Complement Activation during Cardiopulmonary Bypass: Evidence for Generation of C3a and C5a Anaphylatoxins
Abstract
We observed complement activation in 15 adults undergoing total cardiopulmonary bypass. Plasma levels of C3a were significantly elevated (P < 0.0001) at the beginning of the procedure, and they continued to increase steadily thereafter. At the end of the procedure, C3a levels were more than five times higher than preoperative levels. Plasma levels of C5a (a factor that binds avidly to neutrophils) did not change significantly during cardiopulmonary bypass. Instead, there was significant neutrophilia (P = 0.03) during bypass, and significant transpulmonary neutropenia (P = 0.0002) occurred when cardiopulmonary circulation was reestablished at partial bypass. The neutropenia is consistent with pulmonary-vascular sequestration of C5a-activated granulocytes. We also found that incubation of blood with the nylon-mesh liner of bubble oxygenators, as well as vigorous oxygenation of whole blood, promotes conversion of complement. We conclude that the complement-derived inflammatory mediators C3a and C5a produced during extracorporeal circulation may contribute to the pathogenesis of "post-pump syndromes."
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Cardiopulmonary bypass (CPB) is an immuno-reactive state in which neutrophils are activated and accumulate in different tissues.
“Cardiopulmonary bypass (CPB) is an immuno-reactive state where neutrophils are activated and accumulate in different tissues.”
From Oral neutrophils are an independent marker of the systemic inflammatory response after cardiac bypass (2014) · cites this paper as [5]
Cites
Complement and Leukocyte-Mediated Pulmonary Dysfunction in Hemodialysis
Craddock, P. R., Fehr, J., Brigham, K. L., et al. (1977) · New England Journal of Medicine · doi:10.1056/nejm197704072961401 · Cited by 1,011 · see citing works
Craddock, P. R., Fehr, J. S., Dalmasso, A. P., Brighan, K. L., & Jacob, H. (1977) · Journal of Clinical Investigation · doi:10.1172/jci108710 · Cited by 992 · see citing works
Craddock, P. R., Hammerschmidt, D. E., White, J. G., et al. (1977) · Journal of Clinical Investigation · doi:10.1172/jci108763 · Cited by 687 · see citing works
Hammerschmidt, D. E., Hudson, L., Weaver, L. J., Craddock, P. R., & Jacob, H. S. (1980) · The Lancet · doi:10.1016/s0140-6736(80)91403-8 · Cited by 556 · see citing works
Demonstration of specific C5a receptor on intact human polymorphonuclear leukocytes.
Chenoweth, D. E., & Hugli, T. E. (1978) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.75.8.3943 · Cited by 510 · see citing works
Self-citationBiological effects of the human complement fragments C5a and C5ades Arg on neutrophil function
Webster, R. O., Hong, S. R., Johnston, R. B., & Henson, P. M. (1980) · Immunopharmacology · doi:10.1016/0162-3109(80)90050-8 · Cited by 261 · see citing works
Neutrophil Aggregation and Swelling Induced by Chemotactic Agents
O’Flaherty, J. T., Kreutzer, D. L., & Ward, P. A. (1977) · The Journal of Immunology · doi:10.4049/jimmunol.119.1.232 · Cited by 166 · see citing works
Craddock, P. R., Hammerschmidt, D. E., Moldow, C. F., et al. (1979) · PubMed · Cited by 157 · see citing works
Complement activation and pulmonary leukotasis during nylon fiber filtration leukapheresis
Hammerschmidt, D. E., Craddock, P. R., McCullough, F., Kronenberg, R., Dalmasso, A., & Jacob, H. (1978) · Blood · doi:10.1182/blood.v51.4.721.721 · Cited by 155 · see citing works
Human C5a and C5a analogs as probes of the neutrophil C5a receptor
Chenoweth, D. E., & Hugli, T. E. (1980) · Molecular Immunology · doi:10.1016/0161-5890(80)90067-x · Cited by 133 · see citing works
Self-citationGlovsky, M. M., Hugli, T. E., Ishizaka, T., Lichtenstein, L. M., & Erickson, B. W. (1979) · Journal of Clinical Investigation · doi:10.1172/jci109527 · Cited by 123 · see citing works
Self-citationGranulocyte aggregometry: a sensitive technique for the detection of C5a and complement activation
Hammerschmidt, D. E., Bowers, T., Lammi-Keefe, C. J., et al. (1980) · Blood · doi:10.1182/blood.v55.6.898.898 · Cited by 117 · see citing works
Changes in serum complement and immunoglobulins following cardiopulmonary bypass.
