Skeletal muscle myofibrillar protein oxidation and exercise capacity in heart failure

Background Heart failure is characterized by limited exercise tolerance and by a skeletal muscle myopathy with atrophy and shift toward fast fibres. An inflammatory status with elevated pro-inflammatory cytokines and exaggerated free radicals production can worsen muscle damage. We have previously demonstrated in a model of heart failure, the monocrotaline treated rat, that oxidation of skeletal muscle actin, tropomyosin and myosin produces a reduction of contractile efficiency, which may further depress muscle function and exercise capacity. Aims To investigate the presence of oxidized myofibrillar proteins in skeletal muscle of CHF patients by means of the Oxyblot technique and to correlate it with exercise capacity. Methods We have analyzed skeletal muscle biopsies taken from six patients with class III–IV NYHA CHF and four control patients (peak VO₂ 12.8 ± 1.9 vs. 29.7 ± 1.7 ml/kg/min, p < 0.0001). Results and conclusions A correlation between degree of myofibrillar oxidation and exercise capacity measured as peak VO₂ was obtained. In the skeletal muscle of CHF patient there was a much higher level of myofibrillar protein oxidation as expressed by the Oxyblot/Red Ponceau (Oxy/RP) ratio as compared to controls (2.1 ± 0.3 vs. 1.02 ± 0.09, p < 0.0001). The VO₂/Oxy/RP was significantly lower in the CHF patients. Higher levels of muscle oxidation were found in patients with lower exercise capacity with an inverse correlation between Oxyblot and VO₂ values (r ² = 0.83). Returned for 1. Revision: 6 August 2007 1. Revision received: 2 October 2007 Returned for 2. Revision: 8 November 2007 2. Revision received: 9 November 2007     

Apoptosis in the skeletal muscle of patients with heart failure: investigation of clinical and biochemical changes

OBJECTIVE—To investigate the contribution of apoptosis in the development of the skeletal myopathy in chronic heart failure.
DESIGN—The electrophoretic pattern of myosin heavy chains (MHC), fibre cross sectional area, number of in situ nick end labelling (TUNEL) positive apoptotic myocyte nuclei, and the tissue levels of caspase-3, Bcl-2, and ubiquitin were determined in biopsies taken from the vastus lateralis muscle. The study involved nine patients with severe chronic heart failure caused by ischaemic heart disease and hibernating myocardium and five controls.
RESULTS—In chronic heart failure patients the vastus lateralis showed a significant increase of MHC_2a and MHC_2b and a greater degree of fibre atrophy, as demonstrated by the decreased cross sectional area. There was also an increased number of TUNEL positive apoptotic myocyte nuclei. Tissue concentrations of Bcl-2 were decreased, while those of caspase-3 and ubiquitin were increased. Peak oxygen consumption (VO₂) was negatively correlated with the number of TUNEL positive nuclei and the fibre cross sectional area. There was a correlation between the number of apoptotic nuclei and the fibre cross sectional area, but no correlation between myosin heavy chains and number of apoptotic nuclei.
CONCLUSIONS—Myocyte apoptosis occurs in the skeletal muscle of patients with chronic heart failure, and its magnitude is associated with the severity of exercise capacity limitation and the degree of muscle atrophy. Muscle atrophy contributes to the limitation of exercise capacity, together with the increased synthesis of fast, more fatiguable myosin heavy chains.


