Octreotide Attenuates Impaired Microcirculation in Postischemic Pancreatitis When Administered Before Induction of Ischemia

Abstract

Ischemia-reperfusion injury of the pancreas causes impairment of microcirculation leading to pancreatitis. Postischemic pancreatitis is the most common reason for graft failure in pancreas transplantation. In animal models, octreotide has been described to have beneficial effects on acute pancreatitis by reducing pancreatic enzyme release and edema formation by preventing the increase of macromolecular extravasation. In contrast to earlier experimental setups, this study investigated the influence of octreotide on ischemia-reperfusion pancreatitis when administered before induction of ischemia. Sprague-Dawley rats were randomly assigned to three groups: (1) sham-operated animals (sham group, n=7); (2) 1 hr ischemia followed by 1 hr reperfusion (control group, n=7); (3) administration of 50 microg/kg octreotide intravenously 15 min before ischemia (octreotide group, n=7). At the end of reperfusion, intravital fluorescence microscopy was performed assessing the functional capillary density (FCD), leukocyte-endothelium interaction (LEI), and the microvascular permeability. Finally serum amylase and lipase were measured. The application of octreotide significantly reduced the ischemia-reperfusion-induced reduction of FCD (318.4+/-44.1 cm/cm vs. 257.4+/-11.7 cm/cm, P<0.001). The increase of LEI due to ischemia-reperfusion (466.9+/-52.2 cells/mm) was reduced in the octreotide group (264.4+/-55.1, P=0.001). Permeability was significantly lower in the octreotide group (0.56+/-0.57x10 cm/sec vs. 2.2.1+/-0.54x10 cm/sec, P<0.001). The level of serum lipase was reduced significantly after octreotide therapy (72.4+/-53.4 U/L vs. 136.7+/-66.5 U/L, P=0.026). Octreotide significantly attenuated pancreatic dysfunction caused by ischemia-reperfusion when given before ischemia. Furthermore, we could prove for the first time a beneficial role of octreotide on preservation of the microvascular barrier for macromolecules.