phosphocreatine and Pulmonary-Disease--Chronic-Obstructive

In recent years, COPD has become increasingly thought of as a systemic disease affecting many tissues and organs in addition to the lungs. The skeletal muscles in particular have been the target of much research focusing on whether the universally observed exercise limitation reflects a systemic myopathic effect of COPD, or simply the consequences of extreme, long-term inactivity. In this paper, the evidence is reviewed for COPD patients without loss of muscle mass and who are not taking systemic steroids. While altered levels of antioxidant defences (lower), circulating inflammatory biomarkers (higher) and anabolic hormones (lower) have been found in COPD, cause and effect remains to be established for the link of inflammation/oxidative stress to muscle dysfunction. Other evidence used to propose a myopathic state (early lactate release, reduced power output, lower metabolic enzyme capacities, greater phosphocreatine breakdown and slower phosphocreatine restoration after exercise, and altered fibre type distribution) also occur in normal subjects who are extremely inactive. Furthermore, intense small muscle mass training can normalize small muscle function in these patients. Based on these data, it remains to be shown that the muscles in COPD patients without loss of muscle mass are myopathic. The interesting discussion about systemic effects of COPD should not get in the way of systematic muscle training, which has been shown to be an effective component of rehabilitation.

Topics: Exercise Therapy; Forced Expiratory Volume; Humans; Insulin-Like Growth Factor I; Interleukin-6; Lactates; Muscle Weakness; Muscle, Skeletal; Muscular Diseases; Oxidative Stress; Phosphocreatine; Physical Fitness; Pulmonary Disease, Chronic Obstructive; Pulmonary Ventilation; Testosterone; Tumor Necrosis Factor-alpha

An alteration of high energy phosphate metabolism in muscles may contribute to exercise intolerance. The objective of this study was to clarify the changes in high energy phosphate metabolites in muscles during exercise in patients with non-hypoxaemic chronic obstructive pulmonary disease (COPD), which influences the impairment of muscle metabolism.. Calf muscle energy metabolism was studied in eight stable non-hypoxaemic COPD patients and eight control subjects, using 31P-magnetic resonance spectroscopy (MRS). MRS spectra were acquired at rest, during exercise at two levels of intensity, and during recovery. The control subjects exercised under both normoxic and hypoxic conditions. The intensity of exercise was standardized by the maximal isometric voluntary contraction (MVC) of the calf muscle and the cross-sectional area (CSA) of calf muscle.. MVC and CSA were lower in COPD patients. No significant differences in intracellular pH, inorganic phosphate/phosphocreatine ratio or percentage recovery in inorganic phosphate/phosphocreatine ratio were observed between the two groups in muscles at rest, during exercise or during recovery.. Muscle metabolites, during exercise standardized by muscle CSA and MVC, did not differ between non-hypoxaemic COPD patients and control subjects. MVC, CSA or both, are assumed to be closely related to muscle metabolism, as no difference in high energy phosphate metabolites was observed for COPD patients compared to control subjects when the load was standardized for MVC and CSA. This suggests that high energy metabolites are consumed to a similar extent in the same muscle volume in non-hypoxaemic COPD patients and control subjects.

Topics: Aged; Exercise; Humans; Hypoxia; Japan; Magnetic Resonance Spectroscopy; Middle Aged; Muscle, Skeletal; Phosphates; Phosphocreatine; Pulmonary Disease, Chronic Obstructive

