Systemic and pulmonary hypertension after abrupt cessation of prostacyclin: role of thromboxane A2

1996 ◽  
Vol 80 (1) ◽  
pp. 191-197 ◽  
Author(s):  
L. L. Cuiper ◽  
P. V. Price ◽  
B. W. Christman
Keyword(s):  
Pulmonary Hypertension ◽  
Thromboxane A2 ◽  
Chronic Administration ◽  
Systemic Arterial Pressure ◽  
Unknown Etiology ◽  
Indwelling Catheters ◽  
Abrupt Cessation ◽  
Pulmonary Capillary ◽  
Pulmonary Arterial

Chronic administration of prostacyclin (PGI2) improves hemodynamics in patients with primary pulmonary hypertension, but abrupt cessation of infusion can cause severe dyspnea of unknown etiology. We hypothesized that the discontinuation of PGI2 results in platelet activation, thromboxane A2 production, and increased pulmonary vascular tone. To test this, six sheep with indwelling catheters were monitored during infusion of PGI2 and after its cessation. Infusion of PGI2 caused a reduction in mean systemic arterial pressure (MAP) and systemic (SVR) and pulmonary vascular resistances (PVR), a rise in cardiac output (CO), and no change in pulmonary arterial or pulmonary capillary wedge pressure (PCWP). After discontinuation of PGI2, MAP and SVR rebounded to 30 and 67% above baseline, respectively, and PVR rose 26%. CO was depressed 23% within 10 min, and PCWP nearly doubled after stoppage of the drug. Concurrent treatment with a cyclooxygenase inhibitor did not attenuate these responses. 11-Dehydro-thromboxane B2 levels were not elevated during infusion or after cessation of PGI2. We conclude that the abrupt cessation of PGI2 infusion leads to systemic and pulmonary hypertension and transient cardiac dysfunction not mediated by cyclooxygenase metabolites of arachidonic acid.

Effect of leukopenia on pulmonary hypertension after heparin-protamine in pigs

1992 ◽  
Vol 73 (1) ◽  
pp. 44-49 ◽  
Author(s):  
H. Habazettl ◽  
P. F. Conzen ◽  
B. Vollmar ◽  
E. Yekebas ◽  
K. Peter
Keyword(s):  
Pulmonary Hypertension ◽  
Thromboxane A2 ◽  
Thromboxane B2 ◽  
Control Group ◽  
Mean Pulmonary Arterial Pressure ◽  
Leukocyte Counts ◽  
Pulmonary Arterial ◽  
Heparin Neutralization

Heparin neutralization by protamine after cardiac surgery and cardiopulmonary bypass may be associated with complement activation, transient leukopenia, thromboxane A2 release, and severe pulmonary hypertension. The role of leukocytes in the heparin-protamine reaction was studied in leukopenic pigs (n = 9) and a control group (n = 8). Leukopenia was induced by pretreatment with cyclophosphamide (30 mg.kg-1.day-1) for 6–7 days. During general anesthesia and after catheterization, baseline recordings of hemodynamics were performed and blood samples were withdrawn. Heparin (250 IU/kg) was injected and measurements were repeated after 10 min. Protamine sulfate (100 mg) was then infused over 2 min and measurements were performed after 2, 5, and 15 min. Prostanoid concentrations were measured by radioimmunoassays. In additional in vitro experiments, the release of thromboxane B2 from washed platelets and leukocytes after heparin-protamine stimulation was measured. Pretreatment with cyclophosphamide reduced leukocyte counts by 95.5% and the number of neutrophils by greater than 99.9%. Protamine infusion increased mean pulmonary arterial pressure by 74 and 46% and pulmonary vascular resistance by 185 and 384% in control and leukopenic animals, respectively. Thromboxane B2 concentrations increased in both groups. Stimulation by heparin, protamine, or heparin and protamine in sequence did not induce any thromboxane A2 release from washed blood cells. It is concluded that leukocytes do not contribute to pulmonary hypertension after heparin-protamine.

scholarly journals High Probability Ventilation-Perfusion Scan in Primary Pulmonary Hypertension

1995 ◽  
Vol 2 (3) ◽  
pp. 179-182
Author(s):  
Sat Sharma ◽  
William D Leslie ◽  
Morley Lertzman
Keyword(s):  
Pulmonary Hypertension ◽  
High Probability ◽  
Primary Pulmonary Hypertension ◽  
Pulmonary Angiography ◽  
Unknown Etiology ◽  
Lung Scan ◽  
Perfusion Defects ◽  
Perfusion Scan ◽  
Pulmonary Arterial

The perfusion lung scan is a valuable noninvasive tool in the evaluation of patients with pulmonary arterial hypertension of undetermined cause and for the exclusion of occult large-vessel pulmonary thromboembolism. Peripheral patchy defects have been reported in primary pulmonary hypertension (PPH) but there are no well documented reports of segmental or larger perfusion defects. A case of a 55-year-old male with severe pulmonary hypertension of unknown etiology who had persistent high probability perfusion scan patterns over a period of two years is reported. No evidence of thromboembolism was present on pulmonary angiography. A discussion of the case and a review of the literature on the role of lung scan in PPH are presented. Most patients with PPH have normal or low probability perfusion scans; high probability scans occur rarely.

scholarly journals EXPRESS: Pulmonary Hypertension Associated With Neurofibromatosis Type 2

2021 ◽  
pp. 204589402110295
Author(s):  
Hirohisa Taniguchi ◽  
Tomoya Takashima ◽  
Ly Tu ◽  
Raphaël Thuillet ◽  
Asuka Furukawa ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Neurofibromatosis Type ◽  
Pulmonary Vascular Remodeling ◽  
Life Threatening ◽  
History Of ◽  
Pulmonary Arterial ◽  
First Time

Although precapillary pulmonary hypertension (PH) is a rare but severe complication of patients with neurofibromatosis type 1 (NF1), its association with NF2 remains unknown. Herein, we report a case of a 44-year-old woman who was initially diagnosed with idiopathic pulmonary arterial hypertension (IPAH) and treated with PAH-specific combination therapy. However, a careful assessment for a relevant family history of the disease and genetic testing reveal that this patient had a mutation in the NF2 gene. Using immunofluorescence and Western blotting, we demonstrated a decrease in endothelial NF2 protein in lungs from IPAH patients compared to control lungs, suggesting a potential role of NF2 in PAH development. To our knowledge, this is the first time that precapillary PH has been described in a patient with NF2. The altered endothelial NF2 expression pattern in PAH lungs should stimulate work to better understand how NF2 is contributing to the pulmonary vascular remodeling associated to these severe life-threatening conditions.

scholarly journals Under pressure: pulmonary hypertension associated with left heart disease

2015 ◽  
Vol 24 (138) ◽  
pp. 665-673 ◽  
Author(s):  
Harrison W. Farber ◽  
Simon Gibbs
Keyword(s):  
Pulmonary Hypertension ◽  
Heart Disease ◽  
Survival Rates ◽  
Left Ventricular ◽  
Left Heart ◽  
Mean Pulmonary Arterial Pressure ◽  
Left Heart Disease ◽  
Right Heart Catheterisation ◽  
Pulmonary Capillary ◽  
Pulmonary Arterial

Pulmonary hypertension (PH) associated with left heart disease (PH-LHD) is the most common type of PH, but its natural history is not well understood. PH-LHD is diagnosed by right heart catheterisation with a mean pulmonary arterial pressure ≥25 mmHg and a pulmonary capillary wedge pressure >15 mmHg. The primary causes of PH-LHD are left ventricular dysfunction of systolic and diastolic origin, and valvular disease. Prognosis is poor and survival rates are low. Limited progress has been made towards specific therapies for PH-LHD, and management focuses on addressing the underlying cause of the disease with supportive therapies, surgery and pharmacological treatments. Clinical trials of therapies for pulmonary arterial hypertension in patients with PH-LHD have thus far been limited and have provided disappointing or conflicting results. Robust, long-term clinical studies in appropriate target populations have the potential to improve the outlook for patients with PH-LHD. Herein, we discuss the knowledge gaps in our understanding of PH-LHD, and describe the current unmet needs and challenges that are faced by clinicians when identifying and managing patients with this disease.

