Dissolution of emboli in rats with experimental cerebral thromboembolism by recombinant human tissue plasminogen activator (TD-2061)

Journal Article · Wed Aug 15 00:00:00 EDT 1990 · Thrombosis Research; (USA)

DOI:https://doi.org/10.1016/0049-3848(90)90052-E· OSTI ID:5734762

Hara, T; Iwamoto, M; Ogawa, H; Yamamoto, A; Tomikawa, M ^[1]

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1. Research Institute, Daiichi Pharmaceutical Co., Ltd., Tokyo, (Japan)

Tissue plasminogen activator (t-PA) is frequently administered clinically as thrombolytic therapy. We injected recombinant t-PA into rats with cerebral {sup 125}I-labeled blood clot emboli to evaluate the dissolutive effect of recombinant human single-chain t-PA (rt-PA; TD-2061) on such emboli and to examine the possibility of improving neurological damage in patients with cerebral thrombosis. When rt-PA was given intravenously at a dose of 350,000 IU/kg 2 minutes before embolization, radioactivity in the affected cerebral hemisphere decreased to 20% of that in the vehicle control 2 hours after embolization. A significant decrease in radioactivity in the cerebral hemisphere was also found on the administration of 700,000 IU/kg of rt-PA 30 or 60 minutes after embolization, but not when rt-PA was administered 2 minutes after embolization. Marked inhibition of abnormal behavior such as hemiplegia was seen on treatment with rt-PA 2 minutes before embolization, but not at all when rt-PA treatment was given 30 or 60 minutes after embolization. The findings suggest that rt-PA can dissolve blood clot emboli in cerebral vessels and that prompt thrombolytic therapy is important to minimize neurological dysfunction in cases of cerebral thromboembolism.

• OSTI ID: 5734762
• Journal Information: Thrombosis Research; (USA), Journal Name: Thrombosis Research; (USA) Vol. 59:4; ISSN 0049-3848; ISSN THBRA
• Country of Publication: United States
• Language: English

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550901* -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BETA DECAY RADIOISOTOPES
BIOLOGICAL FUNCTIONS
BODY
BRAIN
CARDIOVASCULAR DISEASES
CENTRAL NERVOUS SYSTEM
CEREBRAL CORTEX
CEREBRUM
CHEMOTHERAPY
DAYS LIVING RADIOISOTOPES
DISEASES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
FIBRINOLYTIC AGENTS
HEMATOLOGIC AGENTS
IN VITRO
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
MAN
NERVOUS SYSTEM
NUCLEI
ODD-EVEN NUCLEI
ORGANS
PLASMINOGEN
PRIMATES
RADIOISOTOPES
RATS
RODENTS
THERAPY
THROMBOSIS
TRACER TECHNIQUES
VASCULAR DISEASES
VERTEBRATES