Senescense and cerebral oxygenation with acute anemia

衰老和脑氧合伴急性贫血

• 批准号: 6828523
• 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/6828523
• 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-术后认知功能障碍(POCD)在心脏手术后早期发生的比例高达80%，从长远来看，可能会严重影响20%的生活质量。虽然与体外循环(CPB)相关的血栓和炎症过程可能是POCD的罪魁祸首，但与传统方法相比，没有CPB的冠状动脉血运重建术并不能消除或显著降低POCD的发生率。最后，POCD也出现在非心脏手术中，这表明POCD背后的机制可能在所有类型的大手术中都是共同的，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。我们认为急性等容贫血(AIA)可能与POCD有关，高龄者可能对其对认知的影响更为敏感。心脏手术，无论有没有体外循环，以及主要的血管和骨科手术，往往与AIA相关，并随后导致更多的慢性贫血。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。对于相同的红细胞压积下降，那些65岁的人脑血流量(CBF)增加了30%，而65岁的人增加了近75%。众所周知，脑血管对AIA的反应包括脑血流量增加、CDO2减少和脑氧摄取量增加。在我们的研究中，较年轻的人群遵循这一模式，CDO2下降，而老年人CDO2意外上升。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O2需求驱动的。我们实验室在成年大鼠身上的早期数据也表明，AIA以及伴随的轻度低血压，损害了大脑的氧合。我们假设衰老与大脑在AIA状态下有效地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作用和认知功能的影响。