PERFUSION AND METABOLISM IN COLLATERALIZED MYOCARDIUM

研究将检查心肌适应的机制 冠状动脉血流受限将决定31P核磁共振 光谱学可以探测到一种独特的高能磷酸盐模式 在可存活但功能失调的区域的休息或应激时的满足 心肌。将产生侧支依赖的心肌区 在使用间歇性冠状动脉闭塞2分钟的狗 通过永久遮挡。动物将在质押时进行研究 使冠脉远端压力增加到60-70毫米汞柱，但收缩 超声晶体监测运动功能减退和血液功能 用微球测量的流量略有减少。心肌 将测定磷酸肌酸(PCr)、三磷酸腺苷(ATP)和无机磷(PI 用31P核磁共振波谱对3个跨室壁左室层进行了检测。 初步研究将表征ATP和PCR含量在 在基础条件下的侧支依赖区域，并检查 对多巴酚丁胺的反应。如果收缩功能没有改善或 在多巴酚丁胺过程中恶化，31P核磁共振波谱将证明 这种异常反应是否是缺血的结果(脑血管耗竭 聚合酶链式反应和PI的积累)或因为功能障碍区域 部分受到保护，不会对变力刺激做出反应。一秒钟 研究将确定运动是否会导致晕厥和ATP丢失 依赖侧支的区域；结果将与动物进行比较 在这种情况下，冠状动脉压力的类似降低是由急性心脏手术引起的 众所周知，外用的狭窄会导致运动引起的眩晕。一个 后续研究将使用13C核磁共振检查13C标记的摄取 葡萄糖和糖酵解的相对葡萄糖利用率， 侧支依赖型糖尿病大鼠的葡萄糖氧化和糖原合成 正常心肌。初步研究表明 侧支依赖心肌中磷酸单酯的蓄积；高 将使用31P核磁共振波谱来鉴定这些 磷酸化糖酵解中间体及其限速 侧支区域糖酵解流量的步骤。最后一项研究 将决定内源性NO的产生是否在 侧支依赖的心肌，以及补充NO是否能改善 能源需求/供应关系，如 聚合酶链反应/三磷酸腺苷比率。

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.