Prolonged overcirculation-induced pulmonary arterial hypertension as a cause of right ventricular failure.

Aims: Three-month chronic systemic-to-pulmonary shunting in growing piglets has been reported as an early pulmonary arterial hypertension (PAH) model with preserved right ventricular (RV) function. We sought to determine whether prolonged shunting might be associated with more severe PAH and RV failure.

Methods And Results: Fourteen growing piglets were randomized to a sham operation or the anastomosis of the left innominate artery to the pulmonary arterial trunk.

Prognostic factors associated with increased survival in patients with pulmonary arterial hypertension treated with subcutaneous treprostinil in randomized, placebo-controlled trials.

Background: Because of the challenges associated with conducting large survival studies of patients with pulmonary arterial hypertension (PAH), we analyzed the surrogate markers predictive of long-term survival in a large cohort of patients treated with subcutaneous treprostinil.

Methods: A retrospective review was conducted using data from a total of 811 patients with New York Heart Association Functional Class (NYHA FC) II to IV PAH, who were treated with subcutaneous treprostinil. Patient baseline disease and on-treatment parameters were analyzed by uni- and multivariate analyses for predictive value of 3-year survival with PAH.

Safety, tolerability and pharmacokinetics of an intravenous bolus of sildenafil in patients with pulmonary arterial hypertension.

Aims: To assess pharmacokinetics and pharmacodynamics of a 10 mg intravenous sildenafil bolus in pulmonary arterial hypertension (PAH) patients stabilized on 20 mg sildenafil orally three times daily.

Methods: Pharmacokinetic parameters were calculated using noncompartmental analysis.

Results: After an acute increase, plasma concentrations stabilized within the range reported previously for a 20 mg oral tablet.

[The cardiopulmonary exercise test in the management of patients with pulmonary hypertension].

The main symptom of patients with pulmonary hypertension (PH) is exercise intolerance. The gold standard for evaluation of exercise capacity is the incremental cardio-pulmonary exercise test (ICPET) on a bicycle ergometer. Exercise tolerance in patients with PH is mainly determined by the capacity to increase cardiac output to meet metabolic demands, which depends on right ventricular function.

Range in pulmonary artery systolic pressure among highly trained athletes.

Background: Although the physiologic range of pulmonary artery systolic pressure (PASP) has been reported, data on how it is manifested in athletes are limited. The aim of the present study was to explore the full spectrum of PASP and the long-term training impact in a large population of highly trained athletes.

Methods: Six hundred fifteen consecutive athletes (370 endurance-trained athletes [ATEs] vs 245 strength-trained athletes [ATSs]; 28.

Sildenafil added to sitaxsentan in overcirculation-induced pulmonary arterial hypertension.

Experimental left-to-right shunt-induced pulmonary arterial hypertension (PAH) can be partially prevented by the endothelin-A receptor blocker sitaxsentan or by the phosphodiesterase-5 inhibitor sildenafil. We hypothesized that the combined administration of these drugs would completely prevent shunt-induced PAH, arguing in favor of a major role of endothelial dysfunction in the initiation of the disease. Twenty-four 3-wk-old piglets were randomized to a sham operation or to placebo, sitaxsentan therapy, or sitaxsentan combined with sildenafil after the anastomosis of the left subclavian artery to the pulmonary arterial trunk.

Early right ventriculo-arterial uncoupling in borderline pulmonary hypertension on experimental heart failure.

Pulmonary hypertension on heart failure (HF) limits exercise capacity and survival probably because of associated right ventricular (RV) failure. This study investigated the mechanisms of RV function adaptation to early pulmonary hypertension in experimental HF. Seven weeks of rapid ventricular pacing in six dogs induced a HF characterized by cardiomegaly and decreased left ventricular ejection fraction.

Right ventricular load at exercise is a cause of persistent exercise limitation in patients with normal resting pulmonary vascular resistance after pulmonary endarterectomy.

Background: Pulmonary endarterectomy (PEA) provides a potential cure for patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, successfully operated patients can continue to suffer from a limitation of exercise capacity, despite normalization of pulmonary vascular resistance (PVR). The purpose of the present study was to explore the cardiopulmonary exercise test (CPET) profile and the pulmonary hemodynamic response to exercise in these patients.

Pulmonary vasoreactivity predicts long-term outcome in patients with Eisenmenger syndrome receiving bosentan therapy.

Background: Vasoreactivity testing is recommended in the management of pulmonary arterial hypertension (PAH), but its clinical relevance in congenital heart disease (CHD)-associated PAH has not been established.

Objective: To determine whether residual pulmonary vascular responsiveness to intravenous. epoprostenol is predictive of clinical outcome in patients with CHD-PAH and Eisenmenger syndrome.

Ventricular-arterial uncoupling in heart failure with preserved ejection fraction after myocardial infarction in dogs - invasive versus echocardiographic evaluation.

Background: Heart failure with preserved left ventricular ejection fraction and abnormal diastolic function is commonly observed after recovery from an acute myocardial infarction. The aim of this study was to investigate the physiopathology of heart failure with preserved ejection fraction in a model of healed myocardial infarction in dogs.

Methods: Echocardiography, levels of neurohormones and conductance catheter measurements of left ventricular pressure-volume relationships were obtained in 17 beagle dogs 2 months after a coronary artery ligation, and in 6 controls.

Pulmonary capillary blood volume and membrane conductance in Andeans and lowlanders at high altitude: a cross-sectional study.

