Muscle carnitine metabolism during incremental dynamic exercise in humans

The changes in muscle content of carnitine and acetylcarnitine have been studied during incremental dynamic exercise. Six subjects exercised for 10 min on an ergometer at 40 and 75% of their maximal oxygen uptake (VO2 max) and to fatigue at 100% of VO2 max (about 4 min). Muscle samples were taken from the quadriceps femoris muscle at rest and after exercise. Muscle content of free carnitine was (means +/- SE) 15.9 +/- 1.7 mmol kg-1 d.wt (dry weight) at rest and remained unchanged after exercise at low intensity but decreased to 5.9 +/- 0.6 and 4.6 +/- 0.5 mmol kg-1 d.wt after exercise at 75 and 100% of VO2 max respectively. Acetylcarnine content at rest was 6.9 +/- 1.9 mmol kg-1 d.wt and increased during exercise in correspondence with the decrease in free carnitine. Muscle content of pyruvate and lactate was unchanged after exercise at 40% of VO2 max but increased at the higher intensities. The parallel increases in acetylcarnitine, pyruvate and lactate indicate that formation of acetylcarnitine is augmented when the availability of glycolytic three-carbon metabolites is high and is consistent with the idea that acetylcarnitine provides a sink for pyruvate and acetyl CoA. This could be of importance for the maintenance of an adequate level of CoA and thus function of the tricarboxylic acid cycle.     

Influence of glucose and fructose ingestion on the capacity for long-term exercise in well-trained men

The aim of the present study was to examine the influence of glucose and fructose ingestion on the capacity to perform prolonged heavy exercise. Eight well-trained healthy volunteers exercised on a bicycle ergometer at 68 +/- 3% of their VO2 max until exhaustion, on three occasions, with 8-day intervals. During the exercise they ingested either glucose (250 ml, 7%), fructose (250 ml, 7%) or water (250 ml) every 20 min in a double-blind randomized study design. Arterial blood samples were collected at rest and during exercise for the determination of substrates and hormones. Muscle glycogen content (m. quadriceps femoris) was measured before and after exercise. The duration of exercise lengthened with repeated exercise (3rd test: 136 +/- 13 min v. 1st test: 110 +/- 12 min, P less than 0.01). Corrected for the sequence effect, total work time until exhaustion was significantly longer with glucose (137 +/- 13 min) than with either fructose (114 +/- 12 min) or water (116 +/- 13 min) (both P less than 0.01). When glucose or fructose was ingested, the arterial plasma glucose concentration was maintained at the normoglycaemic level; with water ingestion, plasma glucose values fell during exercise in seven subjects and remained at the resting level in the eighth subject. The muscle glycogen concentration was 467 +/- 29 mmol kg d.w.-1 at rest and fell to approximately half the initial value at exhaustion. In the subgroup of seven subjects in whom glucose values decreased with water intake, the mean rate of glycogen degradation was significantly lower (P less than 0.05) with the ingestion of glucose (1.3 +/- 0.4 mmol kg d.w.-1 min-1) as compared to fructose (2.1 +/- 0.5 mmol kg d.w.-1 min-1) or water (2.3 +/- 0.5 mmol kg d.w.-1 min-1). Intermittent glucose ingestion (3 X 17.5 g h-1) during prolonged, heavy bicycle exercise postpones exhaustion and exerts a glycogen-conserving effect in the working muscles. In contrast, fructose ingestion during exercise maintains the glucose concentration at the basal level but fails to influence either muscle glycogen degradation or endurance performance.     

Hypoxaemia increases the accumulation of inosine monophosphate (IMP) in human skeletal muscle during submaximal exercise

The effect of hypoxaemia on the muscle content of inosine monophosphate (IMP) during short-term, low-intensity exercise has been investigated. Six men cycled twice for 5 min at 120 +/- 6 W (mean +/- SE), which corresponded to approximately 50% of their maximal normoxic O2 uptake, breathing air (N) on one occasion and 11% O2 in N2 (H) on the other. Oxygen uptake at the end of the exercise period was similar between treatments. No significant difference was observed between H and N in the muscle metabolite contents at rest. Muscle content of phosphocreatine (PCr) decreased and lactate increased during exercise. Post-exercise PCr during H was 80% of the value during N (P greater than 0.05) and post-exercise muscle lactate was fourfold higher during H than during N (P less than 0.001). Post-exercise muscle content of ADP was significantly higher during H than during N (P less than 0.01), while ATP and AMP remained constant under both H and N exercise (P greater than 0.05 H vs N). IMP was not detectable in pre-exercise muscle samples (less than 0.01 mmol kg-1 dry wt) but increased during N exercise (0.03 +/- 0.01 mmol kg-1 dry wt, wt, P less than 0.05) and even more during H exercise (0.16 +/- 0.05 mmol kg-1 dry wt, P less than 0.05, H vs N). Post-exercise IMP was negatively related to PCr (r = -0.90) and positively related to lactate (r = 0.88). It is concluded that hypoxaemia results in an enhanced accumulation of IMP during submaximal exercise and that the IMP level is related to the degree of anaerobic energy utilization.     

Muscle ammonia and amino acid metabolism during dynamic exercise in man

The effect of dynamic exercise on muscle and blood ammonia (NH3) and amino acid contents has been investigated. Eight healthy men cycled at 50% and 97% of maximal oxygen uptake for 10 min and 5.2 min (to fatigue), respectively. Biopsies (quadriceps femoris muscle), arterial and femoral venous blood samples were obtained at rest and during exercise. Muscle NH3 at rest and after submaximal exercise was (means +/- SE) 0.5 +/- 0.1 mmol/kg dry muscle (d.m.) and increased to 4.1 +/- 0.5 mmol/kg d.m. at fatigue (P less than 0.001). The total adenine nucleotide (TAN) pool (TAN = ATP + ADP + AMP) did not change after submaximal exercise but decreased significantly at fatigue (P less than 0.001). The decrease in TAN was similar to the increase in NH3. Muscle lactate was 3 +/- 1 mmol/kg d.m. at rest and increased to 104 +/- 5 mmol/kg d.m. at fatigue. Whole blood and plasma NH3 did not change significantly during submaximal but both increased significantly during maximal exercise (P less than 0.001). During maximal exercise the leg released 7,120 mumol/min of lactate, whereas only 89 mumol/min of NH3 were released. NH3 accumulation in muscle could buffer only 3% of the hydrogen ions released from lactate, and NH3 release could account for only 1% of the net hydrogen ion transport out of the cell. Muscle glutamine was constant throughout the study, whereas glutamate decreased and alanine increased during exercise (P less than 0.001). No significant changes in either arterial whole blood glutamine or glutamate were observed. Arterial plasma glutamine and glutamate concentrations, however, increased and decreased (P less than 0.001), respectively, during exercise. It is concluded that (1) muscle and blood NH3 levels increase only during strenuous exercise and (2) NH3 accumulation is of minor importance for regulating acid-base balance in body fluids during exercise.     

Influence of passive lower-body heating on muscle metabolic perturbation and high-intensity exercise tolerance in humans

The purpose of this investigation was to determine the influence of heat stress on the dynamics of muscle metabolic perturbation during high-intensity exercise. Seven healthy males completed single-legged knee-extensor exercise until the limit of tolerance on two separate occasions. In a randomized order the subjects underwent 40 min of lower-body immersion in warm water at 42°C prior to exercise (HOT) or received no prior thermal manipulation (CON). Following the intervention, muscle metabolism was measured at rest and throughout exercise using (31)P-MRS. The tolerable duration of high-intensity exercise was reduced by 36% after passive heating (CON: 474?±?146 vs. HOT: 303?±?76?s; P?=?0.005). Intramuscular pH was lower over the first 60?s of exercise (CON: 7.05?±?0.02 vs. HOT: 7.00?±?0.03; P?=?0.019) in HOT compared to CON. The rate of muscle [PCr] degradation during exercise was greater in the HOT condition (CON: -0.17?±?0.08 vs. HOT: -0.25?±?0.10%?s(-1); P?=?0.006) and pH also tended to change more rapidly in HOT (P?=?0.09). Muscle [PCr] (CON: 26?±?14 vs. HOT: 29?±?10%), [Pi] (CON: 504?±?236 vs. HOT: 486?±?186%) and pH (CON: 6.84?±?0.13 vs. HOT: 6.80?±?0.14; P?>?0.05) were not statistically different at the limit of tolerance (P?>?0.05 for all comparisons). These results suggest that the reduced time-to-exhaustion during high-intensity knee-extensor exercise following lower-body heating might be related, in part, to accelerated rates of change of intramuscular [PCr] and pH towards 'critical' values that limit muscle function.     

Metabolism changes in single human fibres during brief maximal exercise

Changes in high-energy phosphate levels in single human skeletal muscle fibres after 10 s of maximal (all-out) dynamic exercise were investigated. Muscle biopsies from vastus lateralis of two volunteers were collected at rest and immediately post exercise. Single muscle fibres were dissected from dry muscle and were assigned into one of four groups according to their myosin heavy chain (MyHC) isoform content: that is type I, IIA, IIAx and IIXa (the latter two groups containing either less or more than 50% IIX MyHC). Fragments of characterised fibres were analysed by HPLC for ATP, inosine-monophosphate (IMP), phosphocreatine (PCr) and creatine levels. After 10 s of exercise, PCr content ([PCr]) declined by approximately 46, 53, 62 and 59 % in type I, IIA, IIAx and IIXa fibres, respectively (P < 0.01 from rest). [ATP] declined only in type II fibres, especially in IIAx and IIXa fibres in which [IMP] reached mean values of 16 +/- 1 and 18 +/- 4 mmol (kg dry mass)(-1), respectively. While [PCr] was reduced in all fibre types during the brief maximal dynamic exercise, it was apparent that type II fibres expressing the IIX myosin heavy chain isoform were under a greatest metabolic stress as indicated by the reductions in [ATP].     

A gated 31P NMR method for the estimation of phosphocreatine recovery time and contractile ATP cost in human muscle

Muscle phosphocreatine (PCr) recovery time constant (an index of muscle aerobic capacity) and contractile ATP cost were estimated from a gated (31)P NMR protocol which does not require intense, repetitive exercise. Subjects performed 2-s duration, maximum voluntary isometric ankle dorsiflexion contractions at 30-s intervals for 8 min (total 15 contractions), while single-shot (31)P spectra (51.7 MHz, TR 3 s) were acquired from the anterior compartment muscle. Spectra from the sixth through 15th contractions were retrospectively sorted, yielding 10 spectra (each 10 averages) gated to times before and after contraction. There was no significant decrease in muscle pH, allowing the calculation of contractile ATP cost directly from the percentage change in PCr during contraction cycles [8.86 +/- 0.82% (SE, n = 11) of PCr at rest], corresponding to an ATP cost of 1.69 +/- 0.16 mM/s (range 0.99-2.49 mM/s), assuming an 8.2 mM ATP concentration. The time constant for PCr recovery (tau 41.8 +/- 4.2 s, range 22.0-60.8 s) was calculated from tau = -Deltat/ln[D/(D + Q)], where Q is the percentage change in PCr due to contraction, D is the additional steady-state percentage drop in PCr from rest and Deltat is the interval between contractions. In the same subjects, the monoexponential PCr recovery time constant after more intense, repetitive isometric ankle dorsiflexion exercise (30 s at 0.5 Hz, 50% duty cycle) was similar to (36.2 +/- 3.5 s, range 16.5-58.8 s) and well correlated with (r = 0.82) the gated result. In contrast to the gated protocol, muscle pH decreased from 7.01 +/- 0.01 to 6.78 +/- 0.04 during recovery after the repetitive protocol. Hence the gated protocol allows the estimation of muscle ATP cost and PCr recovery without intense exercise or muscle acidification.     

Effect of Caffeine Co-Ingested with Carbohydrate or Fat on Metabolism and Performance in Endurance-Trained Men

