BACKGROUND. 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. METHODS. 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. RESULTS. 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 (greater than or equal to 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 less than 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 less than 0.02). CONCLUSIONS. 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.
Source Information
Department of Medicine, Johns Hopkins Hospital, Baltimore.
This article has been cited by other articles:
Gupta, A., Chacko, V. P., Weiss, R. G.
(2009). Abnormal energetics and ATP depletion in pressure-overload mouse hearts: in vivo high-energy phosphate concentration measures by noninvasive magnetic resonance. Am. J. Physiol. Heart Circ. Physiol.
297: H59-H64
[Abstract][Full Text]
Hudsmith, L. E., Neubauer, S.
(2009). Magnetic resonance spectroscopy in myocardial disease.. J Am Coll Cardiol Img
2: 87-96
[Abstract][Full Text]
Maslov, M. Y., Chacko, V. P., Stuber, M., Moens, A. L., Kass, D. A., Champion, H. C., Weiss, R. G.
(2007). Altered high-energy phosphate metabolism predicts contractile dysfunction and subsequent ventricular remodeling in pressure-overload hypertrophy mice. Am. J. Physiol. Heart Circ. Physiol.
292: H387-H391
[Abstract][Full Text]
Chung, Y.
(2006). Oxygen reperfusion is limited in the postischemic hypertrophic myocardium. Am. J. Physiol. Heart Circ. Physiol.
290: H2075-H2084
[Abstract][Full Text]
Naumova, A. V., Chacko, V. P., Ouwerkerk, R., Stull, L., Marban, E., Weiss, R. G.
(2006). Xanthine oxidase inhibitors improve energetics and function after infarction in failing mouse hearts. Am. J. Physiol. Heart Circ. Physiol.
290: H837-H843
[Abstract][Full Text]
Caus, T., Kober, F., Marin, P., Mouly-Bandini, A., Quilici, J., Metras, D., Cozzone, P. J., Bernard, M.
(2006). Non-invasive diagnostic of cardiac allograft vasculopathy by 31P magnetic resonance chemical shift imaging. Eur. J. Cardiothorac. Surg.
29: 45-49
[Abstract][Full Text]
Weiss, R. G., Gerstenblith, G., Bottomley, P. A.
(2005). ATP flux through creatine kinase in the normal, stressed, and failing human heart. Proc. Natl. Acad. Sci. USA
102: 808-813
[Abstract][Full Text]
Pennell, D. J., Sechtem, U. P., Higgins, C. B., Manning, W. J., Pohost, G. M., Rademakers, F. E., van Rossum, A. C., Shaw, L. J., Yucel, E. K.
(2004). Clinical indications for cardiovascular magnetic resonance (CMR): Consensus Panel report. Eur Heart J
25: 1940-1965
[Full Text]
Naumova, A. V., Weiss, R. G., Chacko, V. P.
(2003). Regulation of murine myocardial energy metabolism during adrenergic stress studied by in vivo 31P NMR spectroscopy. Am. J. Physiol. Heart Circ. Physiol.
285: H1976-H1979
[Abstract][Full Text]
Pohost, G. M., Hung, L., Doyle, M.
(2003). Clinical Use of Cardiovascular Magnetic Resonance. Circulation
108: 647-653
[Full Text]
Balaban, R. S., Bose, S., French, S. A., Territo, P. R.
(2003). Role of calcium in metabolic signaling between cardiac sarcoplasmic reticulum and mitochondria in vitro. Am. J. Physiol. Cell Physiol.
284: C285-C293
[Abstract][Full Text]
Beyerbacht, H. P., Lamb, H. J., van der Laarse, A., Vliegen, H. W., Leujes, F., Hazekamp, M. G., de Roos, A., van der Wall, E. E.
(2001). Aortic Valve Replacement in Patients with Aortic Valve Stenosis Improves Myocardial Metabolism and Diastolic Function. Radiology
219: 637-643
[Abstract][Full Text]
Saeed, M.
(2001). New Concepts in Characterization of Ischemically Injured Myocardium by MRI. Exp. Biol. Med.
226: 367-376
[Abstract][Full Text]
Chacko, V. P., Aresta, F., Chacko, S. M., Weiss, R. G.
(2000). MRI/MRS assessment of in vivo murine cardiac metabolism, morphology, and function at physiological heart rates. Am. J. Physiol. Heart Circ. Physiol.
279: H2218-H2224
[Abstract][Full Text]
Buchthal, S. D., den Hollander, J. A., Merz, C. N. B., Rogers, W. J., Pepine, C. J., Reichek, N., Sharaf, B. L., Reis, S., Kelsey, S. F., Pohost, G. M.
