A Hyperbaric Warm Perfusion System Preserves Tissue Composites Ex vivo and Delays the Onset of Acute Rejection.

BACKGROUND: Ischemia-reperfusion injury (IRI) precipitates acute rejection of vascularized composite allografts (VCA). Hyperbaric preservation of tissues ex vivo, between harvest and revascularization, may reduce IRI and mitigate acute rejection of VCA. METHODS: A porcine heterotopic musculocutaneous gracilis flap model was used. In phase 1, control autografts (n = 5) were infused with University of Wisconsin Solution (UWS) and stored at 4°C for 3 hours. Intervention autografts (n = 5) were placed in a hyperbaric oxygen organ preservation system for 5 hours and infused with hyperoxygenated UWS at 20°C and 3 atm. Grafts were replanted into the animals' necks. In phase 2, similarly treated control (n = 8) and intervention grafts (n = 8) were allotransplanted into the necks of animals separated by a typed and standardized genetic mismatch. No systemic immunosuppression was given. Systemic markers of IRI, and clinical and histopathological assessments of necrosis and rejection were performed. RESULTS: Autotransplanted tissue composites preserved in the hyperbaric chamber showed histopathological evidence of less muscle necrosis at 3 hours (p = 0.05). Despite a longer period of ischemia, no evidence was found of a difference in systemic markers of IRI following revascularization in these groups. Allotransplanted tissues supported ex vivo within the hyperbaric perfusion device experienced acute rejection significantly later than corresponding controls. CONCLUSION: Hyperbaric warm perfusion preserves musculocutaneous tissue composites ex vivo for longer than standard cold preservation in this model. This translates into a delay in acute rejection of allotransplanted tissue composites.

Resuscitation with whole blood or blood components improves survival and lessens the pathophysiological burden of trauma and haemorrhagic shock in a pre-clinical porcine model.

PURPOSE: In military trauma, disaster medicine, and casualties injured in remote locations, times to advanced medical and surgical treatment are often prolonged, potentially reducing survival and increasing morbidity. Since resuscitation with blood/blood components improves survival over short pre-surgical times, this study aimed to evaluate the quality of resuscitation afforded by blood/blood products or crystalloid resuscitation over extended 'pre-hospital' timelines in a porcine model of militarily relevant traumatic haemorrhagic shock. METHODS: This study underwent local ethical review and was done under the authority of Animals (Scientific Procedures) Act 1986. Forty-five terminally anaesthetised pigs received a soft tissue injury to the right thigh, haemorrhage (30% blood volume and a Grade IV liver injury) and fluid resuscitation initiated 30 min later [Group 1 (no fluid); 2 (0.9% saline); 3 (1:1 packed red blood cells:plasma); 4 (fresh whole blood); or 5 (plasma)]. Fluid (3 ml/kg bolus) was administered during the resuscitation period (maximum duration 450 min) when the systolic blood pressure fell below 80 mmHg. Surviving animals were culled with an overdose of anaesthetic. RESULTS: Survival time was significantly shorter for Group 1 compared to the other groups (P < 0.05). Despite the same triggers for resuscitation when compared to blood/blood components, saline was associated with a shorter survival time (P = 0.145), greater pathophysiological burden and significantly greater resuscitation fluid volume (P < 0.0001). CONCLUSION: When times to advanced medical care are prolonged, resuscitation with blood/blood components is recommended over saline due to the superior quality and stability of resuscitation achieved, which are likely to lead to improved patient outcomes.