Pulmonary Arterial Impedance Research Articles

Effects of nitric oxide inhalation on pulmonary arterial impedance: differences between normal and pulmonary hypertension male rats.

Nitric oxide (NO) inhalation improves pulmonary hemodynamics in participants with pulmonary arterial hypertension (PAH). Although it can reduce pulmonary vascular resistance (PVR) in PAH, its impact on the dynamic mechanics of pulmonary arteries and its potential difference between control and participants with PAH remain unclear. PA impedance provides a comprehensive description of PA mechanics. With an arterial model, PA impedance can be parameterized into peripheral pulmonary resistance (Rp), arterial compliance (Cp), characteristic impedance of the proximal arteries (Zc), and transmission time from the main PA to the reflection site. This study investigated the effects of inhaled NO on PA impedance and its associated parameters in control and monocrotaline-induced pulmonary arterial hypertension (MCT-PAH) male rats (6/group). Measurements were obtained at baseline and during NO inhalation at 40 and 80 ppm. In both groups, NO inhalation decreased PVR and increased the left atrial pressure. Notably, its impact on PA impedance was frequency dependent, as revealed by reduced PA impedance modulus in the low-frequency range below 10 Hz, with little effect on the high-frequency range. Furthermore, NO inhalation attenuated Rp, increased Cp, and prolonged transmission time without affecting Zc. It reduced Rp more pronouncedly in MCT-PAH rats, whereas it increased Cp and delayed transmission time more effectively in control rats. In conclusion, the therapeutic effects of inhaled NO on PA impedance were frequency dependent and may differ between the control and MCT-PAH groups, suggesting that the effect on the mechanics differs depending on the pathological state.NEW & NOTEWORTHY Nitric oxide inhalation decreased pulmonary arterial impedance in the low-frequency range (<10 Hz) with little impact on the high-frequency range. It reduced peripheral pulmonary resistance more pronouncedly in pulmonary hypertension rats, whereas it increased arterial compliance and transmission time in control rats. Its effect on the mechanics of the pulmonary arteries may differ depending on the pathological status.

Increased left atrial pressure distorts pulmonary arterial impedance estimates in the low-range of frequency in rats

BACKGROUD: Post-capillary pulmonary hypertension (PH), characterized as increased downstream pressure such as left atrial pressure (LAP), is the most prevalent type of PH and a significant contributor to right heart failure. Accurate estimation of pulmonary arterial characteristics, serving as right ventricular afterload, is crucial for management of PH. These characteristics can be captured comprehensively through pulmonary arterial impedance (PAZ), which elucidates pulmonary arterial pressure-flow relationship within the frequency domain. Although LAP waveforms are potential to affect the contours of pulmonary arterial pressure (PAP) and flow (PAF) waveforms, it remains unknown whether increased LAP affects the accuracy of PAZ measurement. This study aimed to investigate the impact of LAP on the accuracy of PAZ using an acute rodent model. METHODS: We measured pulmonary arterial blood flow (PAF), PAP, and LAP simultaneously in eight male Sprague-Dawley rats. PAZ was calculated as a reciprocal of admittance. Admittance was calculated in the following two ways: 1) one-input (PAP) and one-output (PAF) analysis (I1O1 analysis): the ratio of PAP(f) to PAF(f) at each frequency, where PAP(f) and PAF(f) are frequency spectra of PAP and PAF, respectively, and 2) two-input (PAP and LAP) and one-output (PAF) analysis (I2O1 analysis): excluding the potential effect of LAP from PAP and PAF. We measured PAZ under both normal physiological condition and post-capillary PH condition. To induce acute post-capillary PH by raising LAP &gt;15 mmHg, we ligated aortic arch at the site between brachiocephalic artery and left common carotid artery and performed blood transfusion from a donor rat (TAL/BT). The accuracy of PAZ was examined as the coherence function representing the linearity between the input and output signals. Results: TAL/BT significantly increased LAP from 3 ± 1mmHg to 21 ± 4 mmHg and PAP from 17 ± 3 mmHg to 34 ± 3 mmHg (p&lt;0.01 for both). The I2O1 analysis provided a consistently accurate estimation of PAZ under both normal and elevated LAP conditions with high coherence function (&gt;0.9) in the wide range of frequency between 0.12 and 10.7 Hz. The I1O1 analysis also estimated the PAZ accurately in normal condition with high coherence function (&gt;0.9) in the wide range of frequency, however, the I1O1 analysis overestimated PAZ in the low-range frequency between 0.12 and 1.0 Hz compared with the I2O1 analysis (I1O1: 0.32±0.10 vs. I2O1 0.23±0.06 mmHg/ml/min, p&lt;0.01), with significantly lower coherence function (I1O1: 0.77±0.05 vs. I2O1: 0.96±0.01, p&lt;0.01). CONCLUSION: Increased LAP may have the impact on the accuracy of PAZ estimation in the low-range frequency. The I2O1 analysis can lead to more accurate assessment of right ventricular afterload in post-capillary PH, compared with the I1O1 analysis. Grant-in-Aid for Young Scientists of the Japanese Society of Cardiovascular Anesthesiologists Project Number 2271000048. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A Novel Method to Assess Pulmonary Arterial Impedance in Patients Undergoing Investigation for Pulmonary Hypertension

In patients with pulmonary hypertension (PH), the pulmonary vasculature becomes a high-pressure, high-resistance, low-compliance system. The effect is to create additional load on the right ventricle (RV) and alter RV-pulmonary arterial (RV-PA) coupling. We evaluated the feasibility of pulmonary arterial impedance (PA-Zc) determination in patients with known or suspected PH during routine cardiac magnetic resonance imaging (MRI) and right heart catheterisation (RHC).

Hemodynamically Unloading the Distal Pulmonary Circulation in Pulmonary Hypertension: A Modeling Study.

Pulmonary hypertension (PH) is a progressive disease that is characterized by a gradual increase in both resistive and reactive pulmonary arterial (PA) impedance. Previous studies in a rodent model of PH have shown that reducing the hemodynamic load in the left lung (by banding the left PA) reverses this remodeling phenomenon. However, banding a single side of the pulmonary circulation is not a viable clinical option, so-using in silico modeling-we evaluated if the banding effect can be recreated by replacing the proximal vasculature with a compliant synthetic PA. We developed a computational model of the pulmonary circulation by combining a one-dimensional model of the proximal vasculature with a zero-dimensional line transmission model to the 12th generation. Using this model, we performed four simulations: (1) Control; (2) PH; (3) PH with a stenosis in the left PA; and (4) PH with proximal vessel compliance returned to Control levels. Simulations revealed that vascular changes associated with PH result in an increase in pulse pressure (PP), maximum pressure (Pmax), maximum wall shear stress (WSS), and maximum circumferential stress (σθθ) relative to controls, in the distal circulation. Banding the left PA reduced these measurements of hemodynamic stress in the left lung, but increases them in the right lung. Furthermore, left PA banding increased reactive PA impedance. However, returning the proximal PA compliance to Control levels simultaneously decreased all measures of hemodynamic stress in both lungs, and returned reactive PA impedance to normal levels. In conclusion, if future in vivo studies support the idea of hemodynamic unloading as an effective therapy for PH, this can be surgically achieved by replacing the proximal PA with a compliant prosthesis, and it will have the added benefit of reducing reactive right ventricular afterload.

RV Failure in Pulmonary Hypertension Amplified by Secondary Hemochromatosis

<h3>Introduction</h3> A 38-year-old female with history of beta thalassemia requiring several blood transfusions yearly presented with fatigue and dyspnea. <h3>Case Report</h3> Transthoracic echocardiogram (TTE) revealed severe RV dysfunction and severe tricuspid regurgitation (figure 1) with elevated estimated RV systolic pressure. A presumptive diagnosis of right heart failure secondary to PH was made and the patient was empirically started on PH-specific therapy. The PH team was consulted. Careful review of the TTE revealed several features that were inconsistent with a RV failing due to high afterload. Systolic interventricular septal flattening occurs when the RV is being subjected to a high pulmonary vascular resistance (PVR). Notching of the RV outflow tract (RVOT) Doppler and earlier time to peak velocity (acceleration time) occurs with high pulmonary arterial impedance. None of these features were present on TTE. Right heart catheterization was confirmatory, demonstrating right atrial pressure 19 mmHg, pulmonary artery pressure 33/22 mmHg, wedge pressure 8 mmHg, PVR 4 Woods units, and cardiac index 2.6 L/min/m². The degree of RV dysfunction was felt to be out of proportion to the degree of PH. Taken together with frequent premature ventricular contractions, cardiac MRI was performed to evaluate for another etiology of RV failure. T2 measurements were consistent with cardiac iron overload (figure 1). Serum ferritin was 26,713 ng/mL. Secondary hemochromatosis was diagnosed due to frequent blood transfusions for thalassemia management. The patient underwent IV iron chelation therapy with improvement in RV function and tricuspid regurgitation. <h3>Summary</h3> The severity of RV failure should be interpreted relative to the severity of PVR elevation in PH. Septal position and RVOT Doppler assessment on TTE can provide valuable insight into the physiology and mechanism of right ventricular failure. This case demonstrates this application, with subsequent use of MRI to confirm a rare diagnosis of RV failure due to secondary hemochromatosis

The pulsatile component of left atrial pressure has little effect on pulmonary artery impedance estimation in normal rats.

Pulmonary artery impedance (PAZ) that measures the pulsatile properties of the vasculature provides diagnostic and prognostic information in patients with pulmonary vascular diseases. While downstream pressure [i.e., left atrial (LA) pressure] should be considered when calculating static properties of pulmonary vasculature, PAZ is commonly estimated without taking into account the pulsatile component of LA pressure. We examined whether PAZ can be estimated with reasonable accuracy without using LA pressure. Pulmonary artery (PA) flow, PA pressure, and LA pressure were measured under irregular pacing in eight normal Sprague‐Dawley rats. PAZ was estimated by analyzing a one‐input, one‐output system (I1O1 analysis) that does not include LA pressure, and a two‐input, one‐output system (I2O1 analysis) that includes LA pressure. Using a tube and 3‐element Windkessel model, PAZ was parameterized as peripheral resistance (RP), arterial compliance (CP), characteristic impedance (ZC), and transmission time to the reflection site (TD). These parameters were not significantly different between the I1O1 and I2O1 analyses (RP: 0.286 ± 0.040 vs. 0.274 ± 0.038 mmHg·min/mL, CP: 0.352 ± 0.049 vs. 0.343 ± 0.041 mL/mmHg, ZC: 0.115 ± 0.005 vs. 0.117 ± 0.005 mmHg·min/mL, TD: 13.2 ± 1.8 vs. 12.9 ± 1.7 msec). In conclusion, the I1O1 analysis that does not use LA pressure estimates PAZ with reasonable accuracy compared with the I2O1 analysis that uses LA pressure in normal rats. Our finding that the pulsatile component of LA pressure contributes little to PAZ estimation may justify the clinical use of the I1O1 analysis.

Computational Fluid Dynamics Modeling of the Human Pulmonary Arteries with Experimental Validation.

Pulmonary hypertension (PH) is a chronic progressive disease characterized by elevated pulmonary arterial pressure, caused by an increase in pulmonary arterial impedance. Computational fluid dynamics (CFD) can be used to identify metrics representative of the stage of PH disease. However, experimental validation of CFD models is often not pursued due to the geometric complexity of the model or uncertainties in the reproduction of the required flow conditions. The goal of this work is to validate experimentally a CFD model of a pulmonary artery phantom using a particle image velocimetry (PIV) technique. Rapid prototyping was used for the construction of the patient-specific pulmonary geometry, derived from chest computed tomography angiography images. CFD simulations were performed with the pulmonary model with a Reynolds number matching those of the experiments. Flow rates, the velocity field, and shear stress distributions obtained with the CFD simulations were compared to their counterparts from the PIV flow visualization experiments. Computationally predicted flow rates were within 1% of the experimental measurements for three of the four branches of the CFD model. The mean velocities in four transversal planes of study were within 5.9 to 13.1% of the experimental mean velocities. Shear stresses were qualitatively similar between the two methods with some discrepancies in the regions of high velocity gradients. The fluid flow differences between the CFD model and the PIV phantom are attributed to experimental inaccuracies and the relative compliance of the phantom. This comparative analysis yielded valuable information on the accuracy of CFD predicted hemodynamics in pulmonary circulation models.

Wave reflection correlates with pulmonary vascular wall thickening in rats with pulmonary arterial hypertension

BackgroundWave reflection is enhanced in patients with pulmonary arterial hypertension (PAH), which may be derived from a mismatch of pulmonary artery (PA) impedance between proximal and distal sites of arteries. Whether enhanced wave reflection correlates with histological remodeling remains unknown, partly because lung biopsy is not clinically recommended for PAH patients due to substantial risks of mortality and morbidity. MethodsPulmonary hypertension was induced by SU5416 injection and 3-week hypoxic exposure (SuHx-PH) in rats, and hemodynamic and histological examinations were performed at 4weeks (SuHx-PH4W) and 8weeks (SuHx-PH8W) after SU5416 injection (n=7 each). Two groups of age-matched normal rats were also analyzed (n=7 each). Using an elastic tube with a 3-element Windkessel model, PA impedance was parameterized as pulmonary artery compliance (CP), peripheral resistance (RP), characteristic impedance (ZC), and transmission time (TD) in conducting arteries. Wave reflection was quantified as reflection gain at 0 Hz (Γgain) in the frequency domain, and as the ratio of peak backward pressure to peak forward pressure (KB/F) in the time domain. ResultsThe SuHx-PH groups demonstrated increased RP and ZC, and decreased CP and TD compared with normal groups. Γgain and KB/F were significantly higher in the SuHx-PH8W group than in the SuHx-PH4W group, and correlated strongly with a histological index of vascular wall thickening (R2=0.839, P<0.001 for Γgain and R2=0.775, P<0.001 for KB/F). ConclusionsEnhanced wave reflection caused by abnormal PA impedance correlates with histological remodeling, and may have a diagnostic value in clinical staging of PAH.

A Zero-Dimensional Model and Protocol for Simulating Patient-Specific Pulmonary Hemodynamics From Limited Clinical Data.

In pulmonary hypertension (PH) diagnosis and management, many useful functional markers have been proposed that are unfeasible for clinical implementation. For example, assessing right ventricular (RV) contractile response to a gradual increase in pulmonary arterial (PA) impedance requires simultaneously recording RV pressure and volume, and under different afterload/preload conditions. In addition to clinical applications, many research projects are hampered by limited retrospective clinical data and could greatly benefit from simulations that extrapolate unavailable hemodynamics. The objective of this study was to develop and validate a 0D computational model, along with a numerical implementation protocol, of the RV-PA axis. Model results are qualitatively compared with published clinical data and quantitatively validated against right heart catheterization (RHC) for 115 pediatric PH patients. The RV-PA circuit is represented using a general elastance function for the RV and a three-element Windkessel initial value problem for the PA. The circuit mathematically sits between two reservoirs of constant pressure, which represent the right and left atriums. We compared Pmax, Pmin, mPAP, cardiac output (CO), and stroke volume (SV) between the model and RHC. The model predicted between 96% and 98% of the variability in pressure and 98-99% in volumetric characteristics (CO and SV). However, Bland Altman plots showed the model to have a consistent bias for most pressure and volumetric parameters, and differences between model and RHC to have considerable error. Future studies will address this issue and compare specific waveforms, but these initial results are extremely promising as preliminary proof of concept of the modeling approach.

Early recovery of tricuspid annular isovolumic acceleration after mitral valve surgery - an observational study.

Patients undergoing mitral valve surgery are at risk for right ventricular (RV) dysfunction resulting from increased left atrial pressure and increased pulmonary artery impedance. Measures of longitudinal measures of RV function, such as displacement, are commonly performed but have been shown to be depressed after cardiac surgery despite good patient recovery. The aim of this observational study was to assess the early perioperative time course of longitudinal transthoracic echocardiographic (TTE) markers of RV function in a patient population undergoing mitral valve surgery. Twenty patients undergoing mitral valve surgery were enrolled in this observational study. Right ventricular longitudinal measurements (tricuspid annular plane systolic excursion [TAPSE], strain, annular velocity [S'], and isovolumic acceleration [IVA]) were performed using TTE and colour Doppler imaging preoperatively (day 1) and postoperatively (days 2 and 6). Comparisons were made between the preoperative and postoperative measurements. Adequate echocardiographic imaging was obtained for all 20 patients. The TAPSE, strain, and S' measures remained depressed for up to one week (i.e., day 6) after surgery compared to preoperative values. The IVA was depressed on the first postoperative day (P > 0.001), but by day 6 it was no different from the preoperative value (P = 0.37). The median [interquartile range] time to discharge from hospital was 7 [6-9] days. Persistent, significant depression of longitudinal markers of RV function despite functional improvement (discharge from hospital) make it difficult to assess recovery during the early perioperative period. Isovolumic acceleration, a load-independent measure of contractility, might be a more reliable measure of early recovery in RV function in this patient population.

NOVEL NON-INVASIVE ASSESSMENT OF PULMONARY ARTERIAL IMPEDANCE USING CARDIAC MAGNETIC RESONANCE IMAGING

The ability to assess pulmonary artery impedance (PAI) non-invasively will help detect early pulmonary artery (PA) remodeling as it takes into account pulsatility of PA. We describe a novel surrogate of invasive PAI, velocity transfer function (VTF), measured on cardiac magnetic resonance (CMR) and

Development of a servo pump system for in vivo loading of pathological pulmonary artery impedance on the right ventricle of normal rats.

Pulmonary artery (PA) impedance provides detailed information on right ventricular (RV) afterload in pulmonary hypertension (PH). This study aimed to examine PA impedance in a rat model of monocrotaline-induced PH (MCT-PH) and to develop an experimental system for in vivo loading of pathological PA impedance on the RV of normal rats. PA impedance was quantified in normal (n= 10) and MCT-PH rats (n= 10) using a three-element Windkessel (3-WK) model. Compared with normal rats, MCT-PH rats had higher characteristic impedance (ZC) and peripheral pulmonary resistance (RP) (ZC: 0.121 ± 0.039 vs. 0.053 ± 0.017 mmHg·min·ml(-1), P< 0.001; RP: 0.581 ± 0.334 vs. 0.252 ± 0.105 mmHg·min·ml(-1), P= 0.013) and lower pulmonary artery compliance (CP) (0.242 ± 0.131 vs. 0.700 ± 0.186 ml/mmHg, P< 0.001). In another group of 10 normal rats, a computer-controlled servo pump was connected to the left PA for loading PA impedance with parameters in pathological ranges designed by the 3-WK model. Activation of the servo pump decreased the error of measured vs. target PA impedance (modulus: from 0.047 ± 0.020 without pump activation to 0.019 ± 0.007 with pump activation,P< 0.001; phase: 0.085 ± 0.028 to 0.043 ± 0.012 radians,P< 0.001). In conclusion, MCT-PH increases ZC and RP and decreases CP Our servo pump system, which is capable of imposing arbitrary PA impedance with pathological parameters, may offer a unique opportunity to delineate the pathological significance of PA impedance in PH.

A pulmonary artery loading system to impose pathological pulmonary artery impedance in rats

A pulmonary artery loading system to impose pathological pulmonary artery impedance in rats

Intrauterine endotoxin-induced impairs pulmonary vascular function and right ventricular performance in infant rats and improvement with early vitamin D therapy.

High pulmonary vascular resistance (PVR), proximal pulmonary artery (PA) impedance, and right ventricular (RV) afterload due to remodeling contribute to the pathogenesis and severity of pulmonary hypertension (PH). Intra-amniotic exposure to endotoxin (ETX) causes sustained PH and high mortality in rat pups at birth, which are associated with impaired vascular growth and RV hypertrophy in survivors. Treatment of ETX-exposed pups with antenatal vitamin D (vit D) improves survival and lung growth, but the effects of ETX exposure on RV-PA coupling in the neonatal lung are unknown. We hypothesized that intrauterine ETX impairs RV-PA coupling through sustained abnormalities of PA stiffening and RV performance that are attenuated with vit D therapy. Fetal rats were exposed to intra-amniotic injections of ETX, ETX+vit D, or saline at 20 days gestation (term = 22 days). At postnatal day 14, pups had pressure-volume measurements of the RV and isolated proximal PA, respectively. Lung homogenates were assayed for extracellular matrix (ECM) composition by Western blot. We found that ETX lungs contain decreased α-elastin, lysyl oxidase, collagen I, and collagen III proteins (P < 0.05) compared control and ETX+vit D lungs. ETX-exposed animals have increased RV mechanical stroke work (P < 0.05 vs. control and ETX+vit D) and elastic potential energy (P < 0.05 vs. control and ETX+vit D). Mechanical stiffness and ECM remodeling are increased in the PA (P < 0.05 vs. control and ETX+vit D). We conclude that intrauterine exposure of fetal rats to ETX during late gestation causes persistent impairment of RV-PA coupling throughout infancy that can be prevented with early vit D treatment.

A servo-control system to impose desired pulmonary artery impedance in rats

A servo-control system to impose desired pulmonary artery impedance in rats

Dexmédétomidine et clonidine : revue de leurs propriétés pharmacodynamiques en vue de définir la place des agonistes alpha-2 adrénergiques dans la sédation en réanimation

Alpha-2 adrenergic agonists (“alpha-2 agonists”) present multiple pharmacodynamic effects: rousable sedation, decreased incidence of delirium in the setting of critical care, preservation of respiratory drive, decreased whole body oxygen consumption, decreased systemic and pulmonary arterial impedance, improved left ventricular systolic and diastolic function, preserved vascular reactivity to exogenous catecholamines, preserved vasomotor baroreflex with lowered set point, preserved kidney function, decreased protein catabolism. These pharmacodynamic effects explain the interest for these drugs in the critical care setting. However, their exact role for sedation in critically ill-patients remains open for further studies. Given the few double-blind randomized multicentric trials available, the present non exhaustive analysis of the literature aims at presenting the utilization of alpha-2 agonists as potential first-line sedative agents, in the critical care setting. Suggestions regarding the use of alpha-2 agonists as sedatives are detailed.

63: Fetal pulmonary arterial vascular impedance reflects changes in fetal oxygenation in primate model at near term gestation

63: Fetal pulmonary arterial vascular impedance reflects changes in fetal oxygenation in primate model at near term gestation

Feasibility of Routine Pulmonary Arterial Impedance Measurements in Pulmonary Hypertension

Right ventricular (RV) afterload is best described by a pulmonary arterial impedance (PVZ) spectrum, which integrates pulmonary vascular resistance (PVR), elastance, and wave reflection. We evaluated the feasibility of PVZ determinations in patients with pulmonary arterial hypertension (PAH) during routine right heart catheterization and Doppler echocardiography. Prospective study. Academic hospital. Twenty-two patients with PAH. Right heart catheterization with a fluid-filled Swan-Ganz catheter, Doppler echocardiography, and administration of inhaled nitric oxide (NO) [10 to 20 ppm; 17 patients], maximum tolerated dose of IV epoprostenol (average, 8.5 ng/kg/min; 5 patients), and IV dobutamine (8 micro g/kg/min; 8 patients). PVZ was calculated from the spectral analysis of synchronized pulmonary artery pressure (Ppa) and flow waves. The mean (+/- SE) Ppa was 63 +/- 3 mm Hg, and the mean PVR was 16 +/- 2 Wood units. The PVZ spectrum was markedly shifted to higher than normal pressures and frequencies, with a mean 0-Hz impedance (Z(0)) of 1,506 +/- 138 dyne. s. cm(-5), and a mean characteristic impedance (Zc) of 124 +/- 11 dyne. s. cm(-5), which are in keeping with data from previous studies. Inhaled NO levels decreased Ppa, PVR, Z(0), and Zc without a change in cardiac output. Epoprostenol administration did not affect Ppa, increased cardiac output, and decreased Z(0) and Zc. Dobutamine administration increased cardiac output and Ppa, and decreased PVR and Z(0), without changing Zc. The determination of PVZ to quantify RV afterload is feasible during routine right heart catheterization and Doppler echocardiography. The measurement is sensitive to pharmacologic interventions.

Correlation of continuous cardiac output measured by a pulmonary artery catheter versus impedance cardiography in ventilated patients

Cardiac output can be measured continuously by an invasive pulmonary artery catheter (PAC) or by noninvasive impedance cardiography. The purpose of this study is to determine how well the two methods correlate in ventilated patients.

Expression of the serotonin 1b receptor in experimental pulmonary hypertension.

The pathogenesis of pulmonary arterial hypertension (PAH) remains uncertain. Both the serotonin and endothelin (ET) systems are believed to be involved. Recent studies pointed to the importance of the serotonin 2B receptor as a limiting step. The current authors investigated the lung tissue expression of serotonin receptors and of the serotonin transporter (5-HTT) by real-time-quantitative polymerase chain reaction in chronic overcirculation-induced PAH in growing piglets, with and without treatment with the dual ET receptor blocker bosentan. Pulmonary haemodynamic changes were described by pulmonary arterial impedance spectra. Three months after the surgical anastomosis of the left subclavian artery to the pulmonary arterial trunk, there was a shift of the impedance spectra to higher ratios of pressure and flow moduli, with increases in both 0 Hz impedance and characteristic impedance, and these changes were completely prevented by bosentan therapy. There was an increase in the expression of the serotonin 1B receptor. There was no change in the expression of the 5-HTT, and of the serotonin 2B, 1D, and 4 receptors. The overexpression of the serotonin 1B receptor was partially prevented by bosentan therapy. The present authors conclude that this early pulmonary arterial hypertension model is characterised by an endothelin receptor-dependent increased expression of the serotonin 1B receptor.