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Aims of the Study: Stiffening of large arteries has been associated with increased cardiovascular outcomes among older subjects. Endurance exercises might attenuate artery stiffness, but little is known about the effects of intermittent training programme. We evaluate the effect of a short Intermittent Work Exercise Training Program (IWEP) on arterial stiffness estimated by the measure of the pulse wave velocity (PWV)., Methods and Subjects: Seventy-one healthy volunteers (mean age: 64.6 years) free of symptomatic cardiac and pulmonary disease performed a 9-week IWEP that consisted of a 30-min cycling twice a week over a 9-week period. Each session involved six 5-min bouts of exercise, each of the latter separated into 4-min cycling at the first ventilatory threshold alternated with 1-min cycling at 90% of the pretraining maximal tolerated power. Before and after the IWEP, the following measurements were made: carotid-radial PWV and carotid-femoral PWV with a tonometer and systolic and diastolic blood pressure., Results: Training resulted in a non-significant decrease of the carotid-radial PWV, a significant decrease of the carotid-femoral PWV from 10.2 to 9.6 m/s (p < 0.001) (that was no longer significant after adjustment for mean arterial pressure) and a significant decrease in both systolic and diastolic blood pressure, respectively, from 129.6 ± 14.9 mmHg to 120.1 ± 14.1 mmHg (p < 0.001) and from 77.2 ± 8.8 mmHg to 71.4 ± 10.1 mmHg (p < 0.001)., Conclusion: The present results support the idea that a short-term intermittent aerobic exercise programme may be an effective lifestyle intervention for reducing rapidly blood pressure and probably central arterial stiffness among older healthy subjects., (© 2013 Blackwell Publishing Ltd.)

Objective: The aim of this study was to evaluate the efficiency of a short-term Intermittent Work Exercise Program (IWEP) among healthy elderly subjects., Study Design and Setting: This longitudinal prospective study took place at the Strasbourg University Hospital geriatric department., Study Participants: One hundred and fifty older volunteers, previously determined as being free from cardiac and pulmonary disease, were separated into two age groups: the "young senior" (60.2 ± 3.1 yr) and the "older senior" groups (70.8 ± 5.2 yr). These groups were then subdivided by gender into the "young female senior", "young male senior" "older female senior" and "older male senior" groups., Intervention: Before and after the IWEP, all subjects were asked to perform an incremental cycle exercise to obtain their first ventilatory threshold (VT1), maximal tolerated power (MTP), peak oxygen uptake (VO2peak) and maximal minute ventilation (MMV). The IWEP consisted of a 30-min cycling exercise which took place twice a week, and was divided into six 5-min stages consisting of 4 min at VT1 intensity and 1 min at 90% MTP., Measurements: An assessment was made of the effects of the IWEP on maximal cardio-respiratory function (MTP, VO2peak, MMV) and endurance parameters (VT1, heart rate [HR] measured at pretraining VT1 and lactate concentrations at pre-training MTP)., Results: This short-term training program resulted in a significant increase of MTP (from 13.2% to 20.6%), VO2peak (from 8.9% to 16.6%) and MMV (from 11.1% to 21.8%) in all groups (p<0.05). VT1 improved from 21% at pretraining to 27%, while HR at pre-training VT1 as well as lactate concentrations at pre-training MTP decreased significantly in all groups (p<0.05). The post-training values for VO2peak and MMV of the "older seniors" were not significantly different (p>0.05) from the "young seniors" pre-training values for the same parameters., Conclusion: The most striking finding in this study is that after only 9 weeks, our short-term "individually-tailored" IWEP significantly improved both maximal cardio-respiratory function and endurance parameters in healthy, previously untrained seniors.

Objectives: To administer a social handicap questionnaire associated with French DRGs (PMSI) to determine the social handicaps of a population hospitalized in a public health establishment and to measure the cost implications for the establishment due to increased length of stay (DMS)., Method: A prospective pilot study has been carried out in the Lariboisière-Fernand Widal Hospital Group in Paris targeting users 50 or more years old hospitalized for short stays in medicine, surgery and obstetrics. Data of the PMSI and answers to the questionnaire for hospitalisations longer than 24 hours have been exploited., Results: Two hundred twenty-two stays from 8 to 23 November 2005 have been analyzed: 140 pertained to patients aged 50-69 years (27.8%) and 82 to patients aged 70 or more years (16.3%). Three-fourths of the persons aged 50-69 and 70 or over presented a social handicap: 45% showed a strong handicap and a third an average handicap. The three indicators "renter/owner", "interior comfort" and "family relations" were the major determinants of social handicap for those aged 70 or more, 50-69 and 50 or more years. For the patients 70 years and over and those 50-69 years, with an average handicap, the indicator was "income" with the domain "patrimony." For strong handicaps, it was the indicator "scolarisation" for the 70 or more years and the indicator "income" for the 50-69 years old. When all classes and populations were pooled, the DMS was significantly lower than that of the ENC (p<0.001 for the 70 years and over; p<0.05 for the 50-69 years). With again all classes and populations pooled, patients 70 and over stayed in hospital 6.50 days less on average compared to data published by the ENC; those 50-69 years stayed 3.57 days less. Persons aged 50 and over with a social handicap remained hospitalized on average more than 2.5 days: 2.2 days for the 70 and over and 3.1 days for the 50-69 years group. In terms of hospital days that produces an increase of 18%, corresponding to a supplementary expenditure attributable to social handicap of approximately 5.9 million euros., Conclusion: This pilot study with a questionnaire disability social PMSI proposing specific aid, but also reducing the DMS, provides several promising information but also indicates the limits of our approach. Among these, we note in particular: (a) its regular feasibility requires constant supervision, wider and well-trained, (b) that the measurement of our tool can only be affirmed after its use in many patients, and (c) the classification of disability in social class could even be discussed again. We still wanted to explore whether through this initiative without much logistical, markers of interest had emerged, which seems to be the case., ((c) 2009 Elsevier Masson SAS. All rights reserved.)

Background: Ageing is known to be associated with a decrease in peak oxygen consumption (VO2peak) and maximal tolerated power (MTP). Regular physical exercise is the most appropriate to improve aerobic capacity, but its effect still remained discussed in old people., Design: The aim of this study was to determine whether a short interval training session would be associated with improvements in exercise efficiency in aged subjects in both genders., Methods: In all, 19 women and 16 men (65.4 +/- 4.9 years) performed a cycle incremental exercise test before and after a 9-week period of aerobic interval training (twice a week, 30 min session where 6 x 4-min at the first ventilatory threshold alternated with 1-min at the second ventilatory threshold) with cycle ergometer. Minute ventilation (MV), O(2) uptake (VO(2)) and CO(2) output (VCO(2)) were measured breath-by-breath and by an open-circuit metabolic cart., Results: Before training, maximal values of MV (MMV), VO2peak, heart rate, systolic blood pressure, MTP, blood lactate at MTP recovery and the power at the first (pVT(1)) and second ventilatory thresholds (pVT(2)) were higher in men compared with women. Nine weeks of interval training induced a significant increase in MMV, VO2peak, MTP, pVT(1) and pVT(2) and decrease in systolic blood pressure in the same way in men than in women, without any significant effect on their maximal heart rate values., Conclusions: These findings suggest that the age-related declines in aerobic index are attenuated by a short exercise interval training sessions in women and men.

