phosphocreatine and Lung-Diseases--Obstructive

31P magnetic resonance spectroscopy (31P MRS) is a non-invasive method to evaluate high energy compounds [adenosine triphosphate (ATP), phosphocreatin (PCr), inorganic phosphates (Pi)] and intracellular pH (pHi) of skeletal muscle during exercise and recovery. It is a clinically applicable method of investigation for severe COPD patients with respiratory failure since exercise is limited to a single group of muscle (calf). Pronounced alterations of muscular metabolism have been shown in these patients: (1) reduced aerobic capacity (as reflected by the ratio of Pi/PCr as a function of power and changes in recovery kinetics of PCr after exercise and (2) increased anaerobic metabolism (reflected by a decrease in intracellular pH). Four different studies reveal similar abnormalities. Acute oxygen administration partially improves these parameters, suggesting that other factors in addition to hypoxaemia may contribute to the metabolic impairment. The effect of increased physical activity on these abnormalities deserve further investigations.

Topics: Adenosine Triphosphate; Anaerobic Threshold; Exercise Test; Humans; Hydrogen-Ion Concentration; Lung Diseases, Obstructive; Magnetic Resonance Spectroscopy; Muscle, Skeletal; Oxygen Inhalation Therapy; Phosphates; Phosphocreatine; Phosphorus Isotopes; Respiratory Insufficiency

Skeletal muscle metabolite depletion exists in advanced chronic obstructive pulmonary disease (COPD) patients with chronic hypoxaemia. The purpose of this study was to investigate if long-term oxygen therapy (LTOT) can improve skeletal muscle energy metabolism. Eight patients with advanced COPD, four with chronic hypoxaemia, were investigated using muscle biopsy specimens from the quadriceps femoris muscle applying the needle biopsy technique. The investigation was performed twice, before and after approximately 8 months of LTOT in the hypoxaemic patients. Eight healthy controls of similar age were also investigated. In the COPD patients, muscle glycogen, ATP and creatine phosphate (CrP) concentrations, were 42% (P < 0.01), 18% (P < 0.05) and 21% (P = n.s.) lower than in the healthy controls, respectively, while creatine (Cr) and lactate concentrations were 21% and 90% higher, respectively in the COPD patients compared to the healthy control subjects (P < 0.05). After LTOT, the 'energy index' CrP/(CrP + Cr) ratio increased by 0.12 in the LTOT patients but decreased by 0.12 in the control COPD patients (P < 0.05). The results indicate an improvement in skeletal muscle energy metabolism during LTOT in COPD patients with chronic hypoxaemia.

Topics: Adenosine Triphosphate; Aged; Creatine; Energy Metabolism; Female; Glycogen; Humans; Hypoxia; Lactates; Long-Term Care; Lung Diseases, Obstructive; Male; Middle Aged; Muscle, Skeletal; Oxygen Inhalation Therapy; Phosphocreatine

Cerebral intracellular energy production (cerebral bioenergetics) via oxidative phosphorylation and the production of adenosine triphosphate (ATP) is critical to cerebral function. To test the hypothesis that patients with chronic stable hypoxia also generate neuronal ATP via an anaerobic metabolism, we studied the changes in cerebral (31)P magnetic resonance spectra ((31)P MRS) in patients with stable chronic obstructive pulmonary disease (COPD), and compared the results with MR spectra from similar areas of the brain in control subjects. Ten patients with stable COPD (age: 65 +/- 9 yr [mean +/- SD]; Pa(O(2)): 8.8 +/- 1.2 kPa; Pa(CO(2)): 6.1 +/- 0.8 kPa; pH 7.42 +/- 0.03, and FEV(1): 41 +/- 20% predicted) and five healthy volunteers underwent cerebral (31)P MRS (TR-5,000 ms) at 1.5 T. When COPD patients were compared with controls, the percentage MR signal with respect to total MR-detectable phosphorus-containing metabolites was increased from inorganic phosphate (Pi) (7.1 +/- 1. 3% versus 3.9 +/- 0.7%, p = 0.0001) and phosphomonoesters (PMEs) (9. 4 +/- 1.2% versus 6.9 +/- 0.3%, p = 0.0001), whereas the signal from phosphodiesters was reduced (34.8 +/- 3.2 versus 40.4 +/- 3.3%, p = 0.015). The ratios of Pi to betaATP (0.8 +/- 0.2 versus 0.4 +/- 0.1, p = 0.001) and of PME to betaATP (1.0 +/- 0.2 versus 0.7 +/- 0.1, p = 0.015) were increased, but the phosphocreatine-to-Pi ratio (2.1 +/- 0.6 versus 3.2 +/- 0.6, p = 0.01) was reduced in patients as compared with controls. This alteration in phosphorus-containing metabolites within cerebral cells provides evidence of extensive use of anaerobic metabolism in hypoxic COPD patients.

