M. Kjaer

Monitoring tissue oxygen availability with near infrared spectroscopy (NIRS) in health and disease.

Near infrared spectroscopy (NIRS) is becoming a widely used research instrument to measure tissue oxygen (O2) status non‐invasively. Continuous‐wave spectrometers are the most commonly used devices, which provide semi‐quantitative changes in oxygenated and deoxygenated hemoglobin in small blood vessels (arterioles, capillaries and venules). Refinement of NIRS hardware and the algorithms used to deconvolute the light absorption signal have improved the resolution and validity of cytochrome oxidase measurements. NIRS has been applied to measure oxygenation in a variety of tissues including muscle, brain and connective tissue, and more recently it has been used in the clinical setting to assess circulatory and metabolic abnormalities. Quantitative measures of blood flow are also possible using NIRS and a light‐absorbing tracer, which can be applied to evaluate circulatory responses to exercise along with the assessment of tissue O2 saturation. The venular O2 saturation can be estimated with NIRS by applying venous occlusion and measuring changes in oxygenated vs. total hemoglobin. These various measurements provide the opportunity to evaluate several important metabolic and circulatory patterns in very localized regions of tissue and may be fruitful in the study of occupational syndromes and a variety of diseases.

The effect of supervised rehabilitation on strength, postural sway, position sense and re‐injury risk after acute ankle ligament sprain

The effect of an early rehabilitation program, including postural training, on ankle joint function after an ankle ligament sprain was investigated prospectively. Ninety‐two subjects, matched for age, sex, and level of sports activity, were randomized to a control or training group. All subject received the same standard information regarding early ankle mobilization. In addition, the training group participated in supervised physical therapy rehabilitation (1 h. twice weekly) with emphasis on balance training. Postural sway, position sense and isometric ankle strength were measured 6 weeks and 4 months after the injury, and at 12 months re‐injury data were obtained. In the training group, there was a significant difference between the injured and uninjured side for plantar flexion (P<0.01), eversion (P<0.01) and inversion (P<0.05), but not for dorsiflexion at 6 weeks. In the control group, there was a significant difference between the injured and uninjured side for plantar flexion (P<0.01), eversion (P<0.01), inversion (P<0.01), and dorsiflexion (P<0.05) at 6 weeks. Postural sway, but not position sense, differed between the injured and uninjured side in both groups (P<0.01) at 6 weeks. The side‐to‐side percent differences were similar in both groups for all variables (P>0.05) at 6 weeks, and there were no side‐to‐side differences at 4 months in either group. In the control group, 11/38 (29%) suffered a re‐injury. while this number was only 2/29 (7%)) in the training group (P<0.05). These data showed that an ankle injury resulted in reduced ankle strength and postural control at 6 weeks, but that these variables had normalized at 4 months, independent of the supervised rehabilitation. However, the findings also demonstrated that supervised rehabilitation may reduce the number of re‐injuries, and therefore may play a role in injury prevention.

Effects of aging on human skeletal muscle after immobilization and retraining

Inactivity is a recognized compounding factor in sarcopenia and muscle weakness in old age. However, while the negative effects of unloading on skeletal muscle in young individuals are well elucidated, only little is known about the consequence of immobilization and the regenerative capacity in elderly individuals. Thus the aim of this study was to examine the effect of aging on changes in muscle contractile properties, specific force, and muscle mass characteristics in 9 old (61-74 yr) and 11 young men (21-27 yr) after 2 wk of immobilization and 4 wk of retraining. Both young and old experienced decreases in maximal muscle strength, resting twitch peak torque and twitch rate of force development, quadriceps muscle volume, pennation angle, and specific force after 2 wk of immobilization (P < 0.05). The decline in quadriceps volume and pennation angle was smaller in old compared with young (P < 0.05). In contrast, only old men experienced a decrease in quadriceps activation. After retraining, both young and old regained their initial muscle strength, but old had smaller gains in quadriceps volume compared with young, and pennation angle increased in young only (P < 0.05). The present study is the first to demonstrate that aging alters the neuromuscular response to short-term disuse and recovery in humans. Notably, immobilization had a greater impact on neuronal motor function in old individuals, while young individuals were more affected at the muscle level. In addition, old individuals showed an attenuated response to retraining after immobilization compared with young individuals.

