Decreased pulmonary vascular distensibility in adolescents conceived by in vitro fertilization.

STUDY QUESTION: What is the functional relevance of decreased pulmonary vascular distensibility in adolescents conceived by IVF? SUMMARY ANSWER: Children born by IVF have a slight decrease in pulmonary vascular distensibility observed during normoxic exercise that is not associated with altered right ventricular function and aerobic exercise capacity. WHAT IS KNOWN ALREADY: General vascular dysfunction and increased hypoxic pulmonary hypertension have been reported in ART children as compared to controls. Pulmonary hypertension or decreased pulmonary vascular distensibility may affect right ventricular function and thereby possibly limit maximal cardiac output and aerobic exercise capacity. STUDY DESIGN, SIZE, DURATION: This prospective case-control study enrolled 15 apparently healthy adolescents conceived by IVF/ICSI after fresh embryo transfer paired in a 2 to 1 ratio to 30 naturally conceived adolescents between March 2015 and May 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Fifteen IVF/ICSI adolescents and 30 controls from singleton gestations matched by age, gender, weight, height and physical activity underwent exercise echocardiography, lung diffusion capacity measurements and a cycloergometer cardiopulmonary exercise test. A pulmonary vascular distensibility coefficient α was determined from the pulmonary arterial pressure (PAP) versus cardiac output (Q) relationships. Pulmonary capillary volume (Vc) was calculated from single breath nitric oxide and carbon monoxide lung diffusion capacity measurements (DLCO and DLNO) at rest and during exercise (100 W). Eight of the IVF subjects and eight controls underwent a 30 min hypoxic challenge at rest with a fraction of inspired oxygen of 0.12 to assess hypoxic pulmonary vasoconstriction. MAIN RESULTS AND THE ROLE OF CHANCE: In normoxia, oxygen uptake (VO2), blood pressure, DLCO, DLNO, echocardiographic indices of right ventricular function, Q and PAP at rest and during exercise were similar in both groups. However, IVF children had a lower pulmonary vascular distensibility coefficient α (1.2 ± 0.3 versus 1.5 ± 0.3%/mmHg, P = 0.02) and a blunted exercise-induced increase in Vc (24 versus 32%, P < 0.05). Hypoxic-induced increase in pulmonary vascular resistance in eight IVF subjects versus eight controls was similar. LIMITATIONS, REASONS FOR CAUTION: The IVF cohort was small, and thus type I or II errors could have occurred in spite of careful matching of each case with two controls. ART evolved over the years, so that it is not certain that the presently reported subtle changes will be reproducible in the future. As the study was limited to singletons born after fresh embryo transfers, our observations cannot be extrapolated to singletons born after frozen embryo transfer. WIDER IMPLICATIONS OF THE FINDINGS: The present study suggests that adolescents conceived by IVF have preserved right ventricular function and aerobic exercise capacity despite a slight alteration in pulmonary vascular distensibility as assessed by two entirely different methods, i.e. exercise echocardiography and lung diffusing capacity measurements. However, the long-term prognostic relevance of this slight decrease in pulmonary vascular distensibility needs to be evaluated in prospective large scale and long-term outcome studies. STUDY FUNDING/COMPETING INTEREST(S): Dr Caravita was supported by an ERS PAH short term research training fellowship (STRTF2014-5264). Dr Pezzuto was funded by an Italian Society of cardiology grant. Dr Motoji was supported by a grant from the Cardiac Surgery Funds, Belgium. All authors have no conflicts of interests to declare.

Effects of ß2-adrenergic stimulation on exercise capacity in normal subjects.

