Muscle Lactate Research Articles

L-theanine attenuates transport stress-induced impairment of meat quality of broilers through improving muscle antioxidant status

This study was to investigate the effect of dietary L-theanine (THE) supplementation (0, 600mg/kg) on growth performance, carcass traits, immune organ indexes, meat quality, and muscle antioxidant status of transported broilers. A total of 180 one-day-old male Ross 308 broilers were randomly allotted to 2 treatment groups including a THE-free group with 12 replicates of 10 birds each and a THE group with 6 replicates of 10 birds each. On the morning of day 42, after a 9-h fast, the birds of THE-free group were divided into 2 equal groups, and then all birds in the 3 groups were placed into 18 crates and were transported according to the following protocols: 0-h transport of birds in the THE-free group (control group), 3-h transport of birds in the THE-free group (T group), and 3-h transport of birds in the THE group (T + THE group). Results showed that dietary THE supplementation improved feed conversion ratio and birds' final body weight (P < 0.05), while transport and dietary THE supplementation did not affect carcass traits of broilers (P > 0.05). Transport increased bird live weight loss, drip loss, L*24h, muscle malondialdehyde (MDA), protein carbonyl (PC) and lactate contents, while it decreased thymus, spleen, and bursa of Fabricius indexes, pH24h, a*, and muscle total antioxidant capacity (T-AOC), catalase (CAT), and glutathione peroxidase (GSH-PX) activities and glycogen content (P < 0.05). Nevertheless, compared with birds in the T group, birds in the T + THE group exhibited increased thymus, spleen, and bursa of Fabricius indexes, pH24h, a*24h, and muscle T-AOC, CAT, and GSH-PX activities and glycogen content, and decreased drip loss, L*24h, and muscle MDA, PC, and lactate contents (P < 0.05). This study provided the first evidence that dietary THE supplementation prevented transport-stress-impaired immune organ indexes and meat quality of broilers, and the reason for maintenance of meat quality by supplementation of THE may be partly ascribed to the changed muscle glycolysis metabolism and antioxidant status.

Regulation of lactate production through p53/β-enolase axis contributes to statin-associated muscle symptoms.

BackgroundStatin-associated muscle symptoms (SAMS) are the major adverse effects of the class of widely used lipid-lowering agents, and the underlying mechanism remains elusive. In this study, we investigated the potential contribution and molecular mechanism of increased lactate production to SAMS in mice.MethodsC57BL/6 J mice were administrated with lovastatin and exercise capacity and blood and muscle lactate levels were measured. A variety of metabolic and molecular experiments were carried out on skeletal muscle cell lines A-204 and C2C12 to confirm the in vivo findings, and to delineate the molecular pathway regulating lactate production by statins.FindingsBlood lactate levels of mice treated with lovastatin increased 23% compared to the control group, which was reproduced in type II predominant glycolytic muscles, accompanied with a 23.1% decrease of maximum swim duration time. The in vitro evidence revealed that statins increased the expression of muscle specific glycolytic enzyme β-enolase through promoting the degradation of basal p53 proteins, resulting in increased of lactate production. Co-administered with dichloroacetate (DCA), a reagent effective in treating lactic acidosis, reverted the elevated lactate levels and the decreased exercise capacity.InterpretationElevated lactate production by statins through the p53/β-enolase axis contributes to SAMS.FundThis work was supported by grants from the Science and Technology Development Fund (FDCT) of Macau (Project codes: 034/2015/A1 and 0013/2019/A1).

Differences in metabolism of triploid and diploidSalmo trutta f. lacustrisunder acclimation conditions and after exposure to stress situations

Differences in metabolism (enzyme activities, metabolites) between diploid and triploid Salmo trutta f. lacustris were investigated under acclimation and stress conditions. Under acclimation conditions enzyme activities differed for 35% of the 27 investigated key regulatory enzymes and temperature optima for 23%. Muscle and liver metabolites related to energy metabolism and diagnostic indices of blood serum were similar, with exception of acetyl-CoA being increased in triploids. Metabolic rate was lower and gill ventilation rate higher in triploids in comparison with diploids. During the tested stress situations (24 hr endurance swimming, 3 hr exposure to hypoxia in water with 32% oxygen saturation) muscle and liver glycogen decreased and serum and muscle lactate increased in both ploidy levels. Specifically, for triploids muscle adenylate energy charge and phosphocreatine levels decreased after endurance swimming and muscle and liver adenylate energy charge after exposure to hypoxia. Acetyl-CoA increased in triploids during both stress situations. In summary, there existed differences in metabolism between the two ploidy levels and the energy metabolism of triploids was less balanced under stress.

MicroRNA-140 inhibits skeletal muscle glycolysis and atrophy in endotoxin-induced sepsis in mice via the WNT signaling pathway.

Sepsis is a systemic inflammatory response syndrome resulting from infection. This study aimed at exploring the role of microRNA-140 (miR-140) in septic mice. Wnt family member 11 (WNT11) was verified to be a target gene of miR-140 after bioinformatic prediction and dual luciferase reporter gene assay. Importantly, miR-140 negatively regulated WNT11. We initially induced the model of sepsis by endotoxin, and then ectopic expression and knockdown experiments were performed to explore the functional role of miR-140 in sepsis. Additionally, cross-sectional areas of muscle fiber, lactic acid production, 3-methylhistidine (3-MH) and tyrosine (Tyr) production in extensor digitorium longus (EDL) muscles, and serum levels of inflammatory factors were examined. The effect of miR-140 on the expression of WNT signaling pathway-related and apoptosis-related factors in skeletal muscle tissue was determined. The experimental results indicated that upregulated miR-140 or silenced WNT11 increased cross-sectional areas of muscle fiber while decreasing lactic acid production, skeletal muscle cell apoptosis [corresponding to downregulated B cell lymphoma 2 (Bcl-2)-associated X protein (Bax) and caspase-3 and upregulated Bcl-2], and the proteolytic rate of Tyr and 3-MH. Also, overexpressed miR-140 or silenced WNT11 reduced inflammation as reflected by decreased serum levels of IL-6, IL-10, and TNF-α. Furthermore, overexpression of miR-140 was shown to suppress the activation of the WNT signaling pathway, accompanied by decreased expression of WNT11, β-catenin, and GSK-3β. Taken together, upregulation of miR-140 could potentially inhibit skeletal muscle lactate release, an indirect measure of glycolysis, and atrophy in septic mice through suppressing the WNT signaling pathway via inhibiting WNT11 expression.

Metabolic and anti-oxidative stress responses to low temperatures during the waterless preservation of the hybrid grouper (Epinephelus fuscogutatus♀ × Epinephelus lanceolatus♂)

Waterless transportation is an alternative method of live aquatic product transportation, which may reduce shipping costs and increase the survival rates of some species. Groupers are economically important fishes that are widely cultivated in Asian countries. However, the waterless transportation of live groupers has yet to be studied. A key to the success of live waterless transportation is the preservation temperature, which needs to be empirically determined for each species. The hybrid pearl gentian grouper (♀E. fuscogutatus × ♂E. lanceolatus) has become the main farmed grouper species in China due to its superior growth performance. In this study, we investigated the effects of temperature on the survival, metabolism, and oxidative stress responses of the pearl gentian grouper during waterless preservation after cold-induced dormancy. Our results showed that the grouper survival duration was 10 h at 15 °C and 18 °C, twice as long as the survival duration at 13 °C and 25 °C (5 h). Levels of serum cortisol, as well as the activity levels of the metabolic enzymes aspartate amino transferase (AST), alanine amino transferase (ALT), acid phosphatase (ACP), and alkaline phosphatase (AKP), were not significantly different between the untreated fishes and the fishes preserved without water for 5 h at 15 °C and 18 °C. In addition, the activity levels of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) in liver and brain tissues of the waterless-preserved fishes were significantly higher than the untreated fishes, while the malondialdehyde (MDA) content was decreased. In the waterless-preserved fishes, blood glucose levels were increased 15.32-fold at 15 °C and 10.99-fold at 18 °C, as compared to the untreated fish, while muscle lactate levels were reduced by 28.21%. There were no significant differences in the levels of free amino acids in the muscle between the untreated and waterless-preserved fishes. Therefore, waterless preservation at 15 °C or 18 °C improved the survival of the pearl gentian groupers by stimulating antioxidant enzyme activity and increasing serum glucose levels. Our study represents the first successful application of waterless preservation techniques to live groupers, sufficient for medium or long distance transportation.

Short-time Transport Stress Affected Biochemical Parameters in Takifugu Rubripes

Transport manipulation is a routine practice during the culture of fishes. Stress responses will occur during transport. In order to assess the impact of short-time transport on the health of juvenile Takifugu rubripes, a 30-minute simulated transportation was carried out. Result showed that Lactate and LDH in serum, muscle and liver of test fish respond rapidly after transport. Serum antioxidative and immune parameters, liver function parameters also changed significantly after transport. Most parameters recovered at 168 hour after transport. In conclusion, at least 168 hours recovery time is recommended forTakifugu rubripes suffered 30 minutes transport stress.

Inclusion of sprints in moderate intensity continuous training leads to muscle oxidative adaptations in trained individuals.

This study examined adaptations in muscle oxidative capacity and exercise performance induced by two work‐ and duration‐matched exercise protocols eliciting different muscle metabolic perturbations in trained individuals. Thirteen male subjects (V˙O2‐max 53.5 ± 7.0 mL·kg−1·min−1) (means ± SD) performed 8 weeks (three sessions/week) of training consisting of 60 min of moderate intensity continuous cycling (157 ± 20 W) either without (C) or with (C+S) inclusion of 30‐s sprints (473 ± 79 W) every 10 min. Total work performed during training was matched between groups. Muscle biopsies and arm venous blood were collected before as well as immediately and 2 h after exercise during the first and last training session. Plasma epinephrine and lactate concentrations after the first and last training session were 2–3‐fold higher in C+S than in C. After the first and last training session, muscle phosphocreatine and pH were lower (12–25 mmol·kg d.w.−1 and 0.2–0.4 units, respectively) and muscle lactate higher (48‐64 mmol·kg d.w.−1) in C+S than in C, whereas exercise‐induced changes in muscle PGC‐1α mRNA levels were similar within‐ and between‐groups. Muscle content of cytochrome c oxidase IV and citrate synthase (CS) increased more in C+S than in C, and content of CS in type II muscle fibers increased in C+S only (9–17%), with no difference between groups. Performance during a 45‐min time‐trial improved by 4 ± 3 and 9 ± 3% in C+S and C, respectively, whereas peak power output at exhaustion during an incremental test increased by 3 ± 3% in C+S only, with no difference between groups. In conclusion, addition of sprints in moderate intensity continuous exercise causes muscle oxidative adaptations in trained male individuals which appear to be independent of the exercise‐induced PGC‐1α mRNA response. Interestingly, time‐trial performance improved similarly between groups, suggesting that changes in content of mitochondrial proteins are of less importance for endurance performance in trained males.

NMR Metabolomic Analysis of Skeletal Muscle, Heart, and Liver of Hatchling Loggerhead Sea Turtles (Caretta caretta) Experimentally Exposed to Crude Oil and/or Corexit.

We used nuclear magnetic spectroscopy (NMR) to evaluate the metabolic impacts of crude oil, Corexit 5900A, a dispersant, and a crude oil Corexit 5900A mixture exposure on skeletal muscle, heart, and liver physiology of hatchling loggerhead sea turtles (Caretta caretta). Tissue samples were obtained from 22 seven-day-old hatchlings after a four day cutaneous exposure to environmentally relevant concentrations of crude oil, Corexit 5900A, a combination of crude oil and Corexit 9500A, or a seawater control. We identified 38 metabolites in the aqueous extracts of the liver, and 30 metabolites in both the skeletal and heart muscle aqueous extracts, including organic acids/osmolytes, energy compounds, amino acids, ketone bodies, nucleosides, and nucleotides. Skeletal muscle lactate, creatines, and taurine concentrations were significantly lower in hatchlings exposed to crude oil than in control hatchlings. Lactate, taurine, and cholines appeared to be the basis of some variation in hatchling heart samples, and liver inosine, uracil, and uridine appeared to be influenced by Corexit and crude oil exposure. Observed decreases in concentrations of lactate and creatines may reflect energy depletion in skeletal muscle of oil-exposed animals, while decreased taurine concentrations in these animals may reflect higher oxidative stress.

Metabolic Response to Claudication in Peripheral Arterial Disease: A Microdialysis Pilot Study

This is a pilot study, and the objective of the study was to investigate the possible uses of microdialysis in the calf muscle to assess the metabolic response to intermittent claudication (IC) and in addition evaluate the simultaneous systemic inflammatory reaction. Dialysate and venous blood sampling was performed before, during and after walking on a treadmill to maximal tolerable claudication (controls 10 min) using 1 microdialysis catheter inserted in the gastrocnemius muscle, 1 subcutaneously in the pectoral region (as a reference), and a peripheral venous catheter. A total of 9 participants were recruited, 6 patients with IC and 3 healthy control subjects. At baseline, patients with IC and control subjects did not differ in metabolic findings (glucose, lactate, pyruvate, and glycerol) in the gastrocnemius muscle. Subcutaneous glucose concentration was higher in control subjects. After physical exertion, gastrocnemius and subcutaneous glycerol, lactate, and pyruvate concentrations increased in patients with IC. Plasma concentrations of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), hepatocyte growth factor, and vascular endothelial growth factor were higher in IC subjects at baseline, and TNF-α, IL-6, and IL-18 increased after walking as did IL-6 and IL-1ß in control subjects. The muscle catheters did not show any signs of harm. Microdialysis can be used to study the ongoing metabolic response during walking and claudication. Our results suggest both an acute local and a systemic inflammatory reaction during development of claudication.

Dietary nucleotides supplementation affect the physicochemical properties, amino acid and fatty acid constituents, apoptosis and antioxidant mechanisms in grass carp (Ctenopharyngodon idellus) muscle

A 60 days feeding trial was conducted to investigate the effects of dietary nucleotides levels on growth performance, proximate composition, physicochemical properties, amino acids constituents, fatty acids composition, apoptosis and antioxidant status related mechanism of grass carp (Ctenopharyngodon idella) (initial weight: 200.00 ± 1.00 g). Six graded levels of dietary nucleotides were designed as 0, 200.0, 400.0, 600.0, 800.0 and 1000.0 mg/kg, respectively. The results showed that, compared with control group, dietary nucleotides supplementation increased the growth of grass carp with higher final body weight, percentage weight gain and specific growth rate, decreased moisture but increased protein and lipid in muscle. However, dietary nucleotides had no effect on ash, calcium and phosphorus in fish fillets (P > .05). Dietary nucleotides supplementation increased the content of umami and sweetness-associated amino acids, flavor nucleotide (inosine mono-phosphate), healthcare n-3 PUFAs (EPA and DHA) and the ratio of n-3/n6 in fish muscle. Meanwhile, dietary nucleotides increased water holding capacity, tenderness and pH to enhance flesh quality, which were partly related to inhibited apoptosis with regulation of apoptosis-related gene expression, decreased hydroxyproline with increase of cathepsins activities and decreased lactate in muscle, respectively. In addition, dietary nucleotides enhanced flesh quality of grass carp fillets concerning increasing antioxidant enzymes activities and its gene expression, which were modulated by signaling molecules (TOR and Nrf2) gene and protein expression in grass carp muscle. In summary, dietary nucleotides supplementation increased growth performance, flavor characteristics, healthy fatty acid contents, physicochemical properties (water holding capacity, tenderness and pH), anti-apoptotic ability and antioxidant capacity in fish. This study demonstrated that nucleotides was a promising feed additives to enhance flesh quality in fish.

Upregulation of the lactate transporter monocarboxylate transporter 1 at the blood-brain barrier in a rat model of attention-deficit/hyperactivity disorder suggests hyperactivity could be a form of self-treatment

The energy deficit hypothesis of attention-deficit/hyperactivity disorder (ADHD) suggests that low lactate production by brain astrocytes causes the symptoms of the disorder. Astrocytes are the main producers of lactate in the brain; however, skeletal muscles can produce the most lactate in the body. The lactate production by skeletal muscles increases with physical activity, as does the expression of the lactate transporter monocarboxylate transporter 1 (MCT1) at the blood-brain barrier (BBB). We hypothesise that children with ADHD, by being hyperactive, increase lactate production by skeletal muscles and transport it into the brain to compensate for low supply by astrocytes. The aim of this study was to explore whether the level of MCT1 is altered in the brain in an animal model of ADHD. The MCT1 expression was quantified on hippocampal brain sections from the best available rat model of ADHD, i.e., the spontaneously hypertensive rat (SHR) (n = 12), and the relevant control, the Wistar Kyoto rat (WKY) (n = 12), by the use of quantitative immunofluorescence laser scanning microscopy and postembedding immunogold electron microscopy. The results revealed significantly higher levels of hippocampal MCT1 immunoreactivity in SHR compared to WKY, particularly at the BBB. These results indicate that lactate flux through MCT1 between the body and the brain could be upregulated in children with ADHD. This study adds to previous research suggesting hyperactivity may be beneficial in ADHD; Children with ADHD possibly display a hyperactive behaviour in order to raise skeletal muscle lactate production, MCT1 expression and flux over the BBB to supply the brain with lactate.

The survival and hepatic and muscle glucose and lactate levels of Rhamdia quelen inoculated with Aeromonas hydrophila and treated with terpinen-4-ol, carvacrol or thymol

The aim of this study was to evaluate the resistance of Rhamdia quelen (silver catfish) to Aeromonas hydrophila infection after treatment with pure and nanoencapsulated forms either terpinen-4-ol, thymol, or carvacrol and the effects of these treatments on fish metabolic responses. After A. hydrophila inoculation, fish were treated with 30 min daily baths for 6 consecutive days with terpinen-4-ol, thymol, or carvacrol in their pure or nanoencapsulated forms at concentrations of 5, 10, 15 or 25 mg L−1. A positive control group, negative control group and saline group were also included. Survival was evaluated at the end of treatment for six consecutive days. Muscle and liver were collected to determine glucose and lactate levels. The fish treated with the nanoencapsulated form of the compounds had a high survival rate, similar to saline group and negative control groups. The carvacrol, thymol and terpinen-4-ol nanoencapsulated forms improved survival of silver catfish infected with A. hydrophila. Muscle and liver glucose and lactate levels are not indicated as biomarkers because they did not present any correlation between the metabolic state of the fish and the bacterial infection.

Behavioural and physiological responses to low- and high-intensity locomotion in Chinese shrimp Fenneropenaeus chinensis.

We explored stroke behaviour, energy sources, and their related metabolic enzymes during multi-intensity swimming and tail-flipping at low- and high-intensity modes in Chinese shrimp Fenneropenaeus chinensis. In swimming, shrimp were encouraged to swim at velocities of 3, 6, 9cms-1 for 200min (low-intensity), and at 12, 15, 18cms-1 until fatigue (high-intensity). In tail-flipping, shrimp were encouraged to tail-flip by tapping cephalothorax at frequencies of 0.020, 0.040, 0.063Hz (one tap every 50, 25, 16s) for 5min (low-intensity), and at 0.083, 0,100, 0.125Hz (one tap every 12, 10, 8s) until no response (high-intensity). Results showed that shrimp increased stroke rates of pleopods and uropods to elevate swimming and tail-flipping ability. For low-intensity locomotion, glycogen was burned in aerobic pathway due to low pleopods beat frequency in swimming; however, glycogen was anaerobically burned due to high uropods beat amplitude in tail-flipping. Anaerobic metabolism occurred in high-intensity locomotion in either swimming or tail-flipping. Critical contents of muscle lactate causing locomotion fatigue might be around threefold of rest condition. Shrimp reduced locomotive time to avoid glycogen exhaustion and lactate accumulation during high-intensity locomotion. These findings highlight our understanding of physiological mechanisms of locomotion activities in shrimp.

