Energy-rich Phosphagens Research Articles

Creatine supplementation in chronic heart failure increases skeletal muscle creatine phosphate and muscle performance

Cardiac creatine levels are depressed in chronic heart failure. Oral supplementation of creatine to healthy volunteers has been shown to increase physical performance. To evaluate the effects of creatine supplementation on ejection fraction, symptom-limited physical endurance and skeletal muscle strength in patients with chronic heart failure. With a double-blind, placebo-controlled design 17 patients (age 43-70 years, ejection fraction < 40) were supplemented with creatine 20 g daily for 10 days. Before and on the last day of supplementation ejection fraction was determined by radionuclide angiography as was symptom-limited 1-legged knee extensor and 2-legged exercise performance on the cycle ergometer. Muscle strength as unilateral concentric knee extensor performance (peak torque, Nm at 180 degrees/s) was also evaluated. Skeletal muscle biopsies were taken for the determination of energy-rich phosphagens. Ejection fraction at rest and at work did not change. Performance before creatine supplementation did not differ between placebo and creatine groups. While no change was seen in the placebo group compared to baseline, creatine supplementation increased skeletal muscle total creatine and creatine phosphate by 17 +/- 4% (P < 0.05) and 12 +/- 4% (P < 0.05), respectively. Increments were seen only in patients with < 140 mmol total creatine/kg d.w. (P < 0.05). One-legged performance (21%, P < 0.05), 2-legged performance (10%, P < 0.05), and peak torque, Nm (5%, P < 0.05) increased. Both peak torque and 1-legged performance increased linearly with increased skeletal muscle phosphocreatine (P < 0.05). The increments in 1-legged, 2-legged and peak torque were significant compared to the placebo group, (P < 0.05). One week of creatine supplementation to patients with chronic heart failure did not increase ejection fraction but increased skeletal muscle energy-rich phosphagens and performance as regards both strength and endurance. This new therapeutic approach merits further attention.

Human skeletal muscle function and metabolism during intense exercise at high O2 and N2 pressures.

The maximal contractile force (peak torque) of the quadriceps femoris was studied during 60 repeated unilateral dynamic knee extensions in nine subjects under three different conditions, viz., during air breathing at normal (1 ATA) and raised (6 ATA) ambient pressures and during O2 breathing at 1.3 ATA. In six subjects the electromyographic (EMG) activity of the working muscle was recorded. Muscle biopsies were obtained from the vastus lateralis before, immediately after, and 1 min after exercise. Tissue specimens were subsequently assayed for various muscle metabolites. Peak torque, as an average of the 60 knee extensions, was higher (P less than 0.05) at 1.3 ATA than at 6 or 1 ATA. Peak torque of the exercising muscle declined more rapidly at 1 ATA than at 1.3 ATA, differing in the final 24 contractions by 14%. At 6 ATA peak torque of the initial 12 contractions was 6% lower (P less than 0.05) than at 1 ATA but equaled 1-ATA values in the latter third of the exercise bout. Although the EMG activity at 1 ATA increased relative to that at 6 ATA as exercise proceeded, the rate of force decline was greater at 1 ATA. Despite greater total work produced at 1.3 ATA than at 1 ATA, the metabolic response to exercise was not substantially altered at increased O2 pressure. However, the restitution rate of energy-rich phosphagens and the elimination of lactate during recovery were greater (P less than 0.05) at 1.3 ATA. These results suggest that hyperoxia may enhance the rate of energy release, whereas high N2 pressure and/or high hydrostatic pressure seem to interfere with neuromuscular activity.

ATP utilization and force during intermittent and continuous muscle contractions

Energy utilization and force generation under anaerobic conditions were studied in electrically stimulated quadriceps femoris muscle of four volunteers. To investigate the effects of intermittent vs. continuous stimulation one leg was stimulated intermittently and the other continuously during 50 s. The same initial force was produced, and biopsy samples were obtained before the stimulation and after 10, 20, and 50 s and analyzed for energy-rich phosphagens, glycolytic intermediates, and phosphorylase. The ATP utilization and glycolysis were greater during intermittent contraction, but glycogenolysis was equal. ATP content decreased to lower values after intermittent contraction (16.4 compared with 19.6 mmol/kg dry muscle after continuous contraction). Force generation was well preserved during continuous contraction but successively decreased after 20 s of intermittent stimulation down to 50% of initial at end of work. The energy cost per unit work was greater during intermittent stimulation and increased with contraction time, whereas it decreased with time during continuous stimulation. The decrease in force generation in intermittent exercise is suggested to be due to the higher energy cost for contraction resulting in greater changes in the intracellular environment with lower ATP and increased H+ and Pi. These changes would decrease both activation of the contractile system and the cross-bridge turnover rate resulting from activation.

