Hélène Perrault

The Mitochondrial Phenotype of Peripheral Muscle in Chronic Obstructive Pulmonary Disease Disuse or Dysfunction

RATIONALE Peripheral muscle alterations have been recognized to contribute to disability in chronic obstructive pulmonary disease (COPD). OBJECTIVES To describe the mitochondrial phenotype in a moderate to severe COPD population and age-matched controls. METHODS Three primary aspects of mitochondrial function were assessed in permeabilized locomotor muscle fibers. MEASUREMENTS AND MAIN RESULTS Respiration rates per milligram of fiber weight were significantly lower in COPD muscle compared with healthy age-matched control muscle under various respiratory states. However, when variations in mitochondrial volume were taken into account by normalizing respiration per unit of citrate synthase activity, differences between the two groups were abolished, suggesting the absence of specific mitochondrial respiratory impairment in COPD. H(2)O(2) production per mitochondrion was higher both under basal and ADP-stimulated states, suggesting that mitochondria from COPD muscle have properties that potentiate H(2)O(2) release. Direct assessment of mitochondrial sensitivity to Ca(2+)-induced opening of the permeability transition pore (PTP) indicated that mitochondria from patients with COPD were more resistant to PTP opening than their counterparts in control subjects. CONCLUSIONS Comparison of these results with those of studies comparing healthy glycolytic with oxidative muscle suggests that these differences may be attributable to greater type II fiber expression in COPD muscle, as mitochondria within this fiber type have respiratory function similar to that of mitochondria from type I fibers, and yet are intrinsically prone to greater release of H(2)O(2) and more resistant to PTP opening. These results thus argue against the presence of pathological mitochondrial alterations in this category of patients with COPD.

Comparison of cardiovascular adjustments to exercise in adolescents 8 to 15 years of age after correction of tetralogy of Fallot, ventricular septal defect or atrial septal defect

Surgical correction of tetralogy of Fallot (TF) has generally been associated with a reduced maximal exercise tolerance, possibly related to the ventriculotomy inherent to the intracardiac repair procedure. This study documents the exercise hemodynamics of a group of patients operated on for TF who showed similar clinical and functional characteristics, and compares these responses to those of age-matched patients operated on for an isolated ventricular septal defect (VSD) or atrial septal defect (ASD) in an attempt to better understand the role of the ventriculotomy in the exercise limitation. Thirty patients, ages 12 to 19 years, operated on before 5 years of age for complete repair of TF (n = 13), VSD (n = 7) or ASD (n = 10) and 10 age-matched control subjects underwent a progressive maximal cycling test to determine the maximal oxygen uptake (VO2 max), and completed submaximal cycling at intensities of 33 and 66% VO2 max, respectively, to determine the cardiac output (CO2-rebreathing). No significant differences in VO2 max were observed (TF = 37.6 +/- 10; VDS = 34.0 +/- 9.2; ASD = 36.5 +/- 7; controls = 41.3 +/- 6.0 ml/kg/min). The maximal heart rate, however, remained lower in all patient groups in comparison with control subjects (p less than or equal to 0.05) (TF = 178 +/- 14; VSD = 172 +/- 17; ASD = 179 +/- 16; controls = 191 +/- 12 beats/min).(ABSTRACT TRUNCATED AT 250 WORDS)

A simple and disposable sweat collector

SummaryApart from in cystic fibrosis, where sweat analysis provides valuable diagnostic information, sweat yields remain an overlooked biological fluid. Technical problems (dilution, condensation, contamination, evaporation, etc.) linked to currently available collection procedures are of concern and thwart their use. To overcome some of these technical difficulties, an original sweat-collection technique is described. A collection capsule is created inside a flexible, adhesive and disposable anchoring membrane pasted onto the skin. A fluid-tight window is positioned in the upper part of the pocket and gives access to its content. Through the collection window, complete emptying of the sweat collector can be achieved repeatedly by suction using a vacutainer tube inserted in a tube holder equipped with a long dull needle. With prior addition of a suitable marker, fractional samplings can also be performed using a precision micropipette. This collecting method allows for kinetic studies on sweat rate and sweat content. The limited bias-inducing manipulations linked to the described technique, coupled with the ease of performing kinetic studies on sweat volume and content, make this original tool a reliable and accurate sweat-collection technique.

Exercise-Induced Cardiac Hypertrophy Fact or Fallacy?

