ENERGY METABOLISM OF THE RIGHT VENTRICLE

右心室的能量代谢

• 批准号: 2226006
• 负责人: GREGORY G SCHWARTZ
• 金额: $ 17.44万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-02-01 至 1999-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2226006
• 关键词: acidity /alkalinity; adenosine triphosphate; bioenergetics; blood flow measurement; cardiac output; creatine phosphate; free fatty acids; heart metabolism; heart pharmacology; heart ventricle; high energy compound; intracardiac pressure; isoproterenol; lactates; mitochondria; myocardial ischemia /hypoxia; nicotinamide adenine dinucleotide; nuclear magnetic resonance spectroscopy; oxidative phosphorylation; oxygen consumption; pulmonary artery; swine; vasoconstriction

In order to maintain normal cardiac function, myocardial ATP synthesis (by oxidative phosphorylation) must be matched precisely to the rate of ATP hydrolysis, which in turn varies rapidly and widely with changing cardiac work. The control mechanisms which couple these processes are uncertain in the left ventricle (LV), and have not been investigated in the right ventricle (RV). A growing body of in vitro data, as well as in vivo observations from this laboratory, indicate that energy metabolism of the RV and LV may differ substantially; therefore, observations made in the LV may not be applicable to the RV. For example, when equal increases in RV oxygen consumption are produced by pulmonary artery constriction or isoproterenol infusion, opposite changes in the phosphocreatine/ATP ratio are observed: a decrease with PA constriction and an increase with isoproterenol. In addition, these two interventions are associated with marked differences in RV substrate uptake. This application proposes to utilize techniques of in vivo NMR spectroscopy, and regional measurements of myocardial blood flow, oxygen and substrate utilization, and NADH fluorescence to address the following questions in the pig heart in situ: Do changes in phosphate metabolites and mitochondrial redox potential both contribute to the regulation of oxidative phosphorylation in the RV? When does each exert predominant control? Do changes in substrate utilization affect the levels of RV phosphate metabolites and redox potential? In the same animal model, are there differences in the energetic responses to increased workload of the RV versus the LV? It is hoped that the answers to these questions will shed light on the control of a critical physiologic process, and elucidate similarities and differences in the energy metabolism of the two ventricles.

为了维持正常的心脏功能，心肌ATP的合成（通过 氧化磷酸化）必须与 ATP 速率精确匹配 水解，反过来又随着心脏的变化而迅速而广泛地变化 工作。耦合这些过程的控制机制在以下方面是不确定的： 左心室 (LV)，尚未对右心室进行研究 心室（RV）。越来越多的体外和体内数据 该实验室的观察表明，能量代谢 RV 和 LV 可能有很大不同；因此，在 LV 中进行的观察 可能不适用于 RV。例如，当 RV 增加相同时 耗氧量是由肺动脉收缩或 异丙肾上腺素输注，磷酸肌酸/ATP 比率发生相反变化 观察到：随 PA 收缩而减少，随 PA 收缩而增加 异丙肾上腺素。此外，这两种干预措施还与 RV 底物摄取存在显着差异。 本申请建议利用体内 NMR 技术 光谱学以及心肌血流量、氧气的区域测量 和底物利用以及 NADH 荧光来解决以下问题 猪心脏原位问题：磷酸盐代谢物是否发生变化 和线粒体氧化还原电位都有助于调节 RV 中的氧化磷酸化？各自在什么时候发挥主导作用 控制？底物利用率的变化是否会影响 RV 水平 磷酸盐代谢物和氧化还原电位？在同一动物模型中， 对工作量增加的积极反应存在差异 RV 与 LV？ 希望这些问题的答案能够为大家带来启发 控制关键的生理过程，并阐明相似性和 两个心室能量代谢的差异。