Biomedical subjects

Michael Kjaer

Publications and source records attributed to Michael Kjaer.

63 records · Page 4Linked to original sources

PubMed2002

Combined inhibition of nitric oxide and prostaglandins reduces human skeletal muscle blood flow during exercise.

The vascular endothelium is an important mediator of tissue vasodilatation, yet the role of the specific substances, nitric oxide (NO) and prostaglandins (PG), in mediating the large increases in muscle perfusion during exercise in humans is unclear. Quadriceps microvascular blood flow was quantified by near infrared spectroscopy and indocyanine green in six healthy humans during dynamic knee extension exercise with and without combined pharmacological inhibition of NO synthase (NOS) and PG by L-NAME and indomethacin, respectively. Microdialysis was applied to determine interstitial release of PG. Compared to control, combined blockade resulted in a 5- to 10-fold lower muscle interstitial PG level. During control incremental knee extension exercise, mean blood flow in the quadriceps muscles rose from 10 +/- 0.8 ml (100 ml tissue)(-1) min(-1) at rest to 124 +/- 19, 245 +/- 24, 329 +/- 24 and 312 +/- 25 ml (100 ml tissue)(-1) min(-1) at 15, 30, 45 and 60 W, respectively. During inhibition of NOS and PG, blood flow was reduced to 8 +/- 0.5 ml (100 ml tissue)(-1) min(-1) at rest, and 100 +/- 13, 163 +/- 21, 217 +/- 23 and 256 +/- 28 ml (100 ml tissue)(-1) min(-1) at 15, 30, 45 and 60 W, respectively (P < 0.05 vs. control). In conclusion, combined inhibition of NOS and PG reduced muscle blood flow during dynamic exercise in humans. These findings demonstrate an important synergistic role of NO and PG for skeletal muscle vasodilatation and hyperaemia during muscular contraction.

Coloring Agents↗

PubMed2002

Substantial elevation of interleukin-6 concentration in peritendinous tissue, in contrast to muscle, following prolonged exercise in humans.

Plasma interleukin-6 (IL-6) concentration has been shown to increase with exercise and various cell types and tissues have been suggested to be responsible for this increase. At present no studies have measured the interstitial concentration of IL-6 in skeletal muscle and connective tissue. The present study represents the first attempt to simultaneously measure IL-6 in plasma, skeletal muscle and peritendinous connective tissue in response to prolonged exercise. Six healthy well-trained volunteers completed a 36 km run (flat, 12 km h(-1)). IL-6 was measured before, 2 h post-exercise and 24 h, 48 h, 72 h and 96 h post-exercise in both the medial gastrocnemius muscle (not measured at rest due to risk of disabling the subsequent exercise, and 24 h and 72 h post-exercise) and the peritendinous tissue around the Achilles tendon using microdialysis catheters with a high molecular mass cut-off value (3000 kDa). The plasma concentration of IL-6 was measured simultaneously, and in addition every hour during the exercise, by enzyme-linked immunosorbent assay (ELISA). The plasma concentration of IL-6 was found to increase throughout the exercise, reaching peak values immediately after completion of the run (50-fold increase). Using the microdialysis technique, the interstitial concentration of IL-6 was found to increase dramatically from 0 +/- 0 pg ml(-1) to 3618 +/- 1239 pg ml(-1) in the peritendinous tissue in the hours following the exercise. The pattern of changes was similar in plasma and peritendinous tissue, although approximately 100-fold higher in the latter. For comparison the interstitial muscle concentration was found to be 465 +/- 176 pg ml(-1) when measured 2 h post-exercise and 223 +/- 113 pg ml(-1) and 198 +/- 96 pg ml(-1) 48 h and 96 h post-exercise, respectively. The present study demonstrates that the connective tissue around the human Achilles tendon produces significant amounts of IL-6 in response to prolonged physical activity, which might contribute to the exercise-induced increase in IL-6 found in plasma.

