Effect of TTC-909 in a middle cerebral artery thrombosis model in stroke-prone spontaneously hypertensive rats.
We investigated the effect of TTC-909, a preparation of the stable prostaglandin I(2) analogue clinprost (isocarbacyclin methylester; methyl 5-[(1S,5S,6R,7R)-7-hydroxy-6-[(E)-(S)-3-hydroxy-1-octenyl] bicyclo[3.3.0]oct-2-en-3-yl] pentanoate) incorporated into lipid microspheres, on infarct volume 24 h after photochemically induced thrombotic occlusion of the middle cerebral artery in stroke-prone spontaneously hypertensive rats (SHR). Under anesthesia, the photosensitizing dye rose bengal (20 mg/kg) was administered intravenously and photoirradiation with green light (wavelength 540 nm) on the middle cerebral artery above the rhinal fissure was achieved using a xenon lamp for 10 min. Infarct volume 24 h after the photochemically induced thrombotic occlusion of the middle cerebral artery was significantly larger in stroke-prone SHR than in Wistar rats. When TTC-909 in doses of 100, 300 and 900 ng/kg/h was intravenously infused for 3 h, starting immediately after the end of the 10-min photoirradiation, the infarct volume was dose-dependently reduced and was statistically significant at a dose of 900 ng/kg/h (p < 0.05). Ozagrel, a thromboxane A(2) synthetase inhibitor, significantly reduced the infarct volume. The model of photochemically induced thrombotic occlusion of the middle cerebral artery in stroke-prone SHR is very useful, because the cerebral infarction is large enough and reproducible. TTC-909 may be effective for the treatment of acute ischemic stroke.
Karasawa
Yasuko
Y
Pharmacology Laboratory, Research Center, Taisho Pharmaceutical Co., Ltd., Yoshino-cho 1-403, Saitama 330-8530, Japan.
Hitomi
Takehiko
T
Komiyama
Hiroko
H
Isobe
Yoshihiko
Y
Kobayashi
Tsunefumi
T
Yoshida
Shigeru
S
Nakaike
Shiro
S
Araki
Hiroaki
H
D000818:Animals; D001921:Brain / Q000473:pathology; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology; D020767:Intracranial Thrombosis / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008689:Methacrylates / Q000627:therapeutic use; D008863:Microspheres; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D005343:Fibrinolytic Agents; D008689:Methacrylates; C068518:TTC 909; D011464:Epoprostenol; D013930:Thromboxane-A Synthase; C034364:ozagrel