FTY720 application following isolated warm liver ischemia improves long-term survival and organ protection in a mouse model.

Abstract

BACKGROUND Ischemia-reperfusion-Injury (I/RI) is a common complication in transplant-, liver-, and heart surgery. The I/RI is mediated and aggravated by different types of leukocytes such as lymphocytes, monocytes, and neutrophil granulocytes, with consecutive enlargement of the expression of adhesion molecules. This study shows an organ-protective effect of an intraoperative FTY720 administration following warm liver ischemia (Pringle's maneuver). METHODS Male c57BL6/J mice (n = 46, body weight [BW] 25 to 30 g) were used. Either FTY720 (1 mg/kg BW), steroids (5 mg/kg BW), or physiological saline solution was administered intraperitoneally. Liver-ischemia was applied for 30 minutes with subsequent follow-up for 48 hours. At termination, all surviving animals were sacrificed. The impact of the drugs administered on long-term survival, time of death, and development of blood T-lymphocyte concentration was determined. Follow-up of T-lymphocyte concentration in peripheral blood was examined throughout FACS-analysis. RESULTS Following 30 minutes of ischemia, FTY720, but not steroid or vehicle treatment, showed a significant protective effect on long-term survival. FACS-analysis showed significant T-lymphocyte depletion in peripheral blood following FTY720 but not steroids or vehicle treatment. CONCLUSION The improved long-term survival following FTY720 application shown in this study might be due to a protective effect of FTY720 in prevention of I/RI. This might be mediated by the T-lymphocyte depletion shown in the FACS-analysis.

Cite this paper

@article{Kaudel2007FTY720AF, title={FTY720 application following isolated warm liver ischemia improves long-term survival and organ protection in a mouse model.}, author={Christian P. Kaudel and Michael Frink and Martijn van Griensven and Uli Schmiddem and Ch Probst and Sigrid Bergmann and Ch Krettek and Jurgen L Klempnauer and Monica E Winkler}, journal={Transplantation proceedings}, year={2007}, volume={39 2}, pages={493-8} }