Polyphenol-Rich Blackcurrant Juice Prevents Endothelial Dysfunction in the Mesenteric Artery of Cirrhotic Rats with Portal Hypertension: Role of Oxidative Stress and the Angiotensin System.

Chronic liver diseases with portal hypertension are characterized by a progressive vasodilatation, endothelial dysfunction, and NADPH oxidase-derived vascular oxidative stress, which have been suggested to involve the angiotensin system. This study evaluated the possibility that oral intake of polyphenol-rich blackcurrant juice (PRBJ), a rich natural source of antioxidants, prevents endothelial dysfunction in a rat model of cirrhosis induced by chronic bile duct ligation (CBDL), and, if so, determined the underlying mechanism. Male Wistar rats received either control drinking water or water containing 60 mg/kg gallic acid equivalents of PRBJ for 3 weeks before undergoing surgery with CBDL or sham surgery. After 4 weeks, vascular reactivity was assessed in mesenteric artery rings using organ chambers. Both the acetylcholine-induced nitric oxide (NO)- and endothelium-dependent hyperpolarization (EDH)-mediated relaxations in mesenteric artery rings were significantly reduced in CBDL rats compared to sham rats. An increased level of oxidative stress and expression of NADPH oxidase subunits, COX-2, NOS, and of the vascular angiotensin system are observed in arterial sections in the CBDL group. Chronic intake of PRBJ prevented the CBDL-induced impaired EDH-mediated relaxation, oxidative stress, and expression of the different target proteins in the arterial wall. In addition, PRBJ prevented the CBDL-induced increase in the plasma level of proinflammatory cytokines (interleukin [IL]-1α, monocyte chemotactic protein 1, and tumor necrosis factor α) and the decrease of the anti-inflammatory cytokine, IL-4. Altogether, these observations indicate that regular ingestion of PRBJ prevents the CBDL-induced endothelial dysfunction in the mesenteric artery most likely by normalizing the level of vascular oxidative stress and the angiotensin system.

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

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.

Effect of the oestrogen receptor antagonist fulvestrant on the cirrhotic rat lung.

It has been postulated that cirrhosis-related lung vasodilatation and the subsequent hepatopulmonary syndrome are partly explained by an increased estradiol level through an enhanced endothelial formation of nitric oxide (NO). In this study, we assessed whether the oestrogen receptor antagonist fulvestrant (F) improves cirrhosis-related lung abnormalities. Cirrhosis was induced in rats by chronic bile duct ligation (CBDL). Four groups were studied: CBDL, CBDL+F, sham, and sham+F. Histological, immunohistochemical, and Western blot analyses were performed on lung samples. In the lung, the endothelial NO synthase and the nitrotyrosine protein expressions were increased in CBDL as compared to sham rats. Both parameters were significantly reduced by fulvestrant in the CBDL rats. Surprisingly, the level of pVASP (an indirect marker of NO formation and action) was decreased in CBDL rats, and fulvestrant had no effect on this parameter. The level of the vascular endothelial growth factor, the diameter of small lung vessels, and the number of macrophages were increased in CBDL lungs in comparison with sham lungs, and these parameters were unaffected by fulvestrant treatment. In conclusion, fulvestrant may not be relevant to improve lung abnormalities in cirrhosis because NO may not be biologically active and because key events contributing to the lung abnormalities are not affected by fulvestrant.

Probiotics (VSL#3) prevent endothelial dysfunction in rats with portal hypertension: role of the angiotensin system.

AIMS: Portal hypertension characterized by generalized vasodilatation with endothelial dysfunction affecting nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) has been suggested to involve bacterial translocation and/or the angiotensin system. The possibility that ingestion of probiotics prevents endothelial dysfunction in rats following common bile duct ligation (CBDL) was evaluated. METHODS: Rats received either control drinking water or the probiotic VSL#3 solution (50 billion bacteria.kg body wt⁻¹.day⁻¹) for 7 weeks. After 3 weeks, rats underwent surgery with either resection of the common bile duct or sham surgery. The reactivity of mesenteric artery rings was assessed in organ chambers, expression of proteins by immunofluorescence and Western blot analysis, oxidative stress using dihydroethidium, and plasma pro-inflammatory cytokine levels by flow cytometry. RESULTS: Both NO- and EDH-mediated relaxations to acetylcholine were reduced in the CBDL group compared to the sham group, and associated with a reduced expression of Cx37, Cx40, Cx43, IKCa and SKCa and an increased expression of endothelial NO synthase (eNOS). In aortic sections, increased expression of NADPH oxidase subunits, angiotensin converting enzyme, AT1 receptors and angiotensin II, and formation of ROS and peroxynitrite were observed. VSL#3 prevented the deleterious effect of CBDL on EDH-mediated relaxations, vascular expression of connexins, IKCa, SKCa and eNOS, oxidative stress, and the angiotensin system. VSL#3 prevented the CBDL-induced increased plasma TNF-α, IL-1α and MCP-1 levels. CONCLUSIONS: These findings indicate that VSL#3 ingestion prevents endothelial dysfunction in the mesenteric artery of CBDL rats, and this effect is associated with an improved vascular oxidative stress most likely by reducing bacterial translocation and the local angiotensin system.

