Effects of Explosive Brain Death on Cytokine Activation of Peripheral Organs in the Rat1

Takada, Moriatsu; Nadeau, Kari; Hancock, Wayne W.; Mackenzie, Harald S.; Shaw, Gray D.; Waaga, Ana Marie; Chandraker, Anil; Sayegh, Mohamed H.; Tilney, Nicholas L.

doi:10.1097/00007890-199806270-00001

Cited by 384 publications

(284 citation statements)

References 34 publications

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“…Experimentally, kidneys and hearts transplanted from BD animals show accelerated acute rejection in comparison to grafts from living donors (2). This is thought to be triggered by an increased release of proinflammatory cytokines (2,5,31), an up-regulation of major histocompatibility complex (MHC/HLA class I and II) antigens and co-stimulating B7 in peripheral organs (5,32).…”

Section: Discussionmentioning

confidence: 99%

Brain Death Impairs Pancreatic Microcirculation

Obermaier

Dobschuetz

Keck

et al. 2004

American Journal of Transplantation

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Brain death (BD) influences the quality of donor grafts in transplantation. To evaluate the impact of BD on pancreas grafts, we investigated the influence of BD on the microcirculation and histology of the pancreas in a rat model of explosive BD. A group of Wistar rats (n = = 7), rendered brain dead by inflating an intracranially inserted Fogarty catheter was compared with controls (CO) using intravital epifluorescence-microscopy over 4 h after BD induction; functional capillary density (FCD), leukocyte adherence (AL) in post-capillary venules, histology and pancreatic enzymes were investigated. Four hours after BD, FCD decreased (333 ± 11 vs. baseline 444 cm/cm 2 ± 5 SEM; p < 0.01) and showed lower values than CO (388 ± 9 p < 0.01). In BD, AL was increased (628 cells/mm 2 ± 110 SEM vs. baseline 123 ± 32, and vs. CO 180 ± 33; p < 0.001). BD caused increased histological damage (CO 1.6 scorepoints ± 0.7 SD vs. BD 8.3 ± 7.1; p < 0.05). Amylase was higher in BD (p < 0.05) but did not reach pathological values. We show for the first time that BD causes relevant changes in pancreatic microcirculation, histology and leukocyte endothelial interaction which might have a serious impact on the function of grafts. New strategies for preventing this damage are therefore highly desirable in order to improve the outcome of pancreas transplantation.

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Section: Discussionmentioning

confidence: 99%

Brain Death Impairs Pancreatic Microcirculation

Obermaier

Dobschuetz

Keck

et al. 2004

American Journal of Transplantation

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“…Following brain death, a systemic inflammatory response known as a "cytokine storm" transpires. Increased proinflammatory cytokines have been found in organs following brain death in rodent models (Takada et al 1998) and in brain-dead patients (Lopau et al 2000), and lung injury similar to acute respiratory distress syndrome (ARDS) can occur as a result of this systemic inflammation following brain death. A second "storm" that occurs following brain death is the catecholamine storm.…”

Section: Donor Lung Injurymentioning

confidence: 99%

Overview of Clinical Lung Transplantation

Yeung

Keshavjee

2014

Cold Spring Harbor Perspectives in Medicine

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Since the first successful lung transplant 30 years ago, lung transplantation has rapidly become an established standard of care to treat end-stage lung disease in selected patients. Advances in lung preservation, surgical technique, and immunosuppression regimens have resulted in the routine performance of lung transplantation around the world for an increasing number of patients, with wider indications. Despite this, donor shortages and chronic lung allograft dysfunction continue to prevent lung transplantation from reaching its full potential. With research into the underlying mechanisms of acute and chronic lung graft dysfunction and advances in personalized diagnostic and therapeutic approaches to both the donor lung and the lung transplant recipient, there is increasing confidence that we will improve short-and long-term outcomes in the near future.

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“…This is especially true in the context of lung transplantation, where the lung represents a primary barrier to the external environment and is equipped with a sophisticated immune compartment. In severe cases of injury and inflammation such as brain or cardiac death, a robust systemic immune response ensues (5), which includes pulmonary inflammation manifesting in a local cytokine storm (6) and mass cellular infiltrates (5). Using current strategies for transplantation, it is here that inflamed donor lungs with a globally activated immune system are transplanted into the recipient.…”

Section: Introductionmentioning

confidence: 99%

Altered Immunogenicity of Donor Lungs via Removal of Passenger Leukocytes Using Ex Vivo Lung Perfusion

Stone

Critchley

Major

et al. 2016

American Journal of Transplantation

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Passenger leukocyte transfer from the donor lung to the recipient is intrinsically involved in acute rejection. Direct presentation of alloantigen expressed on donor leukocytes is recognized by recipient T cells, promoting acute cellular rejection. We utilized ex vivo lung perfusion (EVLP) to study passenger leukocyte migration from donor lungs into the recipient and to evaluate the effects of donor leukocyte depletion prior to transplantation. For this purpose, female pigs received male left lungs either following 3 h of EVLP or retrieved using standard protocols. Recipients were monitored for 24 h and sequential samples were collected. EVLPreduced donor leukocyte transfer into the recipient and migration to recipient lymph nodes was markedly reduced. Recipient T cell infiltration of the donor lung was significantly diminished via EVLP. Donor leukocyte removal during EVLP reduces direct allorecognition and T cell priming, diminishing recipient T cell infiltration, the hallmark of acute rejection.

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Effects of Explosive Brain Death on Cytokine Activation of Peripheral Organs in the Rat1

Cited by 384 publications

References 34 publications

Brain Death Impairs Pancreatic Microcirculation

Brain Death Impairs Pancreatic Microcirculation

Overview of Clinical Lung Transplantation

Altered Immunogenicity of Donor Lungs via Removal of Passenger Leukocytes Using Ex Vivo Lung Perfusion

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