Effects of High-Intensity Interval Training Using the 3/7 Resistance Training Method on Metabolic Stress in People with Heart Failure and Coronary Artery Disease: A Randomized Cross-Over Study.

The 3/7 resistance training (RT) method involves performing sets with increasing numbers of repetitions, and shorter rest periods than the 3x9 method. Therefore, it could induce more metabolic stress in people with heart failure with reduced ejection fraction (HFrEF) or coronary artery disease (CAD). This randomized cross-over study tested this hypothesis. Eleven individuals with HFrEF and thirteen with CAD performed high-intensity interval training (HIIT) for 30 min, followed by 3x9 or 3/7 RT according to group allocation. pH, HCO3-, lactate, and growth hormone were measured at baseline, after HIIT, and after RT. pH and HCO3- decreased, and lactate increased after both RT methods. In the CAD group, lactate increased more (6.99 ± 2.37 vs. 9.20 ± 3.57 mmol/L, p = 0.025), pH tended to decrease more (7.29 ± 0.06 vs. 7.33 ± 0.04, p = 0.060), and HCO3- decreased more (18.6 ± 3.1 vs. 21.1 ± 2.5 mmol/L, p = 0.004) after 3/7 than 3x9 RT. In the HFrEF group, lactate, pH, and HCO3- concentrations did not differ between RT methods (all p > 0.248). RT did not increase growth hormone in either patient group. In conclusion, the 3/7 RT method induced more metabolic stress than the 3x9 method in people with CAD but not HFrEF.

Standardised Exercise Prescription for Patients with Chronic Coronary Syndrome and/or Heart Failure: A Consensus Statement from the EXPERT Working Group.

Whereas exercise training, as part of multidisciplinary rehabilitation, is a key component in the management of patients with chronic coronary syndrome (CCS) and/or congestive heart failure (CHF), physicians and exercise professionals disagree among themselves on the type and characteristics of the exercise to be prescribed to these patients, and the exercise prescriptions are not consistent with the international guidelines. This impacts the efficacy and quality of the intervention of rehabilitation. To overcome these barriers, a digital training and decision support system [i.e. EXercise Prescription in Everyday practice & Rehabilitative Training (EXPERT) tool], i.e. a stepwise aid to exercise prescription in patients with CCS and/or CHF, affected by concomitant risk factors and comorbidities, in the setting of multidisciplinary rehabilitation, was developed. The EXPERT working group members reviewed the literature and formulated exercise recommendations (exercise training intensity, frequency, volume, type, session and programme duration) and safety precautions for CCS and/or CHF (including heart transplantation). Also, highly prevalent comorbidities (e.g. peripheral arterial disease) or cardiac devices (e.g. pacemaker, implanted cardioverter defibrillator, left-ventricular assist device) were considered, as well as indications for the in-hospital phase (e.g. after coronary revascularisation or hospitalisation for CHF). The contributions of physical fitness, medications and adverse events during exercise testing were also considered. The EXPERT tool was developed on the basis of this evidence. In this paper, the exercise prescriptions for patients with CCS and/or CHF formulated for the EXPERT tool are presented. Finally, to demonstrate how the EXPERT tool proposes exercise prescriptions in patients with CCS and/or CHF with different combinations of CVD risk factors, three patient cases with solutions are presented.

How Does the Method Used to Measure the VE/VCO2 Slope Affect Its Value? A Cross-Sectional and Retrospective Cohort Study.

Cardiopulmonary exercise testing (CPET) was limited to peak oxygen consumption analysis (VO2peak), and now the ventilation/carbon dioxide production (VE/VCO2) slope is recognized as having independent prognostic value. Unlike VO2peak, the VE/VCO2 slope does not require maximal effort, making it more feasible. There is no consensus on how to measure the VE/VCO2 slope; therefore, we assessed whether different methods affect its value. This is a retrospective study assessing sociodemographic data, left ventricular ejection fraction, CPET parameters, and indications of patients referred for CPET. The VE/VCO2 slope was measured to the first ventilatory threshold (VT1-slope), secondary threshold (VT2-slope), and included all test data (full-slope). Of the 697 CPETs analyzed, 308 reached VT2. All VE/VCO2 slopes increased with age, regardless of test indications. In patients not reaching VT2, the VT1-slope was 32 vs. 36 (p < 0.001) for the full-slope; in those surpassing VT2, the VT1-slope was 29 vs. 33 (p < 0.001) for the VT2-slope and 37 (all p < 0.001) for the full-slope. The mean difference between the submaximal and full-slopes was ±4 units, sufficient to reclassify patients from low to high risk for heart failure or pulmonary hypertension. We conclude that the method used for determining the VE/VCO2 slope greatly influences the result, the significant variations limiting its prognostic value. The calculation method must be standardized to improve its prognostic value.

Hemodynamic Tolerance of New Resistance Training Methods in Patients With Heart Failure and Coronary Artery Disease: A RANDOMIZED CROSSOVER STUDY.

PURPOSE: The purpose of this study was to determine and compare the effectiveness of three different resistance training (RT) methods for cardiac rehabilitation. METHODS: Individuals with heart failure with reduced ejection fraction (HFrEF, n = 23) or coronary artery disease (CAD, n = 22) and healthy controls (CTRL, n = 29) participated in this randomized crossover trial of RT exercises at 70% of the one-maximal repetition on a leg extension machine. Peak heart rate (HR) and blood pressure (BP) were measured noninvasively. The three RT methods were five sets of increasing repetitions from three to seven (RISE), of decreasing repetitions from seven to three (DROP), and three sets of nine repetitions (USUAL). Interset rest intervals were 15 sec for RISE and DROP and 60 sec for USUAL. RESULTS: Peak HR differed on average by <4 bpm between methods in the HFrEF and CAD groups ( P < .02). Rises in systolic BP (SBP) in the HFrEF group were comparable across methods. In the CAD group, mean SBP at peak exercise increased more in RISE and DROP than in USUAL ( P < .001), but the increase was ≤10 mm Hg. In the CTRL group, SBP was higher for DROP than for USUAL (152 ± 22 vs 144 ± 24 mm Hg, respectively; P < .01). Peak cardiac output and perceived exertion did not differ between methods. CONCLUSIONS: The RISE, DROP, and USUAL RT methods induced a similar perception of effort and similar increases in peak HR and BP. The RISE and DROP methods appear more efficient as they allow a comparable training volume in a shorter time than the USUAL method.

Beta-Adrenergic Receptor Blockade Effects on Cardio-Pulmonary Exercise Testing in Healthy Young Adults: A Randomized, Placebo-Controlled Trial.

BACKGROUND: Beta-blockers are increasingly prescribed while the effects of beta-adrenergic receptor blockade on cardio-pulmonary exercise test (CPET)-derived parameters remain under-studied. METHODS: Twenty-one young healthy adults repeated three CPET at the same time with an interval of 7 days between each test. The tests were performed 3 h after a random, double-blind, cross-over single-dose intake of placebo, 2.5 mg or 5.0 mg bisoprolol, a cardio-selective beta1-adrenoreceptor antagonist. Gas exchange, heart rate (HR) and blood pressure (BP) were measured at rest and during cyclo-ergometric incremental CPET. RESULTS: Maximal workload and VO2max were unaffected by the treatment, with maximal respiratory exchange ratio > 1.15 in all tests. A beta-blocker dose-dependent effect reduced resting and maximal BP and HR and the chronotropic response to exercise, evaluated by the HR/VO2 slope (placebo: 2.9 ± 0.4 beat/ml/kg; 2.5 mg bisoprolol: 2.4 ± 0.5 beat/ml/kg; 5.0 mg bisoprolol: 2.3 ± 0.4 beat/ml/kg, p < 0.001). Ventilation efficiency measured by the VE/VCO2 slope and the ventilatory equivalent for CO2 at the ventilatory threshold were not affected by beta1-receptor blockade. Post-exercise chronotropic recovery measured after 1 min was enhanced under beta1-blocker (placebo: 26 ± 7 bpm; 2.5 mg bisoprolol: 32 ± 6 bpm; 5.0 mg bisoprolol: 33 ± 6 bpm, p < 0.01). CONCLUSION: The present results suggest that a single dose of bisoprolol does not affect metabolism, respiratory response and exercise capacity. However, beta-adrenergic blockade dose dependently reduces exercise hemodynamic response by lowering BP and the chronotropic response.

Benefits of Cardio-Pulmonary Rehabilitation in Moderate to Severe Forms of COVID-19 Infection.

Our aim was to evaluate the benefits of cardio-pulmonary rehabilitation on severe to moderate COVID-19 patients. 25 discharged COVID-19 patients underwent a cardio-pulmonary test (CPET), a spirometry test and a measure of carbon monoxide lung diffusion capacity (DLCO) at the beginning of their rehabilitation program and after 23 ± 5 rehabilitation sessions. This rehabilitation program combined interval training exercises on a bike and resistance exercises for major muscle groups. We then compared their progress in rehabilitation to that obtained with cardiac patients. At the beginning of their rehabilitation program, COVID-19 patients presented a reduced physical capacity with a maximal aerobic capacity (VO2 max) at 71% of predicted value, a maximal workload at 70% of predicted value and an exercise hyperventilation measured by a higher VE/VCO2 slope. Exercise was mainly limited by muscle deconditioning. After rehabilitation, the VO2 max and maximal workload increased in COVID 19 patients by 18% and 26%, respectively. In patients with ischemic heart disease the post-rehabilitation gains in VO2 max and maximal workload were 22% and 25%, respectively. Moreover, exercise hyperventilation decreased by 10% in both groups. On the other hand, the intrinsic pulmonary function of COVID 19 patients improved following natural recovery. In conclusion, even if cardio-pulmonary rehabilitation is probably not the only parameter which explains the partial recovery of moderate to severe COVID-19 patients, it certainly helps to improve their physical capacity and reduce exercise hyperventilation.

Are Trait Emotional Competencies and Heart Rate Variability Linked to Mental Health of Coronary Heart Disease Patients?

PURPOSE: Depression and anxiety have been extensively associated with adverse outcomes in coronary heart disease patients. However, psychological and physiological processes underlying the persistence of these troubles in coronary heart disease patients attending cardiac rehabilitation are poorly investigated. Trait emotional competencies and heart rate variability could be some of these processes. Thus, the aim of this study was to assess the predictive value of trait emotional competencies and heart rate variability on depression and anxiety symptoms persistence in coronary heart disease patients. METHODS: Eighty-four patients who recently presented a myocardial infarction were evaluated at the beginning of cardiac rehabilitation. Forty-two patients continued their rehabilitation program and were then assessed three months later. They completed the Profile of Emotional Competence as well as the Hospital Anxiety and Depression Scale and underwent a 5-minute resting heart rate variability measure. RESULTS: Low trait emotional competencies score predicted depression symptoms persistence, but unexpectedly, high trait emotional competencies score was also associated with withdrawal from cardiac rehabilitation. Contrary to our expectations, heart rate variability did not predict depression or anxiety symptoms persistence and was not associated with trait emotional competencies. CONCLUSIONS: This study is the first to report an association between trait emotional competencies and depression symptoms persistence in coronary heart disease patients. However, heart rate variability was not associated with either depression or anxiety supporting the idea of mixed literature and highlighting the need of future research.

Exercise Prescription in Patients with Different Combinations of Cardiovascular Disease Risk Factors: A Consensus Statement from the EXPERT Working Group.

