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 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.
Mima
T
T
Department of Neurosurgery, Kochi Medical School, Nankoku City, Japan. mimat-koc@umin.ac.jp
Jin
Y J
YJ
Hirayama
T
T
Mostafa
M G
MG
Mori
K
K
D000818:Animals; D000991:Antithrombins / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives; D002540:Cerebral Cortex / Q000098:blood supply* / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D003643:Death; D005849:Gerbillinae; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D010875:Pipecolic Acids / Q000627:therapeutic use*; D016548:Prosencephalon / Q000098:blood supply* / Q000473:pathology; D012039:Regional Blood Flow / Q000187:drug effects; D013449:Sulfonamides; D013997:Time Factors
D000991:Antithrombins; D010875:Pipecolic Acids; D013449:Sulfonamides; D001120:Arginine; C031942:argatroban