BRAIN OXYGENATION AND METABOLISM

一支由调查人员、外科专家组成的团队 麻省理工学院麻醉学和外科基础研究人员 生物化学和生物物理学，将批判性地评估脑氧合作用和 低流量低温体外循环期间和术后的代谢 (LFCPB)和深低温停循环(DHCA)。这些研究将 加深我们对细胞和分子机制的理解 导致大脑和视网膜功能障碍的原因 体外循环(CPB)，以便制定有效的策略 为了保护大脑。 具体地说，将检验以下假设： 1.在体外循环期间，有一种代谢上重要的 新生儿脑和视网膜氧分压缺乏 小猪。 这种缺氧症会导致： A/.血清S-100蛋白升高。 B/。细胞外多巴胺水平的增加。 C/.增加羟基自由基的生成。 D/.热休克蛋白的诱导表达。 2.体外循环期间细胞外多巴胺水平升高 有助于发展细胞代谢紊乱和细胞 功能通过： A/.细胞自发自氧化过程中自由基的产生 在单胺氧化酶的酶促氧化过程中过量的多巴胺。 B/。导致类D_1和类D_2的灵敏度改变 通过改变受体激动剂的Kd和/或受体的数量 (BMA)。 C/.导致血管收缩，进而导致搭桥后 低灌注率。 3.聚乙二醇化血红蛋白(PEG)可提供显著的 改善氧气输送和防止新陈代谢 CPB的骚乱。

A team of investigators, surgical specialists from the Departments of Anesthesiology and Surgery and basic researchers from the Department of Biochemistry & Biophysics, will critically evaluate brain oxygenation and metabolism during and after low flow hypothermic cardiopulmonary bypass (LFCPB) and deep hypothermic circulatory arrest (DHCA). These studies will increase our understanding of the cellular and molecular mechanisms responsible for a brain and retinal dysfunction resulting from cardiopulmonary bypass (CPB) so that effective strategies can be developed for protecting the brain. Specifically, the following hypotheses will be tested: 1. During cardiopulmonary bypass there is a metabolically important deficiency in the oxygen pressure in the brain and retina of newborn piglets. This oxygen deficiency will result in: a/. increases in serum S-100 protein. b/. increases in the extracellular level of dopamine. c/. Increase generation of hydroxyl radicals. d/. induction of expression of heat shock protein. 2. Increases in the extracellular level of dopamine during bypass contributes to development of disturbance of cellular metabolism and cell function through: a/. Generation of free radicals during spontaneous autooxidation of the excess dopamine an during its enzymatic oxidation of monoamine oxidase. b/. Causing alterations in the sensitivity of the D1-like and D2-like receptors by modifying the Kd for agonists and/or the number of receptors (Bma). c/. Causing vasoconstriction which in turn is responsible for post-bypass hypoperfusion. 3. Polyethylene glycol modified hemoglobin (PEG) can provide significant improvements in oxygen delivery and protection from the metabolic disturbances of CPB.