The effects of cold exposure (cold water immersion, whole- and partial- body cryostimulation) on cardiovascular and cardiac autonomic control responses in healthy individuals: A systematic review, meta-analysis and meta-regression.

BACKGROUND: Cryostimulation and cold-water immersion (CWI) have recently gained widespread attention due to their association with changes in cardiovascular and cardiac autonomic control responses. Therefore, the aim of the present systematic review and meta-analysis was to identify the global impact of such cold exposures on cardiovascular and cardiac autonomic activity. METHODS: Three databases (PubMed, Embase, Web-of-Science) were used. Studies were eligible for inclusion if they were conducted on healthy participants using cryostimulation and/or CWI. The outcomes included measurements of blood pressure (BP), heart rate (HR), and heart rate variability (HRV) indices: RR interval (RR), Root mean square of successive RR interval differences (RMSSD), low frequency band (LF), high frequency band (HF), and LF/HF ratio. RESULTS: Among the 27 articles included in our systematic literature review, only 24 were incorporated into the meta-analysis. Our results reveal a significant increase in HRV indices: RMSSD (Standardized mean difference (SMD) = 0.61, p < 0.001), RR (SMD = 0.77, p < 0.001), and HF (SMD = 0.46, p < 0.001), as well as significantly reduced LF (SMD = -0.41, p < 0.001) and LF/HF ratio (SMD = -0.25, p < 0.01), which persisted up to 15 min following cold exposure. Significantly decreased heart rate (SMD = -0.16, p < 0.05), accompanied by slightly increased mean BP (SMD = 0.28, p < 0.001), was also observed. These results seem to depend on individual characteristics and the cooling techniques. CONCLUSION: Our meta-analysis suggests that cryostimulation and/or CWI exposure enhance parasympathetic nervous activity. There is scarce scientific literature regarding the effect of individual characteristics on cold-induced physiological responses.

Does branched-chain amino acid supplementation improve pulmonary rehabilitation effect in COPD?

BACKGROUND: Muscle wasting is frequent in chronic obstructive lung disease (COPD) and associated with low branched-chain amino acids (BCAA). We hypothesized that BCAA supplementation could potentiate the effect of a pulmonary rehabilitation program (PRP) by inducing muscular change. MATERIALS AND METHODS: Sixty COPD patients (GOLD 2-3) were involved in an ambulatory 4-week PRP either with BCAA oral daily supplementation or placebo daily supplementation in a randomized double-blind design. Maximal exercise test including quadriceps oxygenation measurements, functional exercise test, muscle strength, lung function tests, body composition, dyspnea and quality of life were assessed before and after PRP. RESULTS: Fifty-four patients (64.9 ± 8.3 years) completed the protocol. In both groups, maximal exercise capacity, functional and muscle performances, quality of life and dyspnea were improved after 4-week PRP (p ≤ 0.01). Changes in muscle oxygenation during the maximal exercise and recovery period were not modified after 4-week PRP in BCAA group. Contrarily, in the placebo group the muscle oxygenation kinetic of recovery was slowed down after PRP. CONCLUSION: This study demonstrated that a 4-week PRP with BCAA supplementation is not more beneficial than PRP alone for patients. A longer duration of supplementation or a more precise targeting of patients would need to be investigated to validate an effect on muscle recovery and to demonstrate other beneficial effects.

Effect of expiratory loaded breathing during moderate exercise on intercostal muscle oxygenation.

BACKGROUND: In patients with obstructive lung disease, maintaining adequate ventilation during exercise may require greater contraction of the respiratory muscles, which may lead to a compression of muscle capillaries. Furthermore, dynamic hyperinflation (DH) is frequent during exercise in these patients, as it allows to reach higher expiratory flows and to satisfy respiratory demand. However, in such situation, intercostal muscles are likely to be stretched, which could affect the diameter of their capillaries. Thus, in a context of high level of expiratory resistance, intercostal muscle oxygenation may be disturbed during exercise, especially if DH occurs. METHODS: Twelve participants (22±2 years) performed two sessions of moderate exercise (20 min) by breathing freely with and without a 20-cmH2O expiratory threshold load (ETL). Tissue saturation index (TSI) and concentration changes from rest (Δ) in oxygenated ([O2Hb]) and total haemoglobin ([tHb]) were measured in the seventh intercostal space using near-infrared spectroscopy. Respiratory, metabolic and cardiac variables were likewise recorded. RESULTS: Throughout exercise, dyspnea was higher and TSI was lower in ETL condition than in control (p<0.01). After a few minutes of exercise, Δ [O2Hb] was also lower in ETL condition, as well as Δ [tHb], when inspiratory capacity started to be reduced (p<0.05). Changes in [O2Hb] and dyspnea were correlated with changes in expiratory flow rate (Vt/Te) (r = -0.66 and 0.66, respectively; p<0.05). CONCLUSION: During exercise with ETL, impaired muscle oxygenation could be due to a limited increase in blood volume resulting from strong muscle contraction and/or occurrence of DH.