(2000). Abnormal Myocardial Phosphorus-31 Nuclear Magnetic Resonance Spectroscopy in Women with Chest Pain but Normal Coronary Angiograms. NEJM
342: 829-835
[Abstract][Full Text]
Pauly, D. F., Pepine, C. J.
(2000). D-Ribose as a Supplement for Cardiac Energy Metabolism. J CARDIOVASC PHARMACOL THER
5: 249-258
[Abstract]
Cortez-Pinto, H., Chatham, J., Chacko, V. P., Arnold, C., Rashid, A., Diehl, A. M.
(1999). Alterations in Liver ATP Homeostasis in Human Nonalcoholic Steatohepatitis: A Pilot Study. JAMA
282: 1659-1664
[Abstract][Full Text]
Lamb, H. J., Beyerbacht, H. P., van der Laarse, A., Stoel, B. C., Doornbos, J., van der Wall, E. E., de Roos, A.
(1999). Diastolic Dysfunction in Hypertensive Heart Disease Is Associated With Altered Myocardial Metabolism. Circulation
99: 2261-2267
[Abstract][Full Text]
Jung, W.-I., Sieverding, L., Breuer, J., Hoess, T., Widmaier, S., Schmidt, O., Bunse, M., van Erckelens, F., Apitz, J., Lutz, O., Dietze, G. J.
(1998). 31P NMR Spectroscopy Detects Metabolic Abnormalities in Asymptomatic Patients With Hypertrophic Cardiomyopathy. Circulation
97: 2536-2542
[Abstract][Full Text]
Conway, M. A., Bottomley, P. A., Ouwerkerk, R., Radda, G. K., Rajagopalan, B.
(1998). Mitral Regurgitation : Impaired Systolic Function, Eccentric Hypertrophy, and Increased Severity Are Linked to Lower Phosphocreatine/ATP Ratios in Humans. Circulation
97: 1716-1723
[Abstract][Full Text]
Lamb, H. J., Beyerbacht, H. P., Ouwerkerk, R., Doornbos, J., Pluim, B. M., van der Wall, E. E., van der Laarse, A., de Roos, A.
(1997). Metabolic Response of Normal Human Myocardium to High-Dose Atropine-Dobutamine Stress Studied by 31P-MRS. Circulation
96: 2969-2977
[Abstract][Full Text]
Neubauer, S., Horn, M., Cramer, M., Harre, K., Newell, J. B., Peters, W., Pabst, T., Ertl, G., Hahn, D., Ingwall, J. S., Kochsiek, K., Kochsiek, K.
(1997). Myocardial Phosphocreatine-to-ATP Ratio Is a Predictor of Mortality in Patients With Dilated Cardiomyopathy. Circulation
96: 2190-2196
[Abstract][Full Text]
Nascimben, L., Ingwall, J. S., Pauletto, P., Friedrich, J., Gwathmey, J. K., Saks, V., Pessina, A. C., Allen, P.D.
(1996). Creatine Kinase System in Failing and Nonfailing Human Myocardium. Circulation
94: 1894-1901
[Abstract][Full Text]
Friedrich, J., Apstein, C. S., Ingwall, J. S.
(1995). 31P Nuclear Magnetic Resonance Spectroscopic Imaging of Regions of Remodeled Myocardium in the Infarcted Rat Heart. Circulation
92: 3527-3538
[Abstract][Full Text]
van der Wall, E. E., Vliegen, H. W., de Roos, A., Bruschke, A. V.G.
(1995). Magnetic Resonance Imaging in Coronary Artery Disease. Circulation
92: 2723-2739
[Abstract][Full Text]
Arai, A. E., Grauer, S. E., Anselone, C. G., Pantely, G. A., Bristow, J. D.
(1995). Metabolic Adaptation to a Gradual Reduction in Myocardial Blood Flow. Circulation
92: 244-252
[Abstract][Full Text]
Pohost, G. M.
(1995). Is 31P-NMR Spectroscopic Imaging a Viable Approach to Assess Myocardial Viability?. Circulation
92: 9-10
[Full Text]
Yabe, T., Mitsunami, K., Inubushi, T., Kinoshita, M.
(1995). Quantitative Measurements of Cardiac Phosphorus Metabolites in Coronary Artery Disease by 31P Magnetic Resonance Spectroscopy. Circulation
92: 15-23
[Abstract][Full Text]
(1990). A SENSITIVE NEW DIAGNOSTIC TEST FOR CORONARY ARTERY DISEASE. JWatch General
1990: 2-2
[Full Text]