title: Time-Dependent Thrombus Resolution After Tissue-Type Plasminogen Activator in Patients With Stroke and Mice.
abstract: OBJECTIVE
  We investigated the relationship between the degree of thrombus resolution and the time from stroke onset or thrombus formation to intravenous tissue-type plasminogen activator (tPA) treatment.
  
  
  METHODS
  In patients with stroke, we measured thrombus volume on thin-section noncontrast brain computed tomographic scans taken at baseline and 1 hour after tPA administration. We determined the association between the time from symptom onset to tPA treatment and the degree of thrombus resolution. In a C57/BL6 mouse model of FeCl3-induced carotid artery thrombosis, we investigated the effect of tPA administered at different time intervals after thrombus formation, using Doppler-based blood flow measurement.
  
  
  RESULTS
  Of 249 patients enrolled, 171 showed thrombus on baseline computed tomography. Thrombus was resolved by ≥50% in 43 patients (25.1%, good volume reduction) and by <50% in 94 patients (55.0%, moderate volume reduction) 1 hour after tPA treatment. In 34 patients (19.9%, nonvolume reduction; either no change or thrombus volume increased), overall thrombus volume increased. The probability of thrombus resolution decreased as the time interval from symptom onset to treatment increased. On multivariate analysis, good volume reduction was independently related with shorter time intervals from symptom onset to tPA treatment (odds ratio, 0.986 per minute saved; 95% confidence interval, 0.974-0.999). In the mouse model, as the interval between thrombus formation and tPA treatment increased, the initiation of recanalization was delayed (P=0.006) and the frequency of final recanalization decreased (P for trends=0.006).
  