ß2-Adrenergic receptor agonists are believed to present with ergogenic properties. However, how combined respiratory, cardiovascular and muscular effects of these drugs might affect exercise capacity remain incompletely understood. The effects of salbutamol were investigated in 23 healthy subjects. The study was randomised, placebo-controlled in double-blind and followed a cross-over design. Salbutamol was given at the dose of 10 µg/min in 11 subjects and 20 µg/min iv in the other 12 subjects. Measurements included muscle sympathetic nerve activity (MSNA), ventilatory responses to hyperoxic hypercapnia (7% CO(2) in O(2,) central chemoreflex), isocapnic hypoxia (10% O(2) in N(2), peripheral chemoreflex) and isometric muscle contraction followed by a local circulatory arrest (metaboreflex), cardiopulmonary exercise test (CPET) variables and isokinetic muscle strength. Salbutamol 10 µg/min increased heart rate and blood pressure, while MSNA burst frequency remained unchanged. Peripheral chemosensitivity increased, as evidenced by an increased ventilatory response to hypoxia, but ventilatory responses to hypercapnia or muscle ischaemia remained unchanged. The effects of salbutamol 20 µg/min were similar. Both doses of salbutamol did not affect CPET. Only the higher dose of salbutamol decreased the anaerobic threshold, but this was not associated with a change in VO(2) max. Salbutamol increased the slopes of ventilation as a function of VO(2) (P < 0.05) and VCO(2) (P < 0.001) during CPET. Maximal isokinetic muscle strength was not affected by salbutamol. In conclusion, the acute administration of either low or high dose salbutamol does not affect exercise capacity in normal subjects, in spite of an earlier anaerobic threshold and increased chemosensitivity.

Exercise stress echocardiography for the study of the pulmonary circulation.

Exercise stress tests have been used for the diagnosis of pulmonary hypertension, but with variable protocols and uncertain limits of normal. The pulmonary haemodynamic response to progressively increased workload and recovery was investigated by Doppler echocardiography in 25 healthy volunteers aged 19-62 yrs (mean 36 yrs). Mean pulmonary artery pressure ((Ppa)) was estimated from the maximum velocity of tricuspid regurgitation. Cardiac output (Q) was calculated from the aortic velocity-time integral. Slopes and extrapolated pressure intercepts of (Ppa)-Q plots were calculated after using the adjustment of Poon for individual variability. A pulmonary vascular distensibility alpha was calculated from each (Ppa)-Q plot to estimate compliance. (Ppa) increased from 14+/-3 mmHg to 30+/-7 mmHg, and decreased to 19+/-4 mmHg after 5 min recovery. The slope of (Ppa)-Q was 1.37+/-0.65 mmHg x min(-1) x L(-1) with an extrapolated pressure intercept of 8.2+/-3.6 mmHg and an alpha of 0.017+/-0.018 mmHg(-1). These results agree with those of previous invasive studies. Multipoint (pa)-Q plots were well described by a linear approximation, from which resistance can be calulated. We conclude that exercise echocardiography of the pulmonary circulation is feasible and provides realistic resistance and compliance estimations. Measurements during recovery are unreliable because of rapid return to baseline.

Pulmonary artery pressure limits exercise capacity at high altitude.

Altitude exposure is associated with decreased exercise capacity and increased pulmonary vascular resistance (PVR). Echocardiographic measurements of pulmonary haemodynamics and a cardiopulmonary exercise test were performed in 13 healthy subjects at sea level, in normoxia and during acute hypoxic breathing (1 h, 12% oxygen in nitrogen), and in 22 healthy subjects after acclimatisation to an altitude of 5,050 m. The measurements were obtained after randomisation, double-blinded to the intake of placebo or the endothelin A receptor blocker sitaxsentan (100 mg·day(-1) for 7 days). Blood and urine were sampled for renal function measurements. Normobaric as well as hypobaric hypoxia increased PVR and decreased maximum workload and oxygen uptake (V'(O(2),max)). Sitaxsentan decreased PVR in acute and chronic hypoxia (both p<0.001), and partly restored V'(O(2),max), by 30 % in acute hypoxia (p<0.001) and 10% in chronic hypoxia (p<0.05). Sitaxsentan-induced changes in PVR and V'(O(2),max) were correlated (p = 0.01). Hypoxia decreased glomerular filtration rate and free water clearance, and increased fractional sodium excretion. These indices of renal function were unaffected by sitaxsentan intake. Selective endothelin A receptor blockade with sitaxsentan improves mild pulmonary hypertension and restores exercise capacity without adverse effects on renal function in hypoxic normal subjects.

Digoxin increases peripheral chemosensitivity and the ventilatory response to exercise in normal subjects.

1. The contribution of peripheral chemoreceptors to the regulation of ventilation during exercise remains incompletely understood. Digoxin has been reported to increase chemoreflex sensitivity in humans. In the present randomized, cross-over, double-blind study, we tested the hypothesis that this increases the ventilatory response to exercise in normal subjects, as assessed by changes in minute ventilation (V(E)) in response to the rate of CO(2) production (VCO(2)). 2. Minute ventilation, end-tidal PCO(2), pulse oximetric O(2) saturation (S(p)O(2)), heart rate and blood pressure (BP) were measured in 11 healthy young male untrained subjects after intravenous infusion of digoxin (0.01 mg/kg) or placebo during normoxia, isocapnic hypoxia and hyperoxic hypercapnoea. All participants underwent a maximum cardiopulmonary exercise test. 3. During normoxia, digoxin increased systolic BP only. During hypoxia, digoxin increased V(E) compared with placebo (P = 0.009) for the same fall in S(p)O(2) (P = NS). Moreover, no significant effects on ventilation and haemodynamic responses were recorded during hypercapnoea. Digoxin increased the V(E) /VCO(2) slope above the anaerobic threshold from 30.4 +/- 2.9 to 32.8 +/- 3.7 (P < 0.05), but did not affect VO(2max). 4. In conclusion, enhanced peripheral chemosensitivity with digoxin increases the ventilatory response to CO(2) production above the anaerobic threshold, but does not affect exercise capacity in healthy humans.

Differential effects of sevoflurane and propofol anesthesia on left ventricular-arterial coupling in dogs.

BACKGROUND: General anesthetics interfere with arterial and ventricular mechanical properties, often altering left ventricular-arterial (LVA) coupling. We hypothesized that sevoflurane and propofol alter LVA coupling by different effects on arterial and ventricular properties. METHODS: Experiments were conducted in six anesthetized open-chest dogs for the measurement of left ventricular pressure and aortic pressure and flow. Measurements were performed during anesthesia with 0.5, 1.0 and 1.5 minimum alveolar concentration sevoflurane and 12, 24 and 36 mg/kg/h propofol. LVA coupling was assessed as the ratio of ventricular end-systolic elastance (E(es), measuring ventricular contractility) to effective arterial elastance (E(a), measuring ventricular afterload). The steady component of afterload, arterial tone, was assessed by systemic vascular resistance and arterial pressure-flow curves. The pulsatile component of afterload was assessed by aortic impedance and compliance. RESULTS: Sevoflurane decreased aortic pressure and cardiac output more than propofol. Sevoflurane reduced arterial tone, increased arterial stiffness and did not affect wave reflections. It increased E(a), decreased E(es) and reduced LVA coupling. Propofol reduced arterial tone, did not affect arterial stiffness and decreased wave reflections. It did not affect E(a), E(es) or LVA coupling. CONCLUSIONS: Sevoflurane increased ventricular afterload and decreased ventricular performance, thereby altering LVA coupling. Propofol did not affect ventricular afterload or ventricular performance, thereby preserving LVA coupling. Thus, propofol preserves LVA coupling in dogs better, and might be a better choice for patients with compromised left ventricular function.

End-points and clinical trial design in pulmonary arterial hypertension: have we made progress?

There is enormous interest in the treatment of pulmonary arterial hypertension (PAH), so it is appropriate to consider the design of trials of new therapies and the end-points to be measured when trying to decide whether or not a therapy is effective. In May 2003, the first meeting devoted solely to the discussion of end-points and trial design in PAH was held in Gleneagles, UK. At that time, most of the randomised controlled trials in PAH had used 6-min walking distance and/or resting haemodynamics as their primary end-points. The present article considers the progress that has been made since 2003. It deals with aspects of clinical trial design (such as noninferiority, superiority and withdrawal trials), considers end-points used in previous and current studies (such as 6-min walking distance, time to clinical worsening, haemodynamics, imaging and plasma brain natriuretic peptide), and considers what end-points might be used in the future. The second end-points meeting was held in Turnberry, UK, in June 2007. It had a similar format to the first meeting. Much of what is presented here is a summary of the workshops from that meeting. An attempt has been made to both summarise the current state of end-points and trial design and suggest new ways in which they could be improved. The present article forms one of a series being published in the European Respiratory Journal on pulmonary hypertension.

Bone morphogenetic protein signalling in heritable versus idiopathic pulmonary hypertension.

Mutations in the gene encoding bone morphogenetic protein (BMP) receptor type 2 (BMPR-2) have been reported in pulmonary arterial hypertension (PAH), but their functional relevance remains incompletely understood. BMP receptor expression was evaluated in human lungs and in cultured pulmonary artery smooth muscle cells (PASMCs) isolated from 19 idiopathic PAH patients and nine heritable PAH patients with demonstrated BMPR-2 mutations. BMP4-treated PASMCs were assessed for Smad and p38 mitogen-activated protein kinase (MAPK) signalling associated with mitosis and apoptosis. Lung tissue and PASMCs from heritable PAH patients presented with decreased BMPR-2 expression and variable increases in BMPR-1A and BMPR-1B expression, while a less important decreased BMPR-2 expression was observed in PASMCs from idiopathic PAH patients. Heritable PAH PASMCs showed no increased phosphorylation of Smad1/5/8 in the presence of BMP4, which actually activated the p38MAPK pathway. Individual responses varied from one mutation to another. PASMCs from PAH patients presented with an in vitro proliferative pattern, which could be inhibited by BMP4 in idiopathic PAH but not in heritable PAH. PASMCs from idiopathic PAH and more so from heritable PAH presented an inhibition of BMP4-induced apoptosis. Most heterogeneous BMPR-2 mutations are associated with defective Smad signalling compensated for by an activation of p38MAPK signalling, accounting for PASMC proliferation and deficient apoptosis.

Pulmonary hypertension in COPD.

Mild-to-moderate pulmonary hypertension is a common complication of chronic obstructive pulmonary disease (COPD); such a complication is associated with increased risks of exacerbation and decreased survival. Pulmonary hypertension usually worsens during exercise, sleep and exacerbation. Pulmonary vascular remodelling in COPD is the main cause of increase in pulmonary artery pressure and is thought to result from the combined effects of hypoxia, inflammation and loss of capillaries in severe emphysema. A small proportion of COPD patients may present with "out-of-proportion" pulmonary hypertension, defined by a mean pulmonary artery pressure >35-40 mmHg (normal is no more than 20 mmHg) and a relatively preserved lung function (with low to normal arterial carbon dioxide tension) that cannot explain prominent dyspnoea and fatigue. The prevalence of out-of-proportion pulmonary hypertension in COPD is estimated to be very close to the prevalence of idiopathic pulmonary arterial hypertension. Cor pulmonale, defined as right ventricular hypertrophy and dilatation secondary to pulmonary hypertension caused by respiratory disorders, is common. More studies are needed to define the contribution of cor pulmonale to decreased exercise capacity in COPD. These studies should include improved imaging techniques and biomarkers, such as the B-type natriuretic peptide and exercise testing protocols with gas exchange measurements. The effects of drugs used in pulmonary arterial hypertension should be tested in chronic obstructive pulmonary disease patients with severe pulmonary hypertension. In the meantime, the treatment of cor pulmonale in chronic obstructive pulmonary disease continues to rest on supplemental oxygen and a variety of measures aimed at the relief of airway obstruction.

Right ventricular function in scleroderma-related pulmonary hypertension.

