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PET Evaluation of Hemorrhagic Shock and Resuscitation

失血性休克和复苏的 PET 评估

基本信息

批准号：
7267946
负责人：
VIBHUDUTTA AWASTHI
金额：
$ 21.77万
依托单位：
UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-08-01 至 2009-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7267946
关键词：
Acidosis Address Adenosine Triphosphate Affinity Albumins Animal Model Animals Arts Biological Assay Blood Blood Volume Blood flow Blood specimen Brain Cardiac Carrying Capacities Cell Respiration Cerebrum Clinical Trials Colloids Core-Binding Factor Creatine Development Doctor of Philosophy Drug Formulations Encapsulated Energy Metabolism Enzymes Evaluation Functional disorder Gases Glucose Goals Healthcare Heart Hemoglobin Hemorrhage Hemorrhagic Shock Human Hypovolemic Shock Image Imaging technology Invasive Investigation Label Lactated Ringer&apos s Solution Life Lipids Liposomes Liquid substance Measurement Measures Metabolism Methods Microdialysis Modeling Monitor Oxygen Oxygen Consumption Phosphocreatine Physiology Positioning Attribute Positron-Emission Tomography Procedures Protocols documentation Pyridoxal Phosphate Pyruvate Pyruvates Rattus Research Research Personnel Resuscitation Sampling Serum Albumin Serum Markers Shock Standards of Weights and Measures Testing Time Tissues Trauma Whole Blood base crystalloid detector improved innovation killings pre-clinical programs radiotracer response stroma free hemoglobin tissue oxygenation

项目摘要

DESCRIPTION (provided by applicant): In the USA, trauma kills approximately 150,000 people each year. Despite such an impact on health care, fluid resuscitation in trauma continues to be a debatable issue. Crystalloids or colloids are commonly used and these fluids augment O2 delivery only by increasing preload. The only fluids that can increase both O2- carrying capacity and preload are hemoglobin based products. Thus, the long-term goal of this research is to develop encapsulated hemoglobin as a complete and universal resuscitative fluid to address multifaceted pathophysiology of hemorrhagic shock. Liposome encapsulated hemoglobin (LEH), as well as other hemoglobin-based O2 carriers (HBOCs), have undergone extensive evaluation. But, an efficient O2 carrier is not necessarily an efficient O2 delivery vehicle. PET has the capability to visually, quantitatively and non- invasively assess O2 delivery and metabolism in response to resuscitation. HYPOTHESES 1) LEH delivers O2 to the brain in the same fashion as RBCs, 2) cerebral O2 delivery from LEH is sustained for a longer period of time than the unencapsulated HBOCs, and 3) LEH encapsulating high-affinity hemoglobin delivers more O2 to the brain than LEH containing low-affinity hemoglobin in severe blood loss. SPECIFIC AIMS are: 1). Develop and validate image-derived cardiac time-activity curve as an arterial input function in MicroPET investigation of rat cerebral oxygen metabolism (CMRO2). 2). Investigate the effect of oxygen affinity of hemoglobin in LEH on cerebral oxygen metabolism after resuscitation in a rat model of hemorrhagic shock. 3).Evaluate the improvement in CMRO2 and energy metabolism after LEH resuscitation against standard resuscitative fluids in a rat model of hemorrhagic shock. We will perform microPET imaging with O-15 radiotracers (O2 gas, CO gas and H2O) to determine CMRO2 and CBF. A rat model of hemorrhagic shock will be resuscitated with LEH, whole blood, Ringer's lactate solution and 5% albumin. Cerebral energy metabolism will be established by tissue markers of aerobic metabolism. This is an innovative proposal that utilizes state-of-the-art imaging technology in a small animal model. The study will not only address important issues pertaining to oxygen metabolism in shock and resuscitation, it may also be useful in evaluation of other artificial oxygen carriers undergoing preclinical and clinical trials.

描述（由申请人提供）：在美国，创伤每年造成约15万人死亡。尽管对医疗保健有这样的影响，创伤中的液体复苏仍然是一个有争议的问题。通常使用晶体或胶体，这些液体仅通过增加前负荷来增加O2输送。唯一能够同时增加携氧能力和前负荷的液体是血红蛋白产品。因此，本研究的长期目标是开发包封血红蛋白作为一种完整和通用的复苏液，以解决失血性休克的多方面病理生理学。脂质体包裹的血红蛋白（莱赫），以及其他血红蛋白为基础的O2载体（HBOCs），已经经历了广泛的评价。但是，有效的O2载体不一定是有效的O2递送载体。PET能够以视觉、定量和非侵入性方式评估复苏后的氧气输送和代谢。假设1）莱赫以与RBC相同的方式将O2递送至大脑，2）来自莱赫的大脑O2递送比未包封的HBOC持续更长的时间，3）在严重失血中，包封高亲和力血红蛋白的莱赫比含有低亲和力血红蛋白的莱赫向大脑递送更多的O2。具体目标是：1）。开发并验证图像衍生的心脏时间-活动曲线作为大鼠脑氧代谢（CMRO 2）MicroPET研究中的动脉输入函数。2）。探讨莱赫中血红蛋白的氧亲和力对失血性休克大鼠复苏后脑氧代谢的影响。3).在失血性休克大鼠模型中，评价莱赫复苏后与标准复苏液相比CMRO 2和能量代谢的改善。我们将使用O-15放射性示踪剂（O2气体、CO气体和H2O）进行microPET成像，以确定CMRO 2和CBF。用莱赫、全血、林格氏乳酸盐溶液和5%白蛋白复苏失血性休克大鼠模型。脑能量代谢将通过有氧代谢的组织标志物来建立。这是一个创新的建议，利用国家的最先进的成像技术在一个小动物模型。该研究不仅将解决休克和复苏中氧代谢的重要问题，还可能有助于评估其他正在进行临床前和临床试验的人工氧载体。