Habitual loading results in tendon hypertrophy and increased stiffness of the human patellar tendon

The purpose of this study was to examine patellar tendon (PT) size and mechanical properties in subjects with a side-to-side strength difference of > or =15% due to sport-induced loading. Seven elite fencers and badminton players were included. Cross-sectional area (CSA) of the PT obtained from MRI and ultrasonography-based measurement of tibial and patellar movement together with PT force during isometric contractions were used to estimate mechanical properties of the PT bilaterally. We found that distal tendon and PT, but not mid-tendon, CSA were greater on the lead extremity compared with the nonlead extremity (distal: 139 +/- 11 vs. 116 +/- 7 mm(2); mid-tendon: 85 +/- 5 vs. 77 +/- 3 mm(2); proximal: 106 +/- 7 vs. 83 +/- 4 mm(2); P < 0.05). Distal tendon CSA was greater than proximal and mid-tendon CSA on both the lead and nonlead extremity (P < 0.05). For a given common force, stress was lower on the lead extremity (52.9 +/- 4.8 MPa) compared with the nonlead extremity (66.0 +/- 8.0 MPa; P < 0.05). PT stiffness was also higher in the lead extremity (4,766 +/- 716 N/mm) compared with the nonlead extremity (3,494 +/- 446 N/mm) (P < 0.05), whereas the modulus did not differ (lead 2.27 +/- 0.27 GPa vs. nonlead 2.16 +/- 0.28 GPa) at a common force. These data show that a habitual loading is associated with a significant increase in PT size and mechanical properties.

Cardiovascular, ventilatory and catecholamine responses to maximal dynamic exercise in partially curarized man.

1. In ten young men the ventilatory, cardiovascular, catecholamine and metabolic responses to maximal dynamic leg exercise on a stationary bicycle were followed during partial neuromuscular blockade with tubocurarine. Maximal exercise was performed when the drug effect was at its maximum as well as during the subsequent reduction in the effect allowing a gradually increasing work intensity. The results were compared with those obtained during submaximal and maximal exercise performed without tubocurarine. Partial neuromuscular blockade decreased hand‐grip strength to 41 +/‐ 1.1% (S.E. of mean) and the maximal work load to 27 +/‐ 2.4% of control values. Voluntary effort was maximal and the rate of perceived exertion was high at all levels of exercise with tubocurarine indicating a maintained intense central nervous motor command. 2. During maximal action of the drug oxygen uptake was 1.67 +/‐ 0.11 l/min while only 0.91 +/‐ 0.13 l/min (P less than 0.01) at the same work intensity without neuromuscular blockade. This difference may reflect a dominant reliance on fast‐twitch muscle fibres when work was performed under the influence of tubocurarine. 3. Compared at a given oxygen uptake ventilation was higher during work with tubocurarine than during control exercise (e.g. 55 +/‐ 4.2 and 40 +/‐ 2.2 l/min, respectively (P less than 0.01), at a mean oxygen uptake of 1.9 l/min), while heart rate did not differ significantly (146 +/‐ 4.4 and 139 +/‐ 3.0 beats/min). With decreasing drug effect both variables increased towards the maximum values of 138 +/‐ 4.5 l/min and 183 +/‐ 3.9 beats/min, respectively, achieved in control experiments at an oxygen uptake of 3.8 +/‐ 0.2 l/min. Like heart rate the mean arterial blood pressure increased with increasing work load and was similar at a given oxygen uptake with and without tubocurarine. 4. During maximal exercise at peak tubocurarine effect plasma adrenaline and noradrenaline concentrations were smaller than during control maximum, 1.6 +/‐ 0.27 versus 3.4 +/‐ 0.55 nmol/l (P less than 0.01) and 7.5 +/‐ 1.3 versus 12.6 +/‐ 1.8 nmol/l (P less than 0.05), respectively. However, comparisons at identical oxygen uptake rates revealed that catecholamine responses were markedly enhanced during tubocurarine treatment. Also, blood lactate concentrations were smaller at peak tubocurarine action than during control maximum, 1.9 +/‐ 0.42 mmol/l and 6.1 +/‐ 0.49 mmol/l (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Structural, biochemical, cellular, and functional changes in skeletal muscle extracellular matrix with aging

The extracellular matrix (ECM) of skeletal muscle is critical for force transmission and for the passive elastic response of skeletal muscle. Structural, biochemical, cellular, and functional changes in skeletal muscle ECM contribute to the deterioration in muscle mechanical properties with aging. Structural changes include an increase in the collagen concentration, a change in the elastic fiber system, and an increase in fat infiltration of skeletal muscle. Biochemical changes include a decreased turnover of collagen with potential accumulation of enzymatically mediated collagen cross‐links and a buildup of advanced glycation end‐product cross‐links. Altered mechanotransduction, poorer activation of satellite cells, poorer chemotactic and delayed inflammatory responses, and a change in modulators of the ECM are important cellular changes. It is possible that the structural and biochemical changes in skeletal muscle ECM contribute to the increased stiffness and impairment in force generated by the contracting muscle fibers seen with aging. The cellular interactions provide and potentially coordinate an adaptation to mechanical loading and ensure successful regeneration after muscle injury. Some of the changes in skeletal muscle ECM with aging may be preventable with resistance or weight training, but it is clear that more human studies are needed on the topic.

