Limited Exercise Tolerance Research Articles

Differential morphofunctional characteristics and gene expression in fast and slow muscle of rats with monocrotaline-induced heart failure

Heart failure (HF) is characterized by limited exercise tolerance, skeletal muscle atrophy, a shift toward fast muscle fiber, and myogenic regulatory factor (MRF) changes. Reactive oxygen species (ROS) also contribute to target organ damage in this syndrome. In this study, we investigated and compared morphofunctional characteristics and gene expression in Soleus (SOL--oxidative and slow twitching muscle) and in Extensor Digitorum Longus (EDL--glycolytic and fast twitching muscle) during HF. Two groups of rats were used: control (CT) and heart failure (HF), induced by a single injection of monocrotaline. MyoD and myogenin gene expression were determined by RT-qPCR, and MHC isoforms by SDS-PAGE; muscle fiber type frequency and cross sectional area (CSA) were analyzed by mATPase. A biochemical study was performed to determine lipid hydroperoxide (LH), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD); myography was used to determine amplitude, rise time, fall time, and fatigue resistance in both muscles. HF showed SOL and EDL muscle atrophy in all muscle fiber types; fiber frequency decreased in type IIC and muscle contraction fall time increased only in SOL muscle. Myogenin mRNA expression was lower in SOL and myoD decreased in HF EDL muscle. LH increased, and SOD and GSH-Px activity decreased only in HF SOL muscle. HF EDL muscle did not present changes in MHC distribution, contractile properties, HL concentration, and antioxidant enzyme activity. In conclusion, our results indicate that monocrotaline induced HF promoted more prominent biochemical, morphological and functional changes in SOL (oxidative and slow twitching muscle). Although further experiments are required to better determine the mechanisms involved in HF pathophysiology, our results contribute to understanding the muscle-specific changes that occur in this syndrome.

Left pulmonary artery agenesis : fortuitous discovery in adulthood

E lies such as tetralogy of Fallot, septal defects, coarctation of the aorta, subvalvular aortic stenosis, transposition of the great arteries, pulmonary stenosis. These are in most cases diagnosed and treated during the patient’s first year of life [1]. On the contrary, isolated UPAA may remain asymptomatic in 30% of cases [2] such as in the current case, or has a benign clinical course osition of the great vessels was associated. Unilateral ulmonary Artery Agenesis (UPAA) is a rare congental anomaly, with less than 200 cases reported in the iterature. UPAA results from a failure of connection etween the sixth aortic arch and the pulmonary trunk. It smost frequently accompaniedby cardiovascular anomaleading to a tardive diagnosis in adulthood. Severe pulmonary hypertension and congestive heart failure are to be feared, which may occur in 40% of cases [2]. Main symptomsarenot specific, including recurrent pulmonary infections, dyspnea or limited exercise tolerance and haemoptysis [3].

Prueba de esfuerzo cardiopulmonar en el manejo del paciente con hipertensión pulmonar

The main symptom of patients with pulmonary hypertension (PH) is exercise intolerance. The gold standard for evaluation of exercise capacity is the incremental cardio-pulmonary exercise test (ICPET) on a bicycle ergometer. Exercise tolerance in patients with PH is mainly determined by the capacity to increase cardiac output to meet metabolic demands, which depends on right ventricular function. Therefore, right ventricular dysfunction is the main factor limiting exercise tolerance in PH. Patients with PH also show hypoxemia during exercise and hyperventilation is also common, both at rest and during exercise, which can be attributed to greater chemosensitivity.The present review analyzes the physiological mechanisms determining exercise tolerance, exercise response in patients with PH, the variables of greatest interest in the study of this disorder, the similarities and differences between ICPET and other, simpler tests such as the 6-minute walk test, and the prognostic value of exercise testing in these patients. Evaluation of exercise tolerance is an essential element in the clinical assessment of patients with PH. Consequently, detailed knowledge of the information provided by exercise testing and its limitation is of undoubted interest in the clinical management of this complex disease.

