A Model of Gradual Onset Brain Death for Transplant-Associated Studies in Rats1

Pratschke, Johann; Mj, Wilhelm; Kusaka, Mamoru; Laskowski, Igor; Nl, Tilney

doi:10.1097/00007890-200002150-00020

Cited by 80 publications

(48 citation statements)

References 10 publications

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“…For raising the intracranial pressure gradually, the balloon was inflated with 40 l/min saline until respiration ceased. Using this protocol, previous studies demonstrated brain death by electroencephalogram and magnetic resonance imaging (10). The absence of reflexes, apnea, and maximally dilated and fixed pupils confirmed the condition.…”

Section: Methodsmentioning

confidence: 65%

“…Brain death induction. Brain death was produced by balloon inflation of a Fogarty catheter introduced into the subdural space through an occipital burr hole as previously described (10). Briefly, anesthesia was induced with diethyl ether in all animals and maintained by intraperitoneal administration of pentobarbital (30 mg/kg Nembutal Sodium Solution; Abbott Laboratories, Chicago, IL).…”

Section: Methodsmentioning

confidence: 99%

“…Several studies demonstrated that deterioration of organs follow brain death by multiple interrelated events, including the effect of massive acute cerebral injury, hypotension, and circulating factors. Brain death is characterized by extensive cortical necrosis that stimulates multiple cell types to release proinflammatory cytokines (PICs), such as tumor necrosis factor-␣ (TNF-␣), interleukin (IL)-1␤, IL-6, and interferon-␥ (7)(8)(9)(10)(11)(12). The mRNA expression of these factors also has been demonstrated in peripheral tissues (11).…”

mentioning

confidence: 99%

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Brain Death Significantly Reduces Isolated Pancreatic Islet Yields and Functionality In Vitro and In Vivo After Transplantation in Rats

et al. 2003

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Although ϳ1 million islets exist in the adult human pancreas, current pancreas preservation and islet isolation techniques recover <50%. Presently, cadaveric donors remain the sole source of pancreatic tissue for transplantation. Brain death is characterized by activation of proinflammatory cytokines and organ injury during preservation and reperfusion. In this study, we assessed the effects of brain death on islet isolation yields and functionality. Brain death was induced in male 250-to 350-g Lewis rats by inflation of a Fogarty catheter placed intracranially. The rats were mechanically ventilated for 2, 4, and 6 h before removal of the pancreas (n ‫؍‬ 6). In controls, the catheter was not inflated (n ‫؍‬ 6). Shortly after brain death induction, a significant increase in serum tumor necrosis factor-␣ (TNF-␣), interleukin (IL)-1␤, and IL-6 was demonstrated in a time-dependent manner. Upregulation of TNF-␣, IL-1␤, and IL-6 mRNA was noted in the pancreas. Brain death donors presented lower insulin release after glucose stimulation assessed by in situ perfusion of the pancreas. Islet recovery was reduced in brain death donors compared with controls (at 6 h 602.3 ؎ 233.4 vs. 1,792.5 ؎ 325.4 islet equivalents, respectively; P < 0.05). Islet viability assessed in dissociated islet cells and in intact cultured islets was reduced in islets recovered from brain death donors, an effect associated with higher nuclear activities of NF-B p50, c-Jun, and ATF-2. Islet functionality evaluated in vitro by static incubation and in vivo after intraportal transplantation in syngeneic streptozotocin-induced diabetic rats was significantly reduced in preparations obtained from brain death donors. In conclusion, brain death significantly reduced islet yields and functionality. These observations may lead to strategies to reduce the effects of brain death on pancreatic islets and improve the results in clinical transplantation.

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Section: Methodsmentioning

confidence: 65%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Brain Death Significantly Reduces Isolated Pancreatic Islet Yields and Functionality In Vitro and In Vivo After Transplantation in Rats

et al. 2003

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“…A continuous and prolonged expansion of a supratentorial balloon catheter or intracranial haemorrhage leads to cerebrospinal ischaemia, starting in the cerebrum with a progression to the mesencephalon, pons, medulla oblongata and spinal cord in a rostro-to-caudal fashion (Schrader et al 1985a). Depending on the anatomical structures involved in central ischaemia, haemodynamic changes occur due to the activation or inhibition of the autonomic nervous system (Pratschke et al 2000). In our study, macroscopic evaluation of the position of the balloon catheter showed that it was located between the skull, the tentorium and the occipital lobe.…”

Section: Discussionmentioning

confidence: 99%

The gradual onset brain death model: a relevant model to study organ donation and its consequences on the outcome after transplantation

et al. 2007

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SummaryOrgans used for transplantation are usually derived from heart-beating brain dead donors. However, brain death is known to have negative effects on donor organ quality, previously studied using a difficult to control sudden onset experimental model. We have now developed a reproducible gradual onset brain death model in rats without requiring inotropic support. Fisher inbred rats weighing 260-300 g were used. Brain death was induced by a gradual inflation of a subdurally placed balloon catheter. During induction and the period following brain death, the animals were mechanically ventilated and blood pressure was continuously monitored. The blood pressure registration showed a characteristic pattern during brain death induction, in which a decrease in blood pressure, a hypotensive period in which the Cushing response occurred, and a sharp peak were consistent findings. After brain death was induced, blood pressure was maintained at normotensive levels up to 4 h. After the experiments, neuropathological evaluation of the brain located haemorrhagic cerebral parenchyma, and immunocytochemistry of liver tissue revealed a significant influx of polymorph nuclear cells, as was previously observed as well. This improved model allows the study of brain death on donor organ quality without the use of inotropic support.

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“…The observation that living donor organs show a better outcome than organs from cadaveric donors (1) cannot be fully attributed to shorter cold ischemia time and better immunological conditions, thus indicating that BD can cause relevant pathopysiological changes. This central catastrophe (2) appears to be a primary injury proceeding the secondary effects of ischemia/reperfusion (3). A combination of these effects leads to enhanced immunogenicity, which, after engraftment, can accelerate the recipient's immune response (4).…”

Section: Introductionmentioning

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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A Model of Gradual Onset Brain Death for Transplant-Associated Studies in Rats1

Cited by 80 publications

References 10 publications

Brain Death Significantly Reduces Isolated Pancreatic Islet Yields and Functionality In Vitro and In Vivo After Transplantation in Rats

Brain Death Significantly Reduces Isolated Pancreatic Islet Yields and Functionality In Vitro and In Vivo After Transplantation in Rats

The gradual onset brain death model: a relevant model to study organ donation and its consequences on the outcome after transplantation

Brain Death Impairs Pancreatic Microcirculation

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