Polyethylene Glycol 35 as a Perfusate Additive for Mitochondrial and Glycocalyx Protection in HOPE Liver Preservation.

Carlos Castro,Rui Teixeira Da Silva,René Adam,Raquel G Bardallo,Maria Calvo,Teresa Carbonell,Carlos Palmeira,Emma Folch-Puy,Arnau Panisello Rosello,Joan Roselló Catafau

doi:10.3390/ijms21165703

Abstract

Organ transplantation is a multifactorial process in which proper graft preservation is a mandatory step for the success of the transplantation. Hypothermic preservation of abdominal organs is mostly based on the use of several commercial solutions, including UW, Celsior, HTK and IGL-1. The presence of the oncotic agents HES (in UW) and PEG35 (in IGL-1) characterize both solution compositions, while HTK and Celsior do not contain any type of oncotic agent. Polyethylene glycols (PEGs) are non-immunogenic, non-toxic and water-soluble polymers, which present a combination of properties of particular interest in the clinical context of ischemia-reperfusion injury (IRI): they limit edema and nitric oxide induction and modulate immunogenicity. Besides static cold storage (SCS), there are other strategies to preserve the organ, such as the use of machine perfusion (MP) in dynamic preservation strategies, which increase graft function and survival as compared to the conventional static hypothermic preservation. Here we report some considerations about using PEG35 as a component of perfusates for MP strategies (such as hypothermic oxygenated perfusion, HOPE) and its benefits for liver graft preservation. Improved liver preservation is closely related to mitochondria integrity, making this organelle a good target to increase graft viability, especially in marginal organs (e.g., steatotic livers). The final goal is to increase the pool of suitable organs, and thereby shorten patient waiting lists, a crucial problem in liver transplantation.

Highlights

For more than 100 years, a fascinating dream has been to keep organs “alive” outside the human body [1]
We demonstrated the relevance of nitric oxide (NO) induced by polyethylene glycol 35 (PEG35), which correlated with an enhanced preservation of the GCX during static preservation when comparing two solutions, Institut Georges Lopez 1 (IGL-1) and HTK [64]
We report a new window of machine perfusion (MP) strategy improvements focused on the exploration of new perfusates with adequate physical characteristics that could confer both cytoprotection and mitochondrial restoring [75]

Summary

Introduction

For more than 100 years, a fascinating dream has been to keep organs “alive” outside the human body [1]. The presence of PEG35 in rinse solution after static preservation in UW confirmed that this polymer is directly responsible for mitochondrial preservation during cold storage, including as well the concomitant activation of cytoprotective factors such as AMP-activated protein kinase (AMPK) and presumably the inherent cytoskeleton rearrangement [19] These data are in accordance with Chiang et al [49], who reported that PEG35 could contribute to a better stabilization of the liver endothelial barrier and cytoskeleton when grafts are subjected to PEG35 rinse. These facts point to the potential benefits of using PEGs as oncotic agents in perfusates to reduce the deleterious effects inherent to dynamic preservation strategies. All of them presumably are involved in the cytoskeleton rearrangement [19,49]

Endothelial Glycocalyx

Concluding Remarks