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定量反映心肌代谢活动的特征性局部机械模式，这是生存能力的主要决定因素。 我们发现，实验药理学抑制心肌细胞能量代谢在s选定的心肌区域导致可重复的心肌内机械畸变。 特别是，在能量依赖性肌松的发作中存在分级延迟。 这些局部功能事件的幅度和离散时间可使用新型多普勒心肌速度梯度（MVG）超声心动图测量。 基于这些发现，我们提出了一个新的概念，连接特定的机械模式，局部心肌舒张心肌细胞能量代谢。 这种机械模式可以作为急性缺血期间持续心肌存活的诊断标志。 我们假设，在体内非侵入性测量的特征性局部机械畸变将与体外测定的肌细胞能量学指标相关。短期目标是研究1）MVG超声心动图的功能参数之间的关系，例如a）从收缩到舒张的转变点的时间，B）收缩后收缩幅度和c）早期舒张幅度;和2）肌细胞能量代谢的同时测量。 可接受的指标为a）三磷酸腺苷转换率，B）磷酸肌酸/无机磷酸盐比值和c）肌酸激酶活性。 目的1：定量与诱导的无氧代谢应激相关的局部心肌力学模式。 目的2：定量急性进行性缺血心肌中心肌细胞代谢改变的心肌内机械模式。目的3：定量表征顿抑、冬眠和再灌注心肌中能量代谢改变的机械模式。 这些目的将通过以下方法实现：A）使用急性心肌能量代谢应激的开胸猪模型，B）用高时间和空间分辨率MVG超声心动图测量心肌机械畸变，以及C）将MVG数据与通过分光光度法分析的心脏活检中的高能磷酸盐水平相关联。 本研究旨在研究急性无氧和有氧代谢应激时心肌细胞能量代谢的一种新的机制。 这项研究对于理解心脏存活性至关重要，并且对于确定急性缺血时离散心肌功能反应的潜在病理生理机制至关重要。

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.