Skeletal muscle ammonia production and repeated, intense exercise in humans

1993 ◽  
Vol 71 (7) ◽  
pp. 484-490 ◽  
Author(s):  
T. Graham ◽  
J. Bangsbo ◽  
B. Saltin
Keyword(s):  
Muscle Glycogen ◽  
Intermittent Exercise ◽  
Lactate Production ◽  
Knee Extensor ◽  
Creatine Phosphate ◽  
High Energy ◽  
High Energy Phosphates ◽  
Wet Weight ◽  
Exercise Fatigue ◽  
The Impact

We investigated the impact of repeated, high-intensity exercise on NH3 metabolism using the single-leg knee extensor model. The muscle glycogen level would be lowered by the initial exercise and low glycogen may stimulate NH3 production independent of any other effects of previous exercise. Therefore a high muscle glycogen condition was included in the protocol so that the pre-exercise glycogen concentration would be at least at a normal resting level for the second exercise. The subjects (n = 6) used previous exercise and (or) diet to begin the exercise with either normal (87.0 ± 14.4 mmol/kg wet weight) or high (176.8 ± 22.9 mmol/kg wet weight) glycogen (C and HG, respectively) in the quadriceps. They exercised (Ex1) one leg to exhaustion (140% leg [Formula: see text]), rested 1 h, repeated the exercise (Ex2), and then repeated the protocol with the opposite leg. The exercise durations of Ex1 and Ex2, respectively, for C were 2.82 ± 0.51 and 2.47 ± 0.47 min (p < 0.05) and for HG were 2.92 ± 0.57 and 2.77 ± 0.50 min. The NH3 efflux was reduced (p < 0.05) from Ex1 to Ex2 in both C (516 ± 159 and 250 ± 69 μmol, respectively) and HG (618 ± 233 and 275 ± 124 μmol, respectively). While NH3 efflux was virtually identical between C and HG in both Ex1 and Ex 2, HG consistently had a greater arterial NH3 concentration (p < 0.05). The decreased efflux in Ex2 compared with Ex1 was not due to greater accumulation of muscle NH3. The changes in creatine phosphate and ATP were very similar in all four exercises; however, the reduced NH3 response in Ex2 was associated with less net lactate production and presumably less muscle acidosis.Key words: AMP deaminase, lactate, purine nucleotide cycle, high energy phosphates, intermittent exercise, fatigue, glycogen.

Effect of hypoxia on myocardial high-energy phosphates in the neonatal mammalian heart

1978 ◽  
Vol 235 (5) ◽  
pp. H475-H481 ◽  
Author(s):  
J. M. Jarmakani ◽  
T. Nagatomo ◽  
M. Nakazawa ◽  
G. A. Langer
Keyword(s):  
Lactate Production ◽  
Creatine Phosphate ◽  
High Energy ◽  
Adult Rabbit ◽  
High Energy Phosphates ◽  
Mechanical Function ◽  
High Energy Phosphate ◽  
Buffer Solution ◽  
Bicarbonate Buffer ◽  
Atp Concentration

The effect of hypoxia on myocardial high-energy phosphate content in the newborn, 2-wk-old, and adult rabbit was determined and compared with mechanical function. Studies were done on the ventricular septum arterially perfused with Krebs-Henseleit bicarbonate buffer solution equilibrated with 95% O2 and 5% CO2 (control) or 95% N2 and 5% CO2 (hypoxia) at 60 beats/min and 27 degrees C. In the adult, ATP concentration decreased to 68%, 56%, and 39% of control after 2, 30, and 60 min of hypoxia, respectively. After 30 min of hypoxia, ATP concentration was not different from control in the newborn but decreased to 82% of control in the 2-wk-old. After 2 min of hypoxia, creatine phosphate concentration decreased to 55% and 10% of control in the newborn and adult rabbit, respectively. Lactate production increased significantly during hypoxia and was greater in the newborn than in the adult. The data indicate that the newborn rabbit is capable of maintaining glycolysis and normal levels of myocardial ATP during hypoxia, which ensures normal myocardial mechanical function for longer periods than in the adult.

Cellular K+ loss and anion efflux during myocardial ischemia and metabolic inhibition

1989 ◽  
Vol 256 (4) ◽  
pp. H1165-H1175 ◽  
Author(s):  
J. N. Weiss ◽  
S. T. Lamp ◽  
K. I. Shine
Keyword(s):  
Inorganic Phosphate ◽  
Lactate Production ◽  
Selective Inhibition ◽  
High Energy ◽  
Metabolic Inhibitors ◽  
Charge Movement ◽  
High Energy Phosphates ◽  
High Energy Phosphate ◽  
Myocardial Hypoxia ◽  
Inhibition Of Glycolysis

It has been suggested that increased K+ efflux during myocardial hypoxia and ischemia may result from efflux of intracellularly generated anions such as lactate and inorganic phosphate (Pi) as a mechanism of balancing transsarcolemmal charge movement. To investigate this hypothesis cellular K+ loss using 42K+ and K+-sensitive electrodes, intracellular potential, venous lactate and Pi, and tissue lactate and high-energy phosphates were measured in isolated arterially perfused rabbit interventricular septa during exposure to metabolic inhibitors, hypoxia, and ischemia. Selective inhibition of glycolysis caused a marked increase in K+ efflux despite a fall in lactate production and maintenance of normal cellular high-energy phosphate content. During ischemia and hypoxia net loss of lactate and Pi exceeded K+ loss by a factor of 2-6. However, removal of glucose prior to ischemia or during hypoxia increased K+ loss but reduced lactate loss without affecting Pi loss. During hypoxia, 30 mM exogenous lactate did not alter K+ loss in a manner consistent with changes in passive electrodiffusion of lactate ion. These findings inhibition which is not related to anion efflux assumes greater importance under conditions in which glycolysis is inhibited, e.g., ischemia. Under conditions in which glycolysis is not inhibited, e.g., hypoxia, K+ efflux does not parallel passive electrodiffusion of lactate ions. However, this finding does not exclude the possibility that K+ loss could be coupled to carrier-mediated lactate ion efflux.

scholarly journals Reductions in mitochondrial O2 consumption and preservation of high-energy phosphate levels after simulated ischemia in chronic hibernating myocardium

2009 ◽  
Vol 297 (1) ◽  
pp. H223-H232 ◽  
Author(s):  
Qingsong Hu ◽  
Gen Suzuki ◽  
Rebeccah F. Young ◽  
Brian J. Page ◽  
James A. Fallavollita ◽  
...  
Keyword(s):  
Mitochondrial Respiration ◽  
Adenine Nucleotides ◽  
Creatine Phosphate ◽  
High Energy ◽  
Atp Depletion ◽  
Hibernating Myocardium ◽  
Wall Thickening ◽  
High Energy Phosphates ◽  
Simulated Ischemia

We performed the present study to determine whether hibernating myocardium is chronically protected from ischemia. Myocardial tissue was rapidly excised from hibernating left anterior descending coronary regions (systolic wall thickening = 2.8 ± 0.2 vs. 5.4 ± 0.3 mm in remote myocardium), and high-energy phosphates were quantified by HPLC during simulated ischemia in vitro (37°C). At baseline, ATP (20.1 ± 1.0 vs. 26.7 ± 2.1 μmol/g dry wt, P < 0.05), ADP (8.1 ± 0.4 vs. 10.3 ± 0.8 μmol/g, P < 0.05), and total adenine nucleotides (31.2 ± 1.3 vs. 40.1 ± 2.9 μmol/g, P < 0.05) were depressed compared with normal myocardium, whereas total creatine, creatine phosphate, and ATP-to-ADP ratios were unchanged. During simulated ischemia, there was a marked attenuation of ATP depletion (5.6 ± 0.9 vs. 13.7 ± 1.7 μmol/g at 20 min in control, P < 0.05) and mitochondrial respiration [145 ± 13 vs. 187 ± 11 ng atoms O2·mg protein−1·min−1 in control (state 3), P < 0.05], whereas lactate accumulation was unaffected. These in vitro changes were accompanied by protection of the hibernating heart from acute stunning during demand-induced ischemia. Thus, despite contractile dysfunction at rest, hibernating myocardium is ischemia tolerant, with reduced mitochondrial respiration and slowing of ATP depletion during simulated ischemia, which may maintain myocyte viability.

Superoxide scavengers augment contractile but not energetic responses to hypoxia in rat diaphragm

2005 ◽  
Vol 98 (5) ◽  
pp. 1753-1760 ◽  
Author(s):  
V. P. Wright ◽  
P. F. Klawitter ◽  
D. F. Iscru ◽  
A. J. Merola ◽  
T. L. Clanton
Keyword(s):  
Contractile Function ◽  
Force Production ◽  
Creatine Phosphate ◽  
High Energy ◽  
Diaphragm Muscle ◽  
Severe Hypoxia ◽  
High Energy Phosphates ◽  
Rat Diaphragm ◽  
Tetanic Force ◽  
Hypoxia Exposure

Acute exposure to severe hypoxia depresses contractile function and induces adaptations in skeletal muscle that are only partially understood. Previous studies have demonstrated that antioxidants (AOXs) given during hypoxia partially protect contractile function, but this has not been a universal finding. This study confirms that specific AOXs, known to act primarily as superoxide scavengers, protect contractile function in severe hypoxia. Furthermore, the hypothesis is tested that the mechanism of protection involves preservation of high-energy phosphates (ATP, creatine phosphate) and reductions of Pi. Rat diaphragm muscle strips were treated with AOXs and subjected to 30 min of hypoxia. Contractile function was examined by using twitch and tetanic stimulations and the degree of elevation in passive force occurring during hypoxia (contracture). High-energy phosphates were measured at the end of 30-min hypoxia exposure. Treatment with the superoxide scavengers 4,5-dihydroxy-1,3-benzenedisulfonic acid (Tiron, 10 mM) or Mn(III)tetrakis(1-methyl-4-pyridyl) porphyrin pentachloride (50 μM) suppressed contracture during hypoxia and protected maximum tetanic force. N-acetylcysteine (10 or 18 mM) had no influence on tetanic force production. Contracture during hypoxia without AOXs was also shown to be dependent on the extracellular Ca2+ concentration. Although hypoxia resulted in only small reductions in ATP concentration, creatine phosphate concentration was decreased to ∼10% of control. There were no consistent influences of the AOX treatments on high-energy phosphates during hypoxia. The results demonstrate that superoxide scavengers can protect contractile function and reduce contracture in hypoxia through a mechanism that does not involve preservation of high-energy phosphates.

Muscle ATP turnover rate during isometric contraction in humans

1986 ◽  
Vol 60 (6) ◽  
pp. 1839-1842 ◽  
Author(s):  
A. Katz ◽  
K. Sahlin ◽  
J. Henriksson
Keyword(s):  
Isometric Contraction ◽  
Turnover Rate ◽  
Knee Extensor ◽  
High Energy ◽  
High Energy Phosphates ◽  
Atp Turnover ◽  
Contraction Duration ◽  
Extensor Muscles ◽  
Before And After ◽  
Fast Twitch

ATP turnover and glycolytic rates during isometric contraction in humans have been investigated. Subjects contracted the knee extensor muscles at two-thirds maximal voluntary force to fatigue (mean +/- SE, 53 +/- 4 s). Biopsies were obtained before and after exercise and analyzed for high-energy phosphates and glycogenolytic-glycolytic intermediates. Total ATP turnover was 190 +/- 7 mmol/kg dry muscle, whereas the average turnover rate was 3.7 +/- 0.2 mmol . kg dry muscle-1 . S-1. The average ATP turnover rate was positively correlated with the percentage of fast-twitch fibers in the postexercise biopsy (r = 0.71; P less than 0.05) and negatively correlated with contraction duration to fatigue (r = -0.88; P less than 0.05). At fatigue, phosphocreatine ranged from 1 to 11 mmol/kg dry muscle (86–99% depletion of value at rest), whereas lactate ranged from 59 to 101. The mean glycolytic rate was 0.83 +/- 0.05 mmol . kg dry muscle-1 . S-1 and was positively correlated with the rate of glucose 6-phosphate accumulation (r = 0.83; P less than 0.05). It is concluded that a major determinant of the ATP turnover rate is the muscle fiber composition, which is probably explained by a higher turnover rate in fast-twitch fibers; fatigue is more closely related to a low phosphocreatine content than to a high lactate content; and the increase in prephosphofructokinase intermediates is important for stimulating glycolysis during contraction.

scholarly journals Redox state and lactate accumulation in human skeletal muscle during dynamic exercise

1987 ◽  
Vol 245 (2) ◽  
pp. 551-556 ◽  
Author(s):  
K Sahlin ◽  
A Katz ◽  
J Henriksson
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Redox State ◽  
Lactate Production ◽  
High Energy ◽  
High Energy Phosphates ◽  
Vo2 Max ◽  
Muscle Lactate ◽  
Lactate Accumulation ◽  
Pyruvate Ratio

The relationship between the redox state and lactate accumulation in contracting human skeletal muscle was investigated. Ten men performed bicycle exercise for 10 min at 40 and 75% of maximal oxygen uptake [VO2(max.)], and to fatigue (4.8 +/- 0.6 min; mean +/- S.E.M.) at 100% VO2(max.). Biopsies from the quadriceps femoris muscle were analysed for NADH, high-energy phosphates and glycolytic intermediates. Muscle NADH was 0.20 +/- 0.02 mmol/kg dry wt. of muscle at rest, and decreased to 0.12 +/- 0.01 (P less than 0.01) after exercise at 40% VO2(max.), but no change occurred in the [lactate]/[pyruvate] ratio. These data, together with previous results on isolated cyanide-poisoned soleus muscle, where NADH increased while [lactate]/[pyruvate] ratio was unchanged [Sahlin & Katz (1986) Biochem. J. 239, 245-248], suggest that the observed changes in muscle NADH occurred within the mitochondria. After exercise at 75 and 100% VO2(max.), muscle NADH increased above the value at rest to 0.27 +/- 0.03 (P less than 0.05) and 0.32 +/- 0.04 (P less than 0.001) mmol/kg respectively. Muscle lactate was unchanged after exercise at 40% VO2(max.), but increased substantially at the higher work loads. At 40% VO2(max.), phosphocreatine decreased by 11% compared with the values at rest, and decreased further at the higher work loads. The decrease in phosphocreatine reflects increased ADP and Pi. It is concluded that muscle NADH decreases during low-intensity exercise, but increases above the value at rest during high-intensity exercise. The increase in muscle NADH is consistent with the hypothesis that the accelerated lactate production during submaximal exercise is due to a limited availability of O2 in the contracting muscle. It is suggested that the increases in NADH, ADP and Pi are metabolic adaptations, which primarily serve to activate the aerobic ATP production, and that the increased anaerobic energy production (phosphocreatine breakdown and lactate formation) is a consequence of these changes.

Transient alterations of creatine, creatine phosphate, N-acetylaspartate and high-energy phosphates after mild traumatic brain injury in the rat

2009 ◽  
Vol 333 (1-2) ◽  
pp. 269-277 ◽  
Author(s):  
Stefano Signoretti ◽  
Valentina Di Pietro ◽  
Roberto Vagnozzi ◽  
Giuseppe Lazzarino ◽  
Angela M. Amorini ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Creatine Phosphate ◽  
High Energy ◽  
High Energy Phosphates

Failing atrial myocardium: energetic deficits accompany structural remodeling and electrical instability

2003 ◽  
Vol 284 (4) ◽  
pp. H1313-H1320 ◽  
Author(s):  
Yong-Mei Cha ◽  
Petras P. Dzeja ◽  
Win K. Shen ◽  
Arshad Jahangir ◽  
Chari Y. T. Hart ◽  
...  
Keyword(s):  
Chronic Atrial Fibrillation ◽  
Creatine Phosphate ◽  
Ventricular Myocardium ◽  
High Energy ◽  
Oxidative Modification ◽  
Potential Contribution ◽  
High Energy Phosphates ◽  
Atrial Myocardium ◽  
Electrical Instability ◽  
Atrial Area

The failing ventricular myocardium is characterized by reduction of high-energy phosphates and reduced activity of the phosphotransfer enzymes creatine kinase (CK) and adenylate kinase (AK), which are responsible for transfer of high-energy phosphoryls from sites of production to sites of utilization, thereby compromising excitation-contraction coupling. In humans with chronic atrial fibrillation (AF) unassociated with congestive heart failure (CHF), impairment of atrial myofibrillar energetics linked to oxidative modification of myofibrillar CK has been observed. However, the bioenergetic status of the failing atrial myocardium and its potential contribution to atrial electrical instability in CHF have not been determined. Dogs with ( n = 6) and without ( n = 6) rapid pacing-induced CHF underwent echocardiography (conscious) and electrophysiological (under anesthesia) studies. CHF dogs had more pronounced mitral regurgitation, higher atrial pressure, larger atrial area, and increased atrial fibrosis. An enhanced propensity to sustain AF was observed in CHF, despite significant increases in atrial effective refractory period and wavelength. Profound deficits in atrial bioenergetics were present with reduced activities of the phosphotransfer enzymes CK and AK, depletion of high-energy phosphates (ATP and creatine phosphate), and reduction of cellular energetic potential (ATP-to-ADP and creatine phosphate-to-Cr ratios). AF duration correlated with left atrial area ( r = 0.73, P = 0.01) and inversely with atrial ATP concentration ( r = −0.75, P = 0.005), CK activity ( r = −0.57, P = 0.054), and AK activity ( r = −0.64, P = 0.02). Atrial levels of malondialdehyde, a marker of oxidative stress, were significantly increased in CHF. Myocardial bioenergetic deficits are a conserved feature of dysfunctional atrial and ventricular myocardium in CHF and may constitute a component of the substrate for AF in CHF.

