scholarly journals Hydrogen: Potential Applications in Solid Organ Transplantation

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Fuxun Yang ◽  
Yu Lei ◽  
Rongan Liu ◽  
Xiaoxiu Luo ◽  
Jiajia Li ◽  
...  
Keyword(s):  
Protective Effect ◽  
Reperfusion Injury ◽  
Organ Transplantation ◽  
Clinical Studies ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Organ Protection ◽  
Potential Applications

Ischemia reperfusion injury (IRI) in organ transplantation has always been an important hotspot in organ protection. Hydrogen, as an antioxidant, has been shown to have anti-inflammatory, antioxidant, and antiapoptotic effects. In this paper, the protective effect of hydrogen against IRI in organ transplantation has been reviewed to provide clues for future clinical studies.

scholarly journals Relaxin Positively Influences Ischemia—Reperfusion Injury in Solid Organ Transplantation: A Comprehensive Review

2020 ◽  
Vol 21 (2) ◽  
pp. 631 ◽  
Author(s):  
Lina Jakubauskiene ◽  
Matas Jakubauskas ◽  
Bettina Leber ◽  
Kestutis Strupas ◽  
Philipp Stiegler ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Organ Transplantation ◽  
Ischemia Reperfusion Injury ◽  
Positive Impact ◽  
Ischemia Reperfusion ◽  
Graft Function ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Comprehensive Review ◽  
Long Term Treatment

In recent decades, solid organ transplantation (SOT) has increased the survival and quality of life for patients with end-stage organ failure by providing a potentially long-term treatment option. Although the availability of organs for transplantation has increased throughout the years, the demand greatly outweighs the supply. One possible solution for this problem is to extend the potential donor pool by using extended criteria donors. However, organs from such donors are more prone to ischemia reperfusion injury (IRI) resulting in higher rates of delayed graft function, acute and chronic graft rejection and worse overall SOT outcomes. This can be overcome by further investigating donor preconditioning strategies, graft perfusion and storage and by finding novel therapeutic agents that could reduce IRI. relaxin (RLX) is a peptide hormone with antifibrotic, antioxidant, anti-inflammatory and cytoprotective properties. The main research until now focused on heart failure; however, several preclinical studies showed its potentials for reducing IRI in SOT. The aim of this comprehensive review is to overview currently available literature on the possible role of RLX in reducing IRI and its positive impact on SOT.

scholarly journals Medical Gases: A Novel Strategy for Attenuating Ischemia—Reperfusion Injury in Organ Transplantation?

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Arunotai Siriussawakul ◽  
Lucinda I. Chen ◽  
John D. Lang
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Hydrogen Sulfide ◽  
Reperfusion Injury ◽  
Organ Transplantation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Inhaled Nitric Oxide ◽  
Clinical Consequence ◽  
Solid Organ

Ischemia reperfusion injury (IRI) is an inevitable clinical consequence in organ transplantation. It can lead to early graft nonfunction and contribute to acute and chronic graft rejection. Advanced molecular biology has revealed the highly complex nature of this phenomenon and few definitive therapies exist. This paper reviews factors involved in the pathophysiology of IRI and potential ways to attenuate it. In recent years, inhaled nitric oxide, carbon monoxide, and hydrogen sulfide have been increasingly explored as plausible novel medical gases that can attenuate IRI via multiple mechanisms, including microvascular vasorelaxation, reduced inflammation, and mitochondrial modulation. Here, we review recent advances in research utilizing inhaled nitric oxide, carbon monoxide, and hydrogen sulfide in animal and human studies of IRI and postulate on its future applications specific to solid organ transplantation.

scholarly journals The Hepatoprotective Effect of Sodium Nitrite on Cold Ischemia-Reperfusion Injury

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Wei Li ◽  
Zihui Meng ◽  
Yuliang Liu ◽  
Rakesh P. Patel ◽  
John D. Lang
Keyword(s):  
Reperfusion Injury ◽  
Sodium Nitrite ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Combined Treatment ◽  
Solid Organ Transplantation ◽  
Liver Graft ◽  
Solid Organ ◽  
Post Transplantation ◽  
Cold Preservation

