What can be learned from brain-death models?

Pratschke, Johann; Neuhaus, P.; Tullius, Stefan G.

doi:10.1111/j.1432-2277.2004.00018.x

Cited by 73 publications

(59 citation statements)

References 52 publications

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“…These events are linked to ischemia after organ procurement and upregulation of inflammatory genes occurring as a result of brain death of the donor (25,32). The heparin coating protects the affected cells from the innate immune response of the blood.…”

Section: Discussionmentioning

confidence: 99%

Islet Surface Heparinization Prevents the Instant Blood-Mediated Inflammatory Reaction in Islet Transplantation

et al. 2007

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OBJECTIVE—In clinical islet transplantation, the instant blood-mediated inflammatory reaction (IBMIR) is a major factor contributing to the poor initial engraftment of the islets. This reaction is triggered by tissue factor and monocyte chemoattractant protein (MCP)-1, expressed by the transplanted pancreatic islets when the islets come in contact with blood in the portal vein. All currently identified systemic inhibitors of the IBMIR are associated with a significantly increased risk of bleeding or other side effects. To avoid systemic treatment, the aim of the present study was to render the islet graft blood biocompatible by applying a continuous heparin coating to the islet surface. RESEARCH DESIGN AND METHODS—A biotin/avidin technique was used to conjugate preformed heparin complexes to the surface of pancreatic islets. This endothelial-like coating was achieved by conjugating barely 40 IU heparin per full-size clinical islet transplant. RESULTS—Both in an in vitro loop model and in an allogeneic porcine model of clinical islet transplantation, this heparin coating provided protection against the IBMIR. Culturing heparinized islets for 24 h did not affect insulin release after glucose challenge, and heparin-coated islets cured diabetic mice in a manner similar to untreated islets. CONCLUSIONS—This novel pretreatment procedure prevents intraportal thrombosis and efficiently inhibits the IBMIR without increasing the bleeding risk and, unlike other pretreatment procedures (e.g., gene therapy), without inducing acute or chronic toxicity in the islets.

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Section: Discussionmentioning

confidence: 99%

Islet Surface Heparinization Prevents the Instant Blood-Mediated Inflammatory Reaction in Islet Transplantation

et al. 2007

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“…There is a growing body of evidence to show that non‐allo‐immunological factors including BD and ischemia reperfusion injury (IRI) play a crucial role in impaired short‐ but, even more importantly, in long‐term graft survival rates 7, 8, 9. The occurrence of BD is linked to hemodynamic fluctuations, organ hypoperfusion, hypothermia, coagulopathy, hormone depletion, and electrolyte abnormalities 10. In this context, donor BD has been shown to provoke increased expression of pro‐inflammatory cytokines, endothelial activation, increased expression of MHC class II molecules, infiltration of the donor organ with immune cells, and activation of the complement system 11.…”

Section: Introductionmentioning

confidence: 99%

Treatment With Tetrahydrobiopterin Overcomes Brain Death–Associated Injury in a Murine Model of Pancreas Transplantation

Oberhuber

Ritschl

Fabritius

et al. 2015

American Journal of Transplantation

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Brain death (BD) has been associated with an immunological priming of donor organs and is thought to exacerbate ischemia reperfusion injury (IRI). Recently, we showed that the essential nitric oxide synthase co‐factor tetrahydrobiopterin (BH4) abrogates IRI following experimental pancreas transplantation. We therefore studied the effects of BD in a murine model of syngeneic pancreas transplantation and tested the therapeutic potential of BH4 treatment. Compared with sham‐operated controls, donor BD resulted in intragraft inflammation reflected by induced IL‐1ß, IL‐6, VCAM‐1, and P‐selectin mRNA expression levels and impaired microcirculation after reperfusion (p < 0.05), whereas pretreatment of the BD donor with BH4 significantly improved microcirculation after reperfusion (p < 0.05). Moreover, BD had a devastating impact on cell viability, whereas BH4‐treated grafts showed a significantly higher percentage of viable cells (p < 0.001). Early parenchymal damage in pancreatic grafts was significantly more pronounced in organs from BD donors than from sham or non‐BD donors (p < 0.05), but BH4 pretreatment significantly ameliorated necrotic lesions in BD organs (p < 0.05). Pretreatment of the BD donor with BH4 resulted in significant recipient survival (p < 0.05). Our data provide novel insights into the impact of BD on pancreatic isografts, further demonstrating the potential of donor pretreatment strategies including BH4 for preventing BD‐associated injury after transplantation.

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“…MHC may increase graft immunogenicity via the T-cell recognition process. 58 In the pig, Skrabal et al 49 found an organspecific regulation of proinflammatory molecules in the kidney, heart, and lung following brain death. Of the cytokines and cytokine-related molecules measured, IL-1b and IL-6 increased in all organs whereas TNF-a only increased in lung tissue.…”

Section: Inflammatory and Immunological Aspects Of Brain Deathmentioning

confidence: 99%

“…63 In summary, brain death is associated with the release of proinflammatory substances and inflammatory responses are detected in all organs suitable for transplantation leading to immunologically activated organs before engraftment, resulting in histological damage, decreased function, and lower graft survival compared with organs from living donors. 58,[64][65][66][67][68] …”

Section: Inflammatory and Immunological Aspects Of Brain Deathmentioning

confidence: 99%

Brain death and its implications for management of the potential organ donor

Bugge

2009

Acta Anaesthesiol Scand

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The systemic physiologic changes that occur during and after brain death affect all organs suitable for transplantation. Major changes occur in the cardiovascular, pulmonary, endocrine, and immunological systems, and, if untreated may soon result in cardiovascular collapse and somatic death. Understanding these complex physiologic changes is mandatory for developing effective strategies for donor resuscitation and management in such a way that the functional integrity of potentially transplantable organs is maintained. This review elucidates these physiological changes and their consequences, and based on these consequences the rationale behind current medical management of brain-dead organ donors is discussed.

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What can be learned from brain-death models?

Cited by 73 publications

References 52 publications

Islet Surface Heparinization Prevents the Instant Blood-Mediated Inflammatory Reaction in Islet Transplantation

Islet Surface Heparinization Prevents the Instant Blood-Mediated Inflammatory Reaction in Islet Transplantation

Treatment With Tetrahydrobiopterin Overcomes Brain Death–Associated Injury in a Murine Model of Pancreas Transplantation

Brain death and its implications for management of the potential organ donor

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