Abstract WMP30: F 2 -Isoprostanes and Isofurans as Markers of Oxidative Stress and Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage

Background: F 2 -Isoprostanes (F 2 -IsoP) and Isofurans (IsoF), specific markers of lipid peroxidation in vivo, have been reported to be elevated and have prognostic implications in aneurysmal subarachnoid hemorrhage (aSAH). We examined associations between these biomarkers and the risk of delayed cerebral ischemia (DCI) following aSAH. Methods: Eighteen patients with aSAH and 7 controls with normal neuroimaging and CSF analysis results underwent CSF sampling and abstraction of clinical, demographic, and laboratory data. Samples (two) of CSF were collected on day 1 and once on days 5-8 post-bleed. F 2 -IsoP and IsoF assays were performed at Vanderbilt Eicosanoid Core Lab by gas chromatography/mass spectroscopy. Levels are expressed in median (IQR) for non-parametric data. Repeated sample measurement were compared using the Wilcoxon signed-rank test, whereas the Mann Whitney test was used for other non-parametric data. Results: Mean age was 62 + 15 (aSAH cases) vs. 52 + 14 (controls) years, p =0.07, and 80% were female. Median Hunt-Hess score was 3 (2-4) and modified Fisher scale 3 (3-4). Thirty five percent of patients developed DCI. F 2 -IsoP were significantly higher in cases than controls 47.5 (30.2-53.5) vs. 26.0 (21.2-34.5) pg/mL, p 0.01. No significant differences were observed in patients with or without DCI (41 (33.5-52) vs. 44 (28.5-55.5) pg/mL). IsoF were elevated in the second CSF sample (41.5 (34-72) pg/mL) in 9 patients, but undetectable in the remainder cases and all controls. Cases who developed DCI had significantly higher IsoF than cases who did not (57 (34-72) vs. 0 (0-34) pg/mL, p= 0.001). Median PaO2 in both groups was similar (130.5 (89.2-189.7) vs. 115 (77.5-176) mmHg). Conclusions: F 2 -IsoP and IsoF serve as overall indicators of oxidative injury following aSAH, but IsoF may also be related to the development of DCI and cerebral vasospasm. Whether IsoF serve as mediators of vasospasm/ischemia or are merely favored byproducts of oxidative damage warrants further investigation. In the absence of higher oxygen tensions, we hypothesize the possibility of neuronal mitochondrial dysfunction in patients with elevated IsoF.