Chronic obstructive pulmonary disease (COPD) is associated with metabolic abnormalities in muscles of the lower limbs, but it is not known whether these abnormalities are generalized or limited to specific muscle groups, nor is there an easy way of predicting their presence.. Metabolism in the quadriceps and biceps of 14 COPD patients and controls was assessed during sustained contraction using 31-phosphorus magnetic resonance spectroscopy ((31) P MRS). T1 MRI was used to measure quadriceps intermuscular adipose tissue (IMAT).. COPD patients had prolonged quadriceps phosphocreatine time (patients: 38.8 ± 12.7 s; controls: 25.2 ± 10.6 s; P = 0.006) and a lower pH (patents: 6.88 ± 0.1; controls: 6.99 ± 0.06; P = 0.002). Biceps measures were not significantly different. IMAT was associated with a nadir pH <7.0 (area under the curve = 0.84).. Anaerobic metabolism during contraction was characteristic of quadriceps, but not biceps, muscles of patients with COPD and was associated with increased IMAT. Because IMAT can be assessed quickly by conventional MRI, it may be a useful approach for identifying patients with abnormal muscle bioenergetics.

Topics: Aged; Energy Metabolism; Exercise; Fats; Female; Forced Expiratory Volume; Humans; Hydrogen-Ion Concentration; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscle Contraction; Phosphocreatine; Phosphorus Isotopes; Pulmonary Disease, Chronic Obstructive; Quadriceps Muscle; ROC Curve; Severity of Illness Index

To better understand the metabolic implications of a higher ATP cost of contraction in chronic obstructive pulmonary disease (COPD), we used (31)P-magnetic resonance spectroscopy ((31)P-MRS) to examine muscle energetics and pH in response to graded exercise. Specifically, in six patients and six well-matched healthy controls, we determined the intracellular threshold for pH (T(pH)) and inorganic phosphate-to-phosphocreatine ratio (T(Pi/PCr)) during progressive dynamic plantar flexion exercise with work rate expressed as both absolute and relative intensity. Patients with COPD displayed a lower peak power output (WRmax) compared with controls (controls 25 ± 4 W, COPD 15 ± 5 W, P = 0.01) while end-exercise pH (controls 6.79 ± 0.15, COPD 6.76 ± 0.21, P = 0.87) and PCr consumption (controls 82 ± 10%, COPD 70 ± 18%, P = 0.26) were similar between groups. Both T(pH) and T(Pi/PCr) occurred at a significantly lower absolute work rate in patients with COPD compared with controls (controls: 14.7 ± 2.4 W for T(pH) and 15.3 ± 2.4 W for T(Pi/PCr); COPD: 9.7 ± 4.5 W for T(pH) and 10.0 ± 4.6 W for T(Pi/PCr), P < 0.05), but these thresholds occurred at the same percentage of WRmax (controls: 63 ± 11% WRmax for T(pH) and 67 ± 18% WRmax for T(Pi/PCr); COPD: 59 ± 9% WRmax for T(pH) and 61 ± 12% WRmax for T(Pi/PCr), P > 0.05). Indexes of mitochondrial function, the PCr recovery time constant (controls 42 ± 7 s, COPD 45 ± 11 s, P = 0.66) and the PCr resynthesis rate (controls 105 ± 21%/min, COPD 91 ± 31%/min, P = 0.43) were similar between groups. In combination, these results reveal that when energy demand is normalized to WRmax, as a consequence of higher ATP cost of contraction, patients with COPD display the same metabolic pattern as healthy subjects, suggesting that skeletal muscle energy production is well preserved in these patients.

Topics: Adenosine Triphosphate; Aged; Energy Metabolism; Exercise; Humans; Hydrogen-Ion Concentration; Kinetics; Magnetic Resonance Spectroscopy; Male; Mitochondria; Muscle Contraction; Muscle, Skeletal; Phosphates; Phosphocreatine; Pulmonary Disease, Chronic Obstructive

