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Biomedical subjects

R Naeije

Publications and source records attributed to R Naeije.

At least 19 recordsLinked to original sources
PubMed2006

Noninvasive and invasive evaluation of pulmonary arterial pressure in highlanders.

The purpose of the present study was to evaluate Doppler echocardiography for the detection of pulmonary hypertension in high-altitude inhabitants. In total, 60 (55 male) patients aged 18-71 yrs were recruited from an ECG screening programme applied to 1,430 inhabitants living at an altitude of 2,500-3,600 m in Kyrgyzstan. Of these, 44 met ECG criteria for right ventricular hypertrophy. All underwent Doppler echocardiography followed by a cardiac catheterisation within 7 days of arrival in Bishkek (Kyrgyzstan; altitude 760 m). Pulmonary flow acceleration time and the maximum velocity of tricuspid regurgitation were measured. Sufficient quality tricuspid regurgitant jets were recovered in only 28% of the patients. Therefore, pulmonary artery pressure was estimated from the pulmonary flow acceleration time, which was recovered in 100% of the patients. It was found that 37 (62%) of the patients had pulmonary hypertension on echocardiography. Pulmonary hypertension was confirmed in 29 patients on catheterisation. Pulmonary hypertension was detected with 70% sensitivity and 88% specificity by echocardiography, as compared to 59% sensitivity and 81 % specificity by ECG. The correlation coefficient between echocardiography and catheterisation studies was r(2) = 0.78. It is concluded that a combination of ECG and echocardiography may be useful for screening high-altitude pulmonary hypertension.

Adolescent↗
PubMed2006

Long-term outcome in pulmonary arterial hypertension patients treated with subcutaneous treprostinil.

Pulmonary arterial hypertension (PAH) is fatal if untreated. Intravenous epoprostenol improves exercise capacity and haemodynamics in PAH, and increases survival in idiopathic PAH (IPAH). To evaluate the effects of subcutaneous (SC) treprostinil, a longer-acting prostacyclin analogue, followed by the addition of other PAH therapies if needed, 860 PAH patients treated with SC treprostinil for up to 4 yrs were followed. Survival is reported as Kaplan-Meier estimates. For 332 IPAH patients with baseline haemodynamics, observed survival is also compared with predicted survival using the National Institute of Health formula. Out of the 860 patients, 199 (23%) discontinued due to adverse events, 136 (16%) died, 117 (14%) discontinued due to deterioration, 29 (3%) withdrew consent and 11 (1%) underwent transplantation. In total, 97 patients (11%) switched from SC treprostinil to an alternative prostacyclin analogue; bosentan was added in 105 patients (12%) and sildenafil in 25 (3%). In conclusion, survival was 87-68% over 1-4 yrs for all 860 patients and 88-70% over 1-4 yrs with subcutaneous treprostinil monotherapy. For the idiopathic pulmonary arterial hypertension subset with baseline haemodynamics (n = 332), survival was 91-72% over 1-4 yrs. In contrast, predicted survival was 69-38% over 1-4 yrs. The safety profile for long-term subcutaneous treprostinil was consistent with previous short-term trials with no unexpected adverse events.

Adolescent↗
PubMed2005

[Pulmonary arterial hypertension in intensive care unit and operating room].

OBJECTIVE: To review the perioperative anaesthetic management of pulmonary arterial hypertension. DATA SOURCES: Extraction from Pubmed database of French and English articles on the perioperative anaesthetic management of pulmonary hypertension for 9 years. DATA SELECTION: The collected articles were reviewed and selected according their quality and originality. The more recent data were selected. DATA SYNTHESIS: Pulmonary arterial hypertension is classically divided in primary and secondary. Primary pulmonary hypertension (familial and sporadic) is relatively severe and rare. Muscularization of the terminal portion of the pulmonary vascular arterial tree, caused by smooth muscle cell hyperplasia is the first change. Pulmonary arterial hypertension linked with disorders of the respiratory system and hypoxemia or pulmonary venous hypertension including mitral valve disease and chronic left ventricular dysfunction are often associated with high morbidity and mortality. The main consequence of pulmonary hypertension development is the occurrence of right-sided circulatory failure. A better understanding of disease pathophysiology will contribute to the development of new therapies increasing then the prognosis of these patients. The management of primary pulmonary hypertension or secondary pulmonary arterial hypertension is a challenge for the anaesthesiologist because the risk of right ventricular failure is markedly increased.