Topics: Adenosine Triphosphate; Aged; Brain; Energy Metabolism; Female; Humans; Hydrogen-Ion Concentration; Lung Diseases, Obstructive; Magnetic Resonance Spectroscopy; Male; Middle Aged; Oxidative Phosphorylation; Phosphates; Phosphocreatine

We investigated the relationship between nutritional status and muscle energy metabolism during exercise in 18 male patients with chronic obstructive pulmonary disease (COPD) and 15 male control subjects using 31P nuclear magnetic resonance spectroscopy (31P-MRS). The patients and control subjects were further categorized as in either a well-nourished (% ideal body weight, % IBW > or = 90) or malnourished (% IBW < 90) state. Muscle energy metabolism was evaluated by determining the ratios PCr/(PCr + Pi) (PCr, phosphocreatine; Pi, inorganic phosphate), and ATP/(PCr + Pi + ATP). The exercise consisted of repetitive hand grips performed against a load. The work rate was normalized for the individual's lean muscle mass by dividing work performed by the forearm fat-free cross-sectional area, which was calculated using 1H-MRS. The PCr/(PCr + Pi) values during exercise did not correlate with the % IBW in any of the groups of control subjects or COPD patients. Furthermore, the PCr/(PCr + Pi) did not correlate with the normalized work rate in either the well-nourished or malnourished subject groups. However, there were correlations within the groups of control subjects and COPD patients. The PCr/(PCr + Pi) values for the normalized work rate were consistently lower in the COPD patients than in the control subjects. These findings suggest that the altered muscle metabolism in COPD patients is not affected by their nutritional status.

Topics: Adenosine Triphosphate; Adult; Aged; Body Weight; Case-Control Studies; Energy Metabolism; Hand; Humans; Hydrogen; Lung Diseases, Obstructive; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscle Contraction; Muscle, Skeletal; Nutrition Disorders; Nutritional Status; Phosphates; Phosphocreatine; Phosphorus; Physical Exertion; Weight Lifting; Work

Patients with respiratory failure have early fatiguability which may be due to limitation of oxygen supply for oxidative (mitochondrial) ATP synthesis. Skeletal muscle in exercise and recovery was studied to examine the effect of chronic hypoxia on mitochondrial activity in vivo.. The skeletal muscle of five patients with respiratory failure (PaO2 < 9 kPa) was studied by phosphorus-31 magnetic resonance spectroscopy and compared with 10 age and sex matched controls. Patients lay in a 1.9 Tesla superconducting magnet with the gastrocnemius muscle overlying a six cm surface coil. Spectra were acquired at rest, during plantar flexion exercise, and during recovery from exercise. Relative concentrations of inorganic phosphate (Pi), phosphocreatine (PCr) and ATP were measured from peak areas, and pH and free ADP concentration were calculated. For the start of exercise, the rates of PCr depletion and estimated lactic acid production were calculated. For the post exercise recovery period, the initial rate of PCr recovery (a quantitative measure of mitochondrial ATP synthesis), the apparent Vmax for mitochondrial ATP synthesis (calculated from initial PCr resynthesis and the end exercise ADP concentration which drives this process), and the recovery half times of PCr, Pi, and ADP (also measures of mitochondrial function) were determined.. Considerably greater and faster PCr depletion and intracellular acidosis were found during exercise. This is consistent with limitation of oxygen supply to the muscle and might explain the early fatiguability of these patients. There was no abnormality in recovery from exercise, however, suggesting that mitochondria function normally after exercise.. These results are consistent with one or more of the following: (a) decreased level of activity of these patients; (b) changes in the fibre type of the muscle; (c) decreased oxygen supply to the muscle during exercise but not during recovery. They are not consistent with an intrinsic defect of mitochondrial ATP synthesis in skeletal muscle in respiratory failure.

