PREVENTION AND TREATMENT OF ISCHEMIA-REPERFUSION SYNDROME

2019 ◽  
Vol 23 (2) ◽  
pp. 41-48
Author(s):  
A. V. Vatazin ◽  
D. V. Artemov ◽  
A. B. Zulkarnaev

The main negative consequences of ischemia-reperfusion of the kidneys are the early developing severe chronic dysfunction of the graft, and in the most severe cases the function of the transplanted kidney is not restored (primary non-functioning graft). As a result of loss of transplant function, the patient usually returns to dialysis. These complications are more common in kidney transplants from “donors with extended criteria,” since these organs are most sensitive to damage resulting from ischemia-reperfusion syndrome (IR syndrome). At the same time, the share of such (suboptimal) donors is gradually increasing in Russia. Cold preservation of the organ in special solutions remains the gold standard for kidney transplantation, however, it is not able to fully protect the organ. The article presents the main promising methods that reduce the severity of ischemic and reperfusion injury: donor conditioning, ischemic preconditioning, various variants of kidney preservation, effects on inflammatory mediators, application of biological target drugs. Nevertheless, the pathogenesis of ischemia-reperfusion syndrome has been studied much better than the methods of its correction. Currently, there are only indirect or experimental evidence that the severity of the syndrome of IR can be reduced due to the pharmacoprotection of the ogran before donation, during preservation, as well as in the early postoperative period. Further research is needed to find ways to reduce the severity of ischemic and reperfusion injury of the graft.

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3592
Author(s):  
Aneta Ostróżka-Cieślik ◽  
Barbara Dolińska ◽  
Florian Ryszka

Selenium has strong antioxidant properties and diverse effects on the immune system. The aim of the study was to analyse the protective effect of selenium as a component of a kidney preservation solution on the prevention of ischemia-reperfusion injury of nephrons. The solution was modified by the addition of Se (1 µg/L), prolactin (0.1 µg/L) and Se with prolactin (1 µg/L Se + 0.1 µg/L PRL). The study used a model for storing isolated porcine kidneys in Biolasol® (modified Biolasol®), which minimizes ischemia-reperfusion injury of grafts. The introduction of Se4+ ions at a dose of 1 µg/L into the Biolasol® preservation solution in the form of Na2SeO3 caused an increase in the activity/concentration of the analysed biochemical parameters: aspartate transaminase, alanine transaminase, urea and protein. This suggests an adverse effect of Se4+ on nephron function during ischemia-reperfusion. The best graft protection was obtained by using Biolasol® modified with the addition of selenium (IV) at a dose of 1 µg/L and prolactin at a concentration of 0.1 µg/L. We proposed the mechanism of prolactin action in the metabolic reduction of selenite (SO32−) during ischemia/reperfusion.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Rui-Hua Li ◽  
Jin Li ◽  
Shi-Lian Kan ◽  
Xi-Nan Zhang

The authors aim to investigate protective effects of fasciotomy against ischemia reperfusion injury of skeletal muscle in rabbit and to compare the treatment effects of prereperfusion + fasciotomy and fasciotomy + postreperfusion against ischemia reperfusion injury of skeletal muscle. 24 healthy male Japanese white rabbits were randomly divided into 3 groups, and 4 hours’ ischemia was established in these rabbits through surgery. Six hours’ reperfusion was performed in group A; reperfusion + postfasciotomy was performed in group B; and prefasciotomy + reperfusion was performed in group C. Result showed that prefasciotomy and postfasciotomy could protect skeletal muscle against ischemia reperfusion injury, reduced MDA (malondialdehyde) expression, MPO (myeloperoxidase) expression, and apoptosis of muscle in the reperfused areas, increased Bcl-2 expression, and decreased Bax expression. The MDA and MPO levels in group B and group C were significantly lower than those in group A, and MDA and MPO levels in group C were significantly lower than those in group B. Prefasciotomy and postfasciotomy could protect against ischemia reperfusion injury in skeletal muscle. The protective effects of prefasciotomy against ischemia reperfusion injury are better than postfasciotomy.


2019 ◽  
Vol 8 (3) ◽  
pp. 216-224
Author(s):  
T. A. Yagudin ◽  
A. T Shabanova ◽  
Hong-Yu Liu

Introduction.The present article, in which a contemporary analysis of the literature on the pathophysiology of ischemic and reperfusion injury (IRI) of the myocardium is presented, focuses on the possible role played by of the calpain system and oxidative stress. Several process development options were proposed, including cytosolic and mitochondrial Ca2+ overload, reactive oxygen stress release, acute inflammatory response and metabolic degradation. The combined effect of all of the above factors produces irreversible ischemic and reperfused damage of cardiomyocytes.Materials and methods.The role of the calpain system in the creation of myocardial IRI was experimentally investigated. It was found that active calpain substrates play a significant role in the processes of cell cycle, apoptosis and differentiation, adversely affecting cardiomyocyte functionality. The calpain system is part of an integrated proteolytic system that is critical to the relationship between the structure and function of the cardiac sarcomere. Uncontrolled activation of calpain is indicated in the pathophysiology of many cardiovascular disorders. As shown by research, inhibitor calpain reduces the size of the zone of infarction following ischemia reperfusion and thus lessens the risk of “stunning” the myocardium. As is known, a consequence of IRI is acute myocardial infarction (AMI), which is a central factor in cardiovascular disease (CVD) and is one of the primary causes of mortality. Understanding the exact pathophysiological mechanisms remains an urgent problem for clinical physicians. To date, the mechanisms of IRI are not fully known, which creates certain difficulties in further treatment and prevention tactics. In addition, myocardial IRI is also an important issue for pathoanatomical service, since sudden coronary death can occur despite timely reperfusion therapy following AMI.Conclusion.The development of strategies for creating conditions that limit the degree of damage to myocardial tissues significantly increases the ability of the heart to withstand ischemic damage.


