C1-inhibitor reduces the ischaemia-reperfusion injury of skeletal muscles in mice after aortic cross-clamping.
BACKGROUND
Both C1-inhibitor (C1-INH) and antibodies against the CD18 adhesion molecule have been shown to reduce ischaemia-reperfusion injuries. The objective of this study was to investigate the effect of increased ischaemia times and to determine whether inhibiting C1 or blocking the CD18 function was protective in skeletal muscle ischaemia-reperfusion injury after aortic cross-clamping.


METHODS
BALB/c mice were subjected to aortic cross-clamping below the renal artery for 60, 75 or 105 min, followed by 3 h of reperfusion. Two-thirds of a total dose of anti-CD18 antibody (40 mg/kg) or human C1-INH (1,000 IU/kg) was given by intraperitoneal injection before ischaemia and one-third immediately after the clamping. Creatine kinase (CK) in the plasma was used as an indicator of muscle injury severity.


RESULTS
There was a consistent rise in the plasma CK concentration proportional to the length of ischaemia (P < 0.0005). C1-INH treatment significantly (P = 0.012) reduced the plasma CK for the ischaemia times of 75 and 105 min. The anti-CD18 antibody did not have any effect, as demonstrated by the CK values that were similar to controls (P = 0.836).


CONCLUSIONS
The data support a beneficial role for C1-INH in the treatment of ischaemia-reperfusion injuries of skeletal muscles.
Nielsen
E W
EW
University of Tromsø and Nordland Hospital, Bodø, Norway. erikwn@fagmed.uit.no
Mollnes
T E
TE
Harlan
J M
JM
Winn
R K
RK
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001011:Aorta; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018821:CD18 Antigens / Q000276:immunology; D003174:Complement C1 Inactivator Proteins / Q000627:therapeutic use*; D050718:Complement C1 Inhibitor Protein; D003250:Constriction; D003402:Creatine Kinase / Q000097:blood; D005260:Female; D007700:Kinetics; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal; D015427:Reperfusion Injury / Q000097:blood / Q000628:therapy*
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D003402:Creatine Kinase