ArticleCritical care (London, England)2009
Nebulized antithrombin limits bacterial outgrowth and lung injury in Streptococcus pneumoniae pneumonia in rats.
Article in Critical care (London, England), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 40 citations in OpenAlex.
- Nebulized anticoagulants for acute lung injury - a systematic review of preclinical and clinical investigations.Critical care (London, England) · 2012Pooled it
- The effect of heparin administration in animal models of sepsis: a prospective study in Escherichia coli-challenged mice and a systematic review and metaregression analysis of published studies.Critical care medicine · 2011Pooled it
- Nebulized heparin is associated with fewer days of mechanical ventilation in critically ill patients: a randomized controlled trial.Critical care (London, England) · 2010Trial
- Review
- Arterial Thrombosis in Acute Respiratory Infections: An Underestimated but Clinically Relevant Problem.Journal of clinical medicine · 2024Review
- Acute respiratory distress syndrome heterogeneity and the septic ARDS subgroup.Frontiers in immunology · 2023Review
- Article
- Antithrombin and Its Role in Host Defense and Inflammation.International journal of molecular sciences · 2021Review
- Targeting coagulation activation in severe COVID-19 pneumonia: lessons from bacterial pneumonia and sepsis.European respiratory review : an official journal of the European Respiratory Society · 2020Review
- Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence.Critical care (London, England) · 2020Review
- "War to the knife" against thromboinflammation to protect endothelial function of COVID-19 patients.Critical care (London, England) · 2020Article
- Effects of nebulized antithrombin and heparin on inflammatory and coagulation alterations in an acute lung injury model in rats.Journal of thrombosis and haemostasis : JTH · 2020Article
- Anticoagulant therapy in acute respiratory distress syndrome.Annals of translational medicine · 2018Review
- Nebulized anticoagulants in lung injury in critically ill patients-an updated systematic review of preclinical and clinical studies.Annals of translational medicine · 2017Review
- Nebulized Heparin Attenuates Pulmonary Coagulopathy and Inflammation through Alveolar Macrophages in a Rat Model of Acute Lung Injury.Thrombosis and haemostasis · 2017Article
- Article
- Antimicrobial effects of helix D-derived peptides of human antithrombin III.The Journal of biological chemistry · 2014Article
- Influenza Virus H1N1 inhibition by serine protease inhibitor (serpin) antithrombin III.International trends in immunity · 2014Article
- Antithrombin attenuates vascular leakage via inhibiting neutrophil activation in acute lung injury.Critical care medicine · 2013Article
- Direct antimicrobial activity of antithrombin?Critical care (London, England) · 2010Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionDisturbed alveolar fibrin turnover is a cardinal feature of severe pneumonia. Clinical studies suggest that natural inhibitors of coagulation exert lung-protective effects via anticoagulant and possibly also anti-inflammatory pathways. Intravenous infusion of the natural anticoagulants increases the risk of bleeding. Local administration may allow for higher treatment dosages and increased local efficacy while at the same time reducing the risk of bleeding. We evaluated the effect of nebulized anticoagulants on pulmonary coagulopathy and inflammation in a rat model of Streptococcus pneumoniae pneumonia.
methodsIn this randomized controlled in vivo laboratory study rats were challenged intratracheally with S. pneumoniae, inducing pneumonia, and randomized to treatment with normal saline (placebo), recombinant human activated protein C (rh-APC), plasma-derived antithrombin (AT), heparin or danaparoid, by means of nebulization.
resultsS. pneumoniae infection increased pulmonary levels of thrombin-antithrombin complexes and fibrin degradation products. All nebulized anticoagulants significantly limited pulmonary coagulopathy. None of the agents except danaparoid resulted in changes in systemic coagulopathy. Treatment with plasma-derived AT reduced outgrowth of S. pneumoniae and histopathologic damage in lungs. In vitro experiments confirmed outgrowth was reduced in bronchoalveolar lavage fluid (BALF) from rats treated with plasma-derived AT compared with placebo. Neutralizing of cationic components in BALF diminished the inhibitory effects on bacterial outgrowth of BALF, suggesting a role for cationic antimicrobial proteins.
conclusionsNebulization of anticoagulants attenuates pulmonary coagulopathy during S. pneumoniae pneumonia in rats while only danaparoid affects systemic coagulation. Nebulized plasma-derived AT reduces bacterial outgrowth and exerts significant lung-protective effects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.