Search PubMed⌕ Search

Biomedical subjects

C J Sundberg

Publications and source records attributed to C J Sundberg.

At least 19 recordsLinked to original sources
PubMed2006

Local changes in the insulin-like growth factor system in human skeletal muscle assessed by microdialysis and arterio-venous differences technique.

IGF-I plays a direct role in whole body glucose homeostasis primarily by stimulating skeletal muscle glucose uptake. IGF-I is also involved in exercise induced muscle hypertrophy. Knowledge regarding local changes in muscle IGF-I bioavailability and its regulation by IGFBPs at rest and during exercise is limited. We have therefore explored changes in total IGF-I levels as well as circulating IGFBP levels and their post-translational modifications over an exercising leg. For the first time we have determined IGF-I levels in exercising skeletal muscle microdialysate in an attempt to assess local IGF-I bioavailability. Eighteen healthy young men performed one legged knee-extension exercise during 45min. Blood samples were taken from the femoral artery and vein of the exercising leg. No significant differences between arterial and venous concentrations of total IGF-I or IGFBP-1 were detected over the leg at any time. IGF-I concentrations increased significantly during exercise in the artery but not in the vein. Total IGFBP-1 increased after exercise in both artery and vein. The increase in non-plus less phosphorylated forms of IGFBP-1 was less pronounced and did not reach statistical significance. The proportion of fragmented IGFBP-3 (IGFBP-3 proteolysis) assessed by Western immunoblotting did not change significantly during or after exercise. Although optimization and validation of IGF-I determinations in muscle microdialysate (md) will be required, our first results using this technique demonstrate a significant 2-fold increase in mdIGF-I collected during and after exercise. We conclude that determination of A-V-differences appears to be of limited value in the assessments of local muscle change in the IGF-system. A substantial release of IGF-I during short time is required to detect significant change in the large circulating store of IGF-I. We suggest that an optimized and validated microdialysis technique for determination of local IGF-I may be advantageous in future studies.

Adult↗
PubMed2005

VEGF-A splice variants and related receptor expression in human skeletal muscle following submaximal exercise.

VEGF-A contributes to muscle tissue angiogenesis following aerobic exercise training. The temporal response of the VEGF-A isoforms and their target receptors has not been comprehensively profiled in human skeletal muscle. We combined submaximal exercise with and without reduced leg blood flow to establish whether ischemia-induced metabolic stress was an important physiological stimuli responsible for regulating the VEGF-A system in humans. Nine healthy men performed two 45-min bouts of one-leg knee-extension exercise, with and without blood flow restriction. Muscle biopsies were obtained at rest and 2 and 6 h after exercise. Expression (mRNA) of the VEGF-A splice variants and related receptors [VEGF receptor (VEGFR)-1, VEGFR-2, and neuropilin-1] was determined by using qPCR. VEGF-A(total) expression increased more robustly after exercise with reduced blood flow, and initially this principally reflected an increase in VEGF-A(165). Six hours after exercise, there was a relatively greater increase in VEGF-A(189), and this response was not influenced by blood flow conditions. VEGFR-1 mRNA expression increased 2 h after exercise, and neuropilin-1 expression was transiently reduced, while all three receptors increased by 6 h. There was no evidence for the expression of the inhibitory VEGF-A(165B) variant in human skeletal muscle. Our study, reflecting both VEGF-A ligand and receptors, implicates metabolic perturbation as a regulator of human muscle angiogenesis and demonstrates that VEGF-A splice variants are distinctly regulated. Our findings also indicate that all three receptor genes exhibit different pretranslational regulation, in response to exercise in humans.

Adaptation, Physiological↗
PubMed2005

Expression of oestrogen receptor alpha and beta is higher in skeletal muscle of highly endurance-trained than of moderately active men.

AIM: Two known oestrogen receptors (ERs), ERalpha and the recently cloned ERbeta, are expressed in the human skeletal muscle of both males and females. The effects of oestrogen and the role of ERs in skeletal muscle tissue are not well known. Oestrogen receptors and some of their target genes are involved in angiogenic processes. It was hypothesized that ERs are expressed at a higher level in a group with higher oxidative capacity, and that such an enhanced expression would parallel expression of the angiogenic factor -- vascular endothelial growth factor (VEGF). METHOD: Muscle biopsies were taken from vastus lateralis in 10 highly endurance-trained males and 10 moderately active males and analysed for the expression of ERs and VEGF. RESULTS: The major findings in the present study were the higher mRNA levels of ERalpha, ERbeta and VEGF in the highly endurance-trained than in the moderately active group. CONCLUSION: These data suggest that the greater mRNA expression of ERalpha and ERbeta and the oestrogen-associated angiogenic factor VEGF support the hypothesis of an involvement of ERs in the adaptation of skeletal muscle to endurance training.

Adolescent↗
PubMed2002

Increased expression of vascular endothelial growth factor in human skeletal muscle in response to short-term one-legged exercise training.

The effects of short-term exercise training on vascular endothelial growth factor (VEGF) and one of its regulatory transcription factors, the hypoxia inducible factor 1 (HIF-1) subunit, were studied in eight healthy males. Muscle and blood samples were obtained before the 1st, and 24 h after the 7th training session. VEGF and HIF-1 mRNA were analysed using RT-PCR, VEGF mRNA localization with in situ hybridization and VEGF protein with ELISA. Concurrent increases in VEGF mRNA and protein levels were observed in skeletal muscle, and the mRNA was expressed within the skeletal muscle fibres and in cells in the interstitium. These data support the idea of a pretranslational regulation of exercise-induced changes in VEGF mRNA, and indicate that increased VEGF protein expression is an early event in skeletal muscle adaptation to training. Furthermore, different cell types may act as sources for the production of angiogenic factors in response to exercise. The levels of HIF-1 mRNA subunits did not change, suggesting no change in HIF-1 mRNA transcript levels in the regulation of training-induced VEGF expression. In contrast to increased tissue VEGF expression, the arterial and femoral venous plasma levels of VEGF were decreased by training, which may indicate an exercise-induced enhancement of the peripheral uptake of VEGF.

Adult↗
PubMed2001

Lactate concentrations in human skeletal muscle biopsy, microdialysate and venous blood during dynamic exercise under blood flow restriction.

The intramuscular microdialysate lactate concentration during dynamic exercise with various degrees of blood flow restriction and its relation to lactate concentration in skeletal muscle biopsy and venous blood were studied. Nine healthy males performed three one-legged knee extension exercises (Ex 1-3). Blood flow was restricted stepwise by applying supra-atmospheric pressure over the working leg. Microdialysate mean (range) lactate concentrations at the end of the exercise periods were 3.2 (0.5-6.6), 4.4 (1.1-9.8) and 7.9 (1.1-11.6) mmol.l(-1)during unrestricted, moderately restricted and severely restricted blood flow respectively. There was a significant correlation between microdialysate and venous lactate concentrations at the end of all three exercise periods. Microdialysate lactate concentration correlated significantly to skeletal muscle biopsy lactate concentration at the end of Ex 1. In conclusion, microdialysate lactate concentration in the working muscle increased step-wise with increasing blood flow restriction. It showed a better correlation to venous than to muscle biopsy lactate, which is possibly partly explained by the characteristics of diffusion between body compartments and differences in time resolution between the methods used.

Adult↗
PubMed2001

Mitochondrial transcription factor A and respiratory complex IV increase in response to exercise training in humans.

Protein levels of mitochondrial transcription factor A (Tfam) and nuclear- and mitochondrial-encoded subunits of respiratory chain complex IV (COX I and COX IV) as well as citrate synthase activity were analysed in muscle biopsy samples of vastus lateralis in six healthy male subjects before and after 4 weeks of one-legged cycle training. One leg was trained with restricted blood flow. The other leg was trained with the same power profile but with non-restricted blood flow. Tfam, COX I and COX IV levels all increased with training, with no differences observed between the legs. The training-induced increase in citrate synthase activity was greater in the leg trained with restricted blood flow. These findings indicate that changed expression of Tfam protein could be one mechanism of exercise-induced mitochondrial biogenesis. The increases of COX I and COX IV indicate a concurrent increase of nuclear- and mitochondrial-encoded subunits of respiratory enzyme complex IV at the protein level in skeletal muscle in response to increased muscle activity. In this study, it was not possible to demonstrate that the greater energy disturbance induced by reduced blood flow further stimulates the expression of mitochondrial proteins, even though it did cause a greater enhancement of citrate synthase activity in concordance with earlier studies.

Adult↗
PubMed2000

Effects of dynamic ischaemic training on human skeletal muscle dimensions.

The effect of training under conditions of local leg ischaemia on muscle area and fibre dimensions was studied in nine males. Leg ischaemia was induced by enclosing the legs in a pressure chamber and sealing the opening with a rubber membrane at the level of the crotch. Air pressure over the legs was 50 mmHg. The subjects performed 16 sessions (45 min) of one-legged supine strenuous ischaemic training during 4 weeks. Exercise intensity was maintained as high as possible during the whole session. The contralateral leg served as a control leg and remained passive during exercise. Before and after the training period, muscle fibre dimensions were determined from biopsy samples taken from the m. vastus lateralis, and leg muscle dimensions were assessed by magnetic resonance imaging (MRI). In the trained leg, mean fibre area increased by 12% (P < 0.05). The MRI-assessed cross-sectional area of the vastus group increased by 4% (P = 0.01). In the control leg, mean fibre area and the cross-sectional area of the vastus group were unchanged, while those of the adductor muscle group decreased by 4% (P < 0.05). It is concluded that a short period of strenuous ischaemic endurance training increases the cross-sectional area of the ischaemically trained muscle group, as measured both by MRI and from muscle biopsy samples. In contrast, the adductor muscles in the contralateral thigh showed a decreased cross-sectional area (as assessed by MRI), possibly due to the effects of the strenuous contralateral training, by mechanisms that have yet to be identified.

Adult↗
PubMed2000

Continuous assessment of local metabolism by microdialysis in critical limb ischaemia.

OBJECTIVE: to investigate the feasibility of using microdialysate glucose, lactate and pyruvate concentrations for grading the severity of blood flow reduction in patients with critical limb ischaemia. PATIENTS AND METHODS: microdialysis catheters were inserted (two subcutaneously and one intramuscularly) in the symptomatic limb of ten patients. To further reduce limb perfusion, the lower leg was elevated during part of the experiment. RESULTS: elevation reduced ankle and toe blood pressure and transcutaneous oxygen tension. Microdialysate glucose concentration decreased at all three catheter sites, while lactate increased in the intramuscular catheter. Two patients interrupted the elevated position prematurely due to severe pain in the foot. They had among the highest lactate levels in the horizontal position and the most marked increases following provocation. Neither initial metabolite concentrations nor concentration changes during elevation were shown to correlate to conventional methods used to assess limb perfusion. CONCLUSIONS: in patients with critical limb ischaemia microdialysis can be used without complications. A significant decrease in glucose concentration may reflect lowered blood flow in the elevated position. Metabolic response, i.e. increase in lactate concentration during profoundly reduced limb perfusion was heterogeneous, indicating an overestimation of the presence of ischaemia in some patients using current diagnostic methods.

Arterial Occlusive Diseases↗
PubMed1999

Exercise-induced expression of angiogenesis-related transcription and growth factors in human skeletal muscle.

mRNA expression of vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), and hypoxia-inducible factor (HIF) subunits HIF-1alpha and HIF-1beta in human skeletal muscle was studied during endurance exercise at different degrees of oxygen delivery. Muscle biopsies were taken before and after 45 min of one-legged knee-extension exercise performed under conditions of nonrestricted or restricted blood flow (approximately 15-20% lower) at the same absolute workload. Exercise increased VEGF mRNA expression by 178% and HIF-1beta by 340%, but not HIF-1alpha and FGF-2. No significant differences between the restricted and nonrestricted groups were observed. The exercise-induced increase in VEGF mRNA was correlated to the exercise changes in HIF-1alpha and HIF-1beta mRNA. The changes in VEGF, HIF-1alpha, and HIF-1beta mRNAs were correlated to the exercise-induced increase in femoral venous plasma lactate concentration. It is concluded that 1) VEGF but not FGF-2 gene expression is upregulated in human skeletal muscle by a single bout of dynamic exercise and that there is a graded response in VEGF mRNA expression related to the metabolic stress and 2) the increase in VEGF mRNA expression correlates to the changes in both HIF-1alpha and HIF-1beta mRNA.

Adult↗
PubMed1999

Metabolic response in type I and type II muscle fibers during a 30-s cycle sprint in men and women.

The acute metabolic response to sprint exercise was studied in 20 male and 19 female students. We hypothesized that the reduction of muscle glycogen content during sprint exercise would be smaller in women than in men and that a possible gender difference in glycogen reduction would be higher in type II than in type I fibers. The exercise-induced increase in blood lactate concentration was 22% smaller in women than in men. A considerable reduction of ATP (50%), phosphocreatine (83%), and glycogen (35%) was found in type II muscle fibers, and it did not differ between the genders. A smaller reduction of ATP (17%) and phosphocreatine (78%) was found in type I fibers, and it did not differ between the genders. However, the exercise-induced reduction in glycogen content in type I fibers was 50% smaller in women than in men. The hypothesis was indeed partly confirmed: the exercise-induced glycogen reduction was attenuated in women compared with men, but the gender difference was in type I rather than in type II fibers. Fiber-type-specific and gender-related differences in the metabolic response to sprint exercise might have implications for the design of training programs for men and women.

Adenosine Triphosphate↗
PubMed1998

[Reduced morbidity and the risk of premature death. Regular physical exercise is beneficial for health at all ages].

Regular physical activity yields benefits to men and women of all ages. The risk of premature death is reduced, as is that of incurring or dying of ischaemic heart disease. These benefits are attainable with only moderate physical activity, such as a 30-minute daily walk, though a "dose-dependent" relationship exists between physical activity and health benefits: "Some exercise is better than none, and more is better than less". Both the World Health Organisation, and the National Institutes of Health in the USA, for example, recommend that clinicians should counsel all patients to enroll in some programme of regular physical activity tailored to suit their health status and personal life-style.

Adult↗
PubMed1998

Substrate availability limits human skeletal muscle oxidative ATP regeneration at the onset of ischemic exercise.

We have demonstrated previously that dichloroacetate can attenuate skeletal muscle fatigue by up to 35% in a canine model of peripheral ischemia (Timmons, J.A., S.M. Poucher, D. Constantin-Teodosiu, V. Worrall, I.A. Macdonald, and P.L. Greenhaff. 1996. J. Clin. Invest. 97:879-883). This was thought to be a consequence of dichloroacetate increasing acetyl group availability early during contraction. In this study we characterized the metabolic effects of dichloroacetate in a human model of peripheral muscle ischemia. On two separate occasions (control-saline or dichloroacetate infusion), nine subjects performed 8 min of single-leg knee extension exercise at an intensity aimed at achieving volitional exhaustion in approximately 8 min. During exercise each subject's lower limbs were exposed to 50 mmHg of positive pressure, which reduces blood flow by approximately 20%. Dichloroacetate increased resting muscle pyruvate dehydrogenase complex activation status by threefold and elevated acetylcarnitine concentration by fivefold. After 3 min of exercise, phosphocreatine degradation and lactate accumulation were both reduced by approximately 50% after dichloroacetate pretreatment, when compared with control conditions. However, after 8 min of exercise no differences existed between treatments. Therefore, it would appear that dichloroacetate can delay the accumulation of metabolites which lead to the development of skeletal muscle fatigue during ischemia but does not alter the metabolic profile when a maximal effort is approached.

Acetylcarnitine↗
PubMed1998

Effect of restricted blood flow on exercise-induced hormone changes in healthy men.

To test the influence of the accumulation of metabolites on exercise-induced hormone responses, plasma concentrations of cortisol, growth hormone (GH), insulin, testosterone, thyrotropin (TSH), free thyroxine (fT4) and triiodothyronine (T3) were compared during exercise performed under normal conditions (control) and under conditions of restricted blood flow of exercising leg muscles (ischaemia) in nine healthy young men. Blood supply was reduced by 15%-20% by the application of 50 mmHg external pressure over the exercising leg. During 45-min cycling exercise during ischaemia the increase in GH concentration was twice as large as under normal conditions. Despite the below-threshold exercise intensity for activation of the pituitary-adrenocortical system under normal exercise conditions ischaemic exercise elicited cortisol and T3 responses (concentration increases of 83% and 9.5%, respectively). Ischaemic exercise attenuated the decrease of plasma insulin concentration found under normal conditions. The concentrations of testosterone, TSH and fT4 were not changed significantly during exercise performed in either condition. The results support the suggested essential role of muscle metaboreceptors in the control of hormone responses during muscle activity.

Adolescent↗
PubMed1998

Muscle acetyl group availability is a major determinant of oxygen deficit in humans during submaximal exercise.

