Prolonged Exercise In Humans Research Articles

Pulmonary ventilation and gas exchange during prolonged exercise in humans: Influence of dehydration, hyperthermia and sympathoadrenal activity.

What is the central question of the study? Ventilation increases during prolonged intense exercise, but the impact of dehydration and hyperthermia, with associated blunting of pulmonary circulation, and independent influences of dehydration, hyperthermia and sympathoadrenal discharge on ventilatory and pulmonary gas exchange responses remain unclear. What is the main finding and its importance? Dehydration and hyperthermia led to hyperventilation and compensatory adjustments in pulmonary CO2 and O2 exchange, such that CO2 output increased and O2 uptake remained unchanged despite the blunted circulation. Isolated hyperthermia and adrenaline infusion, but not isolated dehydration, increased ventilation to levels similar to combined dehydration and hyperthermia. Hyperthermia is the main stimulus increasing ventilation during prolonged intense exercise, partly via sympathoadrenal activation. The mechanisms driving hyperthermic hyperventilation during exercise are unclear. In a series of retrospective analyses, we evaluated the impact of combined versus isolated dehydration and hyperthermia and the effects of sympathoadrenal discharge on ventilation and pulmonary gas exchange during prolonged intense exercise. In the first study, endurance-trained males performed two submaximal cycling exercise trials in the heat. On day 1, participants cycled until volitional exhaustion (135± 11min) while experiencing progressive dehydration and hyperthermia. On day 2, participants maintained euhydration andcore temperature (Tc ) during a time-matched exercise (control). At rest and during the first 20min of exercise, pulmonary ventilation ( ), arterial blood gases, CO2 output and O2 uptake were similar in both trials. At 135±11min, however, was elevated with dehydration and hyperthermia, and this was accompanied by lower arterial partial pressure of CO2 , higher breathing frequency, arterial partial pressure of O2 , arteriovenous CO2 and O2 differences, and elevated CO2 output and unchanged O2 uptake despite a reduced pulmonary circulation. The increased was closely related to the rise in Tc and circulating catecholamines (R2 ≥0.818, P≤0.034). In three additional studies in different participants, hyperthermia independently increased to an extent similar to combined dehydration and hyperthermia, whereas prevention of hyperthermia in dehydrated individuals restored to control levels. Furthermore, adrenaline infusion during exercise elevated both Tc and . These findings indicate that: (1) adjustments in pulmonary gas exchange limit homeostatic disturbances in the face of a blunted pulmonary circulation; (2) hyperthermia is the main stimulus increasing ventilation during prolonged intense exercise; and (3) sympathoadrenal activation might partly mediate the hyperthermic hyperventilation.

Erythropoietin enhances whole body lipid oxidation during prolonged exercise in humans.

Animal studies have suggested that erythropoietin, besides its well-known hematopoietic effects, can modulate metabolism and prevent fat accumulation. We investigated the effects of repeated injections of recombinant human erythropoietin (EPO) on the balance of substrate oxidation during aerobic exercise in humans. Twelve healthy aerobically trained males received subcutaneously either moderate dose of EPO (50 U/kg, EPO) or saline injections (NaCl 0.9 %, control) three times a week for 4 weeks. Body weight, % fat, maximal aerobic capacity, and substrate utilization during exercise were assessed before and after treatment, while hemoglobin and hematocrit were monitored regularly during the treatment. Carbohydrate and fat oxidation were evaluated via indirect calorimetry, during a submaximal exercise performed at 75 % of the participants' maximal aerobic capacity (V̇(O2max)) for 60 min. Results showed that 4 weeks of EPO treatment significantly enhanced fat oxidation (+56 % in EPO versus -9 % in control) during exercise, independent of its effects on hematological parameters or V̇(O2max). This study shows that EPO can modulate substrate utilization during exercise, leading to enhanced fat utilization and lower use of carbohydrates. This opens new research directions exploring whether systemic EPO levels, in physiological conditions, participate to the modulation of fat oxidation.

Role of carotid body chemoreceptors in glucoregulation during prolonged exercise in humans

This study was performed to examine the role of the carotid bodies (CB) in glucoregulation during prolonged exercise in humans. Six healthy males (35 ± 5 yrs) completed two 120 minute bouts of cycling exercise (65% VO2max), during a dopamine infusion (D; 2 μg/kg/min) to acutely inactivate the CB, or a placebo, saline infusion (P). Arterial blood was drawn for glucose and counter‐regulatory hormones at baseline and during exercise (60–80: 60–80 minute mean; EE: end exercise). All variables at baseline were similar between conditions. Glucose concentration decreased throughout exercise and was similar between trials (60–80: 90 ± 7 vs. 98 ± 14; EE: 75 ± 12 vs. 80 ± 10 mg/dl; D vs. P respectively). However, when compared to baseline values, EE glucose had a greater decrease in 4 subjects during D, whereas 2 subjects had a greater attenuation during P. Glucagon was similar at 60–80 (108 ± 42 vs. 84 ± 40 pg/ml; D vs. P respectively), but was greater at EE in D than P (204 ± 104 vs. 136 ± 70 pg/ml). Cortisol (60–80: 13 ± 5 vs. 16 ± 4; EE: 22 ± 3 vs. 20 ± 7 μg/dl; D vs. P respectively) and growth hormone (60–80: 13 ± 3 vs. 12 ± 3; EE: 12 ± 4 vs. 10 ± 4 ng/ml; D vs. P respectively) concentrations were not different between conditions. Our preliminary results indicate that blood glucose during exercise with CB desensitization varies between subjects, and that the CB might contribute to blood glucose regulation during exercise. Funding: NIH R01DK090541

The impact of obesity on cardiac troponin levels after prolonged exercise in humans.

Elevated cardiac troponin I (cTnI), a marker for cardiac damage, has been reported after high-intensity exercise in healthy subjects. Currently, little is known about the impact of prolonged moderate-intensity exercise on cTnI release, but also the impact of obesity on this response. 97 volunteers (55 men and 42 women), stratified for BMI, performed a single bout of walking exercise (30–50 km). We examined cTnI-levels before and immediately after the exercise bout in lean (BMI < 25 kg/m2, n = 30, 57 ± 19 years), overweight (25 ≤ BMI < 30 kg/m2, n = 29, 56 ± 11 years), and obese subjects (BMI ≥ 30 kg/m2, n = 28, 53 ± 9 years). Walking was performed at a self-selected pace. cTnI was assessed using a high-sensitive cTnI-assay (Centaur; clinical cut-off value ≥0.04 μg/L). We recorded subject characteristics (body weight, blood pressure, presence of cardiovascular risk) and examined exercise intensity by recording heart rate. Mean cTnI-levels increased significantly from 0.010 ± 0.006 to 0.024 ± 0.046 μg/L (P < 0.001). The exercise-induced increase in cTnI was not different between lean, overweight and obese subjects (two-way ANOVA interaction; P = 0.27). In 11 participants, cTnI was elevated above the clinical cut-off value for myocardial infarction. Logistic regression analysis identified exercise intensity (P < 0.001), but not BMI, body fat percentage or waist circumference to significantly relate to positive troponin tests. In conclusion, prolonged, moderate-intensity exercise results in a comparable increase in cTnI-levels in lean, overweight and obese subjects. Therefore, measures of obesity unlikely relate to the magnitude of the post-exercise elevation in cTnI.

