NMR STUDIES OF MYOCARDIAL HYPERTROPHY

核磁共振（NMR）光谱，其允许 代谢物和阳离子的非侵入性、顺序评价， 用于研究小动物的灌注心脏。 虽然31 P NMR已被广泛用于评价高能磷酸盐代谢， 只有少数心脏组织的研究采用了核磁共振活性同位素 2 H、35 Cl和23 Na，它们允许测量细胞内水， 胞内钠 此外，相对较少的研究利用了 31 P NMR作为测定细胞内游离Mg 2+和 博士 虽然信号传导增加了心肌的血流动力学负荷， 生长仍然未知，增加细胞内Na+已被牵连， 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Ca 2+（通过Na+：Ca 2+交换）， 细胞内K+（通过Na+，K+-ATP酶）和细胞内游离Mg 2+（通过 Mg 2+：Na+共转运）。 所述研究的长期目标 在这个建议中，确定Na+水平的具体变化， 传输特性可能标志着发展（和逆转） 心肌肥大和对其他阳离子水平的伴随影响 和运输系统。 心肌肥厚是长期代偿机制之一 心脏压力 然而，肥大伴随主动脉瓣狭窄， 高血压或充血性心肌病，最初是一种适应性的 反应，可导致心力衰竭，由于过度生长不足 或异常功能。 高血压左室肥厚 患者与近10倍的风险增加有关， 出现充血性心力衰竭 心肌肥大（主动脉瓣狭窄）的特定动物模型将是 使用2 H、23 Na、31 P和35 C1 NMR进行研究（体外），以测量 细胞内阳离子和高能磷酸盐， 在肥大过程中发生的化学活动。 还将采用图像定位（1H、23 Na和31 P）NMR光谱 在这些研究中的一些中，为了测量细胞内游离镁、pH、高 能量磷酸盐、钠和特定代谢物（即，乳酸盐） 心脏的不同区域（左心室、右心室）。

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.