Complement activation is a secondary rather than a causative factor in rabbit pulmonary artery ischemia/reperfusion injury.
We have previously demonstrated that reperfusion of a rabbit lung in vivo after 24 h of unilateral pulmonary artery occlusion results in edema, transient leukopenia, and intravascular leukocyte aggregation. We hypothesized that complement was activated by reperfusion and that this in turn contributed to lung injury. In the preliminary phase of the study, we found that ischemia followed by reperfusion resulted in a drop in C3 to 15 +/- 10% (mean +/- SEM) of the prereperfusion value as compared with no change in a group of control animals that had undergone an identical thoracotomy but without pulmonary artery occlusion and reperfusion (p less than 0.05). We then studied three groups of animals to determine if complement depletion with cobra venom factor (CVF) prior to ischemia and reperfusion would prevent the injury. Rabbits treated with CVF but without occlusion and reperfusion did not develop significant lung edema, with left and right lung wet/dry ratios of 5.32 +/- 0.11 and 5.26 +/- 0.12, respectively. For rabbits that were not treated with CVF but underwent ischemia and reperfusion, the comparable numbers were 6.15 +/- 0.36 and 5.19 +/- 0.32 (p less than 0.05 for right versus left). For CVF-treated rabbits that underwent ischemia and reperfusion, the right/left difference persisted (6.77 +/- 0.48 versus 5.35 +/- 0.14, p less than 0.01). Immunocytochemistry documented C3 deposition in non-CVF rabbits that underwent ischemia and reperfusion but not in CVF-treated rabbits. We conclude that ischemia/reperfusion of the lung results in complement activation, but it is not a complement-dependent injury.
Bishop
M J
MJ
Department of Anesthesiology, University of Washington School of Medicine, Seattle.
Giclas
P C
PC
Guidotti
S M
SM
Su
M L
ML
Chi
E Y
EY
D000818:Animals; D003167:Complement Activation / Q000502:physiology*; D004546:Elapid Venoms / Q000494:pharmacology; D007150:Immunohistochemistry; D007511:Ischemia / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D011651:Pulmonary Artery / Q000503:physiopathology; D011654:Pulmonary Edema / Q000473:pathology; D011817:Rabbits; D012039:Regional Blood Flow; D015427:Reperfusion Injury / Q000097:blood* / Q000473:pathology
D004546:Elapid Venoms; C016310:cobra venom factor