Development of ex situ normothermic reperfusion as an innovative method to assess pancreases after preservation

Abstract

Summary Static cold storage (SCS) is the standard method for pancreas preservation prior to transplantation; however, it does not permit organ assessment. Normothermic reperfusion (NR) is utilized clinically for other organs to assess viability. Our aim was to develop NR using normothermic machine perfusion technique to simulate reperfusion at the time of transplantation, enabling evaluation of oxygenated hypothermic machine perfusion (HMPO2) as a newer strategy to optimize pancreas preservation. 13 porcine pancreases procured after circulatory death were divided into 3 groups: 4 pancreases preserved using SCS, and 2 groups preserved by HMPO2 (n = 4 and n = 5, differing by type of preservation solution). Duration of perfusion or cold storage was 6 hours before the 1‐hour assessment using NR. Outcome measures were perfusion characteristics, biochemistry and change in tissue water mass as oedema assessment. During NR, the HMPO2 groups demonstrated better perfusion characteristics, normal macroscopic appearances, decreased water mass and one HMPO2 group demonstrated a response to glucose stimulation. Conversely, the SCS group showed an increased water mass and developed early macroscopic appearances of oedema, interstitial haemorrhage and minimal portal outflow. This study suggests that ex situ assessment of pancreases by NR is promising, and that HMPO2 may be better than SCS.

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

“…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 ). We have not included histological evaluation in this study due to findings from a previous work on slaughterhouse pig kidneys.…”

Machine Perfusion of the Pancreas: What Can We Learn from five Decades of Experimental Studies?

“…Authors often claim to use an oxygenated perfusate with however no further details on oxygenator type or size and the lack of perfusate oxygen partial pressures (Table 1). Only two recent studies present perfusate oxygen levels [41,59]. Lemkuil et al from the UK have demonstrated the perfusate oxygen-dependent ATP-reloading of the pancreas, similar as seen with other solid organs.…”

Reanimating Pancreatic Grafts Subjected to Prolonged Cold Ischemic Injury Using Normothermic Ex Vivo Perfusion

“…They reported noninferiority of the latter compared with CS in terms of survival and endocrine and exocrine graft function. Another experimental model by Ogbemudia et al 23 in 2021 compared the outcome of hypothermic oxygenated machine perfusion versus CS for 6 h by subjecting the grafts to 1 h of normothermic regional perfusion for reperfusion after ischemia. They reported better perfusion characteristics, decreased macroscopic edema, and normal macroscopic appearance compared with CS during reperfusion, suggesting a role of ex situ machine perfusion in alleviating tissue injuries associated with cold ischemia.…”