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Rev Mal Respir ; 37(2): 171-179, 2020 Feb.
Article Fr | MEDLINE | ID: mdl-32061440

Right ventricular failure (RVF) is a common cause of admission to the intensive care unit and its presence is a major prognostic factor in acute pulmonary embolism (PE) and chronic pulmonary hypertension (PH). RVF results from an incapacity of the RV to adapt to an increase in afterload so it can become critical in acute PE and chronic PH. The presence of RVF in cases of acute PE with haemodynamic instability is an indication for thrombolytic therapy. RVF represents the most common cause of death in chronic PH. Factors triggering RV failure in PH, such as infection, PE, arrhythmias, or unplanned withdrawal of pulmonary arterial hypertension (PAH)-targeted therapy, have to be considered and treated if identified. However, RVF may also represent progression to end-stage disease. The management of RVF in patients with PH requires expertise and consists of optimization of fluid balance (with diuretics), cardiac output (with inotropic support such as dobutamine), perfusion pressure (with norepinephrine), and reduction of RV afterload with PAH-targeted therapies. Extracorporeal life support, lung transplantation or heart-lung transplantation should be considered in cases of refractory RVF in eligible patients.

Hypertension, Pulmonary/therapy , Pulmonary Embolism/therapy , Vascular Diseases/therapy , Ventricular Dysfunction, Right/therapy , Acute Disease , Critical Care/methods , Extracorporeal Membrane Oxygenation , Heart Failure/epidemiology , Heart Failure/etiology , Heart Failure/therapy , Heart-Lung Transplantation , Humans , Hypertension, Pulmonary/complications , Hypertension, Pulmonary/epidemiology , Hypertension, Pulmonary/physiopathology , Intensive Care Units , Lung Transplantation , Pulmonary Circulation/physiology , Pulmonary Embolism/complications , Pulmonary Embolism/epidemiology , Pulmonary Embolism/physiopathology , Vascular Diseases/complications , Vascular Diseases/epidemiology , Vascular Diseases/physiopathology , Ventricular Dysfunction, Right/complications , Ventricular Dysfunction, Right/epidemiology , Ventricular Dysfunction, Right/physiopathology
Respir Med Res ; 76: 48-53, 2019 Nov.
Article En | MEDLINE | ID: mdl-31557688

Klippel-Trenaunay syndrome (KTS) is a congenital disorder characterized by cutaneous capillary malformations, soft tissue and bone hypertrophy, and multiple capillary, venous or lymphatic malformations. KTS is associated with recurrent thromboembolic events. We reported herein five cases of chronic thromboembolic pulmonary hypertension (CTEPH) associated with KTS (age minimum-maximum 26-50 years old, 3 males/2 females). Hemodynamics showed severe pulmonary hypertension (PH) with pulmonary vascular resistance ranging from 5.6 to 18.3 Wood units (WU), associated with marked clinical impairment (NYHA functional class III or IV in 4 patients). Computed tomography (CT) of the chest and pulmonary angiography confirmed proximal CTEPH accessible to surgical intervention in one patient and distal forms of CTEPH in 4 patients. Evolution after pulmonary endarterectomy showed hemodynamic normalization, while the patients with distal CTEPH had severe outcomes with 2 early deaths after PH diagnosis (44 and 35 months respectively). One patient with distal CTEPH was still alive 16 years after diagnosis on specific PH therapy and one was transplanted after 15 years because of right heart failure (death after 12 months). Histological analysis of the lung explants showed typical chronic thromboembolic material specific for CTEPH. In conclusion, KTS may be complicated by severe CTEPH requiring careful anticoagulation and multidisciplinary follow-up in expert centers to screen for disease potentially accessible to endarterectomy. In the modern management era of CTEPH, balloon pulmonary angioplasty will certainly be an interesting option in patients with inoperable disease.

