Maximal short term exercise capacity in healthy subjects aged 15-70 years

Fifty males and 50 females, 15-71 years of age, exercised maximally for 30 s on an isokinetic ergometer at a pedalling frequency of 60 rev./min. Results were compared with maximal oxygen uptake (VO2 max.) obtained in a progressive incremental exercise test. Total work in 30 s was higher in males than females, declined linearly by about 6% per decade of age (r = -0.65), and was related closely to height (r = 0.75) and to lean thigh volume estimated anthropometrically (r = 0.84). A close association with vital capacity (r = 0.86) was also found that accounted statistically for the combined effects of age and height. The percentage decline in power during 30 s (fatigue index) was lower in subjects reporting greater leisure activity. A close relationship was found between total work in 30 s and VO2max. (r = 0.86), with vital capacity and leisure activity exerting additional influences on VO2max. (P less than 0.001; multiple r = 0.93). The well-established reduction with age in VO2max. is associated with an apparent parallel reduction in the power output capacity of large muscle groups recruited in heavy dynamic leg exercise.     

Deficiency of skeletal muscle succinate dehydrogenase and aconitase. Pathophysiology of exercise in a novel human muscle oxidative defect.

We evaluated a 22-yr-old Swedish man with lifelong exercise intolerance marked by premature exertional muscle fatigue, dyspnea, and cardiac palpitations with superimposed episodes lasting days to weeks of increased muscle fatigability and weakness associated with painful muscle swelling and pigmenturia. Cycle exercise testing revealed low maximal oxygen uptake (12 ml/min per kg; healthy sedentary men = 39 +/- 5) with exaggerated increases in venous lactate and pyruvate in relation to oxygen uptake (VO2) but low lactate/pyruvate ratios in maximal exercise. The severe oxidative limitation was characterized by impaired muscle oxygen extraction indicated by subnormal systemic arteriovenous oxygen difference (a-v O2 diff) in maximal exercise (patient = 4.0 ml/dl, normal men = 16.7 +/- 2.1) despite normal oxygen carrying capacity and Hgb-O2 P50. In contrast maximal oxygen delivery (cardiac output, Q) was high compared to sedentary healthy men (Qmax, patient = 303 ml/min per kg, normal men 238 +/- 36) and the slope of increase in Q relative to VO2 (i.e., delta Q/delta VO2) from rest to exercise was exaggerated (delta Q/delta VO2, patient = 29, normal men = 4.7 +/- 0.6) indicating uncoupling of the normal approximately 1:1 relationship between oxygen delivery and utilization in dynamic exercise. Studies of isolated skeletal muscle mitochondria in our patient revealed markedly impaired succinate oxidation with normal glutamate oxidation implying a metabolic defect at the level of complex II of the mitochondrial respiratory chain. A defect in Complex II in skeletal muscle was confirmed by the finding of deficiency of succinate dehydrogenase as determined histochemically and biochemically. Immunoblot analysis showed low amounts of the 30-kD (iron-sulfur) and 13.5-kD proteins with near normal levels of the 70-kD protein of complex II. Deficiency of succinate dehydrogenase was associated with decreased levels of mitochondrial aconitase assessed enzymatically and immunologically whereas activities of other tricarboxylic acid cycle enzymes were increased compared to normal subjects. The exercise findings are consistent with the hypothesis that this defect impairs muscle oxidative metabolism by limiting the rate of NADH production by the tricarboxylic acid cycle.     

Relationship of skeletal muscle perfusion measured by contrast-enhanced ultrasonography to histologic microvascular density.

OBJECTIVE: The purpose of this study was to compare skeletal muscle perfusion measured by contrast-enhanced ultrasonography (CEUS) with microvascular density in muscle biopsies. METHODS: Power Doppler sonography after intravenous bolus injection of Levovist (SH U 508A; Schering AG, Berlin, Germany) was used to examine perfusion of vastus lateralis muscle in 23 healthy volunteers. Local blood volume (B), blood flow velocity (v), and blood flow (f) were calculated by analyzing replenishment kinetics. CEUS perfusion was compared with vascularization of biopsy samples from vastus lateralis muscle. Subjects were selected such that their aerobic capacity (maximal oxygen uptake [VO(2)max]) per body weight ranged between 23 and 66 mL . min(-1) . kg(-1) to render a large variability of skeletal muscle capillarization. Moreover, subjects' venous blood hematocrit (Hkt) was determined to estimate the plasmatic intravascular volume fraction (1-Hkt=PVF) in which the microbubbles can distribute. RESULTS: Median capillary density was 331/mm(2) (range, 207-469/mm(2)), and median capillary fiber contacts (CFC) were 3.6 (range, 2.3-6.5). CFC was correlated with VO(2)max (r=0.59; P<.01). Among CEUS parameters, B showed the closest correlation to CFC (r=0.53; P<.01). When CFC was normalized for PVF, correlation of B to CFC was r=0.64 (P<.01). CEUS could depict the physiologic large variability of vastus lateralis muscle perfusion at rest (median [range]: B, 2.5 [0.1-12.3] approximately mL; v, 0.3 [0.1-3.7] mm/s; f, 0.7 [0.1-5.3] approximately mL . min(-1) . 100 g tissue(-1)). CONCLUSIONS: B is significantly related to fiber-adjacent capillarization and may represent physiologic capillary recruitment (eg, through metabolic fiber-related signals). CEUS is feasible for skeletal muscle perfusion quantification.     

VO(2max) prediction from multi-frequency bioelectrical impedance analysis

Bioelectrical impedance analysis (BIA) has been shown to be highly related to skeletal muscle mass and blood volume, both of which are important determinants of maximal oxygen uptake (VO(2max)). The aim of the present study was therefore to investigate the ability of whole-body and segmental multi-frequency BIA to improve current nonexercise VO(2max) prediction models. Data for VO(2max) (mL min(-1)), anthropometry, self-reported physical activity (PA-R) and BIA were collected in 115 men and women. Multiple linear regression analysis (MLR) was used to develop the most parsimonious prediction model. Segmental BIA was not superior to whole-body measurements. Correlation coefficients between VO(2max) and resistance indices were significantly higher at 500 kHz compared to 50 kHz (p < 0.05). Intracellular resistance index, however, showed the highest correlation with VO(2max) (r = 0.89). After adjusting for age, gender and PA-R, MLR revealed that the inclusion of intracellular resistance index was slightly, but significantly (p < 0.001), superior to models based on anthropometry. Subgroup analyses indicated that the true benefit of BIA might be most prevalent in subjects with particularly low VO(2max) (<2500 mL min(-1)). In short, whole-body BIA marginally improves the accuracy of nonexercise VO(2max) prediction models and its advantage is most pronounced in individuals with particularly low VO(2max).     

Different alterations in the insulin-stimulated glucose uptake in the athlete's heart and skeletal muscle.

Physical training increases skeletal muscle insulin sensitivity. Since training also causes functional and structural changes in the myocardium, we compared glucose uptake rates in the heart and skeletal muscles of trained and untrained individuals. Seven male endurance athletes (VO2max 72 +/- 2 ml/kg/min) and seven sedentary subjects matched for characteristics other than VO2max (43 +/- 2 ml/kg/min) were studied. Whole body glucose uptake was determined with a 2-h euglycemic hyperinsulinemic clamp, and regional glucose uptake in femoral and arm muscles, and myocardium using 18F-fluoro-2-deoxy-D-glucose and positron emission tomography. Glucose uptake in the athletes was increased by 68% in whole body (P < 0.0001), by 99% in the femoral muscles (P < 0.01), and by 62% in arm muscles (P = 0.06), but it was decreased by 33% in the heart muscle (P < 0.05) as compared with the sedentary subjects. The total glucose uptake rate in the heart was similar in the athletes and control subjects. Left ventricular mass in the athletes was 79% greater (P < 0.001) and the meridional wall stress smaller (P < 0.001) as estimated by echocardiography. VO2max correlated directly with left ventricular mass (r = 0.87, P < 0.001) and inversely with left ventricular wall stress (r = -0.86, P < 0.001). Myocardial glucose uptake correlated directly with the rate-pressure product (r = 0.75, P < 0.02) and inversely with left ventricular mass (r = -0.60, P < 0.05) or with the whole body glucose disposal (r = -0.68, P < 0.01). Thus, in athletes, (a) insulin-stimulated glucose uptake is enhanced in the whole body and skeletal muscles, (b) whereas myocardial glucose uptake per muscle mass is reduced possibly due to decreased wall stress and energy requirements or the use of alternative fuels, or both.     

Muscle strength in relation to disease severity in patients with congestive heart failure

OBJECTIVE: Indices of exercise capacity such as peak oxygen uptake (VO2peak) and muscle strength are important in association with reduced mortality. The present study compared differences in VO2peak and muscle strength indices (grip strength and knee extensor and flexor muscle strength) with disease severity and investigated the relation of these variables in congestive heart failure (CHF) patients. DESIGN: The study comprised 102 patients with stable CHF (93 men, age 61.4 +/- 10.2 yrs) with left ventricular ejection fraction (LVEF) <40% by echocardiography. We used New York Heart Association (NYHA) functional class to index disease severity. VO2peak, grip strength, knee extensor, and flexor muscle strength were determined. Patients were divided into three groups by NYHA class: class I (n = 39), class II (n = 49), and class III (n = 14). RESULTS: Age, sex, and LVEF did not differ according to NYHA class. VO2peak and all muscle strength indices decreased with increases in NYHA class (P < 0.05). VO2peak correlated positively with all muscle strengths (P < 0.05). Stepwise linear regression analysis revealed that grip and knee extensor strength were important in predicting VO2peak. CONCLUSIONS: Exercise capacity and disease severity in CHF patients may be influenced not only by lower-limb but also upper-limb muscle strength.     

Maximal oxygen consumption in patients with lung disease.

A theoretical model for oxygen transport assuming a series linkage of ventilation, diffusion, oxygen uptake by erythrocytes, cardiac output, and oxygen release was used to calculate expected values for maximal oxygen intake (VO2max) of patients with various pulmonary disorders 22 patients with either restrictive or obstructive ventilatory impairment were studied at rest and maximal exercise. When exercise measurements of maximal pulmonary blood flow (QCmax), oxygen capacity, membrane diffusing capacity for CO, pulmonary capillary blood volume, alveolar ventilation, and mixed venous oxygen saturation were employed as input values, predictions of VO2max from the model correlated closely with measured values (r = 0.978). Measured VO2max was 976+/-389 ml/min (45.3+/-13% of predicted normal), and VO2max predicted from the model was 1,111+/-427 ml/min. The discrepancy may in part reflect uneven matching of alveolar ventilation, pulmonary capillary blood flow, and membrane diffusing capacity for CO within the lung; uniform matching is assumed in the model so that mismatching will impair gas exchange beyond our predictions. Although QCmax was less than predicted in most patients (63.6+/-19.6% of predicted) the model suggests that raising QCmax to normal could have raised VO2max only 11.6+/-8.8% in the face of existent impairment of intrapulmonary gas exchange. Since pulmonary functions measured at rest correlated well with exercise parameters needed in the model to predict VO2max we developed a nomogram for predicting VO2max from resting CO diffusing capacity, the forced one second expired volume, and the resting ratio of dead space to tidal volume. The correlation coefficient between measured and predicted VO2max, by using this nomogram, was 0.942.     

Insulin action on heart and skeletal muscle glucose uptake in essential hypertension.

