The Efficacy of Normobaric Oxygen on Chronic Cerebral Ischemia

INTRODUCTION Chronic cerebral ischemia (CCI), which is firstly proposed by Japanese scholars in 1990s, is considered as a pathological status induced by persistent reduction of cerebral blood volume and flow (CBV and CBF), leading to ischemia and hypoxia in the brain tissue. Long-time ischemic-hypoxic injury can cause various atypical brain dysfunctions, such as headache, dizziness, cognitive decline and emotional abnormalities. Under the low-perfusion background, the brain tissue is more vulnerable to ischemic-hypoxic insult; thus, the incidence of ischemic events amongst individuals with CCI is substantially higher than those without. It has been reported that intracranial atherosclerotic stenosis (ICAS), internal jugular venous stenosis (IJVS) and cardiogenic cerebral circulation insufficiency are the common pathogenesis of CCI, with the hypoperfusion as a vital mechanism accounting for these clinical presentations.

Normobaric oxygen (NBO) is a routine adjuvant hyperoxygenation intervention supplied by nasal cannula or facemask (such as Venturi mask), with one atmosphere pressure (1ATA=101.325kPa). Evidence available shows that NBO may be a safe, convenient and promising therapeutic strategy for multi-organ protection, which has garnered increasing attention of researchers over the past years. However, some studies do not support the favorite efficacy of NBO. For instance, a large meta-analysis conducted by Chu et al. revealed that in acutely ill adult patients, oxygen supplementation might increase mortality without improving patient-important outcomes. The negative results can contribute to acute critical conditions and some serious complications such as infection, arrhythmia and dyspnea. In contrast to previous experimental data confirming the NBO protection on acute stroke, a recent multi-center randomized clinical trial concludes that this oxygen supplement does not reduce the rate of death or disability. The incongruent conclusions between clinical and animal studies may be attributable to the protective mechanisms of NBO behind cerebral ischemia, the rationale for the protective effect afforded by NBO is freezing penumbra and extending the time window for reperfusion, meaning that NBO may be not applicable for patients with permanent vessel occlusion. Animal research has corroborated that NBO can reduce infarct size and improve post-stroke outcomes after thrombolysis in ischemic stroke, and a large multi-center randomized prospective trial is ongoing.

Theoretically, low cerebral blood perfusion in CCI patients exposes the brain tissue to an ischemic-hypoxic condition, which is similar to that in penumbra in acute ischemic stroke. Therefore, given the prominent effectiveness in penumbra, NBO, which can supply abundant oxygen, may yield some benefits to the ischemic-hypoxic brain tissue in CCI patients. However, there is no study investigating the oxygen supplementation applied in CCI up to now.

THEORY OF THE HYPOTHESIS

The investigators' hypothesis is that NBO can enhance oxygen content in the ischemic-hypoxic brain tissue in CCI patients and subsequently improve both short-term symptoms and long-term clinical outcomes. The basis of the hypothesis is inferred by several convinced theories presented as follows: