Endothelial Dysfunction in Steatotic Human Donor Livers: A Pilot Study of the Underlying Mechanism During Subnormothermic Machine Perfusion

Beijert, Irene; Mert, Safak; Huang, Viola; Karimian, Negin; Geerts, Sharon; Hafiz, Ehab; Markmann, James F.; Yeh, Heidi; Porte, Robert J.; Uygun, Korkut

doi:10.1097/txd.0000000000000779

Cited by 12 publications

(7 citation statements)

References 50 publications

(58 reference statements)

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“…Thus, the integrity of the glycocalyx after SCS could be of utmost importance for the vascularization of the grafts. This could be even more true for the sensitive steatotic livers as demonstrated on steatotic grafts subjected to subnormothermic machine perfusion which had a perturbed microcirculatory state in case of glycocalyx dysfunction [ 26 ]. Moreover, the glycocalyx is known to be involved in the production of NO by the endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Glycocalyx Preservation and NO Production in Fatty Livers—The Protective Role of High Molecular Polyethylene Glycol in Cold Ischemia Injury

Lopez

Panisello‐Roselló

Benítez

et al. 2018

IJMS

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Improving the protection of marginal liver grafts during static cold storage is a major hurdle to increase the donor pool of organs. The endothelium glycocalyx quality of preservation influences future inflammatory and oxidative responses. One cellular pathway responsible for the formation of nitric oxide by endothelial cells is dependent on the stimulation of proteoglycans present in the glycocalyx. We investigated the impact of the glycocalyx preservation in static cold storage of fatty liver preserved in different preservation solutions on the endothelium-mediated production of NO. Zucker fatty rat livers were preserved 24 h in static cold storage in either Institut Georges Lopez-1 (IGL-1) (n = 10), IGL-0 (i.e., without PEG35) (n = 5) or Histidine-Tryptophan-Ketoglutarate (HTK) (n = 10) preservation solutions before being processed for analysis. For Sham group (n = 5), the fatty livers were immediately analyzed after procurement. The level of transaminases and nitrites/nitrates were measured in the washing perfusate. Glycocalyx proteins expressions, Syndecan-1, glypican-1 and heparan sulfate (HS), were determined in the tissue (ELISA). Steatotic livers preserved 24 h in IGL-1 preservation solution have a significant lower level of transaminases (aspartate aminotransferase (AST), alanine aminotransferase (ALT)) and less histological damages than steatotic livers preserved 24 h with HTK (p = 0.0152). The syndecan-1 is significantly better preserved in IGL-1 group compared to HTK (p < 0.0001) and we observed the same tendency compared to IGL-0. No significant differences were observed with glypican-1. HS expression in HTK group was significantly higher compared to the three other groups. HS level in IGL-1 was even lower than IGL-0 (p = 0.0005) which was similar to Sham group. The better protection of the glycocalyx proteins in IGL-1 group was correlated with a higher production of NO than HTK (p = 0.0055) or IGL-0 (p = 0.0433). IGL-1 protective mechanisms through the formation of NO could be due to its better protective effects on the glycocalyx during SCS compared to other preservation solutions. This beneficial effect could involve the preservation state of syndecan-1 and the internalization of HS.

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Section: Discussionmentioning

confidence: 99%

Glycocalyx Preservation and NO Production in Fatty Livers—The Protective Role of High Molecular Polyethylene Glycol in Cold Ischemia Injury

Lopez

Panisello‐Roselló

Benítez

et al. 2018

IJMS

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“…Although criteria to define marginality are arbitrary, extended criteria grafts are most frequently those with moderate or severe graft steatosis or from donors of an advanced age or after circulatory death (DCD). Utilizing these grafts has been associated with an increased rate of primary non-function (PNF), early allograft dysfunction (EAD), graft cholangiopathy (GC), and with reduced graft survival 1–6 . In this regard, various machine perfusion techniques have emerged as valuable alternatives to static cold storage (SCS), allowing a safer utilization of ECDs 7–15 .…”

Section: Introductionmentioning

confidence: 99%

Hypothermic Oxygenated Machine Perfusion of Liver Grafts from Brain-Dead Donors

Patrono

Surra

Catalano

et al. 2019

Sci Rep

114

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Hypothermic oxygenated machine perfusion (HOPE) was introduced in liver transplantation (LT) to mitigate ischemia-reperfusion injury. Available clinical data mainly concern LT with donors after circulatory-determined death, whereas data on brain-dead donors (DBD) are scarce. To assess the impact of end-ischemic HOPE in DBD LT, data on primary adult LTs performed between March 2016 and June 2018 were analyzed. HOPE was used in selected cases of donor age >80 years, apparent severe graft steatosis, or ischemia time ≥10 hours. Outcomes of HOPE-treated cases were compared with those after static cold storage. Propensity score matching (1:2) and Bayesian model averaging were used to overcome selection bias. During the study period, 25 (8.5%) out of 294 grafts were treated with HOPE. After matching, HOPE was associated with a lower severe post-reperfusion syndrome (PRS) rate (4% versus 20%, p = 0.13) and stage 2–3 acute kidney injury (AKI) (16% versus 42%, p = 0.046). Furthermore, Bayesian model averaging showed lower transaminases peak and a lower early allograft dysfunction (EAD) rate after HOPE. A steeper decline in arterial graft resistance throughout perfusion was associated with lower EAD rate. HOPE determines a significant reduction of ischemia reperfusion injury in DBD LT.

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“…Такие органы плохо восстанавливаются после трансплантации. Ишемическое и реперфузионное повреждение нарушает микроциркуляцию из-за нарушения эндотелиальной выстилки сосудов [8], повышает окислительное повреждение митохондрий, а также повышает агрегацию нейтрофилов и приводит к дисбалансу высвобождения цитокинов [6]. Все это увеличивает риск дисфунк ции органа после трансплантации [7].…”

Section: Introductionunclassified

Liver steatosis in brain death donors

Voronov

Минина

Чомаев

et al. 2021

RJTAO

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Aim. To study the frequency of fatty hepatosis in liver biopsies of consecutive brain death donors before cold preservation. Materials and methods. Liver biopsies (before cold preservation) of 300 consecutive donors with brain death were studied. Histological preparations were stained with hematoxylin and eosin, and tricolor Masson staining was performed. Results. The frequency of different degrees of fat hepatosis in men and women did not differ significantly (>0.05). Fat dystrophy of hepatocytes was absent in more than half of the cases (n = 182; 60.7%). A slight degree of fatty degeneration was diagnosed in 57 (19,0%) donors. In total, 239 (79.7%) donor livers were absolutely suitable for transplantation. Moderate degree of steatosis, which is associated with early biliary complications, was detected in 18 (6.0%) cases, and severe degree, which is a contraindication to the use of the organ for transplantation, was detected in 43 (14.3%) cases. Conclusion. Before cold preservation, liver from brain death donors is relatively rarely unsuitable for transplantation.

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Endothelial Dysfunction in Steatotic Human Donor Livers: A Pilot Study of the Underlying Mechanism During Subnormothermic Machine Perfusion

Abstract: Supplemental digital content is available in the text.

Cited by 12 publications

References 50 publications

Glycocalyx Preservation and NO Production in Fatty Livers—The Protective Role of High Molecular Polyethylene Glycol in Cold Ischemia Injury

Glycocalyx Preservation and NO Production in Fatty Livers—The Protective Role of High Molecular Polyethylene Glycol in Cold Ischemia Injury

Hypothermic Oxygenated Machine Perfusion of Liver Grafts from Brain-Dead Donors

Liver steatosis in brain death donors

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