Essential hypertension is characterized by skeletal muscle insulin resistance but it is unknown whether insulin resistance also affects heart glucose uptake. We quantitated whole body (euglycemic insulin clamp) and heart and skeletal muscle (positron emission tomography and 18F-fluoro-2-deoxy-D-glucose) glucose uptake rates in 10 mild essential hypertensive (age 33 +/- 1 yr, body mass index 23.7 +/- 0.8 kg/m2, blood pressure 146 +/- 3/97 +/- 3 mmHg, VO2max 37 +/- 3 ml/kg per min) and 14 normal subjects (29 +/- 2 yr, 22.5 +/- 0.5 kg/m2, 118 +/- 4/69 +/- 3 mmHg, 43 +/- 2 ml/kg per min). Left ventricular mass was similar in the hypertensive (155 +/- 15 g) and the normotensive (164 +/- 13 g) subjects. In the hypertensives, both whole body (28 +/- 3 vs 44 +/- 3 mumol/kg per min, P < 0.01) and femoral (64 +/- 11 vs 94 +/- 8 mumol/kg muscle per min, P < 0.05) glucose uptake rates were decreased compared to the controls. In contrast, heart glucose uptake was 33% increased in the hypertensives (939 +/- 51 vs 707 +/- 46 mumol/kg muscle per min, P < 0.005), and correlated with systolic blood pressure (r = 0.66, P < 0.001) and the minute work index (r = 0.48, P < 0.05). We conclude that insulin-stimulated glucose uptake is decreased in skeletal muscle but increased in proportion to cardiac work in essential hypertension. The increase in heart glucose uptake in mild essential hypertensives with a normal left ventricular mass may reflect increased oxygen consumption and represent an early signal which precedes the development of left ventricular hypertrophy.     

Walking performance,oxygen uptake kinetics and resting muscle pyruvate dehydrogenase complex activity in peripheral arterial disease

In the present study, we tested the hypothesis that walking intolerance in intermittent claudication (IC) is related to both slowed whole body oxygen uptake (VO2) kinetics and altered activity of the active fraction of the pyruvate dehydrogenase complex (PDCa) in skeletal muscle. Ten patients with IC and peripheral arterial disease [ankle/brachial index (ABI)=0.73 +/- 0.13] and eight healthy controls (ABI=1.17 +/- 0.13) completed three maximal walking tests. From these tests, averaged estimates of walking time, peak VO2 and the time constant of VO2 (tau) during submaximal walking were obtained. A muscle sample was taken from the gastrocnemius medialis muscle at rest and analysed for PDCa and several other biochemical variables. Walking time and peak VO2 were approx. 50% lower in patients with IC than controls, and tau was 2-fold higher (P<0.05). tau was significantly correlated with walking time (r=-0.72) and peak VO2 (r=-0.66) in patients with IC, but not in controls. PDCa was not significantly lower in patients with IC than controls; however, PDCa tended to be correlated with tau (r=-0.56, P=0.09) in patients with IC, but not in controls (r=-0.14). A similar correlation was observed between resting ABI and tau (r=-0.63, P=0.05) in patients with IC. These data suggest that the impaired VO2 kinetics contributes to walking intolerance in IC and that, within a group of patients with IC, differences in VO2 kinetics might be partly linked to differences in muscle carbohydrate oxidation.     

Effect of the VO2 time-averaging interval on the reproducibility of VO2max in healthy athletic subjects

AIMS: Limited research has investigated the most appropriate oxygen uptake (VO2) data averaging method to obtain reliable and valid maximal oxygen uptake (VO2max) values. This study investigated the effect of the VO2 time-averaging interval on the reproducibility of VO2max. METHODS AND RESULTS: Twenty-two competitive distance runners (six female) performed two identical incremental treadmill tests to their limit of exercise tolerance separated by at least 48 h. Commencing at 7 km h(-1), running speed was increased by 1 km h(-1) per minute for five stages and 0.5 km h(-1) thereafter. Breath-by-breath VO2 data collected during each incremental test were time-averaged over 10-, 15-, 20-, 30- and 60-s and the highest averaged VO2 value was regarded as VO2max for each time-averaging interval. The VO2max values derived from different VO2 time-averaging intervals were significantly different for the first (F = 39.6; P<0.001) and second (F = 68.9; P<0.001) incremental test. There was a tendency for VO2max to significantly increase as the time-averaging interval became shorter. The reproducibility of VO2max was similar for all five VO2 time-averages, with no significant differences between the within-subject variance (F = 0.4; P = 0.6). CONCLUSION: The results of this study suggests that the reproducibility of VO2max is not affected by the length of the VO2 time-average interval. However, VO2max was significantly altered by changing the VO2 time-averaging interval between 10 and 60 s. Consistency in the VO2 time-averaging interval is therefore an important methodological consideration for repeated determinations of VO2max.     