2020 ◽  
Vol 21 (21) ◽  
pp. 8156
Author(s):  
Sebastien Giraud ◽  
Raphaël Thuillier ◽  
Jérome Cau ◽  
Thierry Hauet

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.


2004 ◽  
Vol 52 (5) ◽  
pp. 310-314 ◽  
Author(s):  
Niamh E. Kieran ◽  
Hamid Rabb

Organ preservation and reperfusion injury have significant detrimental effects on both short- and long-term organ function. Ischemia reperfusion injury (IRI) underlies organ transplant dysfunction, myocardial infarction, stroke, and shock. Multiple molecular pathways are engaged in reactive oxygen production, apoptosis, signaling, and tissue regeneration. There has been an increased understanding of the important role of immune and inflammatory pathways in IRI, both in humans and in experimental models. Both cellular and soluble components of the immune system are directly activated during IRI, and there is evidence that immune mediators directly contribute to organ dysfunction. Immune activation during IRI likely underlies the enhanced immunogenicity of ischemic organs, with resultant increased rejection and fibrosis. Novel human therapies targeting T and B cells for classic immune diseases can now be considered to prevent and treat IRI. Organ preservation injury and cold ischemia could well have distinct pathophysiology from warm IRI and represent an opportunity to develop improved preservation methods.


Author(s):  
S. V. Zhuravel ◽  
N. K. Kuznetsova ◽  
V. E. Aleksandrova ◽  
I. I. Goncharova

Background. A pressing issue is the choice of an anesthetic agent for liver transplantation. The mechanism of the organprotective properties of desflurane and sevoflurane is not fully understood. It is important to understand the effects of desflurane and sevoflurane on the severity of ischemia-reperfusion injury of the liver graftAim. To study the effect of desflurane and sevoflurane on the intraoperative and early postoperative period in liver transplantation.Material and methods. The study included 47 patients with liver cirrhosis of various etiologies who underwent cadaveric liver transplantation between February and December 2020. The groups compared in the study included 24 patients who received desflurane and 23 patients who received sevoflurane.Results. There were no statistically significant differences in the effect of desflurane and sevoflurane on hemodynamic parameters, on the need for vasopressor drugs. Episodes of bradycardia and cardiac arrhythmias were significantly more frequent when using sevoflurane. Patients were extubated significantly faster after surgery in the desflurane group. In the early postoperative period, desflurane and sevoflurane did not adversely affect significantly the liver graft function and the degree of its ischemia-reperfusion injury. The groups appeared comparable in rates of using the renal replacement therapy, the incidence of the graft dysfunction development in the postoperative period, and the surgery outcomes.Conclusions. The use of modern inhalation anesthetics desflurane and sevoflurane to maintain anesthesia during liver transplantation does not adversely affect the course of the intraoperative and early postoperative period.


2021 ◽  
Vol 8 ◽  
Author(s):  
Ruta Zulpaite ◽  
Povilas Miknevicius ◽  
Bettina Leber ◽  
Kestutis Strupas ◽  
Philipp Stiegler ◽  
...  

Kidney transplantation remains the gold standard treatment for patients suffering from end-stage kidney disease. To meet the constantly growing organ demands grafts donated after circulatory death (DCD) or retrieved from extended criteria donors (ECD) are increasingly utilized. Not surprisingly, usage of those organs is challenging due to their susceptibility to ischemia-reperfusion injury, high immunogenicity, and demanding immune regulation after implantation. Lately, a lot of effort has been put into improvement of kidney preservation strategies. After demonstrating a definite advantage over static cold storage in reduction of delayed graft function rates in randomized-controlled clinical trials, hypothermic machine perfusion has already found its place in clinical practice of kidney transplantation. Nevertheless, an active investigation of perfusion variables, such as temperature (normothermic or subnormothermic), oxygen supply and perfusate composition, is already bringing evidence that ex-vivo machine perfusion has a potential not only to maintain kidney viability, but also serve as a platform for organ conditioning, targeted treatment and even improve its quality. Many different therapies, including pharmacological agents, gene therapy, mesenchymal stromal cells, or nanoparticles (NPs), have been successfully delivered directly to the kidney during ex-vivo machine perfusion in experimental models, making a big step toward achievement of two main goals in transplant surgery: minimization of graft ischemia-reperfusion injury and reduction of immunogenicity (or even reaching tolerance). In this comprehensive review current state of evidence regarding ex-vivo kidney machine perfusion and its capacity in kidney graft treatment is presented. Moreover, challenges in application of these novel techniques in clinical practice are discussed.


2019 ◽  
Author(s):  
Min Li ◽  
Yingwu Mei ◽  
Jingeng Liu ◽  
Kaikai Fan ◽  
Xinyue Gu ◽  
...  

ABSTRACTArsenite (NaAsO2) is a potent toxin that significantly contributes to human pathogenesis. Chronic exposure to arsenite results in various diseases. The physiologically important biological target(s) of arsenite exposure is largely unknown. Here we found that transient sodium arsenite treatment (1) blocks nigericin or Rotenone induced IL-1β secretion; (2) inhibits mitochondrial respiration with complex I–linked substrate; (3) induces Heme oxygenase-1 (HO-1) in myocardial tissue. (4) attenuates the myocardial ischemia-reperfusion injury in an in vivo model of rats. The causal relationship among these activities needs further investigation.


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