Dj, P., Cantrell, J. W., Karp, R. B., et al. (1972) · PubMed · Cited by 114 · see citing works
C3e: An Acidic Fragment of Human C3 with Leukocytosis-Inducing Activity
Ghebrehiwet, B., & Müller‐Eberhard, H. J. (1979) · The Journal of Immunology · doi:10.4049/jimmunol.123.2.616 · Cited by 112 · see citing works
Effect of intravascular complement activation on granulocyte adhesiveness and distribution
O’Flaherty, J. T., Craddock, P., & Jacob, H. (1978) · Blood · doi:10.1182/blood.v51.4.731.bloodjournal514731 · Cited by 100 · see citing works
Complement activation during cardiopulmonary bypass
Haslam, P. L., Townsend, P., & Branthwaite, M. A. (1980) · Anaesthesia · doi:10.1111/j.1365-2044.1980.tb03715.x · Cited by 86 · see citing works
Nylon fiber leukapheresis: associated complement component changes and cranulocytopenia
Nusbacher, J., Rosenfeld, S., MacPherson, J. L., Thiem, P. A., & Leddy, J. P. (1978) · Blood · doi:10.1182/blood.v51.2.359.359 · Cited by 79 · see citing works
Effect of intravascular complement activation on granulocyte adhesiveness and distribution
O’Flaherty, J. T., Craddock, P., & Jacob, H. (1978) · Blood · doi:10.1182/blood.v51.4.731.731 · Cited by 77 · see citing works
Postperfusion Pulmonary Vasculitis
Neville, W. E. (1963) · Archives of Surgery · doi:10.1001/archsurg.1963.01310070128017 · Cited by 61 · see citing works
Bolanowski, P. J. P., Bauer, J., Machiedo, G. W., et al. (1977) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/s0022-5223(19)39949-0 · Cited by 43 · see citing works
Open-Heart Surgery at the Mayo Clinic
Kirklin, J. W. (1980) · Mayo Clinic Proceedings · doi:10.1016/s0025-6196(24)00529-9 · Cited by 39 · see citing works
Self-citationUptake of 125I-labelled C3a by cultured human endothelial cells.
Denney, J. B., & Johnson, A. R. (1979) · PubMed · Cited by 13 · see citing works
SERUM COMPLEMENT STUDIES DURING AND FOLLOWING CARDIOPULMONARY BYPASS
Parker, D. J., Cook, S. D., & Turner-Warwick, M. E. H. (1975) · Elsevier eBooks · doi:10.1016/b978-0-12-392250-2.50038-8 · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Biglioli, P. (2003) · European Journal of Cardio-Thoracic Surgery · doi:10.1016/s1010-7940(03)00295-1 · Cited by 209 · see citing works
Effects of Cardiopulmonary Bypass on Pulmonary Leukostasis and Complement Activation
Howard, R. J. (1988) · Archives of Surgery · doi:10.1001/archsurg.1988.01400360066010 · Cited by 104 · see citing works
Wilcox, M. E., Charbonney, E., d’Empaire, P. P., Duggal, A., Pinto, R., Javid, A., Dos Santos, C., Rubenfeld, G. D., Sutherland, S., Liles, W. C., et al. (2014) · Journal of Inflammation · doi:10.1186/s12950-014-0032-5 · Cited by 17 · see citing works
“the bypass circuit, mechanical shear stress and hemodilution, [3-6] and as a result accumulate in different tissues.”
Background
- Authors
- Chenoweth, D. E., Cooper, S. W., Hugli, T. E., Stewart, R. W., Blackstone, E. H., & Kirklin, J. W.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1981-02-26
- Volume
- 304
- Issue
- 9
- Pages
- 497-503
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2330568965
- Cited by
- 1,146
- References
- 23
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 13 · 2023: 6 · 2022: 12 · 2021: 7 · 2020: 7 · 2019: 8 · 2018: 9 · 2017: 10 · 2016: 13 · 2015: 9 · 2014: 15 · 2013: 14 · 2012: 15
- FWCI
- 56.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cardiac and Coronary Surgery Techniques
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Health Sciences › Medicine › Biochemistry › Blood transfusion and management
- Keywords
- complement activation, cardiopulmonary bypass, C3a, C5a, neutrophilia, inflammatory mediators, extracorporeal circulation
- MeSH terms
- Adult, Aged, Anaphylatoxins, Complement Activation, Complement C3, Complement C5, Humans, Leukocyte Count, Middle Aged, Neutropenia, Nylons, Oxygenators, Peptide Biosynthesis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
