Methods and compositions for treatment for coronary and arterial aneurysmal subarachnoid hemorrhage

Abstract

Methods and compositions for treating a complication associated with aneurysmal subarachnoid hemorrhage (SAH), the method comprising administering an effective amount of a nitric oxide precursor to a subject in need thereof. Methods and compositions for treating vasospasm, the method comprising administering an effective amount of a nitric oxide precursor to a subject in need thereof.

1 . A method of treating a complication associated with aneurysmal subarachnoid hemorrhage (SAH), the method comprising administering an effective amount of a nitric oxide precursor to a subject in need thereof. 
   
   
       2 . The method of  claim 1 , wherein the subject has suffered trauma that results in SAH. 
   
   
       3 . The method of  claim 1 , wherein the nitric oxide precursor comprises at least one of citrulline, a precursor that generates citrulline in vivo, a pharmaceutically acceptable salt thereof, and combinations thereof. 
   
   
       4 . The method of  claim 1 , wherein the administering is intravenously or orally. 
   
   
       5 . The method of  claim 1 , wherein the nitric oxide precursor is administered in a dose ranging from about 100 mg to about 30,000 mg. 
   
   
       6 . The method of  claim 5 , wherein the nitric oxide precursor is administered in a dose ranging from about 250 mg to about 1,000 mg. 
   
   
       7 . A method of treating vasospasm, the method comprising administering an effective amount of a nitric oxide precursor to a subject in need thereof. 
   
   
       8 . The method of  claim 7 , wherein the vasospasm is associated with aneurysmal subarachnoid hemorrhage in the subject. 
   
   
       9 . The method of  claim 7 , wherein the subject has suffered trauma that results in vasospasm. 
   
   
       10 . The method of  claim 7 , wherein the vasospasm is associated with atherosclerosis in the subject. 
   
   
       11 . The method of  claim 10 , wherein the atherosclerosis is associated with coronary arterial disease, with carotid arterial disease, with peripheral arterial disease, or combinations thereof. 
   
   
       12 . The method of  claim 7 , wherein the nitric oxide precursor comprises at least one of citrulline, a precursor that generates citrulline in vivo, a pharmaceutically acceptable salt thereof, and combinations thereof. 
   
   
       13 . The method of  claim 7 , wherein the administering is intravenously or orally. 
   
   
       14 . The method of  claim 7 , wherein the nitric oxide precursor is administered in a dose ranging from about 100 mg to about 30,000 mg. 
   
   
       15 . The method of  claim 14 , wherein the nitric oxide precursor is administered in a dose ranging from about 250 mg to about 1,000 mg. 
   
   
       16 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an amount of citrulline effective to raise plasma citrulline level to treat a complication associated with aneurysmal subarachnoid hemorrhage (SAH) or vasospasm in a subject, wherein the level is determined by comparing plasma citrulline levels in a subject to be treated to that observed in a subject not suffering from a complication associated with aneurysmal subarachnoid hemorrhage (SAH) or vasospasm. 
   
   
       17 . The pharmaceutical composition of  claim 16 , wherein the amount of citrulline effective to raise plasma citrulline level in a subject to at least 5 μmol/liter, optionally at least 10 μmol/liter, optionally at least 20 μmol/liter, optionally at least 25 μmol/liter, and optionally about 37 μmol/liter. 
   
   
       18 . The pharmaceutical composition of  claim 16 , wherein the pharmaceutical composition is adapted for intravenous or oral administration.