  
  CONCLUSIONS
  Early administration of tPA after stroke onset is associated with better thrombus resolution.
authors.affiliation: From the Department of Neurology (Y.D.K., H.S.N., S.H.K., D.S., K.L., J.Y., J.H.H.), Severance Integrative Research Institutes for Cerebral and Cardiovascular Diseases (I.K., S.-H.Y.), Department of Biostatistics (H.S.L.), Yonsei University College of Medicine, Seoul, Korea; Department of Neurology, Yonsei Wonju University College of Medicine, Wonju, Korea (S.H.K.); and Department of Radiology, Gachon University, Gil Medical Center, Incheon, Korea (E.Y.K.).
authors.forename: Young Dae
authors.initials: YD
authors.lastname: Kim
authors.affiliation: From the Department of Neurology (Y.D.K., H.S.N., S.H.K., D.S., K.L., J.Y., J.H.H.), Severance Integrative Research Institutes for Cerebral and Cardiovascular Diseases (I.K., S.-H.Y.), Department of Biostatistics (H.S.L.), Yonsei University College of Medicine, Seoul, Korea; Department of Neurology, Yonsei Wonju University College of Medicine, Wonju, Korea (S.H.K.); and Department of Radiology, Gachon University, Gil Medical Center, Incheon, Korea (E.Y.K.).
authors.forename: Hyo Suk
authors.initials: HS
authors.lastname: Nam
authors.affiliation: From the Department of Neurology (Y.D.K., H.S.N., S.H.K., D.S., K.L., J.Y., J.H.H.), Severance Integrative Research Institutes for Cerebral and Cardiovascular Diseases (I.K., S.-H.Y.), Department of Biostatistics (H.S.L.), Yonsei University College of Medicine, Seoul, Korea; Department of Neurology, Yonsei Wonju University College of Medicine, Wonju, Korea (S.H.K.); and Department of Radiology, Gachon University, Gil Medical Center, Incheon, Korea (E.Y.K.).
authors.forename: Seo Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: From the Department of Neurology (Y.D.K., H.S.N., S.H.K., D.S., K.L., J.Y., J.H.H.), Severance Integrative Research Institutes for Cerebral and Cardiovascular Diseases (I.K., S.-H.Y.), Department of Biostatistics (H.S.L.), Yonsei University College of Medicine, Seoul, Korea; Department of Neurology, Yonsei Wonju University College of Medicine, Wonju, Korea (S.H.K.); and Department of Radiology, Gachon University, Gil Medical Center, Incheon, Korea (E.Y.K.).
authors.forename: Eung Yeop
authors.initials: EY
authors.lastname: Kim
authors.affiliation: From the Department of Neurology (Y.D.K., H.S.N., S.H.K., D.S., K.L., J.Y., J.H.H.), Severance Integrative Research Institutes for Cerebral and Cardiovascular Diseases (I.K., S.-H.Y.), Department of Biostatistics (H.S.L.), Yonsei University College of Medicine, Seoul, Korea; Department of Neurology, Yonsei Wonju University College of Medicine, Wonju, Korea (S.H.K.); and Department of Radiology, Gachon University, Gil Medical Center, Incheon, Korea (E.Y.K.).
authors.forename: Dongbeom
authors.initials: D
authors.lastname: Song
authors.affiliation: From the Department of Neurology (Y.D.K., H.S.N., S.H.K., D.S., K.L., J.Y., J.H.H.), Severance Integrative Research Institutes for Cerebral and Cardiovascular Diseases (I.K., S.-H.Y.), Department of Biostatistics (H.S.L.), Yonsei University College of Medicine, Seoul, Korea; Department of Neurology, Yonsei Wonju University College of Medicine, Wonju, Korea (S.H.K.); and Department of Radiology, Gachon University, Gil Medical Center, Incheon, Korea (E.Y.K.).
authors.forename: Il
authors.initials: I
authors.lastname: Kwon
authors.affiliation: From the Department of Neurology (Y.D.K., H.S.N., S.H.K., D.S., K.L., J.Y., J.H.H.), Severance Integrative Research Institutes for Cerebral and Cardiovascular Diseases (I.K., S.-H.Y.), Department of Biostatistics (H.S.L.), Yonsei University College of Medicine, Seoul, Korea; Department of Neurology, Yonsei Wonju University College of Medicine, Wonju, Korea (S.H.K.); and Department of Radiology, Gachon University, Gil Medical Center, Incheon, Korea (E.Y.K.).
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Yang
authors.affiliation: From the Department of Neurology (Y.D.K., H.S.N., S.H.K., D.S., K.L., J.Y., J.H.H.), Severance Integrative Research Institutes for Cerebral and Cardiovascular Diseases (I.K., S.-H.Y.), Department of Biostatistics (H.S.L.), Yonsei University College of Medicine, Seoul, Korea; Department of Neurology, Yonsei Wonju University College of Medicine, Wonju, Korea (S.H.K.); and Department of Radiology, Gachon University, Gil Medical Center, Incheon, Korea (E.Y.K.).
authors.forename: Kijeong
authors.initials: K
authors.lastname: Lee
authors.affiliation: From the Department of Neurology (Y.D.K., H.S.N., S.H.K., D.S., K.L., J.Y., J.H.H.), Severance Integrative Research Institutes for Cerebral and Cardiovascular Diseases (I.K., S.-H.Y.), Department of Biostatistics (H.S.L.), Yonsei University College of Medicine, Seoul, Korea; Department of Neurology, Yonsei Wonju University College of Medicine, Wonju, Korea (S.H.K.); and Department of Radiology, Gachon University, Gil Medical Center, Incheon, Korea (E.Y.K.).
authors.forename: Joonsang
authors.initials: J
authors.lastname: Yoo
authors.affiliation: From the Department of Neurology (Y.D.K., H.S.N., S.H.K., D.S., K.L., J.Y., J.H.H.), Severance Integrative Research Institutes for Cerebral and Cardiovascular Diseases (I.K., S.-H.Y.), Department of Biostatistics (H.S.L.), Yonsei University College of Medicine, Seoul, Korea; Department of Neurology, Yonsei Wonju University College of Medicine, Wonju, Korea (S.H.K.); and Department of Radiology, Gachon University, Gil Medical Center, Incheon, Korea (E.Y.K.).
authors.forename: Hye Sun
authors.initials: HS
authors.lastname: Lee
authors.affiliation: From the Department of Neurology (Y.D.K., H.S.N., S.H.K., D.S., K.L., J.Y., J.H.H.), Severance Integrative Research Institutes for Cerebral and Cardiovascular Diseases (I.K., S.-H.Y.), Department of Biostatistics (H.S.L.), Yonsei University College of Medicine, Seoul, Korea; Department of Neurology, Yonsei Wonju University College of Medicine, Wonju, Korea (S.H.K.); and Department of Radiology, Gachon University, Gil Medical Center, Incheon, Korea (E.Y.K.). jhheo@yuhs.ac.
authors.forename: Ji Hoe
authors.initials: JH
authors.lastname: Heo
mesh_terms: D000368:Aged; D000818:Animals; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D013045:Species Specificity; D020521:Stroke / Q000175:diagnosis* / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000639:trends*; D013927:Thrombosis / Q000175:diagnosis* / Q000188:drug therapy*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D010959:Tissue Plasminogen Activator
keywords: 3D image; ferric chloride; stroke; thrombolytic therapy; thrombosis