As the number of elderly persons in our country increases, more attention is being given to geriatric healthcare needs and successful ageing is becoming an important topic in medical literature. Concept of successful ageing is in first line on a preventive approach of care for older people. Promotion of regular physical activity is one of the main non-pharmaceutical measures proposed to older subjects as low rate of physical activity is frequently noticed in this age group. Moderate but regular physical activity is associated with a reduction in total mortality among older people, a positive effect on primary prevention of coronary heart disease and a significant benefit on the lipid profile. Improving body composition with a reduction in fat mass, reducing blood pressure and prevention of stroke, as well as type 2 diabetes, are also well established. Prevention of some cancers (especially that of breast and colon), increasing bone density and prevention of falls are also reported. Moreover, some longitudinal studies suggest that physical activity is linked to a reduced risk of developing dementia and Alzheimer's disease in particular.

Physical activity and sports are considered as one of the determinants of health. The aim of this study is to review the rationale for the formulation of this public health issue and its integration in national action plans. The study shows that fourteen national programmes were drafted and implemented between 2001 and 2006 by seven institutions. The research methodology was based on crossing data obtained from semi-directed interviews and documents regarding the design, implementation and follow-up of these programmes. For the conditions of the success, the fourteen actions scored an average of 175.0 +/- 66.9 out of 300%. Public health actors and professionals must be given more opportunities to involve themselves and engage in developing stronger relationships and linkages, in particular with the institutional and community settings. In general, the most invested parts of a programme are the structural and operational aspects of activities. Six significant points surfaced from the study: consideration of drug use as an addictive behaviour; recognition of the psychological stress of professional athletes; acknowledgment of youth as being at high risk for doping behaviour; integration of the concept that physical activity and sports must take the benefit/risk perspective into account; and the necessity to promote health. Through the exchange of numerous local and regional experiences, an optimisation of their synergistic connections was made possible on a continuum extending from "health promotion through physical activity and sports" to "prevention of drug-use and doping behaviours". Professionals have been able to develop actions in the above-mentioned domains across this continuum that have, to date, remained isolated. Proposals are made to strengthen these dynamics. Other health determinants and public health priorities could be investigated with the same methodology.

Physical activity and exercise are recognized as one of the determinants of health. This study aims to produce a review of the logical foundations at work that support the identification of a public health problem for this determinant and how to address it through national action. The research is based on cross-analysis of data from semi-directed interviews and data extracted from documents on the development, implementation and follow-up of such actions and programmes. The study shows that fourteen national programmes were created and implemented by seven different agencies. These fourteen activities scored an average of 175 +/- 66.9 out of 300%. Actors and professionals in the field must be given more capacity to be implicated and involved while simultaneously encouraging the strengthening of relationships with their environment, in particular the institutional and organizational settings as well as the community components. In general, the structural and operational aspects of action are those which receive the most investment in such activities. Six main points arose as important: doping considered as a addictive mechanism, acknowledgement of the psychological suffering of professional athletes, youth at high risk of doping, and that the concepts of physical activity and sports should take into account a risk/ benefit analysis and the necessity to first and foremost promote health. The act of sharing and exchanging a number of experiences, at the local and regional level, resulted in the identification of synergies between these experiences on a continuum from "health promotion through physical activity and sports" to "prevention of doping". Within this framework, professionals were able to develop activities in the aforementioned domains, which until now had remained isolated and marginal. Recommendations were made to reinforce and strengthen this dynamic. Other determinants of health and public health priorities could be explored using the same methodology.

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. Heart rate (HR), stroke volume (SV), cardiac output (Q), oxygen uptake (V(.-)(O(2))), and electromyographic (EMG) activity of quadriceps muscles were measured in 11 subjects during heavy concentric (heavy CON: 270 +/- 13 W; V(.-)(O(2)) = 3.59 +/- 0.20 l/min), heavy eccentric (heavy ECC: 270 +/- 13 W, V(.-)(O(2)) = 1.17 +/- 0.15 l/min), and light concentric (light CON: 70 +/- 9 W, V(.-)(O(2)) = 1.14 +/- 0.12 l/min) cycle bouts. Using a reductionist approach, the circulatory responses observed between heavy CON vs. light CON (difference in V(.-)(O(2)) and power output) was ascribed either to metabolic demand, as estimated from heavy CON vs. heavy ECC (similar power output, different V(.-)(O(2))), or to muscle mechanical tension, as estimated from heavy ECC vs. light CON (similar V(.-)(O(2)), different power output). 74% of the Q response was determined by the metabolic demand, also accounting for 65% and 84% of HR and SV responses, respectively. Consequently, muscle mechanical tension determined 26%, 35%, and 16% of the Q, HR, and SV responses, respectively. Q was significantly related to V(.-)(O(2)) (r(2) = 0.83) and EMG activity (r(2) = 0.82; both P < 0.001). These results suggest that the exercise-induced circulatory response is mainly under metabolic control and support the idea that the level of muscle activation plays a role in the cardiovascular regulation during cycle exercise in humans.

The purpose of the study was to determine the potential beneficial effect of six weeks oral L-arginine supplementation (LAS) on endurance exercise, an important determinant of daily-life activity in patients with chronic stable heart failure (CHF). After an initial incremental maximal exercise test, CHF patients performed an identical thirty-minute interval endurance exercise test before and after six weeks with (L-arginine group; ARG) or without LAS (control group; CTL). Hemodynamic, respiratory, and metabolic parameters were determined at rest, during exercise, and during recovery. Mean heart rate decreased throughout exercise and recovery after LAS (- 8.2 +/- 1.4 b x min(-1); p = 0.003 and - 6.7 +/- 1.6 b x min(-1); p < 0.001, respectively), systemic blood pressure and respiratory parameters remaining unchanged. Resting L-argininaemia increased from 102 +/- 11 to 181 +/- 37 micromol x l(-1) (p < 0.004) and exercise-induced peak increase in plasma lactate was blunted after LAS (4.13 +/- 0.75 vs. 3.13 +/- 0.39 mmol x l(-1); p = 0.02). No significant change was observed in the control group. In heart failure patients, six weeks oral LAS enhances endurance exercise tolerance, reducing both heart rate and circulating lactates. This suggests that chronic LAS might be useful as a therapeutic adjuvant in order to improve the patient's physical fitness.

