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.</p

Prostacyclin and thromboxane in cerebral vasospasm: effects of prostacyclin on experimentally-induced cerebral vasospasm.

The basilar artery was exposed transclivally , and a vascular spasm was produced by topical application of a lysed erythrocyte solution. The maximum fall in the mean arterial blood pressure (MABP) after administering of 2 micrograms/ kgBW and 15 micrograms/ kgBW of PGI2, ranged from 35 to 45 mmHg and from 65 to 85 mmHg, respectively. The drop in MABP after an injection of papaverine hydrochloride (1.5 mg/ kgBW ) was between 30 and 40 mmHg. If MABP did not fall, the vessel diameter did not change. Although papaverine elicited marked dilation of both normal and spastic basilar arteries, PGI2 did not dilate normal basilar arteries and produced only a slight dilation of spastic basilar arteries. Subarachnoid hemorrhage (SAH) was simulated by an intracisternal injection of fresh autologous arterial blood 3 days prior to experimentation. Changes in regional cerebral blood flow (rCBF) were measured by the heat clearance method, before and after an intravenous administration of either PGI2 or papaverine hydrochloride. Changes in rCBF fell into 3 categories: Type A, no change; Type B, a change which varied with the arterial blood pressure, and Type C, an increase rCBF despite systemic hypotension. Type A or B was observed in 17 out of 19 cats with SAH in which PGI2 was administered intravenously, and Type C was observed in only 2 cats. Thirteen untreated control cats produced a Type A or B response in 12, and Type C response in only one cat. There were no significant differences between the control and SAH groups. When 15-hydroperoxy-5, 8, 11, 13-eicosatetraenoic acid (15-HPETE) was infused, the same results prevailed. Papaverine hydrochloride increased rCBF either transiently or continuously in all cats. These results suggest that PGI2 dilates extracranial rather than intracranial vessels regardless of the presence or absence of cerebral vasospasm.</p