NMR STUDIES OF MYOCARDIAL HYPERTROPHY

核磁共振(核磁共振)波谱，它允许 对代谢物和阳离子进行非侵入性的顺序评估 用于小动物心脏灌流的研究。虽然31便士 核磁共振已被广泛用于评估高能磷酸盐代谢， 只有少数对心脏组织的研究使用了核磁共振活性同位素 2H、35Cl和23Na，它们允许测量细胞内的水和 细胞内钠离子。此外，相对较少的研究利用 ~(31)P核磁共振作为一种测量细胞内游离镁离子和 PH值。 尽管信号转导增加了进入心肌的血流动力学负荷 生长尚不清楚，细胞内Na+增加被认为是 至少有一个因素。Na+内流增加间接影响细胞内 PH(通过Na+/H+交换)，细胞内游离钙(通过Na+：Ca2+交换)， 细胞内K+(通过Na+，K+-ATPase)和细胞内游离镁2+(通过 Mg2+：Na+共转运)。这项研究的长期目标描述 这项建议的目的是确定Na+水平和 传输特性可能标志着 心肌肥厚及其对其他阳离子水平的影响 和运输系统。 心肌肥大是代偿的长期机制之一 治疗心脏应激。然而，肥厚伴主动脉狭窄， 高血压或充血性心肌病，最初是一种适应性 反应过度，可因生长不足或过度而导致心力衰竭 或功能异常。高血压病患者左心室肥厚 患者患癌症的风险几乎增加10倍。 发展为充血性心力衰竭。 一种特定的心肌肥厚(主动脉狭窄)动物模型将 研究(在体外)使用~2H，~(23)Na，~(31)P和~(35)C核磁共振来测量 细胞内阳离子和高能磷酸盐，并定义变化 在肥大过程中发生的化学活动。 还将使用图像局部化(1H、23Na和31P)核磁共振波谱 在一些这样的研究中，测量细胞内游离镁、pH、高 能量磷酸盐、钠和特定代谢物(即乳酸)中 心脏的不同区域(左、右室)。

Nuclear Magnetic Resonance (NMR) spectroscopy, which permits the noninvasive, sequential evaluation of metabolites and cations, has been employed in the study of perfused hearts of small animals. Although 31P NMR has been used extensively to evaluate high energy phosphate metabolism, only a few studies of cardiac tissue have employed the NMR active isotopes 2H, 35C1, and 23Na, which permit the measurement of intracellular water and intracellular sodium. In addition, relatively few studies have exploited the potential of 31P NMR as a method to measure intracellular free Mg2+ and pH. Although the signals transducing increased hemodynamic load into myocardial growth remain unknown, increased intracellular Na+ has been implicated as at least one factor. Increased Na+ influx indirectly affects intracellular pH (via Na+/H+ exchange), intracellular free Ca2+ (via Na+:Ca2+ exchange), intracellular K+ (via Na+,K+-ATPase), and intracellular free Mg2+ (via Mg2+:Na+ cotransport). the long term objective of the research described in this proposal is to determine specific alterations in Na+ levels and transport properties which might signal the development (and reversal) of myocardial hypertrophy and the concomitant effects on other cation levels and transport systems. Myocardial hypertrophy is one of the long-term mechanisms of compensation for cardiac stress. However, hypertrophy accompanying aortic stenosis, hypertension, or congestive cardiomyopathies, initially an adaptive response, can result in heart failure due to inadequate of excessive growth or abnormal function. Left ventricular hypertrophy in hypertensive patients is associated with an almost 10-fold increase in the risk of developing congestive heart failure. A specific animal model of myocardial hypertrophy (aortic stenosis) will be studied (in vitro) using 2H, 23Na, 31P, and 35C1 NMR to measure intracellular cations and high energy phosphates and to define the changes in their chemical activities which occur during the course of hypertrophy. Image-localized (1H, 23Na, and 31P) NMR spectroscopy will also be employed in some of these studies to measure intracellular free magnesium, pH, high energy phosphates, sodium, and specific metabolites (ie. lactate) in various regions (left ventricle, right ventricle) of the heart.