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Sample records for pulmonary arterial pressure

  1. Pulmonary Artery Denervation Reduces Pulmonary Artery Pressure and Induces Histological Changes in an Acute Porcine Model of Pulmonary Hypertension

    PubMed Central

    Arnold, Nadine D.; Chang, William; Watson, Oliver; Swift, Andrew J.; Condliffe, Robin; Elliot, Charlie A.; Kiely, David G.; Suvarna, S. Kim; Gunn, Julian; Lawrie, Allan

    2015-01-01

    Background— Pulmonary arterial hypertension is a devastating disease with high morbidity and mortality and limited treatment options. Recent studies have shown that pulmonary artery denervation improves pulmonary hemodynamics in an experimental model and in an early clinical trial. We aimed to evaluate the nerve distribution around the pulmonary artery, to determine the effect of radiofrequency pulmonary artery denervation on acute pulmonary hypertension induced by vasoconstriction, and to demonstrate denervation of the pulmonary artery at a histological level. Methods and Results— Histological evaluation identified a circumferential distribution of nerves around the proximal pulmonary arteries. Nerves were smaller in diameter, greater in number, and located in closer proximity to the luminal aspect of the pulmonary arterial wall beyond the pulmonary artery bifurcation. To determine the effect of pulmonary arterial denervation acute pulmonary hypertension was induced in 8 pigs by intravenous infusion of thromboxane A2 analogue. Animals were assigned to either pulmonary artery denervation, using a prototype radiofrequency catheter and generator, or a sham procedure. Pulmonary artery denervation resulted in reduced mean pulmonary artery pressure and pulmonary vascular resistance and increased cardiac output. Ablation lesions on the luminal surface of the pulmonary artery were accompanied by histological and biochemical alteration in adventitial nerves and correlated with improved hemodynamic parameters. Conclusions— Pulmonary artery denervation offers the possibility of a new treatment option for patients with pulmonary arterial hypertension. Further work is required to determine the long-term efficacy and safety. PMID:26553697

  2. Determinants of an elevated pulmonary arterial pressure in patients with pulmonary arterial hypertension.

    PubMed

    Sakao, Seiichiro; Voelkel, Norbert F; Tanabe, Nobuhiro; Tatsumi, Koichiro

    2015-01-01

    Given the difficulty of diagnosing early-stage pulmonary arterial hypertension (PAH) due to the lack of signs and symptoms, and the risk of an open lung biopsy, the precise pathological features of presymptomatic stage lung tissue remain unknown. It has been suggested that the maximum elevation of the mean pulmonary arterial pressure (P pa) is achieved during the early symptomatic stage, indicating that the elevation of the mean P pa is primarily driven by the pulmonary vascular tone and/or some degree of pulmonary vascular remodeling completed during this stage. Recently, the examination of a rat model of severe PAH suggested that the severe PAH may be primarily determined by the presence of intimal lesions and/or the vascular tone in the early stage. Human data seem to indicate that intimal lesions are essential for the severely increased pulmonary arterial blood pressure in the late stage of the disease.However, many questions remain. For instance, how does the pulmonary hemodynamics change during the course of the disease, and what drives the development of severe PAH? Although it is generally acknowledged that both pulmonary vascular remodeling and the vascular tone are important determinants of an elevated pulmonary arterial pressure, which is the root cause of the time-dependent progression of the disease? Here we review the recent histopathological concepts of PAH with respect to the progression of the lung vascular disease.

  3. Rarefaction and blood pressure in systemic and pulmonary arteries.

    PubMed

    Olufsen, Mette S; Hill, N A; Vaughan, Gareth D A; Sainsbury, Christopher; Johnson, Martin

    2012-08-01

    The effects of vascular rarefaction (the loss of small arteries) on the circulation of blood are studied using a multiscale mathematical model that can predict blood flow and pressure in the systemic and pulmonary arteries. We augmented a model originally developed for the systemic arteries (Olufsen et al. 1998, 1999, 2000, 2004) to (a) predict flow and pressure in the pulmonary arteries, and (b) predict pressure propagation along the small arteries in the vascular beds. The systemic and pulmonary arteries are modelled as separate, bifurcating trees of compliant and tapering vessels. Each tree is divided into two parts representing the `large' and `small' arteries. Blood flow and pressure in the large arteries are predicted using a nonlinear cross-sectional area-averaged model for a Newtonian fluid in an elastic tube with inflow obtained from magnetic resonance measurements. Each terminal vessel within the network of the large arteries is coupled to a vascular bed of small `resistance' arteries, which are modelled as asymmetric structured trees with specified area and asymmetry ratios between the parent and daughter arteries. For the systemic circulation, each structured tree represents a specific vascular bed corresponding to major organs and limbs. For the pulmonary circulation, there are four vascular beds supplied by the interlobar arteries. This manuscript presents the first theoretical calculations of the propagation of the pressure and flow waves along systemic and pulmonary large and small arteries. Results for all networks were in agreement with published observations. Two studies were done with this model. First, we showed how rarefaction can be modelled by pruning the tree of arteries in the microvascular system. This was done by modulating parameters used for designing the structured trees. Results showed that rarefaction leads to increased mean and decreased pulse pressure in the large arteries. Second, we investigated the impact of decreasing vessel

  4. Relationship between colloid osmotic pressure and pulmonary artery wedge pressure in patients with acute cardiorespiratory failure.

    PubMed

    Weil, M H; Henning, R J; Morissette, M; Michaels, S

    1978-04-01

    Close relationships between progressive respiratory failure, roentgenographic signs of pulmonary opacification and decreases in the difference between colloid osmotic pressure of plasma and the pulmonary artery wedge pressure (colloid-hydrosatic pressure gradient) were demonstrated in 49 critically ill patients with multisystem failure, in patients in shock. The potential importance of this relationship is underscored by the observation that fatal progression of pulmonary edema was related to a critical reduction in the colloid-hydrostatic pressure gradient to levels of less than 0 mm Hg. More often, reduction in colloid osmotic pressure rather than increases in left ventricular filling pressure (pulmonary artery wedge pressure) accounted for the decline in colloid-hydrostatic pressure gradient. Routine measurement of colloid osmotic pressure, preferably in conjunction with pulmonary artery wedge pressure, is likely to improve understanding of the mechanisms of acute pulmonary edema.

  5. A new system for ambulatory pulmonary artery pressure recording

    PubMed Central

    Simon, J; Gibbs, R; MacLachlan, Donald; Fox, Kim M

    1992-01-01

    Objective—To develop a complete system for the measurement, recording, and analysis of ambulatory pulmonary artery pressure. Design—The new system consists of a pulmonary artery catheter, an ambulatory recorder, and a desktop computer. Pulmonary artery pressure is measured by a micromanometer tipped catheter with an in vivo calibration system to allow correction for zero drift. This catheter is plugged into a small battery powered recorder. The recorder has two input channels, one for pressure and one for an event marker. The pressure wave is sampled 32 times/s, processed by an in built computer, compressed, and stored in semiconductor memory. On completion of a recording, data is transferred from the ambulatory recorder through a serial data link to an Acorn Archimedes desktop computer on which further data processing, statistical analysis, graphics, and printouts can be obtained. Results—The system has been used in 18 patients, with technically successful recording in 14, less than 15 minutes of data loss in three, and 12 hours of data loss in one. Conclusions—A new system for ambulatory pulmonary artery monitoring has been developed and used clinically with success. It may provide new perspectives on the pathophysiology of disease as it applies to everyday life. PMID:1389746

  6. Catheter fragmentation of acute massive pulmonary thromboembolism: distal embolisation and pulmonary arterial pressure elevation.

    PubMed

    Nakazawa, K; Tajima, H; Murata, S; Kumita, S-I; Yamamoto, T; Tanaka, K

    2008-11-01

    The aim of this study was to evaluate the relationship between pulmonary arterial pressure and distal embolisation during catheter fragmentation for the treatment of acute massive pulmonary thromboembolism with haemodynamic impairment. 25 patients with haemodynamic impairment (8 men and 17 women; aged 27-82 years) were treated by mechanical thrombus fragmentation with a modified rotating pigtail catheter. After thrombus fragmentation, all patients received local fibrinolytic therapy, followed by manual clot aspiration using a percutaneous transluminal coronary angioplasty (PTCA) guide catheter. Pulmonary arterial pressure was continuously recorded during the procedure. The Friedman test and Wilcoxon test were applied for statistical analysis. Distal embolisation was confirmed by digital subtraction angiography in 7 of the 25 patients. A significant rise in mean pulmonary arterial pressure occurred after thrombus fragmentation (before: 34.1 mmHg; after: 37.9 mmHg; p<0.05), and this group showed a significant decrease in mean pulmonary arterial pressure after thrombus aspiration (25.7 mmHg; p<0.05). No distal embolisation was seen in 18 of the 25 patients, and a significant decrease in mean pulmonary arterial pressure was confirmed after thrombus fragmentation (before: 34.2 mmHg; after: 28.1 mmHg: p<0.01), and after thrombus aspiration (23.3 mmHg; p<0.01). In conclusion, distal embolisation and a rise in pulmonary arterial pressure can occur during mechanical fragmentation using a rotating pigtail catheter for the treatment of life-threatening acute massive pulmonary thromboembolism; thrombolysis and thrombus aspiration can provide partial recanalization and haemodynamic stabilization. Continuous monitoring of pulmonary arterial pressure may contribute to the safety of these interventional procedures. PMID:18941044

  7. Pulmonary and systemic arterial pressure in hyaline membrane disease.

    PubMed Central

    Skinner, J R; Boys, R J; Hunter, S; Hey, E N

    1992-01-01

    Systolic pulmonary arterial pressure was determined serially over the first 10 days of life in 33 babies with hyaline membrane disease by measuring the peak velocity of pansystolic tricuspid valve regurgitation, using Doppler ultrasound, and applying the Bernoulli equation. Results are presented in age groups 0-12, 13-36, 37-72, and 73-96 hours respectively. The incidence of tricuspid valve regurgitation was 92, 97, 80, and 64% (falling to 35% by day 10) compared with 53, 50, 31, and 0% in 17 healthy premature infants. In comparing healthy babies with those with hyaline membrane disease, no allowance was made for right atrial pressure. The derived 'right ventricle to right atrial (RV-RA) pressure difference', was expressed as a ratio of systemic arterial (systolic) pressure. Over the first three days, this ratio fell much faster in the healthy babies. Values were 0.78:1, 0.77:1, and 0.72:1 in babies with hyaline membrane disease and 0.87:1, 0.53:1, and 0.44:1 in healthy babies. Ductal patency was prolonged in babies with hyaline membrane disease (75% on day 4 compared with 6% in healthy babies). The incidence of bidirectional ductal flow, indicating balanced pulmonary and systemic arterial pressures, was 79, 53, 30, and 20%, and in healthy babies was 41% at 0-12 hours and zero thereafter. Pulmonary arterial pressure was then calculated by adding a right atrial pressure estimate of 5 mm Hg to the RV-RA difference when the babies were ventilated. Babies of lower gestation had lower values. The pulmonary: systemic arterial pressure ratio showed considerable temporal variability, but fell with age and was raised by high mean airway pressure and pneumothorax (through a reduction in systemic pressure), and less noticeably by carbon dioxide tension. It did not correlate significantly with other indices of disease severity. Hyaline membrane disease is associated with delayed postnatal circulatory adaptation characterized by pulmonary hypertension, systemic hypotension, and

  8. Estimating pulmonary artery pressures by echocardiography in patients with emphysema.

    PubMed

    Fisher, M R; Criner, G J; Fishman, A P; Hassoun, P M; Minai, O A; Scharf, S M; Fessler, H E

    2007-11-01

    In patients with emphysema being evaluated for lung volume reduction surgery, Doppler echocardiography has been used to screen for pulmonary hypertension as an indicator of increased peri-operative risk. To determine the accuracy of this test, the present authors compared the results of right heart catheterisations and Doppler echocardiograms in 163 patients participating in the cardiovascular substudy of the National Emphysema Treatment Trial. Substudy patients had both catheterisation and Doppler echocardiography performed before and after randomisation. In 74 paired catheterisations and echocardiograms carried out on 63 patients, the mean values of invasively measured pulmonary artery systolic pressures and the estimated right ventricular systolic pressures were similar. However, using the World Health Organization's definitions of pulmonary hypertension, echocardiography had a sensitivity of 60%, specificity of 74%, positive predictive value of 68% and a negative predictive value of 67% compared with the invasive measurement. Bland-Altman analysis revealed a bias of 0.37 kPa with 95% limits of agreement from -2.5-3.2 kPa. In patients with severe emphysema, echocardiographic estimates of pulmonary artery pressures correlate very weakly with right heart catheterisations, and the test characteristics (e.g. sensitivity, specificity, etc.) of echocardiographic assessments are poor.

  9. Giant high-pressure pulmonary artery aneurysm in an elderly patient with chronic obstructive pulmonary disease.

    PubMed

    Morais, Sandra A; Oliveira, Hugo M; de Almeida, José R; Eiras, Eduardo; Silva, Ana Catarina; Gavina, Cristina

    2016-03-01

    The authors report the case of a 74-year-old man, with a history of chronic obstructive pulmonary disease (COPD), GOLD grade 3, stable for the past two decades, who was admitted to our center with severe right heart failure. The chest radiograph showed moderate heart enlargement mainly of the right atrium and pulmonary artery, similar to previous chest radiographs in the previous 20 years. The transthoracic echocardiogram showed a pulmonary artery aneurysm (PAA), dilatation of the right chambers with pulmonary artery systolic pressure of 52 mmHg, and preserved right ventricular systolic function. A thoracic computed tomography scan confirmed the presence of a giant PAA 72 mm in diameter. The patient was started on high-dose diuretics, with significant clinical improvement. After optimization of medical therapy right heart catheterization was carried out with the patient in optimal clinical condition, which revealed mild precapillary pulmonary hypertension with a mean pulmonary artery pressure of 26 mmHg. On the basis of the clinical and imaging findings a stable, giant, high-pressure, PAA was diagnosed secondary to pulmonary hypertension induced by COPD, with a 20-year follow-up without need for surgical repair, which helped in our decision to maintain medical surveillance. The recent onset of heart failure is explained by the unfavorable evolution of COPD. This case may change the attitude expressed in previous studies favoring the choice of an invasive approach to treat giant high-pressure PAAs, instead supporting the maintenance of medical treatment.

  10. Contribution of calcium-activated chloride channel to elevated pulmonary artery pressure in pulmonary arterial hypertension induced by high pulmonary blood flow

    PubMed Central

    Wang, Kai; Chen, Chuansi; Ma, Jianfa; Lao, Jinquan; Pang, Yusheng

    2015-01-01

    The correlation between calcium-activated chloride channel (CaCC) and pulmonary arterial hypertension (PAH) induced by high pulmonary blood flow remains uncertain. In this study, we investigated the possible role and effects of CaCC in this disease. Sixty rats were randomly assigned to normal, sham, and shunt groups. Rats in the shunt group underwent abdominal aorta and inferior vena cava shunt surgery. The pulmonary artery pressure was measured by catheterization. Pathological changes, right ventricle hypertrophy index (RVHI), arterial wall area/vessel area (W/V), and arterial wall thickness/vessel external diameter (T/D) were analyzed by optical microscopy. Electrophysiological characteristics of pulmonary arterial smooth muscle cells (PASMCs) were investigated using patch clamp technology. After 11 weeks of shunting, PAH and pulmonary vascular structural remodeling (PVSR) developed, accompanied by increased pulmonary pressure and pathological interstitial pulmonary changes. Compared with normal and sham groups, pulmonary artery pressure, RVHI, W/V, and T/D of the shunt group rats increased significantly. Electrophysiological results showed primary CaCC characteristics. Compared with normal and sham groups, membrane capacitance and current density of PASMCs in the shunt group increased significantly, which were subsequently attenuated following chloride channel blocker niflumic acid (NFA) treatment. To conclude, CaCC contributed to PAH induced by high pulmonary blood flow and may represent a potential target for treatment of PAH. PMID:25755701

  11. Contribution of calcium-activated chloride channel to elevated pulmonary artery pressure in pulmonary arterial hypertension induced by high pulmonary blood flow.

