Blockade of complement activation prevents local and pulmonary albumin leak after lower torso ischemia-reperfusion.
Lower torso ischemia and reperfusion leads to both local and remote tissue injuries. The purpose of this study was to assess the role of complement in mediating the local and remote microvascular permeability after bilateral hind limb tourniquet ischemia. Four hours of ischemia and 4 hours of reperfusion produced an increased skeletal muscle permeability index (muscle/blood 125I albumin ratio) of 2.90 +/- 0.35 compared with the index in nonischemic muscle of 0.25 +/- 0.02 (p < 0.01). Muscle wet-to-dry-weight ratio increased from 3.93 +/- 0.04 in sham to 5.55 +/- 0.09 in ischemic muscle (p < 0.0001). Lung permeability rose at 4 hours as indicated by the increased bronchoalveolar lavage (BAL)/blood 125I albumin ratio 4.36 +/- 0.41 x 10(-3) versus sham 2.64 +/- 0.28 x 10(-3) (p < 0.05) and neutrophil sequestration 0.28 +/- 0.02 U/g myeloperoxidase (MPO) versus sham 0.14 +/- 0.02 U/g (p < 0.001). Serum lytic activity of the classical but not the alternate complement pathway was reduced. The soluble complement receptor (sCR1) was used to inhibit complement activity and attenuated the increase in the permeability index after reperfusion in ischemic muscle 1.11 +/- 0.08 (p < 0.01) and reduced the lung BAL/blood 125I albumin ratio to sham levels 2.46 +/- 0.39 x 10(-3) (p < 0.05) at 6 mg/animal, without reducing the lung neutrophil sequestration, 0.24 +/- 0.02 U/g. The authors conclude that complement activation occurred during tourniquet ischemia and mediated permeability changes in the ischemic muscle and the lungs during reperfusion.
Lindsay
T F
TF
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Hill
J
J
Ortiz
F
F
Rudolph
A
A
Valeri
C R
CR
Hechtman
H B
HB
Moore
F D
FD
D000418:Albumins / Q000378:metabolism*; D000818:Animals; D001810:Blood Volume; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003167:Complement Activation; D006614:Hindlimb / Q000098:blood supply; D008168:Lung / Q000378:metabolism*; D008297:Male; D009132:Muscles / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D010539:Permeability; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011951:Receptors, Complement / Q000378:metabolism; D015427:Reperfusion Injury / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
D000418:Albumins; D011951:Receptors, Complement; D009195:Peroxidase