Rebuttal from Nybo and Secher

Point:CounterpointHumans do/do not demonstrate selective brain cooling during hyperthermiaRebuttal from Nybo and SecherPublished Online:01 Feb 2011https://doi.org/10.1152/japplphysiol.00992.2010cMoreSectionsPDF (42 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations White et al. mention three mechanisms for selective brain cooling that all represent potential routes for cerebral heat dissipation. However, heat removal through the skull is very limited and both at rest and during exercise with and without hyperthermia the main part of the metabolic heat produced in the brain is released via the venous blood leaving the brain (4, 7, 8). Therefore, the brain temperature is mainly dictated by the cerebral metabolic rate, the cerebral blood flow, and the temperature of the arterial blood. As discussed in the Counterpoint in this debate, ventilation-induced precooling of the carotid blood may increase from rest to exercise, but it should be considered that heat removed via this mechanism is restricted to ∼0.1 J·g−1·min−1 compared with a total cerebral heat production of ∼0.6 J·g−1·min−1. Furthermore, our previous evaluation of the cerebral heat balance reveals that <5% of the heat produced by the brain may be removed through the skull (7). White et al. question this assessment of the cerebral heat balance—specifically the reduction in cerebral blood flow during exercise-induced hyperthermia. Yet it has to be acknowledged that the reduction in the perfusion of the brain during exercise with heat stress has been verified by independent techniques (5, 6) and it is well known that cerebral blood flow declines when hyperventilation reduces the arterial Pco2 as observed during passive and exercise-induced hyperthermia (3, 9).When special cooling devices are applied (1) it is possible to create significant cooling of the brain, but in “natural settings,” i.e., resting or freely moving humans the rate of heat loss through the aforementioned mechanisms is limited. It would require unphysiological flow rates and/or temperature gradients if heat loss through the skull or via the emissary veins should have a significant effect on the brain temperature (2, 4).So, are humans capable of demonstrating selective brain cooling? Yes—but humans can also fly in the sky. However, both situations require specialized technical support.REFERENCES1. Boller M , Lampe JW , Katz JM , Barbut D , Becker LB. Feasibility of intra-arrest hypothermia induction: A novel nasopharyngeal approach achieves preferential brain cooling. Resuscitation 81: 1025–1030, 2010.Crossref | ISI | Google Scholar2. Brengelmann GL. Specialized brain cooling in humans? FASEB 7: 1148–1153, 1993.Crossref | ISI | Google Scholar3. Kety S , Schmidt C. The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men. J Clin Invest 27: 484–492, 1948.Crossref | PubMed | ISI | Google Scholar4. Nelson DA , Nunneley SA. Brain temperature and limits on transcranial cooling in humans: quantitative modeling results. Eur J Appl Physiol Occup Physiol 78: 353–359, 1998.Crossref | ISI | Google Scholar5. Nybo L , Møller K , Volianitis S , Nielsen B , Secher NH. Effects of hyperthermia on cerebral blood flow and metabolism during prolonged exercise in humans. J Appl Physiol 93: 58–64, 2002.Link | ISI | Google Scholar6. Nybo L , Nielsen B. Middle cerebral artery blood flow velocity is reduced with hyperthermia during prolonged exercise in humans. J Physiol 534: 279–286, 2001.Crossref | PubMed | ISI | Google Scholar7. Nybo L , Secher NH , Nielsen B. Inadequate heat release from the human brain during prolonged exercise with hyperthermia. J Physiol 545: 697–704, 2002.Crossref | PubMed | ISI | Google Scholar8. Shevelev IA. Functional imaging of the brain by infrared radiation (thermoencephaloscopy). Prog Neurobiol 56: 267–305, 1998.Crossref | ISI | Google Scholar9. White MD , Cabanac M. Exercise hyperpnea and hyperthermia in humans. J Appl Physiol 81: 1249–1254, 1996.Link | ISI | Google Scholar Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation More from this issue > Volume 110Issue 2February 2011Pages 573-574 Copyright & PermissionsCopyright © 2011 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.00992.2010cHistory Published online 1 February 2011 Published in print 1 February 2011 Metrics

In humans IL‐6 is released from the brain during and after exercise and paralleled by enhanced IL‐6 mRNA expression in the hippocampus of mice

