Lactate efflux from exercising human skeletal muscle: role of intracellular P O 2

1998 ◽  
Vol 85 (2) ◽  
pp. 627-634 ◽  
Author(s):  
Russell S. Richardson ◽  
Elizabeth A. Noyszewski ◽  
John S. Leigh ◽  
Peter D. Wagner

It remains controversial whether lactate formation during progressive dynamic exercise from submaximal to maximal effort is due to muscle hypoxia. To study this question, we used direct measures of arterial and femoral venous lactate concentration, a thermodilution blood flow technique, phosphorus magnetic resonance spectroscopy (MRS), and myoglobin (Mb) saturation measured by 1H nuclear MRS in six trained subjects performing single-leg quadriceps exercise. We calculated net lactate efflux from the muscle and intracellular[Formula: see text] with subjects breathing room air and 12% O2. Data were obtained at 50, 75, 90, and 100% of quadriceps maximal O2 consumption at each fraction of inspired O2. Mb saturation was significantly lower in hypoxia than in normoxia [40 ± 3 vs. 49 ± 3% (SE)] throughout incremental exercise to maximal work rate. With the assumption of a[Formula: see text] at which 50% of Mb-binding sites are bound with O2 of 3.2 Torr, Mb-associated [Formula: see text] averaged 3.1 ± 0.3 and 2.3 ± 0.2 Torr in normoxia and hypoxia, respectively. Net blood lactate efflux was unrelated to intracellular[Formula: see text] across the range of incremental exercise to maximum ( r = 0.03 and 0.07 in normoxia and hypoxia, respectively) but linearly related to O2 consumption ( r = 0.97 and 0.99 in normoxia and hypoxia, respectively) with a greater slope in 12% O2. Net lactate efflux was also linearly related to intracellular pH ( r = 0.94 and 0.98 in normoxia and hypoxia, respectively). These data suggest that with increasing work rate, at a given fraction of inspired O2, lactate efflux is unrelated to muscle cytoplasmic [Formula: see text], yet the efflux is higher in hypoxia. Catecholamine values from comparable studies are included and indicate that lactate efflux in hypoxia may be due to systemic rather than intracellular hypoxia.

Author(s):  
T Mann

Background. Lactate or, as it was customarily known, ‘lactic acid’ was one of the first molecules to attract the attention of early exercise scientists, mainly because blood lactate concentration could be measured and was shown to increase with increasing exercise intensity. This connection resulted in lactate being associated with numerous other events associated with high-intensity exercise including muscle cramps, fatigue, acidosis and post-exercise muscle soreness. Nobel prize-winning research by AV Hill and Otto Meyerhof provided a rational explanation linking lactate to anaerobiosis and acidosis, which resulted in this relationship being widely accepted as fact. It was only following isotopic tracer studies of George Brooks and others that the true role of lactate during rest and exercise was revealed. Conclusions. Lactate is now acknowledged as an important intermediate of carbohydrate metabolism, taken up from the blood by tissues such as skeletal and cardiac muscle as a substrate for oxidation. Furthermore, lactate formation consumes a proton, thereby buffering against muscle acidosis. For this reason, lactate production forms an essential aid to endurance performance rather than a hindrance.


1986 ◽  
Vol 60 (3) ◽  
pp. 777-781 ◽  
Author(s):  
J. Simon ◽  
J. L. Young ◽  
D. K. Blood ◽  
K. R. Segal ◽  
R. B. Case ◽  
...  

Six trained male cyclists and six untrained sedentary men were studied to determine whether the plasma lactate threshold (PLT) and ventilation threshold (VT) occur at the same work rate in both fit and unfit populations. The PLT was determined from a marked increase in plasma lactate concentration ([La]) and VT from a nonlinear increase in expired minute ventilation (VE) during incremental leg-cycling tests; work rate was increased 30 W every 2 min until volitional exhaustion. The trained subjects' mean VO2 max (63.8 ml O2 X kg-1 X min-1) and VT (65.8% VO2 max) were significantly higher (P less than 0.05) than the untrained subjects' mean VO2max (35.5 ml O2 X kg-1 X min-1) and VT (51.4% VO2 max). The trained subjects' mean PLT (68.8% VO2 max) and VT did not differ significantly, but the untrained subjects' mean PLT (61.6% VO2 max) was significantly higher than their VT. The trained subjects' mean peak [La] (10.5 mmol X l-1) did not differ significantly from the untrained subjects' mean peak [La] (11.5 mmol X l-1). However, the time of appearance of the peak [La] during passive recovery was inversely related to VO2 max. These results suggest that variance in lactate diffusion and/or removal processes between the trained and untrained subjects may account in part for the different relationships between the VT and PLT in each population.


Author(s):  
T Mann

Background. Lactate or, as it was customarily known, ‘lactic acid’ was one of the first molecules to attract the attention of early exercise scientists, mainly because blood lactate concentration could be measured and was shown to increase with increasing exercise intensity. This connection resulted in lactate being associated with numerous other events associated with high-intensity exercise including muscle cramps, fatigue, acidosis and post-exercise muscle soreness. Nobel prize-winning research by AV Hill and Otto Meyerhof provided a rational explanation linking lactate to anaerobiosis and acidosis, which resulted in this relationship being widely accepted as fact. It was only following isotopic tracer studies of George Brooks and others that the true role of lactate during rest and exercise was revealed. Conclusions. Lactate is now acknowledged as an important intermediate of carbohydrate metabolism, taken up from the blood by tissues such as skeletal and cardiac muscle as a substrate for oxidation. Furthermore, lactate formation consumes a proton, thereby buffering against muscle acidosis. For this reason, lactate production forms an essential aid to endurance performance rather than a hindrance.


1999 ◽  
Vol 86 (3) ◽  
pp. 1048-1053 ◽  
Author(s):  
R. S. Richardson ◽  
B. Grassi ◽  
T. P. Gavin ◽  
L. J. Haseler ◽  
K. Tagore ◽  
...  

Maximal O2 delivery and O2 uptake (V˙o 2) per 100 g of active muscle mass are far greater during knee extensor (KE) than during cycle exercise: 73 and 60 ml ⋅ min−1 ⋅ 100 g−1 (2.4 kg of muscle) (R. S. Richardson, D. R. Knight, D. C. Poole, S. S. Kurdak, M. C. Hogan, B. Grassi, and P. D. Wagner. Am. J. Physiol. 268 ( Heart Circ. Physiol. 37): H1453–H1461, 1995) and 28 and 25 ml ⋅ min−1 ⋅ 100 g−1 (7.5 kg of muscle) (D. R. Knight, W. Schaffartzik, H. J. Guy, R. Predilleto, M. C. Hogan, and P. D. Wagner. J. Appl. Physiol. 75: 2586–2593, 1993), respectively. Although this is evidence of muscle O2 supply dependence in itself, it raises the following question: With such high O2 delivery in KE, are the quadriceps still O2 supply dependent at maximal exercise? To answer this question, seven trained subjects performed maximum KE exercise in hypoxia [0.12 inspired O2 fraction ([Formula: see text])], normoxia (0.21 [Formula: see text]), and hyperoxia (1.0 [Formula: see text]) in a balanced order. The protocol (after warm-up) was a square wave to a previously determined maximum work rate followed by incremental stages to ensure that a true maximum was achieved under each condition. Direct measures of arterial and venous blood O2 concentration in combination with a thermodilution blood flow technique allowed the determination of O2 delivery and muscleV˙o 2. Maximal O2 delivery increased with inspired O2: 1.3 ± 0.1, 1.6 ± 0.2, and 1.9 ± 0.2 l/min at 0.12, 0.21, and 1.0 [Formula: see text], respectively ( P < 0.05). Maximal work rate was affected by variations in inspired O2 (−25 and +14% at 0.12 and 1.0 [Formula: see text], respectively, compared with normoxia, P < 0.05) as was maximal V˙o 2(V˙o 2 max): 1.04 ± 0.13, 1.24 ± 0.16, and 1.45 ± 0.19 l/min at 0.12, 0.21, and 1.0[Formula: see text], respectively ( P < 0.05). Calculated mean capillary [Formula: see text] also varied with[Formula: see text] (28.3 ± 1.0, 34.8 ± 2.0, and 40.7 ± 1.9 Torr at 0.12, 0.21, and 1.0 [Formula: see text], respectively, P < 0.05) and was proportionally related to changes inV˙o 2 max, supporting our previous finding that a decrease in O2 supply will proportionately decrease muscleV˙o 2 max. As even in the isolated quadriceps (where normoxic O2 delivery is the highest recorded in humans) an increase in O2 supply by hyperoxia allows the achievement of a greater V˙o 2 max, we conclude that, in normoxic conditions of isolated KE exercise, KEV˙o 2 max in trained subjects is not limited by mitochondrial metabolic rate but, rather, by O2 supply.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Monica del C. Gomez-Alonso ◽  
Anja Kretschmer ◽  
Rory Wilson ◽  
Liliane Pfeiffer ◽  
Ville Karhunen ◽  
...  

Abstract Background The discovery of robust and trans-ethnically replicated DNA methylation markers of metabolic phenotypes, has hinted at a potential role of epigenetic mechanisms in lipid metabolism. However, DNA methylation and the lipid compositions and lipid concentrations of lipoprotein sizes have been scarcely studied. Here, we present an epigenome-wide association study (EWAS) (N = 5414 total) of mostly lipid-related metabolic measures, including a fine profiling of lipoproteins. As lipoproteins are the main players in the different stages of lipid metabolism, examination of epigenetic markers of detailed lipoprotein features might improve the diagnosis, prognosis, and treatment of metabolic disturbances. Results We conducted an EWAS of leukocyte DNA methylation and 226 metabolic measurements determined by nuclear magnetic resonance spectroscopy in the population-based KORA F4 study (N = 1662) and replicated the results in the LOLIPOP, NFBC1966, and YFS cohorts (N = 3752). Follow-up analyses in the discovery cohort included investigations into gene transcripts, metabolic-measure ratios for pathway analysis, and disease endpoints. We identified 161 associations (p value < 4.7 × 10−10), covering 16 CpG sites at 11 loci and 57 metabolic measures. Identified metabolic measures were primarily medium and small lipoproteins, and fatty acids. For apolipoprotein B-containing lipoproteins, the associations mainly involved triglyceride composition and concentrations of cholesterol esters, triglycerides, free cholesterol, and phospholipids. All associations for HDL lipoproteins involved triglyceride measures only. Associated metabolic measure ratios, proxies of enzymatic activity, highlight amino acid, glucose, and lipid pathways as being potentially epigenetically implicated. Five CpG sites in four genes were associated with differential expression of transcripts in blood or adipose tissue. CpG sites in ABCG1 and PHGDH showed associations with metabolic measures, gene transcription, and metabolic measure ratios and were additionally linked to obesity or previous myocardial infarction, extending previously reported observations. Conclusion Our study provides evidence of a link between DNA methylation and the lipid compositions and lipid concentrations of different lipoprotein size subclasses, thus offering in-depth insights into well-known associations of DNA methylation with total serum lipids. The results support detailed profiling of lipid metabolism to improve the molecular understanding of dyslipidemia and related disease mechanisms.


2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Gabriel Sigmund ◽  
Cristina Santín ◽  
Marc Pignitter ◽  
Nathalie Tepe ◽  
Stefan H. Doerr ◽  
...  

AbstractGlobally landscape fires produce about 256 Tg of pyrogenic carbon or charcoal each year. The role of charcoal as a source of environmentally persistent free radicals, which are precursors of potentially harmful reactive oxygen species, is poorly constrained. Here, we analyse 60 charcoal samples collected from 10 wildfires, that include crown as well as surface fires in forest, shrubland and grassland spanning different boreal, temperate, subtropical and tropical climate. Using electron spin resonance spectroscopy, we measure high concentrations of environmentally persistent free radicals in charcoal samples, much higher than those found in soils. Concentrations increased with degree of carbonization and woody fuels favoured higher concentrations. Moreover, environmentally persistent free radicals remained stable for an unexpectedly long time of at least 5 years. We suggest that wildfire charcoal is an important global source of environmentally persistent free radicals, and therefore potentially of harmful reactive oxygen species.


Author(s):  
Witalo Kassiano ◽  
Bruna Daniella de Vasconcelos Costa ◽  
João Pedro Nunes ◽  
Andreo Fernando Aguiar ◽  
Belmiro F. de Salles ◽  
...  

AbstractSpecialized resistance training techniques (e.g., drop-set, rest-pause) are commonly used by well-trained subjects for maximizing muscle hypertrophy. Most of these techniques were designed to allow a greater training volume (i.e., total repetitions×load), due to the supposition that it elicits greater muscle mass gains. However, many studies that compared the traditional resistance training configuration with specialized techniques seek to equalize the volume between groups, making it difficult to determine the inherent hypertrophic potential of these advanced strategies, as well as, this equalization restricts part of the practical extrapolation on these findings. In this scenario, the objectives of this manuscript were 1) to present the nuance of the evidence that deals with the effectiveness of these specialized resistance training techniques and — primarily — to 2) propose possible ways to explore the hypertrophic potential of such strategies with greater ecological validity without losing the methodological rigor of controlling possible intervening variables; and thus, contributing to increasing the applicability of the findings and improving the effectiveness of hypertrophy-oriented resistance training programs.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii159-ii160
Author(s):  
Roberta Rudà ◽  
Riccardo Pascuzzo ◽  
Francesca Mo ◽  
Alessia Pellerino ◽  
Peter B Barker ◽  
...  

Abstract BACKGROUND There is lack of information on the role of excitatory and inhibitory neurotransmitters in the development of seizures in patients with lower grade gliomas. Increase of glutamate and downregulation of GABA have been suggested in preclinical models and human surgical samples to be associated with brain tumor-related epilepsy. MATERIAL AND METHODS We prospectively investigated with the use of magnetic resonance spectroscopy (MRS) the differences in the ratio of metabolites (glutamate/GABA, glutamate/creatine and GABA/creatine) in the peritumoral areas between patients with or without seizures in a series of lower grade gliomas. Tumors were classified according to WHO Classification of 2016 as follows:11 grade II IDH mutated and 1p/19q codeleted; 3 grade III IDH mutated and 1p/19q codeleted; 6 grade II IDH mutated and 1p/19q intact; 1 grade III IDH mutated and 1p/19q intact; 1 grade II IDH wild-type. Patients received surgery alone or followed by temozolomide chemotherapy according to the presence of risk factors. RESULTS At baseline evaluation, maximum glutamate/GABA values were significantly higher (p=0.023) in the peritumoral area of patients with seizures (1.008 ± 0.368) with respect to those without seizures (0.691 ± 0.170). No other metabolites ratio showed significant differences between the two groups. Similar results were obtained when analyzing the metabolites ratio in the examinations during the follow-up. In the cohort of patients with seizures (n.14) variations of metabolite ratios were not associated with tumor location, 1p/19q codeletion, use of AEDs, concomitant chemotherapy or seizure characteristics (type, duration, frequency). CONCLUSIONS The study is ongoing with the aim of analyzing further the correlations between ratio of metabolites and status of the tumor (stable vs progressive).


2006 ◽  
Vol 5 (6) ◽  
pp. 916-923 ◽  
Author(s):  
Crystal R. Icenhour ◽  
Theodore J. Kottom ◽  
Andrew H. Limper

ABSTRACT Pneumocystis continues to represent an important opportunistic fungal pathogen of those with compromised immunity. Thus, it is crucial to identify factors that affect its viability and pathogenicity. We previously reported the first identification of melanins in Pneumocystis. In the present study, we sought to further characterize these components and define the function for these melanins. Melanins extracted from Pneumocystis and melanized Pneumocystis cells were analyzed by electron spin resonance spectroscopy, revealing spectra consistent with melanins from other fungi. Immunofluorescence assays using anti-melanin monoclonal antibodies showed that melanins are widely present across Pneumocystis host species, including mouse-, ferret-, and human-derived Pneumocystis organisms, as well as Pneumocystis carinii derived from rat. Using immunoelectron microscopy, melanins were found to localize to the cell wall and cytoplasm of P. carinii cysts, as well as to intracystic bodies within mature cysts. Next, the role of melanins on the maintenance of Pneumocystis viability was determined by using quantitative reverse transcription-PCR measurement of the heat shock protein mRNA under adverse environmental conditions. Using a new method to promote the melanization of Pneumocystis, we observed that strongly melanized Pneumocystis retained viability to a greater degree when exposed to UV irradiation or desiccation compared to less-pigmented organisms. These studies support our previous identification of Pneumocystis melanins across the genus, further characterize these Pneumocystis components, and demonstrate that melanins protect Pneumocystis from environmental stressors.


Sign in / Sign up

Export Citation Format

Share Document