Lung injury in a surfactant-deficient lung is modified by indomethacin

1990 ◽  
Vol 69 (6) ◽  
pp. 2067-2071 ◽  
Author(s):  
R. Burger ◽  
D. Fung ◽  
A. C. Bryan
Keyword(s):  
Pulmonary Hypertension ◽  
Lung Injury ◽  
Thromboxane A2 ◽  
Neutrophil Infiltration ◽  
Lung Lavage ◽  
Thromboxane A2 Receptor ◽  
Beneficial Effects ◽  
Thromboxane Receptor ◽  
Pulmonary Arterial ◽  
Arterial Po2

Repetitive total lung lavage in adult rabbits leads to a reproducible severe surfactant-deficient lung injury. Hypoxemia requiring mechanical ventilation occurs, accompanied by a substantial pulmonary hypertension, a large intra-alveolar protein leak, peripheral neutropenia, and pathological features of marked neutrophil infiltration with extensive hyaline membrane formation. Pretreatment with indomethacin abolishes postlavage pulmonary hypertension, preserves a slightly better lung function with higher arterial PO2, and prevents the postlavage peripheral neutropenia found in untreated animals. Pretreatment with a thromboxane A2 receptor blocker (L 655,240, Merck Frosst, Canada) also completely attenuated pulmonary hypertension, providing evidence that thromboxane A2 mediates pulmonary arterial hypertension after lung lavage. However, specific thromboxane receptor blockade had no other long-lasting beneficial effects on the ongoing injury in this model.

Role of Ambrisentan in the Management of Pulmonary Hypertension

2008 ◽  
Vol 42 (11) ◽  
pp. 1653-1659 ◽  
Author(s):  
Sandra L Hrometz ◽  
Kelly M Shields
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
English Language ◽  
Data Extraction ◽  
Information Service ◽  
Study Selection ◽  
Pulmonary Arterial ◽  
Improve Exercise Capacity

Objective: To review the role of ambrisentan in the treatment of pulmonary arterial hypertension (PAH). Data Sources: Literature was accessed through MEDLINE (1950-June 2008), Iowa Drug Information Service (1966–March 2008), EMBASE (1966-June 2008), bibliographies of pertinent articles, and unpublished data provided by the manufacturer and the Food and Drug Administration (FDA). Search terms included ambrisentan, endothelin antagonist, pulmonary hypertension, and pulmonary arterial hypertension. Due to limited literature available, additional criteria to limit searches were not used. Study Selection and Data Extraction: Abstracts and original preclinical and clinical research reports available in the English language were Identified for review. All manufacturer-provided data were also evaluated. Literature related to ambrisentan, endothelin antagonists, pulmonary hypertension, and pulmonary arterial hypertension were included. Four clinical trials evaluated the efficacy of ambrisentan in adults with symptomatic PAH. Data Synthesis: Ambrisentan is the latest endothelin-receptor antagonist (ERA) to obtain FDA approval for the treatment of PAH. It joins the first FDA-approved ERA, bosentan. Like bosentan, ambrisentan is available orally (with once-daily dosing compared with bosentan's twice-daily dosing) and has been shown to improve exercise capacity and delay clinical worsening. As with bosentan, the most significant safety concerns with ambrisentan relate to potential liver injury and a contraindication in pregnancy. Although ambrisentan has higher affinity for the endothelin type A receptor than for the endothelin type B receptor, specific advantages of this selectivity, in terms of efficacy compared with bosentan, a nonselective agent, have not been demonstrated. Conclusions: Ambrisentan has been shown to be an effective ERA in patients with PAH. A significant advantage of ambrisentan is the lack of any clinically important drug interactions with warfarin and sildenafil, which are frequently used by patients being treated for PAH.