Plasma interleukin-6 (IL-6) increases during exercise by release from active muscles and during prolonged exercise also from the brain. The IL-6 release from muscles continues into recovery and we tested whether the brain also releases IL-6 in recovery from prolonged exercise in humans. Additionally, it was evaluated in mice whether brain release of IL-6 reflected enhanced IL-6 mRNA expression in the brain as modulated by brain glycogen levels. Nine healthy male subjects completed 4 h of ergometer rowing while the arterio-jugular venous difference (a-v diff) for IL-6 was determined. The IL-6 mRNA and the glycogen content were determined in mouse hippocampus, cerebellum and cortex before and after 2 h treadmill running (N = 8). At rest, the IL-6 a-v diff was negligible but decreased to -2.2 ± 1.9 pg ml(-1) at the end of exercise and remained low (-2.1 ± 2.1 pg ml(-1) ) 1 h into the recovery (P < 0.05 vs. rest). IL-6 mRNA was expressed in the three parts of the brain with the lowest content in the hippocampus (P < 0.05) coupled to the highest glycogen content (3.2 ± 0.8 mmol kg(-1) ). Treadmill running increased the hippocampal IL-6 mRNA content 2-3-fold (P < 0.05), while the hippocampal glycogen content decreased to 2.6 ± 0.6 mmol kg(-1) (P < 0.05) with no significant changes in the two other parts of the brain. Human brain releases IL-6 both during and in recovery from prolonged exercise and mouse data suggest that concurrent changes in IL-6 mRNA and glycogen levels make the hippocampus a likely source of the IL-6 release from the brain.

The carotid baroreflex is reset following prolonged exercise in humans

Alterations in the carotid baroreflex (CBR) control of arterial pressure may explain the reduction in arterial pressure and left ventricular (LV) function after prolonged exercise. We examined the CBR control of heart rate (HR) and mean arterial pressure (MAP), in addition to changes in LV function, pre- to post-exercise. Seven males (age, mean ± SEM; 29 ± 4 years) completed 4 h of ergometer rowing at a workload of 10-15% below the lactate threshold. The CBR control of HR and MAP was assessed via the rapid neck-suction/pressure protocol. LV systolic function was measured by echocardiography, where ejection fraction (EF), the ratio of systolic blood pressure to end systolic volume (SBP/ESV) and stroke volume (SV) were estimated. Following exercise MAP was reduced (12 ± 3%) and HR was elevated (35 ± 5%; P < 0.05). Furthermore, CBR control of MAP was relocated to the left on the stimulus-response curve (P < 0.05) demonstrating that the CBR operated around a lower arterial pressure. Concomitantly, LV systolic function was reduced, indicated by a decrease in EF (22 ± 2%), SBP/ESV (32 ± 14%) and SV (25 ± 5%, P < 0.05). The reduced EF and SBP/ESV were associated with the decreased MAP operating point (r² = 0.71 and r² = 0.47, respectively, P < 0.05). The CBR is reset after prolonged exercise to a lower prevailing arterial pressure. This resetting of the CBR may contribute to the reduction arterial pressure and LV function after exercise.

Carbohydrate Administration and Exercise Performance

It is well established that carbohydrate (CHO) administration increases performance during prolonged exercise in humans and animals. The mechanism(s), which could mediate the improvement in exercise performance associated with CHO administration, however, remain(s) unclear. This review focuses on possible underlying mechanisms that could explain the increase in exercise performance observed with the administration of CHO during prolonged muscle contractions in humans and animals. The beneficial effect of CHO ingestion on performance during prolonged exercise could be due to several factors including (i) an attenuation in central fatigue; (ii) a better maintenance of CHO oxidation rates; (iii) muscle glycogen sparing; (iv) changes in muscle metabolite levels; (v) reduced exercise-induced strain; and (vi) a better maintenance of excitation-contraction coupling. In general, the literature indicates that CHO ingestion during exercise does not reduce the utilization of muscle glycogen. In addition, data from a meta-analysis suggest that a dose-dependent relationship was not shown between CHO ingestion during exercise and an increase in performance. This could support the idea that providing enough CHO to maintain CHO oxidation during exercise may not always be associated with an increase in performance. Emerging evidence from the literature shows that increasing neural drive and attenuating central fatigue may play an important role in increasing performance during exercise with CHO supplementation. In addition, CHO administration during exercise appears to provide protection from disrupted cell homeostasis/integrity, which could translate into better muscle function and an increase in performance. Finally, it appears that during prolonged exercise when the ability of metabolism to match energy demand is exceeded, adjustments seem to be made in the activity of the Na+/K+ pump. Therefore, muscle fatigue could be acting as a protective mechanism during prolonged contractions. This could be alleviated when CHO is administered resulting in the better maintenance of the electrical properties of the muscle fibre membrane. The mechanism(s) by which CHO administration increases performance during prolonged exercise is(are) complex, likely involving multiple factors acting at numerous cellular sites. In addition, due to the large variation in types of exercise, durations, intensities, feeding schedules and CHO types it is difficult to assess if the mechanism(s) that could explain the increase in performance with CHO administration during exercise is(are) similar in different situations. Experiments concerning the identification of potential mechanism(s) by which performance is increased with CHO administration during exercise will add to our understanding of the mechanism(s) of muscle/central fatigue. This knowledge could have significant implications for improving exercise performance.

