Hiroshi Kawai (#), Kazuo Umemura and Mitsuyoshi Nakashima
Department of Pharmacology, Hamamatsu University School of Medicine, 3600 Handa-cho, Hamamatsu 431-31, Japan
(#) Present address: Pharmaceuticals Laboratory 2, Yokohama Research Center, Mitsubishi Chemical Corporation, 1000 Kamoshida, Aoba-ku, Yokohama 227, Japan
Abstract: Ischemic cerebral infarcts induce hypercoagulation and microthrombosis in the surrounding region, thus leading to vascular occlusion. We determined whether microthrombi contribute to the spreading of ischemic lesions following thrombotic middle cerebral artery (MCA) occlusion and also determined whether argatroban, a selective thrombin inhibitor, reduces the formation of the microthrombi and the area of the ischemic lesions. The rat left MCA was occluded by a platelet-rich thrombus formed following the photochemical reaction between rose bengal and green light. Microthrombi were histologically identified in the left hemisphere. The extent of ischemic lesions and microthrombi containing fibrin increased in a time-dependent manner after MCA occlusion. Argatroban inhibited the formation of microthrombi up to 3 hr after MCA occlusion; beyond 3 hr, it was ineffective. Argatroban also significantly (P<0.01) reduced the size of ischemic cerebral lesions at 6 hr after MCA occlusion. It is concluded that the formation of microthrombi contributes to the progression of ischemic lesions in the early stage. It is likely that thrombin generated following thrombotic MCA occlusion contributes to the progression of ischemic lesions by promoting the formation of microthrombi. Argatroban can reduce the formation of microthrombi and ischemic lesions in the early stage.
Thrombin, Argatroban, Microthrombosis, Thrombotic middle cerebral artery occlusion
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