The inhaled ETA receptor antagonist LU-135252 acts as a selective pulmonary vasodilator

2002 ◽  
Vol 103 (s2002) ◽  
pp. 21S-24S ◽  
Author(s):  
Maria DEJA ◽  
Steffen WOLF ◽  
Thilo BUSCH ◽  
Bodil PETERSEN ◽  
Ursel JAGHZIES ◽  
...  
Keyword(s):  
Gas Exchange ◽  
Pulmonary Artery ◽  
Receptor Antagonist ◽  
Experimental Model ◽  
Pulmonary Artery Pressure ◽  
Artery Pressure ◽  
Mean Pulmonary Artery Pressure ◽  
Pulmonary Vasodilator ◽  
Eta Receptor ◽  
Eta Receptor Antagonist

To investigate the hypothesis that the inhaled ETA receptor antagonist LU-135252 acts as selective pulmonary vasodilator, we compared inhaled LU-135252 and inhaled nitric oxide (iNO) in an experimental model of acute lung injury (ALI), in a prospective, randomized, controlled animal study. A total of 30 anaesthetized, tracheotomized and mechanically ventilated pigs underwent induction of ALI by repeated saline washout of surfactant. The animals were then randomly assigned to receive the nebulized ETA receptor antagonist LU-135252 (0.3mg·kg-1, inhaled over 20min; ETA-A group; n = 10), inhaled NO (30p.p.m. continuously; iNO group; n = 10) or nebulized saline buffer (5ml inhaled over 20min; control group; n = 10). Measurements of pulmonary gas exchange and haemodynamics were performed hourly over a 4h period after induction of ALI. In the ETA-A group, the arterial oxygen tension (Pao2) increased from 58±3 to 377±39mmHg at 4h after intervention, while the intrapulmonary shunt (QS/QT) decreased from 53±4% to 18±2% (P<0.01 compared with controls). In the iNO group, PaO2 increased from 62±4 to 224±48mmHg, and QS/QT decreased from 47±2% to 27±5%, at 4h after induction of ALI (P<0.05 compared with controls). In the ETA-A and iNO groups, the increase in mean pulmonary artery pressure was significantly attenuated compared with controls (ETA-A group, 14±4%; iNO group, 6±4%; values at 4h; P<0.01compared with controls). In contrast, there were no significant differences in changes of mean arterial pressure and cardiac output between groups. Thus, in this experimental model of ALI, both inhaled LU-135252 and iNO significantly improved gas exchange and prevented an increase in mean pulmonary artery pressure, without significant systemic effects, when compared with controls. Our results indicate the occurrence of selective pulmonary vasodilation in both treatment groups.

Endothelin-A receptor antagonist prevents acute hypoxia-induced pulmonary hypertension in the rat

1995 ◽  
Vol 268 (1) ◽  
pp. L95-L100 ◽  
Author(s):  
S. Oparil ◽  
S. J. Chen ◽  
Q. C. Meng ◽  
T. S. Elton ◽  
M. Yano ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Receptor Antagonist ◽  
Pulmonary Artery Pressure ◽  
Saline Control ◽  
Mrna Levels ◽  
Artery Pressure ◽  
Endothelin 1 ◽  
Eta Receptor ◽  
Endothelin A

Exposure to hypoxia is associated with increased pulmonary artery pressure and plasma endothelin-1(ET-1) levels and with selective enhancement in ET-1 peptide and mRNA and endothelin-A (ETA) receptor mRNA levels in rat lung. The current study tested the hypothesis that endogenous ET-1 can account for hypoxia-induced pulmonary hypertension via a paracrine effect on ETA receptors in lung. Intravenous infusion of the ETA receptor antagonist BQ-123 (D-Trp-D-Asp-Pro-D-Val-Leu) (0.4 mg/microliters at 1 microliter/h) into Sprague-Dawley rats beginning 4 h before and for 90 min during normobaric hypoxia (10% O2) markedly attenuated the hypoxic response: mean pulmonary artery pressure increased from 17.2 +/- 0.7 to 29.0 +/- 1.2 mmHg in saline control rats but did not increase from baseline in BQ-123-treated rats. BQ-123 did not alter systemic arterial pressure, heart rate, or plasma endothelin-1 levels. These findings suggest that ET-1 synthesized in lung in response to hypoxia acts locally on ETA receptors to cause pulmonary hypertension.

scholarly journals Long term effects of non-invasive mechanical ventilation on pulmonary haemodynamics in patients with chronic respiratory failure

Thorax ◽  
2001 ◽  
Vol 56 (7) ◽  
pp. 524-528
Author(s):  
B Schönhofer ◽  
T Barchfeld ◽  
M Wenzel ◽  
D Köhler
Keyword(s):  
Mechanical Ventilation ◽  
Respiratory Failure ◽  
Gas Exchange ◽  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Chronic Respiratory Failure ◽  
Artery Pressure ◽  
Mean Pulmonary Artery Pressure ◽  
Pulmonary Haemodynamics

BACKGROUNDIt is not known whether long term nocturnal mechanical ventilation (NMV) reduces pulmonary hypertension in patients with chronic respiratory failure (CRF).METHODSPulmonary haemodynamics, spirometric values, and gas exchange were studied in 33 patients requiring NMV due to CRF (20 with thoracic restriction, 13 with chronic obstructive pulmonary disease (COPD)) at baseline and after 1 year of NMV given in the volume cycled mode. Patients with COPD also received supplemental oxygen.RESULTSLong term NMV improved gas exchange while lung function remained unchanged. Mean pulmonary artery pressure at rest before NMV was higher in patients with thoracic restriction than in those with COPD (33 (10) mm Hgv 25 (6) mm Hg). After 1 year of NMV mean pulmonary artery pressure decreased in patients with thoracic restriction to 25 (6) mm Hg (mean change –8.5 mm Hg (95% CI –12.6 to –4.3), p<0.01) but did not change significantly in patients with COPD (mean change 2.2 mm Hg (95% CI –0.3 to 4.8)).CONCLUSIONSLong term NMV in CRF improves pulmonary haemodynamics in patients with thoracic restriction but not in patients with COPD.

scholarly journals Regional CO2 tension quantitatively mediates homeostatic redistribution of ventilation following acute pulmonary thromboembolism in pigs

2009 ◽  
Vol 107 (3) ◽  
pp. 755-762 ◽  
Author(s):  
John Y. C. Tsang ◽  
Wayne J. E. Lamm ◽  
Erik R. Swenson
Keyword(s):  
Gas Exchange ◽  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Airway Resistance ◽  
Pulmonary Thromboembolism ◽  
Regional Ventilation ◽  
Fluorescent Microspheres ◽  
Artery Pressure ◽  
Mean Pulmonary Artery Pressure ◽  
Acute Pulmonary Thromboembolism

Previous studies reported that regional CO2 tension might affect regional ventilation (V̇) following acute pulmonary thromboembolism (APTE). We investigated the pathophysiology and magnitude of these changes. Eight anesthetized and ventilated piglets received autologous clots at time = 0 min until mean pulmonary artery pressure was 2.5 times baseline. The distribution of V̇ and perfusion (Q̇) at four different times (−5, 30, 60, 120 min) was mapped by fluorescent microspheres. Regional V̇ and Q̇ were examined postmortem by sectioning the air-dried lung into 900–1,000 samples of ∼2 cm3 each. After the redistribution of regional Q̇ by APTE, but in the scenario assuming that no V̇ shift had yet occurred, CO2 tension in different lung regions at 30 min post-APTE (PXCO2) was estimated from the V̇/Q̇ data and divided into four distinct clusters: i.e., PXCO2 < 10 Torr; 10 < PXCO2 < 25 Torr; 25 < PXCO2 < 50 Torr; PXCO2 > 50 Torr. Our data showed that the clusters in higher V̇/Q̇ regions (with a PXCO2 < 25 Torr) received ∼35% less V̇ when measured within 30 min of APTE, whereas, in contrast, the lower V̇/Q̇ regions showed no statistically significant increases in their V̇. However, after 30 min, there was minimal further redistribution of V̇. We conclude that there are significant compensatory V̇ shifts out of regions of low CO2 tension soon following APTE, and that these variations in regional CO2 tension, which initiate CO2-dependent changes in airway resistance and lung parenchymal compliance, can lead to improved gas exchange.

Inflammation and Congenital Heart Disease Associated Pulmonary Hypertension

2015 ◽  
Vol 18 (1) ◽  
pp. 038 ◽  
Author(s):  
Mete Gursoy ◽  
Ece Salihoglu ◽  
Ali Can Hatemi ◽  
A. Faruk Hokenek ◽  
Suleyman Ozkan ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Neutrophil To Lymphocyte Ratio ◽  
Cell Distribution ◽  
Inflammation Markers ◽  
Distribution Width ◽  
Artery Pressure ◽  
Lymphocyte Ratio ◽  
Mean Pulmonary Artery Pressure ◽  
Pulmonary Arterial

<strong>Background:</strong> Increased blood flow may trigger pulmonary arterial wall inflammation, which may influence progression of pulmonary artery hypertension in patients with congenital heart disease. In this study, we aimed to investigate the correlation between preoperative inflammation markers and pulmonary arterial hypertension. <br /><strong>Methods:</strong> A total of 201 patients with pulmonary hypertension were enrolled in this study retrospectively; they had undergone open heart surgery between January 2012 and December 2013. Patients’ preoperative C-reactive protein (CRP), neutrophil to lymphocyte ratio, red blood cell distribution width, pulmonary pressures, and postoperative outcomes were evaluated.<br /><strong>Results:</strong> Patient age, neutrophil to lymphocyte ratio, red blood cell distribution width, and CRP were found to be significantly correlated with both preoperative peak and mean pulmonary artery pressures. These data were entered into a linear logistic regression analysis. Patient age, neutrophil to lymphocyte ratio, and CRP were found to be independently correlated with peak pulmonary pressure (P &lt; .001, P &lt; .001, and P = .004) and mean pulmonary artery pressure (P &lt; .001, P &lt; .001, and P = .001), whereas preoperative mean pulmonary artery pressure was found to be independently correlated with intensive care unit stay (P &lt; .001). No parameter was found to be significantly correlated with extubation time and mortality. Eighteen patients had experienced pulmonary hypertensive crisis; in this subgroup, patients’ mean pulmonary artery pressure and neutrophil to lymphocyte ratio were found to be significant (P = .047, P = .003). <br /><strong>Conclusion:</strong> Preoperative inflammation markers may be correlated with the progression of pulmonary hypertensive disease, but further studies with larger sample size are needed to determine the predictive role of these markers for postoperative outcomes.<br /><br />

Prognostic importance of mitral e′ velocity in constrictive pericarditis

2020 ◽  
Author(s):  
Jeong Hoon Yang ◽  
William R Miranda ◽  
Rick A Nishimura ◽  
Kevin L Greason ◽  
Hartzell V Schaff ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Constrictive Pericarditis ◽  
Multivariable Analysis ◽  
Artery Pressure ◽  
Myocardial Disease ◽  
Mean Pulmonary Artery Pressure ◽  
Diastolic Velocity ◽  
Long Term Mortality

Abstract Aims  Increased medial mitral annulus early diastolic velocity (e′) plays an important role in the echocardiographic diagnosis of constrictive pericarditis (CP) and mitral e′ velocity is also a marker of underlying myocardial disease. We assessed the prognostic implication of mitral e′ for long-term mortality after pericardiectomy in patients with CP. Methods and results  We studied 104 surgically confirmed CP patients who underwent echocardiography and cardiac catheterization within 7 days between 2005 and 2013. Patients were classified as primary CP (n = 45) or mixed CP (n = 59) based on the clinical history of concomitant myocardial disease. On multivariable analysis, medial e′ velocity and mean pulmonary artery pressure were independently associated with long-term mortality post-pericardiectomy. There were significant differences in survival rates among the groups divided by cut-off values of 9.0 cm/s and 29 mmHg for medial e′ and mean pulmonary artery pressure, respectively (both P &lt; 0.001). Ninety-two patients (88.5%) had elevated pulmonary artery wedge pressure (PAWP) (≥15 mmHg); there was no significant correlation between medial E/e′ and PAWP (r = 0.002, P = 0.998). However, despite the similar PAWP between primary CP and mixed CP groups (21.6 ± 5.4 vs. 21.2 ± 5.8, P = 0.774), all primary CP individuals with elevated PAWP had medial E/e′ &lt;15 as opposed to 34 patients (57.6%) in the mixed CP group (P &lt; 0.001). Conclusion  Increased mitral e′ velocity is associated with better outcomes in patients with CP. A paradoxical distribution of the relationship between E/e′ and PAWP is present in these patients but there is no direct inverse correlation between them.

Survival and predictors of mortality in patients after the Fontan operation

2020 ◽  
Vol 28 (9) ◽  
pp. 572-576
Author(s):  
Saviga Sethasathien ◽  
Suchaya Silvilairat ◽  
Hathaiporn Kraikruan ◽  
Rekwan Sittiwangkul ◽  
Krit Makonkawkeyoon ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Fontan Operation ◽  
Hazard Ratio ◽  
Early Mortality ◽  
Atrioventricular Valve ◽  
Valve Regurgitation ◽  
Artery Pressure ◽  
Mean Pulmonary Artery Pressure ◽  
Atrioventricular Valve Regurgitation