Translation and Cultural Adaptation of PROactive Instruments for COPD in French and Influence of Weather and Pollution on Its Difficulty Score.

Introduction: The recently developed daily and clinical visit PROactive physical activity in COPD (PPAC) instruments are hybrid tools to objectively quantify the level of physical activity and the difficulties experienced in everyday life. Our aim was to translate these instruments for the French-speaking chronic obstructive pulmonary disease (COPD) community worldwide and evaluate the influence of weather and pollution on difficulty score. Methods: The translation procedure was conducted following the guidelines for cross-cultural adaptation process. The translated clinical visit (C-PPAC) was tested among COPD patients in France. A retest was conducted after an interval of at least 2 weeks. The C-PPAC difficulty score was then tested to see how sensitive it was to the influence of weather and outdoor pollution. Results: One hundred and seventeen COPD patients (age 65±9 years; FEV1: 51±20%) from 9 regions in France were included. The French version of C-PPAC was found comprehensible by the patients with an average score of 4.8/5 on a Likert-scale. It showed good internal consistency with Cronbach's α>0.90 and a good test retest reliability with an intraclass correlation coefficient of ≥0.80. The difficulty score was negatively correlated with duration of daylight (ρ=-0.266; p<0.01) and influenced by the intensity of rainfall (light vs. heavy rainfall: 68±16 vs. 76±14 respectively, p=0.045). The score was lower in patients receiving long term oxygen therapy (60±15 vs. 71±15, p<0.01), but not correlated with the pollution indices. Conclusion: The French versions of the questionnaires of the PPAC instruments are accepted and comprehensible to COPD patients. The difficulty score of C-PPAC is sensitive to duration of daylight and rainfall. Such weather factors must be taken into consideration when evaluating the physical activity behavior using these tools in COPD.

Intercostal muscle oxygenation during expiratory load breathing at rest.

BACKGROUND: During acute bronchial obstruction, despite a higher work of breathing, blood supply and oxygen availability may be reduced in intercostal muscles because of mechanical constraints. This hypothesis was assessed in healthy subjects breathing with and without expiratory load (ETL). METHODS: Eleven men (24 ± 2 years) breathed at rest for 5 min in unloaded condition and for 20 min through a 20-cmH2O ETL. Tissue saturation index (TSI) and changes (Δ) in concentration of total and oxy-haemoglobin ([tHb] and [O2Hb]) were measured in the seventh intercostal space by near-infrared spectroscopy. RESULTS: [tHb] and [O2Hb] decreased with ETL (-5.16 µM and -3.54 µM; p < 0.05). TSI did not vary. Negative correlations were observed between Δ[O2Hb] and changes in expiratory flow rate (ΔVt/Te) and between ΔTSI and Δ V˙E (r = -0.78 and -0.74; p ≤ 0.01). CONCLUSION: Despite decreases in Hb concentrations, saturation in oxygen was not reduced with ETL in intercostal muscles, suggesting a satisfactory ventilatory and/or hemodynamic arrangement.

Determining the minimally important difference in quadriceps strength in individuals with COPD using a fixed dynamometer.

