Ciclosporin aggravates tissue damage in ischemia reperfusion-induced acute pancreatitis.
OBJECTIVE
Ischemia reperfusion (I/R)-associated early graft pancreatitis is a major complication after pancreas transplantation. The influence of immunosuppressants on graft pancreatitis remains unclear. The aim of this study was to evaluate ciclosporin and tacrolimus in experimental pancreatic I/R.


METHODS
Moderate pancreatitis was induced in rats by I/R injury. Animals were assigned to 4 groups: (1) control without I/R, (2) I/R without therapy, (3) I/R + ciclosporin, or (4) I/R + tacrolimus. After 24 hours, pancreatic damage was evaluated by amylase, endothelin 1, thromboxane A2, and histology. Additionally, microcirculation was evaluated 12 hours after reperfusion by intravital microscopy.


RESULTS
I/R significantly increased amylase compared with controls, with maximum levels after ciclosporin treatment. Histology showed comparable tissue injury in control and tacrolimus-treated animals. Ciclosporin-treated animals developed significantly (P < 0.05) more inflammation and necrosis compared with the other groups. Erythrocyte velocity evaluated by intravital microscopy was reduced in all animals after I/R. This was significantly pronounced after ciclosporin application. There was a significant increase of adherent leukocytes and platelets in ciclosporin-treated animals compared with both other groups.


CONCLUSIONS
Tacrolimus does not negatively influence I/R-induced pancreatitis, whereas ciclosporin aggravates pancreatic tissue damage after I/R. These effects should be evaluated in the clinical setting of pancreas transplantation.
Department of Surgery, University of Heidelberg, Heidelberg, Germany. Thilo_Hackert@med.uni-heidelberg.de
Thilo
T
Hackert
Dagmar
D
Pfeil
Werner
W
Hartwig
Stefan
S
Fritz
Martha-Maria
MM
Gebhard
Ernst
E
Klar
Jens
J
Werner
D000208:Acute Disease; D000818:Animals; D001794:Blood Pressure; D016572:Cyclosporine / Q000009:adverse effects*; D004195:Disease Models, Animal; D006339:Heart Rate; D007166:Immunosuppressive Agents / Q000009:adverse effects; D010179:Pancreas / Q000098:blood supply; D016035:Pancreas Transplantation; D010195:Pancreatitis / Q000473:pathology* / Q000601:surgery; D051381:Rats; D015427:Reperfusion Injury / Q000473:pathology*; D016559:Tacrolimus / Q000009:adverse effects
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus