Cerebral vasospasm is the leading cause of poor postoperative outcome of patients with subarachnoid hemorrhage due to ruptured aneurysms. Constriction of the arterial lumen begins about 4 days after the hemorrhage. Patients begin to show symptoms and signs of spasm at about the seventh day which last for 2-3 weeks. However, the spastic arteries begin to dilate by themselves after the fourth week if the patient can tolerate the ischemic insult. The primary cause of spasm is the degradation products of red blood cells in subarachnoid clot. However, further details of the mechanism have yet to be clarified. Both constriction of smooth muscle cells and inflammation seem to be involved. After the patient is secured from further bleeding by a successful neck clipping or intravascular treatment by GDC (Guglielmi detachable coil), 30% of the patients suffer from vasospasm in various forms, resulting in neurological deficits that range from mild cognitive dysfunction, sensorimotor paralysis, and aphasia, to death. Although, nimodip-ine, a calcium entry blocker, is widely used in the Western world, its effect has not always been satisfactory. HA1077 has been used in about 12,000 patients each year since it was approved in Japan in 1995. A recent comparative study in China between HA1077 and nimodipine on patients with subarach-noid hemorrhage (SAH) showed that HA1077 is equal to or better than ni-modipine (unpublished data).
In this chapter, clinical effects as well as pharmacological analysis of HA1077 using model animals with experimental vasospasm or cerebral infarction will be further described.
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