Whereas exercise training is key in the management of patients with cardiovascular disease (CVD) risk (obesity, diabetes, dyslipidaemia, hypertension), clinicians experience difficulties in how to optimally prescribe exercise in patients with different CVD risk factors. Therefore, a consensus statement for state-of-the-art exercise prescription in patients with combinations of CVD risk factors as integrated into a digital training and decision support system (the EXercise Prescription in Everyday practice & Rehabilitative Training (EXPERT) tool) needed to be established. EXPERT working group members systematically reviewed the literature for meta-analyses, systematic reviews and/or clinical studies addressing exercise prescriptions in specific CVD risk factors and formulated exercise recommendations (exercise training intensity, frequency, volume and type, session and programme duration) and exercise safety precautions, for obesity, arterial hypertension, type 1 and 2 diabetes, and dyslipidaemia. The impact of physical fitness, CVD risk altering medications and adverse events during exercise testing was further taken into account to fine-tune this exercise prescription. An algorithm, supported by the interactive EXPERT tool, was developed by Hasselt University based on these data. Specific exercise recommendations were formulated with the aim to decrease adipose tissue mass, improve glycaemic control and blood lipid profile, and lower blood pressure. The impact of medications to improve CVD risk, adverse events during exercise testing and physical fitness was also taken into account. Simulations were made of how the EXPERT tool provides exercise prescriptions according to the variables provided. In this paper, state-of-the-art exercise prescription to patients with combinations of CVD risk factors is formulated, and it is shown how the EXPERT tool may assist clinicians. This contributes to an appropriately tailored exercise regimen for every CVD risk patient.

Left ventricular assist device: exercise capacity evolution and rehabilitation added value.

BACKGROUND: With more than 15,000 implanted patients worldwide and a survival rate of 80% at 1-year and 59% at 5-years, left ventricular assist device (LVAD) implantation has become an interesting strategy in the management of heart failure patients who are resistant to other kinds of treatment. There are limited data in the literature on the change over time of exercise capacity in LVAD patients, as well as limited knowledge about the beneficial effects that rehabilitation might have on these patients. Therefore, the aim of our study was to evaluate the evolution of exercise capacity on a cohort of patients implanted with the same device (HeartWare©) and to analyse the potential impact of rehabilitation. METHODS: Sixty-two patients implanted with a LVAD between June 2011 and June 2015 were screened. Exercise capacity was evaluated by cardiopulmonary exercise testing at 6 weeks, 6 and 12 months after implantation. RESULTS: We have observed significant differences in the exercise capacity and evolution between the trained and non-trained patients. Some of the trained patients nearly normalised their exercise capacity at the end of the rehabilitation programme. CONCLUSIONS: Exercise capacity of patient implanted with a HeartWare© LVAD increased in the early period after implantation. Rehabilitation allowed implanted patients to have a significantly better evolution compared to non-rehabilitated patients.

The European Association of Preventive Cardiology Exercise Prescription in Everyday Practice and Rehabilitative Training (EXPERT) tool: A digital training and decision support system for optimized exercise prescription in cardiovascular disease. Concept, definitions and construction methodology.

Background Exercise rehabilitation is highly recommended by current guidelines on prevention of cardiovascular disease, but its implementation is still poor. Many clinicians experience difficulties in prescribing exercise in the presence of different concomitant cardiovascular diseases and risk factors within the same patient. It was aimed to develop a digital training and decision support system for exercise prescription in cardiovascular disease patients in clinical practice: the European Association of Preventive Cardiology Exercise Prescription in Everyday Practice and Rehabilitative Training (EXPERT) tool. Methods EXPERT working group members were requested to define (a) diagnostic criteria for specific cardiovascular diseases, cardiovascular disease risk factors, and other chronic non-cardiovascular conditions, (b) primary goals of exercise intervention, (c) disease-specific prescription of exercise training (intensity, frequency, volume, type, session and programme duration), and (d) exercise training safety advices. The impact of exercise tolerance, common cardiovascular medications and adverse events during exercise testing were further taken into account for optimized exercise prescription. Results Exercise training recommendations and safety advices were formulated for 10 cardiovascular diseases, five cardiovascular disease risk factors (type 1 and 2 diabetes, obesity, hypertension, hypercholesterolaemia), and three common chronic non-cardiovascular conditions (lung and renal failure and sarcopaenia), but also accounted for baseline exercise tolerance, common cardiovascular medications and occurrence of adverse events during exercise testing. An algorithm, supported by an interactive tool, was constructed based on these data. This training and decision support system automatically provides an exercise prescription according to the variables provided. Conclusion This digital training and decision support system may contribute in overcoming barriers in exercise implementation in common cardiovascular diseases.

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.

Exercise testing to predict outcome in idiopathic versus associated pulmonary arterial hypertension.