We examined the effect of caffeine co-ingested with either carbohydrate or fat on metabolism and performance in eight endurance-trained subjects who performed a random order of four experimental trials consisting of 120 min of steady-state ergometer cycling at 70 % of maximal O(2) uptake (SS) followed by a time trial in which subjects completed a set amount of work (7 kJ kg-1) as quickly as possible. One hour before SS subjects ingested either 2.6 g kg-1 carbohydrate (CHO); 2.6 g kg-1 CHO + 6 mg kg-1 caffeine (CHO + CAF); 1.2 g kg-1 fat with 2000 U I.V. heparin (FAT); or 1.2 g kg-1 fat with 2000 U I.V. heparin + 6 mg kg-1 caffeine (FAT + CAF). The rate of carbohydrate oxidation was higher (micromol kg-1 min-1: CHO, 243 +/- 39 and CHO + CAF, 239 +/- 30 vs. FAT, 196 +/- 48 and FAT + CAF, 191 +/- 55; P < 0.05, values are means +/- S.D.) and the rate of fat oxidation lower (micromol kg-1 min-1: CHO, 19 +/- 8 and CHO + CAF, 22 +/- 7 vs. FAT, 35 +/- 19 and FAT + CAF, 37 +/- 17; P < 0.05) with carbohydrate than fat ingestion. Yet despite lower carbohydrate use with fat feeding, the time taken to complete the time trial was less after carbohydrate than after fat ingestion (min: CHO, 30.37 +/- 7.42 and CHO + CAF, 29.12 +/- 5.62 vs. FAT, 33.02 +/- 8.50 and FAT + CAF, 32.78 +/- 7.70; P < 0.05). We conclude that (1) caffeine co-ingested with either carbohydrate or fat meals has no additive effect on substrate utilization or exercise performance and (2) carbohydrate ingestion before exercise improves subsequent time trial performance compared with fat ingestion. Experimental Physiology (2001) 86.1, 137-144.     

Effects of recovery time on phosphocreatine kinetics during repeated bouts of heavy-intensity exercise

The purpose of this study was to examine the kinetics of phosphocreatine (PCr) breakdown in repeated bouts of heavy-intensity exercise separated by three different durations of resting recovery. Healthy young adult male subjects (n = 7) performed three protocols involving two identical bouts of heavy-intensity dynamic plantar flexion exercise separated by 3, 6, and 15 min of rest. Muscle high-energy phosphates and intracellular acid-base status were measured using phosphorus-31 magnetic resonance spectroscopy. In addition, the change in concentration of total haemoglobin (Delta[Hb(tot)]) and deoxy-haemoglobin (Delta[HHb]) were monitored using near-infrared spectroscopy. Prior exercise resulted in an elevated (P < 0.05) intracellular hydrogen ion ([H(+)](i)) after 3 min (182 +/- 72 (SD) nM; pH 6.73) and 6 min (112 +/- 19 nM; pH 6.95) but not after 15 min (93 +/- 8 nM; pH 7.03) compared to pre-exercise in Con (90 +/- 3 nM; pHi 7.05). The on-transient time constant (tau) of the PCr primary component was not different amongst the exercise bouts. However, in each of the subsequent bouts the amplitude of the PCr slow component, total PCr breakdown, and rise in [H(+)](i) were reduced (P < 0.05). At exercise onset, Delta[Hb(tot)] was increased (P < 0.05) and the Delta[HHb] kinetic response was slowed (P < 0.05) in the exercise after 3 min, consistent with improved muscle perfusion. In summary, neither the level of acidosis or muscle perfusion at the onset of exercise appeared to be directly related to the time course of the on-transient PCr primary component or the magnitude of the PCr slow component during subsequent bouts of exercise.     

PPARδ agonism inhibits skeletal muscle PDC activity, mitochondrial ATP production and force generation during prolonged contraction

We have recently shown that PPARδ agonism, used clinically to treat insulin resistance, increases fat oxidation and up-regulates mitochondrial PDK4 mRNA and protein expression in resting skeletal muscle. We hypothesized that PDK4 up-regulation, which inhibits pyruvate dehydrogenase complex (PDC)-dependent carbohydrate (CHO) oxidation, would negatively affect muscle function during sustained contraction where the demand on CHO is markedly increased. Three groups of eight male Wistar rats each received either vehicle or a PPARδ agonist (GW610742X) at two doses (5 and 100 mg (kg body mass (bm))⁻¹ orally for 6 days. On the seventh day, the gastrocnemius–soleus–plantaris muscle group was isolated and snap frozen, or underwent 30 min of electrically evoked submaximal intensity isometric contraction using a perfused hindlimb model. During contraction, the rate of muscle PDC activation was significantly lower at 100 mg (kg bm)⁻¹ compared with control ( P < 0.01). Furthermore, the rates of muscle PCr hydrolysis and lactate accumulation were significantly increased at 100 mg (kg bm)⁻¹ compared with control, reflecting lower mitochondrial ATP generation. Muscle tension development during contraction was significantly lower at 100 mg (kg bm)⁻¹ compared with control (25%; P < 0.05). The present data demonstrate that PPARδ agonism inhibits muscle CHO oxidation at the level of PDC during prolonged contraction, and is paralleled by the activation of anaerobic metabolism, which collectively impair contractile function.     

NADH in human skeletal muscle during short-term intense exercise

The influence of high-intensity bicycle exercise on the redox level and lactate accumulation in skeletal muscle (m. quadriceps femoris) of man has been investigated. Six subjects exercised to exhaustion at a load corresponding to 100% VO2max. Muscle content of NADH, determined by the bioluminescence technique, increased from (means +/- SEM) 0.089 +/- 0.007 mmol/kg dry wt. at rest to 0.190 +/- 0.031 after 2 min of exercise (P less than 0.05) and to 0.213 +/- 0.021 at exhaustion (P less than 0.05). Values after 2 min exercise and at exhaustion were not statistically different (P greater than 0.05). Muscle lactate was increased 13-fold after 2 min of exercise and 22-fold at exhaustion as compared to the resting value. After 10 min recovery NADH was restored back to the pre-exercise level whereas muscle lactate was still elevated. The increase of muscle NADH during exercise is in contrast to earlier studies on isolated animal muscles, where an oxidation of NADH was observed during contractions. The difference might be due to the experimental model (isolated muscle vs. in vivo) or to the analytical method (qualitative data by reflectance fluorimetri from the surface of intact muscle vs. quantitative data from muscle extracts). Calculations of the cytosolic NADH concentration from the lactate dehydrogenase equilibrium show that 95% or more of the NADH is confined to the mitochondrial compartment. The observed increase of muscle NADH therefore imply that the redox potential of the mitochondria is decreased during intense exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of prior exercise on muscle [phosphorylcreatine] and deoxygenation kinetics during high-intensity exercise in men

(31)Phosphate-magnetic resonance spectroscopy and near infrared spectroscopy (NIRS) were used for the simultaneous assessment of changes in quadriceps muscle metabolism and oxygenation during consecutive bouts of high-intensity exercise. Six male subjects completed two 6 min bouts of single-legged knee-extension exercise at 80% of the peak work rate separated by 6 min of rest while positioned inside the bore of a 1.5 T superconducting magnet. The total haemoglobin and oxyhaemoglobin concentrations in the area of the quadriceps muscle interrogated with NIRS were significantly higher in the baseline period prior to the second compared with the first exercise bout, consistent with an enhanced muscle oxygenation. Intramuscular phosphorylcreatine concentration ([PCr]) dynamics were not different over the fundamental region of the response (time constant for bout 1, 51 +/- 15 s versus bout 2, 52 +/- 17 s). However, the [PCr] dynamics over the entire response were faster in the second bout (mean response time for bout 1, 72 +/- 16 s versus bout 2, 57 +/- 8 s; P < 0.05), as a consequence of a greater fall in [PCr] in the fundamental phase and a reduction in the magnitude of the 'slow component' in [PCr] beyond 3 min of exercise (bout 1, 10 +/- 6% versus bout 2, 5 +/- 3%; P < 0.05). These data suggest that the increased muscle O(2) availability afforded by the performance of a prior bout of high-intensity exercise does not significantly alter the kinetics of [PCr] hydrolysis at the onset of a subsequent bout of high-intensity exercise. The greater fall in [PCr] over the fundamental phase of the response following prior high-intensity exercise indicates that residual fatigue acutely reduces muscle efficiency.     

No effect of carbohydrate feeding on 16 km cycling time trial performance

The aim of this study is to investigate the effects of CHO ingestion during high intensity exercise performance lasting approximately 25 min. Twelve endurance trained male cyclists (age 19-41 years; body mass 73.2 +/- 4.2 kg; VO(2)max 66.4 +/- 6.2 ml kg(-1) min(-1)) completed a simulated 16 km time trial (457 +/- 37 kJ) time trial in the lab on three occasions. Once they received a 6% carbohydrate electrolyte solution (CHO) and twice they received the same electrolyte containing placebo drink (PLA). Carbohydrate or placebo drinks were ingested 5 min before the start (4 ml kg(-1)) and at 25, 50, and 75% of completion of the time trial (1.4 ml kg(-1)). The CHO drink was a 6% sucrose-glucose-electrolyte solution. No differences were observed in the time to complete the time trials with either treatment. Time in min:s were 25:30 +/- 1:34 and 25:27 +/- 1:46 for the two placebo trials and 25:38 +/- 1:59 in the CHO trial. Power output during the time trials was also remarkably similar: 300 +/- 37 W, 301 +/- 39 W and 299 +/- 40 W, respectively. Pacing strategies and heart rate were identical in all three trials. From the two placebo trials, a coefficient of variation for this performance task was calculated to be 1.1%. Data from this study provides evidence that carbohydrate ingestion during short high intensity exercise (approximately 30 min, 85-90% VO(2)max) does not improve performance. Furthermore, this study found a very low coefficient of variation (1.1%) for a simulated 16 km time trial.     

Effects of ammonium chloride ingestion on phosphocreatine metabolism during moderate- and heavy-intensity plantar-flexion exercise

This study examined the effects of NH₄Cl ingestion on phosphocreatine (PCr) metabolism during 9 min of moderate- (MOD) and heavy- (HVY) intensity constant-load isotonic plantar-flexion exercise. Healthy young adult male subjects (n = 8) completed both a control (CON) and NH₄Cl ingestion (ACID) trial. Phosphorus-31 magnetic resonance spectroscopy was used to monitor changes in intracellular pH (pHi), [Pi], [PCr], and [ATP]. During the Middle (3–6 min) and Late (6–9 min) stages of HVY, ACID was associated with a higher (P < 0.05) intracellular hydrogen-ion concentration ([H⁺]i) [Middle: 246 (SD 36) vs. 202 (SD 36) mmol/l]; [Late: 236 (SD 35) vs. 200 (SD 39) mmol/l]. In addition, ACID was associated with a lower (P < 0.05) [PCr] relative to CON during the Early (0–3 min) [18.1 (SD 5.1) vs. 20.4 (SD 5.4) mmol/l] and Middle stages [14.1 (SD 5.4) vs. 16.7 (SD 6.0) mmol/l] of HVY. The amplitude of the primary component of PCr breakdown during the transition to HVY was greater in ACID than CON [14.5 (SD 5.8 vs. 11.3 (SD 4.8) mmol/l], however, the PCr slow component (continued slow decline in [PCr]) showed no difference (P > 0.05). The time constant for PCr breakdown (τPCr) was greater in HVY than MOD for both conditions [58 (SD 22) vs. 28 (SD 15) s ACID; 51 (SD 20) vs. 29 (SD 14) s CON] (P < 0.05). In summary, ACID increased PCr breakdown during the transition from MOD to HVY, but did not increase the magnitude of the PCr slow component.     

Effect of creatine supplementation on intramuscular TCr,metabolism and performance during intermittent,supramaximal exercise in humans

This study examined the effect of (a) creatine supplementation on exercise metabolism and performance and (b) changes in intramuscular total creatine stores following a 5 day supplementation period and a 28 day wash-out period. Six men performed four exercise trials, each consisting of four 1 min cycling bouts, punctuated by 1 min of rest followed by a fifth bout to fatigue, all at a workload estimated to require 115 or 125% VO_{2, max} After three familiarization trials, one trial was conducted following a creatine monohydrate supplementation protocol (CREAT); the other after 28 d without creatine supplementation, in which the last 5 d involved placebo ingestion (CON). Intramuscular TCr was elevated (P < 0.05) in CREAT compared with the final familiarization trial (FAM3) and CON. Concentrations of this metabolite in these latter trials were not different. In addition, a main effect (P < 0.05) for treatment was observed for PCr when the data from CREAT were compared with CON. In contrast, no differences were observed in the total adenine nucleotide pool (ATP + ADP +AMP), inosine 5′-monophosphate, ammonia, lactate or glycogen when comparing CREAT with CON. Despite the differences in TCr and PCr concentrations when comparing CREAT with other trials, no difference was observed in exercise duration in the fifth work bout. These data demonstrate that creatine supplementation results in an increase in TCr but this has no effect on performance during exercise of this nature, where the creatine kinase system is not the principal energy supplier. In addition 28 d without supplementation is a sufficient time to return intramuscular TCr stores to basal levels.     