Cirrhotic cardiomyopathy and hepatopulmonary syndrome: prevalence and prognosis in a series of patients.

Hepatopulmonary syndrome (HPS) is of prognostic value in patients awaiting for orthotopic liver transplantation (OLT), but little is known about the effect of cirrhotic cardiomyopathy (CCM). The aim of the present study was to estimate the prevalence and possible relation between respiratory and cardiac abnormalities in a same series of patients awaiting OLT. Special attention was paid to the prognostic value of CCM in comparison to HPS. Eighty-three patients were included (19 females, 64 males; 52.1 ± 10.0 yrs). All had lung function testing with arterial blood gases and echocardiographic evaluation at rest with a contrast echocardiography in case of arterial oxygenation defect. To estimate the presence of CCM, patients underwent a complete left and right echocardiography and Doppler examination. Complete echocardiographic assessment could be obtained in 64 of the 83 patients of the study. HPS was observed in 16.9% (14/83) and CCM in 23.4% (15/64) of patients. There was a tendency of more serious adverse events before and after OLT in patients with HPS in comparison to others but CCM was not of prognostic value. HPS and CCM were frequent in these patients awaiting OLT but both abnormalities were not found in the same patients. CCM was neither related to death before OLT nor to death or serious adverse events after OLT.

Skeletal muscle mitochondrial dysfunction precedes right ventricular impairment in experimental pulmonary hypertension.

We assessed the time courses of mitochondrial biogenesis factors and respiration in the right ventricle (RV), gastrocnemius (GAS), and left ventricle (LV) in a model of pulmonary-hypertensive rats. Monocrotaline (MT) rats and controls were studied 2 and 4 weeks after injection. Compensated and decompensated heart failure stages were defined according to obvious congestion signs. mRNA expression and protein level of peroxisome proliferator activated receptor gamma co-activator 1α (PGC-1α), citrate synthase (CS) mRNA and activity, and mitochondrial respiration were investigated. In addition, mRNA expression of sirtuin1, nuclear respiratory factor 1, and mitochondrial transcription factor A were studied. As early as 2 weeks, the expression of the studied genes was decreased in the MT GAS. At 4 weeks, the MT GAS and MT RV showed decreased mRNA levels whatever the stage of disease, but PGC-1α protein and CS activity were significantly reduced only at the decompensated stage. The functional result was a significant fall in mitochondrial respiration at the decompensated stage in the RV and GAS. The mRNA expression and mitochondrial respiration were not significantly modified in the MT LV. MT rats demonstrated an early decrease in expression of genes involved in mitochondrial biogenesis in a skeletal muscle, whereas reduced protein expression, and the resulting mitochondrial respiratory dysfunction appeared only in rats with overt heart failure, in the GAS and RV. Dissociations between mRNA and protein levels at the compensated stage deserve to be further studied.

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.

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, ß(2)-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.

Can exhaled NO fraction predict radiotherapy-induced lung toxicity in lung cancer patients?

BACKGROUND: A large increase in nitric oxide fraction (FeNO) after radiotherapy (RT) for lung cancer may predict RT-induced lung toxicity. METHODS: In this study, we assessed the relationships between FeNO variations and respiratory symptoms, CT scan changes or dose volume histogram (DVH) parameters after RT. We measured FeNO before RT, 4, 5, 6, 10 weeks, 4 and 7.5 months after RT in 65 lung cancer patients. RESULTS: Eleven lung cancer patients (17%) complained of significant respiratory symptoms and 21 (31%) had radiation pneumonitis images in > 1/3 of the irradiated lung after RT. Thirteen patients (20%) showed increases in FeNO > 10 ppb. The sensitivity and specificity of a > 10 ppb FeNO increase for the diagnosis of RT-associated respiratory symptoms were 18% and 83%, respectively. There was no correlation between DVH parameters or CT scan changes after RT and FeNO variations. Three patients (5%) showed intriguingly strong (2 or 3-fold, up to 55 ppb) and sustained increases in FeNO at 4 and 5 weeks, followed by significant respiratory symptoms and/or radiation-pneumonitis images. CONCLUSION: Serial FeNO measurements during RT had a low ability to identify lung cancer patients who developed symptoms or images of radiation pneumonitis. However, three patients presented with a particular pattern which deserves to be investigated.

