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


CONCLUSIONS
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.
Kaudel
C P
CP
Department of Transplant Surgery, Hannover Medical School, Hannover, Germany. kaudel.philipp@mh-hannover.de
Frink
M
M
van Griensven
M
M
Schmiddem
U
U
Probst
C
C
Bergmann
S
S
Krettek
C
C
Klempnauer
J
J
Winkler
M
M
D000818:Animals; D000068876:Fingolimod Hydrochloride; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D011409:Propylene Glycols / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000401:mortality / Q000517:prevention & control*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016019:Survival Analysis; D013997:Time Factors
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine