Changes In Phosphocreatine Concentration Research Articles

Changes in phosphocreatine concentration of skeletal muscle during high-intensity intermittent exercise in children and adults

The aim of the present study was to test the hypotheses that a greater oxidative capacity in children results in a lower phosphocreatine (PCr) depletion, a faster PCr resynthesis and a lower muscle acidification during high-intensity intermittent exercise compared to adults. Sixteen children (9.4 ± 0.5 years) and 16 adults (26.1 ± 0.3 years) completed a protocol consisting of a dynamic plantar flexion (10 bouts of 30-s exercise at 25 % of one repetition maximum separated by 20-s recovery), followed by 10 min of passive recovery. Changes of PCr, ATP, inorganic phosphate, and phosphomonoesters were measured by means of (31)Phosphorous-magnetic resonance spectroscopy during and post-exercise. Average PCr (percentage of [PCr] at initial rest (%[PCr]i)) at the end of the exercise (adults 17 ± 12 %[PCr]i, children 38 ± 17 %[PCr]i, P < 0.01) and recovery periods (adults 37 ± 14 %[PCr]i, children 57 ± 17 %[PCr]i, P < 0.01) was significantly lower in adults compared to children, induced by a stronger PCr decrease during the first exercise interval (adults -73 ± 10 %[PCr]i, children -55 ± 15 %[PCr]i, P < 0.01). End-exercise pH was significantly higher in children compared to adults (children 6.90 + 0.20, -0.14; adults 6.67 + 0.23, -0.15, P < 0.05). From our results we suggest relatively higher rates of oxidative ATP formation in children's muscle for covering the ATP demand of high-intensity intermittent exercise compared to adults, enabling children to begin each exercise interval with significantly higher PCr concentrations and leading to an overall lower muscle acidification.

Early onset of rejection in concordant hamster xeno hearts display signs of necrosis, but not apoptosis, correlating to the phosphocreatine concentration

Background: The importance of apoptosis contra necrosis for ischemia/reperfusion (RP) and acute rejection in concordant rodent xenotransplantation is largely unknown. We explored this question by comparing rodent allo and concordant xenotransplants with different morphological methods to detect apoptosis and biochemical data on the levels of high-energy phosphates obtained with in vitro 31Phosphorous Magnetic Resonance Spectroscopy ( 31P MRS). More specifically, we applied a hitherto unused method in transplantation research, apoptosis specific biotin labeled oligonucleotides designed with a 10 base pair stem region and a 20 nucleotides large loop that form a hairpin like shape. The results obtained with this method were compared to results obtained with the more widely used in situ 3′-end labeling of DNA (TUNEL) assay and extraction and gel electrophoresis of labeled DNA (DNA laddering). Methods: Cervical heart transplantations were performed between inbred Lewis (L) (RT1 1) to L, L to DA (RT1 a) rats, hamster (H) to H and H to L (X) ( n=5 for all groups except for X, n=9). All hearts were subjected to 30 min of cold ischemia (+4 °C) and 6 h of RP before explantation. In vitro 31P MRS was used to determine the phosphocreatine (PCr), beta-adenosine triphosphate (β-ATP) concentrations and the PCr/β-ATP ratio of the transplants. We correlated the biochemical data to haematoxylin and eosin (H & E) stained tissue slides scored for rejection, infiltration of antibodies and complement depositions, DNA extraction and gel electrophoresis of labeled DNA (DNA laddering), in situ 3′-end labeling of DNA (TUNEL) and the apoptosis specific hairpin probe assays scoring. Results: The rejection score of the xeno grafts differed significantly compared to their syngeneic hamster to hamster controls (2.40±0.25 vs. 1.20±0.20; P=0.005) and they had a significantly higher TUNEL score, 228±15 vs. 2.44±0.32 ( P=0.009), that correlated to changes in PCr concentration ( P<0.001) and to the PCr/β-ATP ratio ( P=0.01). The uptake was mainly (90–95%) located to 1–2 μm large extra cellular ‘granule’. A picture resembling early necrosis was seen on the H & E stainings and reflected in the Billingham rejection score above. Conclusions: After 6 h of RP the onset of acute rejection in the concordant hamster xeno hearts displayed features of early, possibly mitochondrial, necrosis, but not apoptosis, which correlated to changes in the PCr concentration and the PCr/β-ATP ratio. The mechanism for the early rejection observed is unclear and might be caused by other factors in the sera apart from cellular components, antibodies and complement factors. Identification of the underlying mechanisms could enable us to design rational therapies that prevent activation of the recipient's innate immune response.

Skeletal muscle mitochondrial dysfunction in alternating hemiplegia of childhood

Alternating hemiplegia of childhood is an uncommon disease characterized by repeated, transient attacks of hemiplegia. Its pathophysiology is uncertain, but attention recently has focused on possible mitochondrial abnormalities. Using 31P magnetic resonance spectroscopy, we studied gastrocnemius muscle in 5 patients with alternating hemiplegia, aged 8 to 30 (mean, 18) years, at rest and during incremental aerobic exercise and recovery. There were no significant differences in resting muscle between patients and a control group aged 7 to 42 (mean, 19) years. Exercise performance was grossly impaired in the patients, the mean duration being 30% of normal. The total change in pH during exercise was somewhat less than in control subjects, while the changes in phosphocreatine concentration and intracellular ADP were similar. Thus the average overall rate of fall of phosphocreatine concentration during exercise was three-fold greater than in control subjects. However, the initial rate of ATP turnover at the start of exercise (a measure of muscle mass and efficiency) was not abnormal. During recovery, both the initial rate of phosphocreatine resynthesis and the calculated mitochondrial capacity were reduced by about 35%. This mitochondrial defect probably explains most of the abnormalities seen during exercise.

Calculated Equilibria of Phosphocreatine and Adenosine Phosphates during Utilization of High Energy Phosphate by Muscle

Abstract Equations have been derived for calculating the concentrations of ATP, ADP, and AMP in equilibrium with phosphocreatine and creatine by use of association constants for the protonated species and Mg2+ complexes of the reactants and the equilibrium constants for the AMP kinase and creatine kinase reactions. The equations have been used to calculate the expected concentrations of free ATP, ADP, and AMP as high energy phosphate is discharged by a representative muscle. Arguments are advanced for the validity of the results as an estimate of in vivo conditions when based only on measured concentrations of phosphocreatine, creatine, and total adenosine phosphates. Changes in phosphocreatine concentration cause rapid changes in the calculated concentrations of ADP and AMP that are consistent with postulated regulatory effects of these compounds on the Embden-Meyerhof pathway. The amount of ADP and AMP formed by a given discharge of high energy phosphate depends upon the H+ concentration, and physiological changes in pH are sufficient to cause significant changes in the rate of glycolysis in this way. The physiological significance of phosphocreatine as an effector is less clear.