Impact of altered alveolar volume on the diffusing capacity of the lung for carbon monoxide in obesity.

BACKGROUND: Studies on the diffusing capacity of the lung for carbon monoxide (DL(CO)) in obese patients are conflicting, some studies showing increased DL(CO) and others unaltered or reduced values in these subjects. OBJECTIVES: To compare obese patients to controls, examine the contribution of alveolar volume (VA) and CO transfer coefficient (K(CO)) to DL(CO), and calculate DL(CO) values adjusted for VA. METHODS: We measured body mass index (BMI), waist circumference (WC), spirometry and DL(CO) in 98 adult obese patients without cardiopulmonary or smoking history and 48 healthy subjects. All tests were performed in the same laboratory. RESULTS: Using conventional reference values, mean DL(CO) and VA were lower (-6%, p < 0.05, and -13%, p < 0.001, respectively), and K(CO) was higher (+9%, p < 0.05) in obese patients than in controls. VA decreased whereas K(CO) increased with increasing BMI and WC in the obese group. Patients with lower DL(CO) had low K(CO) in addition to decreased VA. In contrast, some obese patients maintained normal VA, which, coupled with high K(CO), resulted in higher DL(CO). The main result is that diffusion capacity differences between obese patients and controls disappeared using reference equations adjusting DL(CO) for VA. CONCLUSIONS: Using conventional reference equations, our obese patients show slightly lower mean DL(CO,) lower mean VA and higher mean K(CO) than controls, but with a large range of DL(CO) values and patterns. Adjusting DL(CO) for VA suggests that low lung volumes are the main cause of low DL(CO) and high K(CO) values in obese patients.

The opening interrupter technique for respiratory resistance measurements in children.

BACKGROUND AND OBJECTIVE: The interrupter resistance (Rint) can be calculated from various estimates of alveolar pressure based on mouth pressure during occlusion. We compared Rint, as measured by the opening interrupter technique (Rint1), and the linear back-extrapolation method (Rint2), with the 'gold standard' airway resistance measured by plethysmography (Raw). METHODS: The study included 32 asthmatic children and 11 children with cystic fibrosis, aged 5 to 18 years, who were categorized into non-obstructed (NObs) (n = 27) and obstructed (Obs) (n = 16) groups. Spirometry and the three different resistance measurements were performed on all children. Rint1 and Raw were assessed after a bronchodilator (BD) test in 16 and nine children, respectively, in the Obs group. RESULTS: Raw (0.48 ± 0.20 kPa.s/L) was lower than Rint1 (1.04 ± 0.34 kPa.s/L) and Rint2 (0.63 ± 0.18 kPa.s/L) (P < 0.001). Raw, but neither Rint1 nor Rint2, was significantly higher in the Obs group than in the NObs group (0.57 ± 0.23 vs 0.42 ± 0.16 kPa.s/L, P < 0.05). The differences Rint1-Raw and Rint2-Raw were correlated with FEV(1) /VC (P < 0.01 and P < 0.001), and Rint1-Raw was correlated with height (P < 0.001). After BD significant changes in Rint1 and Raw were observed in 5/9 and 7/9 children, respectively. CONCLUSIONS: Rint2, as well as Rint1, may be underestimated in the most Obs children and may therefore fail to detect severe obstruction. Rint1 is likely to include a non-negligible contribution from the tissue component, especially in the youngest children. Although not different between Obs and NObs children at baseline, Rint1 did detect bronchodilation in some Obs children.

Losartan prevents portal hypertension-induced, redox-mediated endothelial dysfunction in the mesenteric artery in rats.