We tested the ability of exercise testing to predict not only survival, but also time to clinical worsening (TTCW) in idiopathic versus associated pulmonary arterial hypertension (PAH). 136 patients with PAH (85 idiopathic and 51 with associated conditions) underwent cardiopulmonary exercise testing and a 6-min walk test. Death or transplantation, and clinical worsening events were recorded. 32 patients died and four had lung transplantation. In a univariate analysis, PAH patients survival was associated with oxygen uptake (V'(O(2))) at peak exercise and at the anaerobic threshold, ventilatory equivalent for carbon dioxide (minute ventilation (V'(E))/carbon dioxide production (V'(CO(2))) at the anaerobic threshold ((at))), V'(E)/V'(CO(2)) slope and distance walked. TTCW was associated with peak V'(O(2)) and V'(O(2),at), V'(E)/V'(CO(2),at), end-tidal carbon dioxide tension measured at the anaerobic threshold, peak oxygen pulse, increase in oxygen pulse and distance walked. In a multivariable analysis, distance walked and V'(E)/V'(CO(2),at) predicted survival, and only peak V'(O(2)) predicted TTCW. The receiver operating characteristic curve-derived cut-off values were 305 m for the 6-min walk distance, 54 for V'(E)/V'(CO(2),at) and 11.6 mL·kg(-1)·min for peak V'(O(2)). In the subgroup with associated PAH, no variable independently predicted either survival or clinical worsening. We conclude that several exercise variables predict survival and clinical stability in idiopathic PAH. Exercise variables are less accurate predictors of outcome in associated PAH.

Acute cardiovascular response to resistance training during cardiac rehabilitation: effect of repetition speed and rest periods.

BACKGROUND: Resistance training has been introduced into rehabilitation to improve the efficiency of the 1980s traditional training. Among the modalities, the choice of recovery period length or repetition speed is hardly explained in term of functional benefit but not in terms of cardiovascular (CV) response. To our knowledge, no investigation has been made on the acute CV effect of repetition speed and rest periods between sets of such training during rehabilitation. DESIGN AND METHODS: Our population included 17 male coronary patients. The experiment was performed on a leg extension device. A task force monitor noninvasive measurement system was used for continuous monitoring of the heart rate, systolic blood pressure and cardiac output. To evaluate the impact of the speed of contraction, individuals performed randomly, 3 x 10 repetitions (75% resistance maximum) at slow, moderate or fast pace. To evaluate the effect of the recovery period, individuals performed randomly, 3 x 10 repetitions separated by 30, 60, 90 or 120 s. RESULTS: We observed a progressive drift of heart rate, systolic blood pressure and cardiac output between each rest period and sets for all the modalities. These drifts were more pronounced when the rhythm of contraction was slow or when the recovery period was short (30 or 60 s). CONCLUSION: This work confirms the results of an earlier study showing that the main factor affecting the CV response is the length of the set. The 'ideal modality' should be three sets of 10 repetitions, at 75% resistance maximum, fast executed, with a 90 s recovery period between successive sets.

Aerobic exercise capacity in COPD patients with and without pulmonary hypertension.

Pulmonary hypertension is a common occurrence in advanced COPD, but its effects on exercise capacity remain undetermined. Exercise testing and an echocardiographic examination were performed in 29 patients with advanced stable COPD. Mean pulmonary artery pressure (mPAP) was calculated from the acceleration time of pulmonary flow. Exercise capacity was evaluated by the distance walked in 6 min (6MWD) and by an incremental cardiopulmonary exercise test (CPET). The patients had a forced expiratory volume in 1s of 1.13+/-0.49 L, and a 6MWD of 305+/-66 m (mean+/-SD). The CPET (n=24) showed a: maximum workload of 52+/-25 W, a peak O(2) uptake of 13.8+/-4.4 mL/kg/min, a peak heart rate of 127+/-22 bpm, a peak respiratory exchange ratio 1.06+/-0.11, a ventilation (V(E))/CO(2) production slope of 37+/-11, and a peak O(2) pulse 7.5+/-2.3 mL. The peak V(E) was 41+/-15 L/min, and the calculated maximum voluntary V(E) 45+/-20 L/min. There was no difference in any of the CPET variables and 6MWD between the patients with a mPAP<30 mm Hg (mPAP 22+/-6 mm Hg, n=15) and those with a mPAP>30 mm Hg (mPAP 38+/-6 mm Hg, n=14). There was no correlation between PAP and any of the exercise measurements. These results suggest that exercise capacity in unselected patients with advanced COPD and mild to moderate pulmonary hypertension is essentially limited by exhaustion of the ventilatory reserve.