High-energy phosphate compounds of rat diaphragm and skeletal muscle fibers

1961 ◽  
Vol 200 (1) ◽  
pp. 182-186 ◽  
Author(s):  
Ruth D. Peterson ◽  
Clarissa H. Beatty ◽  
Rose M. Bocek
Keyword(s):  
Uric Acid ◽  
Absorption Maximum ◽  
Room Temperature ◽  
Creatine Phosphate ◽  
High Energy ◽  
High Energy Phosphates ◽  
Rat Diaphragm ◽  
High Energy Phosphate ◽  
Atp Levels

The metabolism of high-energy phosphates in a muscle fiber preparation and diaphragm has been investigated. During dissection the creatine phosphate (CrP) level of fibers decreased but was reconstituted during soaking to 61% of the in situ value and remained uncharged during incubation. Dissection and soaking did not affect the adenosinetriphosphate + adenosinediphosphate (ATP + ADP) levels but incubation caused small decreases. Similar decreases in CrP and ATP levels of diaphragm occurred during incubation. The decreases in the ATP levels in fibers and diaphragm correlated with decreases in adenine absorption. A concomitant shift occurred in the absorption peak of fiber media toward the absorption maximum of hypoxanthine. In contrast, the curves for diaphragm media showed a progressive shift toward the absorption maximum for uric acid. Uricase analyses demonstrated uric acid in diaphragm media. The mesothelial covering of the diaphragm was shown to have a separate and distinct metabolism which converts hypoxanthine to uric acid. Soaking the fibers in iced buffer instead of buffer at room temperature decreased the CrP levels after incubation, ATP values were unaffected.

Exercise hyperthermia as a factor limiting physical performance: temperature effect on muscle metabolism

1985 ◽  
Vol 59 (3) ◽  
pp. 766-773 ◽  
Author(s):  
S. Kozlowski ◽  
Z. Brzezinska ◽  
B. Kruk ◽  
H. Kaciuba-Uscilko ◽  
J. E. Greenleaf ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Muscle Metabolism ◽  
Creatine Phosphate ◽  
High Energy ◽  
High Energy Phosphates ◽  
Glycogen Depletion ◽  
Heavy Exercise ◽  
High Energy Phosphate ◽  
Glycolytic Intermediates ◽  
Temperature Equilibrium

The muscle contents of high-energy phosphates and their derivatives [ATP, ADP, AMP, creatine phosphate (CrP), and creatine], glycogen, some glycolytic intermediates, pyruvate, and lactate were compared in 11 dogs performing prolonged heavy exercise until exhaustion (at ambient temperature 20.0 +/- 1.0 degrees C) without and with trunk cooling using ice packs. Without cooling, dogs were able to run for 57 +/- 8 min, and their rectal (Tre) and muscle (Tm) temperatures increased to 41.8 +/- 0.2 and 43.0 +/- 0.2 degrees C, respectively. Compared with noncooling, duration of exercise with cooling was longer by approximately 45% while Tre and Tm at the time corresponding to the end of exercise without cooling were lower by 1.1 +/- 0.2 and 1.2 +/- 0.2 degrees C, respectively. The muscle contents of high-energy phosphates (ATP + CrP) decreased less, the rate of glycogen depletion was lower, and the increases in the contents of AMP, pyruvate, and lactate as well as in the muscle-to-blood lactate ratio were smaller. The muscle content of lactate was positively correlated with Tm. The data indicate that with higher body temperature equilibrium between high-energy phosphate breakdown and resynthesis was shifted to the lower values of ATP and CrP and glycolysis was accelerated. The results suggest that hyperthermia developing during prolonged muscular work exerts an adverse effect on muscle metabolism that may be relevant to limitation of endurance.

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