Acute Anemia Elicits Cognitive Dysfunction and Evidence of Cerebral Cellular Hypoxia in Older Rats with Systemic Hypertension

Abstract

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.

Review article: Risks of anemia and related management strategies: can perioperative blood management improve patient safety?

“…In the absence of these responses, healthy young mice experience a shift in their mean lethal Hb concentration from 25 gÁL -1 to a higher value near 35 gÁL -1 . 21 Experimental models have shown that these hypoxic cellular responses are also upregulated during chronic anemia 27 and in older hypertensive rodents, 28 suggesting that they may have relevance to both the pediatric and the older adult patient populations that undergo anesthesia for surgical treatment. The overall conclusion from current experimental models strongly suggests that impaired oxygen delivery and tissue hypoxia contribute to increased mortality during acute anemia.…”

A Pilot Study Evaluating Presurgery Neuroanatomical Biomarkers for Postoperative Cognitive Decline After Total Knee Arthroplasty in Older Adults

“…Potential perioperative events that may negatively interact with preoperative leukoaraiosislacunae volume include acute anemia (60)(61)(62)(63), hypotension (64), oxygen desaturation (65)(66)(67), and the production of emboli. In our sample, we acquired valid emboli data on 15 of our surgery participants.…”

Impact of Acute Normovolemic Hemodilution in Organ and Cell Structure

“…Such effects seem to be worse in aged patients, given the greater incidence of cognitive dysfunction in this population (Moller et al, 1998). This hypothesis was demonstrated in an experimental study by Li et al (2010), who showed the association between acute anemia (i.e. hemoglobin 5 g/dL) and age-dependent visual-spatial working memory and learning impairment in rats.…”

“…hemoglobin 5 g/dL) and age-dependent visual-spatial working memory and learning impairment in rats. They also showed an increase in hypoxia-inducible factor (HIF) and related molecular markers of cellular hypoxia, in the presence of normal systemic and local cerebral tissue oxygenation, which was more evident in older animals (Li et al, 2010).…”