Anesthesia↗
PubMed2005

Increased plasma levels of adrenomedullin, a vasoactive peptide, in patients with end-stage pulmonary disease.

AIM: To study adrenomedullin (AM) plasma levels in patients with severe lung disease and to analyze the relationship between AM and heart changes, hemodynamics and blood gases. METHODS: Case control study of 56 patients (36 men, 20 women) with severe lung disease and 9 control subjects (7 men, 2 women). Patients with end-stage pulmonary disease, including chronic obstructive pulmonary disease (COPD, n=11), cystic fibrosis (CF, 26), idiopatic pulmonary fibrosis (ILD, n=9), and idiopatic pulmonary arterial hypertension (PAH, n=10), who were evaluated for lung trasplantation between January 1997 and September 2000, and nine patients who underwent lung surgery for a solitary benign nodule. AM plasma levels in pulmonary artery (mixed venous blood, vein) and aorta or femoral artery (arterial, art), art and vein blood gases, pulmonary hemodynamics, systemic hemodynamics, two-dimensional transthoracic echocardiography and echo-Doppler study. RESULTS: Plasma AM (art and ven) levels were higher among patients' group compared to the controls (AMart p<0.02 and AMven p<0.04) for CF, ILD, PAH (AMart, pg ml(-1) Controls 13.7+/-3.6, COPD 22.8+/-6.2, CF 28.1+/-11.4, ILD 34.1+/-14.3, PAH 35.1+/-18.9; AMven, pg ml(-1) Controls 14.2+/-4.8, COPD 28.1+/-12.6, CF 31.7+/-14.1, ILD 38.7+/-16.5, PAH 40.1+/-4.4). We found with a trend towards higher concentration in ILD and PAH patients compared to COPD and CF but no statistical significant differences. Mixed-venous AM was higher than arterial AM in all groups resulting in AM uptake (AMPulmUp pg min(-1) Controls 4.8+/-22.6, COPD 21.1+/-44.9, CF 20.6+/-45.1, ILD 23.7+/-38.5, PAH 29.9+/-49.7). The univariate analysis showed a weak but significant correlation between AMart and mean systemic arterial pressure, heart rate, mean pulmonary arterial pressure and systemic vascular resistance. In the multivariate analysis, four variables emerged as independent factors of AMart including mean pulmonary arterial pressure, heart rate, mean systemic arterial pressure and left ventricular diastolic diameter (F=8.6, p<0.00001, r=0.60, r2=0.32). A similar weak correlation was apparent between AMven, systemic vascular resistance, and mean pulmonary arterial pressure. The results of multivariate analysis identify right atrial enlargement, mean right atrial pressure, heart rate and left ventricular dimensions as the only independent variables related to AMven (F=4.3, p<0.0004 r=0.56, r2=0.26). AM pulmonary uptake was significantly correlated with AMven (r=0.65), but not with hemodynamic, blood gas and echocardiographic variables. CONCLUSIONS: AM plasma levels are elevated in patients with severe lung disease in face of a preserved pulmonary uptake. These results suggest that the high AM plasma levels in patients with severe lung disease are not caused by a reduced pulmonary clearance, instead suggesting a systemic production.

Adrenomedullin↗
PubMed2005

Effect of treatments on the progression of COPD: report of a workshop held in Leuven, 11-12 March 2004.

During the last decade several long term studies of interventions in patients with COPD have been published. This review analyses the potential of these interventions to alter the progression of the condition. The only treatment that has unequivocally been shown to reduce the rate of decline in FEV(1) is smoking cessation. Active psychological intervention in combination with pharmacotherapy is required. Other treatments may have an effect on the rate of decline in FEV(1) but this appears to be very small, at most. Several treatments affect the exacerbation rate and therefore might affect the progression of the disease. Further studies are warranted to examine this effect.

Administration, Inhalation↗
PubMed2005

Physiological response to the six-minute walk test in pulmonary arterial hypertension.