Topics: Adenosine Triphosphate; Aged; Energy Metabolism; Exercise; Female; Humans; Hypoxia; Lung Diseases, Obstructive; Magnetic Resonance Spectroscopy; Male; Middle Aged; Mitochondria, Muscle; Muscles; Phosphocreatine; Phosphorus; Respiratory Insufficiency

To evaluate the energy metabolism of peripheral skeletal muscle during exercise in patients with chronic respiratory impairment, the 31P-nuclear magnetic resonance (NMR) spectra of forearm muscle were investigated in nine patients and nine age-matched control subjects. We calculated the phosphocreatine (PCr) to PCr + inorganic phosphate (PI) ratio, the time constant of PCr recovery and the intracellular pH. The exercise consisted of repetitive hand grips against a 2-kg load every 3 s for 6 min (0.33 W). The patients showed a marked decrease in the PCr/(PCr + PI) ratio and pH in the muscle during exercise in contrast to the control subjects whose PCr/(PCr + PI) showed a minor decrease without any change in pH. The relationship between PCr utilization and pH demonstrated that anaerobic glycolysis switched on earlier in patients with chronic respiratory impairment. A split PI peak was observed in five of nine patients during exercise. The PCr/(PCr + PI) ratio during the last minute of exercise correlated significantly with the vital capacity (% predicted), with the FEV1/FVC, with the body weight, with the maximum strength of hand grip, and with the muscle mass. The results indicate impaired oxidative phosphorylation and the early activation of anaerobic glycolysis in the muscles of patients with chronic respiratory impairment. Several factors related to chronic respiratory impairment, such as disuse, malnutrition and dysoxia, would contribute to the metabolic changes observed in the muscles examined.

Topics: Aged; Anaerobic Threshold; Energy Metabolism; Exercise; Forearm; Glycolysis; Humans; Hydrogen-Ion Concentration; Lung Diseases, Obstructive; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscles; Phosphates; Phosphocreatine

The calf muscle metabolism of 7 patients with stable chronic respiratory failure (PaO2 below 65 Torr) was studied using 31P NMR spectroscopy. NMR spectra were acquired at rest, during the course of 360 pedal movements at 20, 35 and 50% of the maximal voluntary contraction (MVC) and during recovery. Eight normal aged-matched subjects served as a control group. In resting muscle, no significant differences were observed between both groups as regards intracellular pH, inorganic phosphate/phosphocreatine (Pi/PCr) and beta-ATP/PCr + Pi + phosphomonoester (PME) ratios. Although effective power outputs were similar for both groups at each work level, patients exhibited a higher Pi/PCr ratio than healthy controls (3.19 +/- 1.01 vs 0.49 +/- 0.05 at 50% MVC; p less than 0.01) and a lower pHi (6.65 +/- 0.11 vs 7.06 +/- 0.02 at 50% MVC; p less than 0.01). Moreover, PCr resynthesis during recovery was slower in patients than in control subjects (t1/2 PCr = 1.26 +/- 0.30 vs 0.47 +/- 0.05 min; p = 0.01). These results suggest impairment of aerobic capacity in a non-ventilatory working muscle, probably due to hypoxemia in patients with chronic respiratory failure.

Topics: Adenosine Triphosphate; Aged; Animals; Chronic Disease; Humans; Lung Diseases, Obstructive; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscles; Phosphates; Phosphocreatine; Phosphorus Radioisotopes; Respiratory Insufficiency

Eighteen patients with advanced COPD, 8 with chronic respiratory failure (RF) and 10 without (nonRF, NRF) were investigated using spirometry, arterial blood gas analysis and biopsies taken from the quadriceps femorls muscle. The biopsies were analysed for ATP, creatine phosphate (CrP), creatine (Cr), lactate and glycogen content. Muscle fibre composition was also studied. Low concentrations of ATP, glycogen and CrP were found in the RF patients. Significant correlations were found between muscle metabolites and arterial blood gas values with the strongest correlation between muscle glycogen and arterial PO2 (r = 0.70; p less than 0.001). A very low percentage of "oxidative" type I muscle fibres was found in both groups. Possible mechanisms causing depletion of muscle metabolites are discussed.

