Prostacyclin and thromboxane in cerebral vasospasm II: Effects of thromboxane synthetase inhibitor (OKY-1581) on experimentally-induced cerebral vasospasm.
OKY-1581, a thromboxane A2 (TXA2) synthetase inhibitor, was administered to cats with normal and constricted basilar arteries. At a dose of 60mg/kg (i.v.), both normal and constricted vessels dilated, and the mean arterial blood pressure (MABP) fell from 55 to 75 mmHg. If MABP remained constant, vessel diameter did not change. Subarachnoid hemorrhage (SAH) was simulated by intracisternal injection of autologous arterial blood. Regional cerebral blood flow (rCBF) was assessed by the heat clearance and H2 clearance methods. The two methods presented similar response profiles. rCBF responses to intravenous OKY-1581 fell into 3 categories: A) no change in rCBF, B) decrease in rCBF related to MABP and C) increase in rCBF in the presence of hypotension. Types A and B were observed in 3 out of 10 control cats and 4 out of 14 SAH-induced cats, with Type C responses in the remainder. There was no significant difference between the groups. While the results do not support a major role for TXA2 in cerebral vasospasm pathogenesis, OKY-1581 may still be useful in the treatment of cerebral vasospasm, as it improves distal and deep circulation and inhibits platelet aggregation.
D000179:Acrylates / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects; D011464:Epoprostenol / Q000096:biosynthesis; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism; D008433:Mathematics; D008689:Methacrylates / Q000627:therapeutic use*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D013928:Thromboxane A2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014664:Vasodilation / Q000187:drug effects
D000179:Acrylates; D008689:Methacrylates; D013928:Thromboxane A2; C031517:2-methyl-3-(4-(3-pyridinylmethyl)phenyl)-2-propenoic acid; D011464:Epoprostenol; D010088:Oxidoreductases; D013930:Thromboxane-A Synthase