The 6-min walk test (6MWT) is commonly used to evaluate exercise capacity in patients with pulmonary arterial hypertension (PAH). However, little is known about the corresponding metabolic stress as measured by cardiopulmonary exercise testing. The present study, therefore, measured ventilatory variables and heart rate during the 6MWT and symptom-limited incremental maximal exercise testing in 20 patients with PAH. The distance walked in 6 min was 450+/-22 m (mean+/-se). During the 6MWT, ventilation, O2 consumption, CO2 production and heart rate increased during the first 3-4 min, and then remained stable. As compared with the maximum values measured during the cardiopulmonary exercise test, O2 consumption tended to be higher (14.2+/-0.6 versus 12.9+/-0.7 mL.kg-1.min-1), while maximum ventilation (46+/-3 versus 57+/-4 L.min-1), respiratory quotient (0.90+/-0.02 versus 1.15+/-0.02) and heart rate (119+/-4 versus 135+/-4 beats.min-1) remained lower. In conclusion, patients with pulmonary arterial hypertension exercise at higher aerobic capacity and lower metabolic stress during the 6MWT than during a cardiopulmonary exercise test.

Exercise Test↗
PubMed2004

Exercise testing in pulmonary arterial hypertension and in chronic heart failure.

Exercise capacity is reduced in pulmonary arterial hypertension and in chronic left heart failure, but it is not known whether the cardiopulmonary exercise testing profile is different in the two conditions at the same severity of functional limitation. Nineteen patients with pulmonary arterial hypertension and 19 with chronic heart failure underwent a 6-min walk test and symptom-limited maximal incremental cycle ergometry. The patients with pulmonary arterial hypertension and chronic heart failure did not differ in New York Heart Association Functional Class (mean +/- SEM 2.8 +/- 0.1 versus 2.8 +/- 0.2), 6-min walking distance (395 +/- 30 versus 419 +/- 20 m), peak work-rate, oxygen consumption, ventilation and cardiac frequency. However, patients with pulmonary arterial hypertension exhibited higher dyspnoea scores (5.8 +/- 0.6 versus 3.8 +/- 0.5) higher ventilatory equivalents for carbon dioxide (58 +/- 3 versus 44 +/- 3 at the anaerobic threshold) and lower peak oxygen pulse (5.9 +/- 0.4 versus 8.7 +/- 0.5 mL x beat(-1), or 53 +/- 4 versus 64 +/- 4% of the predicted value). It is concluded that the cardiopulmonary exercise testing profile in pulmonary arterial hypertension differs from that in chronic heart failure by showing more dyspnoea at comparable work-rates, related to greater reductions in ventilatory efficiency and stroke volume.

Adult↗
PubMed2004

End points in pulmonary arterial hypertension: the way forward.

Pulmonary arterial hypertension is a rare disease of poor prognosis. Despite its rarity >1,000 patients have been randomised in placebo-controlled trials using novel therapies, including prostacyclin analogues, endothelin receptor antagonists and, most recently, phosphodiesterase 5 inhibitors. Nearly all of these trials have used exercise capacity, measured by the unencouraged 6-min walking distance, as the primary end point and a variety of other measurements as secondary end points. This approach has been productive, leading to the licensing of a number of effective treatments. Future clinical trials, however, will probably assess drug combinations, make comparisons between drugs and include less severely ill patients. It is, therefore, timely to examine the end points used. The authors discussed the various end points that have been used in the past and possible end points that might be used in the future. End points considered included measurements of: exercise capacity, haemodynamics, quality of life, imaging of the right heart and circulation, and chemical markers of pulmonary hypertension. Many of these show promise but will have to be used in parallel and compared with conventional end points such as the 6-min walking distance before their value can be demonstrated convincingly to the regulatory authorities.

Antihypertensive Agents↗
PubMed2004

Pathobiology of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a syndrome of dyspnea, fatigue, chest pain and syncope defined by an increase in pulmonary vascular resistance (PVR) of unknown cause. The pathobiology of PAH remains incompletely understood. The gene of the idiopathic form of PAH (IPAH) has been located on chromosome 2, and shown to present mutations of a sequence that encodes for a transforming growth factor receptor, bone morphogenenetic protein receptor 2 (BMPR2). Severe pulmonary hypertension is associated with an increased expression of the angiogenic factor, angiopoietin-1, which shuts off the expression of BMPR1A, a transmembrane protein necessary for BMPR2 signalling, and thereby causes pulmonary artery smooth muscle cell proliferation. Additional biological abnormalities have been identified at all pulmonary arterial wall compartments of PAH patients. The endothelium produces an excess of endo-thelin, a potent vasoconstrictor and mitogenic mediator, while synthesis and release of antagonistic prostacyclin and nitric oxide is decreased. Pulmonary vascular smooth muscle cells present with an increased expression of a serotonin transporter, allowing for vasoconstrictive and mitogenic effects of increased circulating serotonin, and also show an increased expression of voltage-dependent potassium channels, which also promotes vasoreactivity and proliferation. The adventitial matrix bound metalloprotases appear to be activated in relation to increased serine elastase, leading to increased production of tenascin, a potent mitogen. While none of these abnormalities isolately explains PAH, their identification has already led to efficient therapeutic interventions, including the administration of prostacyclin derivatives and anti-endothelin compounds.