Formation of inosine monophosphate (IMP) in human skeletal muscle during incremental dynamic exercise

The influence of exercise intensity on the accumulation of inosine monophosphate (IMP) in human skeletal muscle has been investigated. Ten men cycled at workloads corresponding to 40%, 75% and 100% of their maximal oxygen uptake (VO2 max). Muscle IMP was below the detection limit (less than 0.01 mmol kg-1 dry wt) at rest and after exercise at 40% of VO2 max, but increased to 0.26 +/- 0.06 (mean +/- SEM) and 3.50 +/- 0.51 mmol kg-1 dry wt after exercise at 75% and 100% of VO2 max respectively. Accumulation of IMP corresponded to a similar decrease in the total adenine nucleotide content. The muscle content of IMP was positively related to lactate and negatively related to phosphocreatine (PCr). IMP was formed in both fibre types, but the IMP content at fatigue was about twice as high in type II fibres as in type I fibres. It was concluded that the IMP content of human skeletal muscle is very low at rest and after low-intensity exercise, but increases after moderate and high-intensity exercise. In contrast to rat muscle, where deamination of AMP predominantly occurs in the fast-twitch muscle fibres, IMP is formed during exercise in both fibre types in human muscle. Accumulation of IMP appears to reflect an imbalance between the rate of utilization and the rate of regeneration of ATP.     

Effect of hypoxia on fatigue development in rat muscle composed of different fibre types

This study investigated the relationship between hypoxia and the rate of fatigue development in contracting rat hindlimb muscles composed primarily of different fibre types. Hindlimb muscles of 11 rats were exposed, and the soleus (SOL) and gastrocnemius/plantaris (GP) were each isolated with circulation intact and attached to individual force transducers. Rats were then equilibrated with either normoxic (N; arterial partial pressure of O(2) 87.7 +/- 1.5 mmHg) or hypoxic conditions (H; arterial partial pressure of O(2) 30.0 +/- 2.4 mmHg) using an inspired O(2) fraction of 0.21 and 0.10, respectively. The stimulation protocol consisted of 2 min each at 0.125, 0.25, 0.33 and 0.5 tetanic contractions s(-1) sequentially for both conditions. Following the 8 min stimulation period, relative developed muscle tension (% of maximal) was nearly identical for both H and N in SOL (54.2 +/- 3.5 versus 54.3 +/- 4.2%), but was significantly (P < 0.05) lower in H than N (10.8 +/- 0.9 versus 43.0 +/- 8.9%) in GP, indicating a greater amount of fatigue during hypoxia only in the GP. Soleus phosphocreatine (PCr) content fell to similar levels (24.1 +/- 1.6 versus 21.1 +/- 4.9 mmol (kg dry weight (dw))(-1)) during both H and N, but in the white portion of the gastrocnemius (WG), PCr was significantly lower following H than N (14.3 +/- 1.5 versus 34.0 +/- 6.0 mmol (kg dw)(-1)). Similarly, muscle lactate increased in both fibre types at fatigue, but only in WG was the increase significantly greater with H (SOL 7.1 +/- 2.0 versus 5.3 +/- 1.1 mmol (kg dw)(-1); WG 13.7 +/- 4.5 versus 5.3 +/- 2.2 mmol (kg dw)(-1)). Increases in calculated muscle [H(+)], free ADP and free AMP were similar between N and H in SOL but were significantly greater during H compared with N in WG. These data demonstrate that hypoxia induces greater fatigue and disruption of cellular homeostasis in rat hindlimb muscle composed primarily of fibres with low oxidative capacity compared with those of a more oxidative type.     

Caffeine administration results in greater tension development in previously fatigued canine muscle in situ

In isolated single skeletal myocytes undergoing long-term fatiguing contractions, caffeine (CAF) can result in nearly immediate restoration of generated tension to near-prefatigue levels by increasing Ca2+ release via activation of sarcoplasmic reticulum release channels. This study tested whether arterial CAF infusion (>5 mm) would cause a similar rapid restoration of tetanic isometric tension during contractions to fatigue in perfused canine hindlimb muscle in situ. Tetanic contractions were elicited by electrical stimulation (200 ms trains, 50 Hz, 1 contraction s(-1)), and biopsies were taken from the muscle at rest and during contractions: (1) following the onset of fatigue (tension approximately 60% of initial value); and (2) following CAF administration. Resting muscle ATP, PCr and lactate contents were 25.2 +/- 0.4, 76.9 +/- 3.3 and 14.4 +/- 3.3 mmol (kg dry weight)(-1), respectively. At fatigue, generated tetanic tension was 61.1 +/- 6.9% of initial contractions. There was a small but statistically significant recovery of tetanic tension (64.9 +/- 6.6% of initial value) with CAF infusion, after which the muscle showed incomplete relaxation. At fatigue, muscle ATP and PCr contents had fallen significantly (P < 0.05) to 18.1 +/- 1.1 and 18.9 +/- 2.1 mmol (kg dry weight)(-1), respectively, and lactate content had increased significantly to 27.7 +/- 5.4 mmol (kg dry weight)(-1). Following CAF, skeletal muscle ATP and PCr contents were significantly lower than corresponding fatigue values (15.0 +/- 1.3 and 10.9 +/- 2.2 mmol (kg dry weight)(-1), respectively), while lactate was unchanged (22.2 +/- 3.9 mmol (kg dry weight)(-1)). These results demonstrate that caffeine can result in a small, but statistically significant, recovery of isometric tension in fatigued canine hindlimb muscle in situ, although not nearly to the same degree as seen in isolated single muscle fibres. This suggests that, in this in situ isolated whole muscle model, alteration of Ca2+ metabolism is probably only one cause of fatigue.     