scholarly journals Right heart catheterisation: best practice and pitfalls in pulmonary hypertension

2015 ◽  
Vol 24 (138) ◽  
pp. 642-652 ◽  
Author(s):  
Stephan Rosenkranz ◽  
Ioana R. Preston
Keyword(s):  
Pulmonary Hypertension ◽  
Clinical Practice ◽  
Best Practice ◽  
Data Interpretation ◽  
Volume Measurement ◽  
Right Heart ◽  
Heart Catheterisation ◽  
Right Heart Catheterisation ◽  
Pulmonary Arterial

Right heart catheterisation (RHC) plays a central role in identifying pulmonary hypertension (PH) disorders, and is required to definitively diagnose pulmonary arterial hypertension (PAH). Despite widespread acceptance, there is a lack of guidance regarding the best practice for performing RHC in clinical practice. In order to ensure the correct evaluation of haemodynamic parameters directly measured or calculated from RHC, attention should be drawn to standardising procedures such as the position of the pressure transducer and catheter balloon inflation volume. Measurement of pulmonary arterial wedge pressure, in particular, is vulnerable to over- or under-wedging, which can give rise to false readings. In turn, errors in RHC measurement and data interpretation can complicate the differentiation of PAH from other PH disorders and lead to misdiagnosis. In addition to diagnosis, the role of RHC in conjunction with noninvasive tests is widening rapidly to encompass monitoring of treatment response and establishing prognosis of patients diagnosed with PAH. However, further standardisation of RHC is warranted to ensure optimal use in routine clinical practice.

scholarly journals Increased TMEM16A-encoded calcium-activated chloride channel activity is associated with pulmonary hypertension

2012 ◽  
Vol 303 (12) ◽  
pp. C1229-C1243 ◽  
Author(s):  
Abigail S. Forrest ◽  
Talia C. Joyce ◽  
Marissa L. Huebner ◽  
Ramon J. Ayon ◽  
Michael Wiwchar ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Electromechanical Coupling ◽  
Pulmonary Arteries ◽  
Doppler Imaging ◽  
Heart Weight ◽  
Channel Activity ◽  
Cl Channels ◽  
Pulmonary Arterial ◽  
Pulmonary Artery Smooth Muscle

Pulmonary artery smooth muscle cells (PASMCs) are more depolarized and display higher Ca2+ levels in pulmonary hypertension (PH). Whether the functional properties and expression of Ca2+-activated Cl− channels (ClCa), an important excitatory mechanism in PASMCs, are altered in PH is unknown. The potential role of ClCa channels in PH was investigated using the monocrotaline (MCT)-induced PH model in the rat. Three weeks postinjection with a single dose of MCT (50 mg/kg ip), the animals developed right ventricular hypertrophy (heart weight measurements) and changes in pulmonary arterial flow (pulse-waved Doppler imaging) that were consistent with increased pulmonary arterial pressure and PH. Whole cell patch experiments revealed an increase in niflumic acid (NFA)-sensitive Ca2+-activated Cl− current [ ICl(Ca)] density in PASMCs from large conduit and small intralobar pulmonary arteries of MCT-treated rats vs. aged-matched saline-injected controls. Quantitative RT-PCR and Western blot analysis revealed that the alterations in ICl(Ca) were accompanied by parallel changes in the expression of TMEM16A, a gene recently shown to encode for ClCa channels. The contraction to serotonin of conduit and intralobar pulmonary arteries from MCT-treated rats exhibited greater sensitivity to nifedipine (1 μM), an l-type Ca2+ channel blocker, and NFA (30 or 100 μM, with or without 10 μM indomethacin to inhibit cyclooxygenases) or T16AInh-A01 (10 μM), TMEM16A/ClCa channel inhibitors, than that of control animals. In conclusion, augmented ClCa/TMEM16A channel activity is a major contributor to the changes in electromechanical coupling of PA in this model of PH. TMEM16A-encoded channels may therefore represent a novel therapeutic target in this disease.