Impaired metabolism in peripheral skeletal muscles potentially contributes to exercise intolerance in chronic obstructive pulmonary disease (COPD). We used (31)P-magnetic resonance spectroscopy ((31)P-MRS) to examine the energy cost and skeletal muscle energetics in six patients with COPD during dynamic plantar flexion exercise compared with six well-matched healthy control subjects. Patients with COPD displayed a higher energy cost of muscle contraction compared with the controls (control: 6.1 ± 3.1% of rest·min(-1)·W(-1), COPD: 13.6 ± 8.3% of rest·min(-1)·W(-1), P = 0.01). Although, the initial phosphocreatine resynthesis rate was also significantly attenuated in patients with COPD compared with controls (control: 74 ± 17% of rest/min, COPD: 52 ± 13% of rest/min, P = 0.04), when scaled to power output, oxidative ATP synthesis was similar between groups (6.5 ± 2.3% of rest·min(-1)·W(-1) in control and 7.8 ± 3.9% of rest·min(-1)·W(-1) in COPD, P = 0.52). Therefore, our results reveal, for the first time that in a small subset of patients with COPD a higher ATP cost of muscle contraction may substantially contribute to the lower mechanical efficiency previously reported in this population. In addition, it appears that some patients with COPD have preserved mitochondrial function and normal energy supply in lower limb skeletal muscle.

Topics: Adenosine Triphosphate; Aged; Case-Control Studies; Energy Metabolism; Exercise Tolerance; Humans; Hydrogen-Ion Concentration; Kinetics; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscle Contraction; Muscle, Skeletal; Oxidation-Reduction; Phosphocreatine; Pulmonary Disease, Chronic Obstructive

Exercise capacity is frequently decreased in patients with chronic obstructive pulmonary disease (COPD), and muscle dysfunction is one factor in this reduction. Studies using (31)-phosphorus magnetic resonance spectroscopy ((31)P-MRS) have shown that phosphocreatine (PCr) and muscle pH (pHi) are significantly decreased in patients with COPD during mild exercise, suggesting the early activation of anaerobic glycolysis in their muscles. Thus, muscle oxygenation states during exercise might differ between patients with COPD and healthy individuals. We simultaneously measured oxygenation state and pHi in the muscles of patients with COPD during the transition from rest to exercise (on-transition) using near infrared spectroscopy (NIRS) and (31)P-MRS. Sixteen patients with COPD (aged 68.6 +/- 7.5 years) and 7 healthy males (controls; aged 63.3 +/- 7.5 years) performed dynamic handgrip exercise (lifting a weight by gripping at a rate of 20 grips per min for 3 min). Patients were classified based on pHi data at the completion of exercise as having a normal (>or= 6.9; n = 8) or a low (< 6.9; n = 8) pHi. The deoxygenated hemoglobin/myoglobin (deoxy-Hb/Mb) in NIRS recordings remained constant or slightly decreased initially (time delay), then increased to reach a plateau. We calculated the time delay and the time constant of deoxy-Hb/Mb kinetics during the on-transition. The time delay was shorter in the group with a low pHi than in the controls. These findings might reflect a slower increase in O(2) delivery in patients with a low pHi, which might partly account for altered muscle energy metabolism.

Topics: Aged; Exercise; Forearm; Health; Hemoglobins; Humans; Hydrogen-Ion Concentration; Kinetics; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscle, Skeletal; Myoglobin; Oxidation-Reduction; Phosphocreatine; Pulmonary Disease, Chronic Obstructive; Rest

Although several studies have shown that plasma concentrations of branched-chain amino acids (BCAAs) are reduced in patients with chronic obstructive pulmonary disease (COPD), little is understood about how low concentrations of BCAAs limit exercise in such patients. The present study investigated whether plasma BCAAs are related to energy metabolism in exercising muscle using (31)P-magnetic resonance spectroscopy (MRS).. We analyzed the plasma amino acid profiles of 23 male patients with COPD (aged 69.2+/-5.1 years) and of 7 healthy males (aged 64.1+/-6.0 years). We normalized the exercise intensity of repetitive lifting by adjusting the weight to 7% of the maximal grip power. The intracellular pH and the phosphocreatine (PCr) index (PCr/(PCr+Pi); Pi, inorganic phosphate) were calculated from MR spectra. We evaluated the relationship between intracellular pH and PCr index at the completion of exercise and the plasma BCAA concentration.. Glutamine concentrations were elevated in patients with COPD compared with healthy individuals. Plasma concentrations of BCAAs correlated with intracellular pH and PCr index at the completion of exercise.. The findings are consistent with the notion that BCAAs affect muscle energy metabolism during exercise in patients with COPD.

