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 su pply of oxygen to the brain. This experiment examined whether a pharma cologically induced rightward shift of the partial pressure of oxygen at which 50% of hemoglobin is saturated (P50) would improve outcome fr om either incomplete and/or near-complete forebrain ischemia-induced h ypoxia in the rat. Methods-For incomplete ischemia (attenuated electro encephalogram), fasted rats (n=17 to 19 per group) were given a synthe tic 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 mmH g. 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 decre ase in mean arterial pressure to 30 mm Hg. In both experiments, contro l rats were given vehicle (0.9% NaCl IV) only. Outcome (defined as per cent dead hippocampal CA1 neurons) was determined at 5 days after isch emia. 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 inco mplete ischemia by 28% (P=0.02), but only when administered at the ons et of reperfusion. RSR13 had no effect on outcome from near-complete i schemia. Conclusion-A postischemic pharmacologically induced increase in P50 may improve outcome from incomplete global cerebral ischemia. M ore severe (near-complete) ischemia negates this benefit.