SSc-associated pulmonary arterial hypertension (PAH) has a poorer prognosis than that of other types of pulmonary hypertension. Recent echocardiographic and haemodynamic studies suggest that right ventriculer (RV) pump function and filling characteristics are altered in SSc-PAH as compared with idiopathic PAH. This could be explained by intrinsic myocardial involvement of the disease, related to abnormal collagen deposition, also observed in the left ventricle, or an increased vulnerability to ischaemia due to coronary vasculopathy, abnormal collagen cross-linking and altered myocyte function. It is also possible that a relatively more important decrease in pulmonary arterial compliance as evidenced by recently reported increased characteristic impedance measurements, would contribute to RV-arterial decoupling. More pathological, imaging and haemodynamic studies are needed for a better understanding for relatively more important vulnerability of the RV in SSc-PAH.

Outcome measures in pulmonary arterial hypertension associated with systemic sclerosis.

SSc is complicated in approximately 10% of the patients by pulmonary arterial hypertension (PAH), a rare dyspnoea-fatigue syndrome caused by an increase in pulmonary vascular resistance. The prognosis of SSc-PAH is particularly poor, with estimated survival rates of approximately 50% at 2 yrs without pulmonary circulation-targeted therapies. Prostacyclins, endothelin receptor antagonists and phosphodiesterase-5 inhibitors have been shown to be efficacious in PAH, with persistent long-term benefit and approximate doubling of survival rate, and these encouraging results appear transposable to the SSc-PAH subcategory. However, PAH as well as SSc-PAH remain incurable, with insufficient functional improvement in many patients. More progress is needed, and this will require more effective drugs and adapted outcome measures.

[Altitude and the right heart]. / Cœur droit et altitude.

INTRODUCTION: Altitude is associated with a decrease in partial pressure of oxygen. Hypoxia induces pulmonary vasoconstriction with subsequent fixed increase in pulmonary artery pressure, and eventual right heart failure. CURRENT KNOWLEDGE: High altitude exposure is associated with an increase in pulmonary artery pressure that is proportional to initial vasoconstriction. Echocardiographic evaluations on a large number of subjects show that the altitude-induced increase in pulmonary pressure is generally modest and does not exceed the 25mmHg that are diagnostic of pulmonary hypertension. This does not greatly increase right ventricular afterload, so that imaging of the right ventricle only shows some alterations of indices of systolic or diastolic function, but preserved contractile reserve during exercise. In less than 1% of cases, hypoxic vasoconstriction is strong and may be a cause of severe pulmonary hypertension and right heart failure. PERSPECTIVES: The prognostic relevance of altitude-induced pulmonary hypertension and associated cardiac function alterations is not known. Treatment of hypoxic pulmonary hypertension relies on evacuation to a lower altitude, oxygen and pulmonary vasodilators. These treatment strategies have not been rigorously evaluated. CONCLUSIONS: Altitude may be a cause of right heart failure. This uncommon complication of altitude exposure requires further epidemiological and therapeutic studies.

Diagnostic workup, etiologies and management of acute right ventricle failure : A state-of-the-art paper.

INTRODUCTION: This is a state-of-the-art article of the diagnostic process, etiologies and management of acute right ventricular (RV) failure in critically ill patients. It is based on a large review of previously published articles in the field, as well as the expertise of the authors. RESULTS: The authors propose the ten key points and directions for future research in the field. RV failure (RVF) is frequent in the ICU, magnified by the frequent need for positive pressure ventilation. While no universal definition of RVF is accepted, we propose that RVF may be defined as a state in which the right ventricle is unable to meet the demands for blood flow without excessive use of the Frank-Starling mechanism (i.e. increase in stroke volume associated with increased preload). Both echocardiography and hemodynamic monitoring play a central role in the evaluation of RVF in the ICU. Management of RVF includes treatment of the causes, respiratory optimization and hemodynamic support. The administration of fluids is potentially deleterious and unlikely to lead to improvement in cardiac output in the majority of cases. Vasopressors are needed in the setting of shock to restore the systemic pressure and avoid RV ischemia; inotropic drug or inodilator therapies may also be needed. In the most severe cases, recent mechanical circulatory support devices are proposed to unload the RV and improve organ perfusion CONCLUSION: RV function evaluation is key in the critically-ill patients for hemodynamic management, as fluid optimization, vasopressor strategy and respiratory support. RV failure may be diagnosed by the association of different devices and parameters, while echocardiography is crucial.

