PSRC 69th Annual Meeting 2024

SUBNORMOTHERMIC MACHINE PERFUSION IN THE NON-HUMAN PRIMATE FOREARM MODEL:

A PRELIMINARY STUDY

H. Oubari, L. Van Dieren, Y. Berkane, JP. Giot, M. Randolph, C.L Cetrulo Jr, K. Uygun, A.G Lellouch.

• The gold standard for preserving vascularized composite allotransplants (VCA) is 4°C Static Cold Storage (SCS).

• Subnormothermic machine perfusion (SNMP) is a promising alternative to SCS.

• SNMP studies are limited to small animal and swine models.

• There is a need for a physiological and preclinical large animal model.

• We describe SNMP for 24hours in the non-human primate forearm model.

• Forearms: n=12, Cynomolgus Monkeys.

• 2 groups: 6 limbs preserved in the standard group 1 for 24hrs VS 6 limbs preserved in the optimized group 2.

• Monitoring: every hour (6 h) , then every 3 hours (18 h).

• Measurements (inflow and outflows): Flow, pressure, weight, temperature, [K], [Ca], [Na], [Cl], [Lactate], [HCO3], [glucose], P02, PCO2, pH.

• Assessments: neurostimulation, contrast X-rays, histology.

A - Brachial artery (a), brachial veins (b), cephalic vein (c), median (d), radial (e) and ulnar (f) nerves.

B - SNMP Set Up. Perfusate reservoir (1), pump (2), oxygenator (3), carbogen mixture (4), bubble trap (5), pressure sensor (6), 3D-printed scale (7), Rapidpoint500® system (8), microcontroller (9), FlirOne® smartphone-based thermal camera (10).

C - Main perfusate compounds and concentrations in both Steen and Steen+ solutions.

D - In group 1, the pressure is aimed to be the stable parameter (red) and 1,5 liters of recirculating Steen solutions are used for the entire experiment.

E - In group 2, the flow rate is kept stable (red), and 1 liter of fresh Steen+ solution is recirculated for 12 hours.

Perfusion and metabolic parameters demonstrating the onset of a compartment syndrome at mid-perfusion in group 1 (red) and an optimal preservation in group 2 (black).

Representative histology of group 2 after 24 hours of SNMP. Proximal artery (*) and vein (°) sections stained with H&E (A) and Tunel (B) demonstrating structural integrity and absence of apoptotic cells. Electron microscopy shows well preserved capillaries (C).

Representative histology of group 2. skin (H&E) X20 before (A) and after (B) perfusion; skin (Tunel) X20 before ( C) and after (D)perfusion; muscle (H&E) 10 before (E) and after (F) perfusion; muscle (Tunel) X10 before ( G) and after (H)perfusion. The only difference noticed is the appearance of limited interstitial edema after 24 hours of SNMP.

•Group 1: The onset of compartment syndrome helped understand the physiology of this experimental model.

•Group 2: stable perfusion was achieved, approaching physiological equilibrium, with no apparent structural damage to the limb. The optimized 24 hours preservation. protocol helped recover muscle contractility after 3 hours of warm ischemia.

•Clinical relevance of the model for VCA from donors in cardiac arrest and major limb replantation.

Support by the DoD through the U.S. Army Medical Research Acquisition Activity (W81XWH-17-1-0440 and W81XWH2210957) is gratefully acknowledged This study also was supported by the following institutional funding and grants: Fondation des Gueules Cassées, France; Agence Régionale de Santé, bourse années recherche, France; Société Française de Chirurgie Plastique Reconstructrice et esthtétique, Prix Zagamé. Shriners Hospital for Children, Boston.

PSRC 69th Annual Meeting 2024

Sub Normothermic Machine Perfusion (snmp) Preservation In The Non-human Primate Forearm Model: A Preliminary Study

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