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 t hrombin inhibitor, argatroban, may ameliorate the postischemic cerebral cir culation and attenuate mortality after 10 min of forebrain ischemia. Postis chemic subcutaneous injection of argatroban (5 mg/kg) significantly attenua ted mortality (9.1%) compared with non-treatment (45.5%) during 14 days' ob servation period. This effect coincided with: (1) increased cortical CBF af ter reperfusion; (2) attenuation of brain edema; and (3) less severe cell d amages 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 ble eding in the surgical wound and 13 bleeding-avoided gerbils did not show si gnificant amelioration in mortality (30.8%). These findings suggest that ar gatroban is an effective anticoagulant for prevention of cell damage after a relatively long forebrain ischemia. (C) 2000 Elsevier Science Ireland Ltd . All rights reserved.