Local administration of insulin‐like growth factor‐I (IGF‐I) stimulates tendon collagen synthesis in humans

Collagen is the predominant structural protein in tendons and ligaments, and can be controlled by hormonal changes. In animals, injections of insulin‐like growth factor I (IGF‐I) has been shown to increase collagen synthesis in tendons and ligaments and to improve structural tissue healing, but the effect of local IGF‐I administration on tendon collagen synthesis in human has not been studied. The purpose of this study was to study whether local injections of IGF‐I would have a stimulating effect on tendon collagen synthesis. Twelve healthy nonsmoking men [age 62 ± 1 years (mean ± SEM), BMI 27 ± 1] participated. Two injections of either human recombinant IGF‐I (0.1 mL Increlex©) or saline (control) into each patellar tendon were performed 24‐h apart, respectively. Tendon collagen fractional synthesis rate (FSR) was measured by stable isotope technique in the hours after the second injection. Simultaneously, interstitial peritendinous (IGF‐I) and [procollagen type I N‐terminal propeptide (PINP)], as a marker for type I collagen synthesis, were determined by microdialysis technique. Tendon collagen FSR and PINP were significantly higher in the IGF‐I leg compared with the control leg (P < 0.05). In conclusion, local IGF‐I administration can directly enhance tendon collagen synthesis both within and around the human tendon tissue.

Ageing is associated with diminished muscle re-growth and myogenic precursor cell expansion early after immobility-induced atrophy in human skeletal muscle

•  Elderly individuals require a prolonged recovery phase in order to return to initial muscle mass levels following short‐term immobilisation. •  The cellular mechanisms responsible for the attenuated re‐growth and associated molecular signalling processes in ageing human skeletal muscle are not fully understood. •  The main study finding was the observation of a less marked muscle mass recovery after immobilisation in elderly compared to young individuals that was paralleled by an elevation in myogenic precursor cell content in young individuals only, whereas the elderly failed to demonstrate any change in myogenic precursor cells. •  No age‐related differences were observed in the expression of major myogenic regulating factors known to promote skeletal muscle hypertrophy or satellite cell proliferation (IGF‐1Ea, MGF, MyoD1, myogenin, HGF gene products). •  In contrast, the expression of myostatin demonstrated a more pronounced up‐regulation following immobilisation along with an attenuated down‐regulation in response to reloading in older compared to young individuals, which may have contributed to the present lack of satellite cell proliferation in ageing muscle.

Expression of extracellular matrix components and related growth factors in human tendon and muscle after acute exercise.

Acute kicking exercise induces collagen synthesis in both tendon and muscle in humans, but it is not known if this relates to increased collagen transcription and if other matrix genes are regulated. Young men performed 1 h of one‐leg kicking at 67% of max workload. Biopsies were taken from the patellar tendon and vastus lateralis muscle of each leg at 2 (n = 10), 6 (n = 11), or 26 h (n = 10) after exercise. Levels of messenger ribonucleic acid mRNA for collagens, noncollagenous matrix proteins, and growth factors were measured with real‐time reverse transcription polymerase chain reaction. In tendon, gene expression was unchanged except for a decrease in insulin‐like growth factor‐IEa (IGF‐IEa; P < 0.05). In muscle, collagen expression was not significantly altered, while levels of connective tissue growth factor (CTGF), IGF‐IEa, transforming growth factor‐β1, ‐2 (TGF‐β), and the TGF‐β receptor II mRNA were increased (P < 0.05). Matrix components tenascin‐C, fibronectin, and decorin were also induced in loaded muscle (P < 0.05), while fibromodulin was unaffected. In conclusion, the relatively robust changes in matrix components and related growth factors in muscle indicate a stimulation of extracellular matrix even with moderate exercise. However, in tendon tissue, this exercise model does not appear to induce any anabolic response on the transcriptional level.

Stimulation of muscle protein synthesis by whey and caseinate ingestion after resistance exercise in elderly individuals

Sarcopenia is a well‐known phenomenon in elderly individuals and resistance exercise together with sufficient amino acid (AA) availability has proved to be a counteractive implement. However, the source of AA and supplement timing require further investigation. The objective was to compare muscle protein synthesis (MPS) to intakes of whey and caseinate after heavy resistance exercise in healthy elderly individuals, and, furthermore, to compare the timing effect of caseinate intake. Twenty‐four elderly men and women (mean ± SEM; 68 ± 1 years) were randomized to one of four groups: caseinate intake before exercise (CasPre), caseinate intake immediately after exercise (CasPost), whey intake immediately after exercise (Whey), or intake of a non‐caloric control drink (Control). Muscle myofibrillar and collagen fractional synthesis rates (FSR) were measured by a primed continuous infusion of l‐[1‐13C]leucine using labeled proteins during a 6‐h recovery period. No differences were observed in muscle myofibrillar and collagen FSR with Whey (0.09 ± 0.01%/h) compared with CasPost (0.09 ± 0.003%/h), and it did not differ between CasPre (0.10 ± 0.01%/h) and CasPost. MPS does not differ with whey and caseinate feeding immediately after heavy resistance exercise in elderly individuals, and MPS is similar with caseinate ingestion before and after exercise.