Keywords: apoptosis; chronic heart failure; exercise capacity; myosin heavy chains     

Association of muscular fitness with rehospitalization for heart failure with reduced ejection fraction

BackgroundLimited information is available regarding the prognostic potential of muscular fitness parameters in heart failure (HF) with reduced ejection fraction (HFrEF).HypothesisWe aimed to investigate the predictive potential of knee extensor muscle strength and power on rehospitalization and evaluate the correlation between exercise capacity and muscular fitness in patients newly diagnosed with HFrEF.MethodsNinety nine patients hospitalized with a new diagnosis of HF were recruited (64 men; aged 58.7 years [standard deviation (SD), 13.2 years]; 32.3% ischemic; ejection fraction, 28% [SD, 8%]). The inclusion criteria were left ventricular ejection fraction <40% and sufficient clinical stability to undergo exercise testing. Aerobic exercise capacity was measured with cardiopulmonary exercise testing. Knee extensor maximal voluntary isometric contraction (MVIC) and muscle power (MP) were measured using the Baltimore therapeutic equipment system. The clinical outcome was HF rehospitalization.ResultsOver a mean follow‐up period of 1709 ± 502 days, 39 patients were rehospitalized due to HF exacerbation. HF rehospitalization was more probable for patients with diabetes and lower oxygen uptake at peak exercise (peak VO₂), knee extensor MVIC, and MP. The Kaplan–Meier survival analysis revealed significantly different cumulative HF rehospitalization rates according to the tertiles of peak VO₂ (P = 0.005) and MP (P = 0.002). Multivariable Cox proportional hazard model showed that the lowest tertiles of peak VO₂ (hazard ratio (HR), 6.26; 95% confidence interval (CI), 1.93–20.27); and MP (HR, 5.29; 95% CI, 1.05–26.53) were associated with HF rehospitalization. Knee extensor muscle power was an independent predictor for rehospitalization in patients with HFrEF.ConclusionKnee extensor muscle power was an independent predictor for rehospitalization in patients with HFrEF.     

High intensity knee extensor training, in patients with chronic heart failure: Major skeletal muscle improvement

Skeletal muscle adaptations to high intensity knee extensorstrength and/or endurance training in patients with chronicheart failure were investigated. Eleven patients with chronicheart failure were randomized into two groups and exercisedthe m. quadriceps femoris 3 days/week for 8 weeks. After training,the maximal exercise intensity tolerated on the ergometer cyclewas raised from 99 (32) to 114 (40) watts (W, P<0·05)for all 11 patients. Peak dynamic knee extensor work rate showedthe greatest increase after endurance training (40%, P<0·01).Maximal dynamic and isometric strength were elevated by 40–45%(P<0·05) after strength training. The cross-sectionalarea of m. quadriceps femoris was increased in the strength-trainedlegs (9%, P<0·05), and the capillary per fibre ratioof m. vastus lateralis was raised by 47 and 58% in the endurance-trainedlegs (P<0·05). The oxidative enzyme activity in m.vastus lateralis was significantly raised above 50% after endurancetraining, whereas glycolytic enzyme activity was unaltered.The peripheral skeletal musculature in patients with chronicheart failure adapts fairly quickly to high intensity knee extensortraining. This results in a marked rise in local, and a smallrise in total work capacity, indicating maintained plasticityof skeletal muscle in chronic heart failure patients.     

Role of Physical Training in Heart Failure with Preserved Ejection Fraction

About 50 % or more of heart failure (HF) patients living in the community have preserved left ventricular ejection fraction (HFpEF), and the proportion is higher among women and the very elderly. A cardinal feature of HFpEF is reduced aerobic capacity, measured objectively as peak exercise pulmonary oxygen uptake (peak VO₂), that results in decreased quality of life. Specifically, peak VO₂ of HFpEF patients is 30–70 % lower than age-, sex-, and comorbidity-matched control patients without HF. The mechanisms for the reduced peak VO₂ are due to cardiovascular and skeletal muscle dysfunction that results in reduced oxygen delivery to and/or utilization by the active muscles. Currently, four randomized controlled exercise intervention trials have been performed in HFpEF patients. These studies have consistently demonstrated that 3–6 months of aerobic training performed alone or in combination with strength training is a safe and effective therapy to increase aerobic capacity and endurance and quality of life in HFpEF patients. Despite these benefits, the physiologic mechanisms underpinning the improvement in peak exercise performance have not been studied; therefore, future studies are required to determine the role of physical training to reverse the impaired cardiovascular and skeletal muscle function in HFpEF patients.     

