15-hydroperoxy-5-8-11-13-eicosatetraenoic-acid and Ischemic-Attack--Transient

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

The in vivo spasmogenic capacity of a lipid hydroperoxide (15-hydroperoxy arachidonic acid: 15-HPAA) was studied in a chronic experiment using the dog. The 15-HPAA was injected into the cisterna magna (0.2 or 2 mg emulsified in bovine serum albumin solution). The changes in diameter of the basilar artery were followed by angiography, and the morphological changes were studied by electron microscopy. The cisternal injection of 0.2 mg of 15-HPAA caused a mild constriction of the basilar artery which lasted about 7 hours. The cisternal injection of 2 mg of 15-HPAA caused a biphasic constriction, the initial phase of which was a moderate narrowing lasting about 10 hours. The second phase started on the 2nd or the 3rd day after injection. The intensity of the arterial narrowing was more pronounced in the second phase than in the first. The prolonged secondary constriction of the basilar artery continued until sacrifice on the 7th day after injection. Electron microscopic study revealed a marked degenerative change in the endothelium and myonecrotic changes in the tunica media. The prolonged arterial constriction in the second phase was invariably associated with remarkable degeneration of the endothelium. On the other hand, myonecrotic changes were limited to a small number of smooth-muscle cells. The results of the present study are consonant with the hypothesis that lipid peroxidation associated with lysis of the subarachnoid clot is involved in the genesis of chronic vasospasm in subarachnoid hemorrhage.

Topics: Animals; Arachidonic Acids; Basilar Artery; Cisterna Magna; Dogs; Injections; Ischemic Attack, Transient; Leukotrienes; Lipid Peroxides; Microscopy, Electron; Peroxides; Radiography; Vasoconstriction