Document Detail


Microbubble-augmented ultrasound sonothrombolysis decreases intracranial hemorrhage in a rabbit model of acute ischemic stroke.
MedLine Citation:
PMID:  21343824     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: Increasing evidence confirms that microbubble (MB)-augmented ultrasound (US) thrombolysis enhances clot lysis with or without tissue plasminogen activator (tPA). Intracranial hemorrhage (ICH) is a major complication militating against tPA use in acute ischemic stroke. We quantified the incidence of ICH associated with tPA thrombolysis and MB + US therapy and compared infarct volumes in a rabbit model of acute ischemic stroke.
MATERIALS AND METHODS: Rabbits (n = 158) received a 1.0-mm clot, angiographically injected into the internal carotid artery causing infarcts. Rabbits were randomized to 6 test groups including (1) control (n = 50), embolized without therapy, (2) US (n = 18), (3) tPA only (n = 27), (4) tPA + US (n = 22), (5) MB + US (n = 27), and (6) tPA + MB + US (n = 14). US groups received pulsed wave US (1 MHz, 0.8 W/cm) for 1 hour; rabbits with tPA received intravenous tPA (0.9 mg/kg) over 1 hour. Rabbits with MB received intravenous MB (0.16 mg/kg) given over 30 minutes. Rabbits were killed 24 hours later and infarct volume and incidence, location, and severity of ICH were determined by histology and pathologic examination.
RESULTS: Percentage of rabbits having ICH outside the infarct area was significantly decreased (P = 0.004) for MB + US (19%) rabbits compared with tPA + US (73%), US only (56%), tPA (48%), tPA + MB + US (36%), and control (36%) rabbits. Incidence and severity of ICH within the infarct did not differ (P > 0.39). Infarct volume was significantly greater (P = 0.002) for rabbits receiving US (0.97% ± 0.17%) than for MB + US (0.20% ± 0.14%), tPA + US (0.15% ± 0.16%), tPA (0.14% ± 0.14%), and tPA + MB + US (0.10% ± 20%) rabbits; these treatments collectively, excluding US only, differed (P = 0.03) from control (0.45% ± 0.10%).
CONCLUSIONS: Treatment with MB + US after embolization decreased the incidence of ICH and efficacy was similar to tPA in reducing infarct volume.
Authors:
Rene Flores; Leah J Hennings; John D Lowery; Aliza T Brown; William C Culp
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Investigative radiology     Volume:  46     ISSN:  1536-0210     ISO Abbreviation:  Invest Radiol     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-06-06     Completed Date:  2011-09-27     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  0045377     Medline TA:  Invest Radiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  419-24     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cerebral Infarction / complications,  therapy*
Disease Models, Animal
Female
Fibrinolytic Agents / therapeutic use*
Intracranial Hemorrhages / etiology,  prevention & control*
Male
Microbubbles / therapeutic use*
Rabbits
Thrombolytic Therapy / methods*
Tissue Plasminogen Activator / therapeutic use*
Ultrasonic Therapy
Grant Support
ID/Acronym/Agency:
R01 HL082481/HL/NHLBI NIH HHS; R01 HL082481-01/HL/NHLBI NIH HHS; R01 HL092481/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Fibrinolytic Agents; EC 3.4.21.68/Tissue Plasminogen Activator
Comments/Corrections

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