Effects of yoga exercise on maximum oxygen uptake,cortisol level,and creatine kinase myocardial bond activity in female patients with skeletal muscle pain syndrome

[Purpose] This study analyzed the effects of yoga exercise on maximum oxygen uptake, cortisol level, and creatine kinase myocardial bond activity in female patients with skeletal muscle pain syndrome. [Subjects] The subjects were 24 female patients with skeletal muscle pain syndrome. [Methods] The subjects were divided into 2 groups: a yoga exercise group (n = 12) and a non-exercise control group (n = 12). Body composition, maximum oxygen uptake, cortisol level, and creatine kinase myocardial bond activity were measured before and after a 12-week yoga exercise program. [Results] After the 12-week yoga exercise program, the exercise group exhibited slightly higher maximum oxygen uptake and creatine kinase myocardial bond activity than the control group, but the differences were not statistically significant. In addition, the exercise group exhibited a significant decrease in cortisol level. [Conclusion] Regular and continuous aerobic exercise such as yoga improves body composition, maximum oxygen uptake, cortisol level, and creatine kinase myocardial bond activity in female patients with skeletal muscle pain syndrome.Key words: VO₂max, Cortisol, Creatine kinase myocardial bond     

Exercise capacity in heart failure patients: relative importance of heart and skeletal muscle

Summary. The knee extensor and the whole-body exercise capacities were measured in 11 chronic heart failure (CHF) patients and 11 healthy age- and sex-matched controls, and were related to ejection fraction and to biochemical and histochemical markers of the musculature. The CHF patients had a 39% lower maximal oxygen uptake measured on an ergometer cycle than the healthy controls (1.54±0.57 vs. 2.51±0.70 1 min^-1, P < 0.001). The low exercise capacity was markedly related to the ejection fraction (r =0.77, P < 0.001)TThe maximal strength of m. quadriceps femoris was 15% lower in the CHF patients than in the controls (P < 0.05). The cross-sectional area (CSA) of m. quadriceps femoris explained 55% (r =0.74, P < 0.001) of the difference in strength between both groups. The endurance capacity of m. quadriceps femoris was 30% lower in CHF patients than in controls, partly as a result of the 25% lower capillary density (P < 0.05) and the 27% lower aerobic enzyme capacity (P < 0.05), as estimated by the citrate synthase activity, in the CHF patients. The citrate synthase activity correlated with the maximal oxygen uptake (r =0.61, P < 0.05). Moreover, the ejection fraction, together with the CSA of m. quadriceps femoris, explained 75% (r =0.86, P < 0.01) of the difference in maximal oxygen uptake between CHF patients and controls. These results demonstrate that CHF patients have both a lower local and a lower whole-body work capacity than healthy controls. This is a function of a smaller leg muscle mass and a lower capillary density and mitochondrial enzyme capacity in the CHF patients; however, a lowered pump capacity of the heart is the factor which limits the exercise capacity the most.     

Physical fitness effect on bone mass in postmenopausal women

This study was conducted to determine if bone mineral mass is influenced by the level of physical fitness in active, healthy, postmenopausal women from 50 through 59 years of age. In vivo neutron activation analysis (NAA) was used to measure calcium or bone mineral in the trunk and proximal femurs. The NAA measurement is expressed as calcium bone index (CaBI), which relates the subject's Ca value to the estimated mean value for normal subjects of the same size based on height and arm span. The normal CaBI is 1.00 +/- 0.12 (ISD). The level of physical fitness was determined by calculating the maximum oxygen uptake (VO2max), attained by a graded exercise test on the treadmill, and evaluating the muscle strength in performing one repetition maximum in the bench press and leg press. The "above-average fit" group (VO2max greater than 29 ml/kg/min) when compared to the "average fit" group (VO2max 21-29 ml/kg/min) had significantly higher CaBI (p less than 0.001) and leg press (p less than 0.01). There was significant correlation between VO2max and CaBI (p less than 0.01). The findings suggest that level of physical activity may modify the amount of bone loss in postmenopausal women.     

