title: Eubaric hyperoxemia and experimental cerebral infarction.
abstract: We explore three questions concerning arterial hyperoxygenation and focal ischemia. (1) Does greater benefit accrue with higher levels of arterial hyperoxemia? (2) Is the net effect of continuous (intraischemic plus postischemic) oxygen therapy toxic, or beneficial to middle cerebral artery infarction? (3) In view of free radical theories of reperfusion injury, does hyperoxia isolated to the reperfusion period damage tissue? Rats subjected to transient, focal, normothermic, normoglycemic ischemia were assessed at 2 weeks' survival. Arterial hyperoxygenation from 98.9 +/- 4.0 to 312.2 +/- 48.4mm Hg during ischemia improved (p < 0.05) neurological function, as did isolated reperfusion hyperoxemia, but treatment with continuous hyperoxemia both during and after ischemia yielded greatest benefit (p < 0.001). Cortical infarcts constituted 6.5 +/- 1.8% of the hemisphere at normoxia, but 2.3 +/- 0.9% at hyperoxic levels (p < 0.01). Hyperoxia isolated to the reperfusion period also reduced cortical necrosis, from 6.5% to 2.7 +/- 1.2%. However, continuous intraischemic and reperfusion hyperoxemia led to only 0.2 +/- 0.1% cortical necrosis (p = 0.0005). Increasing the degree of hyperoxemia did not augment the benefit. We conclude that (1) eubaric hyperoxemia improves neurological and neuropathological outcome, (2) continuous oxygen therapy offers the greatest benefit, and (3) reperfusion hyperoxemia is beneficial. The findings should allay clinical concerns regarding oxygen-induced reperfusion injury, and, by obviating hyperbaric chambers, encourage clinical trials studying arterial hyperoxemia in treating stroke.
authors.affiliation: Department of Pathology and Laboratory Medicine, Health Sciences Centre, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1. rauer@ucalgary.ca
authors.forename: Erin P
authors.initials: EP
authors.lastname: Flynn
authors.forename: Roland N
authors.initials: RN
authors.lastname: Auer
mesh_terms: D000818:Animals; D001158:Arteries; D001274:Atmospheric Pressure; D004334:Drug Administration Schedule; D018496:Hyperoxia / Q000097:blood*; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D010100:Oxygen / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology
chemical_list: D018696:Neuroprotective Agents; D010100:Oxygen