    PubMed

    Wang, Kai; Chen, Chuansi; Ma, Jianfa; Lao, Jinquan; Pang, Yusheng

    2015-01-01

    The correlation between calcium-activated chloride channel (CaCC) and pulmonary arterial hypertension (PAH) induced by high pulmonary blood flow remains uncertain. In this study, we investigated the possible role and effects of CaCC in this disease. Sixty rats were randomly assigned to normal, sham, and shunt groups. Rats in the shunt group underwent abdominal aorta and inferior vena cava shunt surgery. The pulmonary artery pressure was measured by catheterization. Pathological changes, right ventricle hypertrophy index (RVHI), arterial wall area/vessel area (W/V), and arterial wall thickness/vessel external diameter (T/D) were analyzed by optical microscopy. Electrophysiological characteristics of pulmonary arterial smooth muscle cells (PASMCs) were investigated using patch clamp technology. After 11 weeks of shunting, PAH and pulmonary vascular structural remodeling (PVSR) developed, accompanied by increased pulmonary pressure and pathological interstitial pulmonary changes. Compared with normal and sham groups, pulmonary artery pressure, RVHI, W/V, and T/D of the shunt group rats increased significantly. Electrophysiological results showed primary CaCC characteristics. Compared with normal and sham groups, membrane capacitance and current density of PASMCs in the shunt group increased significantly, which were subsequently attenuated following chloride channel blocker niflumic acid (NFA) treatment. To conclude, CaCC contributed to PAH induced by high pulmonary blood flow and may represent a potential target for treatment of PAH.

  12. Pulmonary capillary pressure measured with a pulmonary arterial double port catheter in surgical patients.

    PubMed

    Yamada, Y; Komatsu, K; Suzukawa, M; Chinzei, M; Chinzei, T; Suwa, K; Numata, K; Hanaoka, K

    1993-12-01

    We developed a pulmonary artery (PA) double port catheter technique for reliable clinical measurements of pulmonary capillary pressure (Ppc). In seven elective surgical patients, the PA double port catheter with the second PA port 1 cm proximal to the balloon was inserted. The two PA ports, connected to identical pressure measuring systems, provided the pulmonary arterial pressures (Ppa) distal and proximal to the balloon. After general anesthesia was stabilized, the two Ppas were measured simultaneously during a PA occlusion maneuver during 10 s of apnea. The instant of occlusion was determined precisely as the time when the two Ppa traces sharply diverged. A single exponential equation was fitted to the segment of distal Ppa tracing starting 0.3 s after the instant of occlusion. Ppc was determined as the value of the exponential fit extrapolated to time 0. In six of seven patients, PA occlusion occurred consistently in the early systolic phase regardless of the timing of balloon inflation. Mean Ppa, Ppc, and pulmonary arterial wedge pressure were 16.6, 11.8, and 7.6 torr. The ratio of venous to total resistance ranged from 0.37 to 0.54 (mean:0.46). We conclude that this technique is clinically feasible and valuable in precise definition of the instant of PA occlusion. By defining PA occlusion consistently, this technique can provide reliable Ppc estimation in the clinical settings. PMID:8250302

  13. Slow and fast changes in transmural pulmonary artery pressure in obstructive sleep apnoea.

    PubMed

    Marrone, O; Bonsignore, M R; Romano, S; Bonsignore, G

    1994-12-01

    Our purpose was to assess how pulmonary artery pressure changes in relation to hypoxia and oesophageal pressure during obstructive sleep apnoeas. Transmural systolic pulmonary artery pressure (Ppa,STM), oxyhaemoglobin saturation (SaO2) and oesophageal pressure were analysed in two samples of consecutive obstructive apnoeas in each of four patients. In the first samples (samples A; probably recorded during non-rapid eye movement (NREM) sleep), SaO2 swings were small and repetitive. In the second samples (samples B; probably recorded during rapid eye movement (REM) sleep), they were large and more variable. Oesophageal pressure oscillated similarly in the two groups of samples. In all cases, transmural systolic pulmonary artery pressure progressively increased throughout apnoeas, and subsequently decreased in the interapnoeic periods. However, both early and end-apnoeic transmural systolic pulmonary artery pressure, remained stable in samples A; whilst they progressively increased in samples B. Transmural systolic pulmonary artery pressure at the beginning of each apnoea was inversely correlated with SaO2 at the end of the preceding apnoea. These results suggest that transmural systolic pulmonary artery pressure is influenced by SaO2, but does not vary at the same speed as SaO2. In all cases, beat-by-beat analysis showed, as expected, that the lower the oesophageal pressure, the higher the transmural systolic pulmonary artery pressure however, at each oesophageal pressure level, transmural systolic pulmonary artery pressure was more variable and higher, in samples B. In conclusion, transmural systolic pulmonary artery pressure in obstructive apnoeas shows rapid changes, which reflect oesophageal pressure variations, and slower changes, which are likely to be caused by SaO2. PMID:7713203

  14. Diving-induced venous gas emboli do not increase pulmonary artery pressure.

    PubMed

    Valic, Z; Duplancić, D; Baković, D; Ivancev, V; Eterović, D; Wisløff, U; Brubakk, A O; Dujić, Z

    2005-10-01

    Venous gas emboli are frequently observed in divers even if proper decompression procedures are followed. This study was initiated to determine if pulmonary artery pressure increases in asymptomatic divers, which could increase the risk of arterial embolization due to passage of venous gas emboli from the right to the left side of the heart. Recordings of venous gas emboli and estimation of pulmonary artery pressure by non-invasive transthoracic echocardiography were applied in 10 recreational scuba diving volunteers before and 20, 40, 60, and 80 min after simulated dives to 18 m (80 min bottom time) in a hyperbaric chamber. The ratio between pulmonary artery acceleration time and right ventricular ejection time was used as an estimate of pulmonary artery pressure. None of investigated divers had signs of decompression sickness. Despite the post-dive presence of the venous gas emboli, measured in the region of the pulmonary valve annulus (mean=1.71 bubbles.cm-2, 40 min after dive), the ratio between pulmonary artery acceleration time and right ventricular ejection time did not decrease, but actually increased (from 0.43+/-0.06 to 0.49+/-0.06, 40 min after dive; p<0.05), suggesting a decrease in pulmonary artery pressure after the dive. We conclude that diving-induced venous gas bubbles do not cause significant changes in the central circulation which could increase the risk of arterial embolization.

  15. Effect of alveolar pressure on pulmonary artery pressure in chronically hypoxic rats.

    PubMed

    Wach, R; Emery, C J; Bee, D; Barer, G R

    1987-02-01

    The effect on pulmonary artery pressure of a rise in alveolar pressure differed in chronically hypoxic rats (10% O2 for 3-5 weeks) compared with control rats. Chronically hypoxic rats have newly muscularised walls in arterioles in the alveolar region. Isolated lungs of chronically hypoxic and control rats were perfused with blood under conditions in which alveolar pressure was greater than left atrial pressure during both normoxia and hypoxia. Alveolar pressure was the effective downstream pressure. Pressure-flow lines were measured at low and high alveolar pressure (5 and 15 mmHg). During normoxia pressure-flow lines of chronically hypoxic rats had a steeper slope (higher resistance) and greater extrapolated intercept on the pressure axis (effective downstream pressure) than control rats. In both groups of rats the change from low to high alveolar pressure during normoxia caused an approximately parallel shift in the pressure-flow line similar to the change in alveolar pressure. During hypoxia, which led to an increase in slope and intercept in both groups of rats, the effect of a rise in alveolar pressure differed in chronically hypoxic from control rats. In control rats there was a small parallel shift in the pressure-flow line that was much less than the increase in alveolar pressure; in chronically hypoxic rats there was a large parallel shift in the pressure-flow line that was greater than the increase in alveolar pressure. Thus in chronically hypoxic rats hypoxic vasoconstriction probably occurred mainly in muscular alveolar vessels, whereas in control rats it probably occurred upstream in extra-alveolar vessels. At constant blood flow the relation between pulmonary artery pressure and alveolar pressure was measured while alveolar pressure was reduced from approximately 15 mmHg to zero during both normoxia and hypoxia. In control and chronically hypoxic rats the slope of this line was less than 1. At an alveolar pressure of 2-3 mmHg there was an inflection

  16. Impact of residual stretch and remodeling on collagen engagement in healthy and pulmonary hypertensive calf pulmonary arteries at physiological pressures.