Evidence of skeletal muscle metabolic reserve during whole body exercise in patients with chronic obstructive pulmonary disease

When freed from central cardiorespiratory limitations, healthy human skeletal muscle has exhibited a significant metabolic reserve. We studied the existence of this reserve in 10 severely compromised (FEV1 = 0.97 +/- SE 0.01) patients with chronic obstructive pulmonary disease (COPD). To manipulate O2 supply and O2 demand in locomotor and respiratory muscles, subjects performed both maximal conventional two-legged cycle ergometry (large muscle mass) and single-leg knee extensor exercise (KE, small muscle mass) while breathing room air (RA), 100% O2, and 79% helium + 21% O2 (HeO2). With each gas mixture, peak ventilation, peak heart rate, and perceived breathlessness were lower in KE than cycle exercise (p < 0. 05). Arterial O2 saturation and maximal work capacity increased in both exercise modalities while subjects breathed 100% O2 (work: +10% bike, +25% KE, p < 0.05). HeO2 increased maximal work capacity on the cycle (+14%, p < 0.05) but had no effect on KE. HeO2 resulted in the greatest maximum minute ventilation in both bike and KE (p < 0. 05) but had no effect on arterial O2 saturation. Thus, a skeletal muscle metabolic reserve in these patients with COPD is evidenced by: (1) greater muscle mass specific work in KE; (2) greater work rates with higher fraction of inspired oxygen (FIO2); (3) an even greater effect of FIO2 during KE (i.e., when the lungs are less challenged); and (4) the positive effect of HeO2 on bicycle work rate. This skeletal muscle metabolic reserve suggests that reduced whole body exercise capacity in COPD is the result of central restraints rather than peripheral skeletal muscle dysfunction, while the beneficial effect of 100% O2 (with no change in maximum ventilation) suggests that the respiratory system is not the sole constraint to oxygen consumption.     

Skeletal muscle abnormalities in rats with experimentally induced heart hypertrophy and failure

Background: In congestive heart failure (CHF), function and metabolism of skeletal muscles are abnormal. Aim: To evaluate whether the reduced oxidative capacity of skeletal muscles in CHF is due to impaired O₂ utilisation. Methods: CHF was induced in rats by injecting 50 mg/Kg monocrotaline. Several animals received the same dose of monocrotaline but only compensated right ventricular hypertrophy and no sign of congestion resulted. Two age- and diet-matched groups of control animals were also studied. In soleus and extensor digitorum longus (EDL) muscles, we studied skeletal muscle blood flow, oxidative capacity and respiratory function of skinned muscle fibres. Results: In CHF, we observed a decrease of muscle blood flow (statistically significant in the soleus, p < 0.05 vs. controls). In compensated rats, a similar trend in blood flow was observed. In both soleus and EDL, a significant reduction of high energy phosphate and a shift of the redox potential towards accumulation of reducing equivalents were observed. The reduction of energy charge was not correlated to the decrease of blood flow. In skinned myofibres, the ratio of O₂ utilised in the presence and in absence of ADP (an index of phoshorilating efficiency) was reduced from 8.9 ± 1.9 to 2.7 ± 0.2 (p < 0.001) and from 5.7 ± 1.0 to 2.0 ± 0.3 (p < 0.01) in soleus and EDL, respectively. Activity of the different complexes of respiratory chain was investigated by means of specific inhibitors, showing major abnormalities at the level of complex I. In fact, inhibition of VO₂ by rotenone was decreased from 83.5 ± 3.2 to 36.4 ± 9.6 % (p < 0.005) and from 81.8 ± 6.1 to 38.2 ± 7.4 % (p < 0.005) in soleus and EDL, respectively. Conclusions: In rats with CHF, abnormalities of oxidative phosphorylation of muscles occur and complex I of the respiratory chain seem to be primarily affected. The metabolic alterations of skeletal muscles in CHF may be explained, at least in part, by an impaired O₂ utilisation. Received: 22 February 2002, Returned for 1. revision: 14 March 2002, 1. Revision received: 5 June 2002, Returned for 2. revision: 21 June 2002, 2. Revision received: 23 August 2002, Accepted: 12 September 2002 Correspondence to: Dr. C. Ceconi     

