Multiorgan procurement increases systemic inflammation in brain dead donors

Auråen, Henrik; Mollnes, Tom Eirik; Bjørtuft, Øystein; Bakkan, Per Arne; Geiran, Odd; Kongerud, Johny; Fiane, Arnt E.; Holm, Are Martin

doi:10.1111/ctr.12175

Cited by 18 publications

(11 citation statements)

References 23 publications

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“…Many studies have argued that the poor outcomes organs following brain death were mainly associated with hemodynamic alterations (21,22), the release of inflammatory cytokines (23–25), consumption of coagulation factors (26,27) and endocrine and hormonal changes (28–30). However, the molecular mechanism underlying how the status of brain death organs influences the transplantation outcomes remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of differentially expressed proteins in kidneys of brain dead rabbits

et al. 2017

Molecular Medicine Reports

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A large number of previous clinical studies have reported a delayed graft function for brain dead donors, when compared with living relatives or cadaveric organ transplantations. However, there is no accurate method for the quality evaluation of kidneys from brain-dead donors. In the present study, two-dimensional gel electrophoresis and MALDI-TOF MS-based comparative proteomic analysis were conducted to profile the differentially-expressed proteins between brain death and the control group renal tissues. A total of 40 age- and sex-matched rabbits were randomly divided into donation following brain death (DBD) and control groups. Following the induction of brain death via intracranial progressive pressure, the renal function and the morphological alterations were measured 2, 6 and 8 h afterwards. The differentially expressed proteins were detected from renal histological evidence at 6 h following brain death. Although 904±19 protein spots in control groups and 916±25 in DBD groups were identified in the two-dimensional gel electrophoresis, >2-fold alterations were identified by MALDI-TOF MS and searched by NCBI database. The authors successfully acquired five downregulated proteins, these were: Prohibitin (isoform CRA_b), beta-1,3-N-acetylgalactosaminyltransferase 1, Annexin A5, superoxide dismutase (mitochondrial) and cytochrome b-c1 complex subunit 1 (mitochondrial precursor). Conversely, the other five upregulated proteins were: PRP38 pre-mRNA processing factor 38 (yeast) domain containing A, calcineurin subunit B type 1, V-type proton ATPase subunit G 1, NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 and peroxiredoxin-3 (mitochondrial). Immunohistochemical results revealed that the expressions of prohibitin (PHB) were gradually increased in a time-dependent manner. The results indicated that there were alterations in levels of several proteins in the kidneys of those with brain death, even if the primary function and the morphological changes were not obvious. PHB may therefore be a novel biomarker for primary quality evaluation of kidneys from brain-dead donors.

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Section: Discussionmentioning

confidence: 99%

Proteomic analysis of differentially expressed proteins in kidneys of brain dead rabbits

et al. 2017

Molecular Medicine Reports

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“…All analyses will be performed at a central laboratory in Oslo, Norway. Standard inflammatory cytokines/chemokines and complement activation will be measured as previously described [18].…”

Section: • Measurements Of Inflammatory Variablesmentioning

confidence: 99%

Design and Rationale of a Scandinavian Multicenter Randomized Study Evaluating if Once-Daily Tacrolimus Versus Twice-Daily Cyclosporine Reduces the 3-year Incidence of Chronic Lung Allograft Dysfunction After Lung Transplantation (ScanCLAD Study)

et al. 2020

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Background:A low level of evidence exists regarding the choice of calcineurin inhibitor (CNI) for immunosuppression after lung transplantation (LTx). Therefore, we designed a randomized clinical trial according to good clinical practice rules to compare tacrolimus with cyclosporine after LTx. Methods: The ScanCLAD study is an investigator-initiated, pragmatic, controlled, randomized, open-label, multicenter study evaluating if an immunosuppressive protocol based on anti-thymocyte globulin (ATG) induction, once-daily tacrolimus dose, mycophenolate mofetil, and corticosteroid reduces the incidence of chronic lung allograft dysfunction (CLAD) after LTx, compared to a cyclosporine-based protocol with all other immunosuppressive and prophylactic drugs being identical between groups. All patients will be followed for 3 years to determine the main endpoint of CLAD. The study is designed for superiority, and power calculations show that 242 patients are needed. Also, the study is designed with more than 10 substudies addressing other important and unresolved issues in LTx. In addition, the ScanCLAD study enabled the synchronization of the treatment and follow-up protocols of the lung transplantation programs of all five Scandinavian lung transplantation centers.

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“…Organs for solid organ transplantation are mostly procured from brain dead donors [9]. By definition, "brain dead" means that the donor has irreversible loss of brain functions [10].…”

Section: Medical Implicationsmentioning

confidence: 99%

Gene expression in the twilight of death

Pozhitkov

Noble

2017

BioEssays

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After a vertebrate dies, many of its organ systems, tissues, and cells remain functional while its body no longer works as a whole. We define this state as the "twilight of death" - the transition from a living body to a decomposed corpse. We claim that the study of the twilight of death is important to ethical, legal and medical science. We examined gene expression at the twilight of death in the zebrafish and mouse reaching the conclusion that apparently thousands of transcripts significantly increase in abundance from life to several hours/days postmortem relative to live controls. Transcript dynamics of different genes provided "proof-of-principle" that models accurately predict an individual's elapsed-time-of-death (i.e. postmortem interval). While many transcripts were associated with survival and stress compensation, others were associated with epigenetic factors, developmental control, and cancer. Future studies are needed to determine whether the high incidence of cancer in transplant recipients is due to the postmortem processes in donor organs.

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Multiorgan procurement increases systemic inflammation in brain dead donors

Cited by 18 publications

References 23 publications

Proteomic analysis of differentially expressed proteins in kidneys of brain dead rabbits

Proteomic analysis of differentially expressed proteins in kidneys of brain dead rabbits

Design and Rationale of a Scandinavian Multicenter Randomized Study Evaluating if Once-Daily Tacrolimus Versus Twice-Daily Cyclosporine Reduces the 3-year Incidence of Chronic Lung Allograft Dysfunction After Lung Transplantation (ScanCLAD Study)

Gene expression in the twilight of death

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