Background: Measurement of quadriceps muscular force is recommended in individuals with COPD, notably during a pulmonary rehabilitation program (PRP). However, the tools used to measure quadriceps maximal voluntary contraction (QMVC) and the clinical relevance of the results, as well as their interpretation for a given patient, remain a matter of debate. The objective of this study was to estimate the minimally important difference (MID) of QMVC using a fixed dynamometer in individuals with COPD undergoing a PRP. Methods: Individuals with COPD undergoing a PRP were included in this study. QMVC was measured using a dynamometer (MicroFET2) fixed on a rigid support according to a standard-ized methodology. Exercise capacity was measured by 6-minute walk distance (6MWD) and evaluation of quality of life with St George's respiratory questionnaire (SGRQ) and Hospital Anxiety and Depression Scale (HADS) total scores. All measures were obtained at baseline and the end of the PRP. The MID was calculated using distribution-based methods. Results: A total of 157 individuals with COPD (age 62.9±9.0 years, forced expiratory volume in 1 second 47.3%±18.6% predicted) were included in this study. At the end of the PRP, the patients had improved their quadriceps force significantly by 8.9±15.6 Nm (P<0.001), as well as 6MWD by 42±50 m (P<0.001), SGRQ total score by -9±17 (P<0.001) and HADS total score by -3±6 (P<0.001). MID estimation using distribution-based analysis was 7.5 Nm by empirical rule effect size and 7.8 Nm by Cohen's effect size. Conclusion: Measurement of QMVC using a fixed dynamometer is a simple and valuable tool capable of assessing improvement in quadriceps muscle force after a PRP. We suggest an MID of 7.5 Nm to identify beneficial changes after a PRP intervention.

No compensatory lung growth after resection in a one-year follow-up cohort of patients with lung cancer.

BACKGROUND: As compensatory lung growth after lung resection has been studied in animals of various ages and in one case report in a young adult, it has not been studied in a cohort of adults operated for lung cancer. METHODS: A prospective study including patients with lung cancer was conducted over two years. Parenchymal mass was calculated using computed tomography before (M0) and at 3 and 12 months (M3 and M12) after surgery. Respiratory function was estimated by plethysmography and CO/NO lung transfer (DLCO and DLNO). Pulmonary capillary blood volume (Vc) and membrane conductance for CO (DmCO) were calculated. Insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) plasma concentrations were measured simultaneously. RESULTS: Forty-nine patients underwent a pneumonectomy (N=12) or a lobectomy (N=37) thirty two completed the protocol. Among all patients, from M3 to M12 the masses of the operated lungs (239±58 to 238±72 g in the lobectomy group) and of the non-operated lungs (393±84 to 377±68 g) did not change. Adjusted by the alveolar volume (VA), DLNO/VA decreased transiently by 7% at M3, returning towards the M0 value at M12. Both Vc and DmCO increased slightly between M3 and M12. IGF-1 and IGFBP-3 concentrations did not change at M3, IGF-1 decreased significantly from M3 to M12. CONCLUSIONS: Compensatory lung growth did not occur over one year after lung surgery. The lung function data could suggest a slight recruitment or distension of capillaries owing to the likely hemodynamic alterations. An angiogenesis process is unlikely.

Sit-to-stand tests for COPD: A literature review.

BACKGROUND: Sit-to-stand tests (STST) have recently been developed as easy-to-use field tests to evaluate exercise tolerance in COPD patients. As several modalities of the test exist, this review presents a synthesis of the advantages and limitations of these tools with the objective of helping health professionals to identify the STST modality most appropriate for their patients. METHOD: Seventeen original articles dealing with STST in COPD patients have been identified and analysed including eleven on 1min-STST and four other versions of the test (ranging from 5 to 10 repetitions and from 30 s to 3 min). In these studies the results obtained in sit-to-stand tests and the recorded physiological variables have been correlated with the results reported in other functional tests. RESULTS: A good set of correlations was achieved between STST performances and the results reported in other functional tests, as well as quality of life scores and prognostic index. According to the different STST versions the processes involved in performance are different and consistent with more or less pronounced associations with various physical qualities. These tests are easy to use in a home environment, with excellent metrological properties and responsiveness to pulmonary rehabilitation, even though repetition of the same movement remains a fragmented and restrictive approach to overall physical evaluation. CONCLUSIONS: The STST appears to be a relevant and valid tool to assess functional status in COPD patients. While all versions of STST have been tested in COPD patients, they should not be considered as equivalent or interchangeable.

Feasibility of intercostal blood flow measurement by echo-Doppler technique in healthy subjects.

Intercostal artery blood flow supplies the external and internal intercostal muscles, which are inspiratory and expiratory muscles. Intercostal blood flow measured by the echo-Doppler (ED) technique has not previously been reported in humans. This study describes the feasibility of this measurement during free and loaded breathing in healthy subjects. Systolic, diastolic and mean blood flows were measured in the eighth dorsal intercostal space during free and loaded breathing using the ED technique. Flows were calculated as the product of the artery intraluminal surface and blood velocity. Ten healthy subjects (42 ± 13·6 years) were included. Integrated electromyogram (iEMG), arterial pressure, cardiac frequency and breathing pattern were also recorded. Mean blood flows were 3·5 ± 1·2 ml min-1 at rest, 6 ± 2·6 ml min-1 while breathing through a combined inspiratory and expiratory resistance and 4·0 ± 1·3 ml min-1 1 min after unloading. Diastolic blood flow was about one-third the systolic blood flow. The changes in blood flows were consistent with those in iEMG. No change in mean blood flow was observed between inspiration and expiration, suggesting a balance in the perfusion of external and internal muscles during breathing. In conclusion, ED is a feasible technique for non-invasive, real-time measurement of intercostal blood flow in humans. In healthy subjects, mean blood flow appeared tightly matched to iEMG activity. This technique may provide a way to assess the vascular adaptations induced by diseases in which respiratory work is increased or cardiac blood flow altered.

Is the 1-minute sit-to-stand test a good tool for the evaluation of the impact of pulmonary rehabilitation? Determination of the minimal important difference in COPD.

BACKGROUND: The 1-minute sit-to-stand (STS) test could be valuable to assess the level of exercise tolerance in chronic obstructive pulmonary disease (COPD). There is a need to provide the minimal important difference (MID) of this test in pulmonary rehabilitation (PR). METHODS: COPD patients undergoing the 1-minute STS test before PR were included. The test was performed at baseline and the end of PR, as well as the 6-minute walk test, and the quadriceps maximum voluntary contraction (QMVC). Home and community-based programs were conducted as recommended. Responsiveness to PR was determined by the difference in the 1-minute STS test between baseline and the end of PR. The MID was evaluated using distribution and anchor-based methods. RESULTS: Forty-eight COPD patients were included. At baseline, the significant predictors of the number of 1-minute STS repetitions were the 6-minute walk distance (6MWD) (r=0.574; P<10-3), age (r=-0.453; P=0.001), being on long-term oxygen treatment (r=-0.454; P=0.017), and the QMVC (r=0.424; P=0.031). The multivariate analysis explained 75.8% of the variance of 1-minute STS repetitions. The improvement of the 1-minute STS repetitions at the end of PR was 3.8±4.2 (P<10-3). It was mainly correlated with the change in QMVC (r=0.572; P=0.004) and 6MWD (r=0.428; P=0.006). Using the distribution-based analysis, an MID of 1.9 (standard error of measurement method) or 3.1 (standard deviation method) was found. With the 6MWD as anchor, the receiver operating characteristic curve identified the MID for the change in 1-minute STS repetitions at 2.5 (sensibility: 80%, specificity: 60%) with area under curve of 0.716. CONCLUSION: The 1-minute STS test is simple and sensitive to measure the efficiency of PR. An improvement of at least three repetitions is consistent with physical benefits after PR.

Pulmonary circulation and gas exchange at exercise in Sherpas at high altitude.

Tibetans have been reported to present with a unique phenotypic adaptation to high altitude characterized by higher resting ventilation and arterial oxygen saturation, no excessive polycythemia, and lower pulmonary arterial pressures (Ppa) compared with other high-altitude populations. How this affects exercise capacity is not exactly known. We measured aerobic exercise capacity during an incremental cardiopulmonary exercise test, lung diffusing capacity for carbon monoxide (DL(CO)) and nitric oxide (DL(NO)) at rest, and mean Ppa (mPpa) and cardiac output by echocardiography at rest and at exercise in 13 Sherpas and in 13 acclimatized lowlander controls at the altitude of 5,050 m in Nepal. In Sherpas vs. lowlanders, arterial oxygen saturation was 86 ± 1 vs. 83 ± 2% (mean ± SE; P = nonsignificant), mPpa at rest 19 ± 1 vs. 23 ± 1 mmHg (P < 0.05), DL(CO) corrected for hemoglobin 61 ± 4 vs. 37 ± 2 ml · min(-1) · mmHg(-1) (P < 0.001), DL(NO) 226 ± 18 vs. 153 ± 9 ml · min(-1) · mmHg(-1) (P < 0.001), maximum oxygen uptake 32 ± 3 vs. 28 ± 1 ml · kg(-1) · min(-1) (P = nonsignificant), and ventilatory equivalent for carbon dioxide at anaerobic threshold 40 ± 2 vs. 48 ± 2 (P < 0.001). Maximum oxygen uptake was correlated directly to DL(CO) and inversely to the slope of mPpa-cardiac index relationships in both Sherpas and acclimatized lowlanders. We conclude that Sherpas compared with acclimatized lowlanders have an unremarkable aerobic exercise capacity, but with less pronounced pulmonary hypertension, lower ventilatory responses, and higher lung diffusing capacity.

Lung membrane conductance and capillary volume derived from the NO and CO transfer in high-altitude newcomers.

Acute exposure to high altitude may induce changes in carbon monoxide (CO) membrane conductance (DmCO) and capillary lung volume (Vc). Measurements were performed in 25 lowlanders at Brussels (D0), at 4,300 m after a 2- or 3-day exposure (D2,3) without preceding climbing, and 5 days later (D7,8), before and after an exercise test, under a trial with two arterial pulmonary vasodilators or a placebo. The nitric oxide (NO)/CO transfer method was used, assuming both infinite and finite values to the NO blood conductance (θNO). Doppler echocardiography provided hemodynamic data. Compared with sea level, lung diffusing capacity for CO increased by 24% at D2,3 and is returned to control at D7,8. The acute increase in lung diffusing capacity for CO resulted from increases in DmCO and Vc with finite and infinite θNO assumptions. The alveolar volume increased by 16% at D2,3 and normalized at D7,8. The mean increase in systolic arterial pulmonary pressure at rest at D2,3 was minimal. In conclusion, the acute increase in Vc may be related to the increase in alveolar volume and to the increase in capillary pressure. Compared with the infinite θNO value, the use of a finite θNO value led to about a twofold increase in DmCO value and to a persistent increase in DmCO at D7,8 compared with D0. After exercise, DmCO decreased slightly less in subjects treated by the vasodilators, suggesting a beneficial effect on interstitial edema.

Pulmonary vascular reserve and exercise capacity at sea level and at high altitude.

It has been suggested that increased pulmonary vascular reserve, as defined by reduced pulmonary vascular resistance (PVR) and increased pulmonary transit of agitated contrast measured by echocardiography, might be associated with increased exercise capacity. Thus, at altitude, where PVR is increased because of hypoxic vasoconstriction, a reduced pulmonary vascular reserve could contribute to reduced exercise capacity. Furthermore, a lower PVR could be associated with higher capillary blood volume and an increased lung diffusing capacity. We reviewed echocardiographic estimates of PVR and measurements of lung diffusing capacity for nitric oxide (DL(NO)) and for carbon monoxide (DL(CO)) at rest, and incremental cardiopulmonary exercise tests in 64 healthy subjects at sea level and during 4 different medical expeditions at altitudes around 5000 m. Altitude exposure was associated with a decrease in maximum oxygen uptake (VO2max), from 42±10 to 32±8 mL/min/kg and increases in PVR, ventilatory equivalents for CO2 (V(E)/VCO2), DL(NO), and DL(CO). By univariate linear regression VO2max at sea level and at altitude was associated with V(E)/VCO2 (p<0.001), mean pulmonary artery pressure (mPpa, p<0.05), stroke volume index (SVI, p<0.05), DL(NO) (p<0.02), and DL(CO) (p=0.05). By multivariable analysis, VO2max at sea level and at altitude was associated with V(E)/VCO2, mPpa, SVI, and DL(NO). The multivariable analysis also showed that the altitude-related decrease in VO2max was associated with increased PVR and V(E)/VCO2. These results suggest that pulmonary vascular reserve, defined by a combination of decreased PVR and increased DL(NO), allows for superior aerobic exercise capacity at a lower ventilatory cost, at sea level and at high altitude.

Exercise pathophysiology in patients with chronic mountain sickness exercise in chronic mountain sickness.