Circuit resistance training in chronic heart failure improves skeletal muscle mitochondrial ATP production rate--a randomized controlled trial

BackgroundWe aimed to determine the role of skeletal muscle mitochondrial ATP production rate (MAPR) in relation to exercise tolerance after resistance training (RT) in chronic heart failure (CHF).Methods and ResultsThirteen CHF patients (New York Heart Association functional class 2.3 ± 0.5; Left ventricular ejection fraction 26 ± 8%; age 70 ± 8 years) underwent testing for peak total body oxygen consumption (VO_2peak), and resting vastus lateralis muscle biopsy. Patients were then randomly allocated to 11 weeks of RT (n = 7), or continuance of usual care (C; n = 6), after which testing was repeated. Muscle samples were analyzed for MAPR, metabolic enzyme activity, and capillary density. VO_2peak and MAPR in the presence of the pyruvate and malate (P+M) substrate combination, representing carbohydrate metabolism, increased in RT (P < .05) and decreased in C (P < .05), with a significant difference between groups (VO_2peak, P = .005; MAPR, P = .03). There was a strong correlation between the change in MAPR and the change in peak total body oxygen consumption (VO_2peak) over the study (r = 0.875; P < .0001), the change in MAPR accounting for 70% of the change in VO_2peak.ConclusionsThese findings suggest that mitochondrial ATP production is a major determinant of aerobic capacity in CHF patients and can be favorably altered by muscle strengthening exercise.     

Beneficial effects of exercise training in heart failure patients with low cardiac output response to exercise – a comparison of two training models

BACKGROUND: Exercise capacity of patients with chronic heart failure (CHF) correlates poorly with estimates of cardiac function. Yet, it has been suggested that only patients without severely impaired cardiac output (CO) benefit from exercise training. Comparisons of different training models have not been made in the same study. AIMS: To evaluate whether the response to different training models diverges according to the cardiac output response to exercise in patients with chronic heart failure. METHODS: Sixteen CHF patients (63 +/- 11 years) with an ejection fraction of 30 +/- 11% underwent a baseline cardiopulmonary exercise test, right heart catheterization and leg muscle biopsy. Cardiac output (CO) response to exercise was defined as the ratio between CO increase and the increase in oxygen uptake (CO response index) during exercise. Patients were randomized into two training regimens, differing with regard to active muscle mass, i.e. whole body and one-legged exercise. RESULTS: Baseline exercise capacity expressed as W kg-1 correlated with the CO response index (r = 0.51, P < 0.05). Exercise capacity on the cycle ergometer increased in both groups but more in the one-legged than in the two-legged training group (P < 0.05). The improvement in exercise capacity did not correlate with base-line exercise capacity. It correlated with CO response index in the one-legged (r = 0.75, P < 0.01) but not in the two-legged training group. CO response index correlated negatively with the pulmonary capillary wedge pressure at peak exercise (r = - 0.60, P < 0.05). The increase in leg muscle citrate synthase activity after training correlated negatively with the baseline CO response index (r = - 0. 50, P < 0.05). CONCLUSIONS: The improvement of exercise capacity after one-legged training correlates with the CO increase in relation to the O2 uptake before training. In patients with low CO response, individualization of the exercise regimen is needed and the benefits of training a limited muscle mass at a time deserve further study.     

慢性心力衰竭患者体重指数与运动耐量的相关性研究

  目的 探讨慢性收缩性心力衰竭（心衰）患者BMI与运动耐量的关系。方法 收集慢性收缩性心衰患者,计算BMI,心肺运动试验测定运动峰耗氧量（PVO₂）,公斤体重耗氧量（PKVO₂）,每搏耗氧量（VO₂/HR）和每分通气量/每分CO₂产生量（VE/VCO₂）。结果 273例慢性收缩性心衰患者中,消瘦者（BMI＜18.5 kg/m²）6例,体重正常者（BMI 18.5~<24.0 kg/m²）113例,超重者（BMI 24.0~<28.0 kg/m²）116例,肥胖者（BMI≥28 kg/m²）38例。肥胖组和超重组患者PVO₂显著高于消瘦组和正常体重组患者［（1077.2±30.9）、（1095.3±54.3）ml/min比（550.2±192.1）、（886.0±31.2）ml/min］,而PKVO₂和VE/VCO₂显著低于消瘦组和正常体重组［（14.6±2.2）、（16.5±0.5）ml·min^-1 ·kg^-1比（14.4±0.5）、（11.6±0.9）ml·min^-1·kg^-1 ,43.4±6.1、42.3±1.5比42.3±1.5、38.6±1.6,P<0.05］。在不同心功能状态下,单相关分析显示,BMI和PVO₂呈正相关（r=0.40, P<0.01）,与PKVO₂和VE/VCO₂分别呈负相关（r=-0.15、-0.25,P值均<0.01）。多元逐步回归分析显示,年龄、性别、BMI和LVEF是PKVO₂的独立影响因素,而年龄和BMI是VE/VCO₂的独立影响因素（P<0.05）。结论 慢性收缩性心衰患者BMI与运动耐量显著相关,且是运动耐量的独立危险因素。     

Exercise training alters skeletal muscle mitochondrial morphometry in heart failure patients

BACKGROUND: Previous research has demonstrated that exercise intolerance in heart failure patients is associated with significant alterations in skeletal muscle ultrastructure and oxidative metabolism that may be more consequential than cardiac output. DESIGN: To examine the effect of exercise training on skeletal muscle mitochondrial size in chronic heart failure patients. METHODS: Six heart failure patients participated in 16-weeks of supervised upper and lower extremity exercise training. At the conclusion of training, percutaneous needle biopsies of the vastus lateralis were taken and electron microscopy was used to assess mitochondrial sizes. RESULTS: The exercise programme resulted in a significant increase in peak maximal oxygen consumption ( P< 0.05) and anaerobic threshold (P < 0.04). Knee extension muscle force increased following training ( P< 0.02). After exercise training, the average size of the mitochondria increased by 23.4% (0.036 to 0.046 mu(2), P< 0.015) and the average shape was unaltered. CONCLUSION: Exercise training with heart failure patients alters skeletal muscle morphology by increasing mitochondrial size, with no change in shape. This may enhance oxidative metabolism resulting in an increased exercise tolerance.     

Peak oxygen uptake and respiratory muscle performance in patients with chronic obstructive pulmonary disease: Clinical findings and implications

The maximal oxygen uptake (VO_2max) is the gold standard measure of aerobic exercise capacity and is an important outcome measure in patients with chronic obstructive pulmonary disease (COPD). And respiratory muscle performance is also an important functional parameter for COPD patients. In addition to the traditional respiratory muscle strength test, the Test of Incremental Respiratory Endurance has recently been introduced and validated in patients with COPD. However, the relationship between VO₂ and respiratory muscle performance in COPD is not well understood. Therefore, this study investigated the correlations among VO₂ and respiratory muscle performance and other functional markers in COPD. A total of 32 patients with COPD were enrolled. All study participants underwent the following assessments: cardiopulmonary exercise test, pulmonary function test, respiratory muscle strength test, peripheral muscle strength test, and bioelectrical impedance analysis. When comparing VO_2peak and respiratory muscle parameters, the sustained maximal inspiratory pressure (SMIP) was the only factor with a significant relationship with VO_2peak. Among other functional parameters, the forced expiratory volume in one second (FEV₁) showed the strongest correlation with VO_2peak. It was followed by phase angle values of lower limbs, leg extension peak torque, age, and total skeletal muscle mass. When comparing respiratory muscle performance with other functional parameters, the SMIP showed the strongest correlation with hand grip strength, followed by peak cough flow, forced vital capacity, maximal inspiratory pressure, and FEV₁. The results showed that the SMIP was more significantly correlated with VO_2peak than the static measurement of respiratory muscle strength. This suggests that TIRE may be a useful assessment tool for patients with COPD. Additionally, FEV₁ and other functional markers were significantly correlated with VO_2peak, suggesting that various parameters may be used to evaluate aerobic power indirectly.     

Maximum oxygen uptake corrected for skeletal muscle mass accurately predicts functional improvements following exercise training in chronic heart failure

BACKGROUND: Skeletal muscle mass and peak oxygen uptake are important predictors of functional status and outcome in patients with stable chronic heart failure. AIMS: To assess changes in skeletal muscle mass and peak oxygen uptake following an exercise training program. METHODS: Thirty-six patients with moderate stable chronic heart failure were randomly allocated to either a bicycle ergometer (bike) or functional electrical muscle stimulators (FES) applied to quadriceps and gastrocnemius muscles to be used daily for six weeks. Dual-energy X-ray absorptionometry (DEXA) scanning was performed before and after training along with symptom limited cardiopulmonary exercise test, quadriceps strength and fatigue resistance, and 6-min walk test. RESULTS: Both exercise modalities resulted in improvements in treadmill exercise time, leg strength, 6-min walk test and peak oxygen uptake per kilogram of skeletal muscle. Despite significant improvements in functional capacity, there were no significant changes in body composition for total skeletal muscle mass, leg muscle mass or total body fat content. Skeletal muscle mass was strongly predictive of maximum oxygen uptake at baseline (r=0.61, p<0.001) and after exercise training (r=0.68, p<0.001). CONCLUSIONS: In moderate stable chronic heart failure, exercise training using bicycle ergometer or FES results in favourable qualitative rather than quantitative changes in skeletal muscle. Correction of maximum oxygen uptake for skeletal muscle mass rather than total body mass is a more sensitive measure of changes associated with exercise training.     

Skeletal muscle abnormalities in chronic heart failure patients: relation to exercise capacity and therapeutic implications

Recent studies suggest that changes in the periphery, like those occurring in the skeletal muscles of patients with chronic heart failure, might play an important role in the origin of symptoms and exercise intolerance in this condition. Biochemical and histologic changes in the skeletal muscles of chronic heart failure patients relate with the degree of exercise intolerance better than hemodynamics parameters. A reduction in skeletal muscle mass represents another important determinant of exercise intolerance in chronic heart failure patients. The relationship between skeletal muscle changes and exercise intolerance suggests the possibility of modifying the peripheral changes in order to improve functional capacity in chronic heart failure patients. Recent studies have shown that the administration of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers can improve the properties of the skeletal muscles. Similarly, exercise training allows improvement in peak oxygen consumption, which parallels important biochemical and histologic changes in the skeletal muscles.     

Vitamin D Status and Exercise Capacity in Older Patients with Heart Failure with Preserved Ejection Fraction

Background: Older patients with heart failure with preserved ejection fraction have severe exercise intolerance. Vitamin D may play a role in cardiovascular and skeletal muscle function, and may therefore be implicated in exercise intolerance in heart failure with preserved ejection fraction. However, there are few data on vitamin D status and its relationship to exercise capacity in heart failure with preserved ejection fraction patients.Methods: Plasma 25-hydroxyvitamin D (25[OH]D) and exercise capacity (peak oxygen consumption, [VO₂], 6-minute walk distance) were measured in 112 older heart failure with preserved ejection fraction patients (mean ± SD age?=?70 ± 8 years) and 37 healthy age-matched controls. General linear models were used to compare 25(OH)D between heart failure with preserved ejection fraction patients and healthy controls, and to determine the cross-sectional association between 25(OH)D and exercise capacity. The association between 25(OH)D and left ventricular function was evaluated secondarily in heart failure with preserved ejection fraction patients.Results: 25(OH)D concentrations were significantly lower in heart failure with preserved ejection fraction vs healthy controls (11.4 ± 0.6 ng/mL vs 19.1 ± 2.1 ng/mL; P?=?.001, adjusted for age, race, sex, body mass index, season). More than 90% of heart failure with preserved ejection fraction patients had 25(OH)D insufficiency (<20 ng/mL) and 30% had frank 25(OH)D deficiency (<10 ng/mL). In heart failure with preserved ejection fraction patients, but not healthy controls, 25(OH)D was significantly correlated with peak VO₂ (r?=?0.26; P?=?0.007) and 6-minute walk distance (r?=?0.34; P < .001).Conclusions: More than 90% of heart failure with preserved ejection fraction patients had 25(OH)D insufficiency, and 30% were frankly deficient. Lower 25(OH)D was associated with lower peak VO₂ and 6-minute walk distance in heart failure with preserved ejection fraction, suggesting that 25(OH)D insufficiency could contribute to exercise intolerance in this patient population. These findings provide the data and rationale for a future randomized trial designed to test the potential for vitamin D supplementation to improve exercise intolerance in heart failure with preserved ejection fraction.     

Plasma adenosine concentration during and after dynamic exercise in patients with chronic heart failure

The purpose of this study was to evaluate the changes of plasma adenosine concentration by dynamic exercise in patients with chronic heart failure. We studied six patients with chronic heart failure (heart failure group) and six normal subjects (normal group). A symptom-limited ramp exercise test was performed with subjects sitting upright on a bicycle ergometer. The first exercise test was performed to determine the anaerobic threshold. The second exercise test was performed 2 days thereafter, and blood samples for assay of adenosine, lactate, and norepinephrine were taken from the antecubital vein at rest, during, and after exercise. In the heart failure group, VO₂ at anaerobic threshold and peak exercise was significantly lower than that in the normal group, whereas there was no difference in respiratory quotient at peak exercise between the two groups. There was a significant increase in the plasma adenosine level from the point before anaerobic threshold to 10 minute after exercise in the normal group, whereas a mild increase in plasma adenosine level was observed only 15 minute after exercise in the heart failure group. The change of plasma adenosine was significantly smaller in the heart failure group (p<0.05). There was a significant relationship between plasma adenosine and lactate levels (r=0.42, n=48,p<0.01). These findings indicate that production of adenosine is decreased in patients with chronic heart failure, and vasodilation of exercising muscle induced by adenosine might be impaired during exercise.     

Lactate threshold is not an onset of insufficient oxygen supply to the working muscle in patients with chronic heart failure

It has been argued that the lactate threshold (LT) serves as an index to reflect circulatory insufficiency in transporting oxygen during submaximal exercise in patients with chronic heart failure (CHF). We examined whether or not the LT was related to an insufficient oxygen supply in patients with CHF. Sixty-nine patients were divided by NYHA classification. All underwent invasive cardiopulmonary exercise testing. The rate of increase in oxygen delivery (O₂D) versus VO₂ (ΔO₂D/ ΔVO₂) was significantly lowered when work rate exceeded LT, that is, 1.32 ± 0.35 to 1.05 ± 0.37 (p < 0.01), 1.22 ± 0.40 to 0.98 ± 0.40 (p < 0.05), and 1.04 ± 0.26 to 0.78 ± 0.39 (p < 0.05) in NYHA classes I, II, and III, respectively. However, the rate of increase in leg O₂D versus leg VO₂ (ΔLO₂D/ΔLVO₂) did not change, that is, 1.25 ± 0.20 to 1.29 ± 0.20 (NS), 1.27 ± 0.23 to 1.21 ± 0.28 (NS), and 1.19 ± 0.24 to 1.15 ± 0.17 (NS) in classes I, II, and III, respectively. Leg venous PO₂ was significantly different among three groups, that is, 23.7 ± 3.4 mmHg, 23.2 ± 2.8 mmHg, and 20.1 ± 2.3 mmHg (p < 0.001), respectively. Thus, the oxygen supply to the working muscle did not become insufficient when work rate exceeded LT, and the LT occurred at different levels of leg PO₂. It was concluded that the LT was not a result of anaerobiosis in patients with CHF.     

Enhanced Echo Intensity of Skeletal Muscle Is Associated With Exercise Intolerance in Patients With Heart Failure

BackgroundSkeletal muscle is quantitatively and qualitatively impaired in patients with heart failure (HF), which is closely linked to lowered exercise capacity. Ultrasonography (US) for skeletal muscle has emerged as a useful, noninvasive tool to evaluate muscle quality and quantity. Here we investigated whether muscle quality based on US-derived echo intensity (EI) is associated with exercise capacity in patients with HF.Methods and ResultsFifty-eight patients with HF (61 ± 12 years) and 28 control subjects (58 ± 14 years) were studied. The quadriceps femoris echo intensity (QEI) was significantly higher and the quadriceps femoris muscle thickness (QMT) was significantly lower in the patients with HF than the controls (88.3 ± 13.4 vs 81.1 ± 7.5, P= .010; 5.21 ± 1.10 vs 6.54 ±1.34 cm, P< .001, respectively). By univariate analysis, QEI was significantly correlated with age, peak oxygen uptake (VO₂), and New York Heart Association class in the HF group. A multivariable analysis revealed that the QEI was independently associated with peak VO₂ after adjustment for age, gender, body mass index, and QMT: β-coefficient = −11.80, 95%CI (−20.73, −2.86), P= .011.ConclusionEnhanced EI in skeletal muscle was independently associated with lowered exercise capacity in HF. The measurement of EI is low-cost, easily accessible, and suitable for assessment of HF-related alterations in skeletal muscle quality.     

Skeletal muscle microvascular exchange capacity is associated with hyperglycaemia in subjects with central obesity

Aims Poor glycaemic control is associated with increased risk of microvascular disease in various organs including the eye and kidney, but the relationship between glycated haemoglobin (HbA_1c) and microvascular function in skeletal muscle has not been described. We tested the association between HbA_1c and a measure of microvascular exchange capacity (K_f) in skeletal muscle in people with central obesity at risk of developing Type 2 diabetes. Methods Microvascular function was measured in 28 women and 19 men [mean (± sd ) age 51 ± 9 years] with central obesity who did not have diabetes. We estimated insulin sensitivity by hyperinsulinaemic–euglycaemic clamp, visceral and total fatness by magnetic resonance imaging, fitness (VO₂ max by treadmill testing), physical activity energy expenditure [metabolic equivalents of tasks (METS) by use of the SenseWear Pro armband] and skeletal muscle microvascular exchange capacity (K_f) by venous occlusion plethysmography. Results In regression modelling, age, sex and fasting plasma glucose accounted for 30.5% of the variance in HbA_1c (r² = 0.31, P = 0.001). Adding K_f to this model explained an additional 26.5% of the variance in HbA_1c (r² = 0.57, P = 0.0001 and K_f was strongly and independently associated with HbA_1c (standardized B coefficient ?0.45 (95% confidence interval ?0.19, ?0.06), P = 0.001). Conclusions We found a strong negative independent association between a measure of skeletal muscle microvascular exchange capacity (K_f) and HbA_1c. K_f was associated with almost as much of the variance in HbA_1c as fasting plasma glucose.