Orthostatic intolerance and coronary reserve: a matter of a certain gravity

A 74-year-old woman came to our attention complaining of the recent onset of shortness of breath during light physical activity. She reported orthostatic light-headedness, occasional dizziness, and pre-syncope symptoms for a duration of the prior year. The past history included mitral valve prolapse with mild regurgitation, dyslipidemia, and paroxysmal atrial fibrillation. At presentation, the current medications included propafenone, aminosalicylic acid, and simvastatin. A 24-h-ECG demonstrated the presence of polymorphic ventricular premature beats and asymptomatic ST-segment depression. The treadmill exercise test showed limited exercise tolerance, and a significant downward sloping ST-segment depression in leads V4–V6 at the beginning of step 2 of the Bruce protocol. An exercise myocardial perfusion scan was consistent with a reduced coronary reserve of the anterior wall. Upon admission, lying and up-right arterial pressures were 130/80 and 90/50 mmHg, respectively, while a physical examination documented a systolic click and a late systolic murmur. After medications were suspended, a new treadmill exercise test (Fig. 1, left panel) demonstrated orthostatic hypotension [1] with tachycardia upon standing, and a further decline of arterial pressure and heart rate increase during the Bruce stage 1. Exercise was interrupted due to pre-syncope symptoms after 204600 when 88% of the predicted maximal heart rate had been reached, and ST depression (-1.0 mm, V5–V6) observed. Considering the patient’s characteristics, the estimated pre-test probability of a significant coronary stenosis was 20–50% [2, 3]. The positive likelihood ratio of exercise stress test and myocardial perfusion scan for a significant coronary artery disease was about 10[4]. Thus, the patient’s post-test probability of a significant coronary stenosis was in the 70–90% range. A coronary angiography was thus performed, but ruled out a stenosis of the major coronary vessels. In the absence of stenosis, a reduction of coronary reserve may be secondary to functional mechanisms [5], including the originally misdiagnosed orthostatic hypotension. We thus hypothesized a critical decline in coronary blood flow during upright physical activity due to an exercise-induced significant decrease in arterial pressure on a pre-existing orthostatic hypotension background. To test our hypothesis, an exercise bicycle test was performed in the lying posture, a position unlikely to affect arterial pressure. Exercise was interrupted at 703500 because of physical exhaustion (Fig. 1, right panel). Neither a significant reduction in arterial pressure nor ST-segment changes was observed along the exercise-induced heart rate increase. The maximum heart rate systolic pressure product [6], a broad index of cardiovascular function, increased more when exercise was performed in a lying position than during up-right posture, compared to baseline, although the increase in heart rate was lower in the supine than in the standing position (Fig. 1). G. Costantino Medicina Interna II, Ospedale Sacco, Milan, Italy

Reply to: The parabolic power–velocity relationship does apply to fatigued states

We thank MacIntosh and Fletcher (2010) for sharing thesepreviously unpublished power–cadence data. We concedethat, on the basis of the only power–cadence data (Beelenand Sargeant 1991) available at the time of writing ourreply to Burnley (2010), we may have underestimated theeffect of cadence on the ability to produce maximal vol-untary cycling power (MVCP) in a fatigued state (Marcoraand Staiano 2010b). Nevertheless, the power–cadence dataprovided by MacIntosh and Fletcher (2010) strengthen,rather than weaken, our conclusion that muscle fatiguedoes not cause exhaustion during high-intensity aerobicexercise (Marcora and Staiano 2010a). In fact, according tothe fatigued power–cadence relationship shown in Fig. 1(open squares) (MacIntosh and Fletcher 2010), fatiguedsubjects that can produce 600 W at 108 RPM are able toproduce 400 W at 40 RPM. Therefore, the fact that oursubjects were able to produce 731 W at 108 RPM in thefinal MVCP test suggests that they were able to produce[400 W at exhaustion (40 RPM).Whether our subjects were able to produce [400 or731 W at exhaustion is totally irrelevant. What is relevantto our conclusion is that, despite significant muscle fatigue,they were able to produce more than 242 W at exhaustion.This finding goes against one of the most fundamentalassumptions in exercise physiology: submaximal exerciseterminates at the point commonly called exhaustionbecause central and/or peripheral fatigue mechanismsreduce muscle function to the point that subjects are nolonger capable of producing the force/power required bythe task despite their maximal voluntary effort (task fail-ure) (Allen et al. 2008; Jones and Burnley 2009).We argue that exhaustion is a form of task disengage-ment, i.e. a conscious decision to withdraw effort when theeffort required by exercise is beyond the maximal effortsubjects are willing to produce in order to succeed in thetask (potential motivation) (Marcora 2008; Marcora et al.2008, 2009, Marcora and Staiano 2010a). Therefore, inwell-motivated subjects, the main factor causing exhaus-tion is perception of effort, not muscle fatigue. In otherwords, it is mind over muscle. Accordingly, future researchon what limits exercise tolerance should investigate thepsychobiology of perceived exertion using appropriatepsychophysical and neurophysiologic methods (Marcora2009) rather than the central and peripheral mechanisms ofmuscle fatigue (Decorte et al. 2010; Jones and Burnley2009).References

