Comparison Between IGL-1 and HTK Preservation Solutions in Deceased Donor Liver Transplantation

Meine, M.H.; Leipnitz, Ian; Zanotelli, Maria Lúcia; Schlindwein, Eduardo; Kiss, Guillermo; Martini, Judith; Fleck, Alfeu de Medeiros; Mucenic, Marcos; Brandão, Ajácio; Marroni, Cláudio Augusto; Cantisani, Guido Pio Gracco

doi:10.1016/j.transproceed.2015.03.033

Cited by 22 publications

(21 citation statements)

References 31 publications

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“…Briefly, UW contains hydroxyethyl starch (HES) as oncotic agent, lactobionate and raffinose (for edema prevention), the antioxidants allopurinol and reduced glutathione, and high potassium and low sodium concentrations [ 12 ]. IGL-1 is identical to UW, except that HES is replaced by polyethylene glycol 35 (PEG 35) and has inverted sodium/potassium ratio, as shown in Table 1 [ 13 ]. For their part, HTK and Celsior have no oncotic agent.…”

Section: Introductionmentioning

confidence: 99%

The Relevance of the UPS in Fatty Liver Graft Preservation: A New Approach for IGL-1 and HTK Solutions

Panisello‐Roselló

Verde

Zaoualí

et al. 2017

IJMS

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The 26S proteasome is the central proteolytic machinery of the ubiquitin proteasome system (UPS), which is involved in the degradation of ubiquitinated protein substrates. Recently, UPS inhibition has been shown to be a key factor in fatty liver graft preservation during organ cold storage using University of Wisconsin solution (UW) and Institute Georges Lopez (IGL-1) solutions. However, the merits of IGL-1 and histidine-tryptophan-ketoglutarate (HTK) solutions for fatty liver preservation have not been compared. Fatty liver grafts from obese Zücker rats were preserved for 24 h at 4 °C. Aspartate aminotransferase and alanine aminotransferase (AST/ALT), glutamate dehydrogenase (GLDH), ATP, adenosine monophosphate protein kinase (AMPK), e-NOS, proteasome activity and liver polyubiquitinated proteins were determined. IGL-1 solution prevented ATP breakdown during cold-storage preservation of steatotic livers to a greater extent than HTK solution. There were concomitant increases in AMPK activation, e-NOS (endothelial NOS (NO synthase)) expression and UPS inhibition. UPS activity is closely related to the composition of the solution used to preserve the organ. IGL-1 solution provided significantly better protection against ischemia-reperfusion for cold-stored fatty liver grafts than HTK solution. The effect is exerted through the activation of the protective AMPK signaling pathway, an increase in e-NOS expression and a dysregulation of the UPS.

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Section: Introductionmentioning

confidence: 99%

The Relevance of the UPS in Fatty Liver Graft Preservation: A New Approach for IGL-1 and HTK Solutions

Panisello‐Roselló

Verde

Zaoualí

et al. 2017

IJMS

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“…Recent HTK limitations in liver transplantation have been pointed out from the European Transplantation Register [ 5 ]. In accordance with this, Meine and cols have recently reported that the use of HTK in liver transplantation trials evidenced higher ischemia-reperfusion damage during the first postoperative days than IGL-1 solution [ 11 ]. In a previous work we demonstrated the relevance of AMP-activated protein kinase (AMPK) in fatty liver preservation when IGL-1 was used and compared to HTK [ 14 ].…”

Section: Introductionmentioning

confidence: 54%

“…Several clinical trials and experimental investigations have been carried out to compare the benefits of all preservation solutions [ 5 , 9 , 10 , 11 , 12 , 13 ]; but the analysis comparing IGL-1 versus HTK are poor [ 5 , 11 ], especially when they deal with the underlying protection mechanisms responsible for the safety of fatty liver graft against cold ischemia reperfusion injury. Recent HTK limitations in liver transplantation have been pointed out from the European Transplantation Register [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Cytoprotective Mechanisms in Fatty Liver Preservation against Cold Ischemia Injury: A Comparison between IGL-1 and HTK