Topics: Aged; Amino Acids, Branched-Chain; Energy Metabolism; Exercise; Forearm; Glutamine; Humans; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscle, Skeletal; Phosphocreatine; Pulmonary Disease, Chronic Obstructive

To investigate energy metabolic and transporter characteristics in resting muscle of patients with moderate to severe chronic obstructive pulmonary disease [COPD; forced expiratory volume in 1 s (FEV(1)) = 42 +/- 6.0% (mean +/- SE)], tissue was extracted from resting vastus lateralis (VL) of 9 COPD patients and compared with that of 12 healthy control subjects (FEV(1) = 114 +/- 3.4%). Compared with controls, lower (P < 0.05) concentrations (mmol/kg dry wt) of ATP (19.6 +/- 0.65 vs. 17.8 +/- 0.69) and phosphocreatine (81.3 +/- 2.3 vs. 69.1 +/- 4.2) were observed in COPD, which occurred in the absence of differences in the total adenine nucleotide and total creatine pools. Higher concentrations were observed in COPD for several glycolytic metabolites (glucose-1-phosphate, glucose-6-phosphate, fructose-6-phosphate, pyruvate) but not lactate. Glycogen storage was not affected by the disease (289 +/- 20 vs. 269 +/- 20 mmol glucosyl units/kg dry wt). Although no difference between groups was observed for the glucose transporter GLUT1, GLUT4 was reduced by 28% in COPD. For the monocarboxylate transporters, MCT4 was 35% lower in COPD, with no differences observed for MCT1. These results indicate that in resting VL, moderate to severe COPD results in a reduction in phosphorylation potential, an apparent elevation of glycolytic flux rate, and a potential defect in glucose and lactate transport as a result of reduced levels of the principal isoforms.

Topics: Adenosine Triphosphate; Aged; Case-Control Studies; Down-Regulation; Energy Metabolism; Female; Forced Expiratory Volume; Glucose; Glucose Transporter Type 1; Glucose Transporter Type 4; Glycogen; Glycolysis; Humans; Lactic Acid; Male; Membrane Transport Proteins; Middle Aged; Monocarboxylic Acid Transporters; Muscle Proteins; Phosphocreatine; Pulmonary Disease, Chronic Obstructive; Quadriceps Muscle; Severity of Illness Index; Symporters

Chronic obstructive pulmonary disease (COPD) is associated with an increased load on the diaphragm. Chronic loading on skeletal muscles results in metabolic changes and fiber-type shifts. Therefore, we investigated whether the load on the human diaphragm imposed by COPD altered oxidative enzyme activity, glycogenolytic enzyme activity and mitochondrial energy generating capacity and efficiency. Biopsies of the diaphragm from COPD patients and control subjects were obtained and activities of L(+)3-hydroxyacylCoA-dehydrogenase (HADH, marker for beta-oxidation capacity) and phosphorylase (marker for glycogenolytic capacity) were measured spectrophotometrically. Mitochondrial energy generating capacity was measured by spectrophotometrical and radiochemical methods. Fiber-type distribution was determined electrophoretically. We found that HADH activity was increased with increasing severity of COPD (P=0.05). No change in glycogenolytic enzyme activity was observed. The activity of the mitochondrial respiratory chain complexes III and IV and oxidation of pyruvate was increased with increasing airflow obstruction. These results suggest that in COPD the diaphragm adapts to a higher workload by increasing the oxidative capacity and mitochondrial function.

Topics: 3-Hydroxyacyl CoA Dehydrogenases; Adenosine Triphosphate; Biopsy; Clinical Enzyme Tests; Diaphragm; Energy Metabolism; Exercise Tolerance; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Mitochondria, Muscle; Phosphocreatine; Phosphorylases; Pulmonary Disease, Chronic Obstructive