Background: Improved preservation techniques could reduce ischemia-reperfusion injuries (IRI) and allow better matching and allocation of VCA grafts across wider distances. A novel SNMP system was evaluated for ex vivo preservation of VCA. Methods: Swine vertical rectus abdominis muscle (VRAM) flaps were preserved for 14h with cold static (CS) (n=8) and SNMP at 21[deg]C using HBOC (n=8). Technical feasibility studies of ex vivo SNMP (n=8) where followed by in vivo studies in heterotopic (cervical) VRAM allotransplantation (n=8) followed for 7 days under triple immunosuppression. In addition to recipient's clinical, histopathological and serum myoglobin monitoring, inflammatory markers and metabolomic analyses were performed on perfusates/tissue pre and post-transplantation. Results: SNMP provided low pressures (50-55 mmHg), low flows (20-80 ml/min) and full oxygenation (FiO₂=60% at 400ml/min) to flaps. SNMP stabilized perfusate's pH (7.55-7.6) while keeping lactate levels under 4 mmol/L. Muscle fiber disruption and necrosis were significantly less in the SNMP group. Early contraction bands (5 hours) were followed by moderate to severe IRI in the CS flaps in vivo. Myoglobin blood levels were significantly higher in recipients of CS flaps. Inflammatory cytokine profiles showed no significant difference between the groups ex vivo. Metabolites involved in pentose (nucleic acid backbone) metabolism were significantly higher in the SNMP group: ribose (↑22 folds, p<0.001), ribonate (↑37 folds, p<0.001), and ribitol (↑10.5 folds, p<0.001). Glycolysis metabolites, increased during SNMP: glucose 6-phosphate (↑23 folds, p=0.01), fructose-6-phosphate (↑12 folds, p=0.03), and phophoenolpyruvate (↑8 folds, p=0.03). Antioxidant pathways were fully functional in the SNMP group: glutathione-cysteine disulfide (↑5.6 folds, p=0.01) and N-acetylcysteine (↑40 folds, p=0.007). CS grafts, faced extensive amino acid metabolism dysregulation: valine (p=0.005),2-methylbutyrylcarnitine (p=0.01),3-hydroxyisobutyrate (p=0.01), and ethylmalonate (p=0.009). Energy-related metabolites were significantly higher in the SNMP group: cAMP: (↑3.7 folds, p=0.02) and adenosine (↑129 fold, p=0.002). Conclusion SNMP/HBOC provides effective ex vivo oxygenation of VRAM allografts. SNMP significantly decreases IRI and post-transplant inflammation compared to CS. SNMP/HBOC may help mitigate IRI, enabling long-distance graft sharing or tandem VCA.

CITATION INFORMATION: Oksuz S, Schweizer R, Minervini M, Banan B, Gorantla V, Fontes P. Subnormothermic Machine Perfusion (SNMP) with a Novel Hemoglobin-Based Oxygen Carrier (HBOC) Solution for Ex Vivo Preservation in Vascularized Composite Allotransplantation (VCA). Am J Transplant. 2016;16 (suppl 3).

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