thromboxane-a2 and Intracranial-Aneurysm

Imbalance between the two arachidonic acid metabolites, prostacyclin (PGI2) and thromboxane A2 (TXA2), is thought to be at least in part responsible for the development of cerebral vasospasm following aneurysm rupture. In 12 patients with subarachnoid hemorrhage the pre- and postoperative serum and CSF levels of PGI2 and TXA2 were measured as a function of their stable hydrolysis products, 6-Keto-PGF1 alpha (PGI2) and thromboxane B2 (TXA2), with a highly specific radioimmunoassay. Serum levels of both metabolites were elevated in half of the patients, but no correlation to the clinical course could be found. However, TXB2 concentration in the CSF was significantly increased preoperatively with close correlation to the amount of intracisternal blood, as detected by CT scan. Furthermore, it could be demonstrated that the postoperative course of the TXB2 concentrations in the CSF reflects the clinical course in such a way that a characteristic secondary rise of TXB2, concentration postoperatively is closely related to the occurrence of cerebral vasospasm and clinical deterioration. The conclusion is drawn that measurement of arachidonic acid metabolites in the CSF may provide important information concerning the pathophysiological events following subarachnoid hemorrhage, especially with regard to incipient cerebral vasospasm.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Arachidonic Acid; Arachidonic Acids; Blood-Brain Barrier; Carotid Artery Diseases; Carotid Artery, Internal; Epoprostenol; Female; Humans; Intracranial Aneurysm; Ischemic Attack, Transient; Male; Middle Aged; Rupture, Spontaneous; Subarachnoid Hemorrhage; Thromboxane A2; Thromboxane B2

Our previous experimental and clinical studies yielded the following results: CSF flow around the subarachnoid vessels is often interrupted by subarachnoid clots; anaerobical incubation of CSF-blood mixture led to a marked fall in the pH value; the vasocontractility of anaerobically incubated CSF-blood mixtures was greater than that of aerobically incubated samples; vasocontraction induced by anaerobically incubated samples was inhibited to a far greater extent the prostaglandin synthesis inhibitor meclofenamic acid than by phenoxybenzamine; cases of asymptomatic marked angiographical vasospasm or of cerebral ischemia with relatively slight angiographical vasospasm were not rarely encountered. Those results lead us to a hypothesis that, in the pathogenesis of cerebral vasospasm, subarachnoid focal acidosis resulting from anaerobical changes of subarachnoid clots may be factor upsetting the balance of the synthesis of TXA2 and PGI2 from PG endoperoxides on the inner surface of cerebral arteries, in favor of TXA2--which plays a role in arterial contraction and in thrombosing with platelet aggregation. On this basis we have been testing the administrations of trapidil, an antagonist and selective synthesis inhibitor of TXA2, in 20 consecutive suitable cases so far, for the prevention of cerebral vasospasm after aneurysmal rupture. Angiographical vasospasm was seen in 9 of the 20 cases, but no signs of cerebral ischemia were detected in 7 of the 9 cases, either clinically or in CT scan. The importance of thrombus formation by platelet aggregation in symptomatic vasospasm are thus suggested.

Topics: Adult; Aged; Cerebral Arteries; Epoprostenol; Female; Humans; Intracranial Aneurysm; Intracranial Embolism and Thrombosis; Ischemic Attack, Transient; Male; Middle Aged; Platelet Aggregation; Subarachnoid Hemorrhage; Thromboxane A2; Trapidil

The results of our previous experimental and clinical studies led us to the hypothesis that, in the pathogenesis of cerebral vasospasm, subarachnoid focal acidosis resulting from anaerobic changes of subarachnoid clots may be a factor upsetting the balanced synthesis of both thromboxane A2 and prostaglandin I2 from prostaglandin endoperoxides on the inner surface of cerebral arteries. Thus, there is a higher concentration of thromboxane A2, a prostanoid that causes arterial contraction and platelet aggregation. We tested the administration of trapidil, an antagonist and selective synthesis inhibitor of thromboxane A2, in a series of 20 cases for the prevention of cerebral vasospasm and cerebral ischemia after aneurysmal rupture. Vasospasm was demonstrated by angiography in 9 of these cases, but only 2 of the 9 showed mild signs of cerebral ischemia. Of the 20 patients, 15 were discharged from the hospital as cured and 3 had a neurological deficit at discharge. Our findings suggest the significance in symptomatic vasospasm of thrombus formation by platelet aggregation and the effectiveness of trapidil as a preventive.

Topics: Adult; Aged; Cerebral Angiography; Female; Humans; Intracranial Aneurysm; Ischemic Attack, Transient; Male; Middle Aged; Pyrimidines; Rupture, Spontaneous; Thromboxane A2; Thromboxanes; Tomography, X-Ray Computed; Trapidil