[Animal models of pulmonary arterial hypertension]. / Modèles animaux d'hypertension artérielle pulmonaire.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a rare syndrome of fatigue and dyspnoea, caused by increased pulmonary vascular resistance and right heart failure without an identifiable pulmonary or cardiac cause. Despite important recent advances in treatment the condition remains incurable. BACKGROUND: Experimental animal models of PAH rely on hypoxic or monocrotaline injected rodents, the creation of left to right shunts in lambs or piglets, ligation of the ductus arteriosus in newborn lambs, genetically manipulated rodents and tissue culture. Hypoxic pulmonary hypertension is usually only moderate and limited to medial hypertrophy with varying degrees of adventitial change, but may progress to extensive remodelling in some species. Monocrotaline induced pulmonary hypertension is severe with prominent medial hypertrophy, inflammatory adventitial remodelling and, initially, pulmonary oedema and endothelial apoptosis. Pulmonary hypertension induced by shunting remains the most realistic model of PAH but causes only moderate increase in vascular resistance due to medial hypertrophy. Pulmonary hypertension of the newborn is severe but largely vasospastic, with predominant medial hypertrophy. An increasing number of genetically manipulated rodents are becoming available for the investigation of specific signalling pathways. VIEWPOINT: While none of the models has yet reproduced PAH each allows investigation of a specific hypothesis. Recent progress has resulted from genetic manipulation and molecular and cellular approaches. CONCLUSIONS: Animal models of PAH share basic biological abnormalities which, together with the study of lung tissue from patients with severe disease should lead to better understanding of the pathology and therapeutic innovation.

Partitioning of pulmonary vascular resistance in primary pulmonary hypertension.

OBJECTIVES: This study sought to determine the site of increased pulmonary vascular resistance (PVR) in primary pulmonary hypertension by standard bedside hemodynamic evaluation. BACKGROUND: The measurement of pulmonary vascular pressures at several levels of flow (Q) allows the discrimination between active and passive, flow-dependent changes in mean pulmonary artery pressure (Ppa), and may detect the presence of an increased pulmonary vascular closing pressure. The determination of a capillary pressure (Pc') from the analysis of a Ppa decay curve after balloon occlusion allows the partitioning of PVR in an arterial and a (capillary + venous) segment. These approaches have not been reported in primary pulmonary hypertension. METHODS: Ppa and Pc' were measured at baseline and after an increase in Q induced either by exercise or by an infusion of dobutamine, at a dosage up to 8 microg/kg body weight per min, in 11 patients with primary pulmonary hypertension. Reversibility of pulmonary hypertension was assessed by the inhalation of 20 ppm nitric oxide (NO), and, in 6 patients, by an infusion of prostacyclin. RESULTS: At baseline, Ppa was 52+/-3 mm Hg (mean value+/-SE), Q 2.2+/-0.2 liters/min per m2, and Pc' 29+/-3 mm Hg. Dobutamine did not affect Pc' and allowed the calculation of an averaged extrapolated pressure intercept of Ppa/Q plots of 34 mm Hg. Inhaled NO had no effect. Prostacyclin decreased Pc' and PVR. Exercise increased Pc' to 40+/-3 mm Hg but did not affect PVR. CONCLUSIONS: ns. These findings are compatible with a major increase of resistance and reactivity at the periphery of the pulmonary arterial tree.

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.

[Pulmonary arterial hypertension in intensive care unit and operating room]. / Hypertension artérielle pulmonaire en anesthésie-réanimation.

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.