[Pharmacological therapeutic prospects of cerebral vasospasm].
New therapies of cerebral vasospasm aim to prevent the effects of subarachnoid haemorrhage. These effects result in red blood cell haemolysis and release of oxyhaemoglobin, free radicals formation and lipid peroxidations, imbalance in endothelial modulation of vasomotor tone and activation of the complement system. Low doses of fibrinolytic agents administered intrathecally accelerate the fibrinolysis of the clot and reduce the oxyhaemoglobin release. The tissue-type plasminogen activator has proven to be effective in preventing vasospasm, but the modalities of this therapy remain to be defined. Free radical reactions may be inhibited by free radical scavengers and inhibitors of lipid peroxidations. Tirilazad is a potent inhibitor of lipid peroxidations, which improves the patients' outcome and has gone to Phase III human trials. Superoxide dismutase and tropolone derivatives are currently evaluated in animal models. Vasomotor tone can be modified in experimental models either by blocking endothelin receptors (BQ-123), or by facilitating the release and enhancing the effect of nitric oxide using protein kinase C inhibitors, drugs that increase intracellular calcium (cyclopiazonic acid, LP-805) and free radicals scavengers (superoxide dismutase). These possibilities are being investigated. Finally, preliminary studies have demonstrated the efficacy of FUT-175, an inhibitor of the complement system, in the prevention of vasospasm. In the next years, these new therapies have to be validated by prospective and randomized clinical trials to propose guidelines for the management of patients at risk of cerebral vasospasm after aneurysmal rupture.
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Service universitaire d'anesthésie-réanimation, CHR de la Citadelle, Liège, Belgique.
D000975:Antioxidants / Q000627:therapeutic use; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D007276:Injections, Intraventricular; D002546:Ischemic Attack, Transient / Q000188:drug therapy*; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors; D010108:Oxyhemoglobins / Q000378:metabolism; D010960:Plasminogen Activators / Q000494:pharmacology / Q000627:therapeutic use*; D011281:Pregnatrienes / Q000627:therapeutic use; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000494:pharmacology
D000975:Antioxidants; D008054:Lipid Peroxides; D010108:Oxyhemoglobins; D011281:Pregnatrienes; D013482:Superoxide Dismutase; D010960:Plasminogen Activators; C053355:tirilazad
Les perspectives thérapeutiques pharmacologiques du vasospasme cérébral.