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 +/- 1.1 ml x kg(-1) x min(-1)] or intermittently in hypoxia (Hyp group; n = 9; VO2 max = 64.2 +/- 1.2 ml x kg(-1) x min(-1)). Into their usual normoxic training schedule, athletes included two weekly high-intensity (second ventilatory threshold) and moderate-duration (24-40 min) training sessions, performed either in normoxia [inspired O2 fraction (FiO2) = 20.9%] or in normobaric hypoxia (FiO2) = 14.5%). Before and after training, all athletes realized 1) a normoxic and hypoxic incremental test to determine VO2 max and ventilatory thresholds (first and second ventilatory threshold), and 2) an all-out test at the pretraining minimal velocity eliciting VO2 max to determine their time to exhaustion (T(lim)) and the parameters of O2 uptake (VO2) kinetics. Only the Hyp group significantly improved VO2 max (+5% at both FiO2, P < 0.05), without changes in blood O2-carrying capacity. Moreover, T(lim) lengthened in the Hyp group only (+35%, P < 0.001), without significant modifications of VO2 kinetics. Despite similar training load, the Nor group displayed no such improvements, with unchanged VO2 max (+1%, nonsignificant), T(lim) (+10%, nonsignificant), and VO2 kinetics. In addition, T(lim) improvements in the Hyp group were not correlated with concomitant modifications of other parameters, including VO2 max or VO2 kinetics. The present IHT model, involving specific high-intensity and moderate-duration hypoxic sessions, may potentialize the metabolic stimuli of training in already trained athletes and elicit peripheral muscle adaptations, resulting in increased endurance performance capacity.

Objective: To study the effect of a wheelchair interval-training program on the ventilatory function of subjects with recent spinal cord injury (SCI)., Design: Evaluation trial before and after a training program., Setting: Center of reeducation and university hospital., Participants: Six subjects (5 men, 1 woman) hospitalized after a recent SCI., Intervention: On a wheelchair ergometer, subjects with SCI performed 30 minutes of interval training 3 times a week for 6 weeks. The training program was part of their reeducation program., Main Outcome Measures: Spirometric values at rest and dynamic ventilatory responses were studied before and after this training program with a spirometric test, a maximal exercise test that increased by 5W every 2 minutes, and a submaximal test., Results: Spirometric values at rest did not change after training. At maximal exercise, peak ventilation (Vepeak, 7.5%), peak breathing frequency (f peak) (-13.4%), peak tidal volume (Vtpeak +28.9%), and the ventilatory reserve (12.9%) improved after training. The oxygen cost of Ve decreased significantly (-20%) after training. We observed for the wheelchair tests that, at the same workload after training, Ve and f decreased and Vt increased., Conclusions: After 6 weeks of our interval-training program in subjects with recent SCI, the increase of Vt and the decrease of oxygen cost of Ve indicated better ventilatory efficiency.

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. Among central factors persistent chronotropic incompetence questions the occurrence and role of the graft reinnervation. Among peripheral factors the energetic impairement of the skeletal muscle seem to result more from microvascular abnormalities than from an actual deficit in oxidative capacity, questioning the mechanism of recovery from the CHF peripheral myopathy and the role of immunosuppressive drugs. Endurance and resistance training programs may reverse at least in part most but not all of these abnormalities. Training permits patients to engage in sports and even to participate in competitive events that are rewarding to them but also to the community because it promotes organ donation and confidence in medical achievements. Mechanisms of exercise impairments and improvements resulting from training are discussed in the perspective of current literature. Areas of future research and recommendations for the practice of sports after HTR are suggested.

Purpose: Endurance training is an important component of rehabilitation in patients with chronic obstructive pulmonary disease (COPD). In our study, we investigated the pulmonary hemodynamics' adaptation during a high-intensity intermittent exercise in such patients., Methods: Eight patients underwent a 30-min exercise, alternating a 4-min work set at their first ventilatory threshold with a 1-min exercise set at 90% of their maximal tolerated power output. Pulmonary arterial pressure was measured by means of a right heart catheter. Cardiac output was calculated using the Fick's principle applied to oxygen., Results: VO(2), cardiac output, and ventilation increased during the first minutes of exercise and remained stable thereafter. Heart rate increased significantly and progressively to its maximal value from rest to the end of the test (P < 0.001). After an initial increase, stroke volume decreased significantly (P < 0.05). Pulmonary arterial pressure increased from rest (mean +/- SEM 23.9 +/- 2.1 mm Hg) to the fifth minute of exercise (41.6 +/- 2.8 mm Hg), and decreased significantly thereafter (35.2 +/- 3.3 mm Hg at the 30th minute) (P < 0.001). Total pulmonary vascular resistance decreased from rest to the end of the test (P < 0.001)., Conclusion: The high-intensity 1-min bouts of work of our intermittent work exercise are well tolerated without pushing the pulmonary arterial pressure dramatically high in COPD patients.

Our objectives were firstly, to study the patterns of the cardiac output (Q(.)) and the arteriovenous oxygen difference [(a-nu(-))O(2)] responses to oxygen uptake (V(.)O(2)) during constant workload exercise (CWE) performed above the respiratory compensation point (RCP), and secondly, to establish the relationships between their kinetics and the time to exhaustion. Nine subjects performed two tests: a maximal incremental exercise test (IET) to determine the maximal V(.)O(2) (V(.)O(2)peak), and a CWE test to exhaustion, performed at p Delta50 (intermediate power between RCP and V(.)O(2)peak). During CWE, V(.)O(2) was measured breath-by-breath, Q(.) was measured beat-by-beat with an impedance device, and blood lactate (LA) was sampled each minute. To calculate ( a-nu(-)O(2), the values of V(.)O(2) and Q(.) were synchronised over 10 s intervals. A fitting method was used to describe the V(.)O(2), Q(.) and ( a-nu(-))O(2) kinetics. The ( a-nu(-)O(2) difference followed a rapid monoexponential function, whereas both V(.)O(2) and Q(.) were best fitted by a single exponential plus linear increase: the time constant (tau) V(.)O(2) [57 (20 s)] was similar to tau ( a-nu(-)O(2), whereas tau for Q(.) was significantly higher [89 (34) s, P <0.05] (values expressed as the mean and standard error). LA started to increase after 2 min CWE then increased rapidly, reaching a similar maximal value as that seen during the IET. During CWE, the rapid component of V(.)O(2) uptake was determined by a rapid and maximal ( a-nu(-)O(2) extraction coupled with a two-fold longer Q(.) increase. It is likely that lactic acidosis markedly increased oxygen availability, which when associated with the slow linear increase of Q(.), may account for the V(.)O(2) slow component. Time to exhaustion was larger in individuals with shorter time delay for ( a-nu(-)O(2) and a greater tau for Q(.).

Purpose: It has been suggested that an intermittent work exercise test (IWET) is as efficient but better tolerated than continuous exercise for rehabilitation. Although systemic and pulmonary cardiovascular adjustments have been investigated for continuous exercise, it has not been done for IWET with exercise bouts near maximal work rate., Methods: In seven healthy subjects, the pulmonary hemodynamics have been studied by the aid of heart catheterization during a strenuous 30-min bicycle IWET where a 4-min work set at the first ventilatory threshold (VT1) alternated with a 1-min work set at the second ventilatory threshold (VT2)., Results: During the IWET, cardiac output increased then remained stable with decreasing stroke volume and increasing heart rate, which became near maximal at the end of the test. Mean pulmonary arterial pressure increased from rest to the fifth minute of exercise and decreased significantly thereafter (P<0.01). An identical evolution was observed for mean systemic arterial pressure (SAP)., Conclusion: Pulmonary hemodynamics adapt well in healthy subjects during a strenuous IWET despite the performance of exercise bouts of near maximal intensity.

Study Design: Before and after investigation of the effects of a wheelchair ergometer Training programme., Objective: To investigate the effects of an original interval-training programme on work capacity and cardiorespiratory variables with spinal cord-injured persons (SCIP's) on a wheelchair-specific ergometer., Setting: BESANCON, FRANCE., Methods: Seven SCIP's (male) performed 45 min of wheelchair ergometry three times per week, for 6 weeks. Training effects on maximal dynamic performance and endurance capacity were studied by comparison of performance and cardiorespiratory responses observed during both a maximal progressive test (10 W/2 min) and the same training session performed before and after training., Results: Training induced significant improvements in maximal tolerated power (+19.6%), in peak oxygen consumption (VO2,+16%), and in oxygen pulse (O2p,+18.7%). At ventilatory threshold, significant improvements were also observed in power output (+63%), VO2VT(+ 34.1), ventilation VEVT(+ 37.1%), and V2pVT(+ 19.9% ). Heart rate and ventilation were significantly lower (-11 and -14.6%, respectively) after training at the same work rate, while VO2 was unchanged. Between the first and the last training session, the total physical work was improved by 24.7%, whereas heart rate was unchanged., Conclusion: An interval-training programme individualised to each paraplegic subject using a wheelchair ergometer can significantly improve the fitness level and endurance capacity.

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 respiration was evaluated on saponin-permeabilized muscle fibers in the absence or presence (maximum respiration rate [V(max)]) of saturating adenosine diphosphate., Results: Mitochondrial function was preserved at the level of sedentary subjects in untrained HTRs, although they showed 28 +/- 5% functional aerobic impairment (FAI). After training, V(max), citrate synthase, cytochrome c oxidase, and mitochondrial creatine kinase (CK) activities were significantly increased by 48%, 40%, 67%, and 53%, respectively (p < 0.05), whereas FAI decreased to 12 +/- 5% (p < 0.01). The control of mitochondrial respiration by creatine and mitochondrial CK was also improved (p < 0.01), suggesting that phosphocreatine synthesis and transfer by the mitochondrial CK become coupled to oxidative phosphorylation, as shown in trained, healthy subjects., Conclusions: In HTRs, the mitochondrial properties of skeletal muscle were preserved and responded well to training, reaching values of physically active, healthy subjects. This suggests that, in HTRs, immunosuppressive drugs do not alter the intrinsic muscle oxidative capacities and that the patients' physical handicap results from nonmitochondrial mechanisms.

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. Musculus vastus lateralis biopsies were obtained from 7 SED group members and 14 patients with early-stage SALS (mean disease duration, 9 months). Muscle fibers were permeabilized with saponine and then skinned and placed in an oxygraphic chamber to measure basal (V(0)) and maximal (V(max)) adenosine diphosphate-stimulated respiration rates and to assess mitochondrial regulation by adenosine diphosphate. Muscle oxidative capacity, evaluated with V(max), was identical in patients in the SALS and SED groups (V(0): SALS, 1.1 +/- 0.1; SED, 0.8 +/- 0.1, micromol 0(2). min(-1). gm(-1)dw and V(max): SALS, 3.1 +/- 0.3; SED, 2.5 +/- 0.3, micromol 0(2). min(-1). gm(-1)dw). This study shows an absence of large mitochondrial damage in skeletal muscle of patients with early-stage SALS, suggesting that mitochondrial dysfunction in the earlier stages of SALS is almost certainly not systemic.

To investigate the effect of L-arginine supplementation (L-ARG) on physiological and metabolic changes during exercise, we determined in a double-blind study the cardiorespiratory (heart rate, oxygen consumption (VO(2)) and carbon dioxide production (VCO(2)) and the metabolic (lactate and ammonia) responses to maximal exercise after either an intravenous L-ARG hydrochloride salt or placebo load in 8 healthy subjects. Exercise-induced increases in heart rate, VO(2) and VCO(2) were not significantly different after L-ARG or placebo. By contrast, peak plasma ammonia and lactate were significantly decreased after L-ARG load (60.6 +/- 8.2 vs. 73.1 +/- 9.1 micro mol x l(-1), p < 0.01 and 7.1 +/- 0.7 vs. 8.2 +/- 1.1 mmol x l(-1), p < 0.01, for ammonia and lactate, respectively). Plasma L-citrulline increased significantly during exercise only after L-ARG load, despite a concomitant decrease in plasma L-ARG. Furthermore, a significant inverse relationship was observed between changes in lactate and L-citrulline concentrations after L-ARG load (r = -0.84, p = 0.009). These results demonstrate that intravenous L-ARG reduces significantly exercise-induced increase in plasma lactate and ammonia. Taken together, the specific L-citrulline increase and the inverse relationship observed between L-citrulline and plasma lactate after L-ARG might support that L-ARG supplementation enhances the L-arginine-nitric oxide (NO) pathway during exercise.

Background: Various combinations of training intensity, duration and frequency are often proposed to people with spinal cord injuries in order to improve their fitness. However, no consensus about a specific training program has been reached for such a population., Objective: This study investigated the effects of a short interval training program specifically designed for patients with spinal cord injuries., Methods: Paraplegic men performed 30-min wheelchair ergometry three times per week, for 4 weeks. Maximal dynamic performance and endurance capacity were studied before and after the training program with an incremental test (10 W/2 min) until volitional fatigue and a constant work rate test, respectively. Cardiorespiratory responses were continuously studied during each of these tests., Results: Training induced significant improvement in maximal tolerated power (+27.9%), and in peak oxygen consumption ([VO2, +18.5%). After training the subjects were able to maintain the load applied during the constant test (total mechanical work +210.7%), for a significantly longer time. The heart rate, [VO2 and ventilation values observed when the volunteers ended their first constant load test were significantly higher (+10%, +10%, +40% respectively) than those obtained after a similar time period during the second constant load test which was performed after the training program., Conclusion: After this short training period, with an appropriate combination of different types of training, duration, intensity and frequency exercises, we observed a significant improvement in the fitness level and endurance capacity of paraplegic subjects.

Objectives: We investigated the in situ properties of muscle mitochondria using the skinned fiber technique in patients with chronic heart failure (CHF) and sedentary (SED) and more active (ACT) controls to determine: 1) whether respiration of muscle tissue in the SED and ACT groups correlates with peak oxygen consumption (pVO(2)), 2) whether it is altered in CHF, and 3) whether this results from deconditioning or CHF-specific myopathy., Background: Skeletal muscle oxidative capacity is thought to partly determine the exercise capacity in humans and its decrease to participate in exercise limitation in CHF., Methods: M. Vastus lateralis biopsies were obtained from 11 SED group members, 10 ACT group members and 15 patients with CHF at the time of transplantation, saponine-skinned and placed in an oxygraphic chamber to measure basal and maximal adenosine diphosphate (ADP)-stimulated (V(max)) respiration rates and to assess mitochondrial regulation by ADP. All patients received angiotensin-converting enzyme (ACE) inhibitors., Results: The pVO(2) differed in the order CHF < SED < ACT. Compared with SED, muscle alterations in CHF appeared as decreased citrate synthase, creatine kinase and lactate dehydrogenase, whereas the myosin heavy chain profile remained unchanged. However, muscle oxidative capacity (V(max), CHF: 3.53 +/- 0.38; SED: 3.17 +/- 0.48; ACT: 7.47 +/- 0.73, micromol O(2).min(-1).g(-1)dw, p < 0.001 vs. CHF and SED) and regulation were identical in patients in the CHF and SED groups, differing in the ACT group only. In patients with CHF, the correlation between pVO(2) and muscle oxidative capacity observed in controls was displaced toward lower pVO(2) values., Conclusions: In these patients, the disease-specific muscle metabolic impairments derive mostly from extramitochondrial mechanisms that disrupt the normal symmorphosis relations. The possible roles of ACE inhibitors and level of activity are discussed.

One of the greatest challenges in exercise physiology is to develop a valid, reliable, non-invasive and affordable measurement of cardiac output (CO). The purpose of this study was to evaluate the reproducibility and accuracy of a new impedance cardiograph device, the Physio Flow, during a 1-min step incremental exercise test from rest to maximal peak effort. A group of 12 subjects was evaluated to determine the reproducibility of the method as follows: (1) each subject performed two comparable tests while their CO was measured by impedance cardiography using the new device (COImp1, COImp2), and (2) in a subgroup of 7 subjects CO was also determined by the direct Fick method (COFick) during the second test. The mean difference between the values obtained by impedance (i.e. COImp1-COImp2) was -0.009 l.min-1 (95% confidence interval: -4.2 l.min-1, 4.2 l.min-1), and CO ranged from 3.55 l.min-1 to 26.75 l.min-1 (n = 146). When expressed as a percentage, the difference (COImp1-COImp2) did not vary with increasing CO. The correlation coefficient between the values of COImp and COFick obtained during the second exercise test was r = 0.94 (P < 0.01, n = 50). The mean difference expressed as percentage was -2.78% (95% confidence interval: -27.44%, 21.78%). We conclude that COImp provides a clinically acceptable evaluation of CO in healthy subjects during an incremental exercise.

Although cyclosporin (CsA) is considered to be the best immunosuppressive molecule in transplantation, it has been suspected to alter mitochondrial respiration of various tissues. We evaluated the acute effect of CsA and its vehicle on maximal oxidative capacity (V(max)) of cardiac, soleus and gastrocnemius muscles of rats by an oxygraphic method in saponin skinned muscle fibres. The effects of Sandimmun (a formulation of CsA), vehicle of Sandimmun (cremophor and ethanol (EtOH)), CsA in EtOH and EtOH alone were tested. Increasing concentrations (5 - 20 - 50 - 100 microM) of CsA (or vehicles) were used. Sandimmun profoundly altered the V(max) of all muscles. For example, at 20 microM, inhibition reached 18+/-3, 23+/-5, 45+/-5%, for heart, soleus and gastrocnemius respectively. There were only minor effects of CsA diluted in EtOH and EtOH alone on V(max) of cardiac muscle. Because the effects of vehicle on V(max) were similar or higher than those of Sandimmun, the inhibition of oxidative capacity could be entirely attributed to the vehicle for all muscles. Next, we investigated the potential sites of action of the vehicle on the different complexes of the mitochondrial respiratory chain by using specific substrates and inhibitors. The vehicle affected mitochondrial respiration mainly at the level of complex I ( approximately -85% in skeletal muscles, and -32% in heart), but also at complex IV ( approximately -26% for all muscles). The mechanism of action of the vehicle on the mitochondrial membrane and the implications for the clinical use of immunosuppressive drugs are discussed.

Purpose: The mechanisms of the training-induced improvements in left ventricular assist (LVAD) patients are unknown., Methods: We measured the hemodynamic, gas exchange, and metabolic and hormonal effects of 6-wk exercise training in a cardiogenic shock patient who was assisted by an LVAD., Results: After training, the peak power and VO2 increased by 166% and 56%, respectively (80 W and 16.1 mL x min(-1) x kg(-1)), whereas the ventilatory drive decreased. Although the LVAD output increased little with exercise, the systemic cardiac output rose (adequately for the VO2) from 5.91 and 4.90 L x min(-1) at rest to 9.75 and 9.47 L x min(-1) at peak work rate, before and after training, respectively. Thus, the left ventricle ejected again through the aortic valve. Unloading and/or retraining resulted in a left ventricular filling pressure decrease. Although the right ventricular ejection fraction increased with exercise, it decreased again at the maximal load after training. For a given work rate the arterial lactate, the norepinephrine (NE) and epinephrine (E) concentrations fell after training, but the enhanced maximal work rate elicited higher NE and E concentrations (4396 and 1848 pg x mL(-1), respectively). The lack of right ventricular unloading might have kept the atrial natriuretic peptide higher after training, but the blood cyclic GMP and endothelin were lower after training., Conclusion: In an LVAD patient, retraining returns the exercise capacity to the class III level by peripheral and left ventricular hemodynamic improvements, but the safety of maximal exercise remains to be proven in terms of right ventricular function and orthosympathetic drive.

Adrenomedullin (ADM) is a newly discovered potent vasorelaxing and natriuretic peptide that recently has been shown to be increased after heart transplantation. To investigate the hemodynamic factors modulating its release and the eventual role of ADM in blood pressure regulation after heart transplantation, seven matched heart-transplant recipients (Htx) and seven normal subjects performed a maximal bicycle exercise test while monitoring for heart rate, blood pressure, and circulating ADM. Baseline heart rate and systemic blood pressure were higher in Htx; left ventricular mass index and ADM tended to be higher after heart transplantation and correlated positively in Htx (r = 0.79, P = 0.03). As expected, exercise-induced increase in heart rate was lower in Htx than in controls (60 +/- 11 % vs. 121 +/- 14 %, respectively) and blood pressure increase was similar in both groups. Maximal exercise increased significantly plasma ADM in both groups (from 25.3 +/- 3.1 to 30.7 +/- 3.5 pmol/L, P < 0.05 and from 15.2 +/- 1.4 to 29.1 +/- 4.4 pmol/L, P = 0.02 in Htx and controls, respectively), the hypotensive peptide level remaining elevated until the 30th min of recovery. A significant inverse relationship was observed between peak mean blood pressure and circulating ADM in Htx (r = -0.86, P < 0.02). Besides showing that circulating ADM is increased after heart transplantation, the present study demonstrates a positive relationship between baseline ADM and left ventricular mass index. Furthermore, maximal exercise-induced increase in ADM is inversely related to mean blood pressure in Htx, suggesting that ADM might participate in blood pressure regulation during exercise after heart transplantation.

The objectives of this study were to evaluate the reliability and accuracy of a new impedance cardiograph device, the Physio Flow, at rest and during a steady-state dynamic leg exercise (work intensity ranging from 10 to 50 W) performed in the supine position. We compared cardiac output determined simultaneously by two methods, the Physio Flow (QcPF) and the direct Fick (QcFick) methods. Forty patients referred for right cardiac catheterisation, 14 with sleep apnoea syndrome and 26 with chronic obstructive pulmonary disease, took part in this study. The subjects' oxygen consumption values ranged from 0.14 to 1.19 l x min(-1). The mean difference between the two methods (QcFick - QcPF) was 0.04 l x min(-1) at rest and 0.29 l x min(-1) during exercise. The limits of agreement, defined as mean difference +/- 2SD, were -1.34, +1.41 l x min(-1)] at rest and -2.34, +2.92 l x min(-1) during exercise. The difference between the two methods exceeded 20% in only 2.5% of the cases at rest, and 9.3% of the cases during exercise. Thoracic hyperinflation did not alter QcPF. We conclude that the Physio Flow provides a clinically acceptable and non-invasive evaluation of cardiac output under these conditions. This new impedance cardiograph device deserves further study using other populations and situations.

Background: Cyclosporine induces daily renal hypoperfusion in subjects with normal atrial natriuretic peptide (ANP) levels, but its acute effects in heart transplant patients with increased ANP remain to be determined., Methods: Cyclosporinemia and creatinine clearance were monitored during 7 hours following cyclosporine administration in 6 heart transplant patients., Conclusions: No acute cyclosporine-induced decrease in creatinine clearance was observed after heart transplantation. These data suggest that maintenance cyclosporine dose may be less nephrotoxic than suspected and that increased ANP might protect the renal function late after heart transplantation.

Purpose: Relative to healthy control individuals with normal hemoglobin (Hb), patients carrying the double heterozygous form of sickle cell disease (HbSC) display an impaired oxygen transport capacity. The present study was undertaken to determine the influence of the decreased oxygen availability associated with the presence of HbSC on the cardiorespiratory and metabolic responses to endurance exercise., Methods: Eleven black men affected by the double heterozygous form of the sickle cell disease (HbSC group) and seven healthy subjects with normal Hb (HbAA group) of the same ethnic origin submitted successively to an incremental exercise test to exhaustion on a cycle ergometer for the determination of their maximal tolerated power and to a 20-min endurance exercise., Results: The HbSC had a significantly lower exercise tolerance than the HbAA. During the endurance exercise, they exhibited furthermore significantly lower VO2, VCO2, and minute ventilation V(E) than the HbAA. Despite the fact that the HbSC exercised at a significantly lower mean absolute work rate than the HbAA, except for the ventilatory equivalent for CO2 (V(E)/VCO2), which was higher (P < 0.001) in the HbSC group, the other parameters recorded during the 20-min endurance exercise (heart rate, arterial PaO2, PaCO2, pH, lactate, and VE/VO2, the ventilatory equivalent for O2) and during the subsequent recovery (blood lactate) were similar for both groups., Conclusion: The study underscores the importance of considering relative work rate as well as absolute work rate to arrive at a correct interpretation of exercise and recovery data. The results give evidence that the modifications of homeostasis brought into play by exercise were shifted toward distinctly lower absolute work rates in HbSC patients.

Because the cardiocirculatory response of heart transplant recipients (HTR) to exercise is delayed, we hypothesized that their O(2) uptake (VO(2)) kinetics at the onset of subthreshold exercise are slowed because of an impaired early "cardiodynamic" phase 1, rather than an abnormal subsequent "metabolic" phase 2. Thus we compared the VO(2) kinetics in 10 HTR submitted to six identical 10-min square-wave exercises set at 75% (36 +/- 5 W) of the load at their ventilatory threshold (VT) to those of 10 controls (C) similarly exercising at the same absolute (40 W; C40W group) and relative load (67 +/- 14 W; C67W group). Time-averaged heart rate, breath-by-breath VO(2), and O(2) pulse (O(2)p) data yielded monoexponential time constants of the VO(2) (s) and O(2)p increase. Separating phase 1 and 2 data permitted assessment of the phase 1 duration and phase 2 VO(2) time constant (). The VO(2) time constant was higher in HTR (38.4 +/- 7.5) than in C40W (22.9 +/- 9.6; P < or = 0. 002) or C67W (30.8 +/- 8.2; P < or = 0.05), as was the O(2)p time constant, resulting from a lower phase 1 VO(2) increase (287 +/- 59 vs. 349 +/- 66 ml/min; P < or = 0.05), O(2)p increase (2.8 +/- 0.6 vs. 3.6 +/- 1.0 ml/beat; P < or = 0.0001), and a longer phase 1 duration (36.7 +/- 12.3 vs. 26.8 +/- 6.0 s; P < or = 0.05), whereas the was similar in HTR and C (31.4 +/- 9.6 vs. 29.9 +/- 5.6 s; P = 0.85). Thus the HTR have slower subthreshold VO(2) kinetics due to an abnormal phase 1, suggesting that the heart is unable to increase its output abruptly when exercise begins. We expected a faster in HTR because of their prolonged phase 1 duration. Because this was not the case, their muscular metabolism may also be impaired at the onset of subthreshold exercise.

