Neurometabolic Outcomes of Different Cardiopulmonary Bypass Strategies

项目描述 接受需要体外循环（CPB）手术的先天性心脏病患者 由于时间相关的缺血和暴露于有毒物质， 大脑代谢物的水平两种相互竞争的CPB方法目前正在实践中， 常见的心脏缺陷：1）深低温停循环（DHCA），其中泵 关闭以提供无血术野，代价是无脑灌注，以及2）顺行 脑灌注（ACP），在整个手术过程中保持脑的选择性灌注。 重要的是，心脏手术中的DHCA与患者的长期神经认知缺陷密切相关， 与循环停止时间的长度成比例的方式。ACP在CPB中的替代使用， 作为一种保护大脑皮层的策略，已成为一种常见的方法，尽管ACP的价值 关于DHCA的争论仍然激烈，缺乏精心设计和客观的比较研究。 在这里，我们建议使用MRI和动态质子磁共振成像对仔猪模型进行临床前研究。 共振光谱（MRS），其测量真实的时间内的代谢物活性，以量化代谢物活性的改变。 在这些CPB策略的所有阶段期间，大脑的代谢状态随时间连续变化。初步 数据显示DHCA引起脑能量代谢的显著改变，（例如，a > 10倍累积， 脑乳酸盐和葡萄糖减少），而ACP没有观察到这种紊乱。重要的是，后 手术定量空间学习评估将用于最强有力地识别代谢标志物 与不良临床结局相关。该项目的成功将首次证明， ACP在预防脑细胞损伤诱导的代谢物紊乱方面优于DHCA， 可能会阻碍正常的认知发展。本研究中使用的真实的时间连续测量将 还提供了深入了解DHCA持续时间和神经系统之间相关性的根本原因， 损伤预计这些研究的数据将为DHCA或ACP治疗时的安全性建立基准。 在临床上需要。我们预计，在仔猪中进行的这项客观研究的结果将 可以直接和快速地转化为临床实践。具体目的是：1）利用体外循环仔猪模型 我们将使用MRS在真实的时间内连续成像大脑代谢状态。CPB模型将 使用两种常用的CPB形式，DHCA和ACP。DHCA和ACP都将 在不同的温度、流量和时间条件下进行，以确定最有效的 保持健康的大脑代谢状态的方法。2）评估神经认知功能 结果并与观察到的脑代谢变化相关。

Project Description Patients with congenital cardiac diseases undergoing surgery requiring cardiopulmonary bypass (CPB) are at risk for impaired neurodevelopmental progression due to time-related ischemia and exposure to toxic levels of brain metabolites. Two competing CPB methodologies are currently practiced for certain commonly occurring cardiac defects: 1) Deep Hypothermic Circulatory Arrest (DHCA), in which the pump is turned off to provide a bloodless surgical field at the expense of no cerebral perfusion, and 2) Antegrade Cerebral Perfusion (ACP), whereby selective perfusion of the brain is maintained throughout surgery. Importantly, DHCA in cardiac surgery is strongly associated with long-term neurocognitive deficits in a manner proportional to length of the circulatory arrest time. The alternative use of ACP for CPB, designed as a strategy to protect the cerebral cortex, has become a common approach, though the value of ACP over DHCA remains hotly debated, with well-designed and objective comparative studies lacking. Here we propose preclinical studies of a piglet model using MRI and dynamic proton magnetic resonance spectroscopy (MRS) which measures metabolite activity in real time, to quantify alterations in the brain’s metabolic state continuously over time during all phases of these CPB strategies. Preliminary data reveal that DHCA causes marked alterations in brain energy metabolism, (e.g., a > 10-fold buildup in brain lactate and a reduction in glucose), while no such derangement is seen with ACP. Importantly, post- surgery quantitative spatial learning assessments will be used to identify metabolic markers most strongly associated with poor clinical outcomes. Success of this project will demonstrate for the first time the advantages of ACP over DHCA in preventing brain cellular injury-inducing metabolite derangements that may hinder normal cognitive development. The real time continuous measurements used in this study will also provide insights into underlying causes of the correlation between DHCA duration and neurological injury. Data from these studies are expected to establish a benchmark for safety when DHCA or ACP is required in the clinical setting. We anticipate that the results of this objective study in the piglet will be directly and rapidly translatable to clinical practice. The Specific Aims are: 1) Using a CPB piglet model we will image the brain metabolic state continuously in real time using MRS. The CPB model will utilize the two commonly used forms of CPB, DHCA and ACP. Both DHCA and ACP will be performed under varying conditions of temperature, flow and time, to determine the most effective methodology to preserve a healthy brain metabolic state., and 2) To evaluate neurocognitive outcomes and correlate with observed alterations in brain metabolism.