The delay in skeletal muscle mitochondrial ATP production at the onset of exercise is thought to be a function of a limited oxygen supply. The delay, termed the oxygen deficit, can be quantified by assessing the above baseline oxygen consumption during the first few minutes of recovery from exercise. During submaximal exercise, the oxygen deficit is reflected by the extent of muscle phosphocreatine (PCr) breakdown. In the present study, nine male subjects performed 8 min of submaximal, single leg knee extension exercise after saline (Control) and dichloroacetate (DCA) infusion on two separate occasions. Administration of DCA increased resting skeletal muscle pyruvate dehydrogenase complex activation status threefold (Control = 0.4 +/- 0.1 vs. DCA = 1.3 +/- 0.1 mmol acetyl-CoA.min-1.kg wet muscle-1 at 37 degrees C, P < 0.01) and elevated acetylcarnitine concentration fivefold (Control = 2.2 +/- 0.5 vs. DCA = 10.9 +/- 1.2 mmol/kg dry mass, P < 0.01). During exercise, PCr degradation was reduced by approximately 50% after DCA (Control = 33.2 +/- 7.1 vs. DCA = 18.4 +/- 7.1 mmol/kg dry mass, P < 0.05). It would appear, therefore, that in humans acetyl group availability is a major determinant of the rate of increase in mitochondrial respiration at the onset of exercise and hence the oxygen deficit.

Acetylation↗
PubMed1997

Effect of acute endurance and strength exercise on circulating calcium-regulating hormones and bone markers in young healthy males.

Physical activity plays a role in the maintenance of the skeleton but the mechanical, metabolic and hormonal mechanisms involved are largely unknown. The influence of acute endurance and strength exercise on circulating levels of calcitonin, parathyroid hormone (PTH), PTH-related peptide (PTHrP), osteocalcin, carboxyterminal cross-linked telopeptide of type I collagen (ICTP) and ionized calcium (Ca2+) was therefore evaluated. Eight healthy young males performed three exercise bouts on separate occasions: endurance exercise, i.e. cycling on a cycle ergometer for 45 min at 55% of Vo2max (E55%) and 15 min at 85% of Vo2max (E85%) and strength exercise at 85% of three repetitions maximum using a leg-press device (STR). Control experiments included the same subjects with the same time schedule but without exercise. Blood samples were taken before, immediately after exercise and during the recovery period. Hormones and bone markers were measured by use of various immunoassays. There was no obvious influence on calcitonin and PTHrP levels, whereas PTH was increased after strength exercise. ICTP and osteocalcin levels correlated positively at all times and showed regular variations. In comparison with the controls, ICTP levels showed a more pronounced decrease following physical activity whereas osteocalcin followed the same pattern as the controls except for after prolonged endurance exercise when a decrease was abolished. In conclusion, an increase in PTH after strength exercise and a pronounced decrease in ICTP after all exercise together with a relative increase in osteocalcin after prolonged endurance exercise might reflect some mechanisms involved in the positive effect of physical activity on bone mass.

Adult↗
PubMed1996

Blood pressure and heart rate responses to sudden changes of gravity during exercise.

Heart rate (HR) and blood pressure responses to sudden changes of gravity during 80- to 100-W leg exercise were studied. One group was exposed to sudden changes between 1.0 and 0 g in the head-to-foot direction (Gz+), starting upright and with repeated 30-s tilts to the supine position. Another group was exposed to sudden Gz+ changes between 1.8 and 0 g in an aircraft performing parabolic flight. Arterial blood pressure at the level of the carotid (carotid distending pressure, CDP) showed a large transient increase by 27-47 mmHg when Gz+ was suddenly decreased and a similar drop when Gz+ was suddenly increased. HR displayed a reverse pattern with larger transients (-22 to -26 min-1) in response to Gz+ decreases and more sluggish changes of lower amplitude in the other direction. Central blood volume, as estimated from the inverse of transthoracic impedance (1/TTI), varied in concert with Gz+. A model is proposed in which HR responses are described as a function of CDP and 1/TTI after a time delay of 2.3-3.0 s and including a low-pass filter function with time constants of 0.34-0.35 s for decreasing HR and time constants of 2.9-4.6 s for increasing HR. The sensitivity of the carotid component was around -0.8 to -1.0 min-1 . mmHg-1 (4-7 ms/mmHg). The cardiopulmonary baroreceptor component was an additive input but was of modest relative importance during the initial HR responses. For steady-state HR responses, however, our model suggests that inputs from carotid and cardiopulmonary receptors are of equal importance.

Adult↗