From the Neuroanesthesia Research Laboratory, Department of
Anesthesiology, Duke University Medical Center, Durham, NC, and Allos
Therapeutics, Inc, Denver, Colo (R.S.).
Correspondence to Hilary P. Grocott, MD, Department of Anesthesiology, Box 3094, Duke University Medical Center, Durham, NC 27705. E-mail h.grocott{at}duke.edu
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.
Department
of Internal Medicine,
Virginia Commonwealth University,
Medical College of Virginia Campus,
Richmond, Virginia
© 1998 American Heart Association, Inc.
Original Contributions
Effects of a Synthetic Allosteric Modifier of Hemoglobin Oxygen Affinity on Outcome From Global Cerebral Ischemia in the Rat
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