Panisello‐Roselló

Verde

Lopez

et al. 2018

IJMS

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Institute Goeorges Lopez 1 (IGL-1) and Histidine-Tryptophan-Ketoglutarate (HTK) preservation solutions are regularly used in clinical for liver transplantation besides University of Wisconsin (UW) solution and Celsior. Several clinical trials and experimental works have been carried out comparing all the solutions, however the comparative IGL-1 and HTK appraisals are poor; especially when they deal with the underlying protection mechanisms of the fatty liver graft during cold storage. Fatty livers from male obese Zücker rats were conserved for 24 h at 4 °C in IGL-1 or HTK preservation solutions. After organ recovery and rinsing of fatty liver grafts with Ringer Lactate solution, we measured the changes in mechanistic target of rapamycin (mTOR) signaling activation, liver autophagy markers (Beclin-1, Beclin-2, LC3B and ATG7) and apoptotic markers (caspase 3, caspase 9 and TUNEL). These determinations were correlated with the prevention of liver injury (aspartate and alanine aminostransferase (AST/ALT), histology) and mitochondrial damage (glutamate dehydrogenase (GLDH) and confocal microscopy findings). Liver grafts preserved in IGL-1 solution showed a marked reduction on p-TOR/mTOR ratio when compared to HTK. This was concomitant with significant increased cyto-protective autophagy and prevention of liver apoptosis, including inflammatory cytokines such as HMGB1. Together, our results revealed that IGL-1 preservation solution better protected fatty liver grafts against cold ischemia damage than HTK solution. IGL-1 protection was associated with a reduced liver damage, higher induced autophagy and decreased apoptosis. All these effects would contribute to limit the subsequent extension of reperfusion injury after graft revascularization in liver transplantation procedures.

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“…The gold standard preservation solutions used in liver transplantation have been the UW and HTK. Recently, the need to have new alternatives has opened the field to new solutions, such as Celsior and Institut Georges Lopez 1, but researchers do not completely agree regarding which one provides better short‐term and longterm outcomes . Although there are a significant number of research projects going on, there is still a lack of evidence supporting the development of new alternatives that will not only improve results but also will allow us to extend the required times for the engraftment.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the need to have new alternatives has opened the field to new solutions, such as Celsior and Institut Georges Lopez 1, but researchers do not completely agree regarding which one provides better short-term and longterm outcomes. (29)(30)(31)(32)(33)(34)(35) Although there are a significant number of research projects going on, there is still a lack of evidence supporting the development of new Original article | 1383 alternatives that will not only improve results but also will allow us to extend the required times for the engraftment. This possibility will clearly improve quality of life for the surgical time, result for the recipients, and availability of organs, as well as perhaps the costs.…”

Section: Discussionmentioning

confidence: 99%

The Novel N,N‐bis‐2‐Hydroxyethyl‐2‐Aminoethanesulfonic Acid–Gluconate–Polyethylene Glycol–Hypothermic Machine Perfusion Solution Improves Static Cold Storage and Reduces Ischemia/Reperfusion Injury in Rat Liver Transplant

et al. 2019

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Organ transplantation is the treatment of choice against terminal and irreversible organ failure. Optimal preservation of the graft is crucial to counteract cold ischemia effects. As we developed an N,N‐bis‐2‐hydroxyethyl‐2‐aminoethanesulfonic acid–gluconate–polyethylene glycol (BGP)–based solution (hypothermic machine perfusion [HMP]), we aimed to analyze the use of this solution on static cold storage (SCS) of rat livers for transplantation as compared with the histidine tryptophan ketoglutarate (HTK) preservation solution. Livers procured from adult male Sprague Dawley rats were preserved with BGP‐HMP or HTK solutions. Liver total water content and metabolites were measured during the SCS at 0°C for 24 hours. The function and viability of the preserved rat livers were first assessed ex vivo after rewarming (90 minutes at 37°C) and in vivo using the experimental model of reduced‐size heterotopic liver transplantation. After SCS, the water and glycogen content in both groups remained unchanged as well as the tissue glutathione concentration. In the ex vivo studies, livers preserved with the BGP‐HMP solution were hemodynamically more efficient and the O2 consumption rate was higher than in livers from the HTK group. Bile production and glycogen content after 90 minutes of normothermic reperfusion was diminished in both groups compared with the control group. Cellular integrity of the BGP‐HMP group was better, and the histological damage was reversible. In the in vivo model, HTK‐preserved livers showed a greater degree of histological injury and higher apoptosis compared with the BGP‐HMP group. In conclusion, our results suggest a better role of the BGP‐HMP solution compared with HTK in preventing ischemia/reperfusion injury in the rat liver model.

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Comparison Between IGL-1 and HTK Preservation Solutions in Deceased Donor Liver Transplantation

Cited by 22 publications

References 31 publications

The Relevance of the UPS in Fatty Liver Graft Preservation: A New Approach for IGL-1 and HTK Solutions

The Relevance of the UPS in Fatty Liver Graft Preservation: A New Approach for IGL-1 and HTK Solutions

Cytoprotective Mechanisms in Fatty Liver Preservation against Cold Ischemia Injury: A Comparison between IGL-1 and HTK

The Novel N,N‐bis‐2‐Hydroxyethyl‐2‐Aminoethanesulfonic Acid–Gluconate–Polyethylene Glycol–Hypothermic Machine Perfusion Solution Improves Static Cold Storage and Reduces Ischemia/Reperfusion Injury in Rat Liver Transplant

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