phosphocreatine and Respiratory-Insufficiency

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

Diaphragm fatigue may contribute to respiratory failure. (31)P-nuclear magnetic resonance spectroscopy is a useful tool to assess energetic changes within the diaphragm during fatigue, as indicated by P(i) accumulation and phosphocreatine (PCr) depletion. We hypothesized that loaded breathing during hypoxia would lead to diaphragm fatigue and inadequate aerobic metabolism. Seven piglets were anesthetized by using halothane inhalation. Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi) at end expiration with the airway occluded. A nuclear magnetic resonance surface coil placed under the right hemidiaphragm measured P(i) and PCr during four conditions: control, inspiratory resistive breathing (IRB), IRB with hypoxia, and recovery (IRB without hypoxia). IRB alone resulted in hypercarbia (32 +/- 7 to 61 +/- 21 Torr) and respiratory acidosis but no change in diaphragm force output or aerobic metabolism. Combined IRB and hypoxia resulted in decreased force output (Pdi decreased by 40%; from 30 +/- 17 to 19 +/- 11 mmHg) and evidence of metabolic stress (ratio of P(i) to PCr increased by 290%; from 0.19 +/- 0.09 to 0.74 +/- 0.27). We conclude that diaphragm fatigue associated with inadequate aerobic oxidative metabolism occurs in the setting of loaded breathing and hypoxia. Conversely, aerobic metabolism and force output of the diaphragm remain unchanged from control during loaded normoxic or hyperoxic breathing despite the onset of respiratory failure.

Topics: Animals; Diaphragm; Hypoxia; Magnetic Resonance Spectroscopy; Muscle Fatigue; Phosphates; Phosphocreatine; Respiratory Insufficiency; Respiratory Mechanics; Swine

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

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

Methods used to obtain and quantify high-quality time-resolved dog brain phosphorus nuclear magnetic resonance (31P NMR) spectra are described. In eight animals the normoxic dog brain spectra showed 10% of total phosphorus in ATP, 14% in phosphocreatine (PCr), and 38% in brain phospholipids containing phosphodiesters. The chemical shift between PCr and inorganic phosphate, 5.09, corresponded to an intracellular brain pH of 7.2. During hypoxia, PCr declined to 0.5 +/- 0.3 (n = 8) of starting levels, prior to any changes in brain ATP. Simultaneous recording of the EEG was obtained in two animals. During hypoxia, progressive PCr depletion was associated with progressive slowing of the EEG, which was essentially silent before significant changes occurred in brain ATP. Finally, the brain 31P NMR spectrum and pH were measured at 90-s intervals, and the sequential changes that followed respiratory arrest were monitored in one dog until high-energy phosphate depletion was complete.

Topics: Adenosine Triphosphate; Animals; Brain; Dogs; Electroencephalography; Hypoxia; Magnetic Resonance Spectroscopy; Phosphates; Phosphocreatine; Phosphorus; Respiratory Insufficiency; Time Factors

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

Topics: Acute Disease; Adenine Nucleotides; Adenosine Triphosphate; Alanine Transaminase; Animals; Aspartate Aminotransferases; Cerebellum; Citrates; Fructosephosphates; Gluconates; Glucose; Glucosephosphates; Glycogen; Hypoxia, Brain; Ischemic Attack, Transient; Ketoglutaric Acids; Lactates; Malates; Male; Medulla Oblongata; Mesencephalon; Mice; Oxygen Consumption; Parietal Lobe; Phosphocreatine; Pons; Pyruvates; Respiratory Insufficiency