phosphocreatine and Body-Weight

Branched-chain amino acids promote muscle-protein synthesis, reduce protein oxidation and have positive effects on mitochondrial biogenesis and reactive oxygen species scavenging. The purpose of the study was to determine the potential benefits of branched-chain amino acids supplementation on changes in force capacities, plasma amino acids concentration and muscle metabolic alterations after exercise-induced muscle damage.. (31)P magnetic resonance spectroscopy and biochemical analyses were used to follow the changes after such damage. Twenty six young healthy men were randomly assigned to supplemented branched-chain amino acids or placebo group. Knee extensors maximal voluntary isometric force was assessed before and on four days following exercise-induced muscle damage. Concentrations in phosphocreatine [PCr], inorganic phosphate [Pi] and pH were measured during a standardized rest-exercise-recovery protocol before, two (D2) and four (D4) days after exercise-induced muscle damage.. No significant difference between groups was found for changes in maximal voluntary isometric force (-24% at D2 and -21% at D4). Plasma alanine concentration significantly increased immediately after exercise-induced muscle damage (+25%) in both groups while concentrations in glycine, histidine, phenylalanine and tyrosine decreased. No difference between groups was found in the increased resting [Pi] (+42% at D2 and +34% at D4), decreased resting pH (-0.04 at D2 and -0.03 at D4) and the slower PCr recovery rate (-18% at D2 and -24% at D4).. The damaged muscle was not able to get benefits out of the increased plasma branched-chain amino acids availability to attenuate changes in indirect markers of muscle damage and muscle metabolic alterations following exercise-induced muscle damage.

Topics: Adult; Alanine; Amino Acids, Branched-Chain; Body Mass Index; Body Weight; Dietary Supplements; Double-Blind Method; Exercise; Glycine; Histidine; Humans; Hydrogen-Ion Concentration; Knee; Magnetic Resonance Spectroscopy; Male; Muscle Proteins; Muscle, Skeletal; Phenylalanine; Phosphates; Phosphocreatine; Tyrosine; Young Adult

A high-fat, high-calorie diet is associated with obesity and type 2 diabetes. However, the relative contribution of metabolic defects to the development of hyperglycaemia and type 2 diabetes is controversial. Accumulation of excess fat in muscle and adipose tissue in insulin resistance and type 2 diabetes may be linked with defective mitochondrial oxidative phosphorylation. The aim of the current study was to investigate acute effects of short-term fat overfeeding on glucose and insulin metabolism in young men. We studied the effects of 5 days' high-fat (60% energy) overfeeding (+50%) versus a control diet on hepatic and peripheral insulin action by a hyperinsulinaemic euglycaemic clamp, muscle mitochondrial function by (31)P magnetic resonance spectroscopy, and gene expression by qrt-PCR and microarray in 26 young men. Hepatic glucose production and fasting glucose levels increased significantly in response to overfeeding. However, peripheral insulin action, muscle mitochondrial function, and general and specific oxidative phosphorylation gene expression were unaffected by high-fat feeding. Insulin secretion increased appropriately to compensate for hepatic, and not for peripheral, insulin resistance. High-fat feeding increased fasting levels of plasma adiponectin, leptin and gastric inhibitory peptide (GIP). High-fat overfeeding increases fasting glucose levels due to increased hepatic glucose production. The increased insulin secretion may compensate for hepatic insulin resistance possibly mediated by elevated GIP secretion. Increased insulin secretion precedes the development of peripheral insulin resistance, mitochondrial dysfunction and obesity in response to overfeeding, suggesting a role for insulin per se as well GIP, in the development of peripheral insulin resistance and obesity.

Topics: Adipokines; Administration, Oral; Adult; Blood Glucose; Body Composition; Body Weight; C-Peptide; Cross-Over Studies; Dietary Fats; Gastric Inhibitory Polypeptide; Gene Expression; Glucose; Glucose Clamp Technique; Glycolysis; Heat-Shock Proteins; Humans; Insulin; Insulin Resistance; Lipids; Liver; Male; Muscle, Skeletal; Oxidative Phosphorylation; Pancreatic Polypeptide; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Phosphates; Phosphocreatine; Transcription Factors

The main aim of this study was to examine the hypothesis that creatine (Cr) feeding enhances myocellular glycogen storage in humans undergoing carbohydrate loading. Twenty trained male subjects were randomly assigned to have their diets supplemented daily with 252 g of glucose polymer (GP) and either 21 g of Cr (CR-GP, n = 10) or placebo (PL-GP, n = 10) for 5 days. Changes in resting myocellular glycogen and phosphocreatine (PCr) were determined with Magnetic Resonance Spectroscopy (13C- and 31P-MRS, respectively). After CR-GP, the levels of intramyocellular glycogen increased from 147 +/- 13 (standard error) mmol x (kg wet weight(-1)) to 172 +/- 13 m mol x (kg wet weight)(-1), while it increased from 134 +/- 17 mmol x (kg wet weight)(-) to 182 +/- 17 mmol x (kg wet weight)(-1) after PL-GP; the increments in intramyocellular glycogen concentrations were not statistically different. The increment in the PCr/ATP ratio after CR-GP (+ 0.20 +/- 0.12) was significantly different compared to PL-GP (- 0.34 +/- 0.16) (p < 0.05). The present results do not support the hypothesis that Cr loading increases muscle glycogen storage.

Topics: Adenosine Triphosphate; Adult; AMP-Activated Protein Kinases; Body Weight; Carbohydrate Metabolism; Carbon Isotopes; Creatine; Diet; Dietary Supplements; Double-Blind Method; Energy Intake; Glucans; Glycogen; Humans; Magnetic Resonance Spectroscopy; Male; Muscle Fibers, Skeletal; Phosphates; Phosphocreatine; Phosphorus Isotopes; Young Adult

Due to the current lack of clarity, we examined whether 5 days of dietary creatine (Cr) supplementation per se can influence the glycogen content of human skeletal muscle. Six healthy male volunteers participated in the study, reporting to the laboratory on four occasions to exercise to the point of volitional exhaustion, each after 3 days of a controlled normal habitual dietary intake. After a familiarization visit, participants cycled to exhaustion in the absence of any supplementation (N), and then 2 wk later again they cycled to exhaustion after 5 days of supplementation with simple sugars (CHO). Finally, after a further 2 wk, they again cycled to exhaustion after 5 days of Cr supplementation. Muscle samples were taken at rest before exercise, at the time point of exhaustion in visit 1, and at subsequent visit time of exhaustion. There was a treatment effect on muscle total Cr content in Cr compared with N and CHO supplementation (P < 0.01). Resting muscle glycogen content was elevated above N following CHO (P < 0.05) but not after Cr. At exhaustion following N, glycogen content was no different from CHO and Cr measured at the same time point during exercise. Cr supplementation under conditions of controlled habitual dietary intake had no effect on muscle glycogen content at rest or after exhaustive exercise. We suggest that any Cr-associated increases in muscle glycogen storage are the result of an interaction between Cr supplementation and other mediators of muscle glycogen storage.

Topics: Adenosine Triphosphate; Administration, Oral; Adult; Blood Glucose; Body Weight; Carbonated Beverages; Creatine; Cross-Over Studies; Dietary Carbohydrates; Dietary Supplements; Exercise; Glycogen; Humans; Male; Muscle Contraction; Muscle Fatigue; Muscle, Skeletal; Phosphocreatine; Reference Values; Time Factors

The purpose of this study was to determine the effect of 30 days of single-dose creatine supplementation with phosphate salts (CPS) on body weight (BW) and anaerobic working capacity (AWC) in men. Using a double-blind design, 32 men randomly received 1 serving of either CPS (5 g Cr + 4 g phosphate) (n = 17) or 20 g of dextrose as placebo (PL) (n = 15) for 30 days. AWC determined from the Critical Power Test and BW were measured at baseline, 10 days, 20 days, 30 days, and 10 days post-supplementation. Results (2 x 5 ANOVA) showed no significant differences between groups for AWC at any time point; however, BW was significantly increased at 10 days in the CPS group (1.0 kg) vs. PL (0.0 kg), and remained elevated for the duration of the study. These findings suggest that a single 5 g x d(-1) dose of CPS for 30 days increases BW but is not effective for increasing AWC in men.

Topics: Adult; Anaerobic Threshold; Analysis of Variance; Body Weight; Dietary Supplements; Double-Blind Method; Drug Administration Schedule; Humans; Male; Muscle, Skeletal; Phosphocreatine; Physical Education and Training; Physical Endurance; Probability; Reference Values; Sensitivity and Specificity

Topics: Administration, Oral; Aspartic Acid; Body Weight; Brain; Creatine; Creatinine; Dose-Response Relationship, Drug; Energy Metabolism; Humans; Huntington Disease; Magnetic Resonance Spectroscopy; Neuropsychological Tests; Patient Compliance; Phosphocreatine; Pilot Projects; Treatment Outcome; Up-Regulation

The purpose of this study was to determine the effects of 2 and 6 days of creatine phosphate loading on anaerobic working capacity (AWC) and body weight (BW) in men and women. Sixty-one men (n = 31) and women (n = 30) randomly received 1 of 3 treatments (4 x 5 g.d(-1) x 6 days) using a double blind design: (a) 18 g dextrose as placebo (PL); (b) 5.0 g Cr + 20 g dextrose (Cr); or (c) 5.0 g Cr + 18 g dextrose + 4 g of sodium and potassium phosphates (CrP). AWC was determined at baseline and following 2 and 6 days of supplementation using the Critical Power Test. BW increased significantly over time, and the mean value for the men was significantly greater compared to that for women, but there were no interactions (p > 0.05). There were gender-specific responses for AWC expressed in both absolute values (kJ) and relative to BW (kJ. kg(-1)), with the women demonstrating no significant interactions. For the men, CrP loading significantly increased AWC following 2 days (23.8%) and 6 days (49.8%) of supplementation vs. PL (kJ and kJ.kg(-1)). Cr supplementation increased AWC 13-15% in both genders compared to PL (1.1%- 3.0% decline); although this result was not statistically significant, it may have some practical significance.

Topics: Adult; Anaerobic Threshold; Analysis of Variance; Body Weight; Cardiotonic Agents; Dietary Supplements; Double-Blind Method; Ergometry; Female; Humans; Male; Phosphocreatine; Sex Factors

The decline in muscle mass (sarcopenia) with aging may be related to a decline in mitochondrial function. However, investigators have yet to reach a consensus as to whether a decline in mitochondrial function can be attenuated by physical activity has yet to reach a consensus.. Using dynamic 31PMRS to measure mitochondrial function, we measured baseline Phosphocreatine (PCr), inorganic phosphate (Pi), phosphodiester (PDE), [ADP], pH and recovery times (t(1/2)) for PCr and [ADP] following exercise, in 45 older (73+/-4 years, SD), and 20 younger subjects (25+/-4 years, SD) who were matched for body mass across high and low activity levels and within age and sex groupings.. Baseline PCr, and Pi, were lower, and PDE higher in the older subjects compared to younger subjects (all P<0.01). The t(1/2)(ADP) was longer in older subjects (P<0.001) controlling for age and sex in the low activity group (P=0.02). In the older low activity groups, t(1/2)(PCr) was longer than high activity groups. Higher PDE levels were positively correlated with longer t(1/2)(PCr) in the older low activity females (both P<0.05).. Our data suggests that mitochondrial function declines with age in healthy, exercising elderly adults and that the decline appears to be influenced by the level of physical activity.

Topics: Adenosine Diphosphate; Aged; Algorithms; Body Composition; Body Weight; Exercise; Female; Humans; Magnetic Resonance Spectroscopy; Male; Mitochondria, Muscle; Muscle, Skeletal; Phosphocreatine; Sex Characteristics

This study investigated the effects of acute creatine (Cr) supplementation on the performance of elite female soccer players undertaking an exercise protocol simulating match play. On two occasions, 7 days apart, 12 players performed 5 x 11-min exercise testing blocks interspersed with 1 min of rest. Each block consisted of 11 all-out 20-m running sprints, 2 agility runs, and 1 precision ball-kicking drill, separated by recovery 20-m walks,jogs, and runs. After the initial testing session, subjects were assigned to either a CREATINE (5 g of Cr, 4 times per day for 6 days) or a PLACEBO group (same dosage of a glucose polymer) using a double-blind research design. Body mass (BM) increased (61.7 +/- 8.9 to 62.5 < or = 8.9 kg, p < .01) in the CREATINE group; however, no change was observed in the PLACEBO group (63.4 < or = 2.9 kg to 63.7 +/- 2.5 kg). No overall change in 20-m sprint times and agility run times were observed, although the CREATINE group achieved faster post-supplementation times in sprints 11, 13, 14, 16, 21, 23, 25, 32, and 39 (p <.05), and agility runs 3, 5, and 8 (p < .05). The accuracy of shooting was unaffected in both groups. In conclusion, acute Cr supplementation improved performance of some repeated sprint and agility tasks simulating soccer match play, despite an increase in BM.

Topics: Adult; Body Weight; Creatine; Dietary Supplements; Double-Blind Method; Exercise Test; Female; Heart Rate; Humans; Hydrogen-Ion Concentration; Lactic Acid; Muscle, Skeletal; Phosphocreatine; Soccer

1. In the non-steady state of moderate intensity exercise, pulmonary O2 uptake (Vp,O2) is temporally dissociated from muscle O2 consumption (Vm,O2) due to the influence of the intervening venous blood volume and the contribution of body O2 stores to ATP synthesis. A monoexponential model of Vp,O2 without a delay term, therefore, implies an obligatory slowing of Vp,O2 kinetics in comparison to Vm, O2. 2. During moderate exercise, an association of Vm,O2 and [phosphocreatine] ([PCr]) kinetics is a necessary consequence of the control of muscular oxidative phosphorylation mediated by some function of [PCr]. It has also been suggested that the kinetics of Vp,O2 will be expressed with a time constant within 10 % of that of Vm,O2. 3. Vp,O2 and intramuscular [PCr] kinetics were investigated simultaneously during moderate exercise of a large muscle mass in a whole-body NMR spectrometer. Six healthy males performed prone constant-load quadriceps exercise. A transmit-receive coil under the right quadriceps allowed determination of intramuscular [PCr]; Vp,O2 was measured breath-by-breath, in concert with [PCr], using a turbine and a mass spectrometer system. 4. Intramuscular [PCr] decreased monoexponentially with no delay in response to exercise. The mean of the time constants (tauPCr) was 35 s (range, 20-64 s) for the six subjects. 5. Two temporal phases were evident in the Vp, O2 response. When the entire Vp,O2 response was modelled to be exponential with no delay, its time constant (tau'Vp,O2) was longer in all subjects (group mean = 62 s; range, 52-92 s) than that of [PCr], reflecting the energy contribution of the O2 stores. 6. Restricting the Vp,O2 model fit to phase II resulted in matching kinetics for Vp,O2 (group mean tauVp,O2 = 36 s; range, 20-68 s) and [PCr], for all subjects. 7. We conclude that during moderate intensity exercise the phase II tauVp,O2 provides a good estimate of tauPCr and by implication that of Vm,O2 (tauVm,O2).

Topics: Adenosine Triphosphate; Adult; Body Weight; Exercise; Humans; Kinetics; Lung; Male; Middle Aged; Muscle, Skeletal; Oxidative Phosphorylation; Oxygen; Oxygen Consumption; Phosphocreatine; Pulmonary Gas Exchange

Age-related reductions in growth hormone (GH) and insulin-like growth factor-I (IGF-I) may contribute to decreased muscle mass and strength in older persons. The relationship of this phenomenon to skeletal muscle bioenergetics has not been reported. We sought to determine whether administration of GH-releasing hormone (GHRH) would sustain increases in GH and IGF-I and improve skeletal muscle function and selected measures of body composition and metabolism. We measured GH secretion, muscle strength, muscle histology, and muscle energy metabolism by phosphorus nuclear magnetic resonance spectroscopy (31P-NMRS), body composition, and endocrine-metabolic functions before and after 6 weeks of treatment. Eleven healthy, ambulatory, non-obese men aged 64 to 76 years with low baseline IGF-I levels were treated at home as outpatients by nightly subcutaneous self-injections of 2 mg GHRH for 6 weeks. We measured GH levels in blood samples obtained every 20 minutes from 8:00 PM to 8:00 AM; AM serum levels of IGF-I, IGF binding protein-3 (IGFBP-3), and GH binding protein (GHBP); muscle strength; muscle histology; the normalized phosphocreatine abundance, PCr/[PCr + Pi], and intracellular pH in forearm muscle by NMRS during both sustained and ramped exercise; body composition by dual-energy x-ray absorptiometry (DEXA); lipid levels; and glucose, insulin, and GH levels during an oral glucose tolerance test (OGTT). GHRH treatment increased mean nocturnal GH release (P < .02), the area under the GH peak ([AUPGH] P < .006), and GH peak amplitude (P < .05), with no change in GH pulse frequency or in levels of IGF-I, IGFBP-3, or GHBP Two of six measures of muscle strength, upright row (P < .02) and shoulder press (P < .04), and a test of muscle endurance, abdominal crunch (P < .03), improved. GHRH treatment did not alter exercise-mediated changes in PCr/[PCr + Pi] or intracellular pH, but decreased or abolished significant relationships between changes in PCr/[PCr + Pi] or pH and indices of muscle strength. GHRH treatment did not change weight, body mass index, waist to hip ratio, DEXA measures of muscle and fat, muscle histology, glucose, insulin, or GH responses to OGTT, or lipids. No significant adverse effects were observed. These data suggest that single nightly doses of GHRH are less effective than multiple daily doses of GHRH in eliciting GH- and/or IGF-I-mediated effects. GHRH treatment may increase muscle strength, and it alters baseline relationships between muscl

Topics: Aged; Aging; Blood Glucose; Blood Pressure; Body Composition; Body Mass Index; Body Weight; Dose-Response Relationship, Drug; Endocrine Glands; Energy Metabolism; Glucose; Glucose Tolerance Test; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Hydrogen-Ion Concentration; Injections, Subcutaneous; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Lipids; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscle Contraction; Muscle, Skeletal; Peptide Fragments; Phosphocreatine

We investigated the effect of creatine supplementation on maximal running performance in a simulated track competition. Twelve competitive male runners were assigned to either a placebo or creatine supplementation group. Both groups completed two maximal 700-m running bouts 60 min apart on an outdoor track. A second identical trial was performed 7 days later, and for 5 days prior to the second trial, subjects ingested 20 g.day-1 of either creatine monohydrate or a placebo. Subjects in the placebo group ran 110.2 +/- 3.5 s and 110.4 +/- 3.0 s for the first trial and 108.5 +/- 2.9 s and 108.0 +/- 1.7 s for the second trial, while the creatine group ran 109.9 +/- 3.2 s and 110.4 +/- 3.6 s for the first trial and 109.7 +/- 3.3 s and 107.8 +/- 2.2 s for the second trial. There were no significant differences between groups by trial or Trial X Time for running time, postexercise blood lactate concentration, or body weight (p > .05). We concluded that creatine supplementation does not enhance performance of single or twice-repeated maximal running bouts lasting 90-120 s.

Topics: Body Weight; Food, Fortified; Humans; Lactic Acid; Male; Matched-Pair Analysis; Phosphocreatine; Running

This study aimed to compare the effects of oral creatine (Cr) supplementation with creatine supplementation in combination with caffeine (Cr+C) on muscle phosphocreatine (PCr) level and performance in healthy male volunteers (n = 9). Before and after 6 days of placebo, Cr (0.5 g x kg-1 x day-1), or Cr (0.5 g x kg-1 x day-1) + C (5 mg x kg-1 x day-1) supplementation, 31P-nuclear magnetic resonance spectroscopy of the gastrocnemius muscle and a maximal intermittent exercise fatigue test of the knee extensors on an isokinetic dynamometer were performed. The exercise consisted of three consecutive maximal isometric contractions and three interval series of 90, 80, and 50 maximal voluntary contractions performed with a rest interval of 2 min between the series. Muscle ATP concentration remained constant over the three experimental conditions. Cr and Cr+C increased (P < 0.05) muscle PCr concentration by 4-6%. Dynamic torque production, however, was increased by 10-23% (P < 0.05) by Cr but was not changed by Cr+C. Torque improvement during Cr was most prominent immediately after the 2-min rest between the exercise bouts. The data show that Cr supplementation elevates muscle PCr concentration and markedly improves performance during intense intermittent exercise. This ergogenic effect, however, is completely eliminated by caffeine intake.

Topics: Adenosine Triphosphate; Adult; Body Weight; Caffeine; Creatine; Diet; Double-Blind Method; Exercise; Exercise Test; Humans; Knee; Male; Muscle Fatigue; Muscle, Skeletal; Phosphocreatine; Phosphodiesterase Inhibitors

Seven male subjects performed repeated bouts of high-intensity exercise, on a cycle ergometer, before and after 6 d of creatine supplementation (20 g Cr H2O day-1). The exercise protocol consisted of five 6-s exercise periods performed at a fixed exercise intensity, interspersed with 30-s recovery periods (Part I), followed (40 s later) by one 10 s exercise period (Part II) where the ability to maintain power output was evaluated. Muscle biopsies were taken from m. vastus lateralis at rest, and immediately after (i) the fifth 6 s exercise period in Part I and (ii) the 10 s exercise period in Part II. In addition, a series of counter movement (CMJ) and squat (SJ) jumps were performed before and after the administration period. As a result of the creatine supplementation, total muscle creatine [creatine (Cr) + phosphocreatine (PCr)] concentration at rest increased from (mean +/- SEM) 128.7 (4.3) to 151.5 (5.5) mmol kg-1 dry wt (P < 0.05). This was accompanied by a 1.1 (0.5) kg increase in body mass (P < 0.05). After the fifth exercise bout in Part I of the exercise protocol, PCr concentration was higher [69.7 (2.3) vs. 45.6 (7.5) mmol kg-1 dry wt, P < 0.05], and muscle lactate was lower [26.2 (5.5) vs. 44.3 (9.9) mmol kg-1 dry wt, P < 0.05] after vs. before supplementation. In Part II, after creatinine supplementation, subjects were better able to maintain power output during the 10-s exercise period (P < 0.05). There was no change in jump performance as a result of the creatine supplementation (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Triphosphate; Adult; Body Weight; Creatine; Exercise; Exercise Test; Glycolysis; Humans; Hypoxanthine; Hypoxanthines; Lactates; Lactic Acid; Male; Muscle Fatigue; Muscle, Skeletal; Phosphocreatine

Diabetes mellitus (DM) associated liver damage is a major health burden. Hepatocellular-damage in DM characterized with elevated endoplasmic reticulum stress (ER) and may enhanced insulin-resistance. Phosphocreatine (PCr) a rapidly high-energy-reserve molecule of phosphates naturally occurs in liver, brain and skeletal muscle. This study aimed to investigate the protective effect of PCr on the liver-injury-associated with DM and to report the mechanism involved. Wistar rat's diabetes model was induced using streptozotocin (STZ), and the animals were treated with 20 mg/kg, or 50 mg/kg PCr injection. Blood glucose level, and body wt were recorded. Liver tissues homogenate were analyzed for liver damage markers alanine transaminase (ALT), aspartate transaminase (AST). Liver tissues proteins further evaluated for apoptosis, endoplasmic reticulum stress (ER), and insulin resistance biomarkers using western blotting. Our results revealed that PCr reduced blood glucose level, improved body wt, ameliorates liver function enzymes. Furthermore, PCr upregulates anti-apoptotic Bcl2 proteins expression, and down-regulates significantly pro-apoptotic casp3 and Bax proteins expression in vivo and invitro. Moreover, ER stress CHOP, GRP78 and ATF4 biomarkers level were significantly attenuated in PCr treated animals comparing to STZ diabetes associated liver-damage model with significant improving in insulin-resistance Akt and IRS-1. Our results revealed that treating with PCr in diabetes-associated liver injury models decreased blood glucose level and possess protective effect in-vitro and in-vivo, which could be suggested as potential therapeutic strategy for diabetes associated liver injury patients.

Topics: Animals; Apoptosis; Biomarkers, Tumor; Blood Glucose; Body Weight; Carcinoma, Hepatocellular; Cell Shape; Cell Survival; Diabetes Mellitus, Experimental; Disease Models, Animal; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Hep G2 Cells; Humans; Insulin Resistance; Liver; Liver Neoplasms; Metabolome; Oxidative Stress; Phosphocreatine; Protective Agents; Rats, Wistar; Signal Transduction; Streptozocin

Age is a known susceptibility factor for the cardiotoxicity of several anticancer drugs, including mitoxantrone (MTX). The impact of anticancer drugs in young patients is underestimated, thus we aimed to evaluate the cardiotoxicity of MTX in juvenile and adult animals. Juvenile (3 week-old) and adult (8-10 week-old) male CD-1 mice were used. Each group was treated with a 9.0mg/kg cumulative dose of MTX or saline; they were maintained in a drug-free period for 3-weeks after the last administration to allow the development of late toxicity (protocol 1), or sacrificed 24h after the last MTX administration to evaluate early cardiotoxicity (protocol 2). In protocol 1, no adult mice survived, while 2 of the juveniles reached the end of the protocol. High plasma aspartate aminotransferase/alanine aminotransferase ratio and a high cardiac reduced/oxidized glutathione ratio were found in the surviving MTX-treated juvenile mice. In protocol 2, a significant decrease in plasma creatine-kinase MB in juveniles was found 24h after the last MTX-administration. Cardiac histology showed that both MTX-treated populations had significant damage, although higher in adults. However, MTX-treated juveniles had a significant increase in fibrotic tissue. The MTX-treated adults had higher values of cardiac GSSG and protein carbonylation, but lower cardiac noradrenaline levels. For the first time, mature adult animals were shown to be more susceptible to MTX as evidenced by several biomarkers, while young animals appear to better adjust to the MTX-induced cardiac injury. Even so, the higher level of fibrotic tissue and the histological damage showed that MTX also causes cardiac damage in the juvenile population.

Topics: Age Factors; Animals; Antineoplastic Agents; Aspartate Aminotransferases; Biomarkers; Body Weight; Cardiotoxicity; Caspase 3; Caspase 8; Caspase 9; Creatine; Creatine Kinase, MB Form; Dose-Response Relationship, Drug; Epinephrine; Fibrosis; Glutathione Disulfide; Heart; Heart Diseases; Kidney; Lipid Peroxidation; Liver; Male; Mice; Mitoxantrone; Myocardium; Norepinephrine; Organ Size; Phosphocreatine; Protein Carbonylation

Previous studies have suggested a relationship between GH and mitochondrial function. However, little is known about the relationship of specific GH indices and in vivo measures of mitochondrial function in humans.. The objective of this study was to determine the association between GH, IGF-I, and phosphocreatine (PCr) recovery, a measure of mitochondrial function, in otherwise healthy adults.. Thirty-seven healthy men and women were studied at a single university medical center. Subjects underwent GH stimulation testing with GH releasing hormone-arginine and measurement of IGF-I. Mitochondrial function was determined by PCr recovery after submaximal exercise by (31)Phosphorous magnetic resonance spectroscopy. Subjects underwent assessment of lean and fat mass with use of dual energy X-ray absorptiometry.. There were no differences in PCr recovery between men and women (men 20.7±1.5 vs. women 24.8±1.4 mM/min; P > 0.05). IGF-I (r = 0.33; P = 0.04) was associated with PCr recovery in all subjects. Among men, IGF-I (r = 0.69; P = 0.003), peak stimulated GH (r = 0.52; P = 0.04), and GH area under the curve (AUC) (r = 0.53; P = 0.04) were significantly associated with PCr recovery. However, neither IGF-I, peak stimulated GH, nor GH AUC (all P > 0.05) were associated with PCr recovery in women. After adjusting for age, race, and physical activity, IGF-I remained significantly associated with PCr recovery (β = 0.10; P = 0.02) among men.. IGF-I, peak stimulated GH, and GH AUC are associated with skeletal muscle PCr recovery in men.

Topics: Absorptiometry, Photon; Adolescent; Adult; Area Under Curve; Body Height; Body Weight; Exercise; Female; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Magnetic Resonance Spectroscopy; Male; Middle Aged; Mitochondria, Muscle; Motor Activity; Muscle, Skeletal; Phosphocreatine; Regression Analysis; Young Adult

The influence of feeding on swimming performance and exercise recovery in fish is poorly understood. Examining swimming behavior and physiological status following periods of feeding and fasting is important because wild fish often face periods of starvation. In the current study, researchers force fed and fasted groups of largemouth bass (Micropterus salmoides) of similar sizes for a period of 16 days. Following this feeding and fasting period, fish were exercised for 60 s and monitored for swimming performance and physiological recovery. Resting metabolic rates were also determined. Fasted fish lost an average of 16 g (nearly 12%) of body mass, while force fed fish maintained body mass. Force fed fish swam 28% further and required nearly 14 s longer to tire during exercise. However, only some physiological conditions differed between feeding groups. Resting muscle glycogen concentrations was twofold greater in force fed fish, at rest and throughout recovery, although it decreased in both feeding treatments following exercise. Liver mass was nearly three times greater in force fed fish, and fasted fish had an average of 65% more cortisol throughout recovery. Similar recovery rates of most physiological responses were observed despite force fed fish having a metabolic rate 75% greater than fasted fish. Results are discussed as they relate to largemouth bass starvation in wild systems and how these physiological differences might be important in an evolutionary context.

Topics: Adenosine Triphosphate; Animals; Basal Metabolism; Bass; Blood Glucose; Body Weight; Chlorides; Citrate (si)-Synthase; Fasting; Fresh Water; Glycogen; Hematocrit; Hemoglobins; Hydrocortisone; L-Lactate Dehydrogenase; Lactic Acid; Liver; Muscle Fibers, Fast-Twitch; Nutritional Status; Organ Size; Phosphocreatine; Physical Conditioning, Animal; Potassium

Hypoxic states of the cardiovacular system are undoubtedly associated with the most frequent diseases of modern time. Therefore, understanding hypoxic resistance encountered after physiological adaptation such as chronic hypoxia, is crucial to better deal with hypoxic insult. In this study, we examine the role of energetic modifications induced by chronic hypoxia (CH) in the higher tolerance to oxygen deprivation.. Swiss mice were exposed to a simulated altitude of 5500 m in a barochamber for 21 days. Isolated perfused hearts were used to study the effects of a decreased oxygen concentration in the perfusate on contractile performance (RPP) and phosphocreatine (PCr) concentration (assessed by (31)P-NMR), and to describe the integrated changes in cardiac energetics regulation by using Modular Control Analysis (MoCA). Oxygen reduction induced a concomitant decrease in RPP (-46%) and in [PCr] (-23%) in Control hearts while CH hearts energetics was unchanged. MoCA demonstrated that this adaptation to hypoxia is the direct consequence of the higher responsiveness (elasticity) of ATP production of CH hearts compared with Controls (-1.88+/-0.38 vs -0.89+/-0.41, p<0.01) measured under low oxygen perfusion. This higher elasticity induces an improved response of energy supply to cellular energy demand. The result is the conservation of a healthy control pattern of contraction in CH hearts, whereas Control hearts are severely controlled by energy supply.. As suggested by the present study, the mechanisms responsible for this increase in elasticity and the consequent improved ability of CH heart metabolism to respond to oxygen deprivation could participate to limit the damages induced by hypoxia.

Topics: Animals; Body Weight; Chronic Disease; Energy Metabolism; Female; Heart; Hypoxia; In Vitro Techniques; Magnetic Resonance Spectroscopy; Mice; Mitochondria, Heart; Myocardial Contraction; Myocardium; Organ Size; Oxygen; Phosphocreatine

Obesity has become an epidemic in children, associated with an increase in insulin resistance and metabolic dysfunction. Mitochondrial function is known to be an important determinant of glucose metabolism in adults. However, little is known about the relationship between mitochondrial function and obesity, insulin resistance, energy expenditure, and pubertal development in children.. Seventy-four participants, 37 overweight (> or = 85th percentile body mass index for age and sex) and 37 normal-weight (< 85th percentile) without personal or family history of diabetes mellitus were enrolled. Subjects were evaluated with an oral glucose tolerance test, metabolic markers, resting energy expenditure, Tanner staging, and (31)P magnetic resonance spectroscopy of skeletal muscle for mitochondrial function.. Overweight and normal-weight children showed no difference in muscle ATP synthesis [phosphocreatine (PCr) recovery after exercise] (32.4 +/- 2.3 vs. 34.1 +/- 2.1, P = 0.58). However, insulin-resistant children had significantly prolonged PCr recovery when compared with insulin-sensitive children, by homeostasis model assessment for insulin resistance quartile (ANOVA, P = 0.04). Similarly, insulin-resistant overweight children had PCr recovery that was prolonged compared with insulin-sensitive overweight children (P = 0.01). PCr recovery was negatively correlated with resting energy expenditure in multivariate modeling (P = 0.03). Mitochondrial function worsened during mid-puberty in association with insulin resistance.. Reduced skeletal muscle mitochondrial oxidative phosphorylation, assessed by PCr recovery, is associated with insulin resistance and an altered metabolic phenotype in children. Normal mitochondrial function may be associated with a healthier metabolic phenotype in overweight children. Further studies are needed to investigate the long-term physiological consequences and potential treatment strategies targeting children with reduced mitochondrial function.

Topics: Adolescent; Body Weight; Calorimetry, Indirect; Child; Dyslipidemias; Energy Metabolism; Feeding Behavior; Female; Glycemic Index; Humans; Insulin; Insulin Resistance; Lipids; Magnetic Resonance Spectroscopy; Male; Mitochondria; Obesity; Overweight; Phenotype; Phosphocreatine; Puberty; Surveys and Questionnaires

Decreasing muscle phosphagen content through dietary administration of the creatine analog beta-guanidinopropionic acid (beta-GPA) improves skeletal muscle oxidative capacity and resistance to fatigue during aerobic exercise in rodents, similar to that observed with endurance training. Surprisingly, the effect of beta-GPA on muscle substrate metabolism has been relatively unexamined, with only a few reports of increased muscle GLUT4 content and insulin-stimulated glucose uptake/clearance in rodent muscle. The effect of chronically decreasing muscle phophagen content on muscle fatty acid (FA) metabolism (transport, oxidation, esterification) is virtually unknown. The purpose of the present study was to examine changes in muscle substrate metabolism in response to 8 wk feeding of beta-GPA. Consistent with other reports, beta-GPA feeding decreased muscle ATP and total creatine content by approximately 50 and 90%, respectively. This decline in energy charge was associated with simultaneous increases in both glucose (GLUT4; +33 to 45%, P < 0.01) and FA (FAT/CD36; +28 to 33%, P < 0.05) transporters in the sarcolemma of red and white muscle. Accordingly, we also observed significant increases in insulin-stimulated glucose transport (+47%, P < 0.05) and AICAR-stimulated palmitate oxidation (+77%, P < 0.01) in the soleus muscle of beta-GPA-fed animals. Phosphorylation of AMPK (+20%, P < 0.05), but not total protein, was significantly increased in both fiber types in response to muscle phosphagen reduction. Thus the content of sarcolemmal transporters for both of the major energy substrates for muscle increased in response to a reduced energy charge. Increased phosphorylation of AMPK may be one of the triggers for this response.

Topics: Adenosine Triphosphate; Adenylate Kinase; Animals; Blood Glucose; Body Weight; CD36 Antigens; Cell Membrane; Creatine; Energy Metabolism; Fatty Acid Transport Proteins; Female; Glucose Transporter Type 4; Guanidines; Insulin; Muscle Fatigue; Muscle, Skeletal; Palmitates; Phosphocreatine; Phosphorylation; Propionates; Rats; Rats, Sprague-Dawley

Diabetes mellitus (DM) alters the energy substrate metabolism in the heart and the early sign of diabetic cardiomyopathy is the diastolic dysfunction. Although it is known that the extracellular matrix must be altered in the presence of diabetes, its local regulation has not been fully elucidated. Our aim was to evaluate in vivo left ventricular (LV) structure; function and bioenergetics in streptozotocin (STZ) induced diabetes mellitus.. Cardiac function was evaluated using echocardiography in anesthetized Sprague–Dawley rats 12 weeks after injection of STZ and in age-matched control rats before and after atrial pacing. In vivo ³¹P magnetic resonance spectroscopy was done to measure the phosphocreatine (PCr) to ATP ratio. Myocardial protein expression of metalloproteinases MMP-2, -9, tissue inhibitor TIMP-1, -2 and collagen was measured using Western blot.. Bodyweight (BW) was decreased in diabetic rats. Heart weight/BW and LV mass/BW ratios were higher in diabetic animals compared to controls (2.3 ± 08 vs 2.1 ± 08 mg/g p <0.05). Heart rate was lower in diabetic rats (293 ± 20 vs 394 ± 36 bpm p <0.05). The velocity of circumferential shortening and peak aortic velocity were lower in diabetic animals and were more pronounced during atrial pacing. The basal PCr/ATP ratio was not different in the two groups. Total collagen was higher in diabetic rats (3.8 ± 0.3 vs 2.9 ± 01 mg/g, p <0.05). Protein expression of MMP-2 was significantly diminished in diabetic rats by ≈ 60%, while MMP-9, TIMP-1 and -2 were unchanged.. Streptozotocin induced diabetes led to increased LV/bodyweight, increased collagen content, and diminished MMP-2 with no change in PCr/ATP. Therefore, remodeling rather than disturbed energetics may underlie diabetic cardiomyopathy.

Topics: Animals; Body Weight; Collagen; Diabetes Mellitus, Experimental; Diabetic Cardiomyopathies; Echocardiography; Energy Metabolism; Magnetic Resonance Spectroscopy; Male; Matrix Metalloproteinase 2; Metalloproteases; Phosphocreatine; Rats; Rats, Sprague-Dawley; Ventricular Remodeling

In some fish, hypertrophic growth of white muscle leads to very large fibers. The associated low-fiber surface area-to-volume ratio (SA/V) and potentially long intracellular diffusion distances may influence the rate of aerobic processes. We examined the effect of intracellular metabolite diffusion on mass-specific scaling of aerobic capacity and an aerobic process, phosphocreatine (PCr) recovery, in isolated white muscle from black sea bass (Centropristis striata). Muscle fiber diameter increased during growth and was >250 mum in adult fish. Mitochondrial volume density and cytochrome-c oxidase activity had similar small scaling exponents with increasing body mass (-0.06 and -0.10, respectively). However, the mitochondria were more clustered at the sarcolemmal membrane in large fibers, which may offset the low SA/V, but leads to greater intracellular diffusion distances between mitochondrial clusters and ATPases. Despite large differences in intracellular diffusion distances, the postcontractile rate of PCr recovery was largely size independent, with a small scaling exponent for the maximal rate (-0.07) similar to that found for the indicators of aerobic capacity. Consistent with this finding, a mathematical reaction-diffusion analysis indicated that the resynthesis of PCr (and other metabolites) was too slow to be substantially limited by diffusion. These results suggest that the recovery rate in these fibers is primarily limited by low mitochondrial density. Additionally, the change in mitochondrial distribution with increasing fiber size suggests that low SA/V and limited O(2) flux are more influential design constraints in fish white muscle, and perhaps other fast-twitch vertebrate muscles, than is intracellular metabolite diffusive flux.

Topics: Animals; Bass; Body Weight; Diffusion; Electron Transport Complex IV; Mitochondria; Muscle Contraction; Muscle Fibers, Fast-Twitch; Muscle, Skeletal; Phosphocreatine

Short-term maximum intensity performance, absolute and related to body mass, is lower in children than adolescents. The underlying mechanisms are not clear. We analysed Wingate Anaerobic Test (WAnT) performance and metabolism in ten boys (mean (SD); age 11.8 (0.5) years, height 1.51 (0.05) m, body mass 36.9 (2.5) kg, muscle mass 13.0 (1.0) kg) and 10 adolescents (16.3 (0.7) years, 1.81 (0.05) m, 67.3 (4.1) kg, 28.2 (1.7) kg). Related to body mass, power of flywheel acceleration (6.0 (1.6) vs. 8.1 (1.1) W kg(-1)), peak power (10.8 (0.7) vs. 11.5 (0.6) W kg(-1)), average power (7.9 (0.5) vs. 8.9 (0.7) W kg(-1)), minimum power (6.1 (0.7) vs. 6.9 (0.9) W kg(-1)) and anaerobic lactic energy (687.6 (75.6) vs. 798.2 (43.0) J kg(-1)) were lower (P < 0.05) in boys than in adolescents. Related to muscle mass the change in lactate (0.69 (0.08) vs. 0.69 (0.04) mmol kg (MM) (-1) s(-1)) and PCr (0.60 (0.17) vs. 0.52 (0.10) mmol kg (MM) (-1) s(-1)) were not different. The corresponding oxygen uptake (1.34 (0.13) vs. 1.09 (0.13) ml kg (MM) (-1) s(-1)), total metabolic rate (132.4 (12.6) vs. 119.7 (8.5) W kg (MM) (-1) ) and PP (30.5 (2.6) vs. 27.5 (1.7 W) kg (MM) (-1) ) were higher (P < 0.01) in boys than in adolescents. The results reflect a lower relative muscle mass combined with no differences in muscular anaerobic but fascilitated aerobic metabolism in boys. Compared with adolescents, boys' performance seemed to be significantly impaired by flywheel inertia but supported by identical brake force related to body mass.

Topics: Adolescent; Algorithms; Anaerobiosis; Biomechanical Phenomena; Body Weight; Child; Data Interpretation, Statistical; Energy Metabolism; Exercise; Exercise Test; Humans; Lactic Acid; Male; Metabolism; Muscle Strength; Organ Size; Oxygen Consumption; Phosphocreatine; Reference Values

The impetus for the novel Energy Formula (EF) which combines the niacin-bound chromium (III) (0.45%) (NBC), standardized extract of Withania somnifera extracts (10.71%), caffeine (22.76%), D-ribose (10.71%) and selected amino acids such as phenylalanine, taurine and glutamine (55.37%) was based on the knowledge of the cardioprotective potentials of the Withania somnifera extract, caffeine and D-ribose as well as their abilities to increase energy levels and the abilities of amino acids to increase the muscle mass and energy levels. The effect of oral supplementation of EF on the safety, myocardial energy levels and cardioprotective ability were investigated in an ischemic-reperfused myocardium model in both male and female Sprague-Dawley rats over 90 days trial period. At the completion of 90 days, the EF-treated male and female rats gained 9.4% and 3.1% less body weights, respectively, as compared to their corresponding control groups. No significant difference was found in the levels of lipid peroxidation and activities of hepatic Aspartate transaminase, Alanine transaminase and Alkaline phosphatase in EF treatment when compared with control animals. The male and female rat hearts were subjected to 30 min of global ischemia followed by 2 h of reperfusion at 30 and 90 days of EF treatment. Cardiovascular functions including heart rate, coronary flow, aortic flow, dp/dt(max), left ventricular developed pressure (LVDP) and infarct size were monitored. The levels of myocardial adenosine triphosphate (ATP), creatine phosphate (CP), phospho-adenosine monophosphate kinase (p-AMPK) levels, were analyzed at the end of 30 and 90 days of treatment. Significant improvement was observed in all parameters in the EF treatment groups as compared to their corresponding controls. Thus the niacin-bound chromium (III) based energy formula is safe and effective supplement to boost energy levels and cardioprotection.

Topics: Adenosine Monophosphate; Adenosine Triphosphate; Animals; Apoptosis; Aspartate Aminotransferases; Blotting, Western; Body Weight; Chromium Compounds; Coronary Circulation; Dietary Supplements; Disease Models, Animal; Female; Heart Rate; Lipid Peroxidation; Male; Models, Biological; Myocardial Infarction; Myocardial Reperfusion Injury; Phosphocreatine; Phosphorylation; Protein Kinases; Rats; Rats, Sprague-Dawley

Glucocorticoid treatments are associated with increased whole-body oxygen consumption. We hypothesised that an impairment of muscle energy metabolism can participate in this increased energy expenditure.. To investigate this possibility, we have studied muscle energetics of dexamethasone-treated rats (1.5 mg kg(-1) day(-1) for 6 days), in vivo by (31)P NMR spectroscopy. Results were compared with control and pair-fed (PF) rats before and after overnight fasting.. Dexamethasone treatment resulted in decreased phosphocreatine (PCr) concentration and PCr:ATP ratio, increased ADP concentration and higher PCr to gamma-ATP flux but no change in beta-ATP to beta-ADP flux in gastrocnemius muscle. Neither 4 days of food restriction (PF rats) nor 24 h fasting affected high-energy phosphate metabolism. In dexamethasone-treated rats, there was an increase in plasma insulin and non-esterified fatty acid concentration.. We conclude that dexamethasone treatment altered resting in vivo skeletal muscle energy metabolism, by decreasing oxidative phosphorylation, producing ATP at the expense of PCr.

Topics: 3-Hydroxybutyric Acid; Adenine Nucleotides; Animals; Body Weight; Dexamethasone; Energy Metabolism; Fatty Acids, Nonesterified; Hydrogen-Ion Concentration; Insulin; Leptin; Magnetic Resonance Spectroscopy; Male; Muscle, Skeletal; Oxygen Consumption; Phosphates; Phosphocreatine; Phosphorus Radioisotopes; Rats; Rats, Sprague-Dawley

Animal models are valuable research tools towards effective prevention of sarcopenia and towards a better understanding of the mechanisms underlying skeletal muscle aging. We investigated whether senescence-accelerated mouse (SAM) strains provide valid models for skeletal muscle aging studies. Male senescence-prone mice SAMP6 and SAMP8 were studied at age 10, 25 and 60 weeks and compared with senescence-resistant strain, SAMR1. Soleus and EDL muscles were tested for in vitro contractile properties, phosphocreatine content, muscle mass and fiber-type distribution. Declined muscle mass and contractility were observed at 60 weeks, the differences being more pronounced in SAMP8 than SAMP6 and more pronounced in soleus than EDL. Likewise, age-related decreases in muscle phosphocreatine content and type-II fiber size were most pronounced in SAMP8 soleus. In conclusion, typical features of muscular senescence occur at relatively young age in SAMP8 and nearly twice as fast as compared with other models. We suggest that soleus muscles of SAMP8 mice provide a cost-effective model for muscular aging studies.

