The Effect of Calcium on Hypothermia-Facilitated Resuscitation of Warm Ischemic Kidney Tissue Slices: A Role for the Mitochondrial Permeability Transition Pore?

McAnulty, Jonathan F.

doi:10.1006/cryo.1997.2055

Cited by 12 publications

(2 citation statements)

References 30 publications

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“…Interestingly, AP39 has been reported to prevent the mitochondrial release of pro-apoptotic factors by inhibiting the Ca 2+ -mediated opening of MPTPs and preventing the collapse of the mitochondrial transmembrane electrochemical gradient, thereby protecting against myocardial IRI and other pathological conditions [ 24 , 42 , 43 , 44 ]. Bearing this mechanism in mind, one could surmise that AP39 prevents the mitochondrial accumulation of Ca 2+ during renal graft preservation by SCS since hypothermia promotes the influx of Ca 2+ and mitochondrial Ca 2+ overload [ 45 , 46 , 47 ]. Hence, the addition of AP39 to the UW solution during the SCS of renal grafts in the present study may have prevented MPTP opening and preserved mitochondrial function, leading to protection against IRI and an improvement in renal graft quality and function.…”

Section: Discussionmentioning

confidence: 99%

Static Cold Storage with Mitochondria-Targeted Hydrogen Sulfide Donor Improves Renal Graft Function in an Ex Vivo Porcine Model of Controlled Donation-after-Cardiac-Death Kidney Transplantation

Dugbartey,

Juriasingani,

Richard-Mohamed

et al. 2023

IJMS

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The global donor kidney shortage crisis has necessitated the use of suboptimal kidneys from donors-after-cardiac-death (DCD). Using an ex vivo porcine model of DCD kidney transplantation, the present study investigates whether the addition of hydrogen sulfide donor, AP39, to University of Wisconsin (UW) solution improves graft quality. Renal pedicles of male pigs were clamped in situ for 30 min and the ureters and arteries were cannulated to mimic DCD. Next, both donor kidneys were nephrectomized and preserved by static cold storage in UW solution with or without AP39 (200 nM) at 4 °C for 4 h followed by reperfusion with stressed autologous blood for 4 h at 37 °C using ex vivo pulsatile perfusion apparatus. Urine and arterial blood samples were collected hourly during reperfusion. After 4 h of reperfusion, kidneys were collected for histopathological analysis. Compared to the UW-only group, UW+AP39 group showed significantly higher pO2 (p < 0.01) and tissue oxygenation (p < 0.05). Also, there were significant increases in urine production and blood flow rate, and reduced levels of urine protein, serum creatinine, blood urea nitrogen, plasma Na+ and K+, as well as reduced intrarenal resistance in the UW+AP39 group compared to the UW-only group. Histologically, AP39 preserved renal structure by reducing the apoptosis of renal tubular cells and immune cell infiltration. Our finding could lay the foundation for improved graft preservation and reduce the increasingly poor outcomes associated with DCD kidney transplantation.

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Section: Discussionmentioning

confidence: 99%

Static Cold Storage with Mitochondria-Targeted Hydrogen Sulfide Donor Improves Renal Graft Function in an Ex Vivo Porcine Model of Controlled Donation-after-Cardiac-Death Kidney Transplantation

Dugbartey,

Juriasingani,

Richard-Mohamed

et al. 2023

IJMS

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show abstract

“…The energy state is affected by warm ischemia and subsequent recirculation [36]. Adequate cellular ATP is required for reestablishing ionic homeostasis and supporting ATP-dependent membrane pump function during the critical reperfusion period [37]. Cold preservation results in poor oxygen supply and delayed reduction in the levels of vasoconstrictive arachidonate substrate; actions that result in weak vasodilatation and a delayed recover of EC after reperfusion following cold storage [38], [39].…”

Section: Discussionmentioning

confidence: 99%

Impact of Normothermic Preservation with Extracellular Type Solution Containing Trehalose on Rat Kidney Grafting from a Cardiac Death Donor

et al. 2012

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Background The aim of this study was to investigate factors that may improve the condition of a marginal kidney preserved with a normothermic solution following cardiac death (CD) in a model of rat kidney transplantation (RTx). Methods Post-euthanasia, Lewis (LEW) donor rats were left for 1 h in a 23°C room. These critical kidney grafts were preserved in University of Wisconsin (UW), lactate Ringer's (LR), or extracellular-trehalose-Kyoto (ETK) solution, followed by intracellular-trehalose-Kyoto (ITK) solution at 4, 23, or 37°C for another 1 h, and finally transplanted into bilaterally nephrectomized LEW recipient rats (n = 4–6). Grafts of rats surviving to day 14 after RTx were evaluated by histopathological examination. The energy activity of these marginal rat kidneys was measured by high-performance liquid chromatography (HPLC; n = 4 per group) and fluorescence intensity assay (n = 6 per group) after preservation with UW or ETK solutions at each temperature. Finally, the transplanted kidney was assessed by an in vivo luciferase imaging system (n = 2). Results Using the 1-h normothermic preservation of post-CD kidneys, five out of six recipients in the ETK group survived until 14 days, in contrast to zero out of six in the UW group ( p <0.01). Preservation with ITK rather than ETK at 23°C tended to have an inferior effect on recipient survival ( p = 0.12). Energy activities of the fresh donor kidneys decreased in a temperature-dependent manner, while those of post-CD kidneys remained at the lower level. ETK was superior to UW in protecting against edema of the post-CD kidneys at the higher temperature. Luminescence intensity of successful grafts recovered within 1 h, while the intensity of grafts of deceased recipients did not change at 1 h post-reperfusion. Conclusions Normothermic storage with extracellular-type solution containing trehalose might prevent reperfusion injury due to temperature-dependent tissue edema.

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Energy Metabolism Following Prolonged Hepatic Cold Preservation: Benefits of Interrupted Hypoxia on the Adenine Nucleotide Pool in Rat Liver

et al. 1999

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The Effect of Calcium on Hypothermia-Facilitated Resuscitation of Warm Ischemic Kidney Tissue Slices: A Role for the Mitochondrial Permeability Transition Pore?

Cited by 12 publications

References 30 publications

Static Cold Storage with Mitochondria-Targeted Hydrogen Sulfide Donor Improves Renal Graft Function in an Ex Vivo Porcine Model of Controlled Donation-after-Cardiac-Death Kidney Transplantation

Static Cold Storage with Mitochondria-Targeted Hydrogen Sulfide Donor Improves Renal Graft Function in an Ex Vivo Porcine Model of Controlled Donation-after-Cardiac-Death Kidney Transplantation

Impact of Normothermic Preservation with Extracellular Type Solution Containing Trehalose on Rat Kidney Grafting from a Cardiac Death Donor

Energy Metabolism Following Prolonged Hepatic Cold Preservation: Benefits of Interrupted Hypoxia on the Adenine Nucleotide Pool in Rat Liver

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