Vagus nerve stimulation inhibits activation of coagulation and fibrinolysis during endotoxemia in rats
Open accessAbstract
Background Sepsis and endotoxemia are associated with concurrent activation of inflammation and the hemostatic mechanism, which both contribute to organ dysfunction and death. Electrical vagus nerve stimulation (VNS) has been found to inhibit tumor necrosis factor (TNF)-alpha release during endotoxemia in rodents.Objective To determine the effect of VNS on activation of coagulation and fibrinolysis.Methods Rats received a sublethal i.v. dose of lipopolysaccharide (LPS) after electrical VNS or sham stimulation. Activation of coagulation and fibrinolysis, as well as cytokine release, was measured before LPS injection and 2, 4 and 6 h thereafter.Results LPS induced activation of the coagulation system (increases in the plasma concentrations of thrombin-antithrombin complexes and D-dimer, and a decrease in antithrombin) and biphasic changes in the fibrinolytic system [early rises of plasminogen activator activity and tissue-type plasminogen activator, followed by a delayed increase in plasminogen activator inhibitor type 1 (PAI-1)]. VNS strongly inhibited all LPS-induced procoagulant responses and more modestly attenuated the fibrinolytic response. In addition, VNS attenuated the LPS-induced increases in plasma and splenic concentrations of the proinflammatory cytokines TNF-alpha and interleukin-6 (IL-6), while not influencing the release of the anti-inflammatory cytokine IL-10.Conclusion These data illustrate a thus far unrecognized effect of VNS and suggest that the cholinergic anti-inflammatory pathway not only impacts on inflammation but also on the coagulant-anticoagulant balance.
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?
Cholinergic stimulation controls endothelial activation, leukocyte recruitment, coagulation, and fibrinolysis, which modulates the development of damage during sepsis.
“Other studies indicate that cholinergic stimulation controls endothelial activation, leukocyte recruitment, coagulation, and fibrinolysis, which modulates the development of damage during sepsis (25,36).”
From Physiology and immunology of the cholinergic antiinflammatory pathway (2007) · cites this paper as [36]
Cites
Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin
Borovikova, L. V., Ivanova, S., Zhang, M., Yang, H., Botchkina, G. I., Watkins, L. R., Wang, H., Abumrad, N., Eaton, J. W., & Tracey, K. J. (2000) · Nature · doi:10.1038/35013070 · Cited by 4,211 · see citing works
Tracey, K. J. (2002) · Nature · doi:10.1038/nature01321 · Cited by 3,728 · see citing works
Nicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammation
Wang, H., Yu, M., Ochani, M., Amella, C. A., Tanovic, M., Susarla, S., Li, J. H., Wang, H., Yang, H., Ulloa, L., et al. (2003) · Nature · doi:10.1038/nature01339 · Cited by 3,228 · see citing works
Disseminated Intravascular Coagulation
Levi, M. M., & Cate, H. T. (1999) · New England Journal of Medicine · doi:10.1056/nejm199908193410807 · Cited by 2,027 · see citing works
Self-citationAnnane, D., Bellissant, É., & Cavaillon, J. (2005) · The Lancet · doi:10.1016/s0140-6736(04)17667-8 · Cited by 1,207 · see citing works
Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis
Wang, H., Liao, H., Ochani, M., Justiniani, M., Lin, X., Yang, L., Al-Abed, Y., Wang, H., Metz, C., Miller, E. J., et al. (2004) · Nature Medicine · doi:10.1038/nm1124 · Cited by 1,170 · see citing works
de Jonge, W. J., van der Zanden, E. P., The, F. O., Bijlsma, M. F., van Westerloo, D. J., Bennink, R. J., Berthoud, H.-R., Uematsu, S., Akira, S., van den Wijngaard, R. M., et al. (2005) · Nature Immunology · doi:10.1038/ni1229 · Cited by 1,074 · see citing works
Bidirectional Relation Between Inflammation and Coagulation
