Effects of a nitric oxide donor on and correlation of changes in cyclic nucleotide levels with experimental vasospasm

Yasuo Aihara, Babak S. Jahromi, Reza Yassari, Tetsuro Sayama, R. Loch Macdonald, Warren R. Selman, E. Sander Connolly, J. Max Findlay, Jeffrey E. Thomas

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

OBJECTIVE: Vasospasm after subarachnoid hemorrhage (SAH) may result from hemoglobin-mediated removal of nitric oxide (NO) from the arterial wall. We tested the ability of the long-acting, water-soluble, NO donor (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-1,2-diolate (DETA/NO), delivered via continuous intracisternal infusion, to prevent vasospasm in a nonhuman primate model of SAH. METHODS: First, vasorelaxation in response to DETA/NO was characterized in vitro by using monkey basilar artery rings under isometric tension. Next, monkeys were randomized to undergo angiography, unilateral SAH, and no treatment (SAH only, n = 4) or treatment with DETA/NO (1 mmol/L, 12 ml/d, n = 4) or decomposed DETA/NO (at the same dose, n = 4). Vasospasm was assessed by angiography, which was performed on Day 0 and Day 7. Levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate (cGMP) were measured in cerebral arteries on Day 7. RESULTS: DETA/NO produced significant relaxation of monkey arteries in vitro, which reached a maximum at concentrations of 10-5 mol/L. In monkeys, angiography demonstrated significant vasospasm of the right intradural cerebral arteries in all three groups, with no significant difference in vasospasm among the groups (P > 0.05, analysis of variance). The ratios of cGMP or cyclic adenosine monophosphate levels in the right and left middle cerebral arteries were not different among the groups (P > 0.05, analysis of variance). There was no significant correlation between arterial cGMP contents and the severity of vasospasm. CONCLUSION: DETA/NO did not prevent vasospasm. There was no correlation between the severity of vasospasm and cyclic adenosine monophosphate and cGMP levels in the cerebral arteries. These results suggest that events downstream of cyclic nucleotides may be abnormal during vasospasm.

Original languageEnglish (US)
Pages (from-to)661-667
Number of pages7
JournalNeurosurgery
Volume52
Issue number3
DOIs
StatePublished - Mar 1 2003
Externally publishedYes

Keywords

  • Cyclic nucleotides
  • Nitric oxide
  • Subarachnoid hemorrhage
  • Vasospasm

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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