Acetyl group accumulation and pyruvate dehydrogenase activity in human muscle during incremental exercise.

The changes in the muscle contents of CoASH and carnitine and their acetylated forms, lactate and the active form of pyruvate dehydrogenase complex were studied during incremental dynamic exercise. Eight subjects exercised for 3-4 minutes on a bicycle ergometer at work loads corresponding to 30, 60 and 90% of their VO2max. Muscle samples were obtained by percutaneous needle biopsy technique at rest, at the end of each work period and after 10 minutes of recovery. During the incremental exercise test there was a continuous increase in muscle lactate, from a basal value of 4.5 mmol kg-1 dry weight to 83 mmol kg-1 at the end of the final period. The active form of pyruvate dehydrogenase complex increased from 0.37 mmol acetyl-CoA formed per minute per kilogram wet weight at rest to 0.80 at 30% VO2max, 1.28 and 1.25 at 60 and 90% VO2max, respectively. Both acetyl-CoA and acetylcarnitine increased at the two highest work loads. The increase of acetyl-CoA was from 12.5 mumol kg-1 dry weight at rest to 27.3 after the highest work load and for acetylcarnitine from 6.0 mmol kg-1 dry weight to 15.2. The CoASH and free carnitine contents fell correspondingly. There was a close relationship between acetyl-CoA and acetylcarnitine accumulation in muscle during exercise, with a binding of approximately 500 mol acetyl groups to carnitine for each mole of acetyl-CoA accumulated. The results imply that the carnitine store in muscle functions as a buffer for excess formation of acetyl groups from pyruvate catalyzed by the pyruvate dehydrogenase complex.     

The effects of face cooling during hyperthermic exercise in man: evidence for an integrated thermal, neuroendocrine and behavioural response

The present study investigated whether face cooling reduced both the perceived exertion (RPE) and prolactin (PRL) release during hyperthermic exercise. Ten, non-heat-acclimated males (23 +/- 2 years; maximal oxygen consumption, 56 +/- 7 ml kg(-1) min(-1) [mean +/- s.d.]) exercised for 40 min on a cycle ergometer at 65% of their peak aerobic power, at an ambient temperature of 33 degrees C (27% relative humidity) with (FC) and without face cooling as a control (CON). With FC, forehead temperature was maintained approximately 6 degrees C lower than CON, while other skin sites were similar or slightly warmer in the FC condition. Rectal temperature increased by approximately 1.5 degrees C with the same time course in both conditions. A relative bradycardia was observed during FC, with heart rate approximately 5 beats min(-1) lower than CON (P < 0.05). Mean plasma lactate was lower during FC (FC, 5.0 +/- 0.3 mmol l(-1); CON, 5.9 +/- 0.3 mmol l(-1); P < 0.05) but no differences were observed for plasma glucose, which remained constant during exercise. Levels of PRL were maintained at 175 +/- 17 mIU l(-1) during exercise for FC, while values for CON increased to a peak of 373 +/- 22 mIU l(-1) so that towards the end of the exercise, for the same rectal temperature, PRL was significantly lower in the FC condition (P < 0.05). Global and breathing RPE were reduced but only towards the end of the 40 min of exercise during FC, whilst subjective thermal comfort was significantly lower during FC (P < 0.05). We confirm the substantial effect that FC has on the secretion of PRL during hyperthermic exercise but show that it makes a relatively small contribution to the perception of effort when compared to the effect of a cool total skin area as occurs with exercise in a thermoneutral environment.