title: Pharmacological correction of hypothermic P(50) shift does not alter outcome from focal cerebral ischemia in rats.
abstract: 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.
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Wainwright
authors.forename: Huaxin
authors.initials: H
authors.lastname: Sheng
authors.forename: Yukie
authors.initials: Y
authors.lastname: Sato
authors.forename: G Burkhard
authors.initials: GB
authors.lastname: Mackensen
authors.forename: Robert P
authors.initials: RP
authors.lastname: Steffen
authors.forename: Robert D
authors.initials: RD
authors.lastname: Pearlstein
authors.forename: David S
authors.initials: DS
authors.lastname: Warner
mesh_terms: D000814:Aniline Compounds; D000818:Animals; D003250:Constriction; D006454:Hemoglobins / Q000378:metabolism*; D007036:Hypothermia, Induced; D002546:Ischemic Attack, Transient / Q000628:therapy*; D008297:Male; D020768:Middle Cerebral Artery; D010100:Oxygen / Q000097:blood*; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013696:Temperature; D013997:Time Factors
chemical_list: D000814:Aniline Compounds; D006454:Hemoglobins; D011422:Propionates; C067396:efaproxiral; D010100:Oxygen