AIM:The present study investigated the effects of hyperthermia on intermittent exercise and repeated sprint performance.METHODS:Seven men completed 40 min of intermittent cycling comprising of 15 s exercise (306 +/- 22 W) and 15 s rest periods (0 W) followed by 5 x 15 s maximal sprints on a cycle ergometer in normal (approximately 20 degrees C, control) and hot (40 degrees C, hyperthermia) environments.RESULTS:Completion of the intermittent protocol in the heat elevated core and muscle temperatures (39.5 +/- 0.2 degrees C; 40.2 +/- 0.4 degrees C), heart rate (178 +/- 11 beats min(-1)), rating of perceived exertion (RPE) (18 +/- 1) and noradrenaline (38.9 +/- 13.2 micromol l(-1)) (all P < 0.05). During the first sprint (n = 6), both peak and mean power output were similar across the environmental conditions. However, mean power over the last four sprints declined to a larger extent during hyperthermia compared with the control trial (P < 0.05). Consequently, average mean power output during the five sprints was lower in hyperthermia (558.0 +/- 146.9 W) compared with control (617.5 +/- 122.6 W; P < 0.05). Power output during the repeated sprints was reduced by hyperthermia despite an elevated muscle temperature that should promote sprint performance. Venous plasma potassium concentrations (H; 5.3 +/- 0.8 mmol l(-1) vs. C; 6.3 +/- 1.0 mmol l(-1), P = 0.06) and muscle lactate levels (H; 76.6 +/- 24.3 mmol kg(-1) dry weight vs. C; 108.8 +/- 20.1 mmol kg(-1) dry weight) were lower following the hyperthermic sprints compared to control.CONCLUSION:Although an elevated muscle temperature is expected to promote sprint performance, power output during the repeated sprints was reduced by hyperthermia. The impaired performance does not seem to relate to the accumulation of recognized metabolic fatigue agents and we, therefore, suggest that it may relate to the influence of high core temperature on the function of the central nervous system.
‘As in peripheral muscles, the force that the respiratory muscles can generate at a given velocity (inspiratory flow) is higher during a stretch-shortening cycle maneuver’ The mechanical aspects of human breathing are determined by the interaction of the lung, the chest-wall, including the abdomen, and the respiratory muscles that act upon them. The respiratory muscles must be coordinated and effectively balanced in their force generation or the efficiency of breathing will be reduced. Locomotor muscles typically undergo a combination of eccentric and concentric contractions which forms a natural type of muscle function called the stretch-shortening cycle (SSC). The purpose of the SSC is to enhance muscular performance during the final phase (concentric action) when compared to the isolated concentric action. In this issue of Acta Physiologica Scandinavica, Tzelepis et al. asked: can inspiratory muscle performance be enhanced with SSC maneuvers? Maximal inspiratory flow–pressure curves were generated by having participants exhale to residual volume quickly or slowly and then inhale maximally against resistance. The quick expiration was performed to pre-stretch the inspiratory muscles immediately prior to their concentric contraction. The actively stretched inspiratory muscles were able to generate 10% greater pressure during the subsequent concentric contraction. It appears that the SSC commonly observed in locomotor muscles is paralleled by the muscles of inspiration. These novel findings should be explored further to include states of high ventilatory demand such as exercise.
AIM This study investigated the effect of prolonged exercise with and without carbohydrate intake on the brain exchange of amino acids, especially focussing on tryptophan and branched-chain amino acids (BCAA). METHODS Five male subjects exercised for 3 h on a cycle ergometer at 200 +/- 7 W on two occasions; either supplemented with a 6% carbohydrate solution or with flavoured water (placebo). Catheters were inserted into the right internal jugular vein and the radial artery of the non-dominant arm. The brain exchange of amino acids during exercise was calculated from the arterial-jugular venous concentration difference multiplied by plasma flow. RESULTS About 106 micromol (22 mg) of tryptophan was taken up by the brain during exercise in the placebo trial, whereas no significant uptake was observed in the carbohydrate trial. In accordance, the arterial concentration of free tryptophan increased from 12 +/- 1 to 20 +/- 2 micromol L(-1) during the placebo trial and was significantly higher compared with the glucose trial (14 +/- 1 micromol L(-1) at the end of exercise). Also, the arterial concentration of total tryptophan (free and albumin-bound) increased during the first 30 min of exercise in both trials, but returned to the basal level at 180 min of exercise. In both trials, BCAA were taken up by the brain while glutamine was released. CONCLUSION The present data show that both tryptophan and BCAA are taken up by the brain during prolonged exercise, and we suggest that the cerebral uptake of tryptophan may relate to increased synthesis of serotonin (5-HT) in the brain.
AIMS Endothelin-1 (ET-1) promotes endothelial cell growth. Endothelial cell proliferation involves the activation of Ca2+-activated K+ channels. In this study, we investigated whether Ca2+-activated K+ channels with big conductance (BK(Ca)) contribute to endothelial cell proliferation induced by ET-1. METHODS The patch-clamp technique was used to analyse BK(Ca) activity in endothelial cells derived from human umbilical cord veins (HUVEC). Endothelial proliferation was examined using cell counts and measuring [3H]-thymidine incorporation. Changes of intracellular Ca2+ levels were examined using fura-2 fluorescence imaging. RESULTS Characteristic BK(Ca) were identified in cultured HUVEC. Continuous perfusion of HUVEC with 10 nmol L(-1) ET-1 caused a significant increase of BK(Ca) open-state probability (n = 14; P < 0.05; cell-attached patches). The ET(B)-receptor antagonist (BQ-788, 1 micromol L(-1)) blocked this effect. Stimulation with Et-1 (10 nmol L(-1)) significantly increased cell growth by 69% (n = 12; P < 0.05). In contrast, the combination of ET-1 (10 nmol L(-1)) and the highly specific BK(Ca) blocker iberiotoxin (IBX; 100 nmol L(-1)) did not cause a significant increase in endothelial cell growth. Ca2+ dependency of ET-1-induced proliferation was tested using the intracellular Ca2+-chelator BAPTA (10 micromol L(-1)). BAPTA abolished ET-1 induced proliferation (n = 12; P < 0.01). In addition, ET-1-induced HUVEC growth was significantly reduced, if cells were kept in a Ca2+-reduced solution (0.3 mmol L(-1)), or by the application of 2 aminoethoxdiphenyl borate (100 micromol L(-1)) which blocks hyperpolarization-induced Ca2+ entry (n = 12; P < 0.05). CONCLUSION Activation of BK(Ca) by ET-1 requires ET(B)-receptor activation and induces a capacitative Ca2+ influx which plays an important role in ET-1-mediated endothelial cell proliferation.
This review presents hormonal responses to various cold exposures and their calorigenic effects in man and some animals. Previous studies in rats have shown that cold exposures activate the hypothalamic-pituitary-thyroid axis. Increased thyroid hormone concentrations lead to heat production via general stimulation of metabolism (obligatory thermogenesis) and possibly via activation of thyroid hormone receptors and uncoupling protein 1 (UCP 1) and deiodinase enzyme genes in the brown adipose tissue (BAT). In human subjects long-term cold exposures do not seem to activate the pituitary-thyroid axis, but rather accelerate the elimination of triiodothyronine (T3), leading to low serum concentrations of free T3 hormone. In corollary to this a hypothyreotic condition with increased serum thyroid-stimulating hormone and impaired mood and cognitive performance can be observed after long-term cold exposures such as wintering. During cold exposures the sympathetic nerve system is activated and noradrenaline is released to blood circulation and to BAT, where it leads to production of cAMP, lipolysis and free fatty acids. Free fatty acids open the mitochondrial proton channel protein in BAT. Protons enter the mitochondria and inhibit ATP synthesis (uncoupling). By this way energy is transformed into heat (facultatory or adaptive thermogenesis). In adult human subjects the amount of BAT is small and adaptive thermogenesis (non-shivering thermogenesis) has a smaller role. UCP 1 with other uncoupling proteins may have other functions in the control of body weight, sugar balance and formation of reactive oxygen species.
Aim: Ageing is one of many factors altering skeletal muscle. Conflicting results from previous studies guided this review to identify what has been found to date regarding microvascular adaptations in skeletal muscle as the result of ageing or inactivity, and endurance or resistance training interventions. Additionally, this review attempts to identify the variety of parameters for determining capillarization and discuss why these might be contributing to the conflicting results.Methods: Electronic database searches were conducted for full-length articles using relevant keywords related to ageing, muscle capillarization and exercise in all fields. Cross-sectional, longitudinal, training and review papers were included. Several studies on younger subject adaptation were also included for comparison.Results: Ageing and inactivity both result in regressive structural and functional changes to skeletal muscle capillarization. The rate and magnitude of decline is still unknown. Endurance training can positively effect structural changes to capillarity. There is conflicting evidence regarding the effects of resistance training. Training intensity may be an important factor. Biopsy sampling, histological staining and several measurement protocols may be providing inaccurate estimations of capillarity.Conclusion: Part of the difficulty in determining the nature of these relationships has been the inconsistency in research conducted regarding age groups and controlling for past and present activity patterns. Further difficulties comparing across studies arise due to the variety of methods and parameters used to sample and analyse muscle tissue. Standardizing methodology will allow future research to yield more consistent results.
The regenerative capacity of skeletal muscle will depend on the number of available satellite cells and their proliferative capacity. We have measured both parameters in ageing, and have shown that although the proliferative capacity of satellite cells is decreasing during muscle growth, it then stabilizes in the adult, whereas the number of satellite cells decreases during ageing. We have also developed a model to evaluate the regenerative capacity of human satellite cells by implantation into regenerating muscles of immunodeficient mice. Using telomere measurements, we have shown that the proliferative capacity of satellite cells is dramatically decreased in muscle dystrophies, thus hampering the possibilities of autologous cell therapy. Immortalization by telomerase was unsuccessful, and we currently investigate the factors involved in cell cycle exits in human myoblasts. We have also observed that insulin-like growth factor-1 (IGF-1), a factor known to provoke hypertrophy, does not increase the proliferative potential of satellite cells, which suggests that hypertrophy is provoked by increasing the number of satellite cells engaged in differentiation, thus possibly decreasing the compartment of reserve cells. We conclude that autologous cell therapy can be applied to specific targets when there is a source of satellite cells which is not yet exhausted. This is the case of Oculo-Pharyngeal Muscular Dystrophy (OPMD), a late onset muscular dystrophy, and we participate to a clinical trial using autologous satellite cells isolated from muscles spared by the disease.
Acta Physiologica ScandinavicaVolume 183, Issue 1 p. 125-126 Integration of mathematical and experimental approaches to resolve insulin signalling P. Sögård, P. Sögård University of Skövde, Skövde, Sweden Department of Surgical Sciences, Karolinska Institute, Stockholm, SwedenSearch for more papers by this authorM. Harlén, M. Harlén University of Skövde, Skövde, SwedenSearch for more papers by this authorL. T. Svensson, L. T. Svensson Arexis AB, Gothenburg, SwedenSearch for more papers by this authorJ. R. Zierath, J. R. Zierath Department of Surgical Sciences, Karolinska Institute, Stockholm, SwedenSearch for more papers by this authorP. Nilsson, P. Nilsson University of Skövde, Skövde, SwedenSearch for more papers by this author P. Sögård, P. Sögård University of Skövde, Skövde, Sweden Department of Surgical Sciences, Karolinska Institute, Stockholm, SwedenSearch for more papers by this authorM. Harlén, M. Harlén University of Skövde, Skövde, SwedenSearch for more papers by this authorL. T. Svensson, L. T. Svensson Arexis AB, Gothenburg, SwedenSearch for more papers by this authorJ. R. Zierath, J. R. Zierath Department of Surgical Sciences, Karolinska Institute, Stockholm, SwedenSearch for more papers by this authorP. Nilsson, P. Nilsson University of Skövde, Skövde, SwedenSearch for more papers by this author First published: 17 January 2005 https://doi.org/10.1111/j.1365-201X.2004.01409.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume183, Issue1January 2005Pages 125-126 RelatedInformation
‘If NCX is calcium-extrusive (forward mode) in diastole, FFR is positive; if it is sodium-extrusive (reverse mode), FFR is negative’ Changing the frequency of the heartbeat changes the force of contraction. The mechanism of the Bowditch effect (alternatively called the Treppe or staircase phenomenon) is still not known in detail, even though Henry Pickering Bowditch first published his observation of the positive force–frequency relation (FFR) in the frog heart in 1871. Altered calcium handling is likely involved, and so far most work has focused on the role of calcium channels. The article by Subramani and colleagues in this issue shows that inhibition of calcium channels in the frog heart seems to have little influence, while interventions affecting the transmembrane sodium gradient alter the FFR: the optimal frequency (at which the relation shifts from positive to negative) is moved to lower frequencies as the sodium gradient is lowered; the authors suggest that this correlates with the direction of sodium–calcium exchange (NCX) in diastole. Thus, just after a heartbeat, the NCX still admits calcium into the cell and enhances calcium store refilling; later in diastole it promotes calcium loss. If the latter phase is shortened, contractile strength will increase, but if diastole is shortened enough so also the initial phase is reduced, force is lowered again. This novel and potentially controversial idea now awaits confirmation from other studies.