Effect of glycogen availability on human skeletal muscle protein turnover during exercise and recovery

We examined the effect of carbohydrate (CHO) availability on whole body and skeletal muscle protein utilization at rest, during exercise, and during recovery in humans. Six men cycled at approximately 75% peak O(2) uptake (Vo(2peak)) to exhaustion to reduce body CHO stores and then consumed either a high-CHO (H-CHO; 71 + or - 3% CHO) or low-CHO (L-CHO; 11 + or - 1% CHO) diet for 2 days before the trial in random order. After each dietary intervention, subjects received a primed constant infusion of [1-(13)C]leucine and l-[ring-(2)H(5)]phenylalanine for measurements of the whole body net protein balance and skeletal muscle protein turnover. Muscle, breath, and arterial and venous blood samples were obtained at rest, during 2 h of two-legged kicking exercise at approximately 45% of kicking Vo(2peak), and during 1 h of recovery. Biopsy samples confirmed that the muscle glycogen concentration was lower in the L-CHO group versus the H-CHO group at rest, after exercise, and after recovery. The net leg protein balance was decreased in the L-CHO group compared with at rest and compared with the H-CHO condition, which was primarily due to an increase in protein degradation (area under the curve of the phenylalanine rate of appearance: 1,331 + or - 162 micromol in the L-CHO group vs. 786 + or - 51 micromol in the H-CHO group, P < 0.05) but also due to a decrease in protein synthesis late in exercise. There were no changes during exercise in the rate of appearance compared with rest in the H-CHO group. Whole body leucine oxidation increased above rest in the L-CHO group only and was higher than in the H-CHO group. The whole body net protein balance was reduced in the L-CHO group, largely due to a decrease in whole body protein synthesis. These data extend previous findings by others and demonstrate, using contemporary stable isotope methodology, that CHO availability influences the rates of skeletal muscle and whole body protein synthesis, degradation, and net balance during prolonged exercise in humans.

Go rinse your mouth: a novel way to improve endurance performance?

Go rinse your mouth: a novel way to improve endurance performance?

Seven days of oral taurine supplementation does not increase muscle taurine content or alter substrate metabolism during prolonged exercise in humans

This study examined 1) the plasma taurine response to acute oral taurine supplementation (T), and 2) the effects of 7 days of T on muscle amino acid content and substrate metabolism during 2 h of cycling at approximately 60% peak oxygen consumption (VO2peak). In the first part of the study, after an overnight fast, 7 volunteers (28+/-3 yr, 184+/-2 cm, 88.0+/-6.6 kg) ingested 1.66 g oral taurine doses with breakfast (8 AM) and lunch (12 noon), and blood samples were taken throughout the day. In the second part of the study, eight men (22+/-1 yr, 181+/-1 cm, 80.9+/-3.8 kg, 4.21+/-0.16 l/min VO2peak) cycled for 2 h after 7 days of placebo (P) ingestion (6 g glucose/day) and again following 7 days of T (5 g/day). In the first part of the study, plasma taurine was 64+/-4 microM before T and rose rapidly to 778+/-139 microM by 10 AM and remained elevated at noon (359+/-56 microM). Plasma taurine reached 973+/-181 microM at 1 PM and was 161+/-31 microM at 4 PM. In the second part of the study, seven days of T had no effect on muscle taurine content (mmol/kg dry muscle) at rest (P, 44+/-15 vs. T, 42+/-15) or after exercise (P, 43+/-12 vs. T, 43+/-11). There was no difference in muscle glycogen or other muscle metabolites between conditions, but there were notable interaction effects for muscle valine, isoleucine, leucine, cystine, glutamate, alanine, and arginine amino acid content following exercise after T. These data indicate that 1) acute T produces a 13-fold increase in plasma taurine concentration; 2) despite the ability to significantly elevate plasma taurine for extended periods throughout the day, 7 days of T does not alter skeletal muscle taurine content or carbohydrate and fat oxidation during exercise; and 3) T appears to have some impact on muscle amino acid response to exercise.

