METABOLIC CONTROL OF CORONARY FLOW--31P NMR SPECTROSCOPY

冠状动脉血流的代谢控制--31P核磁共振波谱

• 批准号: 3087553
• 负责人: GREGORY G SCHWARTZ
• 金额: $ 7.54万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-01 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3087553
• 关键词: cellular respiration; coronary occlusion /thrombosis; heart circulation; heart metabolism; hemodynamics; high energy compound; nuclear magnetic resonance spectroscopy; oxygen consumption; phosphates; reactive hyperemia; respiratory oxygen; swine; ultrasound blood flow measurement; vasodilation

Coronary blood flow (CBF) is closely coupled to myocardial oxygen requirements (MV02). However, the mechanisms which link the regulation of CBF to changes in myocardial energy metabolism remain unknown. The purpose of the proposed work is to investigate the mechanism of CBF regulation by examining the relationship between instantaneous CBF and intracellular myocardial energy state (assessed by 31P NMR spectroscopy) in the transient phases of both functional and reactive myocardial hyperemia. The following specific hypotheses will be tested: 1. The level of myocardial high energy phosphates is tightly controlled despite changes in MVO2 by means of a rapid and precise regulation of CBF, and hence oxygen delivery. 2. Myocardial reactive hyperemia (RH), with its prolonged duration and gross overpayment of blood flow debt, is related to a temporary dissociation of instantaneous CBF from myocardial energy state Open-chest, anesthetized pigs with instrumentation including an extramural Doppler coronary flow probe will be studied in a 1- meter, 2 Tesla magnetic resonance spectrometer. Hemodynamic data, including phasic CBF, and 31P NMR spectra will be obtained while the experimental system is perturbed by a step augmentation of MV02 (by paired ventricular pacing and/or aortic constriction) or a step decrease in myocardial oxygen delivery (brief coronary occlusion). The first hypothesis predicts that a step increase in MV02 will be followed by a brief decline in high energy phosphate levels, compensatory coronary vasodilation with increased 02 delivery, and a rapid restoration of high energy phosphates to control levels. The second hypothesis predicts that myocardial high energy phosphates, partially depleted during coronary occlusion, are restored to normal upon release of the occlusion sooner than RH flow returns to its baseline. This would indicate that RH flows is in excess of that required to restore myocardial metabolic conditions. These studies will provide insight into the normal metabolic regulation of CBF, and the mechanisms of functional and reactive myocardial hyperemia. Subsequent studies will examine the potential abnormalities of such regulation in experimental models of coronary artery disease, left ventricular pressure or volume overload, or in the clinical syndrome of "impaired coronary vasodilator reserve". This work may also lead to a better understanding of the myocardial metabolic consequences of brief coronary occlusion during angioplasty.

冠脉血流量(CBF)与心肌梗死密切相关 需氧量(MV02)。然而，这些机制 脑血流量的调节与心肌能量的变化 新陈代谢尚不清楚。 拟议工作的目的是研究这种机制。 通过考察CBF监管与 瞬时脑血流量与细胞内心肌能量状态 (由31P核磁共振谱评估)在瞬变阶段 功能性和反应性心肌充血。 我们将检验以下具体假设： 1.心肌高能磷酸盐水平密切相关 在MVO2发生变化的情况下通过快速和 精确调节脑血流量，从而实现氧气输送。 2.心肌反应性充血(RH)，随时间延长 持续时间和血液流动债务的总超额偿付，与 瞬时脑血流量与心肌的暂时分离 能态 开胸麻醉猪，器械包括 壁外多普勒冠状动脉血流探头的研究将在1- 仪器，2特斯拉磁共振光谱仪。血流动力学 将获得包括相CBF和31P核磁共振谱在内的数据 当实验系统被一个步骤扰动时 MV02的增大(通过配对的心室起搏和/或主动脉 收缩)或心肌氧供给量阶段性下降 (短暂冠状动脉闭塞)。 第一个假设预测MV02的阶跃增加将是 随后高能磷酸盐水平短暂下降， 代偿性冠状动脉血管扩张与增加的02分流， 以及快速恢复高能磷酸盐以控制 级别。第二种假说预测，心肌高密度 能量磷酸盐，在冠状动脉闭塞过程中部分耗尽， 在咬合解除后较早恢复正常 RH流回到它的基线。这将表明RH 血流量超过恢复心肌所需的血流量 新陈代谢状况。 这些研究将提供对正常新陈代谢的洞察 脑血流量的调节及其功能性和反应性机制 心肌充血。随后的研究将检查 这种调节在实验模型中的潜在异常 冠状动脉疾病、左心室压力或容量 超负荷，或在临床上表现为“冠状动脉受损” 血管扩张剂储备“。这项工作也可能导致更好的 对Brief的心肌代谢后果的认识 血管成形术中的冠状动脉闭塞。