Effects of thromboxane synthetase inhibitor (RS-5186) on experimentally-induced cerebral vasospasm.
RS-5186, which inhibits thromboxane A2 (TXA2) synthetase activity, ameliorated delayed cerebral vasospasm in a canine two-hemorrhage model. Subarachnoid hemorrhage was induced in 15 dogs, which were divided into two groups. In the RS-5186-treated group (9 dogs), 50 mg kg-1 of RS-5186 was administered twice a day for seven days. The remaining six dogs without administration of RS-5186 were used as a control group. In the RS-5186-treated group, the angiographic diameter of the basilar artery on Day 7 after subarachnoid hemorrhage was constricted to 60.9% +/- 11.6% (n = 9, mean +/- SD) of that on Day 0, before subarachnoid hemorrhage. The corresponding value was 42.8% +/- 6.1% (n = 6) in the control group. There was a statistically significant difference between these percentages. In the RS-5186-treated group, plasma thromboxane B2 level on Day 7 was 144.3 +/- 28.1 pg ml-1 (n = 4), which was lower than the 815.5 +/- 162.0 pg ml-1 (n = 4) in the control group (p < 0.0005). The plasma 6-keto-prostaglandin F1 alpha level on Day 7 was 180.5 +/- 66.5 pg ml-1 (n = 4) in the RS-5186-treated group, and higher than 107.3 +/- 12.4 pg ml-1 (n = 4) in the control group (p = 0.0734). Thus, administration of RS-5186 reduced TXA2 plasma level and had a beneficial effect on angiographically-detected delayed vasospasm.
Takeuchi
H
H
Division of Neurosurgery, Institute of Neurological Sciences, Tottori University, Yonago, Japan.
Tanabe
M
M
Okamoto
H
H
Yamazaki
M
M
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000473:pathology; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011464:Epoprostenol / Q000096:biosynthesis; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D013345:Subarachnoid Hemorrhage / Q000150:complications; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use*; D013928:Thromboxane A2 / Q000096:biosynthesis; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors* / Q000502:physiology; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000201:enzymology
D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D013876:Thiophenes; C055806:RS 5186; D013928:Thromboxane A2; D011464:Epoprostenol; D013930:Thromboxane-A Synthase