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Review
. 2020 Dec 28;22(1):235.
doi: 10.3390/ijms22010235.

Oxygen Transport during Ex Situ Machine Perfusion of Donor Livers Using Red Blood Cells or Artificial Oxygen Carriers

Silke B Bodewes  1   2 , Otto B van Leeuwen  1   3 , Adam M Thorne  1   3 , Bianca Lascaris  1   3 , Rinse Ubbink  3 , Ton Lisman  2 , Diethard Monbaliu  4   5 , Vincent E De Meijer  1 , Maarten W N Nijsten  6 , Robert J Porte  1
Affiliations
Review

Oxygen Transport during Ex Situ Machine Perfusion of Donor Livers Using Red Blood Cells or Artificial Oxygen Carriers

Silke B Bodewes et al. Int J Mol Sci. .

Abstract

Oxygenated ex situ machine perfusion of donor livers is an alternative for static cold preservation that can be performed at temperatures from 0 °C to 37 °C. Organ metabolism depends on oxygen to produce adenosine triphosphate and temperatures below 37 °C reduce the metabolic rate and oxygen requirements. The transport and delivery of oxygen in machine perfusion are key determinants in preserving organ viability and cellular function. Oxygen delivery is more challenging than carbon dioxide removal, and oxygenation of the perfusion fluid is temperature dependent. The maximal oxygen content of water-based solutions is inversely related to the temperature, while cellular oxygen demand correlates positively with temperature. Machine perfusion above 20 °C will therefore require an oxygen carrier to enable sufficient oxygen delivery to the liver. Human red blood cells are the most physiological oxygen carriers. Alternative artificial oxygen transporters are hemoglobin-based oxygen carriers, perfluorocarbons, and an extracellular oxygen carrier derived from a marine invertebrate. We describe the principles of oxygen transport, delivery, and consumption in machine perfusion for donor livers using different oxygen carrier-based perfusion solutions and we discuss the properties, advantages, and disadvantages of these carriers and their use.

Keywords: artificial oxygen carriers; carbon dioxide; gas transport; liver; machine perfusion; oxygen; temperature.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Graphical presentation of the relation between partial oxygen (PO2) pressure and the O2 content of different solutions. Note how poorly O2 dissolves in water (blue curve). To achieve a useful O2 content without an oxygen carrier, a saturation of 100% O2 is required, i.e., a partial pressure of 760 mm Hg. Perfluorocarbons (PFC; yellow curve) can dissolve 20 times more O2. The red blood cell (RBC) and hemoglobin-based oxygen carrier-201 (HBOC-201) curves assume a concentration equivalent with 7.76 mmol/L of O2 binding places [30]. Additionally, note that the only small apparent shifts in the dissociation curves result from the supraphysiological PO2 of 760 mmHg.
Figure 2
Figure 2
Graphical presentation of the relation between perfusion temperature and oxygen (O2) consumption (green curve) and O2 delivery. Metabolic rate and O2 consumption rise with approximately 10% for each increase in temperature measured in degrees Celsius. Note that the amount of O2 that is dissolved in water (blue curve) decreases at higher temperatures. At body temperature, O2 consumption/requirement will be larger than the amount that can be delivered by dissolved O2 alone, as indicated by the crossing green and blue curves. The addition of an oxygen carrier such as red blood cells (RBC) or hemoglobin-based oxygen carrier 201 (HBOC-201; red curve) can dramatically increase O2 content and delivery. Note that, as in whole body physiology, during organ perfusion oxygen delivery must be considerably higher than oxygen consumption, because oxygen consuming tissues such as the liver [31] can only extract a fraction of the delivered oxygen. The numbers displayed here assume oxygenation with 100% oxygen, a hemoglobin or HBOC-201 concentration equivalent to 7.76 mmol/L of O2-binding sites and a perfusion flow of 2300 mL/min.
Figure 3
Figure 3
Visualizing the large differences in size between various oxygen carriers: red blood cells (RBC), hemoglobin vesicles (Hb-Vs), hemoglobin-based oxygen carrier 201 (HBOC-201), human hemoglobin (Hb).
See this image and copyright information in PMC

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