BACKGROUND & AIMS: Advanced stages of portal hypertension are characterized by generalized vasodilatation and a hyperdynamic syndrome that leads to complications such as hepatopulmonary syndrome. We assessed the endothelial function--particularly the formation of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF)--in rats following common bile duct ligation (CBDL) to determine the underlying mechanisms of these processes. METHODS: Reactivity of mesenteric artery rings from male Wistar rats was determined in organ chambers. The expression levels of connexins (Cx) (Cx37, Cx40, Cx43), intermediate and small conductance Ca(2+)-activated K(+) channels (IK(Ca), SK(Ca)), endothelial NO synthase (eNOS), NADPH oxidase subunits, and nitrotyrosines were assessed by immunohistochemistry in mesenteric and pulmonary arteries. The vascular formation of reactive oxygen species (ROS) was evaluated using dihydroethidine. Control rats or those that had undergone CBDL were given either the NADPH oxidase inhibitor apocynin or the angiotensin II receptor type 1 antagonist losartan. RESULTS: Decreased EDHF-mediated relaxations to acetylcholine and red wine polyphenols were observed in CBDL rats, compared with controls, whereas the level of NO-mediated relaxation was similar. Impaired EDHF-mediated relaxations were associated with reduced vascular expression of Cx37, Cx40, Cx43, IK(Ca) and SK(Ca); increased expression of eNOS and NADPH oxidase subunits; and increased vascular formation of ROS and peroxynitrites. These effects were prevented by exposure to apocynin or losartan. CONCLUSIONS: CBDL is associated with reduced EDHF-mediated relaxations in the mesenteric artery, whereas NO-mediated relaxations persisted. These findings indicate that impaired EDHF-mediated relaxation involves an excessive vascular oxidative stress, most likely following activation of angiotensin II type 1 receptors.

Lung function after lobectomy: a randomized, double-blinded trial comparing thoracic epidural ropivacaine/sufentanil and intravenous morphine for patient-controlled analgesia.

BACKGROUND: Although thoracic epidural analgesia (TEA) is considered superior to IV opioids for postoperative analgesia after thoracic surgery, a few studies clearly demonstrate an improvement in pulmonary function attributable to TEA using a local anesthetic in combination with an opioid. METHODS: In this prospective, randomized, double-blind study, we compared the effects of TEA with ropivacaine and sufentanil (TEA group) to IV morphine (IV group), as they affected pain and pulmonary function after lobectomy in 68 patients. Pain intensity, forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, forced expiratory flows, and sniff nasal inspiratory pressure as a marker of inspiratory muscle strength were measured from the first to the fourth postoperative day. RESULTS: Pain relief was better in the TEA group at rest and on coughing (P < 0.001). The impairment of FVC and FEV1 was less in the TEA group when compared with that in the IV group (P < 0.001 and P = 0.003, respectively). Sniff nasal inspiratory pressure, FEV1/FVC ratio, and expiratory flow values decreased similarly in both groups. In-hospital mortality, as well as postoperative pulmonary complications, was not different between groups. CONCLUSION: After lobectomy, TEA enables a significant increase in pulmonary function concomitant with better pain relief than systemic morphine, although a modest intercostal motor block may occur.

Does thoracic bioimpedance accurately determine cardiac output in COPD patients during maximal or intermittent exercise?

STUDY OBJECTIVES: The monitoring of cardiac output (CO) during exercise rehabilitation in patients with COPD, often including strenuous exercise, is advisable. Invasive methods (thermodilution, Fick method) are accurate, but for clinical routine use noninvasive CO estimation is required. We have shown that impedance cardiography (Physio Flow; Manatec Biomedical; Macheren, France) is reliable in COPD patients at rest and during a recumbent, light-intensity exercise. The aim of our study was to evaluate the validity of this noninvasive device in COPD patients during a maximal incremental exercise test (IET) and also during a strenuous intermittent work exercise test (IWET). DESIGN: Prospective comparative study of the impedance cardiograph vs the direct Fick method applied to oxygen. PATIENTS: Eight patients with moderate-to-severe COPD (59 +/- 6 years old; FEV(1), 38 +/- 15% predicted; residual volume, 194 +/- 64% predicted) [mean +/- SD]. MEASUREMENTS AND MAIN RESULTS: Forty-nine simultaneous measurements of CO by means of the direct Fick method (COfick) and CO measured by the impedance cardiograph (COpf) were obtained during the IET, and 108 measurements were made during the IWET. The correlation coefficients between the two measurements were r = 0.85 and r = 0.71 for the IET and the IWET, respectively. COpf was higher than COfick. The difference between the two methods was 3.2 +/- 2.9 L/min during the IET and 2.5 +/- 2.1 L/min during the IWET. Expressed as a percentage of the mean of the two measurements, this corresponded to 31 +/- 21% and 25 +/- 20%, respectively. CONCLUSIONS: The relatively high number of values differing by > 20% precludes the use of impedance cardiography in clinical routine in such a difficult setting (hyperinflated patients and intense exercise).

Intermittent exercise test in chronic obstructive pulmonary disease patients: how do the pulmonary hemodynamics adapt?

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.

Cardiac output and oxygen release during very high-intensity exercise performed until exhaustion.

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(.).

Pulmonary hemodynamics during a strenuous intermittent exercise in healthy subjects.

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.