Diagnostic Methods Nuclear Magnetic Resonance Spectroscopy

Exertional fatigue is a major limiting symptom in patients with heart failure. To investigate the metabolic basis of this fatigue, we used gated nuclear magnetic resonance spectroscopy to compare inorganic phosphate (P), phosphocreatine (PCr) and pH levels, and fatigue (1 to 4+) during mild forearm exercise in eight normal men and nine men with heart failure. Wrist flexion every 5 sec for 7 min was performed at 1, 2, and 3 J (average power output = 0.2, 0.4, and 0.6 W). In both groups linear relationships were noted between power output and P/PCr; the slope of this relationship was used to compare PCr depletion patterns. At rest both groups had similar Pi/PCr ratios (normal subjects 0.12 0.06, those with heart failure 0.15 ± 0.03) and pH (normal subjects 7.04 + 0.13, those with heart failure 7.10 0. 11). In normal subjects exercise resulted in a progressive increase in Pi/PCr (slope = 1.17 + 0.20 Pi/PCr units/W), a reduction in pH only at 0.6 W (0.2 W: 7.03 ± 0.10, 0.4 W: 7.01 0.10, 0.6 W: 6.88 ± 16) and moderate fatigue (0.2 W: 0 + 0, 0.4 W: 1.3 + 0.5, 0.6 W: 1.9 ± 0.6). In patients with heart failure exercise resulted in significantly greater fatigue at all workloads (0.2 W: 1.0 ± 0.5, 0.4 W: 1.9 0.6, 0.6 W: 2.9 ± 0.5). This fatigue was associated with twice as rapid an increase in Pi/PCr (slope = 2.63 + 2.14 PPCr units/W, p < .04 vs normal) and greater acidosis (0.2 W: 6.89 + 0.11, 0.4 W: 6.78 ± 0.22, 0.6 W: 6.75 + 0.23; p < .02 at 0.2 and 0.4 W vs normal). These data suggest that exertional fatigue in patients with heart failure may result from greater than normal PCr depletion and/or acidosis in the working muscle. Circulation 71, No. 1, 5742, 1985. EXERTIONAL FATIGUE is a major limiting symptom in patients with chronic heart failure both during maximal exercise and during normal daily activities.1 Therefore, identification of therapeutic modalities that would improve this fatigue is an important clinical objective. To achieve this objective, however, it is imperative that the mechanism responsible for exertional fatigue in patients with heart failure be identified. Recently we have demonstrated that the exertional fatigue that characteristically limits patients with heart failure during maximal bicycle exercise is associated with reduced leg blood flow and achievement of what appears to be a critical level of marked leg oxygen From the Cardiovascular Section, Department of Medicine and of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia. Address for correspondence: John R. Wilson, M.D., Cardiovascular Section, 943 Gates, Hospital of the University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104. Received Aug. 20, 1984; accepted Sept. 27, 1984. Dr. Wilson is the recipient of New Investigator Award HL-30665 from the NIH. extraction and lactate release.3 We therefore have postulated that this fatigue is due to lactic acidosis in working muscle.3 In normal subjects and experimental animals, muscular fatigue during maximal exercise also appears to result from intracellular acidosis.t Patients with heart failure do not, however, usually perform maximal exercise during normal daily activities. Therefore, it remains unclear whether the exertional fatigue experienced by such patients during less strenuous exercise is also associated with metabolic abnormalities in working muscle. The coupling of forearm exercise with phosphorus-3 1 nuclear magnetic resonance (31P NMR) provides a new noninvasive approach to the continuous monitoring of skeletal muscle metabolism in normal subjects7-9 and patients with pathologic conditions. 10. 11 This approach allows dynamic evaluation of inorganic phosphate (P1), phosphocreatine (PCr), and ATP levels in intact tissues. In addition, 31p NMR can be used to access intracellular pH since the chemical shift between Pi and PCr is dependent on pH.'2 These phosphate compounds and pH are key variaVol. 71, No. 1, January 1985 57 by gest on A ril 9, 2017 http://ciajournals.org/ D ow nladed from