Effects of active immunization against porcine Sox6 on meat quality and myosin heavy chain isoform expression in growing-finishing pigs

A feeding trial for 91 days was conducted to investigate effects of active immunization against porcine Sox6 (pSox6) on meat quality and myosin heavy chain (MyHC) isoform expression in growing-finishing pigs. Twenty-four castrated Duroc × Landrace × Yarkshire pigs were randomly divided into three groups: (1) Control group; (2) 1 mg/head pSox6 active immunity group; (3) 4 mg/head pSox6 active immunity group (4 mg/head group). The results showed that pigs in 4 mg/head group had a greater a* (Redness) and a higher marbling score, while no significant effect was observed in L* (Lightness), b* (Yellowness), intramuscular fat and cooking loss. Muscle succinic dehydrogenase activity in pSox6 active immunization groups was significantly increased, and muscle lactate dehydrogenase activity was significantly reduced. Meanwhile, active immunization against pSox6 upregulated the mRNA expression of MyHC I, while no effect was observed on the mRNA expressions of MyHC IIa, MyHC IIx, MyHC IIb. In addition, pigs in the 4 mg/head group exhibited lower Sox6 mRNA level and higher MyHC I protein level, while no significant influence was observed on MyHC IIb protein level. Together, our data imply that active immunization against pSox6 could improve the pork quality and promote the MyHC I expression in growing-finishing pigs.

Air Exposure in Catshark (Scyliorhinus canicula) Modify Muscle Texture Properties: A Pilot Study

Sharks are captured by tons for human consumption. Improving the quality of their meat will produce fillets that may have a higher economic value in the market, and thus be beneficial for the management of this fishery. In other animal species destined for human consumption, a negative relationship between pre-slaughtering stress and meat quality has been demonstrated. By studying the commercial small-spotted catshark (Scyliorhinus canicula), this work aimed at linking pre-slaughter handling of captured sharks and muscle fillets quality. An experimental group of adult and subadult living catsharks captured by hand and exposed to air (for 18 min, which is the minimum time this species is exposed to air in the fishing deck during fisheries procedures), and an undisturbed group, were evaluated. After air exposure, catsharks returned to water for recovery. Muscle lactate and water content were quantified after acute exposure (for 18 min), 5 h and 24 h. This challenge elicited stress responses in the muscle such as increased lactate levels and immediate dehydration, followed by recovery of lactate levels and overhydration. Muscle consistency, a relevant variable describing quality of seafood according to its ability to be swallowed by the consumer, paralleled muscle water content changes. The results indicated for the first time that handling alive sharks exposed to air results in muscle fillets with different texture properties. Whether these changes in muscle texture induce higher quality fillets has yet to be proven. Our recommendation is to minimize time of air exposure experienced by sharks when captured, including fast slaughtering instead of leaving them to die by asphyxia, as current on-board procedures.

Lactate administration activates the ERK1/2, mTORC1, and AMPK pathways differentially according to skeletal muscle type in mouse.

Skeletal muscle is described as an endocrine organ, constitutively or intermittently secreting bioactive molecules. The signaling pathways by which these molecules mediate changes in skeletal muscle and regulate interorgan crosstalk are only partly understood. Lactate is widely described as a signaling molecule in different cells, but the role of lactate as a signaling molecule in mature skeletal muscle has not been fully unveiled. The aim of this study was to determine the role of lactate on activation of signaling pathways in adult mouse skeletal muscle. Male mice were injected intraperitoneally with lactate or saline, and tissues were dissected after 40 min. Phosphorylation levels of relevant proteins in muscle were assessed by Western blotting. After lactate administration, we found an increase in p‐ERK1/2Thr202/Tyr204 (3.5‐fold; P = 0.004) and p‐p70S6KT hr389 (1.9‐fold; P = 0.01) in quadriceps; and an increase in p‐rpS6Ser235/236 in both quadriceps (6.3‐fold; P = 0.01) and EDL (2.3‐fold; P = 0.01), without changes in soleus. There was a tendency toward an increase in p‐AMPKT hr172 (1.7‐fold; P = 0.08), with a significant increase in p‐ACCS er79 (1.5‐fold; P = 0.04) in soleus, without changes in quadriceps and EDL. These results support the hypothesis that lactate plays a role in the molecular signaling related to hypertrophy and to oxidative metabolism on adult skeletal muscle and suggest that this activation depends on the skeletal muscle type. The mechanisms that underlie the effect of lactate in mature skeletal muscles remain to be established.