Levi, M. M., van der Poll, T., & Buller, H. R. (2004) · Circulation · doi:10.1161/01.cir.0000131660.51520.9a · Cited by 942 · see citing works
Self-citationvan Deventer, S. J. H., Buller, H. R., ten Cate, J. W., Aarden, L. A., Hack, C. E., & Sturk, A. (1990) · Blood · doi:10.1182/blood.v76.12.2520.bloodjournal76122520 · Cited by 850 · see citing works
Pharmacological stimulation of the cholinergic antiinflammatory pathway
Bernik, T. R., Friedman, S. G., Ochani, M., DiRaimo, R., Ulloa, L., Yang, H., Sudan, S., Czura, C. J., Ivanova, S. M., & Tracey, K. J. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20011714 · Cited by 529 · see citing works
Saeed, R. W., Varma, S., Peng-Nemeroff, T., Sherry, B., Balakhaneh, D., Huston, J., Tracey, K. J., Al-Abed, Y., & Metz, C. N. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20040463 · Cited by 489 · see citing works
Suffredini, A. F., Harpel, P. C., & Parrillo, J. E. (1989) · New England Journal of Medicine · doi:10.1056/nejm198905043201802 · Cited by 486 · see citing works
Verheijen, J. H., Mullaart, E., Chang, G. T. G., Kluft, C., & Wijngaards, G. (1982) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1657277 · Cited by 475 · see citing works
Levi, M. M., Cate, H. T., Bauer, K., et al. (1994) · Journal of Clinical Investigation · doi:10.1172/jci116934 · Cited by 412 · see citing works
Self-citationvan der Poll, T., Levi, M. M., Hack, C. E., Cate, H. T., van Deventer, S. J. H., Eerenberg, A. J. M., de Groot, E. R., Jansen, J., Gallati, H., & Buller, H. R. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.179.4.1253 · Cited by 383 · see citing works
Self-citationThe Vagus Nerve and Nicotinic Receptors Modulate Experimental Pancreatitis Severity in Mice
van Westerloo, D. J., Giebelen, I. A., Florquin, S., Bruno, M. J., LaRosa, G. J., Ulloa, L., Tracey, K. J., & van der Poll, T. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.02.022 · Cited by 377 · see citing works
Self-citationThe Cholinergic Anti‐Inflammatory Pathway Regulates the Host Response during Septic Peritonitis
van Westerloo, D. J., Giebelen, I. A. J., Florquin, S., Daalhuisen, J., Bruno, M. J., de Vos, A. F., Tracey, K. J., & van der Poll, T. (2005) · The Journal of Infectious Diseases · doi:10.1086/430323 · Cited by 316 · see citing works
Self-citationGuarini, S., Altavilla, D., Cainazzo, M.-M., Giuliani, D., Bigiani, A., Marini, H., Squadrito, G., Minutoli, L., Bertolini, A., Marini, R., et al. (2003) · Circulation · doi:10.1161/01.cir.0000050627.90734.ed · Cited by 315 · see citing works
de Jonge, E., Dekkers, P. E. P., Creasey, A. A., et al. (2000) · Blood · doi:10.1182/blood.v95.4.1124.002k20_1124_1129 · Cited by 259 · see citing works
Cholinergic antiinflammatory pathway inhibition of tumor necrosis factor during ischemia reperfusion
Bernik, T. R., Friedman, S. G., Ochani, M., DiRaimo, R., Susarla, S., Czura, C. J., & Tracey, K. J. (2002) · Journal of Vascular Surgery · doi:10.1067/mva.2002.129643 · Cited by 228 · see citing works
van der Poll, T., Levi, M. M., van Deventer, S. J. H., Cate, H. T., Haagmans, B. L., Biemond, B. J., Buller, H. R., Hack, C. E., & ten Cate, J. W. (1994) · Blood · doi:10.1182/blood.v83.2.446.bloodjournal832446 · Cited by 158 · see citing works
Self-citationInterleukin-10 Inhibits Activation of Coagulation and Fibrinolysis During Human Endotoxemia
Pajkrt, D., van der Poll, T., Levi, M. M., Cutler, D. L., Affrime, M. B., van den Ende, A., ten Cate, J. W., & van Deventer, S. J. H. (1997) · Blood · doi:10.1182/blood.v89.8.2701 · Cited by 156 · see citing works
Self-citationvan der Poll, T., Coyle, S. M., Levi, M. M., Jansen, P. M., Dentener, M. A., Barbosa, K., Buurman, W. A., Hack, C. E., ten Cate, J. W., Agosti, J. M., et al. (1997) · PubMed · doi:10.1182/blood.v89.10.3727 · Cited by 147 · see citing works
