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ABSTRACT: Background: Pulmonary hypertension (PH) of various causes leads to a poor prognosis. Pulmonary vasoreactivity testing during right heart catheterization (RHC) has prognostic and therapeutic consequences. Objective: To characterize the acute hemodynamic response to short-term oxygen supplementation (SHOT) in adult PH patients and its impact on prognosis. Methods: After a stable baseline period, 104 patients with PH [pulmonary arterial hypertension (PAH; n = 56), chronic thromboembolic (PH; n = 22) or respiratory diseases (PH; n = 26)], who were mainly therapy-naïve (86.5%) (mean pO(2) 64.5 ± 1.2 mm Hg), received a standardized SHOT during RHC and hemodynamic response was assessed for its prognostic potential. Results: SHOT significantly reduced heart rate (HR: 78.9 ± 1.5 to 74 ± 1.5 beats/min), cardiac output (4 ± 0.1 to 3.8 ± 0.1 l/min), pulmonary arterial pressure (46.4 ± 1.3 to 42.3 ± 1.3 mm Hg) and pulmonary vascular resistance (10.1 ± 0.5 to 9.6 ± 0.5 Wood units; all p < 0.001) compared to baseline. The magnitude of this effect varied between the different PH groups. During a median follow-up of 25.1 months (range: 0.2-73.3 months), HR <72 beats/min in response to SHOT was associated with a better prognosis in patients with PH due to chronic thromboembolism to the lung and PH from chronic lung disease. Conclusions: SHOT leads to characteristic hemodynamic responses across different forms of PH. The preserved capability to acutely respond to SHOT with HR reduction is of prognostic significance in patients with non PAH PH.
Respiration 10/2012; · 2.26 Impact Factor
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ABSTRACT: Inhalation of vasoactive substances is an effective treatment of pulmonary hypertension. The B-type natriuretic peptide (BNP) leads to relaxation of smooth muscle cells, caused by an increased formation of cyclic guanosine monophosphate (cGMP). The biologic activity of BNP using an inhalative approach has not been addressed.
In order to assess the vasorelaxing capacity of exogenous BNP in the isolated ventilated and buffer perfused rabbit lung model, a stable pulmonary vasoconstriction was established by either the application of endothelin-1 or the thromboxane A(2) mimetic U46619. This was followed by an intravascular or aerosol application of BNP. CGMP was measured in the recirculating buffer fluid using a radioimmunoassay technique.
During a stable plateau of U46619 induced pulmonary vasoconstriction (mean pulmonary artery pressure, PAP 25.5+/-0.23 mmHg), the intravascular administration of BNP induced a rapid vasodilation (mean PAP 18.13+/-0.95 mmHg, p<0.001). This vasodilation was dose dependent and was paralleled by a 6-fold increase of cGMP. When BNP was aerosolized, pulmonary vasoconstriction was also significantly alleviated in the U46619 model (mean PAP 22+/-2.1 mmHg) and during endothelin-1 induced vasoconstriction (mean PAP 17.1+/-2.47 mmHg). Correspondingly, inhalation caused a significant augmentation of cGMP levels was.
The vasodilative capability of BNP as an indicator of the biologic activity of this peptide is preserved during its aerosolization. Presumably these vascular actions are caused at least in part by an increased availability of cGMP.
Pulmonary Pharmacology & Therapeutics 07/2009; 22(6):548-53. · 2.80 Impact Factor
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ABSTRACT: Endothelin 1 (ET-1) is a potent pulmonary vasoconstrictor and mediator of lung diseases. Antagonism of the ET-1-mediated effects has become an important therapeutic approach. ET-1 (A and B) receptors are differentially distributed in the lung vasculature. Whereas the ET(A) receptors mainly mediate vasoconstriction, the endothelial ET(B) receptor seems to have vasodilative properties. We sought to determine if antagonism of ET receptors can be achieved by inhalation of specific blockers in a model of ET-1-mediated pulmonary hypertension.
AJP Lung Cellular and Molecular Physiology 05/2008; 294(4):L772-7. · 3.66 Impact Factor
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ABSTRACT: N-terminal pro-brain natriuretic peptide (NT-proBNP) is a byproduct of the brain natriuretic peptide (BNP) that was shown to be of prognostic value in pulmonary hypertension (PH). The role of NT-proBNP in PH has to be determined, especially under the influence of renal impairment that might lead to an accumulation of the peptide, and may be a sign of increased mortality per se.
We assessed NT-proBNP, BNP, renal function, and hemodynamic parameters (during right-heart catheterization) in 118 consecutive patients with isolated PH, excluding left-heart disease. Depending on the calculated creatinine clearance, patients were classified into different groups of renal function. Correlation analysis was performed on all key parameters. Results were then compared between the levels of renal function. The prognostic value of each parameter was assessed during a mean follow-up period of 10 months.
Twenty-two patients (approximately 19%) had significantly impaired renal function (creatinine clearance < 60 mL/min). Although the overall levels of NT-proBNP were correlated with hemodynamics, we observed no correlation in the group with significant renal dysfunction. Moreover, NT-proBNP was related to creatinine clearance. Finally, NT-proBNP and renal insufficiency were independent predictors of death during univariate and multivariate analysis, whereas BNP only predicted mortality in univariate analysis.
The diagnostic accuracy of NT-proBNP as a parameter of the hemodynamic status is diminished by renal function. However, NT-proBNP could be superior to BNP as a survival parameter in PH because it integrates hemodynamic impairment and renal insufficiency, which serves as a sign of increased mortality per se.
Chest 03/2007; 131(2):402-9. · 5.25 Impact Factor
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ABSTRACT: The detection of pulmonary hypertension in patients with chronic lung disease has prognostic implications. The brain natriuretic peptide (BNP) has been suggested as a noninvasive marker for the presence and severity of pulmonary hypertension.
We evaluated circulating BNP levels as a parameter for the presence and severity of pulmonary hypertension in patients with chronic lung disease.
BNP levels were measured in 176 consecutive patients with various pulmonary diseases. Right heart catheterization, lung functional testing, and a 6-min walk test were performed. The mean follow-up time was nearly 1 yr.
Significant pulmonary hypertension (mean pulmonary artery pressure > 35 mm Hg) was diagnosed in more than one-fourth of patients and led to decreased exercise tolerance and life expectancy. Elevated BNP concentrations identified significant pulmonary hypertension with a sensitivity of 0.85 and specificity of 0.88 and predicted mortality. Moreover, BNP served as a risk factor of death independent of lung functional impairment or hypoxemia in uni- and multivariate analysis.
We suggest BNP as a prognostic marker and as screening parameter for significant pulmonary hypertension in chronic lung disease.
American Journal of Respiratory and Critical Care Medicine 05/2006; 173(7):744-50. · 11.08 Impact Factor
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ABSTRACT: Pulmonary arterial hypertension (PAH) leads to substantial morbidity and mortality. Noninvasive parameters in the follow-up assessment of PAH could be helpful in clinical decision making. The brain natriuretic peptide (BNP) has been shown to correlate with the functional status and prognosis of these patients and could be a valuable parameter in this respect. The aim of our study was to investigate whether BNP levels could reflect clinical and hemodynamic changes, including the response to therapy during long-term follow-up in patients with PAH.
We measured pulmonary hemodynamics, functional parameters including the 6-min walk distance (6MWD), and plasma BNP levels at baseline and after a mean (+/- SEM) follow-up period of 12.6 +/- 1.5 months in patients with PAH.
In group A (n = 18), with decreasing BNP levels mean pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) decreased (PAP, 60.89 +/- 3.44 to 53.47 +/- 3.24 mm Hg; PVR, 1,207.47 +/- 111.75 to 942.35 +/- 103.15 dyne.s.cm(-5); p < 0.01) and 6MWD increased (408.24 +/- 29.57 to 470 +/- 25.54 m; p < 0.01). In group B (n = 12), with increasing BNP levels mean PAP and PVR increased (PAP, 52 +/- 3.31 to 60.17 +/- 5.03 mm Hg; PVR, 946.13 +/- 115.35 to 1,236.6 +/- 180.23 dyne . s . cm(-5); p < 0.01) and mean 6MWD decreased from 463.64 +/- 27.77 to 367.27 +/- 38.87 m (p < 0.05). Comparing groups revealed statistically significant differences regarding changes in PAP (group A, -11.58 +/- 3.57%; group B, +13.29 +/- 5.44%; p = 0.001) and PVR (group A, -19.21 +/- 5.87%, group B, +30.35 +/- 7.72%; p < 0.001). Correlations existed between the changes in BNP levels and pulmonary hemodynamics.
We concluded that BNP levels parallel changes in pulmonary hemodynamics and functional parameters, including the 6MWD, in PAH patients. Consequently, we suggest BNP as a parameter for the follow-up assessment of PAH patients.
Chest 10/2005; 128(4):2368-74. · 5.25 Impact Factor
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ABSTRACT: Idiopathic pulmonary arterial hypertension is a rare but serious and life-threatening disease that leads to right heart failure and death within 2.8 years without specific treatment. This review focuses on the stable prostacyclin analog iloprost, its biologic action and pharmacology and, finally, on its clinical development, efficacy and safety in patients with idiopathic pulmonary arterial hypertension, which led to its approval for this indication. Furthermore, this review assesses the role of iloprost compared with other newly developed drugs, such as the endothelin receptor antagonist bosentan and the phosphodiesterase-5 inhibitor sildenafil, as well as other modes of application of prostacyclin and its analogs for the treatment of idiopathic pulmonary arterial hypertension. Based on the different modes of action of these substances, a combination of these treatments could be most promising for the future.
Expert Review of Cardiovascular Therapy 04/2005; 3(2):215-23.
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ABSTRACT: Pulmonary hypertension (PH) can develop in lung fibrosis, and contributes to increased morbidity and mortality. Noninvasive parameters in the evaluation of PH in lung disease could aid in the management of these subjects. In this study, we aimed to characterize the role of brain natriuretic peptide (BNP) and the six-minute walk distance (6-MWD) in the assessment of pulmonary hypertension (PH) in subjects with lung fibrosis. Subjects with lung fibrosis and elevated BNP levels (n = 20) had significantly more severe PH during right heart catheterization than those with lung fibrosis, and normal BNP levels (mean pulmonary arterial pressure (40.85 +/- 3.2 mm Hg vs. 23.42+/-1.44 mm Hg, respectively) (n = 19) (p < 0.001). Significant correlations between lung volumes and BNP concentrations were not observed. A weak correlation existed between capillary pO(2) and 6-MWD (r = 0.42; p < 0.001). The presence of moderate-severe PH was associated with significant reduction of the 6-MWD. BNP concentrations predicted moderate-severe PH with 100% sensitivity and high specificity (89%). We conclude that BNP is an excellent marker for the presence of PH in patients with lung fibrosis. In addition, our data suggest that PH contributes significantly to exercise limitation in patients with severe lung fibrosis, raising the possibility that treatment of PH may be beneficial in these patients.
American Journal of Respiratory and Critical Care Medicine 09/2004; 170(4):360-5. · 11.08 Impact Factor
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ABSTRACT: The aim of this study was to investigate the potential role of brain natriuretic peptide (BNP) levels in the assessment of functional status and right heart performance in primary pulmonary hypertension (PPH).
Primary pulmonary hypertension is a progressive disease leading to right heart failure and death. Right heart catheterization and maximal or submaximal exercise tests are employed to assess the course of the disease and the effect of therapeutic interventions. Additional noninvasive and reproducible parameters would be helpful to assess the status of patients with PPH. The natriuretic peptide system is up-regulated in PPH patients. Brain natriuretic peptide (BNP) is produced from the cardiac ventricles and elevated in PPH. The aim of our study was to evaluate the clinical significance of BNP in PPH patients.
Correlation analysis was performed for plasma BNP levels of 28 PPH patients and World Health Organization (WHO) functional class (WHO-class), distance walked in 6 min, peak oxygen uptake (peak Vo(2)), and oxygen pulse during spiroergometry and various hemodynamic parameters, including pulmonary vascular resistance (PVR), pulmonary artery pressure (PAP), right atrial pressure (RAP), and cardiac index.
The BNP levels were inversely correlated with the 6-min walk (r = -0.70; p < 0.001) and peak Vo(2) (r = -0.61; p < 0.01), and positive correlation was observed with WHO-class (r = 0.79; p < 0.001). Moreover, BNP levels were also correlated to PVR (r = 0.61; p < 0.01), PAP (r = 0.48; p < 0.05), and RAP (r = 0.78; p < 0.01), and were inversely related to cardiac index (r = -0.48; p < 0.05).
Our data suggest that plasma BNP levels are closely related to the functional impairment of PPH patients and parallel the extent of pulmonary hemodynamic changes and right heart failure. Serial measurements of plasma BNP concentrations may help improve the management of PPH patients.
Journal of the American College of Cardiology 04/2004; 43(5):764-70. · 14.16 Impact Factor
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ABSTRACT: Different vasodilators and different routes of application are used for the treatment of primary pulmonary hypertension (PPH). Recently, sildenafil, a phosphodiesterase-V inhibitor, has been shown to have beneficial hemodynamic effects in PPH. However, the hemodynamic effects of sildenafil have not been characterized and compared to other vasodilators such as inhaled nitric oxide (iNO) or iloprost in PPH in the same group of patients.
We investigated prospectively 10 consecutive patients with PPH using iNO, iloprost aerosol, and oral sildenafil to test acute hemodynamic response during right-heart catheterization.
iNO, iloprost aerosol, and sildenafil caused a significant fall of mean pulmonary artery pressure and pulmonary vascular resistance (PVR) [p < 0.05]. Correspondingly, cardiac output and mixed venous saturation increased slightly in all groups. Systemic arterial pressure and vascular resistance were mainly unaltered. Using a PVR reduction of > or =20% to define a significant response, 7 of 10 patients were responders to iloprost aerosol, whereas 4 of 10 patients responded to iNO and oral sildenafil. Improvement of oxygenation as indicated by an increase of arterial oxygen tension was observed with iloprost aerosol (p < 0.01).
All of the three substances, iNO, iloprost aerosol, and oral sildenafil, significantly improved pulmonary hemodynamics in patients with PPH. The most prominent hemodynamic effects and improvement of oxygenation were observed with iloprost aerosol.
Chest 02/2004; 125(2):580-6. · 5.25 Impact Factor
