Document Detail


Thrombolytic efficacy of a modified tissue-type plasminogen activator, SUN9216, in the rat middle cerebral artery thrombosis model.
MedLine Citation:
PMID:  7813575     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have developed a model whereby the middle cerebral artery in an experimental animal can be occluded by a photochemical reaction between rose bengal and green light. This causes endothelial injury followed by platelet adhesion, aggregation and formation of a platelet-rich thrombus at the site of the photochemical reaction. SUN9216, a modified tissue-type plasminogen activator, is a new thrombolytic agent which consists of the fibrin kringle 1 domain of plasminogen and the two kringles, the serine protease domains of the native tissue-type plasminogen activator. The mannose glycosylation site on the kringle 1 of tissue-type plasminogen activator is modified to yield a compound with a longer half-life in the blood than native tissue-type plasminogen activator. We evaluated the thrombolytic effects of recombinant tissue-type plasminogen activator and SUN9216 in the thrombotically occluded rat middle cerebral artery. SUN9216 was administered by continuous infusion or as a single bolus injection 30 min after the middle cerebral artery had been occluded by a thrombus. Both SUN9216 and recombinant tissue-type plasminogen activator caused reopening of the middle cerebral artery by thrombolysis. The efficacy of SUN9216 was higher than that of recombinant tissue-type plasminogen activator. Further, the area of ischaemic cerebral damage caused by the middle cerebral artery occlusion was significantly (P < 0.05) reduced by SUN9216, but in this respect, recombinant tissue-type plasminogen activator was ineffective.
Authors:
K Umemura; Y Toshima; M Nakashima
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  European journal of pharmacology     Volume:  262     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  1994 Sep 
Date Detail:
Created Date:  1995-02-08     Completed Date:  1995-02-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  27-31     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Hamamatu University School of Medicine, Japan.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Brain Ischemia / drug therapy
Cerebral Arteries / drug effects*,  pathology
Cerebral Infarction / drug therapy*
Disease Models, Animal
Glycosylation
Image Processing, Computer-Assisted
Infusions, Intra-Arterial
Intracranial Embolism and Thrombosis / chemically induced,  drug therapy*
Male
Rats
Rats, Wistar
Recombinant Proteins / administration & dosage,  pharmacology,  therapeutic use
Tissue Plasminogen Activator / administration & dosage,  chemistry,  metabolism,  pharmacology,  therapeutic use*
Chemical
Reg. No./Substance:
0/Recombinant Proteins; 153484-31-2/SUN 9216; EC 3.4.21.68/Tissue Plasminogen Activator

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