Argatroban, a thrombin inhibitor, decreased mortality after 10 min of forebrain ischemia in the gerbil

We investigated whether anticoagulant therapy with heparin or a selective thrombin inhibitor, argatroban, may ameliorate the postischemic cerebral circulation and attenuate mortality after 10 min of forebrain ischemia. Postischemic subcutaneous injection of argatroban (5 mg/kg) significantly attenua...

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Bibliographic Details
Published in:Neuroscience letters 2000-01, Vol.279 (2), p.93-96
Main Authors: Mima, Tatsuo, Jin, Yong-Jian, Hirayama, Teruyoshi, Gulam Mostafa, Mohammed, Mori, Koreaki
Format: Article
Language:English
Subjects:
Animals
Antithrombins - therapeutic use
Argatroban
Biological and medical sciences
Blood. Blood coagulation. Reticuloendothelial system
Brain edema
Cerebral blood flow
Cerebral Cortex - blood supply
Cerebral Cortex - pathology
Cerebrovascular Circulation - drug effects
Cerebrovascular Circulation - physiology
Death
Forebrain
Gerbil
Gerbillinae
Ischemic Attack, Transient - drug therapy
Ischemic Attack, Transient - pathology
Ischemic Attack, Transient - physiopathology
Medical sciences
Meriones unguiculatus
Pharmacology. Drug treatments
Pipecolic Acids - therapeutic use
Prosencephalon - blood supply
Prosencephalon - pathology
Regional Blood Flow - drug effects
Survival study
Thrombin
Time Factors
Transient cerebral ischemia
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Summary:We investigated whether anticoagulant therapy with heparin or a selective thrombin inhibitor, argatroban, may ameliorate the postischemic cerebral circulation and attenuate mortality after 10 min of forebrain ischemia. Postischemic subcutaneous injection of argatroban (5 mg/kg) significantly attenuated mortality (9.1%) compared with non-treatment (45.5%) during 14 days’ observation period. This effect coincided with: (1) increased cortical CBF after reperfusion; (2) attenuation of brain edema; and (3) less severe cell damages in the cerebral cortex. In contrast, nine of the 22 gerbils treated with heparin (830 IU/kg) were found dead on the next day due to massive bleeding in the surgical wound and 13 bleeding-avoided gerbils did not show significant amelioration in mortality (30.8%). These findings suggest that argatroban is an effective anticoagulant for prevention of cell damage after a relatively long forebrain ischemia.
ISSN:0304-3940
1872-7972
DOI:10.1016/S0304-3940(99)00959-3