TY - JOUR
T1 - Acute anemia elicits cognitive dysfunction and evidence of cerebral cellular hypoxia in older rats with systemic hypertension
AU - Li, Min
AU - Bertout, Jessica A.
AU - Ratcliffe, Sarah J.
AU - Eckenhoff, Maryellen F.
AU - Simon, M. Celeste
AU - Floyd, Thomas F.
N1 - Funding Information:
Received from the Departments of Anesthesiology and Critical Care, and Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. Submitted for publication December 30, 2009. Accepted for publication May 13, 2010. Funding was provided by the National Institutes of Health ( NIH RO3 AG023226-01A1, R01 HL066310 ), Rockville, MD; University of Pennsylvania Institute on Aging, Philadelphia, Pennsylvania; and the University of Pennsylvania Research Foundation, Philadelphia, Pennsylvania.
PY - 2010/10
Y1 - 2010/10
N2 - Background: Postoperative cognitive dysfunction occurs frequently after cardiac, major vascular, and major orthopedic surgery. Aging and hypertensive cerebrovascular disease are leading risk factors for this disorder. Acute anemia, common to major surgery, has been identified as a possible contributor to postoperative cognitive dysfunction. The effect of hypoxia upon cognition and the cellular and molecular processes involved in learning and memory has been well described. Cerebrovascular changes related to chronic hypertension may expose cells to increased hypoxia with anemia. Methods: Young to aged spontaneously hypertensive rats underwent testing for visuospatial memory and learning in the Morris water maze, measurement of cerebral tissue oxygenation via tissue oxygen probe, and measurement of hypoxia- sensitive genes and proteins, under conditions of sham and experimental isovolemic anemia. Results: Acute isovolemic anemia elicited evidence of agingdependent visuospatial working memory and learning impairment. Isovolemic anemia did not result in cerebral tissue hypoxia, when measured via tissue oxygen probe. Evidence of cellular hypoxia was, however, identified in response to the anemic challenge, as hypoxia-sensitive genes and proteins were up-regulated. Importantly, cellular hypoxic gene responses were increased with anemia in an age-dependent manner in this model of aging with chronic hypertension. Conclusions: In a translational model of chronic hypertension, clinically relevant levels of acute anemia were associated with an age-dependent visuospatial working memory and learning impairment that was matched by an age-dependent cellular sensitivity to anemic hypoxia. These data offer support for a possible link between anemic hypoxia and postoperative cognitive dysfunction in humans.
AB - Background: Postoperative cognitive dysfunction occurs frequently after cardiac, major vascular, and major orthopedic surgery. Aging and hypertensive cerebrovascular disease are leading risk factors for this disorder. Acute anemia, common to major surgery, has been identified as a possible contributor to postoperative cognitive dysfunction. The effect of hypoxia upon cognition and the cellular and molecular processes involved in learning and memory has been well described. Cerebrovascular changes related to chronic hypertension may expose cells to increased hypoxia with anemia. Methods: Young to aged spontaneously hypertensive rats underwent testing for visuospatial memory and learning in the Morris water maze, measurement of cerebral tissue oxygenation via tissue oxygen probe, and measurement of hypoxia- sensitive genes and proteins, under conditions of sham and experimental isovolemic anemia. Results: Acute isovolemic anemia elicited evidence of agingdependent visuospatial working memory and learning impairment. Isovolemic anemia did not result in cerebral tissue hypoxia, when measured via tissue oxygen probe. Evidence of cellular hypoxia was, however, identified in response to the anemic challenge, as hypoxia-sensitive genes and proteins were up-regulated. Importantly, cellular hypoxic gene responses were increased with anemia in an age-dependent manner in this model of aging with chronic hypertension. Conclusions: In a translational model of chronic hypertension, clinically relevant levels of acute anemia were associated with an age-dependent visuospatial working memory and learning impairment that was matched by an age-dependent cellular sensitivity to anemic hypoxia. These data offer support for a possible link between anemic hypoxia and postoperative cognitive dysfunction in humans.
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U2 - 10.1097/ALN.0b013e3181eaaef9
DO - 10.1097/ALN.0b013e3181eaaef9
M3 - Article
C2 - 20808217
AN - SCOPUS:77957925029
SN - 0003-3022
VL - 113
SP - 845
EP - 858
JO - Anesthesiology
JF - Anesthesiology
IS - 4
ER -