used in several ex vivo perfusion investigations.…”

Development of a Novel Ex Vivo Porcine Hepatic Segmental Perfusion Proof-of-Concept Model Towards More Ethical Translational Research

“…Ex vivo perfusion of porcine organs has proved to be a valuable tool in translational research due to the remarkable similarities between human and porcine anatomy and physiology. These porcine organ perfusion models have been employed for the study of organ transplantation and the development of ex vivo perfusion technology but have also been used widely to study invasive diseases [ 1 ]. Wanford et al used ex vivo perfusion models of porcine liver and spleen to demonstrate intracellular replication of Klebsiella pneumoniae in tissue macrophages, highlighting the pathophysiology of hepatic abscess formation and the importance of optimising antimicrobial treatment strategies [ 2 ].…”