Evidence for Abnormal Na+/H+ Antiport Activity Detected by Phosphorus Nuclear Magnetic Resonance Spectroscopy in Exercising Skeletal Muscle of Patients with Essential Hypertension

1990 ◽  
Vol 79 (5) ◽  
pp. 491-497 ◽  
Author(s):  
C. R. K. Dudley ◽  
D. J. Taylor ◽  
L. L. Ng ◽  
G. J. Kemp ◽  
P. J. Ratcliffe ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Essential Hypertension ◽  
Resonance Spectroscopy ◽  
Isotonic Exercise ◽  
Muscle Ph ◽  
Acid Load ◽  
Exercise Induced ◽  
Acid Loading

1. Exercise-induced pH changes in skeletal muscle were studied in a group of eight subjects with essential hypertension by using 31P n.m.r. spectroscopy. 2. Leucocyte Na+/H+ antiport activity was measured in vitro in the same subjects using a pH-sensitive fluorescent dye. 3. Resting skeletal muscle pH and unstimulated leucocyte pH values were similar to those in control subjects, but increased Na+/H+ antiport activity was demonstrated in the leucocytes from hypertensive subjects by acid loading in vitro. Decreased skeletal muscle acidification and an increased rate of pH recovery was also demonstrated in vivo in these same patients during an acid load induced by isotonic exercise. 4. These findings suggest that the increased cellular Na+/H+ antiport activity, which has been demonstrated in vitro in essential hypertension, also affects the biochemical response of skeletal muscle to physiological levels of exercise. This strengthens the argument that increased Na+/H+ antiport activity in hypertension is a generalized and physiologically relevant cellular abnormality.

Carbohydrate metabolism in human skeletal muscle during exercise is not regulated by G-1,6-P2

1988 ◽  
Vol 65 (1) ◽  
pp. 487-489 ◽  
Author(s):  
A. Katz ◽  
K. Sahlin ◽  
J. Henriksson
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Work Load ◽  
Short Term ◽  
Catalytic Function ◽  
Muscle Ph ◽  
Induced Changes ◽  
Femoris Muscle

Glucose 1,6-bisphosphate (G-1,6-P2) is a potent activator of phosphofructokinase (PFK) and an inhibitor of hexokinase in vitro. It has been suggested that increases in G-1,6-P2 are a main means by which PFK can achieve significant catalytic function in vivo despite falling pH and that increases in G-1,6-P2 will inhibit hexokinase in vivo. The purpose of the present study was to determine whether contraction-induced changes in flux through PFK and hexokinase are associated with changes in G-1,6-P2 in skeletal muscle. Ten men performed bicycle exercise for 10 min at 40 and 75% of maximal O2 uptake (VO2max) and to fatigue [4.8 +/- 0.6 (SE) min] at 100% VO2max. Biopsies were obtained from the quadriceps femoris muscle at rest and after each work load and analyzed for G-1,6-P2. G-1,6-P2 averaged 111 +/- 13 mumol/kg dry wt at rest and 121 +/- 16, 123 +/- 15, and 123 +/- 11 mumol/kg dry wt after the low-, moderate-, and high-intensity exercise bouts, respectively (P less than 0.05 for all means vs. rest). Flux through PFK was estimated to increase exponentially as the exercise intensity increased and muscle pH decreased at the higher work loads, whereas flux through hexokinase was estimated to increase during exercise at 40 and 75% VO2max but decrease sharply at 100% VO2max. These data demonstrate that flux through neither PFK nor hexokinase is mediated by changes in G-1,6-P2 in human skeletal muscle during short-term dynamic exercise.

The biological roles of exercise-induced cytokines: IL-6, IL-8, and IL-15

2007 ◽  
Vol 32 (5) ◽  
pp. 833-839 ◽  
Author(s):  
Anders Rinnov Nielsen ◽  
Bente Klarlund Pedersen
Keyword(s):  
Skeletal Muscle ◽  
Systemic Circulation ◽  
Glucose Disposal ◽  
Acid Oxidation ◽  
Tissue Mass ◽  
Protein Levels ◽  
Exercise Induced ◽  
Net Release

Skeletal muscle fibers express several cytokines, including interleukin (IL)-6, IL-8, and IL-15. Solid evidence exists that muscular IL-6 and IL-8 are regulated by muscle contractions, at both the mRNA and the protein levels. IL-6 increases insulin-stimulated glucose disposal and fatty acid oxidation in humans in vivo. Both IL-6 and IL-8 are released from working skeletal muscle, but because IL-6 contributes to the systemic circulation only a small transient net release of IL-8 is found from working muscle, suggesting that IL-8 may exert its effects locally in the muscle. IL-15 is a recently discovered growth factor, which is highly expressed in skeletal muscle. Interestingly, although IL-15 has been demonstrated as having anabolic effects on skeletal muscle in vitro and in vivo, it seems to play a role in reducing adipose tissue mass, and a role for IL-15 in muscle–fat cross-talk has been hypothesized. In conclusion, muscle-derived cytokines appear to have important roles in metabolism, and exercise plays a role in orchestrating the interplay between cytokines and metabolism.

Moderate and intense muscular exercises induce marked intramyocellular metabolic acidosis in sickle cell disease mice

2017 ◽  
Vol 122 (5) ◽  
pp. 1362-1369 ◽  
Author(s):  
Benjamin Chatel ◽  
Laurent A. Messonnier ◽  
Christophe Hourdé ◽  
Christophe Vilmen ◽  
Monique Bernard ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Ph Regulation ◽  
Resonance Spectroscopy ◽  
Cell Disease ◽  
Ph Homeostasis ◽  
Muscle Energetics ◽  
Muscle Ph ◽  
Exercise Induced

Sickle cell disease (SCD) is associated with an impaired oxygen delivery to skeletal muscle that could alter ATP production processes. The present study aimed to determine the effects of sickle hemoglobin (HbS) on muscle pH homeostasis in response to exercise in homozygous (HbSS, n = 9) and heterozygous (HbAS, n = 10) SCD (Townes) mice in comparison to control (HbAA, n = 10) littermates. Magnetic resonance spectroscopy of phosphorus 31 enabled to measure intramuscular pH and phosphocreatine (PCr) concentration during rest-stimulation-recovery protocols at two different intensities. Maximal activity of some enzymes involved in muscle energetics and content of proteins involved in pH regulation were also investigated. HbSS mice presented a more pronounced exercise-induced intramuscular acidosis, whatever the intensity of exercise. Moreover, the depletion of PCr was also exacerbated in HbSS mice in response to intense exercise as compared with both HbAA and HbAS mice ( P < 0.01). While no difference was observed concerning proteins involved in muscle pH regulation, the activity of enolase (a glycolytic enzyme) was higher in both HbSS and HbAS mice as compared with controls ( P < 0.05). Interestingly, HbAS mice presented also metabolic impairments as compared with their control counterparts. This study has identified for the first time an exacerbated exercise-induced intramuscular acidosis in SCD mice.NEW & NOTEWORTHY The main finding of the present study was that the exercise-induced intramuscular acidosis was systematically more pronounced in sickle cell disease (SCD) mice as compared with their control counterparts. This result is important since it has been demonstrated in vitro that acidosis can trigger hemoglobin polymerization. From that point of view, our results tend to support the idea that high-intensity exercise may increase the risk of hemoglobin polymerization in SCD.

Skeletal muscle mitochondrial function studied by kinetic analysis of postexercise phosphocreatine resynthesis

1995 ◽  
Vol 78 (6) ◽  
pp. 2131-2139 ◽  
Author(s):  
C. H. Thompson ◽  
G. J. Kemp ◽  
A. L. Sanderson ◽  
G. K. Radda
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Function ◽  
Maximum Rate ◽  
Atp Synthesis ◽  
Resonance Spectroscopy ◽  
Mitochondrial Regulation ◽  
Cardiac Infarction ◽  
Theoretical Approaches

To investigate mitochondrial regulation and its response to a defect in oxidative metabolism, we used 31P-magnetic resonance spectroscopy to study phosphocreatine (PCr) recovery in rat leg muscle after sciatic nerve stimulation at 1-4 Hz. We studied normal animals and animals with defective skeletal muscle mitochondrial function after experimental cardiac infarction. To analyze these data, we used three current theoretical approaches to the control of mitochondrial ATP synthesis, based on its hyperbolic relationship to cytosolic ADP concentration and on its linear relationships to PCr concentration and the free energy of ATP hydrolysis. The mitochondrial ADP concentration for one-half maximum rate of ATP synthesis appeared at least twice as high as the 30 microM expected from in vitro studies. According to all three approaches, the apparent maximum rate of ATP synthesis was independent of stimulation frequency and end-exercise pH and PCr and ADP concentrations and was reduced by approximately 50% after experimental cardiac infarction. Analysis of PCr recovery kinetics is a robust and practical way to study mitochondrial regulation and to quantify effective mitochondrial defects in vivo.

scholarly journals Comparison of in vivo postexercise phosphocreatine recovery and resting ATP synthesis flux for the assessment of skeletal muscle mitochondrial function

2010 ◽  
Vol 299 (5) ◽  
pp. C1136-C1143 ◽  
Author(s):  
N. M. A. van den Broek ◽  
J. Ciapaite ◽  
K. Nicolay ◽  
J. J. Prompers
Keyword(s):  
Skeletal Muscle ◽  
Oxygen Consumption ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Atp Synthesis ◽  
Resonance Spectroscopy ◽  
Isolated Mitochondria ◽  
Significant Difference

31P magnetic resonance spectroscopy (MRS) has been used to assess skeletal muscle mitochondrial function in vivo by measuring 1) phosphocreatine (PCr) recovery after exercise or 2) resting ATP synthesis flux with saturation transfer (ST). In this study, we compared both parameters in a rat model of mitochondrial dysfunction with the aim of establishing the most appropriate method for the assessment of in vivo muscle mitochondrial function. Mitochondrial dysfunction was induced in adult Wistar rats by daily subcutaneous injections with the complex I inhibitor diphenyleneiodonium (DPI) for 2 wk. In vivo 31P MRS measurements were supplemented by in vitro measurements of oxygen consumption in isolated mitochondria. Two weeks of DPI treatment induced mitochondrial dysfunction, as evidenced by a 20% lower maximal ADP-stimulated oxygen consumption rate in isolated mitochondria from DPI-treated rats oxidizing pyruvate plus malate. This was paralleled by a 46% decrease in in vivo oxidative capacity, determined from postexercise PCr recovery. Interestingly, no significant difference in resting, ST-based ATP synthesis flux was observed between DPI-treated rats and controls. These results show that PCr recovery after exercise has a more direct relationship with skeletal muscle mitochondrial function than the ATP synthesis flux measured with 31P ST MRS in the resting state.

scholarly journals Intracellular energetics and critical Po2 in resting ischemic human skeletal muscle in vivo

2010 ◽  
Vol 299 (5) ◽  
pp. R1415-R1422 ◽  
Author(s):  
Ian R. Lanza ◽  
Michael A. Tevald ◽  
Douglas E. Befroy ◽  
Jane A. Kent-Braun
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Ex Vivo ◽  
High Energy ◽  
Resonance Spectroscopy ◽  
High Energy Phosphates ◽  
Atp Production ◽  
Resting Muscle

During ischemia and some types of muscular contractions, oxygen tension (Po2) declines to the point that mitochondrial ATP synthesis becomes limited by oxygen availability. Although this critical Po2 has been determined in animal tissue in vitro and in situ, there remains controversy concerning potential disparities between values measured in vivo and ex vivo. To address this issue, we used concurrent heteronuclear magnetic resonance spectroscopy (MRS) to determine the critical intracellular Po2 in resting human skeletal muscle in vivo. We interleaved measurements of deoxymyoglobin using 1H-MRS with measures of high-energy phosphates and pH using 31P-MRS, during 15 min of ischemia in the tibialis anterior muscles of 6 young men. ATP production and intramyocellular Po2 were quantified throughout ischemia. Critical Po2, determined as the Po2 corresponding to the point where PCr begins to decline (PCrip) in resting muscle during ischemia, was 0.35 ± 0.20 Torr, means ± SD. This in vivo value is consistent with reported values ex vivo and does not support the notion that critical Po2 in resting muscle is higher when measured in vivo. Furthermore, we observed a 4.5-fold range of critical Po2 values among the individuals studied. Regression analyses revealed that time to PCrip was associated with critical Po2 and the rate of myoglobin desaturation ( r = 0.83, P = 0.04) but not the rate of ATP consumption during ischemia. The apparent dissociation between ATP demand and myoglobin deoxygenation during ischemia suggests that some degree of uncoupling between intracellular energetics and oxygenation is a potentially important factor that influences critical Po2 in vivo.

In vitro Lipolysis as a Tool for the Establishment of IVIVC for Lipid-Based Drug Delivery Systems

2019 ◽  
Vol 16 (8) ◽  
pp. 688-697
Author(s):  
Ravinder Verma ◽  
Deepak Kaushik
Keyword(s):  
Drug Delivery ◽  
Ph Value ◽  
Electron Paramagnetic Resonance Spectroscopy ◽  
Rapid Screening ◽  
Resonance Spectroscopy ◽  
Fed State ◽  
In Vitro Lipolysis ◽  
Ph Stat

: In vitro lipolysis has emerged as a powerful tool in the development of in vitro in vivo correlation for Lipid-based Drug Delivery System (LbDDS). In vitro lipolysis possesses the ability to mimic the assimilation of LbDDS in the human biological system. The digestion medium for in vitro lipolysis commonly contains an aqueous buffer media, bile salts, phospholipids and sodium chloride. The concentrations of these compounds are defined by the physiological conditions prevailing in the fasted or fed state. The pH of the medium is monitored by a pH-sensitive electrode connected to a computercontrolled pH-stat device capable of maintaining a predefined pH value via titration with sodium hydroxide. Copenhagen, Monash and Jerusalem are used as different models for in vitro lipolysis studies. The most common approach used in evaluating the kinetics of lipolysis of emulsion-based encapsulation systems is the pH-stat titration technique. This is widely used in both the nutritional and the pharmacological research fields as a rapid screening tool. Analytical tools for the assessment of in vitro lipolysis include HPLC, GC, HPTLC, SEM, Cryo TEM, Electron paramagnetic resonance spectroscopy, Raman spectroscopy and Nanoparticle Tracking Analysis (NTA) for the characterization of the lipids and colloidal phases after digestion of lipids. Various researches have been carried out for the establishment of IVIVC by using in vitro lipolysis models. The current publication also presents an updated review of various researches in the field of in vitro lipolysis.

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