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

Publication ,  Journal Article
Grocott, HP; Bart, RD; Sheng, H; Miura, Y; Steffen, R; Pearlstein, RD; Warner, DS
Published in: Stroke
August 1998

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.

Duke Scholars

Published In

Stroke

DOI

ISSN

0039-2499

Publication Date

August 1998

Volume

29

Issue

8

Start / End Page

1650 / 1655

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Reperfusion Injury
  • Rats, Wistar
  • Rats, Sprague-Dawley
  • Rats
  • Propionates
  • Oxyhemoglobins
  • Oxygen
  • Neurology & Neurosurgery
  • Male
 

Citation

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ICMJE
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Grocott, H. P., Bart, R. D., Sheng, H., Miura, Y., Steffen, R., Pearlstein, R. D., & Warner, D. S. (1998). Effects of a synthetic allosteric modifier of hemoglobin oxygen affinity on outcome from global cerebral ischemia in the rat. Stroke, 29(8), 1650–1655. https://doi.org/10.1161/01.str.29.8.1650
Grocott, H. P., R. D. Bart, H. Sheng, Y. Miura, R. Steffen, R. D. Pearlstein, and D. S. Warner. “Effects of a synthetic allosteric modifier of hemoglobin oxygen affinity on outcome from global cerebral ischemia in the rat.Stroke 29, no. 8 (August 1998): 1650–55. https://doi.org/10.1161/01.str.29.8.1650.
Grocott HP, Bart RD, Sheng H, Miura Y, Steffen R, Pearlstein RD, et al. Effects of a synthetic allosteric modifier of hemoglobin oxygen affinity on outcome from global cerebral ischemia in the rat. Stroke. 1998 Aug;29(8):1650–5.
Grocott, H. P., et al. “Effects of a synthetic allosteric modifier of hemoglobin oxygen affinity on outcome from global cerebral ischemia in the rat.Stroke, vol. 29, no. 8, Aug. 1998, pp. 1650–55. Pubmed, doi:10.1161/01.str.29.8.1650.
Grocott HP, Bart RD, Sheng H, Miura Y, Steffen R, Pearlstein RD, Warner DS. Effects of a synthetic allosteric modifier of hemoglobin oxygen affinity on outcome from global cerebral ischemia in the rat. Stroke. 1998 Aug;29(8):1650–1655.

Published In

Stroke

DOI

ISSN

0039-2499

Publication Date

August 1998

Volume

29

Issue

8

Start / End Page

1650 / 1655

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Reperfusion Injury
  • Rats, Wistar
  • Rats, Sprague-Dawley
  • Rats
  • Propionates
  • Oxyhemoglobins
  • Oxygen
  • Neurology & Neurosurgery
  • Male