Muscle energy metabolism in uremia

Energy-rich phosphagens were measured in 11 patients with end-stage chronic renal failure and 11 nonuremic subjects. A significant decrease of ATP, phosphocreatine, total adenine nucleotides, lactate, and energy charge was found. The present results can be referred both to glycolytic sequence disturbances and to the lack of substrates characteristic of uremia.

Muscle Biopsy Studies in Patients with Moderate Liver Cirrhosis with Special Reference to Energy-Rich Phosphagens and Electrolytes

Energy-rich phosphagens, water, and electrolytes were determined in skeletal muscle biopsy specimens from five elderly women and five elderly men with moderate liver cirrhosis. At the time of the study the patients were in their usual condition without evidence of deterioration of the disease. When compared with findings in apparently healthy subjects of similar age, the distribution and level of electrolytes and water were within normal limits in the female patients. The male patients showed increased contents of muscle water, and Mg2+ was reduced. The values calculated for the intracellular concentration of K+ and Mg2+ were also below normal. The pattern and levels of energy-rich phosphagens were abnormal in all but one female patient. As a general finding, ATP and the total level of adenine nucleotides were markedly reduced, as were phosphocreatine, the ATP/ADP ratio, and the energy charge potential.

Myoglobin content in leg skeletal muscle in patients with chronic obstructive lung disease.

Myoglobin was determined in biopsy specimens from the quadriceps muscle of 3 female and 15 male 48-to 78-year-old patients with chronic obstructive lung disease. The patients were examined after an overnight rest. All but 2 were slightly to moderately hypoxemic. The myoglobin level was in all but 1 instance below the mean previously observed for apparently healthy subjects of similar age. The results are in line with earlier findings of an abnormal pattern of energy-rich phosphagens in the skeletal muscle of patients with chronic obstructive lung disease.

The effect of physical training in elderly subjects with special reference to energy-rich phosphagens and myoglobin in leg skeletal muscle.

Energy-rich phosphagens and myoglobin were determined in leg skeletal muscles of seven, 61- to 80-year-old, apparently healthy male subjects. The study repeated after the participants had been exercising on an ergometer bicycle twice weekly for 6 weeks. Before training, myoglobin and all intramuscular energy-rich phosphagens were within the range recorded for a larger series of subjects of similar age. When re-examined after training the myoglobin level remained the same but creatine decreased significantly and the ratio between phosphocreatine and total creatine increased. A slight but significant rise was also observed for the ATP/ADP ratio. It is concluded that age-related changes of intramuscular phosphagens in elderly subjects in part might be due to physical inactivity.

Energy-rich phosphagens, electrolytes and free amino acids in leg skeletal muscle of patients with chronic obstructive lung disease.

Intramuscular (m. quadriceps) contents of electrolytes, free amino acids and energy-rich phosphagens were determined in 12 patients (51--81 years of age) with moderate chronic obstructive lung disease. At the time of the study the patients were in their habitual condition. After an overnight rest, 8 patients showed hypoxia and five of these also hypercapnia. Compared to apparently healthy controls of similar age and studied under identical conditions, the patients had increased intramuscular concentrations of sodium, chloride and extracellular water, whereas magnesium was slightly reduced. ATP and phosphocreatine, as well as the ATP/ADP and phosphocreatine/total creatine ratios, were reduced. The ATP/ADP ratio correlated significantly to intracellular magnesium. Plasma amino acids were essentially similar in controls and patients but the intramuscular contents of essential amino acids and of the three branched-chain amino acids were slightly enhanced in the patients.

Effect of aging on energy-rich phosphagens in human skeletal muscles.

1. Biopsy specimens of muscle obtained after an overnight rest from 14 men and eight women, apparently healthy subjects (age range 52-79 years), were analysed for pyruvate, lactate and energy-rich phosphagens. 2. Values for metabolites showed no sex differences. Compared with previous findings in men and women about 40 years younger, the intramuscular concentrations of both total adenine nucleotides and phosphocreatine were approximately 5% lower in the elderly. Creatine was correspondingly increased, but total creatine was unchanged, as were the ATP and the ATP/ADP ratio. 3. It was concluded that energy-rich compounds showed significant but small age-related variations.