31P MRS STUDY OF HEART ENERGETICS DURING VOLUME LOADING

容量负荷期间心脏能量的 31P MRS 研究

• 批准号: 3355890
• 负责人: MARY D OSBAKKEN
• 金额: $ 12.17万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3355890
• 关键词: NAD(H) analog; adenosine diphosphate; bioenergetics; blood pressure; cardiac output; cats; creatine phosphate; dogs; heart rate; myocardium; norepinephrine; nuclear magnetic resonance spectroscopy; oxidation reduction reaction; oxygen tension; phosphates; phosphorylation

The major objective of the proposed project is to continue the development of MRS into a tool for exploring in vivo myocardial bioenergetics. Two major hypotheses will be addressed. 1) The effects of acute and chronic volume overload on myocardial energetics can be predicted by MRS determination of heart phosphocreatine (PCr) concentration as estimated by the ratio of PCr to adenosine triphosphate (PCr/ATP) or to inorganic phosphate (PCr/Pi). These parameters can then be used to estimate adenosine diphosphate (ADP) and phosphorylation potential, respectively. 2) Heart work and bioenergetics are related by Michaelis-Menten Kinetics, and metabolic instability and thus mechanical instability can be predicted by a change in the slope of curves relating heart work t substrate utilization. In exploring these hypotheses, MRS parameters will be related to measures of O2 availability and use, NADH redox state and heart work parameters (heart rate x blood pressure, cardiac output, pressure-volume work). MRS data will also be compared to measurements of heart metabolites obtained with routine analytical biochemical techniques to evaluate the sensitivity and reproducibility of MRS measurements compared to traditional methods. The acute studies will be performed on anesthetized dogs and cats, and the chronic studies will be performed on anesthetized dogs. All animals will be intubated, mechanically ventilated, and instrumented for physiological monitoring. Two types of experiments will be done: 1) acute volume overload will be created via surgical placement of cannulae between the abdominal aorta and vena cava. After control studies are done, the shunts will be opened and workload related to energy metabolism. After the animal has stabilized (no change in PCr/ATP or PCr/Pi ratio), pressure loading will be added to the volume load with norephinephrine (NE) to determine the metabolic stability of an acutely volume loaded heart. 2) A chronic volume overload condition will be created via surgical anastomosis of the abdominal aorta to vena cava. These animals will be studied monthly for 2-12 months to determine the effects of chronic volume overload on myocardial energetics. After control studies are done for each time period, the heart will be pressure loaded with norephinephrine to increase heart work to determine whether chronic volume loading effects a change in myocardial energetics. These combined data will be used to determine whether volume loading is associated with energetic changes, a question heretofore, not answered.

拟议项目的主要目标是继续 磁共振波谱技术在活体心肌研究中的应用 生物能量学。两个主要的假设将被提出。1) 急、慢性容量超负荷对心肌的影响 能量学可以通过心脏的磁共振波谱测定来预测 磷酸肌酸(PCr)浓度由以下比率估计 聚合酶链式反应扩增至三磷酸腺苷或无机物 磷酸盐(PCR/PI)。然后可以使用这些参数来 评估二磷酸腺苷(ADP)和磷酸化 潜力分别为。2)心脏功和生物能量学 米氏动力学与新陈代谢不稳定性的关系 因此，机械不稳定性可以通过以下变化来预测 与心功和底物利用率相关的曲线斜率。在……里面 探索这些假设，MRS参数将与 氧气供应和利用、NADH氧化还原状态和心脏的测量 工作参数(心率x血压，心输出量， 压力-体积功)。MRS数据还将与 心脏代谢物的常规测量 分析生化技术以评估敏感性和 磁共振波谱测量的重复性与传统方法的比较 方法：研究方法。急性研究将在麻醉状态下进行 狗和猫，慢性研究将在 麻醉的狗。所有的动物都要机械插管 通风，并配备仪器进行生理监测。二 将进行以下类型的实验：1)严重的容量超载 通过外科手术将插管放置在 腹主动脉和下腔静脉。在对照研究完成后， 将开通分流，与能源相关的工作量 新陈代谢。在动物已经稳定之后(没有变化 聚合酶链式反应/三磷酸腺苷或聚合酶链式反应/PI比值)，压力载荷将添加到 用去甲肾上腺素(NE)测定容量负荷 急性容量负荷心脏的代谢稳定性。2)A 慢性容量超载情况将通过外科手术造成 腹主动脉与下腔静脉的吻合。这些动物 将在2-12个月内每月进行研究，以确定效果 慢性容量超负荷对心肌能量的影响。之后 对照研究是针对每个时间段进行的，心脏将 负荷去甲肾上腺素的压力增加心脏做功到 确定慢性卷负载是否会影响 心肌能量学。这些合并后的数据将用于 确定体积负荷是否与能量相关 变化，这是一个到目前为止还没有回答的问题。