BACKGROUND: Chronic mountain sickness (CMS) is characterized by a combination of excessive erythrocytosis,severe hypoxemia, and pulmonary hypertension, all of which affect exercise capacity. METHODS: Thirteen patients with CMS and 15 healthy highlander and 15 newcomer lowlander control subjects were investigated at an altitude of 4,350 m (Cerro de Pasco, Peru). All of them underwent measurements of diffusing capacity of lung for nitric oxide and carbon monoxide at rest, echocardiography for estimation of mean pulmonary arterial pressure and cardiac output at rest and at exercise, and an incremental cycle ergometer cardiopulmonary exercise test. RESULTS: The patients with CMS, the healthy highlanders, and the newcomer lowlanders reached a similar maximal oxygen uptake at 32 1, 32 2, and 33 2 mL/min/kg, respectively, mean SE( P 5 .8), with ventilatory equivalents for C O 2 vs end-tidal P CO 2 , measured at the anaerobic threshold,of 0.9 0.1, 1.2 0.1, and 1.4 0.1 mm Hg, respectively ( P , .001); arterial oxygen content of 26 1, 21 2, and 16 1 mL/dL, respectively ( P , .001); diffusing capacity for carbon monoxide corrected for alveolar volume of 155% 4%, 150% 5%, and 120% 3% predicted, respectively( P , .001), with diffusing capacity for nitric oxide and carbon monoxide ratios of 4.7 0.1 at sea level decreased to 3.6 0.1, 3.7 0.1, and 3.9 0.1, respectively ( P , .05) and a maximal exercise mean pulmonary arterial pressure at 56 4, 42 3, and 31 2 mm Hg, respectively ( P , .001). CONCLUSIONS: The aerobic exercise capacity of patients with CMS is preserved in spite of severe pulmonary hypertension and relative hypoventilation, probably by a combination of increased oxygen carrying capacity of the blood and lung diffusion, the latter being predominantly due to an increased capillary blood volume.

Improvement in lung diffusion by endothelin A receptor blockade at high altitude.

Lung diffusing capacity has been reported variably in high-altitude newcomers and may be in relation to different pulmonary vascular resistance (PVR). Twenty-two healthy volunteers were investigated at sea level and at 5,050 m before and after random double-blind intake of the endothelin A receptor blocker sitaxsentan (100 mg/day) vs. a placebo during 1 wk. PVR was estimated by Doppler echocardiography, and exercise capacity by maximal oxygen uptake (Vo(2 max)). The diffusing capacities for nitric oxide (DL(NO)) and carbon monoxide (DL(CO)) were measured using a single-breath method before and 30 min after maximal exercise. The membrane component of DL(CO) (Dm) and capillary volume (Vc) was calculated with corrections for hemoglobin, alveolar volume, and barometric pressure. Altitude exposure was associated with unchanged DL(CO), DL(NO), and Dm but a slight decrease in Vc. Exercise at altitude decreased DL(NO) and Dm. Sitaxsentan intake improved Vo(2 max) together with an increase in resting and postexercise DL(NO) and Dm. Sitaxsentan-induced decrease in PVR was inversely correlated to DL(NO). Both DL(CO) and DL(NO) were correlated to Vo(2 max) at sea level (r = 0.41-0.42, P < 0.1) and more so at altitude (r = 0.56-0.59, P < 0.05). Pharmacological pulmonary vasodilation improves the membrane component of lung diffusion in high-altitude newcomers, which may contribute to exercise capacity.

Pulmonary capillary blood volume and membrane conductance in Andeans and lowlanders at high altitude: a cross-sectional study.

Lung carbon monoxide (CO) transfer and pulmonary capillary blood volume (Vc) at high altitudes have been reported as being higher in native highlanders compared to acclimatised lowlanders but large discrepancies appears between the studies. This finding raises the question of whether hypoxia induces pulmonary angiogenesis. Eighteen highlanders living in Bolivia and 16 European lowlander volunteers were studied. The latter were studied both at sea level and after acclimatisation to high altitude. Membrane conductance (Dm(CO)) and Vc, corrected for the haemoglobin concentration (Vc(cor)), were calculated using the NO/CO transfer technique. Pulmonary arterial pressure and left atrial pressures were estimated using echocardiography. Highlanders exhibited significantly higher NO and CO transfer than acclimatised lowlanders, with Vc(cor)/VA and Dm(CO)/VA being 49 and 17% greater (VA: alveolar volume) in highlanders, respectively. In acclimatised lowlanders, Dm(CO) and Dm(CO)/VA values were lower at high altitudes than at sea level. Echocardiographic estimates of cardiac output and pulmonary arterial pressure were significantly elevated at high altitudes as compared to sea level. The decrease in Dm(CO) in lowlanders might be due to altered gas transport in the airways due to the low density of air at high altitudes. The disproportionate increase in Vc in Andeans compared to the change in Dm(CO) suggests that the recruitment of capillaries is associated with a thickening of the blood capillary sheet. Since there was no correlation between the increase in Vc and the slight alterations in haemodynamics, this data suggests that chronic hypoxia might stimulate pulmonary angiogenesis in Andeans who live at high altitudes.

