Cristina Pistea

Cryopreservation with dimethyl sulfoxide prevents accurate analysis of skinned skeletal muscle fibers mitochondrial respiration

Impact of cryopreservation protocols on skeletal muscle mitochondrial respiration remains controversial. We showed that oxygen consumption with main mitochondrial substrates in rat skeletal muscles was higher in fresh samples than in cryopreserved samples and that this difference was not fixed but grow significantly with respiration rates with wide fluctuations around the mean difference. Very close results were observed whatever the muscle type and the substrate used. Importantly, the deleterious effects of ischemia-reperfusion observed on fresh samples vanished when cryopreserved samples were studied. These data demonstrate that this technic should probably be performed only extemporaneously.

Impact of 3D Conformal Radiotherapy on Lung Function of Patients with Lung Cancer: A Prospective Study

Background: The development of three-dimensional conformal radiotherapy (3D-RT) has enabled the restriction of the dose to normal lung, limiting radiation-induced lung injury. Objectives: This study was designed to describe the time course of lung function until 7.5 months after 3D-RT in patients with lung cancer, and assess the relationship between lung function changes and dose-volume histogram (DVH) analysis or computed tomography scan changes. Radiation doses were optimized according to recent guidelines. Methods: Sixty-five lung cancer patients treated with 3D-RT agreed to participate in this prospective, hospital-based study. Lung volumes, forced expiratory volume in 1 s (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO) were measured before radiotherapy (RT), 10 weeks, 4 and 7.5 months after the beginning of 3D-RT. Results: Eleven lung cancer patients (17%) developed grade 2-3 respiratory symptoms after RT. At 7.5 months, vital capacity (VC) was 96 ± 2%, total lung capacity (TLC) 95 ± 2%, FEV1 93 ± 2% and DLCO 90 ± 2% of the initial value. Only 15% of patients showed pulmonary function reduction >20%. Patients with FEV1 or DLCO <60% before RT did not show significant changes after RT. There were weak correlations between reduction of VC, TLC, FEV1 or DLCO and radiation dosimetric parameters and between reduction of VC or FEV1 and radiation-induced pneumonitis images. Conclusions: In lung cancer, the reduction of lung function within 7.5 months after 3D-RT was small and correlated, albeit weakly, with DVH parameters. Patients with initially impaired lung function showed tiny changes in spirometry and DLCO values.

Cardio-respiratory responses to hypoxia combined with CO2 inhalation during maximal exercise

We measured the effects of adding CO2 to an inhaled hypoxic gas mixture on cardio-respiratory parameters during maximal exercise. Eight young males performed four incremental maximal exercise tests on cycle under ambient air, hypoxia (FIO2 0.125), inhaled CO2 (FICO2 0.045), and combination of hypoxia and inhaled CO2. The highest ventilation (VE) and VE/CO2 output were recorded in CO2 inhalation and combined treatments. Arterial O2 partial pressure was higher in combined than in hypoxia treatment, but the difference between the treatments narrowed from rest to end-exercise, at least partly because the magnitude of the increase in VE (%) at exercise was smaller in combined treatment than in hypoxia. Arterial O2 content was higher in combined treatment than in hypoxia at rest, but no more at maximal exercise. Cardiac output was higher and O2 extraction lower when breathing O2-poor gas mixtures than under the two other treatments. For a given oxygen consumption, hypoxia and combined treatment showed similar cardiac output and O2 extraction.

Ability of pulmonary function decline to predict death in amyotrophic lateral sclerosis patients

Abstract Objectives: Objectives were to evaluate the relative risk of death associated with lung function decline in patients with amyotrophic lateral sclerosis (ALS), and to examine the ability of ALS patients to perform volitional pulmonary function tests (PFTs). Methods: The PFTs of 256 consecutive patients referred to the Strasbourg University Hospital ALS Centre over an eight-year period were reviewed. Slow vital capacity (VC), maximal inspiratory and expiratory pressures (MIP, MEP), sniff nasal inspiratory pressure (SNIP), and peak cough flow (PCF) were performed at diagnosis and then every four months. The instantaneous risk of death associated with PFTs deterioration was calculated using time-dependent covariate Cox models. The changes of each PFT over time were examined and compared. Results: A total of 985 acceptable PFT sessions were recorded. The risk of death was significantly associated with the decline in pulmonary function, regardless of the PFT parameter and its expression. When VC, MIP/SNIP and MEP (% of predicted) decreased by 10%, or PCF decreased by 50 L/min, the risk of death was multiplied by 1.31 (95% CI 1.21–1.41), 1.48 (1.32–1.66), 1.54 (1.32–1.79), and 1.32 (1.19–1.75), respectively. MIP, SNIP and MEP were decreased earlier in the course of disease and plunged deeper than VC within months before death, but were more affected by learning effect. Conclusions: This study provides tools to calculate the increase in risk of death from a PFT decline. At an individual level, since each test showed some flaws, the use of a combination of PFTs for ALS respiratory monitoring is recommended.