Effect of systemic inflammation on inspiratory and limb muscle strength and bulk in cystic fibrosis.

RATIONALE: Diaphragm thickness is increased in cystic fibrosis (CF), but it shows a marked variability between patients. The variable response of the diaphragm to loading may reflect the combined and opposite effects of training by the respiratory disease and systemic inflammation. OBJECTIVES: To assess the impact of systemic inflammation on diaphragm and limb muscle strength and bulk in adult patients with CF. METHODS: In 38 stable patients with CF and 20 matched control subjects, we measured fat-free mass (FFM), inspiratory muscle strength, diaphragm thickness, quadriceps and biceps strength and cross-sectional area, and circulating levels of leukocytes, C-reactive protein, IL-6, IL-8, IL-17, tumor necrosis factor-alpha, tumor necrosis factor-alpha soluble receptors, and immunoglobulin G. MEASUREMENTS AND MAIN RESULTS: Patients had increases in several inflammatory markers that correlated with the severity of lung disease and nutritional depletion. Compared with control subjects, patients with CF had increased diaphragm thickness and inspiratory muscle strength and showed a trend toward a reduction in limb muscle strength and bulk. Multiple regression analyses identified FFM and airway resistance as independent predictors of diaphragm thickness, but systemic inflammation had no (or only a minor) predictive effect on FFM, inspiratory muscle strength, diaphragm thickness, and limb muscle strength and bulk. CONCLUSIONS: In patients with CF, the intensity of systemic inflammation does not account significantly for the variance of FFM and diaphragm or limb muscle strength and bulk. Training of the diaphragm in CF occurs despite the presence of systemic inflammation.

Bosentan decreases pulmonary vascular resistance and improves exercise capacity in acute hypoxia.

BACKGROUND: Altitude exposure is associated with mild pulmonary hypertension and decreased exercise capacity. We tested the hypothesis that pulmonary vascular resistance (PVR) contributes to decreased exercise capacity in hypoxic healthy subjects. METHODS: An incremental cycle ergometer cardiopulmonary exercise test and echocardiographic estimation of pulmonary artery pressure (Ppa) and cardiac output to calculate total PVR were performed in 11 healthy volunteers in normoxia and after 1 h of hypoxic breathing (12% O(2)). The measurements were performed in a random order at 1-week intervals after the receiving either a placebo or bosentan, following a double-blind randomized crossover design. Bosentan was administered twice a day for 3 days, 62.5 mg on the first day and 125 mg on the next 2 days. RESULTS: Hypoxic breathing decreased the mean (+/- SE) pulse oximetric saturation (Spo(2)) from 99 +/- 1% to 3 +/- 1% and increased the mean PVR from 5.6 +/- 0.3 to 7.2 +/- 0.5 mm Hg/L/min/m(2), together with a decrease in mean maximum O(2) uptake (Vo(2)max) from 47 +/- 2 to 35 +/- 2 mL/kg/min. Bosentan had no effect on normoxic measurements and did not affect hypoxic Spo(2), but decreased PVR to 5.6 +/- 0.3 mm Hg/L/min/m(2) (p < 0.01) and increased Vo(2)max to 39 +/- 2 mL/kg/min (p < 0.01) in hypoxia. Bosentan therapy, on average, restored 30% of the hypoxia-induced decrease in Vo(2)max. Bosentan-induced changes in Ppa and Vo(2)max were correlated (p = 0.01). CONCLUSIONS: We conclude that hypoxic pulmonary hypertension partially limits exercise capacity in healthy subjects, and that bosentan therapy can prevent it.

Effects of sildenafil on exercise capacity in hypoxic normal subjects.