Mechanism of enhanced insulin sensitivity in athletes. Increased blood flow, muscle glucose transport protein (GLUT-4) concentration, and glycogen synthase activity.

We examined the mechanisms of enhanced insulin sensitivity in 9 male healthy athletes (age, 25 +/- 1 yr; maximal aerobic power [VO2max], 57.6 +/- 1.0 ml/kg per min) as compared with 10 sedentary control subjects (age, 28 +/- 2 yr; VO2max, 44.1 +/- 2.3 ml/kg per min). In the athletes, whole body glucose disposal (240-min insulin clamp) was 32% (P < 0.01) and nonoxidative glucose disposal (indirect calorimetry) was 62% higher (P < 0.01) than in the controls. Muscle glycogen content increased by 39% in the athletes (P < 0.05) but did not change in the controls during insulin clamp. VO2max correlated with whole body (r = 0.60, P < 0.01) and nonoxidative glucose disposal (r = 0.64, P < 0.001). In the athletes forearm blood flow was 64% greater (P < 0.05) than in the controls, whereas their muscle capillary density was normal. Basal blood flow was related to VO2max (r = 0.63, P < 0.05) and glucose disposal during insulin infusion (r = 0.65, P < 0.05). The forearm glucose uptake in the athletes was increased by 3.3-fold (P < 0.01) in the basal state and by 73% (P < 0.05) during insulin infusion. Muscle glucose transport protein (GLUT-4) concentration was 93% greater in the athletes than controls (P < 0.01) and it was related to VO2max (r = 0.61, P < 0.01) and to whole body glucose disposal (r = 0.60, P < 0.01). Muscle glycogen synthase activity was 33% greater in the athletes than in the controls (P < 0.05), and the basal glycogen synthase fractional activity was closely related to blood flow (r = 0.88, P < 0.001). In conclusion: (a) athletes are characterized by enhanced muscle blood flow and glucose uptake. (b) The cellular mechanisms of glucose uptake are increased GLUT-4 protein content, glycogen synthase activity, and glucose storage as glycogen. (c) A close correlation between glycogen synthase fractional activity and blood flow suggests that they are causally related in promoting glucose disposal.     

六分钟步行试验与摄氧量的相关性研究

背景:6 min步行试验是一种亚极量水平的运动试验,其操作简便、费用低廉,因而应用较广泛,然而将步行距离转换为最大运动能力是不易的.目的:课题组创新性地在6 min步行实验中引入做功的概念,将无线遥测呼吸气体分析仪同时应用于6 min步行试验和心肺运动试验,分析6 min步行试验中的距离、做功与峰值摄氧量与Bruce方案测得的最大摄氧量之间的相关性.设计、时间及地点:实验于2009-03/05在南京东南大学附属中大医院康复医学科完成.对象:健康受试者来自在中大医院康复医学科实习的学生,共25名,男14名,女11名;年龄(22.0±2.3)岁.方法:25名志愿者先按Bruce方案进行极量心肺运动试验,检测每位受试者极量运动时的最大摄氧量和无氧阈,再接受6 min步行试验,测量每位受试者的6 min步行距离、做功和峰值摄氧量.心肺运动试验和6 min步行试验均采用便携式K4b~2气体分析仪实时检测气体交换参数,以获得最大摄氧量和峰值摄氧量.主要观察指标:①摄氧量、心率、呼吸频率随时间的变化规律.②步行距离、做功、摄氧量、心率、呼吸频率的前后比较.③心肺运动试验中的最大摄氧量、无氧阈与6 min步行试验中的峰值摄氧量比较.④距离、做功与峰值摄氧量、最大摄氧量之间的相关性.结果:心肺运动试验测得的无氧阈与6 min步行试验测得的峰值摄氧量之间差异无显著性意义(P > 0.05).6 min步行距离与峰值摄氧量和最大摄氧量均无明显相关;6 min步行做功与峰值摄氧量呈线性相关(r=0.779 7,P < 0.001);6 min步行做功与最大摄氧量亦呈线性相关(r=0.894 1,P < 0.001).结论:6 min步行试验是一种无氧阈水平的运动试验.6 min步行做功既可反映受试者亚极量运动的能力,也能反映受试者极量运动的能力.     

