Hypothermia decreases the arterial PO(2) at which
hemoglobin is 50% saturated (P(50)), increasing
hemoglobin O(2)-binding affinity. We used
RSR13, a synthetic allosteric modifier of
hemoglobin that increases P(50), to study the role of altered
hemoglobin O(2)-binding affinity in mild hypothermic neuroprotection.
RSR13 (150 mg/kg iv) restored P(50) to normothermic values. Rats underwent 70 min of
middle cerebral artery occlusion (MCAO) at 30.0, 34.0, or 37.5 degrees C with
hemoglobin saturation held at 98-100%. The 34.0 degrees C group received
RSR13 or vehicle before
ischemia. After 7 days of recovery,
infarct volumes were reduced in all hypothermic groups, without evidence of a detrimental effect on
infarct size or neurological score as a result of P(50) correction. To examine for a beneficial effect of P(50) correction,
ischemia duration was increased to 120 min in rats maintained at 34.0 degrees C. Correction of P(50) by
RSR13 did not alter
cerebral infarct sizes or neurological scores. The decrease in P(50), caused by mild
hypothermia, could not be associated with
infarct size or neurological deficit resulting from ischemic
brain hypoxia in rats.