A Pilot Study of Normobaric Oxygen Therapy in Acute Ischemic Stroke

Abstract

Background and Purpose-Therapies that transiently prevent ischemic neuronal death can potentially extend therapeutic time windows for stroke thrombolysis. We conducted a pilot study to investigate the effects of high-flow oxygen in acute ischemic stroke. Methods-We randomized patients with acute stroke (Ͻ12 hours) and perfusion-diffusion "mismatch" on magnetic resonance imaging (MRI) to high-flow oxygen therapy via facemask for 8 hours (nϭ9) or room air (controls, nϭ7). Stroke scale scores and MRI scans were obtained at baseline, 4 hours, 24 hours, 1 week, and 3 months. Clinical deficits and MR abnormalities were compared between groups. Results-Stroke scale scores were similar at baseline, tended to improve at 4 hours (during therapy) and 1 week, and significantly improved at 24 hours in hyperoxia-treated patients. There was no significant difference at 3 months. Mean (ϮSD) relative diffusion MRI lesion volumes were significantly reduced in hyperoxia-treated patients at 4 hours (87.8Ϯ22% versus 149.1Ϯ41%; Pϭ0.004) but not subsequent time points. The percentage of MRI voxels improving from baseline "ischemic" to 4-hour "non-ischemic" values tended to be higher in hyperoxia-treated patients. Cerebral blood volume and blood flow within ischemic regions improved with hyperoxia. These "during-therapy" benefits occurred without arterial recanalization. By 24 hours, MRI showed reperfusion and asymptomatic petechial hemorrhages in 50% of hyperoxia-treated patients versus 17% of controls (Pϭ0.6). Conclusions-High-flow

Oxygen Therapy Reduces Secondary Hemorrhage after Thrombolysis in Thromboembolic Cerebral Ischemia

“…A strength of our study is that our experimental setup frequently induced parenchymal hemorrhage after TT-MCAO, which is clinically more relevant than hemorrhagic transfomation. NBO tended to increase hemorrhagic transformation in a clinical pilot study (Singhal et al, 2005a) but this increase in petechial-type 'asymptomatic' secondary hemorrhage was related to a higher rate of reperfusion.…”

Hyperoxia promotes astrocyte cell death after oxygen and glucose deprivation

“…The current study performed in vitro using transient OGD taken together with the in vivo studies using transient global cerebral ischemia and reperfusion indicate that avoidance of hyperoxia during reoxgenation is an effective approach to reducing prelethal oxidative stress and subsequently improving brain cell survival. Caution should be taken in applying these results to other forms of brain injury, e.g., ischemic stroke and head trauma, as systemic hyperoxia may result in brain tissue normoxia and improved outcome under conditions that can exist in these disorders where tissue oxygenation can limit aerobic cerebral energy metabolism (Menzel et al, 1999;Singhal et al, 2005). Astrocyte oxygen/glucose deprivation (OGD) paradigm.…”

Postischemic hyperoxia reduces hippocampal pyruvate dehydrogenase activity

“…Our present findings demonstrating reduced hippocampal protein tyrosine nitration and retention of PDHC enzyme activity with normoxic resuscitation support the need for additional preclinical and clinical studies to resolve this issue. The concept that hyperoxia worsens oxidative tissue damage and neurologic outcome after acute brain injury may not, however, apply to other forms of injury, e.g., stroke and trauma, as evidence suggests that hyperoxia can under some circumstances be beneficial [73][74][75][76][77]. The time during which the brain is exposed to high O 2 can also determine whether hyperoxia is helpful or detrimental.…”