Self-citationGUARINI, S. (2004) · Cardiovascular Research · doi:10.1016/j.cardiores.2004.03.029 · Cited by 131 · see citing works
Biemond, B. J., Levi, M. M., Cate, H. T., et al. (1995) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1653755 · Cited by 124 · see citing works
Self-citationInflammation and Coagulation: Implications for the Septic Patient
Dellinger, R. P. (2003) · Clinical Infectious Diseases · doi:10.1086/374835 · Cited by 121 · see citing works
Pradier, O., Gerard, C. M., Delvaux, A., Lybin, M., Abramowicz, D., Capel, P., Velu, T. J., & Goldman, M. (1993) · European Journal of Immunology · doi:10.1002/eji.1830231048 · Cited by 98 · see citing works
Altavilla, D., Guarini, S., Bitto, A., Mioni, C., Giuliani, D., Bigiani, A., Squadrito, G., Minutoli, L., Venuti, F. S., Messineo, F., et al. (2006) · Shock · doi:10.1097/01.shk.0000209539.91553.82 · Cited by 98 · see citing works
Effect of interleukin-6 blockade on tissue factor-induced coagulation in human endotoxemia
Derhaschnig, U., Bergmair, D., Marsik, C. L., Kanter‐Schlifke, I., Wijdenes, J., & Jilma, B. (2004) · Critical Care Medicine · doi:10.1097/01.ccm.0000126265.08175.be · Cited by 79 · see citing works
Interleukin‐10 inhibits endotoxin‐induced tissue factor mRNA production by human monocytes
Ramani, M., Ollivier, V., Khechai, F., Vu, T., Ternisien, C., Bridey, F., & de Prost, D. (1993) · FEBS Letters · doi:10.1016/0014-5793(93)81693-t · Cited by 55 · see citing works
Renckens, R., Weijer, S., de Vos, A. F., Pater, J. M., Meijers, J. C. M., Hack, C. E., Levi, M. M., & van der Poll, T. (2004) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000118280.95422.48 · Cited by 41 · see citing works
Self-citationCate, H. T., Lamping, R. J., Henny, C. P., et al. (1984) · Clinical Chemistry · doi:10.1093/clinchem/30.6.860 · Cited by 40 · see citing works
LIJNEN, H. R., Webb, P. D., HOEF, B. V., et al. (1992) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1648419 · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Physiology and immunology of the cholinergic antiinflammatory pathway
Tracey, K. J. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30555 · Cited by 1,563 · see citing works
SARS-CoV-2 Dissemination Through Peripheral Nerves Explains Multiple Organ Injury
Fenrich, M., Mrdenovic, S., Balog, M., Tomic, S., Zjalic, M., Roncevic, A., Mandic, D., Debeljak, Z., & Heffer, M. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00229 · Cited by 95 · see citing works
- Authors
- VAN WESTERLOO, D. J., GIEBELEN, I. A. J., MEIJERS, J. C. M., DAALHUISEN, J., DE VOS, A. F., LEVI, M., & VAN DER POLL, T.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Venue
- Journal of Thrombosis and Haemostasis
- Publisher
- Elsevier BV
- Published
- 2006-09
- Volume
- 4
- Issue
- 9
- Pages
- 1997-2002
- ISSN
- 1538-7836 (ISSN-L)
- OpenAlex
- W2144080450
- Cited by
- 84
- References
- 33
- Citations by year
- 2025: 4 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 9 · 2017: 1 · 2016: 5 · 2015: 4 · 2014: 8 · 2013: 7 · 2012: 5
- FWCI
- 4.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Thrombosis and Haemostasis (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Keywords
- vagus nerve stimulation, endotoxemia, lipopolysaccharide, coagulation activation, fibrinolysis, cholinergic anti-inflammatory pathway, TNF-α, interleukin-6, IL-10, thrombin-antithrombin complex, D-dimer, plasminogen activator inhibitor-1, tissue plasminogen activator, sepsis, hemostasis
- MeSH terms
- Animals, Blood Coagulation, Electric Stimulation, Electric Stimulation Therapy, Fibrinolysis, Inflammation, Kinetics, Lipopolysaccharides, Male, Rats, Inbred Lew, Tumor Necrosis Factor-alpha, Vagus Nerve, Interleukin-6, Interleukin-10, Endotoxemia, Rats
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