Commentaries on Viewpoint: Fatigue mechanisms determining exercise performance: Integrative physiology is systems physiology

Commentaries on Viewpoint: Fatigue mechanisms determining exercise performance: Integrative physiology is systems physiology

The carotid baroreflex is reset following prolonged exercise in humans

Alterations in the carotid baroreflex (CBR) control of arterial pressure may explain the reduction in arterial pressure and left ventricular (LV) function observed after prolonged exercise. We examined the CBR control of heart rate (HR) and mean arterial pressure (MAP), in addition to changes in LV function, pre‐ to post exercise. Seven males (age, 29 ± 7 yrs) completed 4 h of ergometer rowing at a workload 10–15% below lactate threshold. CBR control of HR and MAP was assessed before and after exercise via the rapid neck suction/pressure method. LV systolic function was assessed by echocardiography, where ejection fraction (EF), systolic pressure/volume ratio (SBP/ESV) and stroke volume (SV) were estimated. After exercise MAP was reduced (12 ± 3%) and HR was elevated (35 ± 5%; P&lt;0.05), indicating a relocation of the CBR operating point. Furthermore, the CBR operating pressure was relocated to the left on the HR and MAP stimulus‐response curve (P&lt;0.05) demonstrating that the CBR operated at a lower arterial pressure. Concomitantly, EF (22 ± 2%), SBP/ESV (32 ± 14%) and SV (25 ± 5%, P&lt;0.05) were reduced after exercise. The reduced EF and SBP/ESV were associated with the decreased MAP operating point (r2=0.71 and r2=0.47, P&lt;0.05). In conclusion, the CBR is reset to a lower prevailing arterial pressure after prolonged exercise, which may contribute to the reduction arterial pressure and LV function observed.

Effects of aerobic training and tea catechin intake on endurance capacity and substrate utilization during prolonged exercise in humans

Effects of aerobic training and tea catechin intake on endurance capacity and substrate utilization during prolonged exercise in humans

ENDURANCE TRAINING ATTENUATES CARDIOVASCULAR DRIFT AT THE SAME ABSOLUTE WORK RATE

Animal studies report decreases in heart rate (HR) drift after endurance training. We tested the hypothesis that endurance training would attenuate HR drift via greater cardiac vagal activity. HR and arterial blood pressure were measured in thirteen healthy young subjects (25±1 yr) during rest and 40 min of cycling at the same work rate (50% of pretraining VO2peak) before and after 8-weeks of endurance training. VO2peak increased 17±3% after training (p < 0.01). Standard deviation of the R-R interval (SDNN) and high frequency power (HF) were calculated from ECG. HR was lower at rest and throughout prolonged exercise after training (p < 0.01). There was a significant interaction of HR responses to exercise with training (p < 0.01) with HR drift greater before training (Δ9±2 vs. Δ4±2 bpm; p < 0.01). HR variability showed an increase in SDNN (Δ0.29 ms2; p < 0.01) and greater HF after training (Δ1.20 ms2; p < 0.01). Mean arterial pressure decreased less during exercise after training (Δ15 mmHg vs. 5 mmHg; p = 0.04). These results indicate that endurance training attenuates HR drift during prolonged exercise in humans by greater parasympathetic tone. NIH DC006459, HL077670, and MO1RR10732

N‐acetylcysteine attenuates the decline in muscle Na+,K+‐pump activity and delays fatigue during prolonged exercise in humans

