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Introduction: In pancreatic ischemia/reperfusion (IR) injury (IRI) the role of nitric oxide (NO) is not completely understood. Using a rat model of normothermic in situ IRI, the effect of endogenous and exogenous NO donors on post-ischemic tissue oxygenation and tissue damage was investigated., Methods: IR was induced by 2-hour normothermic in situ ischemia of a pancreatic tail segment pedunculated on the splenic vessels with 2 h of reperfusion in an untreated, an L-arginine- and a sodium-nitroprusside-treated group (Wistar rats, n = 7/group). Animals without ischemia served as controls. Tissue oxygenation (pO(2ti)) was monitored using a pO2-sensitive Clark-type electrode. Histological investigation was performed following a semiquantitative score (edema, vacuolization, PMN infiltration, necrosis). Plasma lipase was another marker of organ damage., Results: The administration of L-arginine and sodium nitroprusside caused a significant amelioration of the decrease in pO2i) after reperfusion compared to IR animals (p < 0.05). Histological damage was also reduced in the NO donor groups (p < 0.05). After reperfusion, plasma lipase in the L-arginine-treated animals was significantly lower compared to IR and sodium nitroprusside (p < 0.05)., Conclusions: The administration of both endogenous and exogenous NO donors is protective in IRI of the rat pancreas which can be seen by an improvement in post-ischemic tissue oxygenation which indicates better nutritive tissue perfusion, amelioration of the histological tissue injury and, in L-arginine animals, lower lipase levels. NO donors could be useful in the prevention and reduction of the pancreatic IRI., (Copyright 2004 S. Karger AG, Basel)

Ischemia/reperfusion injury plays an important role in the development of graft pancreatitis and thrombosis after pancreas transplantation. Up to now there are few therapeutic options for this severe complication because very little is known about pancreatic ischemia/reperfusion injury. The same pathomechanisms may also be involved in the induction and determination of the course of acute pancreatitis. We observed the effect of 2 h of warm in situ ischemia on the postischemic tissue oxygenation, histological organ damage, and pancreatic enzymes. Experiments were performed in 21 male Wistar rats. In sham-operated animals without ischemia, the pancreas was not dissected. In the ischemia/reperfusion group a pancreatic tail-segment was carefully separated from the head, and ischemia was induced by clamping the splenic vessels for 2 h, after flushing the pancreatic tail-segment with heparinized saline. Animals treated similarly, but with opening of the clamps some seconds after induction of ischemia, served as controls. The animals were observed for 2 h after reperfusion. Tissue oxygenation was monitored by a PO2-sensitive probe (LICOX, GMS, Kiel, Germany) which was implanted into the pancreatic tissue. Blood samples were taken before, 5 min, 60 min, and 120 min after reperfusion. At the end of the experiment the pancreatic tail was excised for histological examination; biopsies froin the non-ischemic pancreatic head served as intraindividual control to exclude side effects on the nonischemic pancreatic head. In the ischemia/reperfusion group, PO2ti was significantly lower 1 h (18.0+/-1.7 mmHg) and 2 h (16.4+/-1.6 mmHg) after reperfusion compared with baseline conditions (32.8+/-5.2 mmHg) and the control group (1 h 30.6+/-1.9 mmHg, 2 h 32.4+/-2.4 mmHg). Histological injury score and plasma lipase activity were significantly higher in the ischemia/reperfusion group compared with the control group. Thus we describe a new experimental model of complete normothermic in situ ischemia of a pancreatic tail-segment with the possibility of flushing the pancreatic tail-segment and selective local application of drugs to the pancreas.