Effects of a synthetic allosteric modifier of hemoglobin oxygen affinity on outcome from global cerebral ischemia in the rat.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Grocott, HP; Bart, RD; Sheng, H; Miura, Y; Steffen, R; Pearlstein, RD; Warner, DS

Published Date

  • August 1998

Published In

Volume / Issue

  • 29 / 8

Start / End Page

  • 1650 - 1655

PubMed ID

  • 9707208

Pubmed Central ID

  • 9707208

International Standard Serial Number (ISSN)

  • 0039-2499

Digital Object Identifier (DOI)

  • 10.1161/01.str.29.8.1650

Language

  • eng

Conference Location

  • United States