Chest Pain↗
PubMed2003

Endogenous endothelins and nitric oxide in hypoxic pulmonary vasoconstriction.

The effects of endothelin receptor blockade on the pulmonary circulation have been reported variably, possibly in relation to a more or less important associated release of endogenous nitric oxide (NO). The aim of this study was to test whether endothelin antagonism would inhibit hypoxic pulmonary vasoconstriction, and if it would not, then would it do so after NO synthase inhibition. Hypoxic pulmonary vasoconstriction (HPV) was evaluated in anesthetised dogs by the increase in the mean pulmonary artery pressure (Ppa) minus occluded Ppa (Ppao) gradient in response to hypoxia (inspiratory oxygen fraction of 0.1) at constant pulmonary blood flow. Bosentan, an endothelin A and B receptor antagonist, did not affect baseline Ppa, Ppao or systemic arterial pressure (Psa) and did not alter HPV (n=8). The NO synthase inhibitor N(G)-nitro-L-arginine (L-NA) did not affect baseline Ppa and Ppao, but increased Psa and enhanced HPV (n=12). The addition of bosentan in these dogs did not affect baseline Ppa or Ppao, but decreased Psa and inhibited HPV. Exhaled NO was decreased by L-NA and by bosentan and abolished by L-NA+bosentan (n=9). The authors conclude that endogenous nitric oxide is released by, and opposes the vasoconstricting effects of, endothelins in vivo, reducing systemic blood pressure and limiting hypoxic pulmonary vasoconstriction.

Animals↗
PubMed2003

Expression of the serotonin 1b receptor in experimental pulmonary hypertension.

The pathogenesis of pulmonary arterial hypertension (PAH) remains uncertain. Both the serotonin and endothelin (ET) systems are believed to be involved. Recent studies pointed to the importance of the serotonin 2B receptor as a limiting step. The current authors investigated the lung tissue expression of serotonin receptors and of the serotonin transporter (5-HTT) by real-time-quantitative polymerase chain reaction in chronic overcirculation-induced PAH in growing piglets, with and without treatment with the dual ET receptor blocker bosentan. Pulmonary haemodynamic changes were described by pulmonary arterial impedance spectra. Three months after the surgical anastomosis of the left subclavian artery to the pulmonary arterial trunk, there was a shift of the impedance spectra to higher ratios of pressure and flow moduli, with increases in both 0 Hz impedance and characteristic impedance, and these changes were completely prevented by bosentan therapy. There was an increase in the expression of the serotonin 1B receptor. There was no change in the expression of the 5-HTT, and of the serotonin 2B, 1D, and 4 receptors. The overexpression of the serotonin 1B receptor was partially prevented by bosentan therapy. The present authors conclude that this early pulmonary arterial hypertension model is characterised by an endothelin receptor-dependent increased expression of the serotonin 1B receptor.

Animals↗
PubMed2003

Single arterial occlusion to locate resistance in patients with pulmonary hypertension.

The purpose of this study was to determine the site of increased resistance using the arterial occlusion technique in patients with severe pulmonary hypertension. Pulmonary vascular resistance was partitioned in arterial and venous components based on double exponential fitting analysis of the pulmonary artery pressure decay curve: after balloon occlusion in 36 patients with pulmonary arterial hypertension (PAH); at baseline and during the inhalation of 20 parts per million of nitric oxide (NO); in four patients with chronic thromboembolic pulmonary hypertension; and in two patients with pulmonary veno-occlusive disease. In the patients with PAH, at baseline, mean pulmonary artery pressure was 56+/-2 mmHg (mean+/-SE), with an arterial component of resistance of 63+/-1%. Inhaled NO did not change the partition of resistance. The arterial component of resistance amounted on average to 42% and 77% in the patients with veno-occlusive disease and the patients with thromboembolic pulmonary hypertension, respectively. However, the partitioning of resistance did not discriminate between these three diagnostic categories. The occlusion technique may help to locate the predominant site of increased resistance in patients with severe pulmonary hypertension, but does not allow for a satisfactory differential diagnosis on an individual basis.