The purpose of the present study was to compare measurements of respiratory system resistance by the interrupter method (Rrsint) with those of airway resistance by plethysmography (Raw) in nonobstructed children with asthma or cystic fibrosis (ratio of forced expiratory volume in 1 sec to vital capacity, FEV(1)/VC >/=80% with a forced expiratory flow rate between 25-75% of forced vital capacity, FEF(25-75) >/=75% of normal values) and in obstructed children with the same diseases (FEV(1)/VC <80% and/or FEF(25-75) <75% of normal values). Eighty-one children (47 asthmatics and 34 suffering from cystic fibrosis) aged 5-18 years (mean 11.2 +/- SD 3.4 years) were included in the study. For the overall group, we observed generally lower values for Raw (4.7 +/- 2. 8 cmH(2)O.L(-).s) than for Rrsint20 (extrapolation of the mouth pressure during occlusion to 40 ms after interruption) (5.6 +/- 1.7 cmH(2)O.L(-1).s) (P < 0.02), or for Rrsint40 (extrapolation of the mouth pressure during occlusion to 60 ms after interruption) (6.6 +/- 2.2 cmH(2)O.L(-1).s) (P < 0.001), but there was no difference between Rrsint20 and Raw in the obstructed subgroup. Moreover, we observed a correlation between the difference (Rrsint20 - Raw) expressed in percentage of predicted values and the degree of obstruction estimated by FEV(1)/VC (r = 0.56, P < 0.001). The differences between the specific resistances (sRrsint20 - sRaw, sRrsint40 - sRaw) were also correlated with the severity of the obstruction (r = 0.65, P < 0.001 and r = 0.57, P < 0.001, respectively). We observed also that the tendency to underestimate resistance by Rrsint in obstructed children was not the same in children with asthma and cystic fibrosis. We conclude that the tendency of Rrsint, as measured with our method, to underestimate airway obstruction appears to increase in proportion to the severity of the airway obstruction., (Copyright 2000 Wiley-Liss, Inc.)

In order to examine whether immunosuppressive treatment could be responsible for the reduced exercise capacity of heart transplant recipients (HTR), we studied the effects of long-term immunosuppressive treatment with cyclosporin A (CsA) and its vehicle (2/3 cremophor and 1/3 alcohol diluted in olive oil) on in situ mitochondrial respiration of different muscles. Rats were fed for 3 weeks with 10 or 25 mg/kg/day CsA in its vehicle (CsA10 and CsA25 groups), or vehicle or H(2)O. Oxygen consumption rate was measured in saponin skinned fibers without (V(0)) and with ADP until maximal respiration (V(max)) was reached and K(M)for ADP as well as V(max)were calculated using non-linear fit of the Michaelis-Menten equation. In the cardiac muscle of the CsA25 group, V(0)and V(max)were decreased by immunosuppressive treatment respectively from 6.33+/-0.51 to 3.18+/-0.3micromol O(2)/min/g dw (P<0.001) and from 29.0+/-1.5 to 18.1+/-1.6micromol O(2)/min/g dw (P<0.001), an effect which could be entirely attributed to the vehicle itself, with no difference between CsA10 and CsA25. Regulation of cardiac mitochondrial respiration by ADP was altered by vehicle with the K(M)for ADP decreasing from 371+/-37 to 180+/-21microm(P<0.001). A similar trend was observed in the diaphragm or soleus, although to a lesser extent. In contrast, V(0)and V(max)decreased in glycolytic gastrocnemius muscle respectively from 1.7+/-0.2 to 0.94+/-0.14 (P<0. 01) and from 6.8+/-0.3 to 5.1+/-0.4micromol O(2)/min/g dw (P<0.001) in the CsA25 group, but the main effects could be attributed to CsA itself. It was concluded that immunosuppressive treatment induces a deleterious effect on cardiac and skeletal muscle oxidative capacities, mainly due to cremophor, the main component of vehicle., (Copyright 2000 Academic Press.)

Heart-transplant recipients (Htx) generally present with body fluid and sodium handling abnormalities and hypertension. To investigate whether neutral endopeptidase inhibition (NEP-I) increases endogenous atrial natriuretic peptide (ANP) and enhances natriuresis and diuresis after heart transplantation, ecadotril was given orally to 8 control subjects and 8 matched Htx, and levels of volume-regulating hormones and renal water, electrolyte, and cyclic guanosine monophosphate (cGMP) excretions were monitored for 210 minutes. Baseline plasma ANP, brain natriuretic peptide (BNP), and cGMP were elevated in Htx, but renin and aldosterone, like urinary parameters, did not differ between groups. NEP-I increased plasma ANP (Htx, 20.6+/-2.3 to 33.2+/-5.9 pmol/L, P<0.01; controls, 7.7+/-1. 2 to 10.6+/-2.6 pmol/L) and cGMP, but not BNP. Renin decreased similarly in both groups, whereas aldosterone decreased significantly only in Htx. Enhanced urinary sodium (1650+/-370% versus 450+/-150%, P=0.01), cGMP, and water excretions were observed in Htx and urinary cGMP positively correlated with natriuresis in 6 of the Htx subjects. Consistent with a normal circadian rhythm of blood pressure, without excluding a possible effect of NEP-I, mean systemic blood pressure increased similarly in both groups at the end of the study (6.9+/-2.0% versus 7.4+/-2.8% in controls and Htx). Thus, systemic hypertension, mild renal impairment, and raised plasma ANP levels are possible contributory factors in the enhanced natriuresis and diuresis with NEP-I in Htx. These results support a physiological role for the cardiac hormone after heart transplantation and suggest that long-term studies may be useful to determine the potential of NEP-I in the treatment of sodium retention and water retention after heart transplantation.

Objective: Adrenomedullin (ADM), secreted by the failing human heart, is a newly discovered potent endogenous vasorelaxing and natriuretic peptide that may play a role in cardiorenal regulation. No data are available on ADM in heart-transplant recipients (Htx) and the aim of this study was to determine the short- and long-term responses of ADM after heart transplantation., Methods: Circulating ADM and its relationship with parameters of cardiovascular hemodynamics, humoral factors and renal function were determined in normal subjects and Htx early (1, 2, 4, 8, 15 and 30 days) and late (32 +/- 16 months) after transplantation. Additionally, ADM was obtained in matched hypertensive and renal-transplant patients (n = 9 in each group)., Results: Plasma ADM, elevated in heart failure patients, further increased transiently at day 1 after transplantation (from 37.9 +/- 15.9 to 125.8 +/- 15.3 pmol/l, P < 0.01) and, although decreasing thereafter, remained elevated until the 30th day after transplantation (52.1 +/- 25.2 pmol/l). Late after transplantation. ADM concentrations were still increased compared to normal values (31.3 +/- 5.3 vs. 19.4 +/- 2.7 pmol/l, P < 0.001). ADM positively correlated with endothelin, atrial natriuretic peptide (ANP) and cyclosporine. ADM was also correlated with increased diastolic (r = 0.68, P < 0.04) and systolic (r = 0.66, P < 0.05) blood pressure in late Htx. No relationship was observed between ADM and left ventricular mass index, aldosterone and creatinine. ADM elevation was similar in hypertensive, renal-transplant patients and in Htx., Conclusions: Circulating ADM is increased after heart transplantation, in relation to hypertension, endothelin, cyclosporine and ANP. In view of ADM's biological properties, these results might suggest a compensatory role for ADM against further development of vasoconstriction and fluid retention states after heart transplantation.

