Senescense and cerebral oxygenation with acute anemia

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DESCRIPTION (provided by applicant): Improving Health and Quality of Life of Older People(2) Cardiovascular & Cerebrovascular Aging-Postoperative cognitive dysfunction(POCD) occurs at a rate of up to 80% early after cardiac surgery and may significantly impair quality of life in 20% in the long term. While embolic and inflammatory processes associated with cardiopulmonary bypass(CPB) have been implicated as likely culprits in POCD, coronary revascularization without CPB has not eliminated nor significantly decreased the incidence of POCD over conventional approaches. Finally, POCD occurs in noncardiac surgery as well suggesting that the mechanisms behind POCD may be common to all types of major surgery, and not related to CPB per se. While mechanisms remain in doubt, advanced age is the greatest risk factor for POCD in cardiac and noncardiac surgery. We suggest that acute isovolemic anemia(AIA) may contribute to POCD and that those of advanced age may be more sensitive to its effects on cognition. Cardiac surgery, conducted with or without CPB, as well as major vascular and orthopedic surgery, are often associated with AIA and subsequently more chronic anemia. Work in our laboratory suggest that the cerebrovascular response to AIA may be age dependent. In response to identical falls in hematocrit, those < 65 years of age experienced a 30% increase in cerebral blood flow(CBF) while those >65 years of age experienced a nearly 75% increase. The well described cerebrovascular response to AIA includes an increase in CBF, a decrease in CDO2, and an increase in cerebral oxygen extraction. Younger cohorts in our study followed this pattern, experiencing a fall in CDO2, while the elderly experienced an unexpected increase in CDO2. Because age is the primary risk factor for POCD, we suggest that the marked increase in CBF and CDO2 may describe to some degree, a physiologic shunt, driven by an insatiated parenchymal O2 demand, in spite of the apparent luxurient CBF. Early data from our laboratory in mature rats also demonstrates that AIA, and the mild, accompanying hypotension, impairs cerebral oxygenation. We hypothesize that senescence is associated with an impairment in the ability of the brain to efficiently extract oxygen in states of AIA, contributing to POCD. We propose to study the effect of AIA on cerebral oxygenation and cognition in young and aged spontaneously hypertensive rats.