Topics: Aging; Animals; Body Weight; Male; Mice; Mice, Inbred Strains; Models, Animal; Muscle Contraction; Muscle Fatigue; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Atrophy; Organ Size; Phosphocreatine; Survival Analysis

The cognitive deficits observed in children with cyanotic congenital heart disease suggest involvement of the developing hippocampus. Chronic postnatal hypoxia present during infancy in these children may play a role in these impairments. To understand the biochemical mechanisms of hippocampal injury in chronic hypoxia, a neurochemical profile consisting of 15 metabolite concentrations and 2 metabolite ratios in the hippocampus was evaluated in a rat model of chronic postnatal hypoxia using in vivo 1H NMR spectroscopy at 9.4 T. Chronic hypoxia was induced by continuously exposing rats (n = 23) to 10% O2 from postnatal day (P) 3 to P28. Fifteen metabolites were quantified from a volume of 9-11 microl centered on the left hippocampus on P14, P21, and P28 and were compared with normoxic controls (n = 14). The developmental trajectory of neurochemicals in chronic hypoxia was similar to that seen in normoxia. However, chronic hypoxia had an effect on the concentrations of the following neurochemicals: aspartate, creatine, phosphocreatine, GABA, glutamate, glutamine, glutathione, myoinositol, N-acetylaspartate (NAA), phosphorylethanolamine, and phosphocreatine/creatine (PCr/Cr) and glutamate/glutamine (Glu/Gln) ratios (P < 0.001 each, except glutamate, P = 0.04). The increased PCr/Cr ratio is consistent with decreased brain energy consumption. Given the well-established link between excitatory neurotransmission and brain energy metabolism, we postulate that elevated glutamate, Glu/Gln ratio, and GABA indicate suppressed excitatory neurotransmission in an energy-limited environment. Decreased NAA and phosphorylethanolamine suggest reduced neuronal integrity and phospholipid metabolism. The altered hippocampal neurochemistry during its development may underlie some of the cognitive deficits present in human infants at risk of chronic hypoxia.

Topics: Age Factors; Analysis of Variance; Animals; Animals, Newborn; Aspartic Acid; Body Weight; Brain Chemistry; Creatine; Energy Metabolism; Female; gamma-Aminobutyric Acid; Hippocampus; Hypoxia; Iron; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Organ Size; Phosphocreatine; Pregnancy; Rats; Rats, Sprague-Dawley; Time Factors; Tritium

Cognitive deficits in human infants at risk for gestationally acquired perinatal iron deficiency suggest involvement of the developing hippocampus. To understand the plausible biological explanations for hippocampal injury in perinatal iron deficiency, a neurochemical profile of 16 metabolites in the iron-deficient rat hippocampus was evaluated longitudinally by 1H NMR spectroscopy at 9.4 T. Metabolites were quantified from an 11-24 microL volume centered in the hippocampus in 18 iron-deficient and 16 iron-sufficient rats on postnatal day (PD) 7, PD10, PD14, PD21 and PD28. Perinatal iron deficiency was induced by feeding the pregnant dam an iron-deficient diet from gestational d 3 to PD7. The brain iron concentration of the iron-deficient group was 60% lower on PD7 and 19% lower on PD28 (P < 0.001 each). The concentration of 12 of the 16 measured metabolites changed over time between PD7 and PD28 in both groups (P < 0.001 each). Compared with the iron-sufficient group, phosphocreatine, glutamate, N-acetylaspartate, aspartate, gamma-aminobutyric acid, phosphorylethanolamine and taurine concentrations, and the phosphocreatine/creatine ratio were elevated in the iron-deficient group (P < 0.02 each). These neurochemical alterations suggest persistent changes in resting energy status, neurotransmission and myelination in perinatal iron deficiency. An altered neurochemical profile of the developing hippocampus may underlie some of the cognitive deficits observed in human infants with perinatal iron deficiency.

Topics: Aging; Animals; Aspartic Acid; Body Weight; Brain; Brain Chemistry; Creatine; Ethanolamines; Female; gamma-Aminobutyric Acid; Glutamic Acid; Hippocampus; Iron; Iron Deficiencies; Liver; Magnetic Resonance Spectroscopy; Male; Myocardium; Organ Size; Phosphocreatine; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Taurine

Glycogen storage disease type II (GSD II) is an inherited progressive muscle disease in which lack of functional acid alpha-glucosidase (AGLU) results in lysosomal accumulation of glycogen. We report on the impact of a null mutation of the acid alpha-glucosidase gene (AGLU(-/-)) in mice on the force production capabilities, contractile mass, oxidative capacity, energy status, morphology, and desmin content of skeletal muscle. Muscle function was assessed in halothane-anesthetized animals, using a recently designed murine isometric dynamometer. Maximal torque production during single tetanic contraction was 50% lower in the knockout mice than in wild type. Loss of developed torque was found to be disproportionate to the 20% loss in muscle mass. During a series of supramaximal contraction, fatigue, expressed as percentile decline of developed torque, did not differ between AGLU(-/-) mice and age-matched controls. Muscle oxidative capacity, energy status, and protein content (normalized to either dry or wet weight) were not changed in knockout mice compared to control. Alterations in muscle cell morphology were clearly visible. Desmin content was increased, whereas alpha-actinin was not. As the decline in muscle mass is insufficient to explain the degree in decline of mechanical performance, we hypothesize that the large clusters of noncontractile material present in the cytoplasm hamper longitudinal force transmission, and hence muscle contractile function. The increase in muscular desmin content is most likely reflecting adaptations to altered intracellular force transmission.

Topics: Actinin; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; alpha-Glucosidases; Animals; Body Weight; Desmin; Glucan 1,4-alpha-Glucosidase; Glycogen; Glycogen Storage Disease Type II; Inosine Monophosphate; Mice; Mice, Knockout; Muscle Contraction; Muscle Fibers, Skeletal; Muscle Weakness; Muscle, Skeletal; Phosphocreatine; Stress, Mechanical

Glucose transport in muscle is a function of the muscle metabolic state, as evidenced by the increase in glucose transport which occurs with conditions of altered aerobic metabolism such as hypoxia or contractile activity. The energy state of the muscle can be determined by the muscle phosphocreatine concentration. Dietary supplementation of creatine has been shown to increase both phosphocreatine (PCr) and creatine (TCr) levels in muscle, although not in the same proportion, so that the PCr/TCr ratio falls suggesting an altered energy state in the cell. The purpose of this study was to determine the effect of increased creatine content on glucose uptake in muscle. PCr and TCr were determined in plantaris muscles from rats following five weeks of dietary supplementation of creatine monohydrate (300 mg/kg/day). (3)H-2-deoxyglucose uptake was measured in epitrochlearis muscles incubated in the presence or absence of a maximally stimulating dose of insulin. Despite a significant increase in creatine content in muscle, neither basal nor insulin-stimulated glucose uptake was altered in creatine supplemented rats. Since PCr levels were not increased with creatine supplementation, these results suggest that the actual concentration of PCr is a more important determinant of glucose uptake than the PCr/TCr ratio.

Topics: Animals; Antimetabolites; Body Weight; Creatine; Deoxyglucose; Glucose; Insulin; Male; Muscle, Skeletal; Organ Size; Phosphocreatine; Rats; Rats, Sprague-Dawley

The mitochondrial uncoupling protein of brown adipose tissue (UCP1) was expressed in skeletal muscle and heart of transgenic mice at levels comparable with the amount found in brown adipose tissue mitochondria. These transgenic mice have a lower body weight, and when related to body weight, food intake and energy expenditure are increased. A specific reduction of muscle mass was observed but varied according to the contractile activity of muscles. Heart and soleus muscle are unaffected, indicating that muscles undergoing regular contractions, and therefore with a continuous mitochondrial ATP production, are protected. In contrast, the gastrocnemius and plantaris muscles showed a severely reduced mass and a fast to slow shift in fiber types promoting mainly IIa and IIx fibers at the expense of fastest and glycolytic type IIb fibers. These observations are interpreted as a consequence of the strong potential dependence of the UCP1 protonophoric activity, which ensures a negligible proton leak at the membrane potential observed when mitochondrial ATP production is intense. Therefore UCP1 is not deleterious for an intense mitochondrial ATP production and this explains the tolerance of the heart to a high expression level of UCP1. In muscles at rest, where ATP production is low, the rise in membrane potential enhances UCP1 activity. The proton return through UCP1 mimics the effect of a sustained ATP production, permanently lowering mitochondrial membrane potential. This very likely constitutes the origin of the signal leading to the transition in fiber types at rest.

Topics: Adenosine Triphosphate; Adipose Tissue, Brown; Animals; Body Weight; Carrier Proteins; Energy Intake; Energy Metabolism; Heart; Ion Channels; Membrane Proteins; Mice; Mice, Transgenic; Mitochondria; Mitochondria, Muscle; Mitochondrial Proteins; Muscle Fibers, Fast-Twitch; Muscle, Skeletal; Myocardial Contraction; Organ Specificity; Phenotype; Phosphocreatine; Rats; Regression Analysis; Rest; Uncoupling Protein 1

The effect of thyroid hormone (T(3)) on the content of myocardial creatine (Cr), Cr phosphate (CrP), and high-energy adenine nucleotides and on cardiac function was examined. In the hearts of control and T(3)-treated rats perfused in vitro, while "low" and "high" contractile work was performed, T(3) treatment resulted in a approximately 50% reduction in CrP, Cr, total Cr content (Cr + CrP), and in the CrP-to-Cr ratio. In addition, there was a slight fall in myocardial content of ATP and a large rise in calculated free ADP (fADP), resulting in a significant decrease in the ATP-to-fADP ratio in the hearts of hyperthyroid compared with euthyroid rats. Moreover, there was a substantial decrease in the level of ATP in hearts of T(3)-treated rats under high work conditions. Importantly, the ratio of cardiac work to oxygen consumption was not altered by thyroid status. Treatment with T(3) also resulted in an almost threefold reduction in the content of Na(+)/Cr transporter mRNA in the ventricular myocardium and skeletal muscle but not in the brain. We conclude with the following: 1) changes in the expression of the Na(+)/Cr transporter mRNA correlate with Cr + CrP in the myocardium; 2) hearts of hyperthyroid rats contain lower levels of ATP and higher levels of fADP under both low and high work conditions but no reduction in efficiency of work output; and 3) the reduction in Cr and ATP in hearts of hyperthyroid rats may be the basis for the reduced maximal work capacity of the hyperthyroid heart.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Blood Pressure; Body Weight; Brain; Creatine; Energy Metabolism; Heart; Heart Rate; Hyperthyroidism; In Vitro Techniques; Intracellular Fluid; Male; Membrane Transport Proteins; Muscle, Skeletal; Myocardium; Organ Size; Oxygen Consumption; Phosphocreatine; Rats; Rats, Sprague-Dawley; RNA, Messenger; Systole; Triiodothyronine

It is increasingly evident that the brain is another site of diabetic end-organ damage. The pathogenesis has not been fully explained, but seems to involve an interplay between aberrant glucose metabolism and vascular changes. Vascular changes, such as deficits in cerebral blood flow, could compromise cerebral energy metabolism. We therefore examined cerebral metabolism in streptozotocin-diabetic rats in vivo by means of localised 31P and 1H magnetic resonance spectroscopy.. Rats were examined 2 weeks and 4 and 8 months after diabetes induction. A non-diabetic group was examined at baseline and after 8 months.. In 31P spectra the phosphocreatine:ATP, phosphocreatine:inorganic phosphate and ATP:inorganic phosphate ratios and intracellular pH in diabetic rats were similar to controls at all time points. In 1H spectra a lactate resonance was detected as frequently in controls as in diabetic rats. Compared with baseline and 8-month controls 1H spectra did, however, show a statistically significant decrease in N-acetylaspartate:total creatine (-14% and -23%) and N-acetylaspartate:choline (-21% and -17%) ratios after 2 weeks and 8 months of diabetes, respectively.. No statistically significant alterations in cerebral energy metabolism were observed after up to 8 months of streptozotocin-diabetes. These findings indicate that cerebral blood flow disturbances in diabetic rats do not compromise the energy status of the brain to a level detectable by magnetic resonance spectroscopy. Reductions in N-acetylaspartate levels in the brain of STZ-diabetic rats were shown by 1H spectroscopy, which could present a marker for early metabolic or functional abnormalities in cerebral neurones in diabetes.

Topics: Adenosine Triphosphate; Animals; Aspartic Acid; Blood Glucose; Body Weight; Brain; Choline; Creatine; Diabetes Mellitus, Experimental; Energy Metabolism; Hydrogen; Lactates; Magnetic Resonance Spectroscopy; Male; Phosphates; Phosphocreatine; Phosphorus; Rats; Rats, Wistar; Reference Values; Time Factors

Heart disease represents an important etiology of mortality in chronic alcoholics. The purpose of the present study was to examine potential mechanisms for the inhibitory effect of chronic alcohol exposure (16 wk) on the regulation of myocardial protein metabolism. Chronic alcohol feeding resulted in a lower heart weight and 25% loss of cardiac protein per heart compared with pair-fed controls. The loss of protein mass resulted in part from a diminished (30%) rate of protein synthesis. Ethanol exerted its inhibition of protein synthesis through diminished translational efficiency rather than lower RNA content. Chronic ethanol administration decreased the abundance of eukaryotic initiation factor (eIF)4G associated with eIF4E in the myocardium by 36% and increased the abundance of the translation response protein (4E-BP1) associated with eIF4E. In addition, chronic alcohol feeding significantly reduced the extent of p70S6 kinase (p70(S6K)) phosphorylation. The decreases in the phosphorylation of 4E-BP1 and p70(S6K) did not result from a reduced abundance of mammalian target of rapamycin (mTOR). These data suggest that a chronic alcohol-induced impairment in myocardial protein synthesis results in part from inhibition in peptide chain initiation secondary to marked changes in eIF4E availability and p70(S6K) phosphorylation.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Alcoholism; Animals; Body Weight; Creatine; Energy Intake; Ethanol; Eukaryotic Initiation Factor-4E; Heart; Heart Ventricles; Male; Myocardium; Organ Size; Peptide Initiation Factors; Phosphocreatine; Phosphorylation; Protein Biosynthesis; Rats; Rats, Sprague-Dawley; Ribosomal Protein S6 Kinases; Ventricular Function

