Evidence map›Paper›PMID 28487393›Full record

ArticleCirculation2017

Potent Thrombolytic Effect of

Sara Martinez de Lizarrondo, Clément Gakuba, Bradley A Herbig, Yohann Repessé, Carine Ali, Cécile V Denis, Peter J Lenting, Emmanuel Touzé, Scott L Diamond, Denis Vivien and 1 more

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04920448 (TOLERANCE STUDY OF N-ACETYLCYSTEINE FOR THROMBOLYSIS IN THE ACUTE PHASE OF ISCHEMIC STROKE / ETUDE DE TOLERANCE DE LA N-ACETYLCYSTEINE POUR LA THROMBOLYSE A LA PHASE AIGUË DE L'INFARCTUS CEREBRAL), which is not on this map. Cited by 93 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed, 1 pooled it
8.8field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

NCT04920448 phase2terminatednot on this mapstarted 2021, after this paper: background citation

Tolerance study of n-acetylcysteine for thrombolysis in the acute phase of ischemic stroke / etude de tolerance de la n-acetylcysteine pour la thrombolyse a la phase aiguë de l'infarctus cerebral

TypeinterventionalSponsorUniversity Hospital, CaenRan2021 to 2024Enrolled12ConditionsStroke, IschemicArmsN-Acetyl cysteine
3 · Its place in the literature

Who cites it

93 citing papers in PubMed, 1 synthesis or guideline pooled it, 153 citations in OpenAlex.

  1. Shell Versus Core Architecture and Biology of Thrombi in Acute Ischemic Stroke: A Systematic Review.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis
    Pooled it
  2. Trial
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Toward improved thrombolysis in ischemic stroke: targeting nonfibrin components.Research and practice in thrombosis and haemostasis · 2026
    Review
  11. Review
  12. Review
  13. Article
  14. Beyond Direct Fibrinolysis: Novel Approaches to Thrombolysis.Pharmaceuticals (Basel, Switzerland) · 2025
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

