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: 3355893
• 负责人: MARY D OSBAKKEN
• 金额: $ 19.07万
• 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 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3355893
• 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 MRS发展成为探索体内心肌的工具 生物能量学。 将讨论两个主要假设。 1） 急性和慢性容量超负荷对心肌的影响 通过心脏MRS测定可以预测能量学 磷酸肌酸 (PCr) 浓度按以下比率估算 PCr 转化为三磷酸腺苷 (PCr/ATP) 或无机 磷酸盐（PCr/Pi）。 然后可以使用这些参数 估计二磷酸腺苷 (ADP) 和磷酸化 潜力，分别。 2) 心脏工作和生物能量学是 米氏动力学和代谢不稳定相关 因此机械不稳定性可以通过变化来预测 与心脏做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 可用性和使用、NADH 氧化还原状态和心脏 工作参数（心率x血压、心输出量、 压力-体积功）。 MRS 数据还将与 常规测量心脏代谢物 分析生化技术来评估敏感性和 与传统的 MRS 测量相比，MRS 测量的再现性 方法。 急性研究将在麻醉状态下进行 狗和猫，并且将进行长期研究 被麻醉的狗。 所有动物都将进行机械插管 通风，并配备生理监测仪器。 二 将进行的实验类型：1）急性容量超负荷 通过手术在两个之间放置插管来创建 腹主动脉和腔静脉。 对照研究完成后， 分流器将打开，工作量与能源相关 代谢。 动物稳定后（没有变化） PCr/ATP 或 PCr/Pi 比率），压力负载将添加到 用去甲肾上腺素 (NE) 确定容量负荷 急性容量负荷心脏的代谢稳定性。 2）A 慢性容量超负荷状况将通过手术造成 腹主动脉与腔静脉的吻合术。 这些动物 将每月进行 2-12 个月的研究以确定效果 慢性容量超负荷对心肌能量学的影响。 后 每个时间段都进行对照研究，心脏将 负载去甲肾上腺素的压力可增加心脏工作 确定慢性容量负荷是否会影响 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，迄今为止的一个问题，尚未得到解答。