Characterization of ischemia/reperfusion injury after pancreas transplantation and reduction by application of monoclonal antibodies against ICAM-1 in the rat.
BACKGROUND
Reperfusion injury contributes to early organ malfunction after transplantation. The aim of this study was to characterize the ischemia-reperfusion injury after pancreas transplantation and to evaluate the effect of monoclonal antibody therapy against ICAM-1.


METHODS
Twenty-five heterotopic pancreas transplantations were performed in syngenic rats in a no-touch technique. Microcirculation and leukocyte-endothelial interaction in the grafts were evaluated by intravital microscopy at 1 hour (I), 6 hours (II), 12 hours (III), and 24 hours (IV) after reperfusion, and 12 hours after reperfusion (V) in the therapeutic group. In (V) antibodies against ICAM-1 were applied as bolus at reperfusion and continuously for 6 hours. Next to intravital microscopy, histologic scores, myeloperoxidase levels, and ICAM-1 expression were determined.


RESULTS
Microcirculation was significantly reduced in capillaries and postcapillary venules in the time course after reperfusion (capillary: 0.96 +/- 0.08 mm/s [I] to 0.45 +/- 0.07 mm/s [IV] [P <.01]) and was improved significantly by therapy with ICAM-1 antibodies (0.98 +/- 0.06 mm/s, (P <.01). Leukocyte-endothelial interaction significantly increased 6 hours after reperfusion (II) (P <.01). These changes were paralleled by an increased endothelial expression of ICAM-1 in immunohistochemistry. Histologic evaluation showed increased inflammation at 12 hours after reperfusion (P <.01), which could be diminished by the administration of ICAM-1 antibodies (P <.05).


CONCLUSIONS
Increased endothelial expression of ICAM-1 after pancreas transplantation is positively correlated with microcirculatory impairment. Important steps of pancreatic inflammation take place approximately 6 hours after reperfusion. Prophylactic application of monoclonal antibodies against ICAM-1 reduces reperfusion injury and successfully prevents the occurrence of graft pancreatitis.
Keck
Tobias
T
Department of General and Digestive Surgery, University of Freiburg, Germany.
Werner
Jen
J
Schneider
Lutz
L
Gebhard
Martha-Maria
MM
Klar
Erns
E
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002448:Cell Adhesion; D006439:Hemodynamics; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology; D008297:Male; D008833:Microcirculation; D010179:Pancreas / Q000378:metabolism; D016035:Pancreas Transplantation / Q000009:adverse effects* / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control / Q000628:therapy
D000911:Antibodies, Monoclonal; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase