PERFUSION AND METABOLISM IN COLLATERALIZED MYOCARDIUM

侧支心肌的灌注和代谢

• 批准号: 2857927
• 负责人: ROBERT James BACHE
• 金额: $ 30.16万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2857927
• 关键词: adenosine triphosphate; bioenergetics; collateral circulation; coronary artery; creatine phosphate; dogs; exercise; glucose metabolism; myocardial ischemia /hypoxia; myocardium; nitric oxide; nuclear magnetic resonance spectroscopy

Studies will examine mechanisms by which the myocardium adapts to limited coronary arterial inflow and will determine whether 31 P NMR spectroscopy can detect a unique pattern of high energy phosphate content at rest or during stress in regions of viable but dysfunctional myocardium. A collateral-dependent myocardial region will be produced in dogs using intermittent 2 minute coronary artery occlusions followed by permanent occlusion. Animals will be studied when collateralization has increased distal coronary pressure to 60-70 mmHg, but contractile function monitored with ultrasonic crystals in hypokinetic and blood flow measured with microspheres is mildly reduced. Myocardial phosphocreatine (PCr), ATP and inorganic phosphate (Pi) will be measured in 3 transmural left ventricular layers using 31 P NMR spectroscopy. An initial study will characterize the ATP and PCr content in the collateral-dependent region during basal conditions, and examine the response to dobutamine. If contractile function fails to improve or deteriorates during a dobutamine, 31 P NMR spectroscopy will demonstrate whether this abnormal response is the result of ischemia (depletion of PCr and accumulation of Pi) or because the dysfunctional region is partially protected from responding to the inotropic stimulus. A second study will determine whether exercise causes stunning with ATP loss in the collateral-dependent region; results will be compared with animals in which a similar reduction of coronary pressure produced by an acutely applied stenosis is known to result in exercise induced stunning. A subsequent study will use 13C NMR to examine uptake of 13C-labeled glucose and the relative rates of glucose utilization for glycolosis, glucose oxidation and glycogen synthesis in collateral-dependent and normal myocardium. Preliminary studies have demonstrated phosphomonoester accumulation in collateral dependent myocardium; high resolution 31 P NMR spectroscopy will be used to identify these phosphorylated glycolytic intermediates and to find the rate limiting steps for glycolytic flux in the collateralized region. A final study will determine whether endogenous NO production is decreased in collateral-dependent myocardium, and whether supplying NO improves the energy demand/supply relationship as indicated by an increase in the PCr/ATP ratio.

研究将检查心肌适应的机制， 有限的冠状动脉流入，并将确定是否31 P NMR 光谱学可以检测到高能磷酸盐独特图案 在静息或应激期间，在存活但功能障碍的区域中的含量 心肌 将产生一个侧支依赖的心肌区域 在狗中使用间歇性2分钟冠状动脉闭塞， 永久性的闭塞。当抵押时，将研究动物 远端冠状动脉压力增加至60-70 mmHg，但收缩性 在运动功能减退和血液中用超声晶体监测功能 用微球测量的流量轻微降低。 心肌 将测量磷酸肌酸（PCr）、ATP和无机磷酸盐（Pi） 在3个透壁左心室层中使用31 P NMR光谱。 最初的研究将表征在细胞中的ATP和PCr含量。 在基础条件下的侧支依赖区，并检查 对多巴酚丁胺的反应 如果收缩功能未能改善或 在多巴酚丁胺治疗期间恶化，31 P NMR光谱将证明 这种异常反应是否是局部缺血的结果（ PCr和Pi的积累），或者因为功能失调的区域 部分地被保护免于对变力性刺激作出反应。 第二 这项研究将确定运动是否会导致昏迷， 侧支依赖区;结果将与动物进行比较 在这种情况下， 已知所施加的狭窄会导致运动诱发的眩晕。 一 随后研究将使用13 C NMR来检查13 C标记的 葡萄糖和用于糖酵解的葡萄糖利用的相对速率， 葡萄糖氧化和糖原合成在侧支依赖性和 正常心肌 初步研究表明 侧支依赖性心肌磷酸单酯蓄积;高 分辨率31 P NMR光谱将用于识别这些 磷酸化糖酵解中间体，并找到限速 侧支区域糖酵解通量的步骤。 最后一项研究 将决定内源性NO的产生是否减少， 侧支依赖性心肌，以及供应NO是否改善了 能源需求/供应关系，如增加所示， PCr/ATP比值。