Oxidative capacities of cardiac and skeletal muscles of heart transplant recipients: mitochondrial effects of cyclosporin-A and its vehicle Cremophor-EL.

Chronic immunosuppressive treatment was suspected to alter maximal muscle oxidative capacity (Vmax ) of heart transplant recipients, leading to a limitation of their exercise tolerance. It remains undefined whether the mitochondrial respiratory chain (MRC) of right ventricle (RV) and vastus lateralis (VL) muscles were altered by immunosuppressants and/or their vehicles. Vmax was measured polarographically in saponin-skinned fibres of RV and VL biopsies of patients and compared with Vmax of healthy VL and myocardium.

Impairment of maximal aerobic power with moderate hypoxia in endurance athletes: do skeletal muscle mitochondria play a role?

This study investigates the role of central vs. peripheral factors in the limitation of maximal oxygen uptake (Vo(2max)) with moderate hypoxia [inspired fraction (Fi(O(2))) =14.5%].

Deciphering the metabolic and mechanical contributions to the exercise-induced circulatory response: insights from eccentric cycling.

Metabolic demand and muscle mechanical tension are closely coupled during exercise, making their respective drives to the circulatory response difficult to establish. This coupling being altered in eccentric cycling, we implemented an experimental design featuring eccentric vs. concentric constant-load cycling bouts to gain insights into the control of the exercise-induced circulatory response in humans.

Exercising with a denervated heart after cardiac transplantation.

Heart transplantation (HTR) is now an accepted life-extending procedure for those dying of intractable heart failure (CHF). HTR patients expect a high quality of life which implies a reasonable exercise capacity. Nevertheless HTR present unique exercise challenges with both central and peripheral factors of limitation that result in peak oxygen uptakes of 60-70% of age-matched normal subjects.

Exercise training in normobaric hypoxia in endurance runners. I. Improvement in aerobic performance capacity.

This study investigates whether a 6-wk intermittent hypoxia training (IHT), designed to avoid reductions in training loads and intensities, improves the endurance performance capacity of competitive distance runners. Eighteen athletes were randomly assigned to train in normoxia [Nor group; n = 9; maximal oxygen uptake (VO2 max) = 61.5 +/- 1.

Exercise training in normobaric hypoxia in endurance runners. II. Improvement of mitochondrial properties in skeletal muscle.

This study investigates whether adaptations of mitochondrial function accompany the improvement of endurance performance capacity observed in well-trained athletes after an intermittent hypoxic training program. Fifteen endurance-trained athletes performed two weekly training sessions on treadmill at the velocity associated with the second ventilatory threshold (VT2) with inspired O2 fraction = 14.5% [hypoxic group (Hyp), n = 8] or with inspired O2 fraction = 21% [normoxic group (Nor), n = 7], integrated into their usual training, for 6 wk.

Muscular mitochondrial function in amyotrophic lateral sclerosis is progressively altered as the disease develops: a temporal study in man.

We performed repeated analysis of mitochondrial respiratory function in skeletal muscle (SM) of patients with early-stage sporadic amyotrophic lateral sclerosis (SALS) to determine whether mitochondrial function was altered as the disease advanced. SM biopsies were obtained from 7 patients with newly diagnosed SALS, the same 7 patients 3 months later, and 7 sedentary controls. Muscle fibers were permeabilized with saponin, then skinned and placed in an oxygraphic chamber to measure basal and maximal adenosine diphosphate (ADP)-stimulated respiration rates and to assess mitochondrial regulation by ADP.

Coordinated changes in mitochondrial function and biogenesis in healthy and diseased human skeletal muscle.

We examined the transcriptional signaling cascade involved in the changes of mitochondrial biogenesis and mitochondrial function of skeletal muscle and of the exercise capacity of humans in response to long-term physical activity and chronic heart failure (CHF). Biopsy samples of vastus lateralis muscle were obtained from 18 healthy subjects with different fitness levels (assessed by maximal oxygen uptake, VO2 peak). We compared 9 sedentary subjects with 10 CHF patients undergoing transplantation.

Improving exercise capacity, 6 wk training tends to reduce circulating endothelin after heart transplantation.

Short-term survival is no longer the pivotal issue after heart transplantation but, most heart-transplant (Htx) patients still present with increased circulating endothelin-1 (ET) and reduced exercise capacity. ET-1 limits both exercise-induced vasodilation and blood flow redistribution toward acting muscles and might be accessible to training. This study was performed to investigate the effect of training on ET-1 and whether an eventual training-induced improvement in exercise capacity may be related to reduced baseline or exercise circulating ET-1 in Htx patients.

Eccentric cycle exercise: training application of specific circulatory adjustments.

Purpose: Despite identical oxygen uptake (VO2), enhanced heart rate (HR) and cardiac output (Q) responses have been reported in eccentric (ECC) versus concentric (CON) cycle exercise. The aim of this study was to describe the specific circulatory adjustments (HR and stroke volume (SV)) to incremental ECC cycle exercise in order to: 1) determine the HR values leading to identical VO2 in ECC and CON cycling; and 2) estimate the interindividual variability of this HR correspondence between the two exercise modes, with emphasis upon rehabilitation and training purposes.

Methods: Eight healthy male subjects (age, 28 +/- 2 yr) participated in this study.

Evaluation of quantitative and qualitative aspects of mitochondrial function in human skeletal and cardiac muscles.

Techniques and protocols of assessment of mitochondrial properties are of physiological and physiopathological important significance. A precise knowledge of the advantages and limitations of the different protocols used to investigate the mitochondrial function, is therefore necessary. This report presents examples of how the skinned (or permeabilized) fibers technique could be applied for the polarographic determination of the actual quantitative and qualitative aspects of mitochondrial function in human muscle samples.

Preserved response of mitochondrial function to short-term endurance training in skeletal muscle of heart transplant recipients.

Objectives: We sought to determine whether intrinsic mitochondrial function and regulation were altered in heart transplant recipients (HTRs) and to investigate the response of mitochondrial function to six-week endurance training in these patients.

Background: Despite the normalization of central oxygen transport during exercise, HTRs are still characterized by limited exercise capacity, which is thought to result from skeletal muscle metabolic abnormalities.

Methods: Twenty HTRS agreed to have vastus lateralis biopsies and exercise testing: before and after training for 12 of them and before and after the same control period for eight subjects unwilling to train.

Mitochondrial electron transport chain function is enhanced in inspiratory muscles of patients with chronic obstructive pulmonary disease.

In chronic obstructive pulmonary disease, inspiratory muscles face increased resistive and elastic workloads and therefore increased energy requirements. The adaptive response of these muscles to this higher energy demand includes increased oxidative enzymes and changes in contractile protein expression but the consequences on mitochondrial function and energy metabolism have not been assessed so far. We investigated the in situ properties of the mitochondria of costal diaphragm and external intercostal muscles using the skinned fiber technique in 9 emphysematous and 11 age-matched control patients.

Mitochondrial respiratory chain function in skeletal muscle of ALS patients.

Evidence implicating mitochondrial dysfunction in the central nervous system of patients with sporadic amyotrophic lateral sclerosis (SALS) has recently been accumulating. In contrast, data on mitochondrial function in skeletal muscle in SALS are scarce and controversial. We investigated the in situ properties of muscle mitochondria in patients with early-stage SALS and sedentary (SED) controls using the skinned fiber technique to determine whether respiration of muscle tissue is altered in early-stage SALS in comparison with SED.