Topics: Adenosine Triphosphate; Biopsy; Creatine; Female; Glycogen; Humans; Lactates; Lactic Acid; Lung Diseases, Obstructive; Male; Middle Aged; Muscles; Phosphocreatine; Respiratory Insufficiency

Quadriceps femoris muscle needle biopsies were performed in ten patients with chronic obstructive pulmonary disease and acute respiratory failure and in ten age- and sex-matched healthy control subjects. The main indices of skeletal muscle cell energy metabolism, intracellular acid-base equilibrium and lactate metabolism were evaluated. Reduced ATP and phosphocreatine content, intracellular acidosis related to hypercapnia, increased muscle lactate without alterations of the muscle lactate concentration gradient were observed in the skeletal muscle of the hypercapnic-hypoxemic COPD patients studied, in which group no correlation was found between hypoxia and energy or lactate metabolism parameters. These results suggest that an overall derangement of cell energy metabolism and acid-base equilibrium is present in severely hypercapnic-hypoxemic chronic obstructive pulmonary disease and that in this condition skeletal muscle seems to metabolize anaerobically-even though, in addition to hypoxia, other factors interfering with both cell energy and lactate metabolism are likely to be present.

Topics: Acid-Base Equilibrium; Acute Disease; Adenosine Triphosphate; Aged; Energy Metabolism; Female; Humans; Hypercapnia; Hypoxia; Lactates; Lactic Acid; Lung Diseases, Obstructive; Male; Middle Aged; Muscles; Phosphocreatine; Respiratory Insufficiency

Twenty-two patients undergoing thoracotomy for the diagnosis or treatment of a suspected pulmonary neoplasm had separate biopsies taken from their external and internal intercostal muscles at the time of surgery. Pulmonary function abnormalities ranged from none to moderate airway obstruction. Seventeen of the twenty-two patients had morphologic changes (targeting, variation in fiber size, splitting, and atrophy) in both respiratory muscles, but not in the control latissimus dorsi. Fiber atrophy was more marked in the internal intercostal muscle and was significantly related to the degree of airway obstruction, but not to age, malignancy, or weight loss. Biochemical analyses revealed decreased adenosine triphosphate (ATP) and phosphocreatine (PC) in 47 of 52 muscles, including the latissimus dorsi. The data suggested a relation between increasing airway obstruction and decreasing amounts of phosphocreatine in both intercostal muscles. This relationship may have been enhanced by the presence of malignancy or weight loss. There was a selective decrease in muscle glycogen found only in the external intercostal muscle that was not affected by airway obstruction, malignancy, or weight loss. Intercostal muscle abnormalities are common in patients with obstructive lung disease who undergo thoracotomy, and are probably multifactorial in origin. It is possible that these abnormalities affect the natural history of lung disease in some patients.

Topics: Adenosine Triphosphate; Aged; Humans; Intercostal Muscles; Lactates; Lung Diseases, Obstructive; Lung Neoplasms; Lung Volume Measurements; Middle Aged; Phosphocreatine

1. The concentration of metabolites in intercostal and quadriceps muscle, and pulmonary function, were studied in twelve patients with chronic obstructive lung disease and acute respiratory failure before, during and after standardized treatment at an intensive care unit. The findings were compared with those obtained in hospitalized patients of comparable age with non-pulmonary diseases. 2. On admission, when the patients had marked hypoxaemia, hypercapnia and acidosis, the concentrations of ATP and creatine phosphate were low in both intercostal and quadriceps muscle, particularly the latter. The lactate concentration was increased in relation to control values but glycogen did not differ significantly. 3. In response to therapy, the Pa,CO2 and the patient's acidosis decreased, the vital capacity increased and lung mechanics improved along with the clinical condition. At the same time there were significant increases in the concentrations of ATP, creatine phosphate and glycogen in intercostal and quadriceps muscles, to values similar to, and for glycogen in excess of, those found in control subjects. Lactate concentration fell significantly during treatment. 4. In view of the low initial muscle concentrations of ATP and creatine phosphate in the patients, it is suggested that dysfunction of the respiratory muscles may be an important component of respiratory failure. Moreover, the concentration of energy-rich compounds in muscle rose significantly as the patients responded to treatment, which emphasizes the importance of adequate nutritional therapy in this disorder.

Topics: Acute Disease; Adenosine Triphosphate; Aged; Chronic Disease; Female; Glycogen; Humans; Intercostal Muscles; Lactates; Lung Diseases, Obstructive; Male; Middle Aged; Muscles; Phosphocreatine; Respiratory Function Tests; Respiratory Insufficiency