BRAIN OXYGENATION AND METABOLISM

一组调查人员，来自各部门的外科专家， 麻醉学和外科学以及基础研究人员 生物化学和生物物理学，将严格评估大脑氧合， 低流量低温体外循环期间和之后的代谢 （LFCPB）和深低温停循环（DHCA）。这些研究将 增加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是 体外循环（CPB），以便制定有效的策略 来保护大脑 具体而言，将检验以下假设： 1.在心肺转流期间，有一个重要的代谢过程 新生儿大脑和视网膜缺氧 猪仔 这种缺氧会导致： a/。血清S-100蛋白升高。 B/.细胞外多巴胺水平的增加。 c。增加羟基自由基的产生。 d。诱导热休克蛋白表达。 2.体外循环期间细胞外多巴胺水平升高 有助于细胞代谢紊乱的发展， 功能通过： a/。自由基的产生在自发自氧化过程中的 过量的多巴胺AN在其单胺氧化酶的酶促氧化过程中。 B/.导致D1样和D2样细胞对 通过改变激动剂的Kd和/或受体的数量 （Bma）. c。导致血管收缩，这反过来又导致分流术后 低灌注 3.聚乙二醇修饰的血红蛋白（PEG）可以提供显著的 改善氧气输送和保护免受代谢 CPB的干扰。

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.