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 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.

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.

Hydrogen Sulfide Confers Protection Against Hepatic Warm Ischemia Reperfusion Injury in Mice

2012 ◽  
Vol 94 (10S) ◽  
pp. 1146
Author(s):  
S. Shimada ◽  
M. Fukai ◽  
K. Yamashita ◽  
K. Wakayama ◽  
T. Kimura ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Warm Ischemia

Selective cyclooxygenase-2 inhibitor ameliorates warm ischemia-reperfusion injury of the canine liver

2001 ◽  
Vol 33 (1-2) ◽  
pp. 862 ◽  
Author(s):  
Y Sunose ◽  
I Takeyoshi ◽  
S Ohwada ◽  
H Tsutsumi ◽  
S Iwazaki ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Warm Ischemia ◽  
Cyclooxygenase 2

scholarly journals Dual and Opposite Costimulatory Targeting with a Novel Human Fusion Recombinant Protein Effectively Prevents Renal Warm Ischemia Reperfusion Injury and Allograft Rejection in Murine Models

2021 ◽  
Vol 22 (3) ◽  
pp. 1216
Author(s):  
Jordi Guiteras ◽  
Laura De Ramon ◽  
Elena Crespo ◽  
Nuria Bolaños ◽  
Silvia Barcelo-Batllori ◽  
...  
Keyword(s):  
Surface Plasmon Resonance ◽  
Recombinant Protein ◽  
Reperfusion Injury ◽  
Surface Plasmon ◽  
Plasmon Resonance ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Warm Ischemia ◽  
Solid Organ ◽  
Inflammatory Models

Many studies have shown both the CD28—D80/86 costimulatory pathway and the PD-1—PD-L1/L2 coinhibitory pathway to be important signals in modulating or decreasing the inflammatory profile in ischemia-reperfusion injury (IRI) or in a solid organ transplant setting. The importance of these two opposing pathways and their potential synergistic effect led our group to design a human fusion recombinant protein with CTLA4 and PD-L2 domains named HYBRI. The objective of our study was to determine the HYBRI binding to the postulated ligands of CTLA4 (CD80) and PD-L2 (PD-1) using the Surface Plasmon Resonance technique and to evaluate the in vivo HYBRI effects on two representative kidney inflammatory models—rat renal IRI and allogeneic kidney transplant. The Surface Plasmon Resonance assay demonstrated the avidity and binding of HYBRI to its targets. HYBRI treatment in the models exerted a high functional and morphological improvement. HYBRI produced a significant amelioration of renal function on day one and two after bilateral warm ischemia and on days seven and nine after transplant, clearly prolonging the animal survival in a life-sustaining renal allograft model. In both models, a significant reduction in histological damage and CD3 and CD68 infiltrating cells was observed. HYBRI decreased the circulating inflammatory cytokines and enriched the FoxP3 peripheral circulating, apart from reducing renal inflammation. In conclusion, the dual and opposite costimulatory targeting with that novel protein offers a good microenvironment profile to protect the ischemic process in the kidney and to prevent the kidney rejection, increasing the animal’s chances of survival. HYBRI largely prevents the progression of inflammation in these rat models.

scholarly journals Hydrogen Sulfide Prevents Ischemia-Reperfusion Injury in Muscle even when Delivered in the Post-ischemic Period

2009 ◽  
Vol 50 (4) ◽  
pp. 972
Author(s):  
P.W. Henderson ◽  
S.P. Singh ◽  
A.L. Weinstein ◽  
V. Nagineni ◽  
J.A. Spector
Keyword(s):  
Hydrogen Sulfide ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ischemic Period

scholarly journals 0110 : Experimental cerebral ischemia in rats increases myocardial vulnerability to ischemia-reperfusion injury ex vivo

2016 ◽  
Vol 8 (3) ◽  
pp. 197
Author(s):  
Laetitia Merle ◽  
Eve Rigal ◽  
Laura Cellier ◽  
Alexandre Meloux ◽  
Luc Rochette ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Experimental Cerebral Ischemia
Sign in / Sign up

Export Citation Format

Share Document