Abstract W P411: Effect of Normobaric Oxygen Therapy (NBO) on Oxidative Stress in Acute Ischemic Stroke

Abstract

BACKGROUND: There is little human data concerning the effect of hyperoxia on markers of oxidative stress after acute ischemic stroke (AIS); rodent studies show conflicting results. METHODS: In this NIH-SPOTRIAS Trial of normobaric oxygen therapy (NBO) in AIS, tPA-ineligible subjects with imaging-confirmed AIS < 9 hours and NIHSS score 4 or higher were randomized to NBO or Medical Air, delivered for 8 hrs. Of n=85 enrolled, we analyzed n=53 (24 NBO, 29 Air) who had NIHSS, oxidative stress biomarkers, and serial CT/MRI obtained at 0 hrs (admission/pre-therapy), 4 hrs (during therapy) and 48 hrs (post-therapy). RESULTS: At baseline, the NBO arm showed a trend for higher DWI lesion volumes (39.8±42 vs 20.3±20 cc, p=0.06), but there was no significant difference between NBO and Air for mean age (73±15y vs 74±14y, p=0.9), median NIHSS (11.5 vs. 9.0, p=0.5), or perfusion-MRI "mean transit time" lesion volumes (100.9 vs 74.3 cc, p=0.6). Pre-therapy antioxidant capacity, assessed with the oxygen radical absorbance capacity assay, was significantly lower in the NBO arm (p=0.02), suggestive of greater baseline oxidative stress associated with larger infarct volumes. Pre-therapy levels of the matrix metalloproteinases MMP-2 and MMP-9, and F2isoProstane (F2isoP, a direct marker of non-enzymatic oxidation of membrane phospholipids) were similar between groups. There was no significant change from 0-4 hours or from 0-48 hours in NIHSS scores, DWI volumes, and levels of MMP-2, MMP-9, and F2isoP (Table). The NBO and Air groups showed no significant differences in rates of tissue reperfusion, or indirect MRI markers of free radical injury such as stroke-related mass effect, brain hemorrhage, or the hyperacute reperfusion injury marker (HARM) sign. CONCLUSION: In patients with acute ischemic stroke, there is no significant change in direct and indirect markers of oxidative stress with hyperoxia therapy.