Time course of production of hydroxyl free radical after subarachnoid hemorrhage in dogs

R. Loch Macdonald, Linda S. Marton, Paula K. Andrus, Edward D. Hall, Lydia Johns, Michael Sajdak

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Vasospasm after subarachnoid hemorrhage (SAH) is associated with lipid peroxidation. However, lipid peroxides increase in a delayed fashion after SAH and may be a byproduct of but not a cause of vasospasm. This study correlated vasospasm with hydroxyl free radical and lipid peroxide levels. 24 dogs had baseline cerebral angiography and induction of SAH by 2 injections of blood into the cisterna magna at baseline and 2 days later. Angiography was repeated 4, 7, 10, 14 or 21 days after the first injection (n = 4 per group) and a microdialysis catheter was inserted into the premedullary cistern. Control dogs (n = 4) underwent angiography and microdialysis but not SAH. Salicylic acid, 100 mg/kg, was administered intravenously, and microdialysis fluid was collected and analyzed by high pressure liquid chromatography for 2,3- and 2,5-dihydroxybenzoic acids (DHBA). Malondialdehyde was measured in subarachnoid clot removed from the prepontine cistern and in the basilar artery itself at the time of euthanasia. Significant vasospasm developed 4 to 14 days after SAH. Malondialdehyde levels were significantly elevated in the basilar artery and subarachnoid clot 4 days after SAH (p < 0.0001, ANOVA) but not at other times. 2,5-DHBA levels were significantly greater than control at 4 to 14 days and they peaked at 4 days (p < 0.05, ANOVA). 2,3-DHBA was significantly increased at 4 days after SAH (p < 0.05, ANOVA). There were significant correlations between basilar artery malondialdehyde levels and vasospasm and cerebrospinal fluid 2,5-DHBA levels and vasospasm. These results suggest the presence of hydroxyl free radical after SAH and demonstrate a correlation between such production, as measured by trapping with salicylate, and the early phase of vasospasm. The correlation with vasospasm implicates free radicals and lipid peroxidation in this phase of vasospasm.

Original languageEnglish
Pages (from-to)979-989
Number of pages11
JournalLife Sciences
Volume75
Issue number8
DOIs
StatePublished - Jul 9 2004

Bibliographical note

Funding Information:
Dr. Macdonald is supported by a grant from the National Institutes of Health, the American Heart Association, an American College of Surgeons Faculty Fellowship, a Young Clinician Investigator Award from the American Association of Neurological Surgeons and the Brain Research Foundation.

Keywords

  • Dog
  • Free radicals
  • Microdialysis
  • Spin trap
  • Subarachnoid hemorrhage
  • Vasospasm

ASJC Scopus subject areas

  • General Pharmacology, Toxicology and Pharmaceutics
  • General Biochemistry, Genetics and Molecular Biology

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