Rosiglitazone improves exercise capacity in individuals with type 2 diabetes

OBJECTIVE: Although exercise is recommended as a cornerstone of treatment for type 2 diabetes, it is often poorly adopted by patients. We have noted that even in the absence of apparent cardiovascular disease, persons with type 2 diabetes have an impaired ability to carry out maximal exercise, and the impairment is correlated with insulin resistance and endothelial dysfunction. We hypothesized that administration of a thiazolidinedione (TZD) agent would improve exercise capacity in type 2 diabetes. RESEARCH DESIGN AND METHODS: Twenty participants with uncomplicated type 2 diabetes were randomly assigned in a double-blind study to receive either 4 mg/day of rosiglitazone or matching placebo after baseline measurements to assess endothelial function (brachial artery diameter by brachial ultrasound), maximal oxygen consumption (VO(2max)), oxygen uptake (VO(2)) kinetics, and insulin sensitivity by hyperinsulinemic-euglycemic clamp. Measurements were reassessed after 4 months of treatment. RESULTS: Participant groups did not differ at baseline in any measure. Rosiglitazone-treated participants (n = 10) had significantly improved VO(2max) (19.8 +/- 5.3 ml . kg(-1) . min(-1) before rosiglitazone vs. 21.2 +/- 5.1 ml . kg(-1) . min(-1) after rosiglitazone, P < 0.01), insulin sensitivity, and endothelial function. A change in VO(2max) correlated with improved insulin sensitivity measured by clamp (r = 0.68, P < 0.05) and with improved brachial artery diameter (r = 0.70, P < 0.05). Placebo-treated participants (n = 10) showed no changes in VO(2max) (19.4 +/- 5.2 ml . kg(-1) . min(-1) before rosiglitazone vs. 18.1 +/- 5.3 ml . kg(-1) . min(-1) after rosiglitazone, NS) or brachial artery diameter. CONCLUSIONS: This is the first known report showing that a TZD improved exercise function in type 2 diabetes. Whether this is due to the observed improvements in insulin sensitivity and/or endothelial function or to another action of the TZD class requires further exploration.     

Effect of hyperthyroidism on fibre-type composition,fibre area,glycogen content and enzyme activity in human skeletal muscle

Summary. Seven hyperthyroid patients were studied by repeated muscle biopsies (vastus lateralis) before and after a period of medical treatment which averaged 10 months. The biopsies were analysed with regard to fibre-type composition, fibre area, capillary density, glycogen content and enzyme activities representing the glycolytic capacity (hexokinase, 6-phosphofructokinase), oxidative capacity (oxoglutarate dehydrogenase, citrate synthase) and Ca²⁺- and Mg²⁺-stimulated ATPase in muscle. In the pretreatment biopsy (hyperthyroid state), there was a significantly lower proportion of type I fibres (30% vs. 41%), a higher capillary density (23%), lower glycogen content (33%), and higher hexokinase activity (32%) compared with the post-treatment biopsy. No significant changes in the activity of the remaining enzymes were observed. The present study indicates that hyperthyroidism induces a transformation from type I to type II fibres in human skeletal muscle. The increase in hexokinase activity probably reflects a higher glucose utilization by skeletal muscle in order to compensate partially for the reduced glycogen content.     

Muscle fibre types, ubiquinone content and exercise capacity in hypertension and effort angina

The composition of skeletal muscle fibre expressed as a percentage of slow twitch (ST), type I or "red" and fast twitch (FT), type II or "white" were determined in patients with hypertension (HT) or with severe ischaemic heart disease (IHD) and compared to age matched controls. Similarly, exercise capacity expressed as the cycle intensity eliciting a blood lactate concentration corresponding to 2.0 mmol x 1-1 were compared with healthy controls. Both patient groups had a higher percentage of FT fibres with relatively lower exercise capacities than their controls. The exercise capacities were reduced even when the relationship of decreased capacity with the percentage of increased FT was considered. There was an increase IHD but not in HT in patients with fibre subgroup FTc, which most probably reflected fibre trauma. Both patient groups were low in the skeletal muscle mitochondrial electron carrier and unspecific antioxidant ubiquinone, coenzyme Q10 or CoQ10. Patients with IHD but not HT showed, however, a faster fall in the ratio CoQ10 over ST% the higher the percentage value of ST. The ratio reflects the antioxidant activity related to CoQ10 in the fibre hosting most of the oxidative metabolism. A low ratio indicates a risk of metabolic lesion and cell trauma. This could explain fibre plasticity and offer an alternative cause to heredity in elucidating in deviating muscle fibre composition in patients with HT and IHD.     

Elevated endothelial-cell-stimulating angiogenic factor activity in rodent glycolytic skeletal muscles.

1. Capillary density is greater in skeletal muscles comprised of predominantly oxidative (type I) fibres than in those comprised of mainly glycolytic (type II) fibres. In order to investigate further the angiogenic mechanisms involved in muscle capillarization, endothelial-cell-stimulating angiogenic factor activities in various rodent skeletal muscles were compared. 2. Eleven untrained adult male Wistar rats were killed and the predominantly oxidative (type I) muscle,s soleus and heart, the predominantly glycolytic (type II) muscle, extensor digitorum longus, and the mixed-fibre muscle, gastrocnemius, were removed. Each sample was separately homogenized and centrifuged and the supernatants were diafiltered to isolate the low-molecular-mass fraction containing endothelial-cell-stimulating angiogenic activity. This was assayed for its ability to activate latent collagenase and was expressed as units, where 1 unit represents the percentage activation of the enzyme h-1 (mg of protein in the supernatant)-1. 3. The results (medians and ranges) demonstrated significantly greater endothelial-cell-stimulating angiogenic factor activity in extensor digitorum longus muscle (2.14 units, 0.62-2.87 units, n = 13) than in soleus (0.82 units, 0.59-1.79 units, n = 15), gastrocnemius (0.34 units, 0.28-0.40 units, n = 4) or heart (0.43 units, 0.16-0.52 units, n = 11) (P less than 0.01 for each) muscle. 4. These findings suggest that endothelial-cell-stimulating angiogenic activity in muscle is either inversely or not related to the local capillary density, which may be at or near a maximum in physiologically contracting, predominantly oxidative muscles.     

Skeletal muscle fibre types and sizes in anorexia nervosa patients

Summary. Fibre type composition and fibre areas in skeletal muscle of anorexia patients were studied on biopsies from the m. quadriceps femoris in five male and five females, whose body weight was 2–3-5 SDs less than expected from the normal weight/height relationship. In two of the males, the muscle studies were also made after rehabilitation. A higher than normal percentage of type I fibres was found in the patients (male, 62 ±12, female, 69 ±7) whereas the percentage of type IIA fibres did not differ from normal individuals (male, 38 ±12, female 24 ±15). Of note was the observation that no type IIB fibres were found and some patients had an increased occurrence of the normally rare type IIC fibres. All muscle fibres were markedly atrophied with the mean cross-sectional area of type IIA fibres being significantly smaller (male, 26-1 ±3–7, female, 21-2 ±10-3, fi.m²×10^-2) than the mean area of type I fibres (male, 34-1 ±4–7, female, 35-3±7-4, (j.m²× 10^-2). In the two males studied after rehabilitation (body weight increased 12 and 19 kg), mean fibre area had increased by 40%. Our results suggested that a predominant part of the reduction in body weight and lean body mass, seen in adolescent children suffering from anorexia nervosa, could be accounted for by a loss of skeletal muscle mass. In the six subjects where marker enzymes of glycolytic (TPDH, LDH) and mitochondrial pathways (CS, HAD) were assayed, the former were 50% and the latter 10–20% below sedentary controls. Maximal oxygen uptake was only 35 (males) and 29 (females) ml/kg min^-1; this contrasted with the physical activity pattern of these patients, yet was in line with their small muscle mass with its low oxidative potential.