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INFLAMMATION/IMMUNITY/MEDIATORS
1Department of General and Visceral Surgery, Albert Ludwigs University, 79106 Freiburg; 2Institute for Surgical Research, Ludwig Maximilians University, 81366 Munich; 3Department of Urology, University of Mainz, 55101 Mainz; 4Department of Otorhinolaryngology, Ludwig Maximilians University, 81377 Munich, Germany; and 5Maria Theresia Klinik, 80336 Munich, Germany
Submitted 17 September 2003 ; accepted in final form 18 December 2003
Components of the activated complement cascade are considered to play a pivotal role in ischemia-reperfusion-induced organ injury. With the use of intravital epifluorescence microscopy, we investigated the effect of complement inhibition by the recombinant soluble complement receptor 1 (sCR1; TP10) on the effect of macromolecular microvascular permeability, functional capillary perfusion, and leukocyte endothelium interaction in postischemic pancreatitis. Anaesthetized Sprague-Dawley rats were subjected to 60 min of normothermic pancreatic ischemia induced by microclipping of the blood-supplying arteries of the organ. Rats who received sCR1 (15 mg/kg body wt iv; n = 7) during reperfusion showed a significant reduction of permeability (1.77 ± 1.34 x 10-8 cm/s; n = 7) of tetramethylrhodamine isothiocyanate-labeled albumin injected 90 min after the onset of reperfusion compared with vehicletreated animals (6.95 ± 1.56 x 10-8 cm/s; n = 7). At 120 min after the onset of reperfusion, the length of red blood cell-perfused capillaries (functional capillary density) was significantly improved (from 279 ± 15.7 to 330 ± 3.7 cm-1; n = 7) and the number of leukocytes adherent to postcapillary venules was significantly reduced (from 314 ± 87 to 163 ± 71 mm-2; n = 7) by sCR1 compared with vehicle treatment. Complement inhibition by sCR1 effectively ameliorates pancreatic ischemia-reperfusion-induced microcirculatory disturbances and might be considered for treatment of postischemic pancreatitis.
permeability; ischemia; reperfusion; acute pancreatitis; transplantation
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