Oxygen consumption of desert pupfish at ecologically relevant temperatures suggests a significant role for anaerobic metabolism.

Oxygen consumption is oftentimes used as a proxy for metabolic rate. However, pupfish acclimated to ecologically relevant temperatures may employ extended periods of anaerobism despite the availability of oxygen-a process we called paradoxical anaerobism. In this study, we evaluated data from pupfish exhibiting stable oxygen consumption. Routine oxygen consumption ([Formula: see text]) of a refuge population derived from Cyprinodon spp. acclimated to 28 and 33°C was evaluated at the ecologically relevant assay temperatures of between 25 and 38°C. Different interpretations of the data are available depending on normalization. For instance, [Formula: see text] of smaller fish, measured per fish, was remarkably stable over a wide range of assay temperatures and was not different between acclimation groups. However, when measured on a mass-specific basis, [Formula: see text] in these same smaller fish increases more predictably as temperature increased. [Formula: see text] of refuge fish and the closely related pupfish, C. nevadensis mionectes, measured near their respective acclimation temperatures, were essentially identical. However, [Formula: see text] of 28°C acclimated fish of both species, when measured at 34°C, was greater than that of the 33°C acclimated fish measured at 28°C. We suggest that this observed 'efficiency' may result from significant anaerobic metabolism use. Experiments investigating factorial aerobic scope ([Formula: see text]/[Formula: see text]) yielded values less than 1 in 21-36% of the 33°C acclimated fish. These values indicate a substantial contribution of anaerobic metabolism to energy utilization by these fish. However, muscle lactate levels are not elevated in exercising fish-a result that is consistent with paradoxical anaerobism use.

Peripheral Muscle Near-Infrared Spectroscopy Variables are Altered Early in Septic Shock.

Noninvasive evaluation of muscle perfusion using near-infrared spectroscopy (NIRS) coupled with a vascular occlusion test (VOT) may provide an early and simple marker of altered perfusion and microcirculatory function in sepsis. The aim of the study was to compare the time-course of NIRS-derived variables with systemic measures of perfusion in an experimental model of peritonitis. Peritonitis was induced in eight anesthetized, mechanically ventilated, adult sheep (24-34 kg), by injecting autologous feces into the peritoneal cavity. Animals were followed until death or for a maximum of 30 h. Muscle tissue oxygen saturation (StO2) was determined using NIRS on the right posterior leg and arterial VOTs were performed by intermittent intra-aortic balloon inflation. Microdialysis was used to measure muscle lactate and pyruvate levels. Muscle StO2 was significantly lower than baseline values from 8 h after sepsis induction, but with considerable intersubject variability. The NIRS VOT ascending (Asc) slope decreased to values <120%/min in most animals from 12 h after sepsis induction. Muscle lactate/pyruvate ratios were higher than baseline from 16 h after sepsis induction. Mixed venous oxygen saturation (SvO2) decreased to <70% and blood lactate levels increased to >2 mmol/L in most of the animals only 24 and 28 h after sepsis induction, respectively. Muscle NIRS StO2 correlated strongly with femoral venous oxygen saturation (r = 0.820) and moderately with SvO2 (r = 0.436). The muscle NIRS Asc slope after a VOT is altered earlier than global markers of tissue hypoperfusion during sepsis. This simple noninvasive test can detect early changes in peripheral perfusion in sepsis.

Metabolic stress-dependent regulation of the mitochondrial biogenic molecular response to high-intensity exercise in human skeletal muscle.

