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Royal Society of Medicine, Colt Foundation Research & Clinical Innovation Meeting 2022
2 Developing a militarily relevant ex-vivo model of traumatic injury and haemorrhagic shock
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  1. Laura Cottey1,2,
  2. Alex Stoll2,
  3. John P Stone3,
  4. Timothy R Entwistle3,
  5. Kavit Amin3,
  6. Jak Kerr3,
  7. William R Cowey3,
  8. Bowers Corban JT3,
  9. Jason E Smith1,4,
  10. Sarah Watts2 and
  11. James E Fildes5
  1. 1Academic Department of Military Emergency Medicine, Royal Centre for Defence Medicine, Birmingham, UK
  2. 2CBR Division, Dstl Porton Down, Salisbury, UK
  3. 3The Ex-Vivo Research Centre, 3F66Building3, Alderley Park, Nether Alderley, Macclesfield, UK
  4. 4University Hospitals Plymouth NHS Trust, Plymouth, UK
  5. 5School of Chemical Engineering, College of Engineering and Physical Sciences, University of Birmingham, UK

Abstract

Background Traumatic injury is a leading cause of death worldwide. There is a crucial need to develop therapies that improve critically injured patient outcomes. Current trauma research models are ethically and financially challenging, with poor translation. However, traumatic injury and haemorrhagic shock can be modelled using ex-vivo normothermic perfusion (EVNP), a methodology adapted from transplantation. The aim of this study was to develop a 24hr EVNP duel porcine limb and kidney model.

Method Eight porcine forelimbs, bilateral kidneys and blood were retrieved via standard protocols. Following <4hrs cold storage, the kidneys were connected to a bespoke Ex-Vivo Research Centre circuit via the renal artery, and a mean arterial pressure (MAP) of 80mmHg was maintained. The perfusate consisted of leukocyte-deplete blood and Ringer’s solution. Once the kidney was haemodynamically stable, the limb was connected via the brachial and radial collateral arteries. Haemodynamic parameters were continuously monitored, biochemical perfusate assessment performed hourly and histopathology baseline and end timepoints samples taken.

Results Perfusion was maintained for 24hrs in all limbs, with blood flows of 345.03mls/min (±54.78 SD) and MAP of 77.57mmHg (±3.82 SD). Three kidneys achieved 24hr perfusion, with flows of 214.53mls/min (±41.6 SD) and MAP of 80.58mmHg (±0.51 SD). Biochemical analysis showed a statistically significant potassium elevation at 24hrs compared to baseline, p=0.0078. A further three kidneys were disconnected from the circuit at 7, 11 and 12hrs, and two kidneys showed decline in flow >15 hrs due to declining haemodynamics. Compared to baseline, evidence of cell death was observed in 24hr muscle samples. In the end-point kidney samples, tubular degeneration, protein loss and necrosis extended along the nephron.

Conclusions Limb EVNP can be successfully achieved for 24hrs, but further protocol improvements are required to sustain renal perfusion for 24hrs alongside adjustments to reduce the ischaemic insult and cell death.

https://doi.org/10.1136/bmjmilitary-2023-RSMabstracts.2

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