Hypertension, Pulmonary/etiology , Klippel-Trenaunay-Weber Syndrome/complications , Pulmonary Embolism/etiology , Adult , Chronic Disease , Female , Humans , Hypertension, Pulmonary/diagnosis , Klippel-Trenaunay-Weber Syndrome/diagnosis , Male , Middle Aged , Pulmonary Embolism/diagnosis , Thromboembolism/diagnosis , Thromboembolism/etiology
Rev Mal Respir ; 36(4): 433-437, 2019 Apr.
Article Fr | MEDLINE | ID: mdl-31010759

Pulmonary arterial hypertension (PAH) is a severe and incurable cardiopulmonary disorder. Research from the past 10 years illustrates the complex and multifactorial aspects of PAH pathophysiology. Furthermore, latest advances in the field have led to a better understanding of the key components underlying this inadequate accumulation of pulmonary vascular cells within the pulmonary arterial walls, leading to pulmonary vascular remodelling. Among the underlying molecular and cellular mechanisms, pulmonary endothelial dysfunction, alterations of the inter-cell communications within the pulmonary arterial walls as well as defects of the inflammatory component and the loss of BMPRII activity play critical roles in the pathogenesis of the disease.

Pulmonary Arterial Hypertension/etiology , Adaptive Immunity/physiology , Autoimmunity/physiology , Bone Morphogenetic Protein Receptors, Type II/genetics , Bone Morphogenetic Protein Receptors, Type II/metabolism , Endothelial Cells/physiology , Humans , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/genetics , Hypertension, Pulmonary/immunology , Hypertension, Pulmonary/physiopathology , Molecular Targeted Therapy/methods , Molecular Targeted Therapy/trends , Myocytes, Smooth Muscle/physiology , Pulmonary Arterial Hypertension/genetics , Pulmonary Arterial Hypertension/immunology , Pulmonary Arterial Hypertension/physiopathology , Pulmonary Artery/pathology , Pulmonary Artery/physiology , Signal Transduction/genetics , Vascular Remodeling/physiology
Rev Med Interne ; 39(12): 925-934, 2018 Dec.
Article Fr | MEDLINE | ID: mdl-30174113

About 70% patients waiting for liver transplantation have a dyspnea. Two pulmonary vascular disorders can be associated with portal hypertension or chronic liver diseases: portopulmonary hypertension (PoPH) related to pulmonary small arteries remodeling and obstruction and hepatopulmonary syndrome (HPS) characterized by pulmonary capillaries dilatations and proliferations. PoPH is defined by the combination of pulmonary arterial hypertension (PAH) (mean pulmonary artery pressure [PAP]≥25mmHg, with normal pulmonary artery wedge pressure≤15mmHg and pulmonary vascular resistance [PVR]>3 Wood units [WU]) and portal hypertension. HPS is a triad of intrapulmonary vascular dilatations, hypoxemia (increased alveolar-arterial oxygen gradient) and liver disease or isolated portal hypertension. The pathophysiology of both syndromes is complex and poorly understood. PoPH and HPS have a negative impact on functional and vital prognosis in patients with portal hypertension. Liver transplantation is the established treatment standard in HPS. PoPH treatment is improved over the years with the use of specific PAH treatment despite the lack of randomized assay in this indication. Liver transplantation could be considered in PoPH leading to stabilization, improvement or recovery in selected patients (mean PAP<35mmHg without severe right ventricular dysfunction and PVR<4 WU).

Liver Diseases , Lung Diseases , Vascular Diseases , Hepatopulmonary Syndrome/diagnosis , Hepatopulmonary Syndrome/epidemiology , Hepatopulmonary Syndrome/therapy , Humans , Hypertension, Portal/diagnosis , Hypertension, Portal/epidemiology , Hypertension, Portal/therapy , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/epidemiology , Hypertension, Pulmonary/therapy , Liver Diseases/complications , Liver Diseases/diagnosis , Liver Diseases/epidemiology , Liver Diseases/therapy , Lung Diseases/complications , Lung Diseases/diagnosis , Lung Diseases/epidemiology , Lung Diseases/therapy , Vascular Diseases/complications , Vascular Diseases/diagnosis , Vascular Diseases/epidemiology , Vascular Diseases/therapy , Vascular Resistance/physiology
Rev Mal Respir ; 35(2): 160-170, 2018 Feb.
Article Fr | MEDLINE | ID: mdl-29501213