SummaryAfter a century of research reports, the notion of exercise-induced cardiac hypertrophy is still an expected adaptation to regular exercise training. Experimental evidence reported both in animals and in humans over the past 3 decades suggests, however, that this conclusion may not be totally warranted. Data from 20 years of echocardiographic investigations of athletes and nonathletes indicate that differences in cardiac dimensions are not very large. Cross-sectional comparisons of over 1000 athletes and roughly 800 control individuals indicate an average difference of 1.6mm in left ventricular (LV) wall thickness and of 5.3mm in end-diastolic diameter. Differences reported after training programmes lasting 4 to 52 weeks are even smaller, with average increases of 0.3mm in LV wall thickness and only 2.1 mm in end-diastolic diameter.This article reviews data from animal and human studies concerning cardiac morphology and exercise training to show that the traditional interpretation of the literature has failed to take into account several methodological considerations or factors that may act as confounders in the interpretation of data. Results from animal studies indicate that the observation of cardiac hypertrophy is equivocal at best. In many reports the reported changes in heart size are not significant, and in instances where significant changes are reported these may be seen to be confounded by a number of factors. For example, in rats the reported training-induced hypertrophy may be related to gender differences in the responsiveness of cardiac dimensions or body andlor organ growth rather than to true heart hypertrophy. Furthermore, the interpretation of results from training studies in rats has often been based on the assumption that the metabolic, haemodynamic and thermoregulatory requirements of swimming and running exercise in rats are similar, which may in fact not be the case. In addition, the use of the heart weightlbodyweight ratio as an index of cardiac hypertrophy. although widespread in animal studies, is open to criticism owing to failure to control for concurrent changes in bodyweight. Several methodological considerations and factors confounding the outcome of exercise training in humans have also been omitted when interpreting echocardiographic cross-sectional and longitudinal findings. For example, in adult echocardiography the practical resolution of the echocardiographic technique amounts to roughly 2.2mm. It follows, therefore, that unless differences of changes in cardiac dimensions exceed the limit of resolution they are meaningless although statistically significant. Results from a meta-analysis of echocardiographic investigations published over the last 20 years indicate that the average change reported for left ventricular (LV) wall thickness remains well under the limit of resolution. The mean increase in LV internal diameter reported equals or slightly exceeds the technical resolution. Its significance, however, may be questioned since neither training brachycardia nor training-induced plasma volume expansion have been taken into account. It is likely, therefore, that ‘increased diastolic filling’ rather than true eccentric hypertrophy explains the differences reported. Another factor that has not been acknowledged in the investigation of the ‘athlete’s heart’ is the fact that ‘athletes’ generally exhibit anthropometric characteristics which typically differentiate them from sedentary individuals. Despite the well known relationship between cardiac dimensions and body size, this was often not considered in the interpretation of cross-sectional data. Re-analysis of cardiac dimensions reported in athletes and their sedentary counterparts indicate that differences in LV wall thickness between groups are in fact eliminated when a correction for body surface are is introduced. Illegal drug supplementations may also contribute to the cross-sectional differences reported.Finally, re-evaluation of the evidence in light of potential confounders indicates that athletes present cardiac dimensions that are proportional to their body size but do not exceed the normal limits. Endurance training induces a modest increase in LV internal diameter which may be explained by increased diastolic filling resulting from resting bradycardia and hypervolaemia.

Altered mitochondrial regulation in quadriceps muscles of patients with COPD

Evidence exists for locomotor muscle impairment in patients with chronic obstructive pulmonary disease (COPD), including fiber type alterations and reduced mitochondrial oxidative capacity. In this study high‐resolution respirometry was used to quantify oxygen flux in permeabilized fibres from biopsies of the vastus lateralis muscle in patients with COPD and compared to healthy control subjects. The main findings of this study were that (i) routine state 2 respiration was higher in COPD; (ii) state 3 respiration in the presence of ADP was similar in both groups with substrate supply of electrons to complex I (COPD 38·28 ± 3·58 versus control 42·85 ± 3·10 pmol s−1 mg tissue−1), but O2 flux with addition of succinate was lower in COPD patients (COPD 63·72 ± 6·33 versus control 95·73 ± 6·53 pmol s−1 mg tissue−1); (iii) excess capacity of cytochrome c oxidase in COPD patients was only ∼50% that of control subjects. These results indicate that quadriceps muscle mitochondrial function is altered in patients with COPD. The regulatory mechanisms underlying these functional abnormalities remain to be uncovered.