    PubMed

    Tian, Lian; Lammers, Steven R; Kao, Philip H; Albietz, Joseph A; Stenmark, Kurt R; Qi, H Jerry; Shandas, Robin; Hunter, Kendall S

    2012-07-01

    Understanding the mechanical behavior of proximal pulmonary arteries (PAs) is crucial to evaluating pulmonary vascular function and right ventricular afterload. Early and current efforts focus on these arteries' histological changes, in vivo pressure-diameter behavior and mechanical properties under in vitro mechanical testing. However, the in vivo stretch and stress states remain poorly characterized. To further understand the mechanical behavior of the proximal PAs under physiological conditions, this study computed the residual stretch and the in vivo circumferential stretch state in the main pulmonary arteries in both control and hypertensive calves by using in vitro and in vivo artery geometry data, and modeled the impact of residual stretch and arterial remodeling on the in vivo circumferential stretch distribution and collagen engagement in the main pulmonary artery. We found that the in vivo circumferential stretch distribution in both groups was nonuniform across the vessel wall with the largest stretch at the outer wall, suggesting that collagen at the outer wall would engage first. It was also found that the circumferential stretch was more uniform in the hypertensive group, partially due to arterial remodeling that occurred during their hypoxic treatment, and that their onset of collagen engagement occurred at a higher pressure. It is concluded that the residual stretch and arterial remodeling have strong impact on the in vivo stretch state and the collagen engagement and thus the mechanical behavior of the main pulmonary artery in calves. PMID:22237861

  17. Non-invasive assessment of pulmonary arterial pressure in healthy neonates.

    PubMed Central

    Skinner, J R; Boys, R J; Hunter, S; Hey, E N

    1991-01-01

    Doppler echocardiograms were carried out on 51 healthy babies three times during the first 72 hours of life to estimate pulmonary arterial systolic pressure by measuring regurgitant tricuspid jet velocity and applying the Bernoulli equation. Tricuspid regurgitation was detected at some stage in all preterm babies and most of those born at full term. Pulmonary arterial pressure could be measured from peak regurgitant velocity in babies with pansystolic regurgitation. The incidence of pansystolic regurgitation among 34 term babies at 0-12, 13-36, and 32-72 hours of age was 22, 27, and 19%, and in 17 preterm babies (within the same age groups) was 53, 50, and 31%, respectively. Estimates of pulmonary artery pressure in the term babies were in accord with known catheter values. Pressure fell rapidly during the first day in all 51 babies. The ratio of pulmonary:systemic arterial pressure was comparable between the two groups throughout. Ductal flow patterns mirrored the fall in this ratio with age--bidirectional flow was associated with a ratio of between 0.88:1 and 1.22:1 and high velocity left to right flow with a ratio of between 0.49:1 and 0.66:1. Both these techniques are noninvasive ways of assessing neonatal pulmonary arterial pressure. Images Figure 1 PMID:2025029

  18. Influence of altitude and age on pulmonary arterial pressure in cattle.

    PubMed

    Will, D H; Horrell, J F; Reeves, J T; Alexander, A F

    1975-12-01

    Pulmonary arterial pressures in native cattle ranging in age from 3 months to 10 yr were found to be increased with increasing altitudes of residence from sea level to 3048 m. At altitudes of 2590 and 3048 m, but not at sea level or 1524 m, the pressures were higher in older than in younger cattle. The magnitude of the pulmonary arterial pressure, and probably the rate of progression of pulmonary hypertension at high altitude, were much less in native cattle than in cattle that were newcomers from low altitude. Natural and artificial selection are believed to have minimized the level of pulmonary hypertension in native high altitude cattle, thus protecting them from high mountain or brisket disease.

  19. Elastin insufficiency predisposes to elevated pulmonary circulatory pressures through changes in elastic artery structure.

    PubMed

    Shifren, Adrian; Durmowicz, Anthony G; Knutsen, Russell H; Faury, Gilles; Mecham, Robert P

    2008-11-01

    Elastin is a major structural component of large elastic arteries and a principal determinant of arterial biomechanical properties. Elastin loss-of-function mutations in humans have been linked to the autosomal-dominant disease supravalvular aortic stenosis, which is characterized by stenotic lesions in both the systemic and pulmonary circulations. To better understand how elastin insufficiency influences the pulmonary circulation, we evaluated pulmonary cardiovascular physiology in a unique set of transgenic and knockout mice with graded vascular elastin dosage (range 45-120% of wild type). The central pulmonary arteries of elastin-insufficient mice had smaller internal diameters (P < 0.0001), thinner walls (P = 0.002), and increased opening angles (P = 0.002) compared with wild-type controls. Pulmonary circulatory pressures, measured by right ventricular catheterization, were significantly elevated in elastin-insufficient mice (P < 0.0001) and showed an inverse correlation with elastin level. Although elastin-insufficient animals exhibited mild to moderate right ventricular hypertrophy (P = 0.0001) and intrapulmonary vascular remodeling, the changes were less than expected, given the high right ventricular pressures, and were attenuated compared with those seen in hypoxia-induced models of pulmonary arterial hypertension. The absence of extensive pathological cardiac remodeling at the high pressures in these animals suggests a developmental adaptation designed to maintain right-sided cardiac output in a vascular system with altered elastin content. PMID:18772328

  20. The mechanical properties of the systemic and pulmonary arteries of Python regius correlate with blood pressures.

    PubMed

    van Soldt, Benjamin J; Danielsen, Carl Christian; Wang, Tobias

    2015-12-01

    Pythons are unique amongst snakes in having different pressures in the aortas and pulmonary arteries because of intraventricular pressure separation. In this study, we investigate whether this correlates with different blood vessel strength in the ball python Python regius. We excised segments from the left, right, and dorsal aortas, and from the two pulmonary arteries. These were subjected to tensile testing. We show that the aortic vessel wall is significantly stronger than the pulmonary artery wall in P. regius. Gross morphological characteristics (vessel wall thickness and correlated absolute amount of collagen content) are likely the most influential factors. Collagen fiber thickness and orientation are likely to have an effect, though the effect of collagen fiber type and cross-links between fibers will need further study. PMID:26780263

  1. The mechanical properties of the systemic and pulmonary arteries of Python regius correlate with blood pressures.

    PubMed

    van Soldt, Benjamin J; Danielsen, Carl Christian; Wang, Tobias

    2015-12-01

    Pythons are unique amongst snakes in having different pressures in the aortas and pulmonary arteries because of intraventricular pressure separation. In this study, we investigate whether this correlates with different blood vessel strength in the ball python Python regius. We excised segments from the left, right, and dorsal aortas, and from the two pulmonary arteries. These were subjected to tensile testing. We show that the aortic vessel wall is significantly stronger than the pulmonary artery wall in P. regius. Gross morphological characteristics (vessel wall thickness and correlated absolute amount of collagen content) are likely the most influential factors. Collagen fiber thickness and orientation are likely to have an effect, though the effect of collagen fiber type and cross-links between fibers will need further study.

  2. Numerical simulation of blood flow and pressure drop in the pulmonary arterial and venous circulation.

    PubMed

    Qureshi, M Umar; Vaughan, Gareth D A; Sainsbury, Christopher; Johnson, Martin; Peskin, Charles S; Olufsen, Mette S; Hill, N A

    2014-10-01

    A novel multiscale mathematical and computational model of the pulmonary circulation is presented and used to analyse both arterial and venous pressure and flow. This work is a major advance over previous studies by Olufsen et al. (Ann Biomed Eng 28:1281-1299, 2012) which only considered the arterial circulation. For the first three generations of vessels within the pulmonary circulation, geometry is specified from patient-specific measurements obtained using magnetic resonance imaging (MRI). Blood flow and pressure in the larger arteries and veins are predicted using a nonlinear, cross-sectional-area-averaged system of equations for a Newtonian fluid in an elastic tube. Inflow into the main pulmonary artery is obtained from MRI measurements, while pressure entering the left atrium from the main pulmonary vein is kept constant at the normal mean value of 2 mmHg. Each terminal vessel in the network of 'large' arteries is connected to its corresponding terminal vein via a network of vessels representing the vascular bed of smaller arteries and veins. We develop and implement an algorithm to calculate the admittance of each vascular bed, using bifurcating structured trees and recursion. The structured-tree models take into account the geometry and material properties of the 'smaller' arteries and veins of radii ≥ 50 μm. We study the effects on flow and pressure associated with three classes of pulmonary hypertension expressed via stiffening of larger and smaller vessels, and vascular rarefaction. The results of simulating these pathological conditions are in agreement with clinical observations, showing that the model has potential for assisting with diagnosis and treatment for circulatory diseases within the lung. PMID:24610385

  3. Numerical simulation of blood flow and pressure drop in the pulmonary arterial and venous circulation.

    PubMed

    Qureshi, M Umar; Vaughan, Gareth D A; Sainsbury, Christopher; Johnson, Martin; Peskin, Charles S; Olufsen, Mette S; Hill, N A

    2014-10-01

    A novel multiscale mathematical and computational model of the pulmonary circulation is presented and used to analyse both arterial and venous pressure and flow. This work is a major advance over previous studies by Olufsen et al. (Ann Biomed Eng 28:1281-1299, 2012) which only considered the arterial circulation. For the first three generations of vessels within the pulmonary circulation, geometry is specified from patient-specific measurements obtained using magnetic resonance imaging (MRI). Blood flow and pressure in the larger arteries and veins are predicted using a nonlinear, cross-sectional-area-averaged system of equations for a Newtonian fluid in an elastic tube. Inflow into the main pulmonary artery is obtained from MRI measurements, while pressure entering the left atrium from the main pulmonary vein is kept constant at the normal mean value of 2 mmHg. Each terminal vessel in the network of 'large' arteries is connected to its corresponding terminal vein via a network of vessels representing the vascular bed of smaller arteries and veins. We develop and implement an algorithm to calculate the admittance of each vascular bed, using bifurcating structured trees and recursion. The structured-tree models take into account the geometry and material properties of the 'smaller' arteries and veins of radii ≥ 50 μm. We study the effects on flow and pressure associated with three classes of pulmonary hypertension expressed via stiffening of larger and smaller vessels, and vascular rarefaction. The results of simulating these pathological conditions are in agreement with clinical observations, showing that the model has potential for assisting with diagnosis and treatment for circulatory diseases within the lung.

  4. Elevated Plasma Endothelin-1 and Pulmonary Arterial Pressure in Children Exposed to Air Pollution

    PubMed Central

    Calderón-Garcidueñas, Lilian; Vincent, Renaud; Mora-Tiscareño, Antonieta; Franco-Lira, Maricela; Henríquez-Roldán, Carlos; Barragán-Mejía, Gerardo; Garrido-García, Luis; Camacho-Reyes, Laura; Valencia-Salazar, Gildardo; Paredes, Rogelio; Romero, Lina; Osnaya, Hector; Villarreal-Calderón, Rafael; Torres-Jardón, Ricardo; Hazucha, Milan J.; Reed, William

    2007-01-01

    Background Controlled exposures of animals and humans to particulate matter (PM) or ozone air pollution cause an increase in plasma levels of endothelin-1, a potent vasoconstrictor that regulates pulmonary arterial pressure. Objectives The primary objective of this field study was to determine whether Mexico City children, who are chronically exposed to levels of PM and O3 that exceed the United States air quality standards, have elevated plasma endothelin-1 levels and pulmonary arterial pressures. Methods We conducted a study of 81 children, 7.9 ± 1.3 years of age, lifelong residents of either northeast (n = 19) or southwest (n = 40) Mexico City or Polotitlán (n = 22), a control city with PM and O3 levels below the U.S. air quality standards. Clinical histories, physical examinations, and complete blood counts were done. Plasma endothelin-1 concentrations were determined by immunoassay, and pulmonary arterial pressures were measured by Doppler echocardiography. Results Mexico City children had higher plasma endothelin-1 concentrations compared with controls (p < 0.001). Mean pulmonary arterial pressure was elevated in children from both northeast (p < 0.001) and southwest (p < 0.05) Mexico City compared with controls. Endothelin-1 levels in Mexico City children were positively correlated with daily outdoor hours (p = 0.012), and 7-day cumulative levels of PM air pollution < 2.5 μm in aerodynamic diameter (PM2.5) before endothelin-1 measurement (p = 0.03). Conclusions Chronic exposure of children to PM2.5 is associated with increased levels of circulating endothelin-1 and elevated mean pulmonary arterial pressure. PMID:17687455

  5. [Significance of pulmonary artery diastolic pressure after myocardial infarction for physical training (author's transl)].

    PubMed

    Koenig, W; Toth, L; Többicke, K; Linden, G; Kohn, E

    1978-07-01

    Functional disorders of the left ventricle after myocardial infarction at rest and with exercise can be evaluated with right heart floating catheter by measuring pulmonary artery diastolic pressure. 45% of 200 patients with myocardial infarctions did not tolerate bicycle exercise test with a work load of 50 Watt during 6 minutes. A routine digitalisation of these patients without strict indication did not improve the results. The upper borderline to admit a physical training program is a pulmonary artery diastolic pressure of 20 mm Hg; this should be realised otherwise additional complications have to be expected in long term follow up. The effects of digitalis should be controlled with floating catheter observations in these patients too. There are some indications, that it is possible with the same technique to evaluate hemodynamic responses on psychological strain. Measurements of pulmonary artery diastolic pressure after myocardial infarction open a wide field for individual therapy from drugs to physical training and even to behaviour therapy for stressfull situations. PMID:685379

  6. Increase of pulmonary arterial pressure in subjects with venous gas emboli after uncomplicated recreational SCUBA diving.

    PubMed

    Marabotti, Claudio; Scalzini, Alessandro; Chiesa, Ferruccio

    2013-04-01

    The presence of circulating gas bubbles has been repeatedly reported after uncomplicated SCUBA dives. The clinical and pathophysiological relevance of this phenomenon is still under debate but some experimental data suggest that silent bubbles may have a damaging potential on pulmonary endothelial cells. The aim of the present study was to evaluate the possible hemodynamic effect on pulmonary circulation of post-dive circulating gas bubbles. To this aim, 16 experienced divers were studied by Doppler-echocardiography in basal conditions and 2.0 ± 0.15 h after an uncomplicated, unrestricted recreational SCUBA dive. At the post-dive examination, circulating bubbles were present in 10/16 subjects (62.5%). Divers with circulating bubbles showed a significant post-dive increase of pulmonary systolic arterial pressure (evaluated by the maximal velocity of the physiological tricuspid regurgitation; P < 0.01)) and right ventricular internal dimension (P < 0.05). Divers without circulating bubbles showed no significant change in cardiac anatomy and pulmonary arterial pressure. Both groups showed a significant post-dive decrease of transmitral E/A ratio (index of left ventricular diastolic function: subjects with bubbles P < 0.01; subjects without bubbles P < 0.05). These results seem to indicate that circulating gas bubbles may lead to a hemodynamically relevant increase of pulmonary arterial pressure, able to induce an acute right ventricular dilation. Post-dive diastolic function changes, observed in both groups, may be explained by a preload reduction due to immersion natriuresis. The results of the present study add some evidence that post-dive circulating bubbles, although symptomless, have an easily detectable pathogenetic potential, inducing unfavorable hemodynamic changes in the lesser circulation.

  7. The relationship of pulmonary vascular resistance and compliance to pulmonary artery wedge pressure during submaximal exercise in healthy older adults

    PubMed Central

    Wright, Stephen P.; Granton, John T.; Esfandiari, Sam; Goodman, Jack M.

    2016-01-01

    Key points A consistent inverse hyperbolic relationship has been observed between pulmonary vascular resistance and compliance, although changes in pulmonary artery wedge pressure (PAWP) may modify this relationship.This relationship predicts that pulmonary artery systolic, diastolic and mean pressure maintain a consistent relationship relative to the PAWP.We show that, in healthy exercising human adults, both pulmonary vascular resistance and compliance decrease in relation to exercise‐associated increases in PAWP.Pulmonary artery systolic, diastolic and mean pressures maintain a consistent relationship with one another, increasing linearly with increasing PAWP.Increases in PAWP in the setting of exercise are directly related to a decrease in pulmonary vascular compliance, despite small decreases in pulmonary vascular resistance, thereby increasing the pulsatile afterload to the right ventricle. Abstract The resistive and pulsatile components of right ventricular afterload (pulmonary vascular resistance, Rp; compliance, Cp) are related by an inverse hyperbolic function, expressed as their product known as RpCp‐time. The RpCp‐time exhibits a narrow range, although it may be altered by the pulmonary artery wedge pressure (PAWP). Identifying the determinants of RpCp‐time should improve our understanding of the physiological behaviour of pulmonary arterial systolic (PASP), diastolic (PADP) and mean (mPAP) pressures in response to perturbations. We examined the effect of exercise in 28 healthy non‐athletic adults (55 ± 6 years) who underwent right heart catheterization to assess haemodynamics and calculate Rp and Cp. Measurements were made at rest and during two consecutive 8–10 min stages of cycle ergometry, at targeted heart‐rates of 100 beats min–1 (Light) and 120 beats min–1 (Moderate). Cardiac output increased progressively during exercise. PASP, PADP, mPAP and PAWP increased for Light exercise, without any further rise for Moderate

  8. Scintigraphic prediction of pulmonary arterial systolic pressure by regional right ventricular ejection fraction during the second half of systole

    SciTech Connect

    Friedman, B.J.; Holman, B.L.

    1982-11-01

    In 49 patients in whom gated equilibrium ventriculography and cardiac catheterization were performed within a 6 day interval, total and fractional portions of global and regional right ventricular ejection fraction (RVEF) were correlated with pulmonary arterial systolic pressure. Pulmonary arterial systolic pressure was normal (30 mm Hg or less) in 27 patients (Group I) and elevated (31 mm Hg or greater) in 22 patients (Group II). The second-half regional RVEF was 38 +/- 8% (mean +/- standard deviation) with a range of 30 to 54% for Group I and 22 +/- 6% with a range of 13 to 32% for Group II. The difference between the means was statistically significant (p less than 0.001). Use of a second-half regional RVEF of 30% as the criterion of elevated pulmonary arterial systolic pressure resulted in a sensitivity of 0.86 and a specificity of 1.00. A power curve fit in which pulmonary arterial systolic pressure . 10.91 (second-half regional RVEF)-0.87 allowed accurate estimation (r . -0.85) of pulmonary arterial systolic pressure from the second-half regional RVEF. It is concluded that second-half regional RVEF may be used to accurately detect pulmonary arterial hypertension and to estimate its extent.

  9. Determinants of ventilation and pulmonary artery pressure during early acclimatization to hypoxia in humans.

    PubMed

    Fatemian, Marzieh; Herigstad, Mari; Croft, Quentin P P; Formenti, Federico; Cardenas, Rosa; Wheeler, Carly; Smith, Thomas G; Friedmannova, Maria; Dorrington, Keith L; Robbins, Peter A

    2016-03-01

    Pulmonary ventilation and pulmonary arterial pressure both rise progressively during the first few hours of human acclimatization to hypoxia. These responses are highly variable between individuals, but the origin of this variability is unknown. Here, we sought to determine whether the variabilities between different measures of response to sustained hypoxia were related, which would suggest a common source of variability. Eighty volunteers individually underwent an 8-h isocapnic exposure to hypoxia (end-tidal P(O2)=55 Torr) in a purpose-built chamber. Measurements of ventilation and pulmonary artery systolic pressure (PASP) assessed by Doppler echocardiography were made during the exposure. Before and after the exposure, measurements were made of the ventilatory sensitivities to acute isocapnic hypoxia (G(pO2)) and hyperoxic hypercapnia, the latter divided into peripheral (G(pCO2)) and central (G(cCO2)) components. Substantial acclimatization was observed in both ventilation and PASP, the latter being 40% greater in women than men. No correlation was found between the magnitudes of pulmonary ventilatory and pulmonary vascular responses. For G(pO2), G(pCO2) and G(cC O2), but not the sensitivity of PASP to acute hypoxia, the magnitude of the increase during acclimatization was proportional to the pre-acclimatization value. Additionally, the change in G(pO2) during acclimatization to hypoxia correlated well with most other measures of ventilatory acclimatization. Of the initial measurements prior to sustained hypoxia, only G(pCO2) predicted the subsequent rise in ventilation and change in G(pO2) during acclimatization. We conclude that the magnitudes of the ventilatory and pulmonary vascular responses to sustained hypoxia are predominantly determined by different factors and that the initial G(pCO2) is a modest predictor of ventilatory acclimatization.

  10. Effects of two types of cobra venom factor on porcine complement activation and pulmonary artery pressure.

    PubMed Central

    Cheung, A K; Parker, C J; Wilcox, L

    1989-01-01

    Autologous porcine plasma that has been incubated with cuprophan haemodialysis membranes causes pulmonary hypertension and peripheral leucopenia following reinfusion into swine. These effects appear to be mediated by biologically active fragments of C3 and C5 that are generated as a consequence of ex vivo activation of complement. Putatively, C5a induces the leucopenia; however, the specific contributions of products of C3 and C5 activation to the pulmonary vasoconstriction have not been elucidated. In the present study, the effects of in vivo infusion of two different types of cobra venom factor (CVF) on peripheral leucocyte count and pulmonary artery pressure in the swine are reported. The CVF from Naja n. naja (CVF(TN)) was shown to activate both porcine C3 and C5, whereas the CVF from Naja h. haje (CVF(NH)) activated only C3. Both types of CVF produced pulmonary hypertension. Significant peripheral leucopenia, however, was observed only with CVF(TN). These results suggest that activation products of C3 contribute to the pulmonary hypertension but not to the peripheral leucopenia observed during haemodialysis using dialysis membranes that activate complement. PMID:12412765

  11. Correlation between caudal pulmonary artery diameter to body surface area ratio and echocardiography-estimated systolic pulmonary arterial pressure in dogs

    PubMed Central

    Lee, Youngjae; Choi, Wooshin; Lee, Donghoon; Chang, Jinhwa; Kang, Ji-Houn; Choi, Jihye

    2016-01-01

    Caudal pulmonary artery diameter (CPAD) to body surface area (BSA) ratios were measured in ventrodorsal thoracic radiographs to assess the correlation between CPAD to BSA ratios and systolic pulmonary arterial pressure (PAP) in dogs. Thoracic radiographs of 44 dogs with systolic pulmonary arterial hypertension (PAH) and 55 normal dogs were evaluated. Systolic PAP was estimated by Doppler echocardiography. CPADs were measured at their largest point at the level of tracheal bifurcation on ventrodorsal radiographs. Both right and left CPAD to BSA ratios were significantly higher in the PAH group than in the normal group (p < 0.0001). Linear regression analysis showed positive associations between PAP and right and left CPAD to BSA ratio (right, p = 0.0230; left, p = 0.0012). The receiver operating characteristic curve analysis revealed that the CPAD to BSA ratio had moderate diagnostic accuracy for detecting PAH. The operating point, sensitivity, specificity, and area under the curve were 28.35, 81.40%, 81.82%, and 0.870; respectively, for the right side and 26.92, 80.00%, 66.67%, and 0.822, respectively, for the left. The significant correlation of CPAD to BSA ratio with echocardiography-estimated systolic PAP supports its use in identifying PAH on survey thoracic radiographs in dogs. PMID:26645336

  12. Environmentally persistent free radicals decrease cardiac function and increase pulmonary artery pressure

    PubMed Central

    Mahne, Sarah; Chuang, Gin C.; Pankey, Edward; Kiruri, Lucy; Kadowitz, Philip J.; Dellinger, Barry

    2012-01-01

    Epidemiological studies have consistently linked inhalation of particulate matter (PM) to increased cardiac morbidity and mortality, especially in at risk populations. However, few studies have examined the effect of PM on baseline cardiac function in otherwise healthy individuals. In addition, airborne PM contain environmentally persistent free radicals (EPFR) capable of redox cycling in biological systems. The purpose of this study was to determine whether nose-only inhalation of EPFRs (20 min/day for 7 days) could decrease baseline left ventricular function in healthy male Sprague-Dawley rats. The model EPFR tested was 1,2-dichlorobenzene chemisorbed to 0.2-μm-diameter silica/CuO particles at 230°C (DCB230). Inhalation of vehicle or silica particles served as controls. Twenty-four hours after the last exposure, rats were anesthetized (isoflurane) and ventilated (3 l/min), and left ventricular function was assessed using pressure-volume catheters. Compared with controls, inhalation of DCB230 significantly decreased baseline stroke volume, cardiac output, and stroke work. End-diastolic volume and end-diastolic pressure were also significantly reduced; however, ventricular contractility and relaxation were not changed. DCB230 also significantly increased pulmonary arterial pressure and produced hyperplasia in small pulmonary arteries. Plasma levels of C-reactive protein were significantly increased by exposure to DCB230, as were levels of heme oxygenase-1 and SOD2 in the left ventricle. Together, these data show that inhalation of EPFRs, but not silica particles, decreases baseline cardiac function in healthy rats by decreasing cardiac filling, secondary to increased pulmonary resistance. These EPFRs also produced systemic inflammation and increased oxidative stress markers in the left ventricle. PMID:22942180

  13. Resting pulmonary artery pressure of 21-24 mmHg predicts abnormal exercise haemodynamics.

    PubMed

    Lau, Edmund M T; Godinas, Laurent; Sitbon, Olivier; Montani, David; Savale, Laurent; Jaïs, Xavier; Lador, Frederic; Gunther, Sven; Celermajer, David S; Simonneau, Gérald; Humbert, Marc; Chemla, Denis; Herve, Philippe

    2016-05-01

    A resting mean pulmonary artery pressure (mPAP) of 21-24 mmHg is above the upper limit of normal but does not reach criteria for the diagnosis of pulmonary hypertension (PH). We sought to determine whether an mPAP of 21-24 mmHg is associated with an increased risk of developing an abnormal pulmonary vascular response during exercise.Consecutive patients (n=290) with resting mPAP <25 mmHg who underwent invasive exercise haemodynamics were analysed. Risk factors for pulmonary vascular disease or left heart disease were present in 63.4% and 43.8% of subjects. An abnormal pulmonary vascular response (or exercise PH) was defined by mPAP >30 mmHg and total pulmonary vascular resistance >3 WU at maximal exercise.Exercise PH occurred in 74 (86.0%) out of 86 versus 96 (47.1%) out of 204 in the mPAP of 21-24 mmHg and mPAP <21 mmHg groups, respectively (OR 6.9, 95% CI: 3.6-13.6; p<0.0001). Patients with mPAP of 21-24 mmHg had lower 6-min walk distance (p=0.002) and higher New York Heart Association functional class status (p=0.03). Decreasing levels of mPAP were associated with a lower prevalence of exercise PH, which occurred in 60.3%, 38.7% and 7.7% of patients with mPAP of 17-20, 13-16 and <13 mmHg, respectively.In an at-risk population, a resting mPAP between 21-24 mmHg is closely associated with exercise PH together with worse functional capacity. PMID:26965292

  14. Clinical characterization and survival of patients with borderline elevation in pulmonary artery pressure.

    PubMed

    Heresi, Gustavo A; Minai, Omar A; Tonelli, Adriano R; Hammel, Jeffrey P; Farha, Samar; Parambil, Joseph G; Dweik, Raed A

    2013-12-01

    Normal resting mean pulmonary artery pressure (PAP) is 8-20 mmHg. Pulmonary hypertension is defined as mean PAP of ≥25 mmHg. Borderline PAP levels of 21-24 mmHg are of unclear significance. We sought to determine the clinical characteristics and survival of subjects with mean PAP of 21-24 mmHg. We examined 1,491 patients enrolled in the Cleveland Clinic Pulmonary Hypertension Registry between February 1990 and May 2012 with baseline right heart catheterization. The relationship between PAP and all-cause mortality was assessed by Cox models and a tree-based analysis. Sixty-three patients had borderline PAP (underlying conditions: 12 left heart disease, 20 respiratory disease, 17 connective-tissue disease, 4 others, and 10 none). We then compared 3 groups: borderline PAP without heart or lung disease ([Formula: see text]), normal PAP without heart or lung disease ([Formula: see text]), and category 1 pulmonary arterial hypertension (PAH; [Formula: see text]). Borderline-PAP patients had levels of hemodynamic and functional compromise between those for normal-PAP patients and those for patients with PAH. Borderline PAP was associated with increased mortality compared to normal PAP (hazard ratio: 4.03 [95% confidence interval: 0.78-20.80], [Formula: see text]). A tree-based analysis demonstrated almost identical cut points in mean PAP (≤20, 21-26, and ≥27 mmHg) associated with differential survival ([Formula: see text]). Connective-tissue disease and an elevated transpulmonary gradient were predictors of worse survival in the borderline-PAP population. Borderline PAP elevation is associated with decreased survival, particularly in the context of connective-tissue disease and an elevated transpulmonary gradient. PMID:25006408

  15. Pulmonary Arterial Hypertension

    MedlinePlus

    ... What Is Pulmonary Hypertension? To understand pulmonary hypertension (PH) it helps to understand how blood ows throughout ... is too high, it is called pulmonary hypertension (PH). How the pressure in the right side of ...

  16. Myosin heavy chain 15 is associated with bovine pulmonary arterial pressure.

    PubMed

    Neary, Marianne T; Neary, Joseph M; Lund, Gretchen K; Holt, Timothy N; Garry, Franklyn B; Mohun, Timothy J; Breckenridge, Ross A

    2014-09-01

    Bovine pulmonary hypertension, brisket disease, causes significant morbidity and mortality at elevations above 2,000 m. Mean pulmonary arterial pressure (mPAP) is moderately heritable, with inheritance estimated to lie within a few major genes. Invasive mPAP measurement is currently the only tool available to identify cattle at risk of hypoxia-induced pulmonary hypertension. A genetic test could allow selection of cattle suitable for high altitude without the need for invasive testing. In this study we evaluated three candidate genes (myosin heavy chain 15 [MYH15], NADH dehydrogenase flavoprotein 2, and FK binding protein 1A) for association with mPAP in 166 yearling Angus bulls grazing at 2,182 m. The T allele (rs29016420) of MYH15 was linked to lower mPAP in a dominant manner (CC 47.2 ± 1.6 mmHg [mean ± standard error of the mean]; CT/TT 42.8 ± 0.7 mmHg; P = 0.02). The proportions of cattle with MYH15 CC, CT, and TT genotypes were 55%, 41%, and 4%, respectively. Given the high frequency of the deleterious allele, it is likely that the relative contribution of MYH15 polymorphisms to pulmonary hypertension is small, supporting previous predictions that the disease is polygenic. We evaluated allelic frequency of MYH15 in the Himalayan yak (Bos grunniens), a closely related species adapted to high altitude, and found 100% prevalence of T allele homozygosity. In summary, we identified a polymorphism in MYH15 significantly associated with mPAP. This finding may aid selection of cattle suitable for high altitude and contribute to understanding human hypoxia-induced pulmonary hypertension.

