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C Schnurr

Publications and source records attributed to C Schnurr.

5 recordsLinked to original sources
PubMedDate not supplied

Reduced liver apoptosis after venous systemic oxygen persufflation in non-heart-beating donors.

Graft injury caused by warm ischemia in livers from non-heart-beating donors (NHBDs) strongly affects posttransplantation outcome and is associated with liver apoptosis, which is mediated by death receptors, such as Fas, a surface receptor of the tumor necrosis factor (TNF)-alpha family. The aim of this study was to test the ability of venous systemic oxygen persufflation (VSOP) to reduce apoptotic changes and Fas activation in the liver after warm ischemic insult in vivo. Livers of male Wistar rats were harvested 30 min after cardiac arrest from non-heart-beating donors (NHBD) with (NHBD + O2) or without (NHBD) application of gaseous oxygen during the cold storage period via the suprahepatic caval vein. After 24 h of storage in University of Wisconsin solution at 4 degrees C, viability of the livers was assessed upon isolated reperfusion in vitro. Conventional signs of tissue damage like enzyme release and bile production showed a significantly elevated nonspecific cell injury in the NHBD group. TUNEL staining revealed increased DNA fragmentation of sinusoidal endothelial cells in the NHBD group and more apoptotic hepatocytes than in the control group. All these alterations could be almost abrogated by the use of VSOP in the NHBD + O2 group. The immunohistochemical staining of Fas antigen expression showed a significantly elevated Fas receptor expression in the NHBD and NHBD + O2 groups, in accord with an eightfold increase of Fas receptor mRNA detected by real-time reverse-transcription polymerase chain reaction (RT-PCR). These results demonstrate that the postischemic apoptotic rate of sinusoidal endothelial cells in NHBD livers can be reduced by the use of VSOP. A significant improvement in liver integrity and viability was obtained with this technique, without influencing the expression of Fas expression.

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PubMedDate not supplied

Fas receptor is upregulated in livers from non-heart-beating donors.

Cell injury in livers from non-heart-beating donors (NHBDs) is not only caused by necrosis, but it is increasingly being recognized that apoptotic transformation contributes to postischemic cell death. It remains unclear which pathways lead to apoptosis. We suggested that apoptosis in NHBD livers might be mediated by the Fas receptor. Therefore the aim of our study was the detection and quantification of the Fas receptor, Fas mRNA and apoptosis in NHBD livers. Livers of male Wistar rats were harvested either from heart-beating donors (control, n = 15) or 30 min after cardiac arrest from NHBDs (n = 15). All livers were stored in University of Wisconsin solution for 24 h at 4 degrees C, and reperfused using a recirculating model with oxygenated Krebs-Henseleit buffer for 120 min at 37 degrees C. Conventional signs of cell damage, such as enzyme release and bile production, showed an elevated nonspecific cell injury in NHBD livers. The immunohistochemical staining of Fas antigen expression revealed a 7% rate of Fas receptor-expressing hepatocytes in the control group, but a considerable increase up to 38% in the NHBD group. No Fas antigen expression was detected on sinusoidal endothelial cells. Real-time RT-PCR detected an approximately eightfold elevated concentration of Fas mRNA transcripts in NHBD livers. We conclude that upregulation of the Fas receptor on hepatocytes in NHBDs will prime these cells to eventually undergo apoptosis upon reperfusion in vivo. Therefore, therapeutic modulation of the Fas pathway must be considered as a new strategy in order to additionally protect NHBD livers which are otherwise prone to parenchymal apoptosis.

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