title: Preclinical evidence toward the use of ketamine for recombinant tissue-type plasminogen activator-mediated thrombolysis under anesthesia or sedation.
abstract: OBJECTIVE
  Endovascular treatment of ischemic stroke usually involves recombinant tissue-type plasminogen activator (rtPA)-mediated thrombolysis in anesthetized patients. Paradoxically, differential influences of anesthetic agents on thrombolysis outcome remain unknown.
  
  
  METHODS
  In situ thrombotic stroke was induced in mice by local injection of thrombin. Four hours after the ischemic onset, mice underwent rtPA-mediated thrombolysis either awake or subjected to different anesthetic regimens (propofol, isoflurane/N2O, ketamine). Infarct volume and arterial recanalization were assessed by MRI at 24 hours.
  
  
  RESULTS
  Whatever the anesthetic regimen, infarct volumes measured at 24 hours were not affected. However, in contrast with other anesthetic agents tested, ketamine dramatically reduced infarct volume when combined with rtPA.
  
  
  CONCLUSIONS
  Altogether these data suggest that ketamine significantly improves the benefit of rtPA-induced thrombolysis after stroke.
authors.affiliation: INSERM U919, University Caen Basse-Normandie, Serine Proteases and Pathophysiology of the Neurovascular Unit, and Department of Neurology, University-Hospital, GIP Cyceron, Bd Becquerel, BP5229, 14074 Caen, France.
authors.forename: Clement
authors.initials: C
authors.lastname: Gakuba
authors.forename: Maxime
authors.initials: M
authors.lastname: Gauberti
authors.forename: Mikael
authors.initials: M
authors.lastname: Mazighi
authors.forename: Gilles
authors.initials: G
authors.lastname: Defer
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Hanouz
authors.forename: Denis
authors.initials: D
authors.lastname: Vivien
mesh_terms: D000778:Anesthetics, Dissociative / Q000627:therapeutic use*; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D007649:Ketamine / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology; D015912:Thrombolytic Therapy / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000778:Anesthetics, Dissociative; D005343:Fibrinolytic Agents; D007649:Ketamine; D010959:Tissue Plasminogen Activator