Genetic counselling in pre-capillary pulmonary hypertension

ESC CardioMed ◽  
2018 ◽  
pp. 2558-2560
Author(s):  
Barbara Girerd ◽  
David Montani ◽  
Marc Humbert
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Genetic Counselling ◽  
Autosomal Dominant ◽  
Autosomal Dominant Disease ◽  
Pulmonary Capillary ◽  
Dominant Disease ◽  
Pulmonary Arterial ◽  
Biallelic Mutations

Pre-capillary pulmonary hypertension can be heritable in the context of pulmonary arterial hypertension (an autosomal dominant disease mainly due to mutations in BMPR2), and pulmonary veno-occlusive disease or pulmonary capillary haemangiomatosis (an autosomal recessive disease due to biallelic mutations in the EIF2AK4 gene). Genetic counselling can be implemented in referral centres for pulmonary hypertension as outlined in this chapter.

P4689How is the impact of updated hemodynamic definitions on frequencies of overall pulmonary hypertension and pre-capillary pulmonary hypertension as compared to those with previous criteria

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Tanyeri ◽  
B Keskin ◽  
O Y Akbal ◽  
A Hakgor ◽  
A Karagoz ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Critical Role ◽  
Right Heart ◽  
Right Heart Catheterisation ◽  
Mean Pressure ◽  
Pulmonary Arterial ◽  
European Society Of Cardiology ◽  
The Impact ◽  
Wedge Pressure

Abstract Background and aim In this study we evaluated the impact of the updated pulmonary hypertension (PH) definitive criteria proposed in 6th World PH Symposium (WSPH) on numbers and frequencies of and pre- versus post-capillary PH as compared to those in European Society of Cardiology (ESC) 2015 PH Guidelines. Methods Study group comprised the retrospectively evaluated 1299 patients (pts) (age 53.1±18.8 years, female 807, 62.1%) who underwent right heart catheterisation (RHC) with different indications between 2006 and 2018. For ESC and WSPH PH definitions, pulmonary arterial mean pressure (PAMP) ≥25 mmHg (definition-A) and PAMP >20 mmHg (definition-B) RHC criteria were used, respectively. For pre-capillary PH definitions, pulmonary artery wedge pressure (PAWP) ≤15 mmHg and pulmonary vascular resistance (PVR) ≥3 Wood units criteria were included in the both definitions. Results In RHC assessments, PAMP ≥25 mmHg and >20 mmHg were noted in 891 (68.6%) and 1051 (80.9%) of overall pts, respectively. Moreover, pre-capillary PH was diagnosed in 284 (21.8%) and 298 (22.9%) with definition-A and B, respectively. Although updated WSPH definition was associated with a net 12.3% and a relative 18% increase in the overall PH diagnosis, net and relative changes in the frequency of the pre-capillary PH were only 1% and 4.9%. Increase in the overall PH with updated WSPH criterias compared to previous ESC definitions was associated with increase in the number of pre-capillary PH (n=298, 22.9%) but not in the overall frequency of post-capillary PH (688, 52.9%). Because PVR was the product of the transpulmonary gradient (PAMP minus PAWP) divided by cardiac output, this measure was found to keep specificity for distinction between pre- versus post-capillary PH even after lowering thetreshold diagnostic for PAMP from 25 to 20 mmHg. Conclusions Although updated WSPH definition was associated with net 12.3% and relative 18% increase in the overall PH diagnosis, its impact on frequencies of pre- versus post-capillary PH within overall PH population was negligible.These seem to be due to critical role of PVR ensuring specificity in pre-capillary PH diagnosis even after lowering the definitive PAMP treshold to 20 mmHg.

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