Complement inhibition with soluble complement receptor type 1 in cardiopulmonary bypass.
Although complement activation during cardiopulmonary bypass (CPB) is well documented, its pathogenic role in postperfusion organ injury is unproven. In this study, soluble human complement receptor type 1 (sCR1), a potent inhibitor of complement activation, was used to determine the contribution of complement activation to pulmonary injury in a porcine model of CPB. In vitro experiments demonstrated that sCR1 inhibits both classic and alternative complement pathways in the pig. Seven control piglets and 6 piglets treated with sCR1 (12 mg/kg intravenously) underwent 2 hours of hypothermic (28 degrees C) CPB followed by 2 hours of observation. In control piglets, total hemolytic complement activity and functional activities of C3 and C5 declined to 61.3%, 67.8%, and 61.4% of prebypass values, respectively, after 2 hours of CPB. Plasma from animals treated with sCR1 had virtually no hemolytic activity (total hemolytic complement activity < 5% of baseline), demonstrating effective complement inhibition. Similar degrees of neutropenia developed in the two groups during CPB, and there was no difference in post-CPB lung tissue myeloperoxidase level. Two hours after CPB, pulmonary vascular resistance increased 338% in control piglets but only 147% in piglets pretreated with sCR1 (p < 0.05); the alveolar-arterial gradient was not significantly different between controls (331 +/- 52 mm Hg) and piglets receiving sCR1 (290 +/- 85 mm Hg). Histologic examination revealed similar degrees of pulmonary edema in both groups. These data constitute direct evidence that complement activation plays a pathogenic role in lung injury after CPB.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Cardiac Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
A M
AM
Gillinov
P A
PA
DeValeria
J A
JA
Winkelstein
I
I
Wilson
W E
WE
Curtis
D
D
Shaw
C G
CG
Yeh
A R
AR
Rudolph
W A
WA
Baumgartner
A
A
Herskowitz
D000818:Animals; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D003167:Complement Activation; D003176:Complement C3 / Q000032:analysis; D003182:Complement C5 / Q000032:analysis; D015941:Complement Hemolytic Activity Assay; D066298:In Vitro Techniques; D007958:Leukocyte Count; D008168:Lung / Q000201:enzymology / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D009195:Peroxidase / Q000032:analysis; D011652:Pulmonary Circulation; D011951:Receptors, Complement / Q000378:metabolism*; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology; D013552:Swine; D014655:Vascular Resistance
D003176:Complement C3; D003182:Complement C5; D011951:Receptors, Complement; D009195:Peroxidase