Diagnosis of Cardiac Viability by Functional Ultrasound

急性缺血后心脏活力的诊断和定量有助于确定治疗策略，并最终影响临床结果。该项目的长期目标是无创超声检测和量化反映心肌代谢活动的局部机械特征模式，这是主要的决定因素。我们发现，在S选择的心肌区域，实验性的药物抑制心肌细胞能量代谢导致了可复制的心肌内机械异常。具体地说，能量依赖性心肌松弛的起始期存在渐进性延迟。使用新型多普勒心肌速度梯度(MVG)超声心动图可测量这些局部功能事件的幅度和离散时间。基于这些发现，我们提出了一个新的概念，将局部心肌松弛的特定机械模式与心肌细胞的能量代谢联系起来。这种机械模式可以作为急性缺血期间持续存活心肌的诊断标志。我们假设，体内非侵入性测量的特征性局部机械像差将与体外检测的心肌细胞能量学测量相关。短期目标是研究MVG超声心动图的功能参数之间的关系，如a)从收缩到松弛过渡的时间，b)收缩后收缩幅度，c)早期松弛的幅度，以及2)心肌细胞能量代谢的模拟测量。公认的衡量标准是a)三磷酸腺苷的转换率，b)肌酸磷酸/无机磷的比率，以及c)肌酸激酶活性。目的：量化与诱导无氧代谢应激相关的局部心肌力学模式。目的：量化急性进展性心肌缺血心肌细胞代谢改变的心肌内力学模式。目的：定量描述顿抑、冬眠和再灌流心肌能量代谢改变的力学模式。这些目标将实现A)使用急性心肌能量代谢应激的开胸猪模型，B)使用高时间和空间分辨率的MVG超声心动图测量心肌机械像差，以及C)将MVG数据与通过分光光度分析的心脏活检组织中的高能磷酸盐水平相关联。这项建议旨在研究一种反映急性无氧和有氧代谢应激期间保存的心肌细胞能量周转的新原理。这项研究对于了解心脏的存活能力是至关重要的，对于确定急性缺血后离散的心肌功能反应的潜在病理生理机制也是至关重要的。

Diagnostic and quantitative of cardiac viability following acute ischermia help in determining therapeutic strategies and ultimately, influence the clinical outcome. The long-term objective of this project is noninvasive ultrasonographic detection and quantitation of characteristic local mechanical patterns that reflect myocardial metabolic activity, the principal determinant viability. We found that experimental pharmacologic inhibition of myocyte energy metabolism in s selected myocardial region leads to reproducible intramyocardial mechanical aberrations. In particular, there is a graded delay in the onset of energy-dependent myocardinal relaxation. Amplitude and discrete timing of these local functional events in measurable using novel Doppler myocardial velocity gradient (MVG) echocardiography. Based on these findings, we propose a new concept of linking specific mechanical patterns of local myocardinal relaxation to myocyte energy metabolism. Such mechanical patterns could serve as diagnostic markers of continuing myocardial viability during acute ischemia. We hypothesize that the characteristic local mechanical aberrations, measured noninvasively in vivo will correlate with measures of myocyte energetics, assayed in vitro. The short-term goal is to study the relationship between 1) functional parameters of MVG echocardiography, such as a) time to the point of transition from contraction to relaxation, b) postsytolic contraction amplitude, and c) magnitude of early relaxation; and 2) simulataneous measures of myocyte energy metabolism. The accepted measures are a) adenosine triphosphate turnover, b) creatine phosphate/ inorganic phosphate ratio, and c) creatine kinase activity. Aim1: Quantitate local myocardial mechanical patterns associated with induced anaerobic metabolic stress. Aim2: Quantitate intramyocardial mechanical patterns of altered myocyte metabolism in acutely progressively ischemic myocardium. Aim3: Quantitatively characterize mechanical patterns of altered energy metabolism in stunned, hibernating, and reperfused myocardium. These aims will be accomplished A) using open- chest pig models of acute myocardial energy metabolism stress, B) measuring the myocardial mechanical aberrations with high temporal and spatial resolution MVG echocardiography, and C) correlating the MVG data to high-energy phosphate levels in cardiac biopsies analyzed by spectrophotometry. This proposal is designed to study a novel principle of myocardial aberrations reflecting preserved myocyte energetic turnover during acute anaerobic and aerobic metabolic stress. This research is fundamentally important for understanding cardiac viability and essential for defining the underlying pathophysiologic mechanism of a discrete myocardial functional response to acute ischemia.