TY - JOUR
T1 - Complement and neutrophil activation during cardiopulmonary bypass
T2 - A study in the complement-deficient dog
AU - Gillinov, A. Marc
AU - Redmond, J. Mark
AU - Winkelstein, Jerry A.
AU - Zehr, Kenton J.
AU - Herskowitz, Ahvie
AU - Baumgartner, William A.
AU - Cameron, Duke E.
N1 - Funding Information:
Supported by US Public Health Service National Institutes of Health grant R01 HL47191-01. We gratefully acknowledge the expert technical assistance of Melissa Haggerty, Ernest King, Jerome Thorton, Andrea Swift, and Missy Lepko. In addition, we thank Lon Garrison for assistance in preparation of the manuscript.
PY - 1994/2
Y1 - 1994/2
N2 - Cardiopulmonary bypass (CPB) is known to cause complement and neutrophil activation, but the relative importance and interaction of these components in CPB-induced inflammation is unknown. In this study, a strain of dogs genetically deficient in the third component of complement (C3) was used to determine the contribution of C3 to neutropnil activation and pulmonary injury after CPB. Eleven dogs (5 C3-deficient and 6 controls) underwent 150 minutes of hypothermic CPB (28 °C) followed by 2 hours of observation. Before CPB, C3 levels were normal in controls and less than 1% of normal in C3-deficient dogs. In control dogs, functional activity of C3 decreased to 53.2% of baseline after 1 hour of CPB and there was immunohistochemical evidence of C3 deposition in lung after CPB; C3-deficient dogs had no C3 deposition in lung. Although similar degrees of neutropenia occurred during CPB in the two groups, expression of neutrophil adhesion molecule subunit CD18 was significantly lower in C3-deficient dogs than controls after 1 hour of CPB (45.9 ± 3.7 versus 82.9 ± 10.0 mean fluorescence units; p < 0.02). Postbypass lung tissue myeloperoxidase content was also less in C3-deficient dogs (43.8 ± 4.6 versus 71.1 ± 8.6 μmol · 10 mg-1· min-1; p < 0.03). Cardiopulmonary bypass-associated lung injury (assessed by alveolar-arterial oxygen gradient, pulmonary vascular resistance, percent lung water, and light and electron microscopic appearance) was similar between groups. These results demonstrate that (1) C3 is deposited on pulmonary vascular endothelium during CPB and 12) C3 mediates increased expression of neutrophil CD18 and neutrophil sequestration in lung after CPB. Furthermore, these results suggest that modulation of complement activation is a potential means to reduce neutrophil activation during CPB, but that prevention of much of the organ injury associated with CPB will require inhibition of multiple arms of the inflammatory cascade.
AB - Cardiopulmonary bypass (CPB) is known to cause complement and neutrophil activation, but the relative importance and interaction of these components in CPB-induced inflammation is unknown. In this study, a strain of dogs genetically deficient in the third component of complement (C3) was used to determine the contribution of C3 to neutropnil activation and pulmonary injury after CPB. Eleven dogs (5 C3-deficient and 6 controls) underwent 150 minutes of hypothermic CPB (28 °C) followed by 2 hours of observation. Before CPB, C3 levels were normal in controls and less than 1% of normal in C3-deficient dogs. In control dogs, functional activity of C3 decreased to 53.2% of baseline after 1 hour of CPB and there was immunohistochemical evidence of C3 deposition in lung after CPB; C3-deficient dogs had no C3 deposition in lung. Although similar degrees of neutropenia occurred during CPB in the two groups, expression of neutrophil adhesion molecule subunit CD18 was significantly lower in C3-deficient dogs than controls after 1 hour of CPB (45.9 ± 3.7 versus 82.9 ± 10.0 mean fluorescence units; p < 0.02). Postbypass lung tissue myeloperoxidase content was also less in C3-deficient dogs (43.8 ± 4.6 versus 71.1 ± 8.6 μmol · 10 mg-1· min-1; p < 0.03). Cardiopulmonary bypass-associated lung injury (assessed by alveolar-arterial oxygen gradient, pulmonary vascular resistance, percent lung water, and light and electron microscopic appearance) was similar between groups. These results demonstrate that (1) C3 is deposited on pulmonary vascular endothelium during CPB and 12) C3 mediates increased expression of neutrophil CD18 and neutrophil sequestration in lung after CPB. Furthermore, these results suggest that modulation of complement activation is a potential means to reduce neutrophil activation during CPB, but that prevention of much of the organ injury associated with CPB will require inhibition of multiple arms of the inflammatory cascade.
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U2 - 10.1016/0003-4975(94)90995-4
DO - 10.1016/0003-4975(94)90995-4
M3 - Article
C2 - 7906115
AN - SCOPUS:0028325016
SN - 0003-4975
VL - 57
SP - 345
EP - 352
JO - The Annals of thoracic surgery
JF - The Annals of thoracic surgery
IS - 2
ER -