Effect of complement inhibition with soluble complement receptor 1 on pig allotransplant lung function.
BACKGROUND
Lung dysfunction after transplantation continues to be a significant clinical problem. Soluble complement receptor 1 (sCR1) is a potent inhibitor of complement activation. We evaluated the inhibitory effect of sCR1 on complement activation and reperfusion injury in pig lung allografts.


METHODS
In a randomized and blinded study, left lung transplantation was performed in 13 pigs. Donor lungs were flushed and then stored for 30 hr at 4 degrees C. Control pigs (n=7) received saline, and the treatment group (n=6) received 15 mg/kg sCR1 1 hr before reperfusion. One hour after reperfusion, the right pulmonary artery was clamped for 10 min to assess the function of the transplanted lung. Pulmonary function was assessed again on day 3.


RESULTS
Complement inhibition was 93% in the sCR1 group and returned to baseline (8% inhibition) after 3 days. There was a trend toward a higher partial pressure of oxygen at 1 hr in the sCR1 group compared with the control group (mean +/- SE: 408+/-42 mmHg vs. 288+/-69 mmHg, P = 0.19). Alveolar ventilation was better in the sCR1 group than in the control group (P = 0.01) at 1 hr. Mixed venous saturation was significantly lower in the control group at both 1 hr (P = 0.02) and 3 days (P = 0.001). The wet/dry weight of the lung tissue was lower in the sCR1 group compared with the control group on day 3 (P < 0.05). Chemiluminescence, an index of phagocyte priming, was lower in the sCR1 group when cells were stimulated with complement opsonized zymosan but not when stimulated with zymosan or phorbol myristate acetate.


CONCLUSIONS
sCR1 improves ventilation, reduces pulmonary edema, and may be beneficial in improving posttransplant lung oxygenation.
Division of Thoracic Surgery, The Toronto Hospital, Ontario, Canada.
A F
AF
Pierre
A M
AM
Xavier
M
M
Liu
S D
SD
Cassivi
T F
TF
Lindsay
H C
HC
Marsh
A S
AS
Slutsky
S H
SH
Keshavjee
D000818:Animals; D016466:CHO Cells; D003179:Complement C3b / Q000032:analysis; D003169:Complement Inactivator Proteins / Q000494:pharmacology*; D006224:Cricetinae; D005455:Fluorescent Antibody Technique; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D016040:Lung Transplantation; D010100:Oxygen / Q000097:blood / Q000378:metabolism; D010313:Partial Pressure; D011897:Random Allocation; D011951:Receptors, Complement / Q000097:blood / Q000502:physiology*; D013552:Swine
D003169:Complement Inactivator Proteins; D011951:Receptors, Complement; C082885:soluble complement inhibitor 1; D003179:Complement C3b; D010100:Oxygen