Low-volume high-intensity exercise training promotes muscle mitochondrial adaptations that resemble those associated with high-volume moderate-intensity exercise training. These training-induced mitochondrial adaptations stem from the cumulative effects of transient transcriptional responses to each acute exercise bout. However, whether metabolic stress is a key mediator of the acute molecular responses to high-intensity exercise is still incompletely understood. Here we show that, by comparing different work-matched low-volume high-intensity exercise protocols, more marked metabolic perturbations were associated with enhanced mitochondrial biogenesis-related muscle mRNA responses. Furthermore, when compared with high-volume moderate-intensity exercise, only the low-volume high-intensity exercise eliciting severe metabolic stress compensated for reduced exercise volume in the induction of mitochondrial biogenic mRNA responses. The present results, besides improving our understanding of the mechanisms mediating exercise-induced mitochondrial biogenesis, may have implications for applied and clinical research that adopts exercise as a means to increase muscle mitochondrial content and function in healthy or diseased individuals. The aim of the present study was to examine the impact of exercise-induced metabolic stress on regulation of the molecular responses promoting skeletal muscle mitochondrial biogenesis. Twelve endurance-trained men performed three cycling exercise protocols characterized by different metabolic profiles in a randomized, counter-balanced order. Specifically, two work-matched low-volume supramaximal-intensity intermittent regimes, consisting of repeated-sprint (RS) and speed endurance (SE) exercise, were employed and compared with a high-volume continuous moderate-intensity exercise (CM) protocol. Vastus lateralis muscle samples were obtained before, immediately after, and 3h after exercise. SE produced the most marked metabolic perturbations as evidenced by the greatest changes in muscle lactate and pH, concomitantly with higher post-exercise plasma adrenaline levels in comparison with RS and CM. Exercise-induced phosphorylation of CaMKII and p38 MAPK was greater in SE than in RS and CM. The exercise-induced PGC-1α mRNA response was higher in SE and CM than in RS, with no difference between SE and CM. Muscle NRF-2, TFAM, MFN2, DRP1 and SOD2 mRNA content was elevated to the same extent by SE and CM, while RS had no effect on these mRNAs. The exercise-induced HSP72 mRNA response was larger in SE than in RS and CM. Thus, the present results suggest that, for a given exercise volume, the initial events associated with mitochondrial biogenesis are modulated by metabolic stress. In addition, high-intensity exercise seems to compensate for reduced exercise volume in the induction of mitochondrial biogenic molecular responses only when the intense exercise elicits marked metabolic perturbations.

Oxidative Stress Contributes to Fracture/Cast-Induced Inflammation and Pain in a Rat Model of Complex Regional Pain Syndrome

Clinical evidence suggests that vitamin C (Vit C) may protect against the development of complex regional pain syndrome (CRPS) after fracture or surgery. Tibia fracture followed by 4 weeks of cast immobilization (fracture/cast) in rats results in nociceptive, vascular, and bone changes resembling clinical CRPS. In this study, fracture/cast rats were treated with the oxidative stress inhibitors Vit C, N-acetyl cysteine, or 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl to examine their effects on CRPS-related nociceptive and vascular changes. Administration of these agents significantly reduced fracture/cast-induced cutaneous allodynia by 64 to 78%, muscle hyperalgesia by 34 to 40%, and hind limb unweighting by 48 to 89%. Treatments with Vit C and N-acetyl cysteine reduced the oxidative stress markers malondialdehyde in the skin, muscle, and sciatic nerve, and lactate in the gastrocnemius muscle of the fracture/cast limb. Furthermore, Vit C treatment inhibited the post-fracture upregulation of substance P and calcitonin gene-related peptide in the sciatic nerve and the increased expression of the pain-related inflammatory mediators, including interleukin (IL)-6, and nerve growth factor in the skin and IL-1β, and IL-6 in the muscle of the post-fracture/cast limb. These data suggest that oxidative stress may contribute to the nociceptive features of the rat CRPS model.Perspective:Vit C reduced the CRPS-like signs, oxidative stress, and the upregulation of neuropeptide production and inflammatory mediators observed after tibia fracture and casting in rats. Limiting oxidative stress by use of Vit C or alternative strategies could reduce the risk of developing CRPS after surgery or other forms of trauma.