scholarly journals The Effects of 6-Chromanol SUL-138 during Hypothermic Machine Perfusion on Porcine Deceased Donor Kidneys

2021 ◽  
Vol 2 (3) ◽  
pp. 304-314
Author(s):  
L. Annick van Furth ◽  
Leonie H. Venema ◽  
Koen D. W. Hendriks ◽  
Pieter C. Vogelaar ◽  
Guido Krenning ◽  
...  
Keyword(s):  
Renal Function ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Autologous Blood ◽  
Warm Ischemia ◽  
Protective Agent ◽  
Machine Perfusion ◽  
Kidney Preservation ◽  
Atp Levels ◽  
Hypothermic Machine Perfusion

Diminishing ischemia-reperfusion injury (IRI) by improving kidney preservation techniques offers great beneficial value for kidney transplant recipients. Mitochondria play an important role in the pathogenesis of IRI and are therefore interesting targets for pharmacological interventions. Hypothermic machine perfusion (HMP), as a preservation strategy, offers the possibility to provide mitochondrial–targeted therapies. This study focuses on the addition of a mitochondrial protective agent SUL—138 during HMP and assesses its effect on kidney function and injury during normothermic reperfusion. In this case, 30 min of warm ischemia was applied to porcine slaughterhouse kidneys before 24 h of non–oxygenated HMP with or without the addition of SUL—138. Functional assessment was performed by 4 h normothermic autologous blood reperfusion. No differences in renal function or perfusion parameters were found between both groups. ATP levels were lower after 30 min of warm ischemia in the SUL–138 group (n.s, p = 0.067) but restored significantly during 24 h of HMP in combination with SUL—138. Aspartate aminotransferase (ASAT) levels were significantly lower for the SUL—138 group. SUL—138 does not influence renal function in this model. Restoration of ATP levels during 24 h of HMP with the addition of SUL in combination with lower ASAT levels could be an indication of improved mitochondrial function.

scholarly journals Hydrogen sulfide (H2S) reduces oxygen and ATP consumption in the isolated perfused pig kidney

2021 ◽  
Vol 108 (Supplement_4) ◽  
Author(s):  
T Agius ◽  
J Songeon ◽  
A Klauser ◽  
A Nastasi ◽  
R Ruttiman ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Oxygen Demand ◽  
Warm Ischemia ◽  
Atp Levels ◽  
Hypothermic Machine Perfusion ◽  
Kidney Perfusion

Abstract Objective Organ donation after circulatory death [DCD] has the potential to reduce the shortage of kidneys available for transplantation. However, many DCD grafts are discarded because of long warm ischemia times. Strategies reducing oxygen demand may minimize damages caused by ischemia/reperfusion injury. Ex-vivo, Hydrogen sulfide (H2S) reduces oxygen and ATP consumption of the isolated perfused kidney, reduces inflammation and improves renal function following ischemia reperfusion injury in rodents. However, the benefits and applicability of H2S in clinically relevant model remain unknown. Methods To mimic DCD, pig kidneys underwent 0 or 60 min of warm ischemia, before oxygenated hypothermic machine perfusion (HMP). NaHS (100µM), an H2S donor, was added to the perfusion media or injected as an intra-arterial bolus before warm ischemia. After 2 hours of HMP, kidneys were transplanted and reperfused for 1 hour before harvest. Kidney function was assesses before, after and during ex vivo perfusion by measuring energy metabolites, Gadolinium elimination by pMRI and histopathological scoring. Results Warm ischemia (60 min) induced significant histological damages, delayed cortical and medullary Gadolinium elimination (perfusion), and reduced ATP levels, but not its precursors (AMP). As expected, ATP levels and kidney perfusion both inversely correlated with the severity of kidney histological injury. NaHS reduced metabolism during warm ischemia, and seemed to increase kidney ATP levels and viability after reperfusion. Conclusion Our preliminary data suggest that the H2S donor NaHS reduces kidney metabolism and protects from warm ischemia. Further experiments will identify the best administration protocol and the clinical relevance of H2S supplementation in the context of organ preservation.

scholarly journals Cold Preflush of Porcine Kidney Grafts Prior to Normothermic Machine Perfusion Aggravates Ischemia Reperfusion Injury

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Gregor Fabry ◽  
Benedict M. Doorschodt ◽  
Tim Grzanna ◽  
Peter Boor ◽  
Aaron Elliott ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Warm Ischemia ◽  
Total Output ◽  
Machine Perfusion ◽  
Buffer Solution ◽  
Preservation Method ◽  
Fractional Excretion Of Sodium ◽  
Normothermic Machine Perfusion

