Senescense and cerebral oxygenation with acute anemia

衰老和脑氧合伴急性贫血

• 批准号: 6945135
• 负责人: Thomas F. Floyd
• 金额: $ 6.5万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6945135
• 关键词: age difference; anemia; arteriosclerosis; blood pressure; cerebral ischemia /hypoxia; cognition disorders; hemoglobin; laboratory rat; neuropsychological tests; oxygen consumption; respiratory oxygenation; ultrasound blood flow measurement

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.

描述（由申请人提供）：改善老年人的健康和生活质量（2）心脑血管老化-心脏手术后早期发生认知功能障碍（POCD）的比例高达80%，长期可能会严重损害20%的生活质量。虽然与心肺转流术（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，无CPB的冠状动脉血运重建术并未消除或显著降低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所共有的，而与CPB本身无关。虽然机制仍不清楚，但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）可能有助于POCD和那些高龄可能更敏感的认知的影响。心脏手术（有或没有CPB）以及大血管和整形外科手术通常与AIA相关，随后是更多的慢性贫血。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。对于红细胞压积的相同福尔斯下降，< 65岁的患者脑血流量（CBF）增加了30%，而>65岁的患者增加了近75%。对AIA的脑血管反应包括CBF增加、CDO 2减少和脑氧摄取增加。我们研究中的年轻队列遵循这种模式，经历了CDO 2的下降，而老年人经历了CDO 2的意外增加。由于年龄是POCD的主要危险因素，我们认为CBF和CDO 2的显著增加可能在某种程度上描述了一种生理分流，尽管CBF明显奢侈，但仍由不饱和的脑实质O2需求驱动。我们实验室在成年大鼠中的早期数据也表明，AIA和伴随的轻度低血压损害脑氧合。我们假设衰老与大脑在AIA状态下有效提取氧气的能力受损有关，从而导致POCD。本研究拟观察AIA对青年和老年自发性高血压大鼠脑氧合和认知功能的影响。