The phosphodiesterase-5 inhibitor sildenafil has been reported to improve hypoxic exercise capacity, but the mechanisms accounting for this observation remain incompletely understood. Sixteen healthy subjects were included in a randomized, double-blind, placebo-controlled, cross-over study on the effects of 50-mg sildenafil on echocardiographic indexes of the pulmonary circulation and on cardiopulmonary cycle exercise in normoxia, in acute normobaric hypoxia (fraction of inspired O2, 0.1), and then again after 2 weeks of acclimatization at 5000 m on Mount Chimborazo (Ecuador). In normoxia, sildenafil had no effect on maximum VO2 or O2 saturation. In acute hypoxia, sildenafil increased maximum VO2 from 27 +/- 5 to 32 +/- 6 mL/min/kg and O2 saturation from 62% +/- 6% to 68% +/- 9%. In chronic hypoxia, sildenafil did not affect maximum VO2 or O2 saturation. Resting mean pulmonary artery pressure increased from 16 +/- 3 mmHg in normoxia to 28 +/- 5 mmHg in normobaric hypoxia and 32 +/- 6 mmHg in hypobaric hypoxia. Sildenafil decreased pulmonary vascular resistance by 30% to 50% in these different conditions. We conclude that sildenafil increases exercise capacity in acute normobaric hypoxia and that this is explained by improved arterial oxygenation, rather than by a decrease in right ventricular afterload.

Increased peripheral chemoreceptors sensitivity and exercise ventilation in heart transplant recipients.

BACKGROUND: Heart failure is characterized by increased ventilation during exercise, which is positively related to increased peripheral and central chemoreceptor sensitivity. Heart transplantation does not normalize the ventilatory response to exercise, and its effects on the chemoreflex control of ventilation remain unknown. We tested the hypothesis that chemoreceptor sensitivity is increased in heart transplant recipients (HTRs) and linked to exercise hyperpnea. METHODS AND RESULTS: We determined the ventilatory, muscle sympathetic nerve activity (MSNA), and circulatory responses to isocapnic hypoxia and hyperoxic hypercapnia 7+/-1 years after transplantation in 19 HTRs with a normal left ventricular ejection fraction of 60+/-2%. Results were compared with those of 11 closely matched referent subjects. Sixteen patients and 10 referent subjects also underwent cycle ergometer exercise tests. HTRs compared with referent subjects presented higher MSNA (52+/-4 versus 34+/-3 bursts/min; P<0.01) and heart rates (83+/-3 versus 68+/-3 bpm; P<0.01) during room air breathing. The ventilatory response to hypoxia was higher in HTRs than in referent subjects (P<0.01, ANOVA). The increase in MSNA also was more marked during hypoxia in the HTRs than in the referent group (P<0.05, ANOVA). Responses to hyperoxic hypercapnia did not differ between the HTRs and the referent group. The ventilatory response to exercise, characterized by the regression slope relating minute ventilation to CO2 output, was steeper in HTRs than in referent subjects (38+/-2 versus 29+/-1 L/mm Hg; P<0.01). Exercise ventilation in HTRs was related to the ventilatory response to isocapnic hypoxia (r=0.57; n=16; P<0.05) and to the ventilatory response to hyperoxic hypercapnia (r=0.50; n=16; P<0.05). CONCLUSIONS: Peripheral chemoreceptor sensitivity is increased in HTRs and is related to exercise hyperpnea after heart transplantation.

Detection and quantification of PAH in drinking water by front-face fluorimetry on a solid sorbent and PLS analysis.

The direct determination in drinking water of perylene, chrysene, pyrene, benzo[a]pyrene, and benzo[k]fluoranthene, by front-face synchronous fluorimetry on a commercial SPE disk, has been evaluated. Sorbent treatment, influence of humic substances, and pH effect are discussed. In pure water the detection limits were estimated to be in the range 0.03-0.01 microg L(-1). A working pH in the range 10-11 was found to minimize the fluorescence quenching effect of humic substances. The proposed method combined with a partial-least-square (PLS) treatment was tested for quantitative analysis of mixtures of four PAH in a spiked drinking water.