Deterioration of Endothelial and Smooth Muscle Cell Function in DCD Kidneys After Static Cold Storage in IGL-1 or UW

Maathuis, Mark-Hugo J.; Groot, Martijn de; Ploeg, Rutger J.; Leuvenink, Henri G. D.

doi:10.1016/j.jss.2008.02.055

Cited by 12 publications

(4 citation statements)

References 35 publications

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“…17 Renal O 2 consumption was measured in pre-and postrenal samples taken from an injection port 2 cm before the kidney and from the renal vein, respectively. In these samples, pO 2 was measured using an ABL700 blood gas analyzer (Radiometer Medical, Denmark).…”

Section: Isolated Perfused Kidneymentioning

confidence: 99%

Hydrogen Sulfide-Induced Hypometabolism Prevents Renal Ischemia/Reperfusion Injury

Bos

Leuvenink

Snijder

et al. 2009

Journal of the American Society of Nephrology

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150

129

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Section: Isolated Perfused Kidneymentioning

confidence: 99%

Hydrogen Sulfide-Induced Hypometabolism Prevents Renal Ischemia/Reperfusion Injury

Bos

Leuvenink

Snijder

et al. 2009

Journal of the American Society of Nephrology

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150

129

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“…Therefore, the cessation of blood flow during static CS likely affects NO production and vasodilation. Indeed, the absence of flow reduces endothelial NO production in vitro (15), and static CS alters NO-dependent vasodilation of DCD kidneys or of saphenous vein segments after reperfusion (16,17). Recently, it was demonstrated that flow cessation and static cold preservation decreased KLF2 and eNOS expression both in vitro and in vivo (18).…”

mentioning

confidence: 99%

Mechanistic Analysis of Nonoxygenated Hypothermic Machine Perfusion’s Protection on Warm Ischemic Kidney Uncovers Greater eNOS Phosphorylation and Vasodilation

Chatauret

Coudroy

Delpech

et al. 2014

American Journal of Transplantation

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Protection of endothelial cell function may explain the benefits of nonoxygenated hypothermic machine perfusion (MP) for marginal kidney preservation. However, this hypothesis remains to be tested with a preclinical model. We postulated that MP protects the nitric oxide (NO) signaling pathway, altered by static cold storage (CS), and improves renal circulation recovery compared to CS. The endothelium releases the vasodilator NO in response to flow via either increased endothelial NO synthase (eNOS) expression (KLF2-dependent) or activation of eNOS by phosphorylation (via Akt, PKA or AMPK). Using a porcine model of kidney transplantation, including 1 h of warm ischemia and preserved 24 h by CS or MP (n ¼ 5), we reported that MP did not alter the cortical levels of KLF2 and eNOS at the end of preservation, but significantly increased eNOS activating phosphorylation compared to CS. eNOS phosphorylation appeared AMPK-dependent and was concomitant to an increased NO-dependent vasodilation of renal arteries measured, ex situ, at the end of preservation. In vivo, laser Doppler showed that cortical microcirculation was improved at reperfusion in MP kidneys. In conclusion, we demonstrate for the first time, in a large-animal model, that MP protects the NO signaling pathway, confirming the value of MP for marginal kidney preservation.Abbreviations: Akt, protein kinase B; AMPKa, 5 0 -adenosine monophosphate-activated protein kinase alpha; ANOVA, analysis of variance; CS, cold storage; CTL, control; DCD, donation after circulatory death; eNOS, endothelial nitric oxide synthase; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; iNOS, inducible nitric oxide synthase; KLF2, Kruppel-like factor 2; L19, ribosomal protein L19; L-NAME, NGnitro-L-arginine methyl ester; MP, machine perfusion; MPS, machine perfusion solution; NO, nitric oxide; PKA, protein kinase A; RPLPO, ribosomal phosphoprotein large P0 subunit; RT-qPCR, reverse transcriptase quantitative polymerase chain reaction; SEM, standard error of the mean; UW, University of Wisconsin; WI-60, 1 h warm ischemia

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“…Especially, the combination of 90-min warm ischemia and 18 hr hypothermic preservation herein represents an enormous challenge for the vasculature of the grafts, resulting in reduced vessel elasticity. This might be related particularly to altered vascular smooth muscle cell functions as recently demonstrated in an isolated perfused kidney DCD model (36). In addition, deficiency of nitric oxide (NO), which is reported for DCD lung transplantation (37), leading to pulmonary arteriolar constriction, could have contributed to this effect.…”

Section: Discussionmentioning

confidence: 70%

Targeted Endothelial Delivery of Nanosized Catalase Immunoconjugates Protects Lung Grafts Donated After Cardiac Death

et al. 2011

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Background Donor organ shortage represents a major problem in lung transplantation. Donation after cardiac death could help to expand the pool of organs, but the additional period of warm ischemia after cardiac arrest aggravates primary graft dysfunction. The pulmonary endothelium of the graft constitutes an important source and target of reactive oxygen species generated during ischemia and reperfusion. Targeted protection of graft pulmonary endothelial cells by the antioxidant enzyme catalase, conjugated with a platelet/endothelial cell adhesion molecule-1 (PECAM-1) antibody to nanosized particles (anti-PECAM/catalase conjugates), might improve outcome in lung transplantation using donors after cardiac death and prolonged hypothermic preservation. Methods Left lung transplantation was performed in 18 pigs. Before cardiac arrest, donors received anti-PECAM/ catalase, unconjugated component mixture or vehicle solution. After 90-min warm and 18-hr hypothermic ischemia, lungs were transplanted, and function was assessed during 6 hr after reperfusion. Samples of bronchoalveolar lavage fluid and lung tissue were taken thereafter. Six sham-operated animals served as controls. Results During 6-hr reperfusion, anti-PECAM/catalase significantly ameliorated graft function, evidenced by major improvements of gas exchange and reduced intrapulmonary shunt fraction. Furthermore, lipid peroxidation, alveolar leakage, and edema formation were reduced in protected grafts. Similarly moderate lung pathology was seen after transplantation. Conclusions Augmentation of the antioxidant capacity of graft pulmonary endothelial cells with anti-PECAM/catalase nanoparticles represents a straightforward approach to enable a safe transplantation of prolonged preserved donation after cardiac death lungs. Anti-PECAM/catalase protection alleviated oxidative stress and allowed immediate reconstitution of normal gas exchange and pulmonary microcirculation, a prerequisite for improved graft and patient outcome.

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Deterioration of Endothelial and Smooth Muscle Cell Function in DCD Kidneys After Static Cold Storage in IGL-1 or UW

Cited by 12 publications

References 35 publications

Hydrogen Sulfide-Induced Hypometabolism Prevents Renal Ischemia/Reperfusion Injury

Hydrogen Sulfide-Induced Hypometabolism Prevents Renal Ischemia/Reperfusion Injury

Mechanistic Analysis of Nonoxygenated Hypothermic Machine Perfusion’s Protection on Warm Ischemic Kidney Uncovers Greater eNOS Phosphorylation and Vasodilation

Targeted Endothelial Delivery of Nanosized Catalase Immunoconjugates Protects Lung Grafts Donated After Cardiac Death

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