Effects of a synthetic allosteric modifier of hemoglobin oxygen affinity on outcome from global cerebral ischemia in the rat.
BACKGROUND AND PURPOSE: Neuronal injury results from an insufficient supply of oxygen to the brain. This experiment examined whether a pharmacologically induced rightward shift of the partial pressure of oxygen at which 50% of hemoglobin is saturated (P50) would improve outcome from either incomplete and/or near-complete forebrain ischemia-induced hypoxia in the rat. METHODS: For incomplete ischemia (attenuated electroencephalogram), fasted rats (n = 17 to 19 per group) were given a synthetic allosteric modifier of hemoglobin affinity for oxygen (RSR13; 150 mg/kg IV) before or immediately after 20 minutes of bilateral carotid occlusion combined with a decrease in mean arterial pressure to 40 mm Hg. For near-complete ischemia (isoelectric electroencephalogram), rats (n = 15 per group) were given RSR13 (150 mg/kg) at onset of reperfusion after 10 minutes of bilateral carotid occlusion combined with a decrease in mean arterial pressure to 30 mm Hg. In both experiments, control rats were given vehicle (0.9% NaCl IV) only. Outcome (defined as percent dead hippocampal CA1 neurons) was determined at 5 days after ischemia. RESULTS: RSR13 (150 mg/kg) produced a 68% rightward shift of P50 (34+/-3 to 57+/-8 mm Hg). RSR13 reduced CA1 damage resulting from incomplete ischemia by 28% (P=0.02), but only when administered at the onset of reperfusion. RSR13 had no effect on outcome from near-complete ischemia. CONCLUSIONS: A postischemic pharmacologically induced increase in P50 may improve outcome from incomplete global cerebral ischemia. More severe (near-complete) ischemia negates this benefit.
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Related Subject Headings
- Treatment Outcome
- Reperfusion Injury
- Rats, Wistar
- Rats, Sprague-Dawley
- Rats
- Propionates
- Oxyhemoglobins
- Oxygen
- Neurology & Neurosurgery
- Male
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Treatment Outcome
- Reperfusion Injury
- Rats, Wistar
- Rats, Sprague-Dawley
- Rats
- Propionates
- Oxyhemoglobins
- Oxygen
- Neurology & Neurosurgery
- Male