Pharmacological correction of hypothermic P(50) shift does not alter outcome from focal cerebral ischemia in rats.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Wainwright, MS; Sheng, H; Sato, Y; Mackensen, GB; Steffen, RP; Pearlstein, RD; Warner, DS

Published Date

  • May 2002

Published In

Volume / Issue

  • 282 / 5

Start / End Page

  • H1863 - H1870

PubMed ID

  • 11959653

Pubmed Central ID

  • 11959653

International Standard Serial Number (ISSN)

  • 0363-6135

Digital Object Identifier (DOI)

  • 10.1152/ajpheart.00863.2001

Language

  • eng

Conference Location

  • United States