15-hydroperoxy-5-8-11-13-eicosatetraenoic-acid and Subarachnoid-Hemorrhage

Severe cerebral vasospasm as confirmed by angiography was induced in dogs by injection of autologous blood into the cisterna magna, and the resultant leukotriene formation in the isolated basilar artery was examined. When stimulated with calcium ionophore (A 23187), the arteries of the treated animals produced a significant amount of leukotrienes B4 (85 +/- 12 pmol/mg protein, n = 3) and C4 (72 +/- 14 pmol/mg), in addition to 5(S)-hydroxy-6,8,11,14-eicosatetraenoic acid. Structural elucidations of these metabolites were performed by radioimmunoassays or gas chromatography-mass spectrometry, following purification with HPLC. The artery of the untreated dog produced none of these compounds from either exogenous or endogenous arachidonic acid, under stimulation with the calcium ionophore. However, the homogenates from both animals converted exogenous leukotriene A4 to leukotrienes B4 and C4. These observations suggest that the normal basilar artery contains no detectable amount of 5-lipoxygenase, and that a prominent activation of this enzyme occurred (2.1 nmol 5-HETE/5 min/mg of protein) after subarachnoidal hemorrhage. The observation that fatty acid hydroperoxides stimulated the 5-lipoxygenase activity indicates a possible role of lipid peroxides in the development of vasospasm.

Topics: Animals; Arachidonate 5-Lipoxygenase; Arachidonate Lipoxygenases; Arachidonic Acid; Arachidonic Acids; Basilar Artery; Chromatography, High Pressure Liquid; Dogs; Enzyme Activation; Gas Chromatography-Mass Spectrometry; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Leukotrienes; Lipid Peroxides; Radioimmunoassay; SRS-A; Subarachnoid Hemorrhage

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.

Topics: Animals; Arachidonic Acids; Basilar Artery; Blood Pressure; Cats; Cerebrovascular Circulation; Epoprostenol; Ischemic Attack, Transient; Leukotrienes; Lipid Peroxides; Papaverine; Subarachnoid Hemorrhage