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Open AccessArticle

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

1
General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20019 Milan, Italy
2
Department of Pathophysiology and Transplantation, Università degli Studi of Milan, 20019 Milan, Italy
3
Department of Anesthesia and Critical Care, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20019 Milan, Italy
4
Center for Preclinical Research, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20019 Milan, Italy
5
Pathology Department, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20019 Milan, Italy
6
Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20019 Milan, Italy
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(11), 1918; https://doi.org/10.3390/jcm8111918
Received: 29 September 2019 / Revised: 3 November 2019 / Accepted: 5 November 2019 / Published: 8 November 2019
(This article belongs to the Special Issue Cutting Edge Preclinical Models in Translational Medicine)
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 (DO2), the aim of this study was to investigate the effectiveness and safety of different DO2, 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 DO2 (p = 0.008) and oxygen consumption ( V O ˙ 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). V O ˙ 2 and DO2 were highly correlated (p < 0.001). Consistently, the main metabolic parameters were directly correlated with DO2 and V O ˙ 2. No human RBC related damage was detected. In conclusion, an optimized DO2 significantly reduces hypoxic damage-related effects occurring during NMP. Human RBCs can be safely used as oxygen carriers. View Full-Text
Keywords: normothermic machine perfusion; rat; human red blood cells; oxygen consumption; oxygen delivery normothermic machine perfusion; rat; human red blood cells; oxygen consumption; oxygen delivery
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Dondossola, D.; Santini, A.; Lonati, C.; Zanella, A.; Merighi, R.; Vivona, L.; Battistin, M.; Galli, A.; Biancolilli, O.; Maggioni, M.; Villa, S.; Gatti, S. Human Red Blood Cells as Oxygen Carriers to Improve Ex-Situ Liver Perfusion in a Rat Model. J. Clin. Med. 2019, 8, 1918.

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