Liver ischemia-reperfusion injury is a major cause of primary graft non-function or initial function failure post-transplantation. In this study, we examined the effects of sodium nitrite supplementation on liver IRI in either Lactated Ringer's (LR) solution or University of Wisconsin (UW) solution. The syngeneic recipients of liver grafts were also treated with or without nitrite by intra-peritoneal injection. Liver AST and LDH release were significantly reduced in both nitrite-supplemented LR and UW preservation solutions compared to their controls. The protective effect of nitrite was more efficacious with longer cold preservation times. Liver histological examination demonstrated better preserved morphology and architecture with nitrite treatment. Hepatocellular apoptosis was significantly reduced in the nitrite-treated livers compared their controls. Moreover, liver grafts with extended cold preservation time of 12 to 24 hours demonstrated improved liver tissue histology and function post-reperfusion with either the nitrite-supplemented preservation solution or in nitrite-treated recipients. Interestingly, combined treatment of both the liver graft and recipient did not confer protection. Thus, nitrite treatment affords significant protection from cold ischemic and reperfusion injury to donor livers and improves liver graft acute function post-transplantation. The results from this study further support the potential for nitrite therapy to mitigate ischemia-reperfusion injury in solid organ transplantation.

scholarly journals Mesenchymal Stromal Cell Therapy in Ischemia/Reperfusion Injury

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Pascal Rowart ◽  
Pauline Erpicum ◽  
Olivier Detry ◽  
Laurent Weekers ◽  
Céline Grégoire ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Graft Function ◽  
Solid Organ Transplantation ◽  
Critical Factor ◽  
Public Health Issue ◽  
Solid Organ ◽  
Short And Long Term

Ischemia/reperfusion injury (IRI) represents a worldwide public health issue of increasing incidence. IRI may virtually affect all organs and tissues and is associated with significant morbidity and mortality. Particularly, the duration of blood supply deprivation has been recognized as a critical factor in stroke, hemorrhagic shock, or myocardial infarction, as well as in solid organ transplantation (SOT). Pathophysiologically, IRI causes multiple cellular and tissular metabolic and architectural changes. Furthermore, the reperfusion of ischemic tissues induces both local and systemic inflammation. In the particular field of SOT, IRI is an unavoidable event, which conditions both short- and long-term outcomes of graft function and survival. Clinically, the treatment of patients with IRI mostly relies on supportive maneuvers since no specific target-oriented therapy has been validated thus far. In the present review, we summarize the current literature on mesenchymal stromal cells (MSC) and their potential use as cell therapy in IRI. MSC have demonstrated immunomodulatory, anti-inflammatory, and tissue repair properties in rodent studies and in preliminary clinical trials, which may open novel avenues in the management of IRI and SOT.

scholarly journals Current Status of Glucocorticoid Usage in Solid Organ Transplantation

2021 ◽  
Author(s):  
Simin Dashti-Khavidaki ◽  
Reza Saidi ◽  
Hong Lu
Keyword(s):  
Side Effects ◽  
Immunosuppressive Therapy ◽  
Organ Transplantation ◽  
Targeted Delivery ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Solid Organ Transplantation ◽  
Current Status ◽  
Solid Organ ◽  
Advantages And Disadvantages

Glucocorticoids (GCs) have been the mainstay of immunosuppressive therapy in solid organ transplantation (SOT) for decades due to their potent effects on the innate immunity and tissue protective effects. But, some SOT centers are reluctant to administer GCs for long-time due to the various side effects. This review summarizes advantages and disadvantages of GCs in SOT. PubMed and Scopus databases were searched from 2011 to April 2021 using search syntaxes cover “transplantation” and “glucocorticoids”.GCs are used in transplant recipients, transplant donors, and organ perfusate solution to improve transplant outcomes. In SOT recipients GCs are administered as induction and maintenance immunosuppressive therapy. GCs are also the cornerstone to treat acute anti-body- and T-cell-mediated rejections. Addition of GCs to organ perfusate solution and pretreatment of transplant donors with GCs are recommended by some guidelines and protocols to reduce ischemia-reperfusion injury peri-transplant. GCs with low bioavailability and high potency for GC receptors such as budesonide, nanoparticle-mediated targeted delivery of GCs to specific organs, and combination use of dexamethasone with inducers of immune-regulatory cells are new methods of GC usage in SOT patients to reduce side effects or induce immune-tolerance instead of immunosuppression. Various side effects on different non-targeted organs/tissues such as bone, cardiovascular, neuromuscular, skin, and gastrointestinal tract have been noted for GCs. There are also potential drug-drug interactions for GCs in SOT patients.

scholarly journals Potential Applications of Extracellular Vesicles in Solid Organ Transplantation

