Studies are designed to determine whether abnormalities of perfusion or alterations of energy production and transfer in hypertrophied myocardium can result in an energy starved state during periods of increased work. Left ventricular hypertrophy will be produced by ascending aortic banding or by creating valvular aortic stenosis in young dogs; hypertrophy occurs as the pressure overload increases during normal growth in the presence of fixed aortic narrowing. At the time of study the transmural distribution of blood flow is measured with microspheres while contractile function is monitored with ultrasonic microcrystals. Myocardial phospho-creating, ATP and inorganic phosphate will be measured in 5 transmural layers across the left ventricular wall using 31P NMR spectroscopy. An initial study will determine whether the decreased vascular density in the hypertrophied heart results in increased dependence on endothelium-dependent nitric oxide mediated vasodilator mechanisms which are of special importance for maintaining subendocardial blood flow. A second study will examine whether the fetal shift of creating kinase (CK) isoenzymes which occurs in severely hypertrophied myocardium results in abnormalities in energy production or transfer. A study will determine whether flux through the CK reaction determined by saturation transfer 31P NMR is decreased in th hypertrophied heart during basal conditions or during high work states, whether this abnormality is related to the severity of hypertrophy, or to the degree of fetal shift of the CK isoenzymes. Data will be collected by transmural layer to determine whether changes are more prominent in the subendocardium. A third study will examine the ability of CK to buffer abrupt increases in ATP hydrolysis by determining whether increases in pacing rate result in transient loss of ATP in hypertrophied but not in normal hearts. Since the CK system should normally act to maintain low cytosolic ADP levels, a fourth study will test whether the fetal shift of CK isoenzymes causes abnormally increased ADP levels in hypertrophied myocardium at equivalent rates of ATP synthesis, and whether this results in abnormally increased levels of interstitial adenosine and increased loss of adenosine and its metabolites into the coronary circulation. A fifth study will determine whether treadmill exercise causes increased loss of purines from the severely hypertrophied heart into the coronary determine whether acceleration of ATP synthesis by supplying the nucleotide precursor ribose can restore myocardial ATP levels toward normal in the hypertrophied myocardium. A final study will determine whether increased myocardial adenosine production in the hypertrophied heart results in greater dependence upon either adenosine receptor stimulation or opening of K+ATP channels for coronary vasodilation during exercise. The results of these studies will identify abnormalities of myocardial bioenergetics which could contribute to the development of dysfunction of the hypertrophied heart.