33 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Sara Martinez de LizarrondoFrom Normandie Univ, UNICAEN, INSERM, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Cyceron, Caen, France (S.M.d.L., C.G., Y.R., C.A., E.T., D.V., M.G.); CHU de Caen, Department of Anesthesiology and Critical Care Medicine, CHU de Caen Côte de Nacre, France (C.G.); Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia (B.A.H., S.L.D.); Laboratoire d'Hématologie, CHU de Caen, France (Y.R.); Institut National de la Santé et de la Recherche Médicale, UMR_S 1176, Univ. Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France (C.V.D., P.J.L.); CHU Caen, Neurology Department, CHU de Caen Côte de Nacre, France (E.T.); CHU Caen, Clinical Research Department, CHU de Caen Côte de Nacre, France (D.V.); and CHU Caen, Department of Diagnostic Imaging and Interventional Radiology, CHU de Caen Côte de Nacre, France (M.G.).
Clément GakubaFrom Normandie Univ, UNICAEN, INSERM, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Cyceron, Caen, France (S.M.d.L., C.G., Y.R., C.A., E.T., D.V., M.G.); CHU de Caen, Department of Anesthesiology and Critical Care Medicine, CHU de Caen Côte de Nacre, France (C.G.); Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia (B.A.H., S.L.D.); Laboratoire d'Hématologie, CHU de Caen, France (Y.R.); Institut National de la Santé et de la Recherche Médicale, UMR_S 1176, Univ. Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France (C.V.D., P.J.L.); CHU Caen, Neurology Department, CHU de Caen Côte de Nacre, France (E.T.); CHU Caen, Clinical Research Department, CHU de Caen Côte de Nacre, France (D.V.); and CHU Caen, Department of Diagnostic Imaging and Interventional Radiology, CHU de Caen Côte de Nacre, France (M.G.).
Bradley A HerbigFrom Normandie Univ, UNICAEN, INSERM, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Cyceron, Caen, France (S.M.d.L., C.G., Y.R., C.A., E.T., D.V., M.G.); CHU de Caen, Department of Anesthesiology and Critical Care Medicine, CHU de Caen Côte de Nacre, France (C.G.); Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia (B.A.H., S.L.D.); Laboratoire d'Hématologie, CHU de Caen, France (Y.R.); Institut National de la Santé et de la Recherche Médicale, UMR_S 1176, Univ. Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France (C.V.D., P.J.L.); CHU Caen, Neurology Department, CHU de Caen Côte de Nacre, France (E.T.); CHU Caen, Clinical Research Department, CHU de Caen Côte de Nacre, France (D.V.); and CHU Caen, Department of Diagnostic Imaging and Interventional Radiology, CHU de Caen Côte de Nacre, France (M.G.).
Yohann RepesséFrom Normandie Univ, UNICAEN, INSERM, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Cyceron, Caen, France (S.M.d.L., C.G., Y.R., C.A., E.T., D.V., M.G.); CHU de Caen, Department of Anesthesiology and Critical Care Medicine, CHU de Caen Côte de Nacre, France (C.G.); Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia (B.A.H., S.L.D.); Laboratoire d'Hématologie, CHU de Caen, France (Y.R.); Institut National de la Santé et de la Recherche Médicale, UMR_S 1176, Univ. Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France (C.V.D., P.J.L.); CHU Caen, Neurology Department, CHU de Caen Côte de Nacre, France (E.T.); CHU Caen, Clinical Research Department, CHU de Caen Côte de Nacre, France (D.V.); and CHU Caen, Department of Diagnostic Imaging and Interventional Radiology, CHU de Caen Côte de Nacre, France (M.G.).
Carine AliFrom Normandie Univ, UNICAEN, INSERM, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Cyceron, Caen, France (S.M.d.L., C.G., Y.R., C.A., E.T., D.V., M.G.); CHU de Caen, Department of Anesthesiology and Critical Care Medicine, CHU de Caen Côte de Nacre, France (C.G.); Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia (B.A.H., S.L.D.); Laboratoire d'Hématologie, CHU de Caen, France (Y.R.); Institut National de la Santé et de la Recherche Médicale, UMR_S 1176, Univ. Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France (C.V.D., P.J.L.); CHU Caen, Neurology Department, CHU de Caen Côte de Nacre, France (E.T.); CHU Caen, Clinical Research Department, CHU de Caen Côte de Nacre, France (D.V.); and CHU Caen, Department of Diagnostic Imaging and Interventional Radiology, CHU de Caen Côte de Nacre, France (M.G.).
Cécile V DenisFrom Normandie Univ, UNICAEN, INSERM, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Cyceron, Caen, France (S.M.d.L., C.G., Y.R., C.A., E.T., D.V., M.G.); CHU de Caen, Department of Anesthesiology and Critical Care Medicine, CHU de Caen Côte de Nacre, France (C.G.); Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia (B.A.H., S.L.D.); Laboratoire d'Hématologie, CHU de Caen, France (Y.R.); Institut National de la Santé et de la Recherche Médicale, UMR_S 1176, Univ. Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France (C.V.D., P.J.L.); CHU Caen, Neurology Department, CHU de Caen Côte de Nacre, France (E.T.); CHU Caen, Clinical Research Department, CHU de Caen Côte de Nacre, France (D.V.); and CHU Caen, Department of Diagnostic Imaging and Interventional Radiology, CHU de Caen Côte de Nacre, France (M.G.).
Peter J LentingFrom Normandie Univ, UNICAEN, INSERM, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Cyceron, Caen, France (S.M.d.L., C.G., Y.R., C.A., E.T., D.V., M.G.); CHU de Caen, Department of Anesthesiology and Critical Care Medicine, CHU de Caen Côte de Nacre, France (C.G.); Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia (B.A.H., S.L.D.); Laboratoire d'Hématologie, CHU de Caen, France (Y.R.); Institut National de la Santé et de la Recherche Médicale, UMR_S 1176, Univ. Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France (C.V.D., P.J.L.); CHU Caen, Neurology Department, CHU de Caen Côte de Nacre, France (E.T.); CHU Caen, Clinical Research Department, CHU de Caen Côte de Nacre, France (D.V.); and CHU Caen, Department of Diagnostic Imaging and Interventional Radiology, CHU de Caen Côte de Nacre, France (M.G.).
Emmanuel TouzéFrom Normandie Univ, UNICAEN, INSERM, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Cyceron, Caen, France (S.M.d.L., C.G., Y.R., C.A., E.T., D.V., M.G.); CHU de Caen, Department of Anesthesiology and Critical Care Medicine, CHU de Caen Côte de Nacre, France (C.G.); Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia (B.A.H., S.L.D.); Laboratoire d'Hématologie, CHU de Caen, France (Y.R.); Institut National de la Santé et de la Recherche Médicale, UMR_S 1176, Univ. Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France (C.V.D., P.J.L.); CHU Caen, Neurology Department, CHU de Caen Côte de Nacre, France (E.T.); CHU Caen, Clinical Research Department, CHU de Caen Côte de Nacre, France (D.V.); and CHU Caen, Department of Diagnostic Imaging and Interventional Radiology, CHU de Caen Côte de Nacre, France (M.G.).
Scott L DiamondFrom Normandie Univ, UNICAEN, INSERM, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Cyceron, Caen, France (S.M.d.L., C.G., Y.R., C.A., E.T., D.V., M.G.); CHU de Caen, Department of Anesthesiology and Critical Care Medicine, CHU de Caen Côte de Nacre, France (C.G.); Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia (B.A.H., S.L.D.); Laboratoire d'Hématologie, CHU de Caen, France (Y.R.); Institut National de la Santé et de la Recherche Médicale, UMR_S 1176, Univ. Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France (C.V.D., P.J.L.); CHU Caen, Neurology Department, CHU de Caen Côte de Nacre, France (E.T.); CHU Caen, Clinical Research Department, CHU de Caen Côte de Nacre, France (D.V.); and CHU Caen, Department of Diagnostic Imaging and Interventional Radiology, CHU de Caen Côte de Nacre, France (M.G.).
Denis VivienFrom Normandie Univ, UNICAEN, INSERM, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Cyceron, Caen, France (S.M.d.L., C.G., Y.R., C.A., E.T., D.V., M.G.); CHU de Caen, Department of Anesthesiology and Critical Care Medicine, CHU de Caen Côte de Nacre, France (C.G.); Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia (B.A.H., S.L.D.); Laboratoire d'Hématologie, CHU de Caen, France (Y.R.); Institut National de la Santé et de la Recherche Médicale, UMR_S 1176, Univ. Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France (C.V.D., P.J.L.); CHU Caen, Neurology Department, CHU de Caen Côte de Nacre, France (E.T.); CHU Caen, Clinical Research Department, CHU de Caen Côte de Nacre, France (D.V.); and CHU Caen, Department of Diagnostic Imaging and Interventional Radiology, CHU de Caen Côte de Nacre, France (M.G.).
Maxime GaubertiFrom Normandie Univ, UNICAEN, INSERM, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Cyceron, Caen, France (S.M.d.L., C.G., Y.R., C.A., E.T., D.V., M.G.); CHU de Caen, Department of Anesthesiology and Critical Care Medicine, CHU de Caen Côte de Nacre, France (C.G.); Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia (B.A.H., S.L.D.); Laboratoire d'Hématologie, CHU de Caen, France (Y.R.); Institut National de la Santé et de la Recherche Médicale, UMR_S 1176, Univ. Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France (C.V.D., P.J.L.); CHU Caen, Neurology Department, CHU de Caen Côte de Nacre, France (E.T.); CHU Caen, Clinical Research Department, CHU de Caen Côte de Nacre, France (D.V.); and CHU Caen, Department of Diagnostic Imaging and Interventional Radiology, CHU de Caen Côte de Nacre, France (M.G.). gauberti@cyceron.fr.
University of Pennsylvania · US