Reactive oxygen species (ROS) have been linked with both depressed Na(+),K(+)-pump activity and skeletal muscle fatigue. This study investigated N-acetylcysteine (NAC) effects on muscle Na(+),K(+)-pump activity and potassium (K(+)) regulation during prolonged, submaximal endurance exercise. Eight well-trained subjects participated in a double-blind, randomised, crossover design, receiving either NAC or saline (CON) intravenous infusion at 125 mg kg(-1) h(-1) for 15 min, then 25 mg kg(-1) h(-1) for 20 min prior to and throughout exercise. Subjects cycled for 45 min at 71% , then continued at 92% until fatigue. Vastus lateralis muscle biopsies were taken before exercise, at 45 min and fatigue and analysed for maximal in vitro Na(+),K(+)-pump activity (K(+)-stimulated 3-O-methyfluorescein phosphatase; 3-O-MFPase). Arterialized venous blood was sampled throughout exercise and analysed for plasma K(+) and other electrolytes. Time to fatigue at 92% was reproducible in preliminary trials (c.v. 5.6 +/- 0.6%) and was prolonged with NAC by 23.8 +/- 8.3% (NAC 6.3 +/- 0.5 versus CON 5.2 +/- 0.6 min, P < 0.05). Maximal 3-O-MFPase activity decreased from rest by 21.6 +/- 2.8% at 45 min and by 23.9 +/- 2.3% at fatigue (P < 0.05). NAC attenuated the percentage decline in maximal 3-O-MFPase activity (%Deltaactivity) at 45 min (P < 0.05) but not at fatigue. When expressed relative to work done, the %Deltaactivity-to-work ratio was attenuated by NAC at 45 min and fatigue (P < 0.005). The rise in plasma [K(+)] during exercise and the Delta[K(+)]-to-work ratio at fatigue were attenuated by NAC (P < 0.05). These results confirm that the antioxidant NAC attenuates muscle fatigue, in part via improved K(+) regulation, and point to a role for ROS in muscle fatigue.

Decreased energy expenditure during prolonged sub-maximal exercise in a warm environment

The purpose of this study was to investigate the influence of a warm environment on thermoregulation and energy expenditure during sub-maximal prolonged exercise in humans. Six healthy male subjects cycled for 120 min at an intensity of 60% maximal oxygen uptake (Vo2max) at three environmental temperatures (10°C, CT; 20°C, MT; and 30°C, WT). Although oxygen uptake at WT showed a significantly lower value compared to those at MT and CT, no significant differences of respiratory exchange ratio were observed among the three environmental trials. A remarkable decrease in total energy expenditure during the 120-min exercise at WT was observed in comparison with those at MT and CT (p<0.05). Changes in rectal temperature, mean skin temperature, and mean body temperature at WT were significantly higher than those at both MT and CT. Although increases in mean body temperature from rest every five minutes during exercise were not different among three environmental temperatures, mean energy expenditures every five minutes at WT were lower compared with those at MT and CT (p<0.05). These results suggest that the increase in energy expenditure for physical exertion is substantially reduced during prolonged sub-maximal exercise in a warm environment. This acute alteration in the energy metabolism may contribute to inhibition of excess heat production and enable prolonged exercise in a warm environment.

Mitral annular myocardial velocity assessment of segmental left ventricular diastolic function after prolonged exercise in humans

