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局部力学模式，这是主要的决定因素。我们发现实验性药物抑制心肌细胞能量代谢在5个选定的心肌区域导致可重复的心内机械畸变。特别是，能量依赖性心肌舒张的发生有一个分级延迟。利用新型多普勒心肌速度梯度（MVG）超声心动图测量这些局部功能事件的振幅和离散时间。基于这些发现，我们提出了将局部心肌舒张的特定机械模式与肌细胞能量代谢联系起来的新概念。这种力学模式可以作为急性缺血时心肌持续活力的诊断指标。我们假设，在体内无创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测量相关。短期目标是研究1)MVG超声心动图的功能参数，如a)收缩到舒张过渡点的时间，b)收缩后收缩幅度，c)早期舒张幅度之间的关系；2)肌细胞能量代谢的同步测量。可接受的测量方法是a)三磷酸腺苷周转率，b)磷酸肌酸/无机磷酸盐比率，c)肌酸激酶活性。目的1：量化与诱导无氧代谢应激相关的局部心肌力学模式。目的2：定量测定急性进行性缺血心肌中心肌细胞代谢改变的心内力学模式。目的3：定量表征休克、冬眠和再灌注心肌能量代谢改变的力学模式。这些目标将实现A)使用猪开胸急性心肌能量代谢应激模型，B)使用高时空分辨率MVG超声心动图测量心肌机械畸变，以及C)通过分光光度法分析心脏活检中MVG数据与高能磷酸盐水平的相关性。本研究旨在研究急性无氧和有氧代谢应激下心肌畸变反映心肌细胞能量转换的新原理。这项研究对于理解心脏活力至关重要，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.