Regional Myocardial Metabolism of High-Energy Phosphates during Isometric Exercise in Patients with Coronary Artery Disease

The maintenance of cellular levels of high-energy phosphates is required for myocardial function and preservation. In animals, severe myocardial ischemia is characterized by the rapid loss of phosphocreatine and a decrease in the ratio of phosphocreatine to ATP. To determine whether ischemic metabolic changes are detectable in humans, we recorded spatially localized phosphorus-31 nuclear-magnetic-resonance (³¹P NMR) spectra from the anterior myocardium before, during, and after isometric hand-grip exercise. The mean (±SD) ratio of phosphocreatine to ATP in the left ventricular wall when subjects were at rest was 1.72±0.15 in normal subjects (n = 11) and 1.59±0.31 in patients with nonischemic heart disease (n = 9), and the ratio did not change during hand-grip exercise in either group. However, in patients with coronary heart disease and ischemia due to severe stenosis (≥70 percent) of the left anterior descending or left main coronary arteries (n = 16), the ratio decreased from 1.45±0.31 at rest to 0.91±0.24 during exercise (P<0.001) and recovered to 1.27±0.38 two minutes after exercise. Only three patients with coronary heart disease had clinical symptoms of ischemia during exercise. Repeat exercise testing in five patients after revascularization yielded values of 1.60±0.20 at rest and 1.62±0.18 during exercise (P not significant), as compared with 1.51±0.19 at rest and 1.02±0.26 during exercise before revascularization (P<0.02). The decrease in the ratio of phosphocreatine to ATP during hand-grip exercise in patients with myocardial ischemia reflects a transient imbalance between oxygen supply and demand in myocardium with compromised blood flow. Exercise testing with ³¹P NMR is a useful method of assessing the effect of ischemia on myocardial metabolism of high-energy phosphates and of monitoring the response to treatment. ALTERED cardiac metabolism is the primary pathophysiologic consequence of myocardial ischemia in humans. To date, however, both investigative and routine characterizations of the presence and severity of myocardial ischemia and its response to therapy have focused on coronary anatomy and on the symptomatic, electrocardiographic, and functional results of changes in myocardial metabolism rather than on the metabolic changes themselves. Positron-emission tomography has been used to evaluate the effects of ischemia and infarction on myocardial substrate uptake but cannot quantify myocardial high-energy phosphate metabolites,^{1 2 3} which are required for the functioning and viability of myocardial cells. Phosphorus-31 nuclear-magnetic-resonance (³¹P NMR) spectroscopy…