The effect of ozagrel sodium on photochemical thrombosis in rat: therapeutic window and combined therapy with heparin sodium.
The therapeutic efficacy of ozagrel sodium (ozagrel), alone and in combination with heparin, and its therapeutic time window were studied in a photochemically induced thrombotic cerebral infarction rat model. Cerebral artery thrombosis was induced by irradiating the brain with green light through intact skull using rose bengal as the photosensitizing dye. One set of animals was treated immediately after thrombosis with (1) vehicle, (2) 10 mg/kg ozagrel in saline, intravenously (i.v.), (3) 150 U/kg unfractioned heparin, subcutaneously (s.c.), or (4) ozagrel, i.v. plus heparin, s.c. Infarct volume was significantly smaller and edema was reduced in the ozagrel-treated groups compared to the vehicle-treated group; heparin did not convey additional benefit. In another set of animals, rats were given either vehicle or 10 mg/kg ozagrel in saline, i.v., 60 min or 120 min after induction of thrombosis. Ozagrel reduced infarct volume, but its effect diminished with delayed administration. The therapeutic window was determined to be less than 60 minutes after induction of thrombosis.
Arii
Kazumasa
K
Second Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan. super7@nms.ac.jp
Igarashi
Hironaka
H
Arii
Takako
T
Katayama
Yasuo
Y
D000818:Animals; D002536:Cerebral Arteries / Q000473:pathology / Q000528:radiation effects; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use*; D007091:Image Processing, Computer-Assisted; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D020767:Intracranial Thrombosis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008027:Light; D008297:Male; D008689:Methacrylates / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D013997:Time Factors; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D008689:Methacrylates; D006493:Heparin; D013930:Thromboxane-A Synthase; C034364:ozagrel