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 aging-dependent 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.
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 aging-dependent 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.
Authors: Anya T McLaren; Philip A Marsden; C David Mazer; Andrew J Baker; Duncan J Stewart; Albert K Y Tsui; Xiaomao Li; Yeni Yucel; Malcolm Robb; Shelley R Boyd; Elaine Liu; Julie Yu; Gregory M T Hare Journal: Am J Physiol Regul Integr Comp Physiol Date: 2006-09-14 Impact factor: 3.619
Authors: Nikolai Axmacher; Daniel P Schmitz; Ilona Weinreich; Christian E Elger; Juergen Fell Journal: Cereb Cortex Date: 2008-04-09 Impact factor: 5.357
Authors: J T Moller; P Cluitmans; L S Rasmussen; P Houx; H Rasmussen; J Canet; P Rabbitt; J Jolles; K Larsen; C D Hanning; O Langeron; T Johnson; P M Lauven; P A Kristensen; A Biedler; H van Beem; O Fraidakis; J H Silverstein; J E Beneken; J S Gravenstein Journal: Lancet Date: 1998-03-21 Impact factor: 79.321
Authors: Lindsay S Cahill; Lisa M Gazdzinski; Albert Ky Tsui; Yu-Qing Zhou; Sharon Portnoy; Elaine Liu; C David Mazer; Gregory Mt Hare; Andrea Kassner; John G Sled Journal: J Cereb Blood Flow Metab Date: 2016-07-20 Impact factor: 6.200
Authors: Nikhil Mistry; C David Mazer; John G Sled; Alan H Lazarus; Lindsay S Cahill; Max Solish; Yu-Qing Zhou; Nadya Romanova; Alexander G M Hare; Allan Doctor; Joseph A Fisher; Keith R Brunt; Jeremy A Simpson; Gregory M T Hare Journal: Am J Physiol Regul Integr Comp Physiol Date: 2018-01-10 Impact factor: 3.619
Authors: Catherine C Price; Jared J Tanner; Ilona Schmalfuss; Cynthia Wilson Garvan; Peter Gearen; David Dickey; Kenneth Heilman; David L McDonagh; David J Libon; Christiana Leonard; Dawn Bowers; Terri G Monk Journal: Anesthesiology Date: 2014-03 Impact factor: 7.892
Authors: Cindy V Leiton; Elyssa Chen; Alissa Cutrone; Kristy Conn; Kennelia Mellanson; Dania M Malik; Michael Klingener; Ryan Lamm; Michael Cutrone; John Petrie; Joher Sheikh; Adriana DiBua; Betsy Cohen; Thomas F Floyd Journal: Hypoxia (Auckl) Date: 2018-11-08