Background As a result of the surgical techniques now being employed, the survival rate in patients after undergoing the Fontan operation has improved. The aims of this study were focused on determining the survival rate and predictors of early mortality. Methods In a retrospective cohort study, 117 consecutive patients who underwent the Fontan operation were recruited. Multivariate Cox proportional regression analysis was used to assess the predictors of early mortality, defined as death within 30 days after the Fontan operation. Results The median follow-up time was 6.1 years. The median age at the time of the Fontan operation was 5.7 years. Survival rates in the patients at 5, 10, and 15 years postoperatively were 92%, 87% and 84%, respectively. Using univariate Cox regression analysis, the predictors of early mortality were found to be postoperative mean pulmonary artery pressure ≥23 mm Hg (hazard ratio 26.0), renal failure (hazard ratio 9.5), heterotaxy syndrome (hazard ratio 5.3), and uncorrected moderate or severe atrioventricular valve regurgitation (hazard ratio 9.4). After adjusting for confounding factors using multivariate Cox regression analysis, the predictors of early mortality were found to be postoperative mean pulmonary artery pressure ≥23 mm Hg (hazard ratio 23.2) and uncorrected moderate or severe atrioventricular valve regurgitation (hazard ratio 8.2). Conclusions Uncorrected moderate or severe atrioventricular valve regurgitation and postoperative mean pulmonary artery pressure ≥23 mm Hg are independent predictors of early mortality after the Fontan operation. Patients with these factors should undergo aggressive management to minimize morbidity and mortality.

scholarly journals P1529 Impact of the new PH guidelines on echocardiographic definition leading to double demand of right heart catheterization

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
C Fauvel ◽  
O Raitiere ◽  
J Burdeau ◽  
N Si Belkacem ◽  
F Bauer
Keyword(s):  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Tricuspid Regurgitation ◽  
Peak Velocity ◽  
Right Heart Catheterization ◽  
Heart Catheterization ◽  
Right Heart ◽  
Artery Pressure ◽  
Mean Pulmonary Artery Pressure ◽  
Definition Of

Abstract Background Doppler echocardiography is the most widespread and well-recognized technique for the screening of patients with pulmonary hypertension (PH). When tricuspid regurgitation peak velocity (TRPV) ≥3.4 m/s, right heart catheterization is requested to confirm mean pulmonary artery pressure &gt;25 mm Hg. In the proceedings from the 6th world symposium on pulmonary arterial hypertension recently released, the new definition of PH has been lowered to mean pulmonary artery pressure &gt; 20 mm Hg. Purpose The purpose of our work was twofold : i) to determine a new cut-off value for TRPV to accommodate the new hemodynamic definition of PH, ii) to investigate the impact on the demand of right heart catheterization (RHC) from our echo CORE lab. Methods We extracted and analyzed both the haemodynamic and echocardiographic records of 130 patients who underwent investigations the same day. Tricuspid regurgitation peak velocity was measured in apical-4 chamber view using continuous-wave doppler modality and compared to mean pulmonary artery pressure recorded from fluid-filled catheter. Results Tricuspid regurgitation peak velocity has a weak correlation with mean pulmonary pressure (y = 9.2x-2.2, r² = 0.22, p &lt; 0.01). Targeting a mean pulmonary pressure on right heart catheterization of 20 mm Hg for the definition of PH, receiver operating characteristic curve analysis demonstrated a good association between TRPV and PH diagnosis (area under the curve, 0.78 ; p &lt; 0.001). The cut-off value obtained for TRPV was 3.0 m/s (Se = 0.78, Sp = 0.37). From 01/01/18 to 31/12/18, 2539 out of 6215 had TRPV recorded from which 283 had TRPV ≥ 3.0 m/s (24,1%) and 615 had TRPV ≥ 3.4 m/s (11,1%). When applied to a community population the new TRPV cutoff &gt; 3m/s used as surrogate for mean pulmonary artery pressure &gt; 20 mm Hg may produce a 111% increase of right heart catheterization demand. Conclusions The new definition of pulmonary hypertension (invasive mean pulmonary artery pressure &gt; 20mm Hg) necessitates revisiting tricuspid regurgitation peak velocity &gt; 3 m/s as a screening test leading to more than twice RHC demand.

Impaired pulmonary gas exchange efficiency, but normal pulmonary artery pressure increases, with hypoxia in men and women with a patent foramen ovale

2020 ◽  
Vol 105 (9) ◽  
pp. 1648-1659
Author(s):  
Joseph W. Duke ◽  
Kara M. Beasley ◽  
Julia P. Speros ◽  
Jonathan E. Elliott ◽  
Steven S. Laurie ◽  
...  
Keyword(s):  
Gas Exchange ◽  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Patent Foramen Ovale ◽  
Pulmonary Gas Exchange ◽  
Foramen Ovale ◽  
Men And Women ◽  
Artery Pressure
Sign in / Sign up

Export Citation Format

Share Document