This study examined high-energy phosphates (HEP) and mitochondrial ATPase protein expression in hearts in which myocardial infarction resulted in either compensated left ventricular remodeling (LVR) or congestive heart failure (CHF). The response of HEP (measured via (31)P magnetic resonance spectroscopy) to a modest increase in the cardiac work state produced by dobutamine-dopamine infusion and pacing (if needed) was examined in 17 pigs after left circumflex coronary artery ligation (9 with LVR and 8 with CHF) and compared with 7 normal pigs. In hearts with LVR, the baseline phosphocreatine (PCr)-to-ATP ratio decreased, and calculated ADP increased; these changes were most severe in hearts with CHF. HEP levels did not change in normal or LVR hearts during dobutamine-dopamine infusion. However, in hearts with CHF, the PCr-to-ATP ratio decreased further, and free ADP increased. The mitochondrial protein levels of the F(0)F(1)-ATPase subunits were normal in hearts with compensated LVR. However, in failing hearts, the alpha-subunit decreased by 36%, the beta-subunit decreased by 16%, the oligomycin sensitivity-conferring protein subunit decreased by 40%, and the initiation factor 1 subunit decreased by 41%. Thus in failing hearts, reductions in mitochondrial F(0)F(1)-ATPase protein expression are associated with increased myocardial free ADP.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Body Weight; Cardiac Pacing, Artificial; Coronary Circulation; Disease Models, Animal; Dobutamine; Dopamine; Heart Failure; Hemodynamics; Infusions, Intravenous; Magnetic Resonance Spectroscopy; Mitochondria, Heart; Myocardial Infarction; Organ Size; Phosphocreatine; Protein Subunits; Proton-Translocating ATPases; Swine; Ventricular Remodeling

The failing myocardium is characterized by reductions of phosphocreatine (PCr) and free creatine content and by decreases of energy reserve via creatine kinase (CK), ie, CK reaction velocity (Flux(CK)). It has remained unclear whether these changes contribute directly to contractile dysfunction. In the present study, myocardial PCr stores in a heart failure model were further depleted by feeding of the PCr analogue beta-guanidinopropionate (GP). Functional and metabolic consequences were studied.. Rats were subjected to sham operation or left coronary artery ligation (MI). Surviving rats were assigned to 4 groups and fed with 0% (n=7, Sham; n=5, MI) or 1% (n=7 Sham+GP, n=8 MI+GP) GP. Two additional groups were fed GP for 2 or 4 weeks before MI. After 8 weeks, hearts were isolated and perfused, and left ventricular pressure-volume curves were obtained. High-energy phosphate metabolism was determined with (31)P NMR spectroscopy. After GP feeding or MI, left ventricular pressure-volume curves were depressed by 33% and 32%, respectively, but GP feeding in MI hearts did not further impair mechanical function. Both MI and GP feeding reduced PCr content and Flux(CK), but here, effects were additive. In MI+GP rats, PCr levels and Flux(CK) were reduced by 87% and 94%, respectively. Although ATP levels were maintained in the GP and MI groups, ATP content was reduced by 18% in MI+GP hearts. Furthermore, 24-hour mortality in GP-prefed rats was 100%.. Rats with an 87% predepletion of myocardial PCr content cannot survive an acute MI. Chronically infarcted hearts subjected to additional PCr depletion cannot maintain ATP homeostasis.

Topics: Adenosine Triphosphate; Animals; Blood Flow Velocity; Body Weight; Chronic Disease; Coronary Circulation; Coronary Vessels; Disease Models, Animal; Guanidines; Heart; Heart Rate; Homeostasis; In Vitro Techniques; Ligation; Magnetic Resonance Spectroscopy; Myocardial Infarction; Organ Size; Phosphocreatine; Phosphorus Isotopes; Propionates; Rats; Rats, Wistar; Survival Rate; Ultrasonography; Ventricular Function, Left

Cardiovascular abnormalities represent the major cause of death in patients with acromegaly. We evaluated cardiac structure, function, and energy status in adult transgenic mice overexpressing bovine GH (bGH) gene. Female transgenic mice expressing bGH gene (n = 11) 8 months old and aged matched controls (n = 11) were used. They were studied with two-dimensional guided M-mode and Doppler echocardiography. The animals (n = 6) for each group were examined with 31P magnetic resonance spectroscopy to determine the cardiac energy status. Transgenic mice had a significantly higher body weight (BW), 53.2+/-2.4 vs. 34.6+/-3.7 g (P < 0.0001) and hypertrophy of left ventricle (LV) compared with normal controls: LV mass/BW 5.6+/-1.6 vs. 2.7+/-0.2 mg/g, P < 0.01. Several indexes of systolic function were depressed in transgenic animals compared with controls mice such as shortening fraction 25+/-3.0% vs. 39.9+/-3.1%; ejection fraction, 57+/-9 vs. 77+/-5; mean velocity of circumferential shortening, 4.5+/-0.8 vs. 7.0+/-1.1 circ/sec, p < 0.01. Creatine phosphate-to-ATP ratio was significantly lower in bGH overexpressing mice (1.3+/-0.08 vs. 2.1+/-0.23 in controls, P < 0.05). Ultrastructural examination of the hearts from transgenic mice revealed substantial changes of mitochondria. This study provides new insight into possible mechanisms behind the deteriorating effects of long exposure to high level of GH on heart function.

Topics: Acromegaly; Adenosine Triphosphate; Animals; Body Weight; Cattle; Echocardiography; Energy Metabolism; Female; Gene Expression; Growth Hormone; Heart Diseases; Hypertrophy, Left Ventricular; Magnetic Resonance Spectroscopy; Mice; Mice, Transgenic; Myocardium; Organ Size; Phosphocreatine; Systole

The present study tests the hypothesis that ketamine, a dissociative anesthetic known to be a non-competitive antagonist of the NMDA receptor, will attenuate hypoxic-ischemic damage in neonatal rat brain. Studies were performed in 7-day-old rat pups which were divided into four groups. Animals of the first group, neither ligated nor exposed to hypoxia, served as controls. The second group was exposed to hypoxic-ischemic conditions and sacrificed immediately afterwards. Animals of the third and fourth groups were treated either with saline or ketamine (20 mg/kg, i.p.) in four doses following hypoxia. Hypoxic-ischemic injury to the left cerebral hemisphere was induced by ligation of the left common carotid artery followed by 1 h of hypoxia with 8% oxygen. Measurements of high energy phosphates (ATP and phosphocreatine) and amino acids (glutamate and glutamine) and neuropathological evaluation of the hippocampal formation were used to assess the effects of hypoxia-ischemia. The combination of common carotid artery ligation and exposure to an hypoxic environment caused major alterations in the ipsilateral hemisphere. In contrast, minor alterations in amino acid concentrations were observed after the end of hypoxia in the contralateral hemisphere. These alterations were restored during the early recovery period. Post-treatment with ketamine was associated with partial restoration of energy stores and amino acid content of the left cerebral hemisphere. Limited attenuation of the damage to the hippocampal formation as demonstrated by a reduction in the number of damaged neurons was also observed. These findings demonstrate that systemically administered ketamine after hypoxia offers partial protection to the newborn rat brain against hypoxic-ischemic injury.

Topics: Adenosine Triphosphate; Amino Acids; Animals; Animals, Newborn; Body Weight; Brain; Brain Ischemia; Carotid Artery Diseases; Female; Functional Laterality; Glutamic Acid; Glutamine; Hypoxia, Brain; Ketamine; Male; Neurons; Neuroprotective Agents; Phosphocreatine; Rats; Rats, Wistar; Time Factors

We evaluated the hypothesis that long-term caloric restriction and exercise would have beneficial effects on muscle bioenergetics and performance in the rat. By themselves, each of these interventions is known to increase longevity, and bioenergetic improvements are thought to be important in this phenomenon. Accordingly, we investigated rats that underwent long-term caloric restriction and were sedentary, ad libitum-fed rats permitted to exercise by daily spontaneous wheel running (AE), and the combination of the dietary and exercise interventions (RE). Ad libitum-fed, sedentary rats comprised the control group. 31P NMR spectra of the gastrocnemius muscle (GM) were collected in vivo at rest and during two periods of electrical stimulation. Neither caloric restriction nor exercise affected the ratio of phosphocreatine to ATP or pH at rest. During the first stimulation and after recovery, the RE group had a significantly smaller decline in pH than did the other groups (P < 0.05). During the second period of stimulation, the decrease in pH was much smaller in all groups than during the first stimulation, with no differences observed among the groups. The combination of caloric restriction and exercise resulted in a significant attenuation in the decline in developed force during the second period of stimulation (P < 0.05). A biochemical correlate of this was a significantly higher concentration of citrate synthase in the GM samples from the RE rats (32.7 +/- 5.4 micromol. min-1. g-1) compared with the AE rats (17.6 +/- 5.7 micromol. min-1. g-1; P < 0.05). Our experiments thus demonstrated a synergistic effect of long-term caloric restriction and free exercise on muscle bioenergetics during electrical stimulation.

Topics: Animals; Body Weight; Diet, Reducing; Energy Intake; Energy Metabolism; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Male; Muscle Contraction; Muscle, Skeletal; Phosphates; Phosphocreatine; Physical Conditioning, Animal; Physical Exertion; Rats; Rats, Wistar

The purpose of this study was to measure noninvasively the absolute concentrations of muscle adenosine triphosphate [ATP], phosphocreatine [PCr], inorganic phosphate (Pi), and glycogen [Gly] of elite soccer players.. Magnetic resonance spectroscopy (31P- and 13C-MRS) was used to measure the concentrations of metabolites in the calf muscles of 18 young male players [age = 17.5 +/- 1.0 (SD) yr].. Average muscle [PCr] and [ATP] were 17.8 +/- 3.3 and 6.0 +/- 1.2 mmol x (kg wet weight)(-1), respectively. The ratios of Pi/PCr and PCr/ATP were 0.15 +/- 0.05 and 3.00 +/- 0.26, respectively. The muscle [Gly] was 144 +/- 54 mmol x (kg wet weight)(-1). There was a high correlation (r = 0.93, P < 0.0001) between muscle ATP and PCr concentrations, but there was no correlation between [Gly] and [PCr] or [ATP]. The concentrations of the different metabolites determined in the present study with noninvasive MRS methods were within the ranges of values reported in human muscle from biochemical analysis of muscle biopsies.. MRS methods can be utilized to assess noninvasively the muscle energetic status of elite soccer players during a soccer season. The high correlation between ATP and PCr might be indicative of fiber type differences in the content of these two metabolites.

Topics: Adenosine Triphosphate; Adolescent; Biopsy; Body Weight; Carbon Isotopes; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Energy Intake; Glycogen; Humans; Leg; Magnetic Resonance Spectroscopy; Male; Muscle, Skeletal; Phosphates; Phosphocreatine; Phosphorus Isotopes; Reproducibility of Results; Soccer

Chronic treatment with beta-receptor blockers or angiotensin-converting enzyme (ACE) inhibitors in heart failure can reduce mortality and improve left ventricular function, but the mechanisms involved in their beneficial action remain to be fully defined. Our hypothesis was that these agents prevent the derangement of cardiac energy metabolism. Rats were subjected to myocardial infarction (MI) or sham operation. Thereafter, animals were treated with bisoprolol, captopril, or remained untreated. Two months later, cardiac function was measured in the isolated heart by a left ventricular balloon (pressure-volume curves), and energy metabolism of residual intact myocardium was analyzed in terms of total and isoenzyme creatine kinase (CK) activity, steady-state levels (ATP, phosphocreatine), and turnover rates (CK reaction velocity) of high-energy phosphates (31P nuclear magnetic resonance) and total creatine content (HPLC). Bisoprolol and partially captopril prevented post-MI hypertrophy and partially prevented left ventricular contractile dysfunction. Residual intact failing myocardium in untreated, infarcted hearts showed a 25% decrease of the total, a 26% decrease of MM-, and a 37% decrease of the mitochondrial CK activity. Total creatine was reduced by 15%, phosphocreatine by 21%, and CK reaction velocity by 41%. Treatment with bisoprolol or captopril largely prevented all of these changes in infarcted hearts. Thus the favorable functional effects of beta-receptor blockers and ACE inhibitors post-MI are accompanied by substantial beneficial effects on cardiac energy metabolism.

Topics: Adenine Nucleotides; Adenosine Triphosphate; Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Bisoprolol; Body Weight; Captopril; Creatine; Creatine Kinase; Energy Metabolism; Isoenzymes; Male; Myocardial Infarction; Myocardium; Organ Size; Phosphocreatine; Rats; Rats, Wistar; Reference Values; Ventricular Function, Left

The present study tests the hypothesis that propentofylline, an adenosine re-uptake inhibitor, will reduce free radical generation during cerebral hypoxia. Ten newborn piglets were pretreated with propentofylline (10 mg/kg), five of which were subjected to hypoxia, while the other five were maintained at normoxia. Five untreated control piglets underwent the same conditions. Hypoxia was induced through a decrease in FiO2 to 0.11 and documented biochemically by a decrease in ATP and phosphocreatine levels. Free radical formation in the cortex was detected directly using electron spin resonance spectroscopy with a spin trap technique. Results demonstrate that free radicals, corresponding to the alkoxyl radical, increased significantly following hypoxia, and that this increase was inhibited by pretreatment with propentofylline. Conjugated dienes, a lipid peroxidation product, also increased following hypoxia and were subsequently inhibited by propentofylline. The administration of propentofylline also significantly limited the hypoxia-induced decrease in tissue levels of ATP and phosphocreatine. These data demonstrate that pretreatment with propentofylline decreased free radical generation and lipid peroxidation as well as preserved high energy phosphates during cerebral hypoxia.

Topics: Adenosine Triphosphate; Animals; Animals, Newborn; Anti-Ulcer Agents; Blood Gas Analysis; Body Weight; Free Radicals; Hypoxia, Brain; Lipid Peroxidation; Phosphocreatine; Swine; Xanthines

The present study investigated whether alterations in the muscle high energy phosphate state initiates the contraction-induced increase in skeletal muscle GLUT4 protein concentration. Sprague-Dawley rats were provided either a normal or a 2% beta-guanidinoproprionic acid (beta-GPA) diet for 8 weeks and then the gastrocnemius of one hind limb was subjected to 0, 14 or 28 days of chronic (24 h day-1) low-frequency electrical stimulation (10 Hz). The beta-GPA diet, in the absence of electrical stimulation, significantly reduced ATP, creatine phosphate, creatine and inorganic phosphate and elevated GLUT4 protein concentration by 60% without altering adenylate cyclase activity or cAMP concentration. Following 14 days of electrical stimulation, GLUT4 protein concentration was elevated above non-stimulated muscle in both groups but was significantly more elevated in the beta-GPA group. Concurrent with this greater rise in GLUT4 protein concentration was a greater decline in the high energy phosphates and a greater rise in cAMP. After 28 days of electrical stimulation, GLUT4 protein concentration and cAMP stabilized and was not different between diet treatments. However, the high energy phosphates were significantly higher in the normal diet rats as opposed to the beta-GPA rats. These findings therefore suggest that a reduction in cellular energy supply initiates the contraction-induced increase in muscle GLUT4 protein concentration, but that a rise in cAMP may potentiate this effect.

Topics: Adenosine Triphosphate; Adenylyl Cyclases; Animals; Body Weight; Cyclic AMP; Diet; Electric Stimulation; Female; Glucose Transporter Type 4; Guanidines; Monosaccharide Transport Proteins; Muscle Proteins; Muscle, Skeletal; Organ Size; Phosphates; Phosphocreatine; Propionates; Rats; Rats, Sprague-Dawley

The effects of 6 weeks of chronic ethanol administration on the lateral fluid percussion (FP) brain injury-induced regional accumulation of lactate and on the levels of total high-energy phosphates were examined in rats. In both the chronic ethanol diet (ethanol diet) and pair-fed isocaloric sucrose control diet (control diet) groups, tissue concentrations of lactate were elevated in the cortices and hippocampi of both the ipsilateral and contralateral hemispheres at 5 min after brain injury. In both diet groups, concentrations of lactate were elevated only in the injured left cortex and the ipsilateral hippocampus at 20 min after FP brain injury. No significant differences were found in the levels of lactate in the cortices and hippocampi of sham animals and brain-injured animals between the ethanol and control diet groups at 5 min and 20 min after injury. In the ethanol and control diet groups, tissue concentrations of total high-energy phosphates (ATP + PCr) were not affected in the cortices and hippocampi at 5 min and 20 min after lateral FP brain injury. No significant differences were found in the levels of total high-energy phosphates in the cortices and hippocampi of the sham and brain-injured animals between the ethanol and control diet groups at 5 min and 20 min after injury. Histologic studies revealed a similar extent of damage in the cortex and in the CA3 region of the ipsilateral hippocampus in both diet groups at 14 days after lateral FP brain injury. These findings suggest that 6 weeks of chronic ethanol administration does not alter brain injury-induced accumulation of lactate, levels of total high energy phosphates, and extent of morphological damage.