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 369 ◽  
Author(s):  
Grange ◽  
Bellucci ◽  
Bussolati ◽  
Ranghino
Keyword(s):  
Extracellular Vesicles ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Ischemia Reperfusion ◽  
Solid Organ Transplantation ◽  
Cell Communication ◽  
Target Cells ◽  
Solid Organ ◽  
Term Survival ◽  
Potential Applications

Extracellular vesicles (EVs) play an important role in cell-to-cell communication by delivering coding and non-coding RNA species and proteins to target cells. Recently, the therapeutic potential of EVs has been shown to extend to the field of solid organ transplantations. Mesenchymal stromal cell-derived EVs (MSC-EVs) in particular have been proposed as a new tool to improve graft survival, thanks to the modulation of tolerance toward the graft, and to their anti-fibrotic and pro-angiogenic effects. Moreover, MSC-EVs may reduce ischemia reperfusion injury, improving the recovery from acute damage. In addition, EVs currently considered helpful tools for preserving donor organs when administered before transplant in the context of hypothermic or normothermic perfusion machines. The addition of EVs to the perfusion solution, recently proposed for kidney, lung, and liver grafts, resulted in the amelioration of donor organ viability and functionality. EVs may therefore be of therapeutic interest in different aspects of the transplantation process for increasing the number of available organs and improving their long-term survival.

scholarly journals Combating Ischemia-Reperfusion Injury with Micronutrients and Natural Compounds During Solid Organ Transplantation: Data of Clinical Trials and Lessons of Preclinical Findings

2021 ◽  
Vol 22 (19) ◽  
pp. 10675
Author(s):  
Christina Mauerhofer ◽  
Lukas Grumet ◽  
Peter Schemmer ◽  
Bettina Leber ◽  
Philipp Stiegler
Keyword(s):  
Oxidative Stress ◽  
Clinical Trials ◽  
Reperfusion Injury ◽  
Clinical Studies ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Natural Compounds ◽  
Data Availability ◽  
Solid Organ ◽  
Inflammatory Status

Although extended donor criteria grafts bear a higher risk of complications such as graft dysfunction, the exceeding demand requires to extent the pool of potential donors. The risk of complications is highly associated with ischemia-reperfusion injury, a condition characterized by high loads of oxidative stress exceeding antioxidative defense mechanisms. The antioxidative properties, along with other beneficial effects like anti-inflammatory, antiapoptotic or antiarrhythmic effects of several micronutrients and natural compounds, have recently emerged increasing research interest resulting in various preclinical and clinical studies. Preclinical studies reported about ameliorated oxidative stress and inflammatory status, resulting in improved graft survival. Although the majority of clinical studies confirmed these results, reporting about improved recovery and superior organ function, others failed to do so. Yet, only a limited number of micronutrients and natural compounds have been investigated in a (large) clinical trial. Despite some ambiguous clinical results and modest clinical data availability, the vast majority of convincing animal and in vitro data, along with low cost and easy availability, encourage the conductance of future clinical trials. These should implement insights gained from animal data.

scholarly journals The Endothelial Glycocalyx and Organ Preservation—From Physiology to Possible Clinical Implications for Solid Organ Transplantation

2021 ◽  
Vol 22 (8) ◽  
pp. 4019
Author(s):  
Simon Mathis ◽  
Gabriel Putzer ◽  
Stefan Schneeberger ◽  
Judith Martini
Keyword(s):  
Organ Transplantation ◽  
Organ Preservation ◽  
Ischemia Reperfusion Injury ◽  
Current Knowledge ◽  
Ischemia Reperfusion ◽  
Solid Organ Transplantation ◽  
Endothelial Glycocalyx ◽  
Solid Organ ◽  
Machine Perfusion ◽  
Normothermic Machine Perfusion

The endothelial glycocalyx is a thin layer consisting of proteoglycans, glycoproteins and glycosaminoglycans that lines the luminal side of vascular endothelial cells. It acts as a barrier and contributes to the maintenance of vascular homeostasis and microperfusion. During solid organ transplantation, the endothelial glycocalyx of the graft is damaged as part of Ischemia Reperfusion Injury (IRI), which is associated with impaired organ function. Although several substances are known to mitigate glycocalyx damage, it has not been possible to use these substances during graft storage on ice. Normothermic machine perfusion (NMP) emerges as an alternative technology for organ preservation and allows for organ evaluation, but also offers the possibility to treat and thus improve organ quality during storage. This review highlights the current knowledge on glycocalyx injury during organ transplantation, presents ways to protect the endothelial glycocalyx and discusses potential glycocalyx protection strategies during normothermic machine perfusion.

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