Senescense and cerebral oxygenation with acute anemia

(2)心脑血管老化-术后认知功能障碍（POCD）在心脏手术后早期发生率高达80%，长期可能显著影响20%的生活质量。虽然与体外循环（CPB）相关的栓塞和炎症过程可能是POCD的罪魁祸首，但与传统方法相比，不进行CPB的冠状动脉血运重建术并没有消除或显著降低POCD的发生率。最后，POCD也发生在非心脏手术中，这表明POCD背后的机制可能是所有类型的大手术共同的，而与CPB本身无关。虽然机制尚不清楚，高龄是心脏和非心脏手术中POCD的最大危险因素。我们认为急性等容性贫血（AIA）可能导致POCD，老年人可能对其对认知的影响更敏感。心脏手术，无论是否进行CPB，以及大血管和骨科手术，通常与AIA相关，随后更多的慢性贫血。我们实验室的工作表明，脑血管对AIA的反应可能与年龄有关。在相同的血细胞比容下降时，65岁以下的人脑血流量（CBF）增加30%，而65岁以下的人脑血流量（CBF）增加近75%。对AIA的良好描述的脑血管反应包括CBF增加，CDO2减少和脑氧提取增加。在我们的研究中，年轻的队列遵循这种模式，经历了CDO2的下降，而老年人经历了意想不到的CDO2的增加。由于年龄是POCD的主要危险因素，我们认为，尽管CBF明显丰富，但CBF和CDO2的显著增加可能在某种程度上描述了一种生理分流，这种分流是由不满足的实质氧需求驱动的。我们实验室对成熟大鼠的早期数据也表明，AIA以及伴随的轻度低血压会损害脑氧合。我们假设衰老与AIA状态下大脑有效提取氧气的能力受损有关，从而导致POCD。我们拟研究AIA对青年和老年自发性高血压大鼠脑氧合和认知的影响。

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.