Sirolimus Improves Early Microcirculation, but Impairs Regeneration After Pancreatic Ischemia-Reperfusion Injury

Abstract

Ischemia and reperfusion injury remains a relevant problem in clinical pancreas transplantation. We investigated the effect of sirolimus (SRL) in a rodent model of 90-min warm pancreatic ischemia. Four groups were studied: (1) sham surgery and vehicle; (2) sham surgery and SRL; (3) warm ischemia and vehicle; (4) warm ischemia and SRL. SRL (1.5 mg/kg/day) and vehicle were administered intraperitoneally for 3 days prior to surgery until the animals were killed. Microcirculation was assessed immediately after reperfusion by means of intravital fluorescence microscopy. Histopathological injury, apoptosis, proliferation and biochemical parameters were analyzed at 2 h, 1 day and 5 days after surgery. Ninety minutes after ischemia, intravital microscopy revealed an improved functional capillary density (p < 0.05) and reduction of adherent leucocytes (p < 0.01) and platelets (p < 0.05) in the SRL-treated group compared to the vehicle-treated controls. In contrast, on day 5 after ischemia, the pancreatic tissue of SRL-treated animals showed a higher grade of histological injury (p < 0.05) and higher rate of apoptotic cells (p < 0.05) than the vehicle controls. In summary, our data indicate that administration of SRL improves microcirculation at a very early stage, but results in an impairment of the recovery phase after pancreatic ischemia-reperfusion injury.