Lung carbon monoxide (CO) transfer and pulmonary capillary blood volume (Vc) at high altitudes have been reported as being higher in native highlanders compared to acclimatised lowlanders but large discrepancies appears between the studies. This finding raises the question of whether hypoxia induces pulmonary angiogenesis. Eighteen highlanders living in Bolivia and 16 European lowlander volunteers were studied.

Activation of apoptotic pathways in experimental acute afterload-induced right ventricular failure.

Objective: The pathobiology of persistent right ventricular failure observed after an acute increase in right ventricular afterload remains incompletely understood. We hypothesized that persistent right ventricular dysfunction might be related to activation of apoptotic pathways.

Design: Prospective, randomized, controlled animal study.

Physiological adaptation of the cardiovascular system to high altitude.

Altitude exposure is associated with major changes in cardiovascular function. The initial cardiovascular response to altitude is characterized by an increase in cardiac output with tachycardia, no change in stroke volume, whereas blood pressure may temporarily be slightly increased. After a few days of acclimatization, cardiac output returns to normal, but heart rate remains increased, so that stroke volume is decreased.

New therapies for pulmonary arterial hypertension: an update on current bench to bedside translation.

Importance Of The Field: Treatments of pulmonary arterial hypertension (PAH) that have so far proven efficacious are all based on the restoration of endothelium control of pulmonary vascular tone and structure, by administration of prostacyclins, endothelin receptor antagonists and phosphodiesterase-5 inhibitors. However, results remain unsatisfactory, with persistent high mortality, insufficient clinical improvement and no convincing report of any reversal of the disease process.

Areas Covered In This Review: New antiproliferative approaches that aim to actively limit pulmonary vascular remodeling are being sought.

Prognostic significance of sympathetic nervous system activation in pulmonary arterial hypertension.

Rationale: The sympathetic nervous system has been reported to be activated in pulmonary arterial hypertension (PAH).

Objectives: We investigated the prognostic significance of muscle sympathetic nervous system activity (MSNA) in PAH.

Methods: Thirty-two patients with PAH were included in the study and underwent a measurement of MSNA over a 6-year period of time.

Exercise capacity and haemodynamics in patients with sickle cell disease with pulmonary hypertension treated with bosentan: results of the ASSET studies.

Doppler-defined pulmonary hypertension (PH) in sickle cell disease (SCD) is associated with 40% mortality at 40 months. To assess the effect of bosentan in SCD-PH, two randomized, double-blind, placebo-controlled, 16-week studies were initiated. Safety concerns are particularly relevant in SCD due to comorbid conditions.

Impedance in isolated mouse lungs for the determination of site of action of vasoactive agents and disease.

Hypoxic pulmonary hypertension is a disease of the lung vasculature that is usually quantified by pulmonary vascular resistance (PVR). However, a more complete description of lung vascular function and right ventricular afterload is provided by pulmonary vascular impedance (PVZ) from spectral analysis of pulsatile pressure-flow relationships. We studied pulsatile pressure-flow relationships in isolated, perfused lungs of mice in normoxia, after induction of hypoxic pulmonary hypertension by 10 days of hypoxic exposure, and after the administration of the vasoactive agents sodium nitroprusside and serotonin in order to gain insight into the effects of disease and vasoactive agents on afterload.

Changes in plasma bradykinin concentration and citric acid cough threshold at high altitude.

Objective: Altitude-related cough is a troublesome condition of unknown etiology. Inhaled tussive agents are used to quantify cough, and the citric acid cough threshold has been shown to fall on ascent to altitude. Cough can occur in patients taking angiotensin-converting enzyme inhibitors due to stimulation of airway sensory receptors by increased levels of bradykinin.

How to measure pulmonary vascular and right ventricular function.

Long-standing pulmonary hypertension causes significant peripheral and proximal arterial remodeling and right ventricular dysfunction. The clinical metric most often used to assess the progression of PH is the pulmonary vascular resistance (PVR). However, even when measured from multipoint pressure-flow curves, PVR provides information only on the peripheral arterial function, not the proximal arterial function and gives only an incomplete description of all the forces that oppose right ventricular (RV) flow output.

How to measure peripheral pulmonary vascular mechanics.

Pulmonary hypertension (PH) is initially a disease of the small, peripheral resistance arteries. Changes in these vessels are best assessed by measurement of pulmonary artery pressure at several levels of flow to generate multi-point pressure-flow curves. This approach is superior to the traditional single-point measurement of pulmonary vascular resistance (PVR) because it allows a flow-independent definition of the resistive properties of that portion of the pulmonary vascular bed and also provides information on its distensibility.

Cardiac insulin-like growth factor-1 and cyclins gene expression in canine models of ischemic or overpacing cardiomyopathy.

Background: Insulin-like growth factor-1 (IGF-1), transforming growth factor beta (TGFbeta) and cyclins are thought to play a role in myocardial hypertrophic response to insults. We investigated these signaling pathways in canine models of ischemic or overpacing-induced cardiomyopathy.

Methods: Echocardiographic recordings and myocardial sampling for measurements of gene expressions of IGF-1, its receptor (IGF-1R), TGFbeta and of cyclins A, B, D1, D2, D3 and E, were obtained in 8 dogs with a healed myocardial infarction, 8 dogs after 7 weeks of overpacing and in 7 healthy control dogs.

The Belgian Eisenmenger syndrome registry: implications for treatment strategies?

Objective: Pulmonary arterial hypertension (PAH), associated with congenital heart disease (CHD), usually results from a systemic-to-pulmonary shunt. Eisenmenger syndrome (ES) is characterised by severe irreversible PAH and reversal of a previous systemic-to-pulmonary shunt. A national registry of ES patients was initiated to optimise patient care and to provide epidemiological information regarding PAH and CHD in Belgium.