Effect of a platelet-activating factor antagonist, E5880, on cerebrovasospasm following subarachnoid hemorrhage in a canine double-hemorrhage model.
We investigated the effects of a platelet-activating factor (PAF) antagonist, E5880 (1-ethyl-2-[N-(2-methoxy)benzoyl-N-[(2)-2-methoxy-3-(4-octadecycarbamoylox)piperidinocarbonyloxy-propyloxy]carbonyl]aminomethyl-pyridiniumchloride), on subarachnoid hemorrhage-induced prolongation of cerebral circulation time and decrease in the basilar artery diameter in a canine double-hemorrhage model. Animals were assigned to three groups, control (saline), E5880 1.2 mg/kg and E5880 2.4 mg/kg. For measurement of cerebral circulation time, regions of interest were chosen at the basilar artery and the straight sinus in order to obtain time-density curves. Cerebral circulation time was defined as the difference between the arterial and venous peaks. Cerebral circulation time and basilar artery diameter were assessed by intra-arterial digital subtraction angiography (IA-DSA) on Days 0, 2 and 7. The prolongation of cerebral circulation time following subarachnoid hemorrhage was significantly inhibited by intravenous administration of 2.4 mg/kg of E5880. Basilar artery constriction was also reduced by E5880. Thus, E5880 had preventive effects on the prolongation of cerebral circulation time and the vasoconstriction of basilar artery in this model. These results suggest that E5880 may have a preventive effect on neurological symptoms aggravated by cerebrovascular lesions following subarachnoid hemorrhage.
Abe
Yoshihisa
Y
Developmental Pharmacology Research Section, Drug Safety and Disposition Research Laboratories, Eisai Company, Limited, Tsukuba City, Ibaraki, 300-2635, Japan. y2-abe@hhc.eisai.co.jp
Kasuya
Hidetoshi
H
Suzuki
Suguru
S
Yamanishi
Yoshiharu
Y
Hori
Tomokatsu
T
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D020301:Vasospasm, Intracranial / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*
D010880:Piperidines; D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; C072429:E 5880