HOPE (hypothermic oxygenated perfusion) strategies in the era of dynamic liver graft preservation

Panisello‐Roselló, Arnau; Roselló‐Catafau, Joan

doi:10.1016/j.ebiom.2020.103071

Cited by 5 publications

(16 citation statements)

References 10 publications

(21 reference statements)

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“…It is an established fact that any preservation solution must contain antioxidants to counteract ox-idative stress during IR. Considering this, the IGL-2 benefits reported here for hypothermic static preservation are consistent with its suitability to be used in HOPE over the currently used perfusates (Belzer-MPS or its generics) [19,20]. Both reasons constitute a solid basis for simplifying the logistics and avoiding mixing different solutions when both static and HOPE need to be combined.…”

Section: Discussionsupporting

confidence: 81%

“…PEG35 solutions (IGL-2 and IGL-1) are related to reduced AST/ALT and especially to GLDH, showing better mitochondrial protection, as previously described [ 14 , 19 , 20 ]. PEG35 improved mitochondrial machinery and ALDH2 functionality, reducing graft cold ischemic injury [ 23 , 24 ].…”

Section: Discussionsupporting

confidence: 67%

“…Considering the relevance of PEG35 concentration according to the previously known results, we expanded our study to one additional group using IGL-2 solution [19,20]. We focused mainly on parameters relevant to the mitochondria (such as ALDH2) that regulate other cytoprotective responses.…”

Section: Resultsmentioning

confidence: 99%

“…This includes the generation of nitric oxide (NO) whose vasodilation properties counterbalance the microcirculation disturbances in fatty liver grafts, favoring graft preservation and revascularization [15][16][17][18]. Keeping in mind the beneficial PEG35 properties, we recently proposed the use of IGL-2 solution (containing PEG35) as a suitable perfusate for dynamic hypothermic oxygenated strategies (HOPE) with promising results [19,20]. This might improve the only perfusate for machine perfusion currently available, Belzer-MPS and generics, containing HES [21], given that the use of a unique solution, such as IGL-2, for static preservation and machine perfusion (MP) would facilitate logistics and avoid the mixture of different solutions [19][20][21] when both techniques are combined.…”

Section: Introductionmentioning

confidence: 99%

“…Keeping in mind the beneficial PEG35 properties, we recently proposed the use of IGL-2 solution (containing PEG35) as a suitable perfusate for dynamic hypothermic oxygenated strategies (HOPE) with promising results [19,20]. This might improve the only perfusate for machine perfusion currently available, Belzer-MPS and generics, containing HES [21], given that the use of a unique solution, such as IGL-2, for static preservation and machine perfusion (MP) would facilitate logistics and avoid the mixture of different solutions [19][20][21] when both techniques are combined. This is the criterion by which we evaluated the IGL-2 benefits in static hypothermic preservation in the present study.…”

Section: Introductionmentioning

confidence: 99%

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Role of PEG35, Mitochondrial ALDH2, and Glutathione in Cold Fatty Liver Graft Preservation: An IGL-2 Approach

Bardallo

Silva

Carbonell

et al. 2021

IJMS

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The total damage inflicted on the liver before transplantation is associated with several surgical manipulations, such as organ recovery, washout of the graft, cold conservation in organ preservation solutions (UW, Celsior, HTK, IGL-1), and rinsing of the organ before implantation. Polyethylene glycol 35 (PEG35) is the oncotic agent present in the IGL-1 solution, which is an alternative to UW and Celsior solutions in liver clinical transplantation. In a model of cold preservation in rats (4 °C; 24 h), we evaluated the effects induced by PEG35 on detoxifying enzymes and nitric oxide, comparing IGL-1 to IGL-0 (which is the same as IGL-1 without PEG). The benefits were also assessed in a new IGL-2 solution characterized by increased concentrations of PEG35 (from 1 g/L to 5 g/L) and glutathione (from 3 mmol/L to 9 mmol/L) compared to IGL-1. We demonstrated that PEG35 promoted the mitochondrial enzyme ALDH2, and in combination with glutathione, prevented the formation of toxic aldehyde adducts (measured as 4-hydroxynonenal) and oxidized proteins (AOPP). In addition, PEG35 promoted the vasodilator factor nitric oxide, which may improve the microcirculatory disturbances in steatotic grafts during preservation and revascularization. All of these results lead to a reduction in damage inflicted on the fatty liver graft during the cold storage preservation. In this communication, we report on the benefits of IGL-2 in hypothermic static preservation, which has already been proved to confer benefits in hypothermic oxygenated dynamic preservation. Hence, the data reported here reinforce the fact that IGL-2 is a suitable alternative to be used as a unique solution/perfusate when hypothermic static and preservation strategies are used, either separately or combined, easing the logistics and avoiding the mixture of different solutions/perfusates, especially when fatty liver grafts are used. Further research regarding new therapeutic and pharmacological insights is needed to explore the underlying mitochondrial mechanisms exerted by PEG35 in static and dynamic graft preservation strategies for clinical liver transplantation purposes.

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Section: Discussionsupporting

confidence: 81%