Topics: Adenosine Triphosphate; Animals; Body Weight; Brain; Brain Injuries; Central Nervous System Depressants; Ethanol; Lactic Acid; Male; Phosphocreatine; Rats; Rats, Sprague-Dawley

Hyperglycemia increases cerebral damage after transient cerebral ischemia. This study used in vivo 31P nuclear magnetic resonance spectroscopy to determine the relationship of intracellular tissue acidosis and delayed recovery of brain high-energy phosphates to increased damage during the reperfusion period. Mongolian gerbils were subjected to transient bilateral carotid ischemia for 20 min with 2 h reperfusion. All gerbils were pretreated intraperitoneally with equivalent volumes in saline of 0.003 units per kilogram of insulin or vehicle, or with 4 grams of glucose per kilogram. The gerbils were then scanned in a 4.7 Tesla Magnetic Resonance Imager-Spectrometer to determine levels of intracellular pH, inorganic phosphate, adenosine triphosphate, and phosphocreatine. In each group, intracellular pH decreased with ischemia, but most significantly in hyperglycemic animals (6.45 +/- 0.15), in which it had not recovered to preischemic levels by the end of the reperfusion period (6.8 +/- 0.1 vs 7.04 +/- 0.1, p < 0.05). High-energy phosphates phosphocreatine-inorganic phosphate and phosphocreatine-adenosine triphosphate showed partial recovery in all groups throughout the reperfusion period; the recovery was not significantly altered by glucose status. Hyperglycemia worsened pH but not the recovery of high-energy phosphates in animals reperfused after 20 min of transient cerebral ischemia. This sustained acidosis may be a primary event in transient damage in hyperglycemic animals.

Topics: Adenosine Triphosphate; Animals; Arterial Occlusive Diseases; Blood Glucose; Body Weight; Brain Ischemia; Carotid Arteries; Energy Metabolism; Gerbillinae; Glucose; Hydrogen-Ion Concentration; Hyperglycemia; Hypoglycemic Agents; Insulin; Magnetic Resonance Spectroscopy; Male; Phosphates; Phosphocreatine; Reperfusion Injury

Sepsis increases phosphocreatine (PCr) breakdown and reduces PCr stores in skeletal muscle. To determine if systemic infection impairs mitochondrial function, in vivo 13P magnetic resonance spectroscopy (31P MRS) studies of the gastrocnemius muscle were performed in virus-free male Wistar rats 24 or 48 hr after cecal ligation and 18-gauge needle single puncture (24 degrees CLP, n = 16; 48 degrees CLP, n = 15) or sham operation (24 degrees SHAM, n = 18; 48 degrees SHAM, n = 13). Physiologic saline (6 ml/100 g body wt) was injected intraperitoneally for fluid resuscitation. Water but no food was allowed in all animals. High resolution (8.45 Tesla) 31P MRS spectra, obtained at rest and during exercise using a 1.4-cm surface coil, were used to calculate PCr/ATP, PCr/P(i) ratios, and intracellular pH. Steady-state muscle exercise was induced by supramaximal sciatic nerve stimulation at 10 Hz for 10 min. Recovery of PCr/(PCr + P(i)) ratios after exercise was fitted to a monoexponential curve. The resultant function was used to calculate the half time for PCr recovery, the initial PCr resynthesis rate, and the maximal oxidative ATP synthesis rate, which reflect the rephosphorylation of ADP and are therefore measures of mitochondrial oxidative capacity. PCr/ATP ratios decreased by 12 and 11%, 24 and 48 hr after CLP, respectively. The PCr/P(i) ratios decreased incrementally (7% in 24 degrees CLP vs 23% in 48 degrees CLP animals). Twenty-four hours after operation the half time for PCr recovery was shortened while the initial PCr resynthesis rate and maximal oxidative ATP synthesis rate were accelerated in CLP animals compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Diphosphate; Animals; Body Weight; Hydrogen-Ion Concentration; Magnesium; Male; Mitochondria, Muscle; Muscle, Skeletal; Oxidation-Reduction; Phosphocreatine; Rats; Rats, Wistar; Sepsis

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

A creatine analogue, beta-guanidinopropionic acid (beta-GPA), was administered in the food (1% w/w) of 8 male rats for 6 weeks, while 8 control rats received a standard diet. Mitochondrial oxidative capacity and cytosolic modulators of mitochondrial oxidative phosphorylation (free ADP, ATP-to-free ADP ratio) were evaluated in the soleus and extensor digitorum longus (EDL) muscles. Mitochondrial adaptation to the diet was significantly different between muscles. Citrate synthase activity and mitochondrial ATP synthesis rate were 35 and 45% higher in EDL muscle, respectively, whereas they were virtually unchanged in the soleus muscle. In both muscles, 3-hydroxyacyl-CoA dehydrogenase activity remained unaffected. Regardless of muscle type, creatine, phosphocreatine and ATP concentrations, as well as the total adenine nucleotide content (ATP + ADP + AMP), were significantly lower in beta-GPA fed rats. Whereas free ADP concentration remained unchanged, a significantly greater decrease in ATP-to-free ADP ratio was observed in EDL than in the soleus muscle. It is suggested that regulation of mitochondrial oxidative phosphorylation, through changes in metabolite concentrations, could be an important factor to consider for mitochondrial adaptation induced by beta-GPA feeding.

Topics: Adenine Nucleotides; Animals; Body Weight; Creatine; Energy Metabolism; Guanidines; Male; Muscle Proteins; Muscles; Organ Size; Oxygen Consumption; Phosphocreatine; Propionates; Rats; Rats, Sprague-Dawley

Starvation significantly alters the distribution of body water. To study the effects of starvation on cellular energetics and water distribution in skeletal muscle, a novel 31P magnetic resonance technique (31P MRS) was developed to measure water compartments. After 31P MRS-visible water space markers which distribute in total body water (dimethyl methylphosphonate, DMMP) and extracellular water (phenylphosphonate, PPA) were infused intravenously, 31P MRS spectra were obtained from the gastrocnemius muscle of male virus-free Wistar rats at baseline and after starvation or ad libitum feeding for 4 days. Muscle water spaces were also measured using the chloride method and Nernst's equation. Muscle water contents as determined by drying were equivalent in the two groups. In vivo measurements of changes in DMMP relative to all of the MRS visible phosphates also demonstrated that the total water space was similar in control and starved rats. However, starvation significantly increased the ratio of PPA/DMMP (0.67 +/- 0.05 vs 0.87 +/- 0.04, Control vs Starvation; P < 0.001), and therefore the ratio of extracellular water to total water in the gastrocnemius. Furthermore, because muscle water contents were comparable between the groups, this expansion of the extracellular space was accompanied by contraction of the intracellular compartment in starved animals. Equivalent changes were detected in vitro using the chloride method. Lastly, phosphocreatine/ATP ratios, which measured changes in high-energy phosphate stores, decreased after starvation (4.09 +/- 0.06 vs 3.61 +/- 0.06; P < 0.001) and were inversely related to changes in PPA/DMMP (r = -0.61; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Triphosphate; Animals; Body Water; Body Weight; Extracellular Space; Hydrogen-Ion Concentration; Magnetic Resonance Imaging; Male; Muscles; Organophosphorus Compounds; Phosphocreatine; Phosphorus; Rats; Rats, Wistar; Starvation

Biopsy samples were obtained from the vastus lateralis muscle of eight subjects after 0, 20, 60, and 120 s of recovery from intense electrically evoked isometric contraction. Later (10 days), the same procedures were performed using the other leg, but subjects ingested 20 g creatine (Cr)/day for the preceding 5 days. Muscle ATP, phosphocreatine (PCr), free Cr, and lactate concentrations were measured, and total Cr was calculated as the sum of PCr and free Cr concentrations. In five of the eight subjects, Cr ingestion substantially increased muscle total Cr concentration (mean 29 +/- 3 mmol/kg dry matter, 25 +/- 3%; range 19-35 mmol/kg dry matter, 15-32%) and PCr resynthesis during recovery (mean 19 +/- 4 mmol/kg dry matter, 35 +/- 6%; range 11-28 mmol/kg dry matter, 23-53%). In the remaining three subjects, Cr ingestion had little effect on muscle total Cr concentration, producing increases of 8-9 mmol/kg dry matter (5-7%), and did not increase PCr resynthesis. The data suggest that a dietary-induced increase in muscle total Cr concentration can increase PCr resynthesis during the 2nd min of recovery from intense contraction.

Topics: Administration, Oral; Adult; Biopsy; Body Weight; Creatine; Humans; Lactates; Male; Muscles; Phosphocreatine; Reference Values; Weight Gain

1. The muscle tension and the state of high-energy phosphate metabolism during contraction of the sartorius muscle in frogs (Rana catesbeiana) starved for 1-5 months was studied by in vivo 31P-NMR spectrometry. 2. Muscle tension began to decrease after 2-month starvation compared with the control group and decreased to about one-third of the control value after a 5-month starvation. 3. Muscle contraction induced by electrical stimulation or the use of anaerobic perfusion fluid did not decrease the concentration of creatine phosphate (PCr) or beta-ATP, and only negligibly changed the PCr/Pi ratio from starvation. 4. These results suggest a decrease in creatine kinase activity in the muscle of starved frogs.

Topics: Animals; Body Weight; Electric Stimulation; Energy Metabolism; Magnetic Resonance Spectroscopy; Muscle Contraction; Muscles; Phosphates; Phosphocreatine; Phosphorus Isotopes; Rana catesbeiana; Starvation

Streptozocin-induced diabetes in rats causes changes in urinary bladder function and increases the responsiveness of isolated bladder strip preparations to contractile agents and field stimulation. We monitored the role of extracellular glucose in the contractile responsiveness of bladder body strips from control, 2-month diabetic, and sucrose-drinking rats to the muscarinic agonist bethanechol. Consumption of sucrose and induction of diabetes caused increases in bladder mass compared with that of controls. In the presence of normal glucose levels (5.6 mmol/L), bladder strips from diabetic rats responded to bethanechol with significantly larger responses than those from control or sucrose-drinking rats. Removal of glucose from the bathing medium caused time-dependent decreases in contractile response of bladder strips from all groups; there were no differences in the percent decrease in response between the three groups. The presence of insulin (100 mU/mL) had no effects on contractile responsiveness or the rate of decline of response. Following return of glucose to the medium, there were progressive increases in contractile responsiveness in all groups, which returned to original contractile values within 60 minutes and were unaffected by insulin. Pyruvate (9.1 mmol/L) was able to substitute for glucose in maintaining the contractile responses. Increasing the glucose concentration of the medium to 30 mmol/L had no effects on contractile responses. Unstimulated bladder adenosine triphosphate (ATP) and creatine phosphate concentrations were similar in control, diabetic, and sucrose-drinking rats. In conclusion, changes in glucose utilization and high-energy phosphate levels cannot explain the increased contractile responsiveness of bladder body strips from diabetic rats to contractile agents.

Topics: Adenosine Triphosphate; Animals; Bethanechol; Bethanechol Compounds; Body Weight; Chromatography, High Pressure Liquid; Diabetes Mellitus, Experimental; Extracellular Space; Glucose; In Vitro Techniques; Male; Muscle Contraction; Muscle, Smooth; Organ Size; Phosphocreatine; Pyruvates; Pyruvic Acid; Rats; Rats, Sprague-Dawley; Urinary Bladder

Cardiac mechanics and metabolic performance were studied in isolated perfused hearts of heat-acclimated (AC) rats (at 34 degrees C for 1 mo) and their age-matched controls (C). Diastolic and systolic pressures, coronary flow, and the appearance of ischemic contracture (IC) were measured during progressive graded ischemia, total ischemia (TI), and reperfusion. ATP, phosphocreatine, and intracellular pH were measured during TI and reperfusion with the use of 31P-nuclear magnetic resonance spectroscopy. Systolic pressure was greater in AC hearts than in C hearts (P < 0.0001). During 50% of perfusion pressure 15 and 46% of AC and C hearts, respectively, showed IC (P < 0.001). During 25% of perfusion pressure 85% of the hearts in both groups developed IC. The onset of IC in AC hearts was delayed compared with in C hearts. On reperfusion 93 and 66% of AC and C hearts, respectively, resumed contraction. Recovery of diastolic pressure was 78 and 36% for the AC and C hearts, respectively (P < 0.05). During TI ATP declined by 0.94 and 1.20 mumol/min in AC and C hearts, respectively, resulting in 21 +/- 2.8% preservation of the ATP pool in AC hearts after 30 min of TI (P < 0.001). The AC group also showed a delayed decline in intracellular pH (P < 0.001). The data suggest beneficial effects of heat acclimation on the heart, which were exhibited by greater pressure generation and by the emergence of protecting features during ischemia and reperfusion, possibly via energy-sparing mechanisms.

Topics: Acclimatization; Adenosine Triphosphate; Animals; Body Weight; Heart; Hot Temperature; In Vitro Techniques; Magnetic Resonance Spectroscopy; Male; Myocardial Contraction; Myocardial Ischemia; Myocardial Reperfusion; Myocardium; Organ Size; Phosphates; Phosphocreatine; Rats

A previous study suggested that muscles from hypocalorically fed rats were limited in their ability to rephosphorylate ADP. During muscle contraction hydrolysis of ATP results in an increase in phosphorus, free ADP, delta GATP, and a reduction in phosphocreatine levels that is reversed during rest by rephosphorylation of ADP to ATP and the resynthesis of phosphocreatine by ATP. We therefore hypothesized that these changes would be restored more slowly during postcontraction rest in hypocalorically fed rats as compared with controls. We compared controls fed ad lib to 2-d fasted and hypocalorically fed rats, losing 20% of their weight. We also compared hypocalorically fed rats that had been refed ad lib for 7 d with age-matched controls fed ad lib. The results showed that ATP, muscle pH, and total muscle creatine levels were not different in all groups. The raised phosphorus and delta GATP levels and lower phosphocreatine/phosphorus ratio at the end of contraction changed more slowly during rest in the hypocaloric rats. These abnormalities were partially corrected by refeeding. The data taken as a whole support the concept of impaired rephosphorylation of ADP in malnourished muscle that is not completely restored by refeeding in stimulated muscle.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Body Weight; Creatine; Diet, Reducing; Energy Metabolism; Fasting; Hydrogen-Ion Concentration; Lactates; Magnesium; Magnetic Resonance Spectroscopy; Male; Muscle Contraction; Muscles; Phosphates; Phosphocreatine; Rats; Rats, Wistar; Thermodynamics

Transmurally localized 31P-nuclear magnetic resonance spectroscopy (NMR) was used to study the effect of severe pressure overload left ventricular hypertrophy (LVH) on myocardial high energy phosphate content. Studies were performed on 8 normal dogs and 12 dogs with severe left ventricular hypertrophy produced by banding the ascending aorta at 8 wk of age. Spatially localized 31P-NMR spectroscopy provided measurements of the transmural distribution of myocardial ATP, phosphocreatine (CP), and inorganic phosphate (Pi); spectra were calibrated from measurements of ATP content in myocardial biopsies using HPLC. Blood flow was measured with microspheres. In hypertrophied hearts during basal conditions, ATP was decreased by 42%, CP by 58%, and the CP/ATP ratio by 32% in comparison with normal. Increasing myocardial blood flow with adenosine did not correct these abnormalities, indicating that they were not the result of persistent hypoperfusion. Atrial pacing at 200 and 240 beats per min caused no change in high energy phosphate content in normal hearts but resulted in further CP depletion with Pi accumulation in the inner left ventricular layers of the hypertrophied hearts. These changes were correlated with redistribution of blood flow away from the subendocardium in LVH hearts. These findings demonstrate that high energy phosphate levels and the CP/ATP ratio are significantly decreased in severe LVH. These abnormalities are proportional to the degree of hypertrophy but are not the result of persistent abnormalities of myocardial perfusion. In contrast, depletion of CP and accumulation of Pi during tachycardia in LVH are closely related to the pacing-induced perfusion abnormalities and likely reflect subendocardial ischemia.

