Human Red Blood Cells as Oxygen Carriers to Improve Ex-Situ Liver Perfusion in a Rat Model

Ex-situ machine perfusion (MP) has been increasingly used to enhance liver quality in different settings. Small animal models can help to implement this procedure. As most normothermic MP (NMP) models employ sub-physiological levels of oxygen delivery (DO(2)), the aim of this study was to investigate the effectiveness and safety of different DO(2), using human red blood cells (RBCs) as oxygen carriers on metabolic recovery in a rat model of NMP. Four experimental groups (n = 5 each) consisted of (1) native (untreated/control), (2) liver static cold storage (SCS) 30 min without NMP, (3) SCS followed by 120 min of NMP with Dulbecco-Modified-Eagle-Medium as perfusate (DMEM), and (4) similar to group 3, but perfusion fluid was added with human RBCs (hematocrit 15%) (BLOOD). Compared to DMEM, the BLOOD group showed increased liver DO(2) (p = 0.008) and oxygen consumption ([Formula: see text] (2)) (p < 0.001); lactate clearance (p < 0.001), potassium (p < 0.001), and glucose (p = 0.029) uptake were enhanced. ATP levels were likewise higher in BLOOD relative to DMEM (p = 0.031). [Formula: see text] (2) and DO(2) were highly correlated (p < 0.001). Consistently, the main metabolic parameters were directly correlated with DO(2) and [Formula: see text] (2). No human RBC related damage was detected. In conclusion, an optimized DO(2) significantly reduces hypoxic damage-related effects occurring during NMP. Human RBCs can be safely used as oxygen carriers.