Ex-vivo Hyperbaric Normothermic Perfusion for 24 Hours Mitigates Reperfusion Injury in Porcine Vascular Composite Allotransplantation (VCA)

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Abstract

Background

Modern body armor, rapid evacuation, and advanced combat casualty care have improved survival after catastrophic extremity and maxillofacial trauma. Vascularized composite allotransplantation (VCA) is a superior restorative option compared to traditional reconstruction in these complex injuries. To mitigate obligate reperfusion injury in VCA, we evaluate the efficacy of a novel normothermic hyperbaric ex-vivo preservation strategy using oxygenated University of Wisconsin (UW) perfusate in a porcine VCA model.

Methods

Porcine myocutaneous heterotopic autotransplants were performed in the anterior cervical neck of Yorkshire swine. Group 1 (control, n=8) flaps underwent cold static preservation (CSP) with UW at 4°C for 5 hours prior to transplant. Group 2 (experimental, n=8) flaps were perfused with hyper-oxygenated Kidney Preservation solution (KPS) for 24 hours at 37°C in a hyperbaric chamber at 3 atm before heterotopic autotransplantation. Flaps were monitored daily for clinical evidence of viability and biopsied per protocol with an end point of 21-days. Histologic analysis was blinded and reviewed by an expert veterinarian pathologist.

Results

Heterotopic autotransplanted tissue remained clinically viable at the 21-day end point. Histological evaluation revealed extensive diffuse necrosis in all controls (at 5 hours, CSP). The experimental flaps placed on hyperbaric ex-vivo perfusion support have preliminarily showed decreased histologic evidence of ischemic injury and necrosis ranging from rare to moderate per the Banff classification system.

Conclusion

Normothermic hyperbaric perfusion appears to dramatically extend the viability of composite tissue in the ex-vivo phase. Injuries secondary to ischemia and cold preservation are mitigated. This technology has the potential to extend the window of time between procurement and transplantation in the growing field of reconstructive transplantation as well as solid organ transplantation. Such innovations would dramatically expand the donor pool and provide superior matches for transplantation candidates.

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