Topics: Adenosine; Adenosine Triphosphate; Animals; Blood Pressure; Body Weight; Creatinine; Dogs; Energy Metabolism; Heart; Heart Rate; Hypertrophy, Left Ventricular; Magnetic Resonance Spectroscopy; Myocardium; Organ Size; Phosphates; Phosphocreatine; Phosphorus; Reference Values

Concentrations of phosphocreatine, creatine, ATP, ADP, AMP, glucose and lactate in the whole brain did not differ between the mice intoxicated with acrylamide and the controls. When the brain was made ischemic, these concentrations changed to the same extent in both groups. The only difference was the lower pyruvate in acrylamide-intoxicated mice under the ischemia. Thus, as far as the whole brain is concerned, acrylamide does not cause gross alterations of energy metabolites, even under ischemia.

Topics: Acrylamide; Acrylamides; Adenosine Triphosphate; Animals; Body Weight; Brain; Brain Ischemia; Energy Metabolism; Glucose; Lactates; Lactic Acid; Male; Mice; Mice, Inbred Strains; Phosphocreatine; Pyruvates; Pyruvic Acid

Freely grafted rat extensor digitorum longus (EDL) muscles were subjected to low-frequency stimulation in an anaerobic environment to determine whether regenerating fast-twitch muscles regain normal glycolytic metabolic capacity. Regenerating muscles were tested at 28, 42, and 76 days after the graft procedure. Stabilized grafts (76 days) produced approximately 60% of the lactate generated by intact, control EDL subjected to the same stimulus paradigm and developed half the estimated increase in H+. The grafts exhibited the same relative decline in force after 5 min of anaerobic stimulation as control EDL but maintained relatively constant levels of ATP while consuming phosphocreatine. This study indicates that regenerating fast-twitch skeletal muscle has a reduced ability to initiate glycolytic activity during exercise. The data also indicate that a small population of regenerating fast-twitch fibers express the slow isoform of myosin heavy chain (beta-MHC) with maximum expression occurring at 56 days postsurgery.

Topics: Adaptation, Physiological; Adenosine Triphosphate; Anaerobiosis; Animals; Base Sequence; Body Weight; DNA; DNA Probes; Female; Glycolysis; Hydrogen-Ion Concentration; Lactates; Molecular Sequence Data; Muscle Contraction; Muscles; Myosins; Phosphocreatine; Rats; Rats, Inbred Strains; Regeneration

Subjective fatigue was quantified before and 20 days after uncomplicated elective abdominal surgery in 12 patients and compared with changes in heart rate, enzyme activities and skeletal muscle substrates before and after bicycle exercise for 10 min at 65 per cent of patients' preoperative maximum work capacity. Fatigue increased from a mean(s.e.m.) preoperative level of 2.5(0.5) arbitrary units to 4.6(0.5) on postoperative day 20 (P less than 0.01). Body-weight, triceps skinfold thickness and arm circumference decreased postoperatively (P less than 0.02). Postoperative values of muscle enzyme activities indicative of oxidative phosphorylation capacity (citrate synthase and 3-OH-acyl coenzyme A dehydrogenase) were lower than preoperative values (P less than 0.05). Lactate dehydrogenase was unaltered and resting values of muscle glycogen and adenosine triphosphate were higher after operation (P less than 0.05). In response to exercise, heart rate, muscle glucose, glucose-6-phosphate and lactate increased (P less than 0.05), while muscle glycogen and creatine phosphate decreased (P less than 0.05). Increase in postoperative fatigue correlated with the increase in heart rate (P less than 0.05), while no significant correlations were found between fatigue and muscle parameters. Our results suggest that lack of exercise and malnutrition may be of importance in the decrease in work capacity and in fatigue after operation.

Topics: Abdomen; Adenosine Triphosphate; Adult; Arm; Body Weight; Citrate (si)-Synthase; Exercise; Exercise Test; Fatigue; Fatty Acid Desaturases; Female; Glycogen; Heart Rate; Humans; L-Lactate Dehydrogenase; Lactates; Male; Middle Aged; Muscles; Phosphocreatine; Postoperative Complications; Skinfold Thickness

The effects of vitamin D deprivation on the chick heart were investigated from three aspects: cardiac contractility (+/- dP/dT), intracellular high-energy phosphorus compounds, and structural differences. Four-week-old vitamin D-deficient chicks were divided into four groups: Group A served as the normal group and received subcutaneous injections of cholecalciferol; Groups B and C were vitamin D-deficient hearts but perfused differently; Group D received daily subcutaneous injections of 5 micrograms of 1,25(OH)2D3. When the isolated spontaneously beating hearts (modified Langendorff preparation) were perfused with Krebs-Henseleit (KH) solution containing a calcium concentration of 2.5mM, the myocardial contractility of the vitamin D-deficient hearts was significantly increased when compared with group A. After the isolated heart had beaten for one hour, the myocardial contractility in the vitamin D-deficient hearts was found to decline to significantly lower values. Presacrifice administration of 1,25(OH)2D3 improved cardiac performance. Vitamin D deficiency resulted in an enhanced rate of decline of the intracellular high-energy phosphorus compounds. No differences were found in the microscopic study. These observations suggest that vitamin D has a role in cardiac function.

Topics: Adenosine Triphosphate; Animals; Body Weight; Calcium; Chickens; In Vitro Techniques; Magnetic Resonance Spectroscopy; Myocardial Contraction; Myocardium; Organ Size; Phosphocreatine; Phosphorus; Vitamin D Deficiency

31P nuclear magnetic resonance (NMR) spectroscopy in vivo and fluorometry were used to measure muscle ATP, total creatine, pH, and Mg2+ in vivo; and to calculate creatine phosphate (CrP), the ratios of CrP/inorganic phosphate (Pi), CrP/ATP, free ADP levels, and the free-energy change in ATP hydrolysis so nutritional effects could be ascertained. These parameters were determined in vivo in resting control, 2-d-fasted, and hypocalorically fed rats and in animals similarly hypocalorically fed and then refed. The ATP, Pi, and intracellular Mg2+ levels were comparable in the four groups. When the fasted and underfed animals were compared with the control and refed animals, there were falls in the ratios of CrP/Pi and CrP/ATP, in the calculated CrP, and the free-energy change of ATP hydrolysis, but a rise in the calculated free ADP. In the hypocaloric group, intracellular pH fell significantly and a large peak was noted in the phosphodiester region. The data are consistent with the hypothesis that ATP levels are maintained at the cost of CrP, suggesting that ATP production is disturbed by aerobic and anaerobic mechanisms.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Bicarbonates; Body Weight; Carbon Dioxide; Creatine; Energy Intake; Energy Metabolism; Fasting; Hair; Hydrogen-Ion Concentration; Hydrolysis; Magnesium; Magnetic Resonance Spectroscopy; Male; Muscles; Partial Pressure; Phosphates; Phosphocreatine; Rats; Rats, Inbred Strains; Skin

In rats with phosphoryl-creatine depletion (fed a standard Randoin-Causeret diet containing 1% beta-guanidine propionic acid) abnormal mitochondria were observed in slow skeletal muscles, often containing paracrystalline inclusions very like those induced by ischaemia or mitochondrial poisons and in human mitochondrial myopathy.

Topics: Animals; Body Weight; Creatine; Guanidines; Male; Microscopy, Electron; Mitochondria, Muscle; Muscles; Muscular Diseases; Phosphocreatine; Propionates; Rats; Rats, Inbred Strains; Time Factors

Topics: Animals; Aspartate Aminotransferases; Body Weight; Chelating Agents; Copper; Female; Kidney; L-Lactate Dehydrogenase; Liver; Phosphocreatine; Rats; Trace Elements; Zinc

31P-Nuclear magnetic resonance (NMR) spectroscopy was used to evaluate in vivo rat quadriceps ATP, phosphocreatine (PCr), inorganic phosphate (Pi) and tissue pH during anesthesia with ketamine/xylazine (K/X) or isoflurane (IS). A surface coil was used to receive signals from the quadriceps muscle of rats positioned in a wide-bore horizontal magnet. The PCr/beta-ATP ratios determined from the NMR spectra were 4.34 +/- 0.19 (K/X) and 4.40 +/- 0.28 (IS). Tissue pH was 7.09 +/- 0.05 (K/X) and 7.13 +/- 0.07 (IS). Metabolic stability of quadriceps PCr and ATP was demonstrated during both K/X and IS anesthesia, but the K/X-anesthetized animals had longer sleep time, lower food consumption, and lower body weight post-anesthesia than the IS-anesthetized animals. The PCr/beta-ATP ratio in quadriceps of repetitively IS-anesthetized rats did not fluctuate diurnally. In addition, the animals recovered rapidly and continued to gain weight following the multiple brief IS anesthetic procedures. These data indicate that serial in vivo investigations of high-energy-phosphate metabolism in small animals can be accomplished using 31P-NMR spectroscopy and IS anesthesia, which has several advantages over K/X anesthesia for these types of studies.

Topics: Adenine Nucleotides; Anesthetics; Animals; Body Weight; Circadian Rhythm; Eating; Energy Metabolism; Isoflurane; Ketamine; Magnetic Resonance Spectroscopy; Muscles; Phosphocreatine; Rats; Xylazine

ATP, ADP, phosphocreatine (PCr), creatine (Cr), glucose, malate, sorbitol, and myo-inositol (MI) were measured by quantitative histochemical techniques in pure neuroectodermal tissue of rat embryos of gestation days 11 and 12 that were dissected from normal and streptozocin-induced diabetic mothers. Neither gestational age nor maternal diabetes affected the tissue's energy potential (ATP-to-ADP and PCr-to-Cr ratios). Diabetes resulted in a fourfold rise in the embryonic glucose and a 25% increase in neuroectodermal malate content. Maternal hyperglycemia caused a rise in fetal sorbitol at days 11 and 12 of gestation. The MI content of the neuroectoderm was not affected by the maternal diabetic state in perfusion embryos (day 11); however, the near doubling of MI that occurs from day 11 to day 12 during normal development was prevented. Thus, embryos isolated from diabetic mothers on gestation day 12 had 30% less MI than embryos isolated from normal mothers. From these data we conclude that a rise in tissue sorbitol is not always accompanied by a fall in tissue MI. These results and recent information in the literature implicate involvement of decreased MI concentrations in the process leading to malformation of the nervous system in diabetic embryopathy.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Body Weight; Creatine; Diabetes Mellitus, Experimental; Ectoderm; Embryo, Mammalian; Energy Metabolism; Female; Gestational Age; Glucose; Histocytochemistry; Inositol; Litter Size; Malates; Phosphocreatine; Pregnancy; Pregnancy in Diabetics; Rats; Rats, Inbred Strains; Sorbitol

Myocardial mechanics and high-energy phosphate content [ATP and creatine phosphate (CrP)] of isolated left ventricular papillary muscle preparations from male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were compared at 6 and 18 mo of age. In comparison with oxygenated (95% O2-5% CO2) glucose-supplied (5.5 mM) papillary muscles from hearts of WKY rats, papillary muscles from hypertrophied hearts of the 18-mo-old SHR exhibited a prolonged time to peak tension, electromechanical delay time, and an increase in resting tension measured at the apex of the length-tension curve. Adenine nucleotide (ATP and ADP) contents of oxygenated papillary muscles were not significantly different between SHR and WKY strains at 6 or 18 mo of age, but CrP content of hearts from adult WKY and SHR were higher than for aged WKY and SHR rats. For up to 30 min of hypoxia (95% N2-5% CO2), muscles from the 18-mo-old SHR and WKY rats demonstrated improved tolerance to hypoxia compared with muscles from younger animals. However, at 60 min of hypoxia the 18-mo-old SHR demonstrated lower active tension and adenylate energy charge [(1/2 ADP + ATP)/(ATP + ADP + AMP)]. At higher glucose concentrations (22 mM), both 18-mo-old WKY and SHR demonstrated improved tolerance to hypoxia; moreover, the differences between strains were no longer evident. Following reoxygenation with 5.5 mM glucose, contracture tension and CrP content recovered to near prehypoxic control levels, whereas developed tension and ATP content remained moderately depressed for all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Triphosphate; Aging; Animals; Body Weight; Glucose; Heart; Hypertension; Hypoxia; Isometric Contraction; Organ Size; Phosphocreatine; Rats; Rats, Inbred SHR; Rats, Inbred WKY

The cardiac functional and metabolic consequences of pyridoxine deficiency were studied in rats maintained on a pyridoxine-deficient diet for 10 weeks. Because food intake was diminished in the pyridoxine-deficient rats, a second group of animals was fed a diet restricted to the intake of the pyridoxine-deficient animals. The inotropic response (developed pressure) to an isoproterenol or Ca2+ concentration response curve was measured simultaneously with high energy phosphate levels using a modified Langendorf apparatus and 31P nuclear magnetic resonance spectroscopy. The inotropic response to Ca2+ and isoproterenol was significantly decreased relative to controls in both the food-deprived and the pyridoxine-deficient groups. Developed pressure after adrenergic stimulation was significantly less in the pyridoxine-deficient than in the food-deprived animals. Phosphocreatine and ATP levels were maintained and did not differ among the control, pyridoxine-deficient, and food-deprived groups during isoproterenol and Ca2+ stress, implying that the diminished inotropy was not due to an abnormality in generation of high energy phosphate levels.

Topics: Adenosine Triphosphate; Animals; Body Weight; Calcium; Energy Intake; Heart; Isoproterenol; Myocardial Contraction; Myocardium; Organ Size; Phosphocreatine; Rats; Vitamin B 6 Deficiency

To demonstrate the importance of creatine and phosphocreatine in skeletal muscle during periods of metabolic stress, thyrotoxicosis was induced in mice fed the creatine transport inhibitor, beta-guanidinopropionic acid (beta-GPA). Adding 2% of beta-GPA to the diet of normal mice inhibited weight gain and caused a 75% reduction of creatine and phosphocreatine concentrations in skeletal muscle. Addition of 0.25% or 2% of thyroid powder to the diet of normal mice was associated with hyperactivity, cardiomegaly, and a high mortality rate. Superimposing thyrotoxicosis on mice already depleted of creatine and phosphocreatine resulted in degeneration of muscle fibers. These results indicate that high concentrations of creatine and phosphocreatine are essential for the maintenance of muscle integrity during periods of metabolic stress.