Inspiratory muscle training enhances pulmonary O2 uptake kinetics and high-intensity exercise tolerance in humans

Fatigue of the respiratory muscles during intense exercise might compromise leg blood flow, thereby constraining oxygen uptake (Vo(2)) and limiting exercise tolerance. We tested the hypothesis that inspiratory muscle training (IMT) would reduce inspiratory muscle fatigue, speed Vo(2) kinetics and enhance exercise tolerance. Sixteen recreationally active subjects (mean + or - SD, age 22 + or - 4 yr) were randomly assigned to receive 4 wk of either pressure threshold IMT [30 breaths twice daily at approximately 50% of maximum inspiratory pressure (MIP)] or sham treatment (60 breaths once daily at approximately 15% of MIP). The subjects completed moderate-, severe- and maximal-intensity "step" exercise transitions on a cycle ergometer before (Pre) and after (Post) the 4-wk intervention period for determination of Vo(2) kinetics and exercise tolerance. There were no significant changes in the physiological variables of interest after Sham. After IMT, baseline MIP was significantly increased (Pre vs. Post: 155 + or - 22 vs. 181 + or - 21 cmH(2)O; P < 0.001), and the degree of inspiratory muscle fatigue was reduced after severe- and maximal-intensity exercise. During severe exercise, the Vo(2) slow component was reduced (Pre vs. Post: 0.60 + or - 0.20 vs. 0.53 + or - 0.24 l/min; P < 0.05) and exercise tolerance was enhanced (Pre vs. Post: 765 + or - 249 vs. 1,061 + or - 304 s; P < 0.01). Similarly, during maximal exercise, the Vo(2) slow component was reduced (Pre vs. Post: 0.28 + or - 0.14 vs. 0.18 + or - 0.07 l/min; P < 0.05) and exercise tolerance was enhanced (Pre vs. Post: 177 + or - 24 vs. 208 + or - 37 s; P < 0.01). Four weeks of IMT, which reduced inspiratory muscle fatigue, resulted in a reduced Vo(2) slow-component amplitude and an improved exercise tolerance during severe- and maximal-intensity exercise. The results indicate that the enhanced exercise tolerance observed after IMT might be related, at least in part, to improved Vo(2) dynamics, presumably as a consequence of increased blood flow to the exercising limbs.

Interstitial lung diseases in children

Interstitial lung disease (ILD) in infants and children comprises a large spectrum of rare respiratory disorders that are mostly chronic and associated with high morbidity and mortality. These disorders are characterized by inflammatory and fibrotic changes that affect alveolar walls. Typical features of ILD include dyspnea, diffuse infiltrates on chest radiographs, and abnormal pulmonary function tests with restrictive ventilatory defect and/or impaired gas exchange. Many pathological situations can impair gas exchange and, therefore, may contribute to progressive lung damage and ILD. Consequently, diagnosis approach needs to be structured with a clinical evaluation requiring a careful history paying attention to exposures and systemic diseases. Several classifications for ILD have been proposed but none is entirely satisfactory especially in children. The present article reviews current concepts of pathophysiological mechanisms, etiology and diagnostic approaches, as well as therapeutic strategies. The following diagnostic grouping is used to discuss the various causes of pediatric ILD: 1) exposure-related ILD; 2) systemic disease-associated ILD; 3) alveolar structure disorder-associated ILD; and 4) ILD specific to infancy. Therapeutic options include mainly anti-inflammatory, immunosuppressive, and/or anti-fibrotic drugs. The outcome is highly variable with a mortality rate around 15%. An overall favorable response to corticosteroid therapy is observed in around 50% of cases, often associated with sequelae such as limited exercise tolerance or the need for long-term oxygen therapy.

Early detection of iron overload in the heart: a key role for MRI!

Hereditary haemochromatosis is autosomal recessive disorder associated with the HLA-A locus on the short arm of chromosome 6 [1]. It is the most common genetic disorder worldwide [2]. About 56,000 babies are born each year with thalassaemia major, of whom 30,000 require lifelong transfusions to survive [3]. The disease is very prevalent in European countries along the Mediterranean Sea and in South East Asia. In other countries it becomes a problem because of immigration from these areas. Excessive iron deposition occurs mostly in the pancreas, pituitary, but also in the heart. In normal subjects, absorption of iron from the gut is inversely correlated with iron stores. In homozygous hereditary haemochromatosis there is increased absorption of iron, which is not regulated by iron stores [4]. This leads to progressive iron accumulation because there is no normal mechanism for excretion of excess iron once it has been absorbed into the body. The clinical manifestations of iron overload include liver disease in 75% of cases, weakness and lethargy in 74%, skin hyperpigmentation in 70%, diabetes mellitus in 48%, arthralgia in 44%, impotence in 45%, electrocardiographic abnormalities in 31% and heart failure and conduction disturbances in 15% [5, 6]. Heart failure remains a major cause of death in these patients, frequently people younger than 35 years [7]. In the majority of patients iron induced cardiomyopathy can be reversed by intense chelation therapy with desferrioxamine and deferiprone [3, 8]. At this moment T2* magnetic resonance imaging is the best way for early detection of iron overload in patients with haemochromatosis [9–11]. T2* is an unique magnetic resonance parameter measured in milliseconds and shortened in relation to the level iron in the heart. The parameter can be used for screening haemochromatosis patients and to guide chelation therapy in those with established cardiac haemochromatosis [8]. The paper of Mavrogeni et al. [12] in this issue of the International Journal of Cardiac Imaging shows, that heart failure patients with severe iron overload indicated by a T2* value less than 10 ms had a lower exercise capacity than patients with a T2* value higher than 10 ms. The authors also show, that there was a excellent relation of the extent of iron overload measured by T2* and exercise tolerance in thalassemia patients. As shown by others, thalassemia patients present prolonged phase II on-transient oxygen kinetics during submaximal, constant workload exercise, compared with healthy controls, possibly suggesting a slower rate of high energy phosphate production and utilization and reduced oxidative capacity of myocytes [13]. This could also account for their significantly limited exercise tolerance. Reduction of exercise tolerance is also s highly associated with the limited functional status of peripheral muscles in these patients [14]. This study shows again that T2* MRI plays a crucial role in screening cardiac haemochromatosis and guidance of chelation therapy. Early detection of cardiac iron load and early initiation of treatment are crucial for survival of these patients. Recently the chelator deferasirox has been shown to be more effective in better at improving myocardial iron [15]. This could improve outcome in thalassemia patients. As shown, early effects of therapy can only be detected with dedicated MRI sequences. Unfortunately these MRI scanners are not always available in those areas, where the prevalence of haemachromatosis patients is extremely high.

One-lung ventilation in a patient with tracheobronchomegaly: a case report and literature review

One-lung ventilation in a patient with tracheobronchomegaly: a case report and literature review

Exercise capacity of a contemporary cohort of children with hypoplastic left heart syndrome after staged palliation☆☆☆

Outcome of staged palliation for hypoplastic left heart syndrome has improved over the past decades. However, only little is known about the exercise capacity of children with palliated hypoplastic left heart syndrome where a systemic right ventricle supports the systemic circulation. The aim of the study was to assess exercise capacity in a contemporary cohort of children with hypoplastic left heart syndrome palliated in a single centre according to a uniform surgical strategy. Standardised cardiopulmonary exercise testing on a treadmill was performed in 46 consecutive hypoplastic left heart patients (median age: 6.0 (4.1-11.4) years). All but one patient reached the anaerobic threshold. Exercise data were compared to normal values obtained with a similar exercise protocol in a large cohort of paediatric volunteers. Oxygen uptake at anaerobic threshold (26.9+/-6.0 ml kg(-1)min(-1); 74.5+/-18.2% of predicted) and maximal oxygen uptake (31.0+/-6.8 ml kg(-1)min(-1); 60.8+/-15.0% of predicted) were significantly reduced compared with controls (P<0.0001 for both). The limitation in exercise capacity was due to an impaired rise in heart rate (158+/-23 bpm; 79.7+/-11.5% of predicted; P<0.0001) and oxygen pulse (4.5+/-1.6 ml per beat; 85.5+/-22.0% of predicted; P<0.0001). Furthermore, respiration during exercise was inefficient with an elevated respiratory rate and reduced maximal tidal volume and minute ventilation at maximal exercise. The exercise capacity of children with hypoplastic left heart syndrome is markedly reduced. Limitations in heart rate increase and stroke volume augmentation are the major contributors to this. An abnormal ventilatory response to exercise also adds to their limitation in exercise tolerance. However, the degree of physical disability does not justify discouraging these patients from school and leisure sports.

Impact of preinduced quadriceps fatigue on exercise response in chronic obstructive pulmonary disease and healthy subjects

Exercise intolerance in chronic obstructive pulmonary disease (COPD) results from a complex interaction between central (ventilatory) and peripheral (limb muscles) components of exercise limitation. The purpose of this study was to evaluate the influence of quadriceps muscle fatigue on exercise tolerance and ventilatory response during constant-workrate cycling exercise testing (CWT) in patients with COPD and healthy subjects. Fifteen patients with COPD and nine age-matched healthy subjects performed, 7 days apart, two CWTs up to exhaustion at 80% of their predetermined maximal work capacity. In a randomized order, one test was performed with preinduced quadriceps fatigue and the other in a fresh state. Quadriceps fatigue was produced by electrostimulation-induced contractions and quantified by maximal voluntary contraction and potentiated twitch force (TwQ(pot)). Endurance time and ventilatory response during CWT were compared between fatigued and fresh state. Endurance time significantly decreased in the fatigued state compared with the fresh condition in COPD (356 +/- 69 s vs. 294 +/- 45 s, P < 0.05) and controls (450 +/- 74 s vs. 340 +/- 45 s, P < 0.05). Controls showed significantly higher ventilation and end-exercise dyspnea scores in the fatigued condition, whereas, in COPD, fatigue did not influence ventilation or dyspnea during exercise. The degree of ventilatory limitation, as expressed by the Ve/maximum voluntary ventilation ratio, was similar in both conditions in patients with COPD. We conclude that it is possible to induce quadriceps fatigue by local electrostimulation-induced contractions. Our findings demonstrate that peripheral muscle fatigue is an additional important factor, besides intense dyspnea, that limits exercise tolerance in COPD.

Impaired oxygen kinetics in beta‐thalassaemia major patients

Beta-thalassaemia major (TM) affects oxygen flow and utilization and reduces patients' exercise capacity. The aim of this study was to assess phase I and phase II oxygen kinetics during submaximal exercise test in thalassaemics and make possible considerations about the pathophysiology of the energy-producing mechanisms and their expected exercise limitation. Twelve TM patients with no clinical evidence of cardiac or respiratory disease and 10 healthy subjects performed incremental, symptom-limited cardiopulmonary exercise testing (CPET) and submaximal, constant workload CPET. Oxygen uptake (VO2), carbon dioxide output and ventilation were measured breath-by-breath. Peak VO2 was reduced in TM patients (22.3 +/- 7.4 vs. 28.8 +/- 4.8 mL kg(-1) min(-1), P < 0.05) as was anaerobic threshold (13.1 +/- 2.7 vs. 17.4 +/- 2.6 mL kg(-1) min(-1), P = 0.002). There was no difference in oxygen cost of work at peak exercise (11.7 +/- 1.9 vs. 12.6 +/- 1.9 mL min(-1) W(-1) for patients and controls respectively, P = ns). Phase I duration was similar in TM patients and controls (24.6 +/- 7.3 vs. 23.3 +/- 6.6 s respectively, P = ns) whereas phase II time constant in patients was significantly prolonged (42.8 +/- 12.0 vs. 32.0 +/- 9.8 s, P < 0.05). TM patients present prolonged phase II on-transient oxygen kinetics during submaximal, constant workload exercise, compared with healthy controls, possibly suggesting a slower rate of high energy phosphate production and utilization and reduced oxidative capacity of myocytes; the latter could also account for their significantly limited exercise tolerance.

2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults

published online Mar 26, 2009; J. Am. Coll. Cardiol. Lynne Warner Stevenson, and Clyde W. Yancy Ganiats, Marvin A. Konstam, Donna M. Mancini, Peter S. Rahko, Marc A. Silver, Abraham, Donald E. Casey, Arthur M. Feldman, Gary S. Francis, Theodore G. Silver, Lynne Warner Stevenson, Clyde W. Yancy, Mariell Jessup, William T. Konstam, Donna M. Mancini, Keith Michl, John A. Oates, Peter S. Rahko, Marc A. M. Feldman, Gary S. Francis, Theodore G. Ganiats, Mariell Jessup, Marvin A. Transplantation, Sharon Ann Hunt, William T. Abraham, Marshall H. Chin, Arthur Force on Practice Guidelines, International Society for Heart and Lung American College of Cardiology Foundation/American Heart Association Task Diagnosis and Management of Heart Failure in Adults 2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the This information is current as of March 27, 2009 http://content.onlinejacc.org/cgi/content/full/j.jacc.2008.11.013v1 located on the World Wide Web at: The online version of this article, along with updated information and services, is

Prevalence of ventricular discordance and its relation to functional capacity in idiopathic dilated cardiomyopathy

Although left ventricular (LV) dilatation is the most distinguishing morphologic feature of idiopathic dilated cardiomyopathy (IDC), right ventricular (RV) dilatation may variably contribute to total cardiac enlargement. The prevalence and functional importance of the relative degree of left and right ventricular dilatation has not been comprehensively studied using cardiac magnetic resonance imaging (MRI). Our prospective study included 58 consecutive IDC patients with a LV ejection fraction <40% and NYHA functional class > or =2. MRI was performed with a 1.5 Tesla scanner for RV and LV dimensional and functional analysis. Cardiopulmonary exercise testing was used for evaluation of exercise capacity. Patients were grouped into tertiles based on the distribution of LV end-diastolic volume. Compared to control subjects a considerable heterogeneity in the relative degree of left and right ventricular dilatation was noted in IDC patients. Within the entire patient group, a strong correlation between the degree of ventricular volume discordance and the extent of LV enlargement was observed (r = 0.8; P < 0.001). Tertile analysis revealed that the LV/RV volume ratio significantly differed in the three subgroups of patients (1.0 +/- 0.3 vs. 1.5 +/- 0.4 vs. 2.1 +/- 0.9; P < 0.001). Only weak correlations between MRI data and patients' functional capacity were found. LV ejection fraction was identified as the only independent predictor of maximum oxygen consumption in our setting. In IDC patients the degree of ventricular volume discordance is strongly related to the extent of left ventricular enlargement. However, comprehensive biventricular assessment of cardiac function by MRI adds little to our understanding of the cardiac mechanisms limiting exercise tolerance when compared to exclusive left ventricular measurements.

Appearances Can Be Deceptive

A frightful ECG tracing suggested a serious cardiac event, but as it turned out, the abnormalities were not spurred by heart disease. A 60-year-old man was found on the floor at home, confused and with weakness of the right arm and leg. He was a heavy drinker and smoker, and he had undergone an aortobifemoral bypass many years earlier. However, he had no history of arterial hypertension or coronary artery disease, and he took no medications. Before this episode, the patient had been active without limited exercise tolerance.

Resting muscle sympathetic nerve activity, cardiac metaiodobenzylguanidine uptake, and exercise tolerance in patients with left ventricular dysfunction

BackgroundSympathetic nerve overactivity and reduced exercise tolerance are characteristic features of patients with heart failure. However, to what extent sympathetic nerve overactivity contributes to limiting exercise tolerance has not been clearly defined. MethodsMyocardial iodine 123-metaiodobenzylguanidine (MIBG) scintigraphy, muscle sympathetic nerve activity (MSNA), and cardiopulmonary exercise testing were performed within 3 days in 30 patients with left ventricular dysfunction (LVD). Cardiac sympathetic nerve activity was estimated using H/M ratio and washout rate (WR) of 123I-MIBG imaging. MSNA was recorded by microneurography. ResultsThe patients with peak VO2 < 20 mL/minute/kg (group II, n = 15) had significantly higher MSNA and WR, and lower H/M ratio than those with peak VO2≧ 20 mL/minute/kg (group I, n = 15) (P < .05). Peak VO2 had negative correlations with MSNA and WR (r = 0.58, 0.56), and positive correlations with early H/M ratio and delayed H/M ratio (r = 0.71, 0.75) in group II. Moreover, MSNA had negative correlations with early H/M ratio and delayed H/M ratio (r = 0.78, 0.66), and a positive correlation with WR (r = 0.79) in group II. However, similar relations were not found in group I. ConclusionsA link between cardiac and peripheral sympathetic nerve activities contributed to limiting exercise tolerance in patients with LVD patients and reduced exercise tolerance.

Mental fatigue impairs physical performance in humans

Mental fatigue is a psychobiological state caused by prolonged periods of demanding cognitive activity. Although the impact of mental fatigue on cognitive and skilled performance is well known, its effect on physical performance has not been thoroughly investigated. In this randomized crossover study, 16 subjects cycled to exhaustion at 80% of their peak power output after 90 min of a demanding cognitive task (mental fatigue) or 90 min of watching emotionally neutral documentaries (control). After experimental treatment, a mood questionnaire revealed a state of mental fatigue (P = 0.005) that significantly reduced time to exhaustion (640 +/- 316 s) compared with the control condition (754 +/- 339 s) (P = 0.003). This negative effect was not mediated by cardiorespiratory and musculoenergetic factors as physiological responses to intense exercise remained largely unaffected. Self-reported success and intrinsic motivation related to the physical task were also unaffected by prior cognitive activity. However, mentally fatigued subjects rated perception of effort during exercise to be significantly higher compared with the control condition (P = 0.007). As ratings of perceived exertion increased similarly over time in both conditions (P < 0.001), mentally fatigued subjects reached their maximal level of perceived exertion and disengaged from the physical task earlier than in the control condition. In conclusion, our study provides experimental evidence that mental fatigue limits exercise tolerance in humans through higher perception of effort rather than cardiorespiratory and musculoenergetic mechanisms. Future research in this area should investigate the common neurocognitive resources shared by physical and mental activity.

Index of Suspicion

Index of Suspicion

Cardiac involvement in adults with Pompe disease

Glycogen storage disease type II or Pompe disease is a neuromuscular disorder caused by deficiency of lysosomal acid alpha- glucosidase. Classic infantile Pompe disease results in massive left ventricular (LV) hypertrophy and failure. Although Pompe disease is often included in the differential diagnosis of LV hypertrophy the true frequency of cardiac involvement in adults with Pompe disease is not known. Forty-six consecutive adult patients (mean age 48 +/- 12, 22 men) with Pompe disease were included. Each patient underwent a clinical examination, electrocardiography, and rest and low-dose dobutamine (in 20 patients) two-dimensional echocardiography including contrast and tissue Doppler imaging. All patients had limited exercise tolerance; a rollator walking aid was used in seven patients (15%), a wheelchair in 13 patients (28%), and assisted ventilation in 14 patients (30%). Prior to this study, one patient was known with permanent atrial fibrillation, His-bundle ablation and a VVI pacemaker and another patient was known with fluid retention. The first patient had increased LV end-diastolic diameter, impaired LV ejection fraction, low systolic mitral annular velocities and diastolic dysfunction grade II. The patient with fluid retention was wheelchair bound and dependent on 24-h assisted ventilation and showed right ventricular and LV hypertrophy (septum 16 mm, posterior wall 15 mm). LV hypertrophy was not seen in any of the other patients. One woman of advanced age had isolated low systolic mitral annular velocities. Mean global systolic LV function, including contractile reserve, was not decreased in patients with Pompe disease. Eight patients (17%) had mild diastolic dysfunction grade I, related to hypertension in four and advanced age in seven. In adult patients with Pompe disease without objective signs of cardiac affection by 12-leads electrocardiography or physical examination, echocardiographic screening for LV hypertrophy seems not effective.

The major limitation to exercise performance in COPD is inadequate energy supply to the respiratory and locomotor muscles

No doubt dynamic hyperinflation and lack of oxidative capacity of skeletal muscles are important causes of exercise limitation in COPD. O'Donnell and Webb and Debigare and Maltais will convince the reader of this by the elegant experiments they have performed. The thesis we will put forward is that