TY - JOUR
T1 - FTY720 Application Following Isolated Warm Liver Ischemia Improves Long-Term Survival and Organ Protection in a Mouse Model
AU - Kaudel, C. P.
AU - Frink, M.
AU - van Griensven, M.
AU - Schmiddem, U.
AU - Probst, C.
AU - Bergmann, S.
AU - Krettek, C.
AU - Klempnauer, J.
AU - Winkler, M.
PY - 2007/3
Y1 - 2007/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33847712567&partnerID=8YFLogxK
U2 - 10.1016/j.transproceed.2007.01.021
DO - 10.1016/j.transproceed.2007.01.021
M3 - Article
C2 - 17362766
AN - SCOPUS:33847712567
SN - 0041-1345
VL - 39
SP - 493
EP - 498
JO - Transplantation Proceedings
JF - Transplantation Proceedings
IS - 2
ER -