Balloon Occlusion↗
PubMed2002

Pathobiology of pulmonary arterial hypertension.

Recent years have witnessed important advances in the understanding of the pathophysiology of primary pulmonary hypertension (PPH). Both genetic and mechanistic studies have succeeded in identifying new molecular pathways relevant to the process of pulmonary vascular remodelling, which underlies PPH. Mutations in the type II bone morphogenetic protein (BMP) receptor (BMPR)-II are now considered to be the genetic basis for familial PPH and approximately 30% of cases of sporadic PPH. The identification of the relevance of the BMP pathway to the aetiology of PPH now raises many questions about the link between the BMPR-II mutant genotype and the PPH phenotype. As PPH does not develop in all subjects with BMPR-II mutations, environmental or associated genetic factors may play a crucial role. Among these, the finding of an association between PPH and the L-allelic variant of the serotonin transporter (5-HTT) gene indicates that 5-HTT, which controls smooth muscle hyperplasia, probably contributes to susceptibility to PPH or is an important modifier of the PPH phenotype. Recognition of these molecular pathways should provide insight into the pathogenesis not only of primary pulmonary hypertension, but also of secondary forms of pulmonary hypertension. This should soon lead to the development of new and more selective therapeutic approaches to pulmonary hypertension.

Bone Morphogenetic Protein Receptors, Type II↗
PubMed2001

Pulmonary hypertension associated with COPD.

Pulmonary hypertension is a common complication of chronic obstructive pulmonary disease (COPD). The increase in pulmonary artery pressures is often mild to moderate, but some patients may suffer from severe pulmonary hypertension, and present with a progressively downhill clinical course because of right-sided heart failure added to ventilatory handicap. The cause of pulmonary hypertension in COPD is generally assumed to be hypoxic pulmonary vasoconstriction leading to permanent medial hypertrophy. However, recent pathological studies point, rather, to extensive remodeling of the pulmonary arterial walls, with prominent intimal changes. These aspects account for minimal reversibility with supplemental oxygen. There may be a case for pharmacological treatment of pulmonary hypertension in selected patients with advanced COPD and right-sided heart failure. Candidate drugs include prostacyclin derivatives, endothelin antagonists and inhaled nitric oxide, all of which have been reported of clinical benefit in primary pulmonary hypertension. However, it will be a challenge for randomized controlled trials to overcome the difficulties of the diagnosis of right ventricular failure and the definition of a relevant primary endpoint in pulmonary hypertensive COPD patients.

Humans↗
PubMed2001

High-altitude pulmonary edema is initially caused by an increase in capillary pressure.

BACKGROUND: High-altitude pulmonary edema (HAPE) is characterized by severe pulmonary hypertension and bronchoalveolar lavage fluid changes indicative of inflammation. It is not known, however, whether the primary event is an increase in pressure or an increase in permeability of the pulmonary capillaries. METHODS AND RESULTS: We studied pulmonary hemodynamics, including capillary pressure determined by the occlusion method, and capillary permeability evaluated by the pulmonary transvascular escape of 67Ga-labeled transferrin, in 16 subjects with a previous HAPE and in 14 control subjects, first at low altitude (490 m) and then within the first 48 hours of ascent to a high-altitude laboratory (4559 m). The HAPE-susceptible subjects, compared with the control subjects, had an enhanced pulmonary vasoreactivity to inspiratory hypoxia at low altitude and higher mean pulmonary artery pressures (37 +/- 2 versus 26 +/- 1 mmHg, P<0.001) and pulmonary capillary pressures (19 +/- 1 versus 13 +/- 1 mmHg, P < 0.001) at high altitude. Nine of the susceptible subjects developed HAPE. All of them had a pulmonary capillary pressure >19 mm Hg (range 20 to 26 mmHg), whereas all 7 susceptible subjects without HAPE had a pulmonary capillary pressure < 19 mm Hg (range 14 to 18 mm Hg). The pulmonary transcapillary escape of radiolabeled transferrin increased slightly from low to high altitude in the HAPE-susceptible subjects but remained within the limits of normal and did not differ significantly from the control subjects. CONCLUSIONS: HAPE is initially caused by an increase in pulmonary capillary pressure.

Adult↗