title: Reversal of cerebral vasospasm via intravenous sodium nitrite after subarachnoid hemorrhage in primates.
abstract: OBJECTIVE
  Subarachnoid hemorrhage (SAH)-induced vasospasm is a significant underlying cause of aneurysm rupture-related morbidity and death. While long-term intravenous infusion of sodium nitrite (NaNO(2)) can prevent cerebral vasospasm after SAH, it is not known if the intravenous administration of this compound can reverse established SAH-induced vasospasm. To determine if the intravenous infusion of NaNO(2) can reverse established vasospasm, the authors infused primates with the compound after SAH-induced vasospasm was established.
  
  
  METHODS
  Subarachnoid hemorrhage-induced vasospasm was created in 14 cynomolgus macaques via subarachnoid implantation of a 5-ml blood clot. On Day 7 after clot implantation, animals were randomized to either control (saline infusion, 5 monkeys) or treatment groups (intravenous NaNO(2) infusion at 300 μg/kg/hr for 3 hours [7 monkeys] or 8 hours [2 monkeys]). Arteriographic vessel diameter was blindly analyzed to determine the degree of vasospasm before, during, and after treatment. Nitric oxide metabolites (nitrite, nitrate, and S-nitrosothiols) were measured in whole blood and CSF.
  
  
  RESULTS
  Moderate-to-severe vasospasm was present in all animals before treatment (control, 36.2% ± 8.8% [mean ± SD]; treatment, 45.5% ± 12.5%; p = 0.9). While saline infusion did not reduce vasospasm, NaNO(2) infusion significantly reduced the degree of vasospasm (26.9% ± 7.6%; p = 0.008). Reversal of the vasospasm lasted more than 2 hours after cessation of the infusion and could be maintained with a prolonged infusion. Nitrite (peak value, 3.7 ± 2.1 μmol/L), nitrate (18.2 ± 5.3 μmol/L), and S-nitrosothiols (33.4 ± 11.4 nmol/L) increased significantly in whole blood, and nitrite increased significantly in CSF.
  
  
  CONCLUSIONS
  These findings indicate that the intravenous infusion of NaNO(2) can reverse SAH-induced vasospasm in primates. Further, these findings indicate that a similar treatment paradigm could be useful in reversing cerebral vasospasm after aneurysmal SAH.
authors: Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1414, USA.
authors: Ali Reza
authors: AR
authors: Fathi
authors: Ryszard M
authors: RM
authors: Pluta
authors: Kamran D
authors: KD
authors: Bakhtian
authors: Meng
authors: M
authors: Qi
authors: Russell R
authors: RR
authors: Lonser
mesh_terms: D000818:Animals; D002533:Cerebral Angiography; D004195:Disease Models, Animal; D007262:Infusions, Intravenous; D008252:Macaca fascicularis; D020768:Middle Cerebral Artery / Q000000981:diagnostic imaging / Q000187:drug effects; D009566:Nitrates / Q000097:blood / Q000134:cerebrospinal fluid; D009569:Nitric Oxide / Q000097:blood / Q000134:cerebrospinal fluid; D009573:Nitrites / Q000097:blood / Q000134:cerebrospinal fluid; D026403:S-Nitrosothiols / Q000097:blood / Q000134:cerebrospinal fluid; D012977:Sodium Nitrite / Q000494:pharmacology*; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000378:metabolism; D016896:Treatment Outcome; D020301:Vasospasm, Intracranial / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism
chemical_list: D009566:Nitrates; D009573:Nitrites; D026403:S-Nitrosothiols; D009569:Nitric Oxide; D012977:Sodium Nitrite