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension (PH) characterized by preferential remodelling of pulmonary venules and angioproliferation. PVOD term includes idiopathic, heritable (biallelic mutations of EIF2AK4 gene), drugs and toxins induced (alkylating agents, organic solvents) and connectivite-associated forms (especially systemic-sclerosis associated form). PVOD and pulmonary arterial hypertension (PAH) share a similar clinical presentation. Lung biopsy is contraindicated in PVOD due to high risk of life-threatening bleeding. A noninvasive diagnostic approach, including oxygen parameters, low diffusing capacity for carbon monoxide and characteristic signs on high-resolution computed tomography of the chest, is used to support a diagnosis of PVOD. PVOD prognosis is worse than other forms of PAH. There is no evidence-based medical therapy for PVOD and life-threatening pulmonary edema may occur following PAH targeted therapy in PVOD. Lung transplantation remains the preferred definitive therapy for eligible patients.

Pulmonary Veno-Occlusive Disease , Animals , Diagnostic Imaging/methods , Disease Models, Animal , Humans , Pulmonary Veno-Occlusive Disease/diagnosis , Pulmonary Veno-Occlusive Disease/epidemiology , Pulmonary Veno-Occlusive Disease/therapy , Rare Diseases/diagnosis , Rare Diseases/epidemiology , Rare Diseases/therapy , Respiratory Function Tests/methods , Risk Factors
Rev Mal Respir ; 31(10): 893-902, 2014 Dec.
Article Fr | MEDLINE | ID: mdl-25496787

The biological mechanisms of aging, and more specifically cellular senescence, are increasingly a subject of research. Cellular senescence may be a common determinant of many age-related diseases, including some chronic lung diseases such as chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis. Many arguments suggest that these diseases are associated with premature senescence of lung cells, which may be involved in the pathophysiology of respiratory alterations. Furthermore, these diseases are associated with systemic manifestations, such as bone loss, muscle wasting and atherosclerosis, which impact on symptoms and prognosis. Whether these alterations are related to a common pathogenic mechanism or develop independently in patients with COPD remains an open question. In this review, we will focus on cellular senescence and COPD. Two concepts will be discussed: (1) the role of cell senescence in the pathophysiology of lung destruction, vascular remodeling and inflammation in COPD, (2) the possible link between the pulmonary and systemic manifestations of COPD which could reflect a general process of accelerated aging.

Cellular Senescence/physiology , Lung Diseases/etiology , Pulmonary Disease, Chronic Obstructive/etiology , Aging/physiology , Animals , Humans , Lung Diseases/pathology , Pulmonary Disease, Chronic Obstructive/pathology , Pulmonary Emphysema/pathology , Signal Transduction/genetics
Rev Mal Respir ; 29(4): 491-500, 2012 Apr.
Article Fr | MEDLINE | ID: mdl-22542407

Pulmonary arterial hypertension (PAH) is a rare but potentially fatal complication of human immunodeficiency virus (HIV). It may occur in HIV-1 or 2 infection, irrespective of the route of transmission or the degree of immunosuppression. The improved survival of patients infected with HIV in the era of highly active antiretroviral therapy (HAART) justifies systematic screening for PAH according to an algorithm in patients with unexplained dyspnea. In all cases, right heart catheterization must be performed to establish the definitive diagnosis of pulmonary hypertension. The prevalence of PAH is about 0.5% in patients with HIV infection. A beneficial effect of HAART on the course of HIV-related PAH has not been clearly established. In contrast, PAH-specific therapies such as epoprostenol and bosentan have been demonstrated to be efficacious for short- and long-term outcomes in this context. Notably, some patients pulmonary hemodynamics and functional class normalized or near normalized with these treatments. Other PAH-specific therapies remain to be evaluated. The advent of HAART associated with the development of PAH-specific therapies has improved the prognosis of patients HIV-related PAH, with a survival rate of about 70% at 3 years.

HIV Infections/complications , HIV-1/physiology , Hypertension, Pulmonary/etiology , Diagnostic Techniques, Cardiovascular , Diagnostic Techniques, Respiratory System , HIV Infections/diagnosis , HIV Infections/epidemiology , HIV Infections/therapy , Humans , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/epidemiology , Hypertension, Pulmonary/therapy , Models, Biological
Arthritis Rheum ; 64(9): 2995-3005, 2012 Sep.
Article En | MEDLINE | ID: mdl-22549387

OBJECTIVE: Pulmonary venoocclusive disease (PVOD) is an uncommon form of pulmonary hypertension (PH) characterized by obstruction of small pulmonary veins. Pulmonary venous involvement has been reported in pathologic assessment of patients with systemic sclerosis (SSc) presenting with precapillary PH. High-resolution computed tomography (HRCT) of the chest is a noninvasive diagnostic tool used to screen for PVOD. No HRCT data are available on SSc patients with precapillary PH. We undertook this study to evaluate the frequency and effect on prognosis of HRCT signs of PVOD in SSc patients with precapillary PH. METHODS: We reviewed chest HRCT data from 26 SSc patients with precapillary PH and 28 SSc patients without pulmonary arterial hypertension (PAH) or interstitial lung disease (ILD). RESULTS: The radiographic triad of HRCT signs of PVOD (lymph node enlargement [57.7% versus 3.6%], centrilobular ground-glass opacities [46.2% versus 10.7%], and septal lines [88.5% versus 7.1%]) was significantly more frequent in SSc patients with precapillary PH than in SSc patients without PAH or ILD (all P < 0.005). Indeed, 61.5% of SSc patients with precapillary PH had ≥ 2 of these signs. Cardiomegaly (P < 0.0001), pulmonary artery enlargement (P < 0.0001), and pericardial effusion (P < 0.0005) were also significantly more frequent in SSc patients with precapillary PH. Pulmonary venous involvement was histologically confirmed in 2 patients with radiographic signs of PVOD. The presence of ≥ 2 radiographic signs of PVOD was associated with the occurrence of pulmonary edema after initiation of PAH-specific therapy (in 8 of 16 patients) and with more rapid progression from diagnosis of PH to death. CONCLUSION: HRCT signs of PVOD are frequently observed in SSc patients with precapillary PH, correlated with histologic assessment, and were associated with a high risk of pulmonary edema.

Hypertension, Pulmonary/diagnostic imaging , Pulmonary Veno-Occlusive Disease/diagnostic imaging , Scleroderma, Systemic/diagnostic imaging , Adult , Aged , Aged, 80 and over , Female , Humans , Hypertension, Pulmonary/complications , Male , Middle Aged , Prognosis , Pulmonary Veno-Occlusive Disease/complications , Radiography , Scleroderma, Systemic/complications
Eur Respir J ; 39(2): 313-8, 2012 Feb.
Article En | MEDLINE | ID: mdl-21737562

The mean pulmonary artery pressure (P(pa)) achieved on mild-to-moderate exercise is age related and its haemodynamic correlates remain to be documented in patients free of pulmonary hypertension (PH). Our retrospective study involved patients free of PH investigated in our centre for possible pulmonary vascular disease between January 1, 2007 and October 31, 2009 who underwent right heart catheterisation at rest and during supine exercise up to 60 W. The 38 out of 99 patients aged <50 yrs were included and a P(pa) of 30 mmHg was considered the upper limit of normal on exercise. The 24 subjects who developed P(pa)>30 mmHg on exercise had higher resting P(pa) (19±3 versus 15±4 mmHg) and indexed pulmonary vascular resistance (PVRi; 3.4±1.5 versus 2.2±1.1 WU·m(2); p<0.05) than the remaining 14 subjects. Resting P(pa) >15 mmHg predicted exercise P(pa) >30 mmHg with 88% sensitivity and 57% specificity. The eight patients with resting P(pa) 22-24 mmHg all had exercise P(pa) >30 mmHg. In subjects aged <50 yrs investigated for possible pulmonary vascular disease and free of PH, patients with mild-to-moderate exercise P(pa) >30 mmHg had higher resting PVRi and higher resting P(pa), although there was no resting P(pa) threshold value that could predict normal response on mild-to-moderate exercise. The clinical relevance of such findings deserves further long-term follow-up studies.

