NMR STUDIES OF MYOCARDIAL HYPERTROPHY

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.