The pulmonary diffusing capacity for carbon monoxide (DLCO) is reduced in chronic heart failure and remains decreased after heart transplantation. This decrease in DLCO may depend on a permanent alteration after transplantation of one or the other of its components: diffusion of the alveolar capillary membrane or the pulmonary capillary blood volume (Vc). Therefore, we measured DLCO, the membrane conductance, and Vc before and after heart transplantation. At the time of hemodynamic measurements, the Roughton and Forster method of measuring DLCO at varying alveolar oxygen concentrations was used to determine the membrane conductance, Vc, DLCO/alveolar volume (VA), the membrane conductance/VA and thetaVc/VA (theta = carbon monoxide conductance of blood, VA = alveolar volume) in 21 patients with class III to IV heart failure before and after transplantation, and in 21 healthy controls. Transplantation normalized pulmonary capillary pressure and increased cardiac index. DLCO was decreased before transplantation (7.11 vs 10.0 mmol/min/kPa in controls), but DLCO/VA was normal (1.67+/-0.44 vs 1.71+/-0.26 mmol/min/kPa/L in controls). DLCO/VA remained unchanged after transplantation, because the decrease in Vc (82+/-30 vs 65+/-18 ml before and after transplantation) and thetaVc/VA was not compensated by the changes in membrane conductance (11+/-4 vs 12+/-5 mmol/min/kPa before and after transplantation, respectively) and membrane conductance/VA. We conclude that the decrease in DLCO in patients with chronic heart failure is due to a restrictive ventilatory pattern because their DLCO/VA remains normal; the decrease in the membrane conductance is compensated by the increase in Vc. After transplantation, the decrease in Vc due to normalization of pulmonary hemodynamics is not completely compensated for by an increase in membrane conductance. Because the membrane conductances, measured before and after transplantation, are negatively correlated with duration of heart failure, its abnormal pulmonary hemodynamics may have irreversibly altered the alveolar capillary membrane.

We investigated the atrial (ANP) and brain natriuretic peptides (BNP), catecholamines, heart rate, and blood pressure responses to graded upright maximal cycling exercise of eight matched healthy subjects and cardiac-denervated heart transplant recipients (HTR). Baseline heart rate and diastolic blood pressure, together with ANP (15.2 +/- 3.7 vs. 4.4 +/- 0.8 pmol/l; P < 0.01) and BNP (14.3 +/- 2. 6 vs. 7.4 +/- 0.6 pmol/l; P < 0.01), were elevated in HTR, but catecholamine levels were similar in both groups. Peak exercise O2 uptake and heart rate were lower in HTR. Exercise-induced maximal ANP increase was similar in both groups (167 +/- 34 vs. 216 +/- 47%). Enhanced BNP increase was significant only in HTR (37 +/- 8 vs. 16 +/- 8%; P < 0.05). Similar norepinephrine but lower peak epinephrine levels were observed in HTR. ANP and heart rate changes from rest to 75% peak exercise were negatively correlated (r = -0.76, P < 0.05), and BNP increase was correlated with left ventricular mass index (r = 0.83, P < 0.01) after heart transplantation. Although ANP increase was not exaggerated, these data support the idea that the chronotropic limitation secondary to sinus node denervation might stimulate ANP release during early exercise in HTR. Furthermore, the BNP response to maximal exercise, which is related to the left ventricular mass index of HTR, is enhanced after heart transplantation.

Lung volume reduction surgery (LVRS) has become an extended surgery for emphysema in order to improve the dyspnea of severely affected patients. Because resection of lung areas may reduce the vascular bed, which is an important factor of pulmonary hypertension in emphysematous patients, especially during exercise, the aim of our study was to assess the outcome of pulmonary hemodynamics and gas exchange at rest and during exercise after LVRS. Nine patients had right heart catheterization before and 3 to 12 mo (mean, 4.5 mo) after LVRS. FEV1 increased from 705 to 1,005 ml (p < 0.05) after LVRS. PaO2, PaCO2 and mean pulmonary artery pressure (Ppa) did not change after LVRS, either at rest or during exercise. However, a significant overall decrease of the respiratory swings of the pulmonary artery diastolic pressure (DeltaPd) at rest (median value, from 12 to 8 mm Hg, p < 0.01) and during exercise (from 20 to 15 mm Hg, p < 0.05) was observed. There was a significant correlation between the change in resting Ppa (Ppa before minus Ppa after LVRS) and the change in resting DeltaPd (r = 0.73, p < 0.03), and also between the change in exercising Ppa and the change in resting DeltaPd (r = 0.80, p < 0.02). Significant correlations were also found between the change in exercising Ppa and the change in exercising PaO2 (r = -0.70, p < 0.05), and between the change in exercising Ppa and the change in exercising PaCO2 (r = 0.76, p < 0. 03). We conclude that pulmonary hemodynamics in most cases are not impaired by LVRS either at rest or during exercise. The possible mechanisms influencing hemodynamics after a lung volume reduction procedure are discussed.

Objectives: We sought to examine the effects of endurance training on the ultrastructural characteristics of skeletal muscle in heart transplant recipients (HTRs) and age-matched control subjects (C)., Background: Deconditioning is one of the factors involved in the peripheral limitation of exercise capacity of HTRs, and training has proven to be beneficial., Methods: Biopsies of the vastus lateralis muscle, analyzed by ultrastructural morphometry, and quadriceps muscle cross-sectional area, assessed by computed tomography (CT), were performed in 12 HTRs and 7 age-matched C before and 6 weeks after an endurance training program. Maximal oxygen uptake (peak VO2) was determined by an incremental exercise test. Additionally muscle biopsies were performed before and after a 6-week control period in four HTRs to check for spontaneous improvement., Results: Training resulted in similar increases in peak VO2 (11% in HTRs, 8.5% in C), ventilatory threshold (23% in HTRs, 32% in C) and total endurance work (54% in HTRs, 31% in C). Volume density of total mitochondria increased significantly (26% in HTRs, 33% in C) with a predominant increase of subsarcolemmal mitochondrial volume density (74% in HTRs, 70% in C). The capillary/fiber ratio increased by 19% in C only. In the nontrained group, none of the structural markers was spontaneously modified., Conclusions: Six weeks of endurance training in HTRs and C led to similar improvements of aerobic work capacity. However, the decreased muscular capillary network in HTRs remained unchanged with training. Immunosuppressive therapy might be responsible for the discrepancy between the normal mitochondrial content and the reduced capillary supply of these patients.