Cardiac Output/physiology , Exercise/physiology , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/physiopathology , Pulmonary Wedge Pressure/physiology , Rest/physiology , Adult , Cardiac Catheterization , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Pulmonary Artery/physiology , ROC Curve , Retrospective Studies , Sensitivity and Specificity , Supine Position
Int J Clin Pract Suppl ; (169): 11-8, 2011 Jan.
Article En | MEDLINE | ID: mdl-21176011

Portopulmonary hypertension (PoPH) is a rare but life-threatening complication of portal hypertension that is characterised by proliferative changes in the pulmonary microvasculature indistinguishable from other forms of pulmonary arterial hypertension (PAH). Although PoPH is most commonly observed in the setting of cirrhosis, patients with non-cirrhotic portal hypertension are also at risk of developing the disorder. A definitive diagnosis requires invasive haemodynamic confirmation by right heart catheterisation and screening for PoPH should be routinely performed in all patients being considered for liver transplantation. Although severe PoPH is considered a contraindication to liver transplantation, there is now compelling data supporting the use of PAH-specific therapies with the aim of improving pulmonary haemodynamics to allow transplantation to be successfully performed. This review explores possible relevant aetiological factors and summarises current diagnostic and therapeutic approaches for PoPH patients.

Hypertension, Portal/complications , Hypertension, Pulmonary/complications , Diuretics/therapeutic use , Endothelin Receptor Antagonists , Hemodynamics/physiology , Humans , Hypertension, Portal/diagnosis , Hypertension, Portal/drug therapy , Hypertension, Portal/physiopathology , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/physiopathology , Phosphodiesterase 5 Inhibitors/therapeutic use , Pulmonary Circulation/physiology
Eur Respir J ; 36(3): 549-55, 2010 Sep.
Article En | MEDLINE | ID: mdl-20562126

Pulmonary arterial hypertension (PAH) is a progressive, fatal disease. We studied 674 consecutive adult patients who were prospectively enrolled in the French PAH registry (121 incident and 553 prevalent cases). Two survival analyses were performed. First, the cohort of 674 patients was followed for 3 yrs after study entry and survival rates described. Then, we focused on the subset with incident idiopathic, familial and anorexigen-associated PAH (n = 56) combined with prevalent patients who were diagnosed <3 yrs prior to study entry (n = 134). In the cohort of 674 patients, 1-, 2-, and 3-yr survival rates were 87% (95% CI 84-90), 76% (95% CI 73-80), and 67% (95% CI 63-71), respectively. In prevalent idiopathic, familial and anorexigen-associated PAH, 1-, 2-, and 3-yr survival rates were higher than in incident patients (p = 0.037). In the combined cohort of patients with idiopathic, familial and anorexigen-associated PAH, multivariable analysis showed that survival could be estimated by means of a novel risk-prediction equation using patient sex, 6-min walk distance, and cardiac output at diagnosis. This study highlights survivor bias in prevalent cohorts of PAH patients. Survival of idiopathic, familial and anorexigen-associated PAH can be characterised by means of a novel risk-prediction equation using patients' characteristics at diagnosis.

Hypertension, Pulmonary , Aged , Cohort Studies , Familial Primary Pulmonary Hypertension , Female , Humans , Hypertension, Pulmonary/epidemiology , Hypertension, Pulmonary/mortality , Male , Middle Aged , Multivariate Analysis , Prevalence , Pulmonary Medicine/methods , Risk Factors , Treatment Outcome
Eur Respir J ; 33(1): 92-8, 2009 Jan.
Article En | MEDLINE | ID: mdl-18799506

Bosentan has proven 4-month efficacy in patients with HIV-associated pulmonary arterial hypertension (PAH-HIV). Herein, the long-term outcome of unselected PAH-HIV patients treated with first-line bosentan is described. Data for 59 consecutive World Health Organization (WHO) functional class II-IV PAH-HIV patients treated with first-line bosentan between May 2002 and July 2007 were analysed. HIV status, 6-min walk distance and haemodynamics were assessed at baseline, after 4 months and every 6-12 months thereafter. After 4 months, 6-min walk distance increased from 358+/-98 to 435+/-89 m and pulmonary vascular resistance decreased from 737+/-328 to 476+/-302 dyn x s x cm(-5). At the final evaluation (29+/-15 months), 6-min walk distance remained stable and pulmonary vascular resistance decreased further to 444+/-356 dyn x s x cm(-5). Haemodynamics normalised in 10 patients. At their last evaluation, these 10 patients were in WHO functional class I, with a 6-min walk distance of 532+/-52 m. Overall survival estimates were 93, 86 and 66% at 1, 2 and 3 yrs, respectively. Bosentan was safe when combined with highly active antiretroviral therapy, with no negative impact on HIV infection control. The present data confirm the long-term benefits of bosentan therapy in HIV-associated pulmonary arterial hypertension patients with improvements in symptoms, 6-min walk distance and haemodynamics, and with favourable overall survival.

