Prevention of chronic experimental cerebral vasospasm with ibuprofen and high-dose methylprednisolone

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✓ Severe chronic cerebral vasospasm was reliably induced in dogs by two injections, 2 days apart, of autologous blood into the cisterna magna. Treatment with ibuprofen or high-dose methylprednisolone after the first injection prevented or reduced vasospasm. Both drugs reduced meningismus and accelerated the rate of neurological recovery. Compared with specimens from normal dogs, rings of basilar arteries obtained from untreated dogs contracted weakly in response to 5-hydroxytryptamine, prostaglandin F, potassium chloride, and barium chloride. Rings of arteries from dogs who received ibuprofen or methylprednisolone contracted more strongly. Electron micrographs of basilar arteries from untreated dogs showed degeneration of smooth muscle, whereas those from treated dogs did not. Thus, what is termed “chronic cerebral vasospasm” probably represents a structural derangement of the blood vessel wall leading to its narrowing, rather than a sustained contraction of the vascular smooth muscle. Administration of high-dose methylprednisolone and ibuprofen can prevent its occurrence.

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Address reprint requests to: Thoralf M. Sundt, Jr., M.D., Cerebrovascular Research, St. Mary's Hospital, Rochester, Minnesota 55901.

© AANS, except where prohibited by US copyright law.

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Figures

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    Average duration of meningeal signs in treated and untreated dogs.

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    Nature and evolution of neurological deficits after experimental subarachnoid hemorrhage.

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    Angiograms in an untreated dog. A: Subtraction angiogram showing the baseline appearance of the basilar artery. B: Final subtraction angiogram of the basilar artery showing severe diffuse spasm on Day 8.

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    Angiograms in an ibuprofen-treated dog. A: Subtraction angiogram showing the baseline appearance of the basilar artery. B: Final subtraction angiogram on Day 8 demonstrating prevention of spasm in the basilar artery.

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    Angiograms in a methylprednisolone-treated dog. A: Subtraction angiogram showing the baseline appearance of the basilar artery. B: Final subtraction angiogram on Day 8 demonstrating prevention of spasm in the basilar artery.

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    Severity of angiographic vasospasm. Animals treated with ibuprofen or methylprednisolone show significantly less vasospasm than untreated animals.

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    Contractile responses of isolated basilar artery rings taken from control, untreated, ibuprofen-treated, and methylprednisolone-treated dogs.

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    Electron micrographs of sections of canine basilar artery. Upper Left: Section from a control dog showing the appearance of the endothelial cells (E) adjacent to the vessel lumen (L), the elastic lamina (EL), and smooth-muscle cells (S). × 1667. Upper Right: Section from an untreated dog showing striking necrosis of the smooth-muscle cells (S). Ultrastructural abnormalities involving the endothelium (E) and the elastic lamina (EL) are also apparent. × 1085. Lower Left: Section from a dog treated with ibuprofen. The appearance of the smooth-muscle cells (S) is indistinguishable from that seen in normal dogs. The endothelium (E) and elastic lamina (EL) still appear abnormal. × 1100. Lower Right: Specimen from a dog treated with methylprednisolone. The appearance of the smooth-muscle cells (S) is indistinguishable from that seen in normal dogs. The endothelium (E) and elastic lamina (EL) still appear abnormal. × 1100.

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