Topics: Animals; Biological Transport; Body Weight; Creatine; Guanidines; Hyperthyroidism; Male; Mice; Muscles; Muscular Diseases; Phosphocreatine; Propionates

The phagocytic behavior of the reticuloendothelial system in the rat was assessed by a quantitative technique following fructose-1,6-diphosphate (FDP) administration. In addition, the effect of FDP on the carbohydrate metabolism of human leukocytes was investigated. The rate of colloidal carbon clearance from the blood was increased significantly in the FDP-treated rats as compared to dextrose and saline controls (p less than 0.001). FDP also attenuated the hepatic decrease of ATP (p less than 0.005) and creatine phosphate (p less than 0.005) that has been observed after intravenous administration of colloidal carbon. Carbohydrate metabolism in human leukocytes was enhanced by FDP, with a concomitant increase in ATP content (p less than 0.001). Experimental evidence suggests that FDP intervenes in the Embden-Meyerhof pathway both as a metabolic regulator and as a high energy substrate. These properties of FDP in stimulating the carbohydrate metabolism have recently been described in man.

Topics: Adenosine Triphosphate; Animals; Body Weight; Carbohydrate Metabolism; Fructosediphosphates; Hexosediphosphates; Humans; Leukocytes; Liver; Mononuclear Phagocyte System; Organ Size; Phagocytosis; Phosphocreatine; Rats; Rats, Inbred Strains; Spleen

The myopathy associated with vitamin D deficiency was examined in vitamin D-deficient and vitamin D-supplemented rats. When compared with either vitamin D-supplemented ad lib. or pair-fed rats, weight gain and muscle mass were decreased in vitamin D-deficient hypocalcemic animals. With the exception of a modest decrease in muscle creatine phosphate levels, muscle composition was unchanged by vitamin D deficiency. Muscle protein turnover rates were determined in both in vivo and in vitro studies and demonstrated that myofibrillar protein degradation was increased in vitamin D deficiency. Normal growth rates could be maintained be feeding the rats vitamin D-deficient diets containing 1.6% calcium, which maintained plasma calcium within the normal range. In addition to its role in maintaining plasma calcium, vitamin D-supplemented rats had significantly higher levels of the anabolic hormone insulin. Vitamin D supplementation may affect muscle protein turnover by preventing hypocalcemia, as well as directly stimulating insulin secretion, rather than by a direct effect within skeletal muscle.

Topics: Animals; Body Weight; Calcium; Cholecalciferol; Insulin; Male; Muscle Proteins; Muscles; Phosphocreatine; Rats; Rats, Inbred Strains; Vitamin D Deficiency

myo-Inositol transport by a viable rat sciatic-nerve preparation is described. Such 'endoneurial' nerve preparations accumulated myo-inositol by an energy-dependent saturable system. Streptozotocin-diabetes reduced myo-inositol transport into sciatic nerve by approx. 40%. Elevated medium glucose concentration reduced myo-inositol transport into control nerves to a similar extent. Fructose and sorbitol did not inhibit myo-inositol transport. Inclusion of an aldose reductase inhibitor in the medium counteracted the reduced myo-inositol transport caused by elevated glucose concentration. The importance of these results to the problem of diabetic neuropathy is discussed.

Topics: Adenosine Triphosphate; Animals; Biological Transport, Active; Body Weight; Diabetes Mellitus, Experimental; Fructose; Glucose; In Vitro Techniques; Inositol; Male; Phosphocreatine; Rats; Rats, Inbred Strains; Sciatic Nerve; Sorbitol

Dietary cyclocreatine has been reported to increase brain high-energy stores in mice and to prolong the generation and utilization of these stores following decapitation. A possible cerebral protective action after 50 days of dietary cyclocreatine 0.5 and 1.0% was therefore examined in mice. Cyclocreatine 0.5% did not increase survival time during hypoxia (5% O2). Cyclocreatine 1.0% in the absence of hypoxia caused significant mortality and decreased weight in survivors despite prophylactic antibiotic treatment. Dietary cyclocreatine offers no cerebral protection against hypoxia in mice.

Topics: Animals; Body Weight; Brain; Decerebrate State; Hypoxia; Imidazolidines; Male; Phosphocreatine; Rats; Time Factors

Creatine administration has no effect on the induction of liver cirrhosis caused by CCl4 in the rat. The muscle creatine content decreases in rats given CCl4 and this change is not modified by creatine treatment. Administered on its own it depresses the level of muscle creatine in normal rats. Creatinine administration increases the uptake of radioactive creatine by the muscle.

Topics: Animals; Body Weight; Collagen; Creatine; Liver Cirrhosis, Experimental; Male; Muscles; Organ Size; Phosphocreatine; Rats; Rats, Inbred Strains

Topics: Animals; Body Weight; Energy Metabolism; Female; Guanidines; Muscle Contraction; Muscles; Phosphocreatine; Propionates; Rats

Cerebral oxidative metabolism during intrauterine growth retardation was investigated utilizing a pregnant-rat model. Dams were subjected to unilateral uterine artery ligation on the 17th day of gestation. At term, they were sacrificed by decapitation and the fetuses delivered by cesarean section. Body and brain weights of fetuses from ligated uterine segments were smaller than those of offspring from nonligated horns of the experimental rats or those from sham-operated dams. Blood glucose at birth was reduced by 25% in growth-retarded fetuses. Cerebral oxidative metabolites, including glycogen, glucose, lactate, ATP, and phosphocreatine, were not different from control levels. These findings suggest that neither tissue hypoxia nor deficient glucose delivery to brain can account for the stunted cerebral growth observed in fetuses following uterine artery ligation.

Topics: Adenosine Triphosphate; Animals; Body Weight; Brain; Female; Fetal Growth Retardation; Fetal Hypoxia; Glucose; Glycogen; Lactates; Organ Size; Oxygen Consumption; Phosphocreatine; Pregnancy; Rats

The purpose of this investigation was to examine the effects of training either once or three times/day on the principal stages of skeletal muscle. The experiments were carried out on male albino rats fed either 3 or 5 times/day a diet containing 20% protein. Experimental animals swam either once or 3 times/day, 6 days/week for 10 weeks with weights attached. The total duration of daily activity was equal for both groups and at 10 weeks each animal was swimming for 60 min/day with 3% of his body weight attached. All the animals were examined at rest after the 10-week training programs. The adequacy of the weight-loading and training schedules was estimated by body weight dynamics and such energy metabolites as creatine phosphate and glycogen. Skeletal muscle RNA and protein synthesis were studied by means of 14C-orotic acid and 14C-leucine incorporation, respectively. Quadriceps and gastrocnemius muscles were used for analysis in all experiments. It was found that the increase in the number of daily training sessions resulted in an increased content and intensity of synthesis of skeletal muscle proteins as evidenced by an increase in the content of amino acids in the muscle, an increased synthesis of both microsomal and ribosomal RNA, an increased stability of (poly-A)-containing messenger RNA, and an increased synthesis of all skeletal muscle protein fractions: myofibrillar, sarcoplasmic, and myostromal.

Topics: Animals; Body Weight; Glycogen; Leucine; Male; Microsomes; Muscle Proteins; Muscles; Orotic Acid; Phosphocreatine; Physical Exertion; Rats; RNA; RNA, Messenger; RNA, Ribosomal; Swimming

The in vivo incorporation of radioactivity from [U-14C]glucose was reduced in undernourished rat pups at ages 6, 10, and 17 days for brain lipids, and at age 10 days for brain amino acids. Brain glucose concentrations were lower at age 20 days (controls 1.58 +/- 0.26 vs. test 1.14 +/- 0.07 mumol/g) but other alterations in brain glucose, glycogen, ATP, or phosphocreatine concentrations were not found. Brain mitochondrial glutamate dehydrogenase activity was 21% and 30% lower in undernourished animals at ages 10 and 20 days, respectively. Brain mitochondrial and supernatant isocitrate dehydrogenase activities and pyruvate kinase activity were similar for undernourished and control animals. Brain glycogen levels were 2-4 times higher in late fetal and newborn control animals (13.6 and 15.3 mumol/g) than in older animals (4.2-5.7 mumol/g). Brain glucose, ATP, and phosphocreatine levels increased from the 15-day fetus to the newborn, but thereafter showed no further increase.

Topics: Adenosine Triphosphate; Amino Acids; Animals; Body Weight; Brain; Glucose; Glutamate Dehydrogenase; Glycogen; Lipid Metabolism; Mitochondria; Nutrition Disorders; Organ Size; Phosphocreatine; Rats

Sprint type strength training was performed 3-4 times a week for 8 weeks by 4 healthy male students (16-18 yrs). The training was carried out on a treadmill at high speed and with high inclination. Muscle biopsies were obtained from vastus lateralis before and after the training period for histochemical classification of slow and fast twitch muscle fibres and for biochemical determination of metabolites and enzyme activities. Muscle fibre type distribution was unchanged, whereas fibre area indicated an increase for both fibre types in 3 subjects after training. The muscle enzyme activities of Mg2+ stimulated ATPase, myokinase and creatine phosphokinase increased 30, 20, and 36 percent, respectively. Muscle concentration of ATP and creatine phosphate (CP) did not change with training. Sargent's jump increased with on average 4 cm (from 47 to 51 cm), maximal voluntary contraction (MVC) with 19 kp (from 165 to 184 kp), and endurance at 50 percent of MVC with 9 s (from 47 to 56 s), respectively. After training all subjects showed a gain in body weight (mean 1.4 kg) and in thigh circumference (mean 1.5 cm) indicating a larger leg muscle volume and consequently also an increase in total ATP and CP.

Topics: Actomyosin; Adenosine Triphosphatases; Adenosine Triphosphate; Adenylate Kinase; Adolescent; Anthropometry; Body Weight; Creatine Kinase; Heart Rate; Humans; L-Lactate Dehydrogenase; Lactates; Male; Muscle Contraction; Muscles; Oxygen Consumption; Phosphocreatine; Phosphotransferases; Physical Exertion; Running; Thigh

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Antimetabolites; Body Weight; Carbon Dioxide; Cardiomegaly; Electrocardiography; Heart; Heart Rate; Hydrogen-Ion Concentration; Lactates; Male; Myocardium; Organ Size; Phosphocreatine; Pyridinium Compounds; Pyrimidines; Pyruvates; Rats; Thiamine; Thiamine Deficiency; Thiazoles

Topics: Adenosine Triphosphate; Amino Acids; Animals; Body Weight; Brain; Brain Chemistry; Carbon Dioxide; Carbon Radioisotopes; Glucose; Glycogen; Hyperthyroidism; Hypothyroidism; Leucine; Lipids; Liver; Organ Size; Phosphocreatine; Rats; Time Factors

Topics: Adenosine Triphosphate; Altitude; Animals; Body Weight; Cardiomegaly; Disease Models, Animal; Heart Ventricles; Hypoxia; Organ Size; Phosphocreatine; Rats; Time Factors

Topics: Adenosine Triphosphate; Animals; Body Weight; Creatine; Energy Metabolism; Glycogen; Growth; Heart Rate; Lactates; Liver Glycogen; Male; Muscles; Myoglobin; Organ Size; Oxygen Consumption; Phosphocreatine; Phosphorus; Physical Exertion; Pyruvates; Rats; Respiration; Stress, Mechanical

Topics: Adenosine Triphosphate; Amino Acids; Animals; Body Weight; Dietary Proteins; Liver; Muscles; Phosphocreatine; Protein Biosynthesis; Proteins; Rats

Topics: Adenosine Triphosphate; Animals; Body Weight; Carbon Isotopes; Cardiomegaly; Female; Glycine; Leucine; Muscle Proteins; Organ Size; Phosphocreatine; Rats

Topics: Adenosine Triphosphate; Adolescent; Blood Pressure; Blood Volume; Body Height; Body Weight; Carbon Dioxide; Cardiac Output; Child; Glucose; Glycogen; Heart Rate; Hemoglobins; Humans; Lactates; Male; Muscles; Oxygen; Oxygen Consumption; Phosphocreatine; Phosphofructokinase-1; Physical Education and Training; Physical Exertion; Potassium; Respiration; Succinate Dehydrogenase

Topics: Adenosine Triphosphate; Animals; Body Weight; Glycogen; Growth; Immobilization; Lactates; Male; Muscles; Organ Size; Oxygen Consumption; Phosphocreatine; Physical Exertion; Pyruvates; Rats

Topics: Adenosine Triphosphate; Adult; Body Height; Body Weight; Fatigue; Glycogen; Humans; Lactates; Male; Methods; Muscle Contraction; Muscles; Phosphocreatine; Physical Exertion; Posture; Thigh; Time Factors

Topics: Adenosine Triphosphate; Animals; Blood Pressure; Body Weight; Cardiac Output; Coronary Circulation; Glycogen; Heart; Hypoxia; Lactates; Male; Myocardium; Oxygen; Oxygen Consumption; Partial Pressure; Phosphocreatine; Physical Education and Training; Pyruvates; Rats; Rats, Inbred Strains; Time Factors

Topics: Adenosine Triphosphate; Adolescent; Adult; Biopsy; Body Weight; Glycogen; Humans; Lactates; Male; Muscles; Oxygen Consumption; Phosphocreatine; Physical Education and Training; Physical Exertion; Skinfold Thickness; Spirometry; Time Factors

Topics: Adenosine Triphosphate; Ammonia; Animals; Body Weight; Brain; Brain Chemistry; Cerebellum; Glutamates; Hydrogen-Ion Concentration; Ketoglutaric Acids; Lactates; NAD; Phosphocreatine; Pyruvates; Quaternary Ammonium Compounds; Rats; Time Factors

Topics: Age Factors; Animals; Body Weight; Glycogen; Liver; Muscles; Phosphocreatine; Rats

Topics: Adenosine Triphosphate; Age Factors; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Blood Glucose; Body Weight; Fasting; Glycogen; Lactates; Lipids; Muscles; Phosphocreatine; Proteins; Swine; Water

Topics: Adult; Biopsy; Body Height; Body Weight; Fatigue; Fluorometry; Glycogen; Glycolysis; Humans; L-Lactate Dehydrogenase; Lactates; Muscles; Oxygen Consumption; Phosphocreatine; Physical Exertion; Potassium; Pyruvates; Sodium; Tissue Extracts; Water

Topics: Adenosine Triphosphate; Aminobutyrates; Animals; Animals, Newborn; Aspartic Acid; Body Weight; Brain; Centrifugation; DNA; Fluorometry; Glucose; Glutamates; Glycogen; Lactates; Liver; Nerve Tissue Proteins; Nutrition Disorders; Phenylalanine; Phosphates; Phosphocreatine; Phosphorus; Rats; RNA; Spectrophotometry

Topics: Adenosine Triphosphate; Animals; Body Weight; Cortisone; Creatine; Creatine Kinase; Diuresis; Fructose-Bisphosphate Aldolase; Male; Muscles; Muscular Atrophy; Phosphocreatine; Phosphorus; Potassium Chloride; Potassium Deficiency; Rabbits

Topics: Adenine Nucleotides; Animals; Body Weight; Cholesterol; Creatine; Glycogen; Heart; Isoproterenol; Lactates; Myocardium; Necrosis; Organ Size; Phosphocreatine; Phospholipids; Propranolol; Rats; Triglycerides