In vivo microscopy reveals that complement inhibition by C1-esterase inhibitor reduces ischemia/reperfusion injury in the liver.
Complement plays a decisive role in postischemic tissue injury, a process responsible for severe damage after organ ischemia. Several pathophysiologic mechanisms initiated upon reperfusion are mediated by complement inducing microcirculatory disturbances. Here, we demonstrate the effects of complement inhibition using C1-esterase inhibitor (C1-INH) on microcirculation after liver ischemia by in vivo microscopy (IVM). In rats, the left liver lobe was clamped for 70 min. C1-INH was given 1 min prior to reperfusion. Controls received Ringer's solution. IVM was performed 30-100 min after reperfusion. Non-perfused acini decreased and sinusoidal perfusion increased substantially after treatment. Leukocyte adherence to sinusoidal and venular endothelium was markedly reduced by C1-INH. Transaminases were significantly decreased by C1-INH. Our data obtained by IVM suggest that complement activation is an early key event of ischemia/reperfusion injury. These observations demonstrate for the first time that reperfusion related microcirculatory disorders can be minimized by C1-INH. This compound should be evaluated in clinical application.
Lehmann
T G
TG
Department of General Surgery, University of Heidelberg, Germany.
Heger
M
M
Münch
S
S
Kirschfink
M
M
Klar
E
E
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D003174:Complement C1 Inactivator Proteins / Q000494:pharmacology*; D003173:Complement C1s / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology; D007962:Leukocytes / Q000502:physiology; D008099:Liver / Q000098:blood supply*; D008102:Liver Circulation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D014699:Venules / Q000502:physiology
D003174:Complement C1 Inactivator Proteins; D003173:Complement C1s