Soluble complement receptor 1 preserves endothelial barrier function and microcirculation in postischemic pancreatitis in the rat.
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 vehicle-treated 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.
von Dobschuetz
E
E
Dept. of General and Visceral Surgery, Albert Ludwigs Univ., Hugstetter Str. 55, 79106 Freiburg, Germany. ernst@von-dobschuetz.de
Bleiziffer
O
O
Pahernik
S
S
Dellian
M
M
Hoffmann
T
T
Messmer
K
K
D000818:Animals; D002196:Capillaries / Q000473:pathology; D002199:Capillary Permeability; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006439:Hemodynamics; D006461:Hemolysis; D007511:Ischemia / Q000150:complications*; D007962:Leukocytes; D008297:Male; D008833:Microcirculation; D010179:Pancreas / Q000098:blood supply*; D010195:Pancreatitis / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011951:Receptors, Complement / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility
D011951:Receptors, Complement