title: Impact of inhibition of complement by sCR1 on hepatic microcirculation after warm ischemia.
abstract: Recent observations provide evidence that complement is implicated as an important factor in the pathophysiology of ischemia/reperfusion injury (IRI). Here, we assessed the effects of complement inhibition on hepatic microcirculation by in vivo microscopy (IVM) using a rat model of warm hepatic ischemia clamping the left pedicle for 70 min. Ten animals received the physiological complement regulator soluble complement receptor type 1 (sCR1) intravenously 1 min prior to reperfusion. Controls were given an equal amount of Ringer's solution (n = 10). Microvascular perfusion and leukocyte adhesion were studied 30 to 100 min after reperfusion by IVM. Microvascular perfusion in hepatic sinusoids was significantly improved in the sCR1 group (80.6 +/- 0.6% of all observed sinusoids were perfused [sCR1] vs 67.3 +/- 1.2% [controls]). The number of adherent leukocytes was reduced in sinusoids (49.9 +/- 3.4 [sCR1] vs 312.3 +/- 14.2 in controls [adherent leukocytes per square millimeter of liver surface]; P < 0.001) as well as in postsinusoidal venules after sCR1 treatment (230.9 +/- 21.7 [sCR1] vs 1906.5 +/- 93.5 [controls] [adherent leukocytes per square millimeter of endothelial surface]; P < 0.001). Reflecting reduced hepatocyte injury, liver transaminases were decreased significantly upon sCR1 treatment compared to controls. Our results provide further evidence that complement plays a decisive role in warm hepatic IRI. Therefore, we conclude that complement inhibition by sCR1 is effective as a therapeutical approach to reduce microcirculatory disorders after reperfusion following warm organ ischemia.
authors.affiliation: Department of General Surgery, University of Heidelberg, Im Neuenheimer Feld 110, Heidelberg 69120, Germany.
authors.forename: T G
authors.initials: TG
authors.lastname: Lehmann
authors.forename: T A
authors.initials: TA
authors.lastname: Koeppel
authors.forename: S
authors.initials: S
authors.lastname: Münch
authors.forename: M
authors.initials: M
authors.lastname: Heger
authors.forename: M
authors.initials: M
authors.lastname: Kirschfink
authors.forename: E
authors.initials: E
authors.lastname: Klar
authors.forename: S
authors.initials: S
authors.lastname: Post
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D003174:Complement C1 Inactivator Proteins / Q000494:pharmacology*; D003173:Complement C1s / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D006439:Hemodynamics; D007275:Injections, Intravenous; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D017078:Laser-Doppler Flowmetry / Q000295:instrumentation; D007962:Leukocytes / Q000502:physiology; D008102:Liver Circulation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects* / Q000503:physiopathology; D008856:Microscopy, Fluorescence; D051381:Rats; D017208:Rats, Wistar; D011951:Receptors, Complement / Q000008:administration & dosage / Q000502:physiology*; D015427:Reperfusion Injury / Q000503:physiopathology*; D013696:Temperature; D013997:Time Factors; D014699:Venules / Q000503:physiopathology; D014741:Video Recording
chemical_list: D003174:Complement C1 Inactivator Proteins; D011951:Receptors, Complement; C082885:soluble complement inhibitor 1; D003173:Complement C1s