Exercise-induced second-degree atrioventricular block in endurance athletes.

Training induces volume- and time-dependent morphological and functional changes in the heart. Heart rhythm disorders, such as atrial arrhythmia (including atrial fibrillation and atrial flutter), are a well-established consequence of such long-term endurance practice. Although resting bradycardia and first-degree atrioventricular persist in veteran athletes, a higher conduction system impairment has never been reported neither at rest nor during exercise. We report here two cases of Type II second-degree atrioventricular block occurring during exercise in middle-age well-trained athletes. Because animal and human studies suggest that a progressive myocardial fibrosis could explain such phenomenon, long-term training could also have consequences on the conduction pathways.

Maximal aerobic capacity in ageing subjects: actual measurements versus predicted values

We evaluated the impact of selection of reference values on the categorisation of measured maximal oxygen consumption (V′O2peak) as “normal” or “abnormal” in an ageing population. We compared measured V′O2peak with predicted values and the lower limit of normal (LLN) calculated with five equations. 99 (58 males and 41 females) disease-free subjects aged ≥70 years completed an incremental maximal exercise test on a cycle ergometer. Mean V′O2peak was 1.88 L·min−1 in men and 1.26 L·min−1 in women. V′O2peak ranged from 89% to 108% of predicted in men, and from 88% to 164% of predicted in women, depending on the reference equation used. The proportion of subjects below the LLN ranged from 5% to 14% in men and 0–22% in women, depending on the reference equation. The LLN was lacking in one study, and was unsuitable for women in another. Most LLNs ranged between 53% and 73% of predicted. Therefore, choosing an 80% cut-off leads to overestimation of the proportion of “abnormal” subjects. To conclude, the proportion of subjects aged ≥70 years with a “low” V′O2peak differs markedly according to the chosen reference equations. In clinical practice, it is still relevant to test a sample of healthy volunteers and select the reference equations that better characterise this sample. As V′O2peak % pred differs markedly with the reference value, reference equation choice is critical in the elderly http://ow.ly/YsXHD

Asthma as a cause of persistent dyspnea in treated myasthenia gravis patients.

Aims: The aim of this study was to evaluate the proportion of patients with treated myasthenia gravis (MG) who present with dyspnea not related to MG. Methods: We analyzed the files of 63 consecutive adult patients with treated MG and persistent dyspnea who had been referred to our Pulmonary Function Test (PFT) Department between 2000 and 2010. Results: We observed that asthma was the first cause of MG-unrelated dyspnea in MG patients, with 9 patients (14%) presenting with asthma-related PFT abnormalities. Six patients had asthma for several years before developing MG, and 3 patients (4%) developed asthma a few months after MG was diagnosed, suggesting a non-coincidental association between the two conditions. In all 3 cases, asthma appeared in elderly patients with severe late-onset AchR-Ab- positive MG, treated with pyridostigmine and corticosteroids and/or intravenous immunoglobulins. In all 3 patients, β2-adrenergic agonist treatment allowed only partial control of dyspnea. In one case, respiratory symptoms were alleviated when pyridostigmine dosage was reduced. Conclusions: Patients with treated MG and persistent dyspnea should be investigated for asthma using PFT before being diagnosed with refractory MG. If asthma is diagnosed, a bronchodilator treatment should be instituted and a reduction in pyridostigmine dosage should be proposed.

CO2 inhalation attenuates exercise-induced rise of pulmonary artery pressure under acute hypoxia condition

Aim: to evaluate the impact of a combination of hypoxia and CO 2 inhalation on pulmonary artery pressure (PAP) during a moderate constant-load exercise. Methods: Eight 20-yr old healthy male subjects performed four constant-load exercise tests in ambient air, hypoxia, CO 2 inhalation and combined conditions, at 40% of maximal tolerated power on cycle, in semi-recumbent position. Cardiac output (CO), systolic PAP(s) and pulmonary vascular resistance (PVR) were measured at rest and after 30 min exercising, using Doppler echocardiography. Blood gases were measured on arterialized blood from earlobe. Results: Conclusions: Hypoxia with or without inhaled CO 2 induced a rise in CO. Hypoxia, CO 2 inhalation and combined conditions increased PAPs and PVR. However, adding CO 2 to an O 2 -poor gas mixture attenuated the increase in PVR, and then limited the hypoxia-induced rise of PAPs at exercise. We hypothesize that CO 2 had a direct vasodilator effect on hypoxia-constricted pulmonary vessels.