Antihypertensive Agents/administration & dosage , HIV Infections/complications , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/virology , Sulfonamides/administration & dosage , Adult , Antiretroviral Therapy, Highly Active , Bosentan , Cohort Studies , Disease-Free Survival , Drug Administration Schedule , Exercise Tolerance , Female , HIV Infections/drug therapy , HIV Infections/physiopathology , Humans , Hypertension, Pulmonary/physiopathology , Male , Middle Aged , Retrospective Studies , Treatment Outcome
Eur Respir Rev ; 18(114): 272-90, 2009 Dec.
Article En | MEDLINE | ID: mdl-20956152

Pulmonary hypertension (PH) comprises a heterogeneous group of disorders characterised by increased pulmonary vascular resistance that results in progressive right ventricular failure. In order to translate current evidence into routine clinical practice, the European Society of Cardiology (ESC) and the European Respiratory Society (ERS) have recently jointly proposed evidence-based guidelines for the optimal management of different PH patient groups. This article describes a series of clinical cases of PH due to various aetiologies that were referred to a large national PH expert referral centre. In each case, the assessment and therapeutic approach undertaken is described in the context of the new ECS/ERS guidelines. The routine diagnostic work-up of suspected idiopathic pulmonary arterial hypertension (PAH) and recommended treatments for patients with functional class II, III and IV disease is emphasised. Familial screening and management of heritable PAH is discussed. Appropriate investigation and therapeutic strategies for patients with chronic thromboembolic disease and PH that is associated with congenital heart disease, pulmonary veno-occlusive disease and systemic sclerosis are also highlighted.

Guideline Adherence , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/therapy , Adult , Aged , Algorithms , Child , Female , Humans , Male , Middle Aged , Practice Guidelines as Topic , Referral and Consultation , Young Adult
Am J Physiol Lung Cell Mol Physiol ; 293(4): L1045-52, 2007 Oct.
Article En | MEDLINE | ID: mdl-17675372

Serotonin [5-hydroxytryptamine (5-HT)] biosynthesis depends on two rate-limiting tryptophan hydroxylases (Tph): Tph1, which is expressed in peripheral organs, and Tph2, which is expressed in neurons. Because 5-HT is involved in pulmonary hypertension (PH), we investigated whether genetic variations in Tph1 and/or Tph2 affected PH development in mice. To examine the functional impact of peripheral Tph1 deficiency on hypoxic PH, we used Tph1(-/-) mice characterized by very low 5-HT synthesis rates and contents in the gut and lung and increased 5-HT synthesis in the forebrain. With chronic hypoxia, 5-HT synthesis in the forebrain increased further. Hypoxic PH, right ventricular hypertrophy, and distal pulmonary artery muscularization were less severe (P < 0.001) than in wild-type controls. The Tph inhibitor p-chlorophenylalanine (100 mgxkg(-1)xday(-1)) further improved these parameters. We then investigated whether mouse strains harboring the C1473G polymorphism of the Tph2 gene showed different PH phenotypes during hypoxia. Forebrain Tph activity was greater and hypoxic PH was more severe in C57Bl/6 and 129X1/SvJ mice homozygous for the 1473C allele than in DBA/2 and BALB/cJ mice homozygous for the 1473G allele. p-Chlorophenylalanine reduced PH in all groups and abolished the difference in PH severity across mouse strains. Hypoxia increased 5-hydroxytryptophan accumulation but decreased 5-HT contents in the forebrain and lung, suggesting accelerated 5-HT turnover during hypoxia. These results provide evidence that dysregulation of 5-HT synthesis is closely linked to the hypoxic PH phenotype in mice and that Tph1 and Tph2 may contribute to PH development.

Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/physiopathology , Hypoxia/complications , Polymorphism, Genetic , Tryptophan Hydroxylase/deficiency , Tryptophan Hydroxylase/genetics , Animals , Chronic Disease , Enzyme Inhibitors/pharmacology , Fenclonine/pharmacology , Hypertension, Pulmonary/genetics , Intestinal Mucosa/metabolism , Lung/metabolism , Mice , Mice, Inbred Strains , Mice, Knockout , Prosencephalon/metabolism , Pulmonary Artery/physiopathology , Serotonin/biosynthesis , Serotonin/metabolism , Severity of Illness Index
Rev Pneumol Clin ; 63(3): 202-10, 2007 Jun.
Article Fr | MEDLINE | ID: mdl-17675944

Bronchiectasis, cancer and tuberculosis account for the majority of haemoptysis requiring intensive care unit admission. Bedside evaluation (volume and bronchoscopic active bleeding) is safe to screen patients for arteriography and bronchial artery embolisation (BAE). First-line interventional arteriography should be favour over surgery in patients with non traumatic life-threatening hemoptysis. Surgery must be reserved in cases of failure or recurrence of bleeding after BAE.

Critical Care , Hemoptysis/therapy , Blood , Bronchoscopy , Embolization, Therapeutic , Hemoptysis/classification , Hemoptysis/etiology , Hemoptysis/surgery , Hospitals, University , Humans , Oxygen Inhalation Therapy , Paris , Tomography, X-Ray Computed
Eur Respir J ; 23(5): 752-8, 2004 May.
Article En | MEDLINE | ID: mdl-15176692

Inhibition of tumour necrosis factor-alpha (TNF-alpha), levels of which are increased in the blood of cirrhotic rats, prevents hyperdynamic circulatory state, mainly by decreasing the vascular overproduction of nitric oxide. Hepatopulmonary syndrome, which is characterised by intrapulmonary vascular dilatation and increased alveolar to arterial oxygen tension difference (PA-a,O2), is mainly related to pulmonary over-production of NO by macrophages accumulated in lung vessels. Since TNF-alpha is a potent activator of macrophagic inducible nitric oxide synthase (NOS), the aim of this study was to investigate whether TNF-alpha inhibition prevented hepatopulmonary syndrome and hyperdynamic circulatory state in rats with cirrhosis. TNF-alpha was inhibited by 5 weeks of pentoxifylline (10 mg x kg body weigh(-1) x day(-1)) in rats with cirrhosis induced by common bile duct ligation. Cardiac output, pulmonary and systemic vascular resistance, PA-a,O2 and cerebral uptake of intravenous technetium-99m-labelled albumin macroaggregates (which reflects intrapulmonary vascular dilatation) were similar in sham- and pentoxifylline-treated cirrhotic rats. Blood TNF-alpha concentrations and pulmonary intravascular macrophage sequestration, as assessed by morphometric analysis and radioactive colloid uptake, were decreased with pentoxifylline. Pentoxifylline also prevented increases in aorta and lung NOS activities and inducible NOS expression. Thus pentoxifylline prevents development of hyperdynamic circulatory state and hepatopulmonary syndrome, probably by inhibiting the effects of tumour necrosis factor-alpha on vascular nitric oxide synthase and intravascular macrophages. These results support an important role for tumour necrosis factor-alpha in the genesis of hepatopulmonary syndrome.

Enzyme Inhibitors/pharmacology , Hepatopulmonary Syndrome/prevention & control , Liver Cirrhosis/physiopathology , Pentoxifylline/pharmacology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Animals , Aorta/enzymology , Bacterial Translocation/drug effects , Blood Cells/pathology , Blood Circulation/drug effects , Hemodynamics/drug effects , Liver Cirrhosis/blood , Liver Cirrhosis/metabolism , Liver Cirrhosis/microbiology , Lung/enzymology , Macrophages/pathology , Male , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/metabolism , Phagocytosis , Pulmonary Circulation/drug effects , Rats , Rats, Wistar , Tumor Necrosis Factor-alpha/metabolism