| Project/Area Number |
01480138
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General pharmacology
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
TODA Noboru Shiga University of Medical Science, Department of Pharmacology, Professor, 医学部, 教授 (50025590)
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| Co-Investigator(Kenkyū-buntansha) |
AYAJIKI Kazuhide Shiga University of Medical Science, Department of Pharmacology, Instructor, 医学部, 助手 (10167968)
YOSHIDA Kazuhide Shiga University of Medical Science, Department of Pharmacology, Instructor, 医学部, 助手 (00210683)
OKAMURA Tomio Shiga University of Medical Science, Department of Pharmacology, Assistant Profe, 医学部, 助教授 (70152337)
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| Project Period (FY) |
1989 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1990: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1989: ¥4,000,000 (Direct Cost: ¥4,000,000)
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| Keywords | Cerebral vasospasm, / subarachnoid hemorrhage, / oxyhemoglobin, / prostaglandin, / endothelium, / cyclooxygenase inhibitor, / calcium entry blocker, / ascorbic acid / 脳動脈 / 血管内皮 |
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| Research Abstract |
In order to anaylze the mechanism underlying cerebral vasospasm after subarachnoid hemorrhage (SAH) and to determine the pharmacological basis for treatment and prophylaxis of the spasm, experiments were carried out in monkey and dog basilar arteries in vivo and in vitro that were exposed to oxyhemoglobin (oxyHb), erythrocyte hemolysate and blood, quite important substances in generating the cerebral vasospasm. The results obtained are as follows. (1) Contractions caused by oxyHb and hemolysate were endothelium-dependent and suppressed by treatment with aspirin, indomethacin and ONO3708, a PG receptor antagonist, but were unaffected by superoxide dismutase and OKY046, a thromboxane A_2 synthesis inhibitor. (2) OxyHb released significant amounts of prostaglandin (PG) E_2 and PGF_<2alpha> into the bathing media, which were measured by immunoradiological method. The stimulated release was depressed by indomethacin. (3) Intracisternal injections of oxyHb or autologous blood produced a basi
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lar artery spasm in anesthetized dogs and monkeys that was determined angiographically. The maximal arterial constriction was attained 2 hrs after oxyHb and 7 days after blood ; the magnitudes of constriction were almost identical. (4) Treatment with aspirin prevented the vasospasm caused by oxyHb, whereas OKY046 was ineffective. Ca^<++> entry blockers were also effective in preventing the Hb-induced spasm. (5) Incubation of oxyHb with ascorbic acid abolished the vasospastic actions of oxyHb in isolated and in vivo basilar arteries.
The findings obtained so far indicate that basilar artery constrictions caused in vivo and in vitro by oxyHb and hemolysate are associated with vasoconstrictor PGs, but not thromboxane A_2, released mainly from the endothelium. Treatment with cyclooxygenase inhbitors, PG receptor antagonists and Ca^<++> entry blockers or cisternal irrigation with artifical fluids containing ascorbic acid may be clinically effective in preventing the genesis of cerebral vasospasm after SAH. Cerebral vasospasm elicited by intracisternal injections of oxyHb would be a useful model for the analysis of mechanisms underlying delayed vasospasm after SAH. Less
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