Achilles Tendon↗

PubMed2002

Training by low-frequency stimulation of tibialis anterior in spinal cord-injured men.

The tibialis anterior muscle of nine paraplegic men was chronically stimulated (2-6 h per day; at 10 Hz, 5 s on, 5 s off) under isometric loading conditions for 5 days per week for 4 weeks. After 4 weeks of training, muscle fatigue resistance in an electrically evoked test had increased by an average of 75% (P <.01, n = 9), but there were no changes in the relative composition of the three myosin heavy chain (MHC) isoforms. Five of the subjects continued training for an additional 5 weeks (2 h per day, 3 days per week). Although there was a tendency for twitch time to peak torque to increase after this additional period, no change occurred in relative MHC isoform content. However, in situ hybridization analysis revealed that even after 2 weeks of stimulation, there was evidence of upregulation of the mRNA for the MHC-I isoform and downregulation of the MHC-IIX isoform, a development that continued in weeks 4 and 9. This study provides evidence, at the level of gene transcription, that a fast-to-slow change in MHC isoform composition may be possible in human muscle when its usage is significantly increased.

Adult↗

PubMed2002

The effect of insulin and glucagon on splanchnic oxygen consumption.

UNLABELLED: The purpose of these experiments was to measure the influence of insulin and glucagon on the splanchnic oxygen consumption. Two experiments were performed. METHODS: In one experiment, the influence of hyperinsulinaemia was investigated in six healthy subjects, who were studied during a euglycaemic hyperinsulinaemic clamp. In another experiment, the influence of glucagon was investigated in seven healthy subjects, who were studied twice during a pancreatic islet clamp with either supplementation of insulin and glucagon, or of insulin alone. In both situations the measurements were performed during euglycaemia. Splanchnic oxygen consumption and net substrate balances were studied by the arterio-hepatic venous catheterisation technique and measurement of splanchnic blood flow in all experiments. RESULTS: During the euglycaemic hyperinsulinaemic clamp, the splanchnic blood flow increased significantly and the splanchnic oxygen consumption decreased by about 20%, while the net splanchnic glucose output reversed to a net uptake. In the pancreatic islet clamp experiments there was a significant difference between the net splanchnic glucose outputs whether glucagon and insulin or only insulin was supplemented. In spite of this, the splanchnic oxygen consumption decreased by about 20% in both situations, i.e. independent of glucagon supplementation. In both experiments there was a pronounced inhibition of lipolysis, which led to decreased fatty acids availability to the liver. This resulted in a concomitant decrease in hepatic ketone body formation. This decrease could account for about 30% of the decrease in splanchnic oxygen consumption. CONCLUSION: The reduction in splanchnic oxygen consumption can be explained by decreased ketogenesis, decreased protein synthesis and changes in splanchnic fuel selection, while changes in the rate of gluconeogenesis does not seem to play a significant role.

Adult↗

PubMed2002

Subcutaneous abdominal adipose tissue lipolysis during exercise determined by arteriovenous measurements in older women.

OBJECTIVES: To characterize the lipolytic response in the subcutaneous abdominal adipose tissue in older women to endurance exercise. DESIGN: Cross-sectional exercise study. SETTING: Exercise laboratory, Copenhagen, Denmark. PARTICIPANTS: Seven healthy, older women (mean age +/- standard error = 75 +/- 2 years); weight: 67.8 +/- 4.9 kg; body fat: 40 +/- 3; maximal oxygen uptake (VO2max): 1.43 +/- 0.07 L.min 1). MEASUREMENTS: Body composition (dual energy x-ray absorptiometry (DEXA)), maximal oxygen uptake (VO2max, maximal cycling test), lipolytic response to exercise (arterial and adipose tissue venous catheterization at rest and during 60 minutes of continuous cycling at a load corresponding to 60 of VO2max), adipose tissue blood flow (ATBF) (133Xenon (133Xe) washout), oxygen consumption and respiratory exchange ratio during exercise (indirect calorimetry), whole blood glycerol, plasma nonesterified fatty acids (NEFA), lactate, glucose, epinephrine, norepinephrine, insulin, serum growth hormone, and hematocrit. RESULTS: Glycerol and NEFA mobilization rates increased by 250 and 180, respectively, from rest to exercise. This was achieved primarily by an increase in veno-arterial differences, because ATBF did not increase significantly. NEFA:glycerol mobilization ratio was about two at rest and remained at that level during exercise, indicating significant local reesterification in both conditions. After an initial decrease, arterial plasma NEFA concentration increased significantly, by 26, indicating that NEFA delivery exceeded muscle uptake. CONCLUSIONS: Older women are capable of prompt and substantial increase in subcutaneous abdominal adipose tissue glycerol and NEFA mobilization rates in response to moderate acute endurance exercise. The lipolytic response matches skeletal muscle NEFA uptake, and decreased ability to mobilize fat during exercise is therefore not likely to cause increased fat mass with advancing age.

Abdomen↗

PubMed2002

Physical capacity influences the response of insulin-like growth factor and its binding proteins to training.

The influence of initial training status on the response of circulating insulin-like growth factor (IGF) and its binding proteins (IGFBP) to prolonged physical training was studied in young men. It was hypothesized that highly standardized training would result in more extensive changes in the circulating IGF system in untrained subjects because of lower fitness level. Seven untrained (UT) and 12 well-trained (WT) individuals performed 11 wk of intense physical training (2-4 h daily). Fasting serum samples were analyzed for total and free IGF-I and -II, for IGFBP-1 to -4, as well as for IGFBP-3 proteolysis. Eleven weeks of physical training resulted in decreased levels of total IGF-I, free IGF-I, and IGFBP-4 in both the UT and WT groups. In the UT group, IGFBP-2 increased, IGFBP-3 decreased [from 4,255 +/- 410 (baseline) to 3,896 +/- 465 (SD) microg/l (week 4); P < 0.05], and IGFBP-3 proteolysis increased [from 28 +/- 8% (baseline) to 37 +/- 7% (week 4) and 39 +/- 12% (week 11); P < 0.05], whereas no significant changes were found in the WT group. In conclusion, intense physical training results in a marked influence on the IGF system and its binding proteins with generally more extensive changes seen in the untrained individuals. Also, prolonged physical training resulted in increased IGFBP-3 proteolysis in previously untrained individuals only, indicating that intense physical training affects trained and untrained individuals differently.

Adult↗

PubMed2002

Lipolysis in human adipose tissue during exercise: comparison of microdialysis and a-v measurements.

Subcutaneous adipose tissue lipolysis was studied in vivo by Fick's arteriovenous (a-v) principle using either calculated (microdialysis) or directly measured (catheterization) adipose tissue venous glycerol concentration. We compared results during steady-state (rest and prolonged continuous exercise), as well as during non-steady-state (onset of exercise and early exercise) experimental settings. Fourteen healthy women [age: 74 +/- 1 (SE) yr] were studied at rest and during 60-min continuous bicycling at 60% of peak O(2) uptake. Calculated and measured subcutaneous abdominal adipose tissue venous glycerol concentrations increased substantially from rest to exercise but were similar both at rest and during later stages of exercise. In contrast, during the initial approximately 40 min of exercise, calculated glycerol concentration was significantly lower (approximately 40%) than measured adipose tissue venous glycerol concentration. Despite several methodological limitations inherent to both techniques, the results strongly suggest that microdialysis and catheterization provide similar estimates of subcutaneous adipose tissue lipolysis in steady-state experimental settings like rest and continuous prolonged exercise. However, during shorter periods of exercise (<40 min), the results from the two techniques may differ quantitatively in the studied subjects. Caution should, therefore, be taken when lipolysis is evaluated, based on results obtained by the two techniques under non-steady-state conditions.

Abdomen↗

PubMed2002

Acute growth hormone administration causes exaggerated increases in plasma lactate and glycerol during moderate to high intensity bicycling in trained young men.

We studied the acute effects of a single, sc GH dose on exercise performance and metabolism during bicycling. Seven highly trained men [age, 26 +/- 1 yr (mean +/- SEM); weight, 77 +/- 3 kg; maximal oxygen uptake, 65 +/- 1 ml O(2).min(-1).kg(-1)] performed 90 min of bicycling 4 h after receiving 7.5 IU (2.5 mg) GH or placebo in a randomized, double-blinded, cross-over design trial. A standardized pre-exercise meal was given 2 h before exercise. Blood was sampled at rest and during exercise and analyzed for GH, IGF-I, glucose, lactate, insulin, glycerol, and nonesterified fatty acids (NEFA). In the placebo trial, all subjects completed the exercise protocol without any difficulties. In contrast, two subjects were not able to complete the exercise protocol in the GH trial, and one subject barely managed to complete the protocol. In addition, GH administration resulted in exaggerated increases in plasma lactate concentrations during exercise (P < 0.0001). The combined lipolytic effect of GH and exercise, evidenced by increased plasma glycerol and serum NEFA concentrations, was 3-fold greater than the effect of exercise alone (P < 0.0001), but this increased substrate availability did not result in increased whole body fat oxidation (indirect calorimetry). Plasma glucose was, on average, 9% higher during exercise after GH administration compared with placebo (P < 0.0001). We conclude that a single, relevant GH dose causes exaggerated increases in plasma lactate and glycerol as well as serum NEFA during 90 min of subsequent bicycling at moderate to high intensity. The exaggerated increase in plasma lactate may be associated with substantially decreased exercise performance.

Adult↗

PubMed2002

GH administration changes myosin heavy chain isoforms in skeletal muscle but does not augment muscle strength or hypertrophy, either alone or combined with resistance exercise training in healthy elderly men.

GH administration, either alone or combined with resistance exercise training (RT), has attracted interest as a means of increasing muscle mass and strength in the elderly. In the present study, 31 healthy, elderly men [age, 74 +/- 1 yr (mean +/- SEM)] were assigned to either RT [3 sessions/wk, 3-5 sets of 8-12 repetition maximum (RM)/session] + placebo (n = 8), RT + GH (n = 8), GH (n = 8), or placebo (n = 7) in a randomized, placebo-controlled, double-blinded (RT + placebo and RT + GH) or single-blinded (GH or placebo) design. Measurements of: 1) isokinetic quadriceps muscle strength; 2) quadriceps muscle power; 3) quadriceps muscle fiber type, size, and myosin heavy chain (MHC) composition; 4) quadriceps cross-sectional area (CSA) [nuclear magnetic resonance imaging (NMRI)]; 5) body composition (dual-energy x-ray absorptiometry scanning); and 6) GH-related serum markers were performed at baseline and after 12 wk. The final GH dose was 1.77 +/- 0.18 IU x d(-1) (approximately 7.2 +/- 0.8 microg x kg(-1) x d(-1)). GH alone had no effect on isokinetic quadriceps muscle strength, power, CSA, or fiber size. However, a substantial increase in MHC 2X isoform was observed with GH administration alone, and this may be regarded as a change into a more youthful MHC composition, possibly induced by the rejuvenating of systemic IGF-I levels. RT + placebo caused substantial increases in quadriceps isokinetic strength, power, and CSA; but these RT induced improvements were not further augmented by additional GH administration. In the RT + GH group, there was a significant decrease in MHC 1 and 2X isoforms, whereas MHC 2A increased. RT, therefore, seems to overrule the changes in MHC composition induced by GH administration alone. Changes in body composition confirmed previous reports of decreased fat mass, increased fat-free mass, and unchanged bone mineral content with GH administration. A high incidence of side effects was reported. Our results do not support a role for GH as a means of increasing muscle strength or mass, either alone or combined with RT, in healthy elderly men; although GH administration alone may induce changes in MHC composition.

Absorptiometry, Photon↗