Cardiovascular responses to dynamic submaximal exercise in children previously treated with anthracycline

This study assessed the long-term (5-year) outcome of pediatric low-dose anthracycline therapy on the circulatory response to moderate exercise. Thirteen patients (13 +/- 4 years old) and 15 age-matched control subjects completed a maximal cycle ergometer protocol as well as two 5-minute cycling tests at 33% and 66% maximal oxygen uptake (V(O2)max) for determination of cardiac index (carbon dioxide rebreathing). V(O2)max was lower in patients than in control subjects (1.3 +/- 0.5 L/min vs 2.3 +/- 0.6 L/min) (p< 0.05). Smaller relative increases in cardiac index for similar increases in relative exercise intensities were found in patients (33% V(O2)max, 73% vs 116%; 66% V(O2)max, 115% vs 192%), as a result of smaller increases in stroke index from rest (33% V(O2)max, 33% vs 54%; 66% V(O2)max, 33% vs 69%; p< 0.05). Similarly, despite normal resting systolic function, patients exhibited a lower stroke index and higher heart rate for any given value of oxygen uptake (milliliters per minute per square meter). Children who had survived cancer exhibited stroke index impairment during exercise similar in intensity to that of recreational activities or play, attesting to a limited inotropic reserve.

A Canadian, multicentre, randomized clinical trial of home-based pulmonary rehabilitation in chronic obstructive pulmonary disease: rationale and methods.

BACKGROUND Pulmonary rehabilitation remains largely underused. Self-monitored, home-based rehabilitation is a promising approach to improving the availability of pulmonary rehabilitation. OBJECTIVE To report the rationale and methods of a trial comparing the effectiveness of self-monitored, home-based rehabilitation with hospital-based, outpatient rehabilitation in patients with chronic obstructive pulmonary disease (COPD). STUDY DESIGN A parallel-group, randomized, noninferiority, multicentre trial will be performed with 240 patients with moderate to severe COPD. INTERVENTION Patients will be randomly assigned to conventional, supervised, hospital-based outpatient rehabilitation or self-monitored, home-based rehabilitation. Both interventions will include a standardized, comprehensive self-management program, in addition to the hospital-based outpatient or home-based exercise program. After the three-month intervention, patients in both groups will be encouraged to continue exercising at home. Patients will be assessed monthly with telephone interviews and in person at enrollment, three months and 12 months. OUTCOMES The dyspnea domain of the Chronic Respiratory Questionnaire (CRQ) at 12 months is the primary outcome variable. Secondary outcome variables include total and domain-specific CRQ scores; exercise tolerance and activity of daily living; health service use over the one-year study period; and direct and indirect costs of COPD treatment. ANALYSIS An intent-to-treat approach will be used as the primary analysis. The primary analysis will focus on the change in the CRQ dyspnea score using a two-sided t distribution based on 95% CIs. The same approach will be used for secondary continuous outcome variables. CONCLUSION The present trial will address two unresolved issues in pulmonary rehabilitation for patients with COPD: the short-term and long-term effectiveness of home-based pulmonary rehabilitation strategies. The authors will also determine if home-based pulmonary rehabilitation can reduce health service use (eg, hospitalizations and emergency visits) and if it can be done at a lower cost than the traditional hospital-based outpatient pulmonary rehabilitation.

Eccentric cycle exercise in severe COPD: feasibility of application.

Eccentric cycling may present an interesting alternative to traditional exercise rehabilitation for patients with advanced COPD, because of the low ventilatory cost associated with lengthening muscle actions. However, due to muscle damage and soreness typically associated with eccentric exercise, there has been reluctance in using this modality in clinical populations. This study assessed the feasibility of applying an eccentric cycling protocol, based on progressive muscle overload, in six severe COPD patients with the aim of minimizing side effects and maximizing compliance. Over 5 weeks, eccentric cycling power was progressively increased in all patients from a minimal 10-Watt workload to a target intensity of 60% peak oxygen consumption (attained in a concentric modality). By 5 weeks, patients were able to cycle on average at a 7-fold higher power output relative to baseline, with heart rate being maintained at ∼85% of peak. All patients complied with the protocol and presented tolerable dyspnea and leg fatigue throughout the study; muscle soreness was minimal and did not compromise increases in power; creatine kinase remained within normal range or was slightly elevated; and most patients showed a breathing reserve > 15 L.min−1. At the target intensity, ventilation and breathing frequency during eccentric cycling were similar to concentric cycling while power was approximately five times higher (p = 0.02). This study showed that an eccentric cycling protocol based on progressive increases in workload is feasible in severe COPD, with no side effects and high compliance, thus warranting further study into its efficacy as a training intervention.

Exercise-induced hypoxaemia in master athletes: effects of a polyunsaturated fatty acid diet.

AbstractExercise-induced hypoxaemia (EIH) has been associated with an oxygen diffusion limitation. Because polyunsaturated fatty acids (PUFA) administration can modify cell membrane fluidity, we hypothesized that the importance of EIH could be reduced after a 6-week PUFA diet. Resting pulmonary functions and a maximal cycling test were performed before and after the diet, in eight master athletes [48 (SD 6 years)]. The partial pressure. of O2 in arterial blood (PaO2), alveolar ventilation (