Funding

Blood Systems BiologyR01HL103419 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DIAMOND, SCOTT L · 2010 to 2019
$7.4M
Reaction and Transport Dynamics in Human BloodR01HL056621 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DIAMOND, SCOTT L · 1996 to 2009
$1.8M
NHLBI NIH HHS R01 HL056621NHLBI NIH HHS R01 HL103419
6 · The paper itself

Abstract

backgroundPlatelet cross-linking during arterial thrombosis involves von Willebrand Factor (VWF) multimers. Therefore, proteolysis of VWF appears promising to disaggregate platelet-rich thrombi and restore vessel patency in acute thrombotic disorders such as ischemic stroke, acute coronary syndrome, or acute limb ischemia.

methodsExperimental models of thrombotic stroke induced by either intra-arterial thrombin injection or ferric chloride application followed by measurement of cerebral blood flow using a combination of laser Doppler flowmetry and MRI were performed to uncover the effects of NAC on arterial thrombi. To investigate the effect of NAC on larger vessels, we also performed ferric chloride-induced carotid artery thrombosis. In vitro experiments were performed to study the molecular bases of NAC thrombolytic effect, including platelet aggregometry, platelet-rich thrombi lysis assays, thromboelastography (ROTEM), and high-shear VWF string formation using microfluidic devices. We also investigated the putative prohemorrhagic effect of NAC in a mouse model of intracranial hemorrhage induced by in situ collagenase type VII injection.

resultsWe demonstrated that intravenous NAC administration promotes lysis of arterial thrombi that are resistant to conventional approaches such as recombinant tissue-type plasminogen activator, direct thrombin inhibitors, and antiplatelet treatments. Through in vitro and in vivo experiments, we provide evidence that the molecular target underlying the thrombolytic effects of NAC is principally the VWF that cross-link platelets in arterial thrombi. Coadministration of NAC and a nonpeptidic GpIIb/IIIa inhibitor further improved its thrombolytic efficacy, essentially by accelerating thrombus dissolution and preventing rethrombosis. Thus, in a new large-vessel thromboembolic stroke model in mice, this cotreatment significantly improved ischemic lesion size and neurological outcome. It is important to note that NAC did not worsen hemorrhagic stroke outcome, suggesting that it exerts thrombolytic effects without significantly impairing normal hemostasis.

conclusionsWe provide evidence that NAC is an effective and safe alternative to currently available antithrombotic agents to restore vessel patency after arterial occlusion.

Indexed as

AcetylcysteineAnimalsBlood PlateletsChloridesDisease Models, AnimalFerric CompoundsFibrinolytic AgentsInfarction, Middle Cerebral ArteryMaleMicePlatelet AggregationRistocetinThromboembolismThrombosisTissue Plasminogen Activatorvon Willebrand FactorAcetylcysteineChloridesferric chlorideFerric CompoundsFibrinolytic AgentsRistocetinTissue Plasminogen Activatorvon Willebrand Factorplasminogen activatorsplatelet aggregationstrokethrombolytic therapyvon Willebrand Factor

Identifiers

PMID28487393
PMCPMC5560034
OpenAlexW2613135848

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.