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: 3355891
• 负责人: MARY D OSBAKKEN
• 金额: $ 20.42万
• 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/3355891
• 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探测中的应用 生物能量学 两个主要的假设将得到解决。 1)的 急性和慢性容量超负荷对心肌的影响 能量学可以通过心脏的MRS测定来预测 磷酸肌酸（PCr）浓度，通过以下比值估计： PCr转化为三磷酸腺苷（PCr/ATP）或转化为无机 磷酸盐（PCr/Pi）。 这些参数可用于 估计腺苷二磷酸（ADP）和磷酸化 潜力，分别。 2)心脏工作和生物能量学是 与Michaelis-Menten动力学和代谢不稳定性相关 因此机械不稳定性可以通过 与心脏功和底物利用率相关的曲线的斜率。 在 探索这些假设，MRS参数将与 测量O2的可用性和使用，NADH氧化还原状态和心脏 工作参数（心率×血压，心输出量， 压力-体积功）。 MRS数据还将与 常规心脏代谢物测量 分析生化技术来评估灵敏度和 与传统测量相比，MRS测量的可重复性 方法. 急性研究将在麻醉后进行 狗和猫，慢性研究将在 麻醉犬 所有动物将机械插管 通气和生理监测仪器。 两 将进行以下类型的实验：1）急性容量超负荷将 通过手术将插管放置在 腹主动脉和腔静脉 在对照研究完成后， 分流将被打开，与能量相关的工作负荷 新陈代谢. 在动物稳定后（无变化） PCr/ATP或PCr/Pi比率），压力负荷将被添加到 去甲肾上腺素（NE）容量负荷，以确定 急性容量负荷心脏的代谢稳定性。 2)一 将通过外科手术造成慢性容量超负荷状况 腹主动脉与腔静脉吻合术。 这些动物 将每月进行研究，持续2-12个月，以确定其影响 对心肌能量的影响。 后 在每个时间段进行对照研究，心脏将 压力负荷去甲肾上腺素，以增加心脏工作， 确定慢性容量负荷是否影响 心肌能量学 这些综合数据将用于 确定容量负荷是否与能量相关 变化，这是一个迄今为止没有答案的问题。