PATHOPHYSIOLOGY OF CHRONIC CEREBRAL VASOSPASM

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DESCRIPTION (Investigator's Abstract): About 30,000 North Americans have rupture of an intracranial aneurysm each year. Because aneurysm rupture, among all forms of intracranial bleeding, almost uniquely deposits a large volume of blood clot on the adventitial side of the basal conducting arteries, it is frequency the cause of a delayed onset, long- lasting arterial constriction known as vasospasm. Vasospasm can be so severe that the vessels may actually be occluded and distal ischemia can result with attendant delayed infarction the second stroke. About two- thirds of ruptured aneurysm patients will show moderate to severe degrees of angiographic vasospasm if subjected to angiography a week or so after the initial hemorrhage. About half of these patients will develop clinical signs of delayed ischemia. The death rate from this phenomenon has fallen steadily in recent years with the widespread avoidance of dehydration and antifibrinolytic agents. In addition, calcium antagonists, hypertension and hypervolemia may have exerted a beneficial effect Currently however, about 15% of patients will still die or he severely damaged by vasospasm. Evidence of ischemic cerebral infarction is noted in about 30% of the fatal cases of aneurysmal ruptures if they survive past the initial few days. Our long--term objectives are: (I) The prevention of vasospasm after subarachnoid hemorrhage (2) The successful treatment of established vasospasm. The specific aims are: 1)To determine which component or components of oxyhemoglobin cause vasospasm. (2) To determine the efficacy of endothelia antagonists in treatment of vasospasm after subarachnoid hemorrhage. (3) To compare the efficacy of tissue-type plasminogen activator and urokinase for lysis of subarachnoid clot and prevention of vasospasm. (4) To investigate calcium homeostasis in the cellular mechanisms of vasospasm by monitoring Ca?+ dependent K+ channels. (5) To characterize the calcium channels in cerebral vascular smooth muscle cells and determine how they are affected by blood components. (6) To study the effect of blood components on potassium channels of cerebrovascular smooth muscle cells. (7) To test the actions of blood components on ion channels of cerebral endothelium.