Aim: To evaluate the source and role of acid-induced intraluminal nitric oxide (NO) production in the oesophagus by studying how the exposure of the oesophagus to acid affects NO release, via the NO-producing enzyme NO synthase and its relation to changes in epithelial barrier integrity.Methods: Ferrets were anaesthetized and their oesophagi were divided at both ends. The test subjects were pre-treated with the intravenous NO synthase inhibitors N(G)-nitro-L-arginine-methyl ester (L-NAME, 100 mg kg(-1)) and 1400W (12 mg kg(-1)). Untreated and N(G)-nitro-D-arginine-methyl ester pre-treated (D-NAME, 100 mg kg(-1)) animals served as controls. The oesophagus was then perfused with either HCl (0.1 M) or physiological saline for 20 min. The intraluminal NO concentration was determined before and after the acid/saline infusion while the transmucosal potential difference (PD) was monitored continuously. Oesophageal biopsies were examined for expression of inducible NO synthase using immunohistochemistry.Results: The intraluminal NO concentration increased after acid exposure. This was blocked by L-NAME and 1400W, but not by D-NAME. The peak PD response was not affected by agents affecting NO synthesis, while the plateau response was attenuated by L-NAME, D-NAME and 1400W. Immunohistochemistry revealed inducible NO synthase expression in the epithelium.Conclusions: Exposing the ferret oesophageal mucosa to acid elicited an increase in juxtamucosal NO formation through the activation of inducible NO synthase. The corresponding electrophysiological observations suggested an association between mucosal NO production and epithelial integrity.
AIM:To investigate the ability of the microdialysis technique to measure capillary selectivity of different sized plasma proteins induced by local administration of platelet activating factor (PAF).METHODS:We used hollow plasmapheresis fibres with 3 cm membrane (cut off 3000 kDa) placed on the back of anaesthetized rats.RESULTS:Platelet activating factor (50 microg mL(-1)) administered locally via the fibre, increased extravasation of radiolabelled 125I-HSA from plasma to the microdialysis fibre by approximately 900% compared both to baseline and the control fibre within 70 min (n = 6, P < 0.05). The extravasation in the control fibre did not change over time. HPLC measurement of plasma proteins in the microdialysis perfusate also demonstrated decreased capillary selectivity for proteins in the diameter range of 73 A, 56 A and 39 A after local administration of PAF (n = 6, P < 0.05). PAF also significantly lowered interstitial fluid (P(if)) pressure after subcutaneous administration (50 microg mL(-1)). Mean arterial pressure (MAP) after intravenous injection of PAF (0.4 microg kg(-1)) fell instantly by about 50 mmHg, and stabilized at 50 mmHg after 15 min (n = 6). MAP was unaltered when PAF was given through the microdialysis fibre (n = 4). Both total tissue water (TTW) and extravasation of albumin, measured as the plasma-to-tissue clearance (E-alb) showed a significant increase after PAF (n = 7, P < 0.05).CONCLUSIONS:The present study demonstrates that PAF induces plasma protein extravasation and decrease capillary selectivity of different sized plasma proteins. It also increases transcapillary fluid flux, and lowers P(if), indicating a role for PAF in the interstitium for generation of transcapillary transport of water and large molecules followed by formation of oedema.
