Organ Preservation into the 2020s: The Era of Dynamic Intervention

Abstract

Organ preservation has been of major importance ever since transplantation developed into a global clinical activity. The relatively simple procedures were developed on a basic comprehension of low-temperature biology as related to organs outside the body. In the past decade, there has been a significant increase in knowledge of the sequelae of effects in preserved organs, and how dynamic intervention by perfusion can be used to mitigate injury and improve the quality of the donated organs. The present review focuses on (1) new information about the cell and molecular events impacting on ischemia/reperfusion injury during organ preservation, (2) strategies which use varied compositions and additives in organ preservation solutions to deal with these, (3) clear definitions of the developing protocols for dynamic organ perfusion preservation, (4) information on how the choice of perfusion solutions can impact on desired attributes of dynamic organ perfusion, and (5) summary and future horizons.

Keywords: Organ preservation; Organ preservation solutions; Transplantation.

Fig. 1

In a physiological state, the healthy GCX maintains normal vascular permeability, response to shear stress, and NO production. Early events in IRI include activation of Kupffer cells and ROS and cytokine production which cause direct or indirect damage to the endothelial GCX in the hepatic sinusoid. This results in increased platelet and leukocyte adhesion as well as a loss of vascular permeability leading to tissue edema. The GCX degradation products act as DAMPs, further exacerbating the inflammatory response with the release of cytokines and recruitment of inflammatory cells (neutrophils, macrophages, CD4+, and natural killer T cells) to the liver after reperfusion. The combined effects of tissue edema, microvascular congestion from platelet and leukocyte aggregation, and direct effect of inflammatory cells lead to liver sinusoidal and hepatocyte cell death. DAMPs, damage-associated molecular patterns; GCX, glycocalyx; IRI, ischemia/reperfusion injury; NO, nitric oxide; ROS, reactive oxygen species.

Fig. 2

Effect of PEG and HES concentration on BG-basic solution COP. Higher concentrations of PEG result in a major COP than the one observed for the same HES concentration. Data were fitted by an exponential equation. COP, colloid osmotic pressure; HES, hydroxyethyl starch; PEG, polyethylene glycol.

Fig. 3

Effect of temperature on oxygen-carrying capacity of BGP-HMP and HTK solutions with respect to water. Oxygen solubility in fresh water and BGP-HMP solution (A) or HTK solution (B). Oxygen solubility values in pure water were taken from the literature and a barometric pressure of 754.4 mm Hg was employed for calculations. Oxygen concentration was calculated as follows: Ln [O₂] = –ΔH / RT + C', [O₂] being the oxygen concentration at a given temperature, T the thermodynamic temperature, R the gas constant (8.314 J/K×mol), ΔH the heat of solution in kJ/mol, and C' a constant. An extrapolation was used for calculating the oxygen concentration at different temperatures, as in the following example: the HTK oxygen solubility at 5°C and 760 mm Hg of barometric pressure was 370 µM O₂, which, as expected, is lower than the oxygen solubility in fresh water in the same conditions (397 µM O₂). Values are presented as the mean ± standard deviation of five measurements. HMP, hypothermic machine perfusion; HTK, histidine-tryptophan-ketoglutarate.

Fig. 4

Effect of temperature on the viscosity of preservation solutions. A Viscosity of BG-basic solution at different PEG concentrations. B Viscosity of BG-basic solution at different HES concentrations. C Effect of temperature on the viscosity of preservation solutions with respect to fresh water. Viaspan® (UW solution), HTK (Bretschneider solution), BGP-HMP (BES-gluconate-PEG for HMP solution), BGP-35 (Bes-gluconate-PEG [40 g/L] for liver microorgan cold storage solution [161]). All data obtained were fitted by an exponential equation showing a good regression coefficient (equations are displayed in the graph). The curves clearly show the increase in viscosity due to the reduction of temperature in all studied solutions. HES, hydroxyethyl starch; HMP, hypothermic machine perfusion; HTK, histidine-tryptophan-ketoglutarate; PEG, polyethylene glycol; UW, University of Wisconsin.