We assessed segmental and global left ventricular (LV) diastolic function via tissue-Doppler imaging (TDI) as well as Doppler flow variables before and after a marathon race to extend our knowledge of exercise-induced changes in cardiac function. Twenty-nine subjects (age 18-62 year) volunteered to participate and were assessed pre- and post-race. Measurements of longitudinal plane TDI myocardial diastolic velocities at five sites on the mitral annulus included peak early myocardial tissue velocity (E'), peak late (or atrial) myocardial tissue velocity (A') and the ratio E'/A'. Standard pulsed-wave Doppler transmitral and pulmonary vein flow indices were also recorded along with measurements of body mass, heart rate, blood pressures and cardiac troponin T (cTnT), a biomarker of myocyte damage. Pre- to post-race changes in LV diastolic function were analysed by repeated measures ANOVA. Delta scores for LV diastolic function were correlated with each other and alterations in indices of LV loading. Diastolic longitudinal segmental and mean TDI data were altered post-race such that the mean E'/A' ratio was significantly depressed (1.51 +/- 0.34 to 1.16 +/- 0.35, P < 0.05). Changes in segmental and global TDI data were not related to an elevated post-race HR, a decreased post-race pre-load or an elevated cTnT. The pulsed wave Doppler ratio of peak early transmitral flow velocity (E)/peak late (or atrial) flow velocity (A) was also significantly reduced post-race (1.75 +/- 0.46 to 1.05 +/- 0.30, P < 0.05); however, it was significantly correlated with post-race changes in heart rate. The lack of change in E/E' from pre- to post-race (3.4 +/- 0.8 and 3.3 +/- 0.7, respectively) suggests that the depression in diastolic function is likely to be due to altered relaxation of the left ventricle; however, the exact aetiology of this change remains to be determined.

Short‐term exercise training in humans reduces AMPK signalling during prolonged exercise independent of muscle glycogen

We examined the effect of short-term exercise training on skeletal muscle AMP-activated protein kinase (AMPK) signalling and muscle metabolism during prolonged exercise in humans. Eight sedentary males completed 120 min of cycling at 66 +/- 1% , then exercise trained for 10 days, before repeating the exercise bout at the same absolute workload. Participants rested for 72 h before each trial while ingesting a high carbohydrate diet (HCHO). Exercise training significantly (P < 0.05) attenuated exercise-induced increases in skeletal muscle free AMP: ATP ratio and glucose disposal and increased fat oxidation. Exercise training abolished the 9-fold increase in AMPK alpha2 activity observed during pretraining exercise. Since training increased muscle glycogen content by 93 +/- 12% (P < 0.01), we conducted a second experiment in seven sedentary male participants where muscle glycogen content was essentially matched pre- and post-training by exercise and a low CHO diet (LCHO; post-training muscle glycogen 52 +/- 7% less than in HCHO, P < 0.001). Despite the difference in muscle glycogen levels in the two studies we obtained very similar results. In both studies the increase in ACCbeta Ser(221) phosphorylation was reduced during exercise after training. In conclusion, there is little activation of AMPK signalling during prolonged exercise following short-term exercise training suggesting that other factors are important in the regulation of glucose disposal and fat oxidation under these circumstances. It appears that muscle glycogen is not an important regulator of AMPK activation during exercise in humans when exercise is begun with normal or high muscle glycogen levels.

L-Arginine infusion increases glucose clearance during prolonged exercise in humans

Nitric oxide synthase (NOS) inhibition has been shown in humans to attenuate exercise-induced increases in muscle glucose uptake. We examined the effect of infusing the NO precursor L-arginine (L-Arg) on glucose kinetics during exercise in humans. Nine endurance-trained males cycled for 120 min at 72+/-1% Vo(2 peak) followed immediately by a 15-min "all-out" cycling performance bout. A [6,6-(2)H]glucose tracer was infused throughout exercise, and either saline alone (Control, CON) or saline containing L-Arg HCL (L-Arg, 30 g at 0.5 g/min) was confused in a double-blind, randomized order during the last 60 min of exercise. L-Arg augmented the increases in glucose rate of appearance, glucose rate of disappearance, and glucose clearance rate (L-Arg: 16.1+/-1.8 ml.min(-1).kg(-1); CON: 11.9+/- 0.7 ml.min(-1).kg(-1) at 120 min, P<0.05) during exercise, with a net effect of reducing plasma glucose concentration during exercise. L-Arg infusion had no significant effect on plasma insulin concentration but attenuated the increase in nonesterified fatty acid and glycerol concentrations during exercise. L-Arg infusion had no effect on cycling exercise performance. In conclusion, L-Arg infusion during exercise significantly increases skeletal muscle glucose clearance in humans. Because plasma insulin concentration was unaffected by L-Arg infusion, greater NO production may have been responsible for this effect.