Abstract Normothermic machine perfusion (NMP) of kidney grafts is a promising new preservation method to improve graft quality and clinical outcome. Routinely, kidneys are washed out of blood remnants and cooled using organ preservation solutions prior to NMP. Here we assessed the effect of cold preflush compared to direct NMP. After 30 min of warm ischemia, porcine kidneys were either preflushed with cold histidine-tryptophan-ketoglutarate solution (PFNMP group) prior to NMP or directly subjected to NMP (DNMP group) using a blood/buffer solution. NMP was performed at a perfusion pressure of 75 mmHg for 6 h. Functional parameters were assessed as well as histopathological and biochemical analyses. Renal function as expressed by creatinine clearance, fractional excretion of sodium and total output of urine was inferior in PFNMP. Urine protein and neutrophil gelatinase-associated lipocalin (NGAL) concentrations as markers for kidney damage were significantly higher in the PFNMP group. Additionally, increased osmotic nephropathy was found after PFNMP. This study demonstrated that cold preflush prior to NMP aggravates ischemia reperfusion injury in comparison to direct NMP of warm ischemia-damaged kidney grafts. With increasing use of NMP systems for kidneys and other organs, further research into graft flushing during retrieval is warranted.

scholarly journals In Vitro/Ex Vivo Models for the Study of Ischemia Reperfusion Injury during Kidney Perfusion

2020 ◽  
Vol 21 (21) ◽  
pp. 8156
Author(s):  
Sebastien Giraud ◽  
Raphaël Thuillier ◽  
Jérome Cau ◽  
Thierry Hauet
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Kidney Graft ◽  
Kidney Preservation ◽  
Hypothermic Machine Perfusion ◽  
Kidney Perfusion ◽  
Marginal Donors

Oxidative stress is a key element of ischemia–reperfusion injury, occurring during kidney preservation and transplantation. Current options for kidney graft preservation prior to transplantation are static cold storage (CS) and hypothermic machine perfusion (HMP), the latter demonstrating clear improvement of preservation quality, particularly for marginal donors, such as extended criteria donors (ECDs) and donation after circulatory death (DCDs). Nevertheless, complications still exist, fostering the need to improve kidney preservation. This review highlights the most promising avenues of in kidney perfusion improvement on two critical aspects: ex vivo and in vitro evaluation.

scholarly journals Ischemia-Reperfusion Injury in Marginal Liver Grafts and the Role of Hypothermic Machine Perfusion: Molecular Mechanisms and Clinical Implications

2020 ◽  
Vol 9 (3) ◽  
pp. 846 ◽  
Author(s):  
Zoltan Czigany ◽  
Isabella Lurje ◽  
Moritz Schmelzle ◽  
Wenzel Schöning ◽  
Robert Öllinger ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Graft Function ◽  
Organ Shortage ◽  
Machine Perfusion ◽  
Hypothermic Machine Perfusion ◽  
Critical Organ

Ischemia-reperfusion injury (IRI) constitutes a significant source of morbidity and mortality after orthotopic liver transplantation (OLT). The allograft is metabolically impaired during warm and cold ischemia and is further damaged by a paradox reperfusion injury after revascularization and reoxygenation. Short-term and long-term complications including post-reperfusion syndrome, delayed graft function, and immune activation have been associated with IRI. Due to the current critical organ shortage, extended criteria grafts are increasingly considered for transplantation, however, with an elevated risk to develop significant features of IRI. In recent years, ex vivo machine perfusion (MP) of the donor liver has witnessed significant advancements. Here, we describe the concept of hypothermic (oxygenated) machine perfusion (HMP/HOPE) approaches and highlight which allografts may benefit from this technology. This review also summarizes clinical applications and the main aspects of ongoing randomized controlled trials on hypothermic perfusion. The mechanistic aspects of IRI and hypothermic MP—which include tissue energy replenishment, optimization of mitochondrial function, and the reduction of oxidative and inflammatory damage following reperfusion—will be comprehensively discussed within the context of current preclinical and clinical evidence. Finally, we highlight novel trends and future perspectives in the field of hypothermic MP in the context of recent findings of basic and translational research.

Hypothermic Machine Perfusion Ameliorates Ischemia-Reperfusion Injury in Rat Lungs From Non-Heart-Beating Donors

2011 ◽  
Vol 92 (8) ◽  
pp. 858-863 ◽  
Author(s):  
Daisuke Nakajima ◽  
Fengshi Chen ◽  
Tetsu Yamada ◽  
Jin Sakamoto ◽  
Akihiro Osumi ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Machine Perfusion ◽  
Rat Lungs ◽  
Hypothermic Machine Perfusion ◽  
Heart Beating
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