The administration of argon during  ex vivo  normothermic perfusion in an experimental model of kidney ischemia–reperfusion injury

Smith, Stephanie F; Adams, Tom; Hosgood, Sarah A.; Nicholson, Michael L.

doi:10.1016/j.jss.2017.05.041

Cited by 18 publications

(22 citation statements)

References 28 publications

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“…These findings open the door for organ treatment during preservation, not only by adding gas to preservation solutions but potentially also by adding it to dynamic preservation and resuscitation techniques. In fact, Smith and colleagues administered argon during 1 h of normothermic machine perfusion of pig kidneys, and showed feasibility although renal function was similar compared with that in controls. Furthermore, if ethical and legal challenges of donor (pre)treatment could be overcome, transplantation lends itself to preconditioning, perconditioning and postconditioning.…”

Section: Discussionmentioning

confidence: 99%

Postconditioning effects of argon or xenon on early graft function in a porcine model of kidney autotransplantation

Deken

Rex

Lerut

et al. 2018

British Journal of Surgery

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Postconditioning with argon or xenon did not improve kidney graft function in this experimental model. Surgical relevance Ischaemia-reperfusion injury is inevitable during renal transplantation and can lead to delayed graft function and primary non-function. Based on mainly small animal experiments, noble gases (argon and xenon) have been proposed to minimize this ischaemia-reperfusion injury and improve outcomes after transplantation. The hypothesis that postconditioning with argon or xenon inhalation would improve graft function was tested in a porcine kidney autotransplantation model. The peak plasma creatinine concentration was similar in the control, argon and xenon groups. No other secondary outcome parameters, including animal survival, were affected by the intervention. Xenon was associated with an increase in autophagy and proapoptotic markers. Despite promising results in small animal models, postconditioning with argon or xenon in a translational model of kidney autotransplantation was not beneficial. Clinical trials would require better results.

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Section: Discussionmentioning

confidence: 99%

Postconditioning effects of argon or xenon on early graft function in a porcine model of kidney autotransplantation

Deken

Rex

Lerut

et al. 2018

British Journal of Surgery

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“…During NMP, using a bespoke red blood cell (RBC) enriched oxygenated and nutrient containing perfusate, the metabolism of the kidney resumes and allows monitoring during perfusion prior to transplantation (6, 7). Application of NMP for assessment and targeted intervention (8) to improve kidney quality is appealing and the effect of the therapy can potentially be monitored before the organ is transplanted. Thus, NMP is postulated as a promising platform to reduce kidney damage and initiate regeneration prior to transplantation.…”

Section: Introductionmentioning

confidence: 99%

Effects of Normothermic Machine Perfusion Conditions on Mesenchymal Stromal Cells

et al. 2019

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Ex-situ normothermic machine perfusion (NMP) of transplant kidneys allows assessment of kidney quality and targeted intervention to initiate repair processes prior to transplantation. Mesenchymal stromal cells (MSC) have been shown to possess the capacity to stimulate kidney repair. Therefore, the combination of NMP and MSC therapy offers potential to repair transplant kidneys. It is however unknown how NMP conditions affect MSC. In this study the effect of NMP perfusion fluid on survival, metabolism and function of thawed cryopreserved human (h)MSC and porcine (p)MSC in suspension conditions was studied. Suspension conditions reduced the viability of pMSC by 40% in both perfusion fluid and culture medium. Viability of hMSC was reduced by suspension conditions by 15% in perfusion fluid, whilst no differences were found in survival in culture medium. Under adherent conditions, survival of the cells was not affected by perfusion fluid. The perfusion fluid did not affect survival of fresh MSC in suspension compared to the control culture medium. The freeze-thawing process impaired the survival of hMSC; 95% survival of fresh hMSC compared to 70% survival of thawed hMSC. Moreover, thawed MSC showed increased levels of reactive oxygen species, which indicates elevated levels of oxidative stress, and reduced mitochondrial activity, which implies reduced metabolism. The adherence of pMSC and hMSC to endothelial cells was reduced after the thawing process, effect which was particularly profound in in the perfusion fluid. To summarize, we observed that conditions required for machine perfusion are influencing the behavior of MSC. The freeze-thawing process reduces survival and metabolism and increases oxidative stress, and diminishes their ability to adhere to endothelial cells. In addition, we found that hMSC and pMSC behaved differently, which has to be taken into consideration when translating results from animal experiments to clinical studies.

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“…Regarding the use of Ar for organ preservation, kidneys and lungs were the preferred targets. [4647485254] Indeed, reduced acute tubular necrosis and inflammatory lesions accompanied by better renal function and faster recovery were observed after heterotopic autotransplantation in which the removed kidney was preserved in a cold storage solution saturated with pure Ar. [4648] Smith et al .…”

Section: Methodsmentioning

confidence: 99%

A complete review of preclinical and clinical uses of the noble gas argon: Evidence of safety and protection

et al. 2019

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The noble gas argon (Ar) is a “biologically” active element and has been extensively studied preclinically for its organ protection properties. This work reviews all preclinical studies employing Ar and describes the clinical uses reported in literature, analyzing 55 pertinent articles found by means of a search on PubMed and Embase. Ventilation with Ar has been tested in different models of acute disease at concentrations ranging from 20% to 80% and for durations between a few minutes up to days. Overall, lesser cell death, smaller infarct size, and better functional recovery after ischemia have been repeatedly observed. Modulation of the molecular pathways involved in cell survival, with resulting anti-apoptotic and pro-survival effects, appeared as the determinant mechanism by which Ar fulfills its protective role. These beneficial effects have been reported regardless of onset and duration of Ar exposure, especially after cardiac arrest. In addition, ventilation with Ar was safe both in animals and humans. Thus, preclinical and clinical data support future clinical studies on the role of inhalatory Ar as an organ protector.

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The administration of argon during ex vivo normothermic perfusion in an experimental model of kidney ischemia–reperfusion injury

Cited by 18 publications

References 28 publications

Postconditioning effects of argon or xenon on early graft function in a porcine model of kidney autotransplantation

Postconditioning effects of argon or xenon on early graft function in a porcine model of kidney autotransplantation

Effects of Normothermic Machine Perfusion Conditions on Mesenchymal Stromal Cells

A complete review of preclinical and clinical uses of the noble gas argon: Evidence of safety and protection

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