The effect of posture-induced changes in peripheral nitric oxide uptake on exhaled nitric oxide.

Airway and alveolar NO contributions to exhaled NO are being extracted from exhaled NO measurements performed at different flow rates. To test the robustness of this method and the validity of the underlying model, we deliberately induced a change in NO uptake in the peripheral lung compartment by changing body posture between supine and prone. In 10 normal subjects, we measured exhaled NO at target flows ranging from 50 to 350 ml/s in supine and prone postures. Using two common methods, bronchial NO production [Jaw(NO)] and alveolar NO concentration (FANO) were extracted from exhaled NO concentration vs. flow or flow(-1) curves. There was no significant Jaw(NO) difference between prone and supine but a significant FANO decrease from prone to supine ranging from 23 to 33% depending on the method used. Total lung capacity was 7% smaller supine than prone (P = 0.03). Besides this purely volumetric effect, which would tend to increase FANO from prone to supine, the observed degree of FANO decrease from prone to supine suggests a greater opposing effect that could be explained by the increased lung capillary blood volume (V(c)) supine vs. prone (P = 0.002) observed in another set of 11 normal subjects. Taken together with the relative changes of NO and CO transfer factors, this V(c) change can be attributed mainly to pulmonary capillary recruitment from prone to supine. Realistic models for exhaled NO simulation should include the possibility that a portion of the pulmonary capillary bed is unavailable for NO uptake, with a maximum capacity of the pulmonary capillary bed in the supine posture.

Does exercise have deleterious consequences for the lungs of patients with chronic heart failure?

Changes in lung function in patients with chronic heart failure (CHF), usually reported at rest, may be exacerbated during exercise and induce post-exercise effects. We investigated the hypothesis that post-exercise induced changes in lung function in CHF patients are due to the consequences of left atrial overload. Twenty-one CHF patients and six healthy subjects (Ctrl) participated in this study. Transfer lung capacity for carbon monoxide (T(LCO)) and maximal expiratory flows (V (max)) were measured before a maximal exercise test and 1h, 2h and 20h afterwards. CHF patients were divided in two groups according to their ventilatory response to the maximal exercise test (V(E) vs. V(CO(2)) relationship slopes above or below 34, i.e., CHF>34 and CHF<34). Compared with the Ctrl group, in CHF groups resting T(LCO) and V(max) were lower. After exercise, further changes in T(LCO) and V(max) were observed in CHF>34. T(LCO) per unit volume (K(CO)) was increased 1h post-exercise while maximal expiratory flow between 25 and 75% of forced vital capacity was decreased 2h and 20h post-exercise. We observed a negative correlation between the delta T(LCO) 1h post-exercise from rest and the delta T(LCO) 2h post-exercise from rest. The decreases in pulmonary V(max) we observed well after exercise following increases in K(CO) in patients with high ventilatory response to exercise (CHF>34) might indicate bronchial congestion resulting from increased left atrial pressure during exercise. We propose that endurance training should be prescribed cautiously for these patients.

Deciphering the nitric oxide to carbon monoxide lung transfer ratio: physiological implications.

Using simultaneous nitric oxide and carbon monoxide lung transfer measurements (T(LNO) and T(LCO)), the membrane transfer capacity (D(m)) and capillary lung volume (V(c)) as well as the dimensionless ratio T(LNO)/T(LCO) can be calculated. The significance of this ratio is yet unclear. Theoretically, the T(LNO)/T(LCO) ratio should be inversely related to the product of both lung alveolar capillary membrane (mu) and blood sheet thicknesses (K). NO and CO transfers were measured in healthy subjects in various conditions likely to be associated with changes in K and/or mu. Experimentally, deflation of the lung from 7.4 to 4.8 l decreased the T(LNO)/T(LCO) ratio from 4.9 to 4.2 (n=25) which was consistent mainly with a thickening of the blood sheet. Compared with continuous negative pressure breathing, continuous positive pressure breathing increased this ratio suggesting a thinning of the capillary sheet. It was also observed with 12 healthy subjects that slight haemodilution that may thicken the blood sheet decreased the T(LNO)/T(LCO) ratio from 4.85 to 4.52. In conclusion, the T(LNO)/T(LCO) ratio is related to the thickness of the alveolar blood barrier. This ratio provides novel information for the analysis of the diffusion properties.