  17. Relation between peripheral chemoreceptors stimulation and pulmonary arterial blood pressure in rats.

    PubMed

    Lagneaux, D

    1986-06-01

    As interactions between peripheral chemoreceptors stimulation (PCS) and pulmonary vasomotor tone remain controversial, experiments were made in rats in order to clear up the effects of PCS on pulmonary arterial pressure (PAP). Different stimulations varying in intensities were used, in rats nervously intact (IR-rats), after vagotomy (XT-rats), after chemodenervation obtained without vagotomy (CDN not XT-rats) or with XT (CDN + XT) and finally after alpha 1-receptors blockade (P-rats = pretreated rats). The observed variations were analysed in view of disentangling reflex part of PCS from a direct activity on the pulmonary vascular bed. Ventilation, PAP and systemic blood pressure (BP) were studied in anaesthetized rats. N2 test, NaCN test, 20 s of 5% O2 inhalation and almitrine bismesylate (ALM) were used as PCS, ranged in the order of their relative intensities, from the ventilatory responses observed in IR-rats. In IR-rats, N2-and CN test produced a similar transient increase of PAP, slightly more extended than the hyperventilation. After XT, the responses were prolonged, but amplified only in CN test. Ventilatory responses disappear after CDN, but as far as pulmonary hypertension is concerned, CDN + XT is more potent than CDN without XT to reduce or even suppress them. This fact is particularly evident with ALM who is the strongest PCS used. Similar reduction of PAP rise was also produced in P-rats in which ventilatory responses remain unchanged. Prolonged hypoxic inhalation induced a progressive fall of systolic BP and of PAP. The return to normal air breathing is followed by BP restoration and a long-lasting PAP increase.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Evolution from electrophysiologic to hemodynamic monitoring: the story of left atrial and pulmonary artery pressure monitors

    PubMed Central

    Mooney, Deirdre M.; Fung, Erik; Doshi, Rahul N.; Shavelle, David M.

    2015-01-01

    Heart failure (HF) is a costly, challenging and highly prevalent medical condition. Hospitalization for acute decompensation is associated with high morbidity and mortality. Despite application of evidence-based medical therapies and technologies, HF remains a formidable challenge for virtually all healthcare systems. Repeat hospitalizations for acute decompensated HF (ADHF) can have major financial impact on institutions and resources. Early and accurate identification of impending ADHF is of paramount importance yet there is limited high quality evidence or infrastructure to guide management in the outpatient setting. Historically, ADHF was identified by physical exam findings or invasive hemodynamic monitoring during a hospital admission; however, advances in medical microelectronics and the advent of device-based diagnostics have enabled long-term ambulatory monitoring of HF patients in the outpatient setting. These monitors have evolved from piggybacking on cardiac implantable electrophysiologic devices to standalone implantable hemodynamic monitors that transduce left atrial or pulmonary artery pressures as surrogate measures of left ventricular filling pressure. As technology evolves, devices will likely continue to miniaturize while their capabilities grow. An important, persistent challenge that remains is developing systems to translate the large volumes of real-time data, particularly data trends, into actionable information that leads to appropriate, safe and timely interventions without overwhelming outpatient cardiology and general medical practices. Future directions for implantable hemodynamic monitors beyond their utility in heart failure may include management of other major chronic diseases such as pulmonary hypertension, end stage renal disease and portal hypertension. PMID:26500556

  19. Doppler assessment of pulmonary artery pressure in neonates at risk of chronic lung disease

    PubMed Central

    Su, B.; Watanabe, T.; Shimizu, M.; Yanagisawa, M.

    1997-01-01

    AIM—To evaluate the pulmonary artery pressure (PAP) change in very low birthweight (VLBW) infants at risk of chronic lung disease (CLD).
METHODS—The time to peak velocity:right ventricular ejection time (TPV:RVET) ratio calculated from the pulmonary artery Doppler waveform, which is inversely related to PAP, was used. The TPV:RVET ratio was corrected for different heart rate (TPV:RVET(c)). Seventy three VLBW infants studied on days 1, 2, 3, 7, 14, 21 and 28 were enrolled for the analysis.
RESULTS—Twenty two infants developed CLD with a characteristic chest radiograph at day 28. Fifty one did not, of whom 17 were oxygen dependent on account of apnoea rather than respiratory disease, and 34 were non-oxygen dependent. The TPV:RVET(c) ratio rose progressively in all three groups over the first three days of life, suggesting a fall in PAP. In the oxygen and non-oxygen dependent groups, the mean (SD) ratio rose to 0.53 (0.09) and 0.57 (0.09), respectively, on day 7, then remained relatively constant thereafter. The CLD group rose more slowly after day 3 and had a significantly lower mean ratio from day 7 onwards compared with the other two groups (day 7: P<0.001, days 14-28: P<0.0001), and fell significantly from 0.47 (0.11) on day 7 to 0.41 (0.07) on day 28 (P=0.01), suggesting a progressive rise in PAP. The mean (SD) ratios at day 28 of all infants were: CLD group 0.41 (0.07); oxygen dependent group 0.66 (0.15); and the non-oxygen group 0.67 (0.11). The CLD group had a significantly lower ratio than the oxygen dependent group and the non-oxygen group (P<0.0001). Using the TPV:RVET(c) ratio of <0.46, infants at risk of developing CLD could be predicted on day 7 (predictive value 82.8%, sensitivity 54.5%, specificity 94.1%).
CONCLUSION—The non-invasive assessment of PAP using the TPV:RVET(c) ratio may be useful in the longitudinal monitoring of PAP change in VLBW infants, and for prediction of chronic lung disease.

 Keywords

  20. Angus sattle at high altitude: Genetic relationships and initial genome-wide association analyses of pulmonary arterial pressure

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Records from yearling Angus (n = 10,647) cattle from elevation 2,340 m were used in genetic analysis of pulmonary arterial pressure (PAP). Bulls were developed within a grain-supplemented performance test, whereas heifers and steers were grazed. The BovineSNP50 Beadchip was used to genotype a subset...

  1. Serial pulsed Doppler assessment of pulmonary artery pressure in very low birth-weight infants.

    PubMed

    Murase, M; Ishida, A

    2000-01-01

    We assessed pulmonary artery pressure (PAP) during the early neonatal period in very low birth-weight (VLBW) infants using serial echocardiographic measurements of the ratio of the pulmonary artery acceleration time to the right ventricular ejection time corrected by heart rate [AT:RVET(c)]. Eighty-four VLBW infants weighing less than 1,500 g were examined using serial color Doppler echocardiography from 3 hours to day 7 after birth. The AT:RVET(c) of infants born after 30 weeks of gestation showed a rapid, significant increase during the early neonatal period, whereas those of the groups born at less than 30 weeks showed no significant increase before day 14. At 24 hours after birth, the AT:RVET(c) values of VLBW infants did not correlate well with either the ratio of the right preejection period to the right ventricular ejection time on M-mode echocardiography or the pressure gradient between the right ventricle and the right atrium, as estimated by tricuspid regurgitation on pulsed Doppler echocardiography. The AT:RVET(c) value for the chronic lung disease (CLD) group did not differ significantly from that for the oxygen-dependent group at any assessment point. During the early neonatal period, the AT:RVET(c) of VLBW infants, as calculated by pulsed Doppler echocardiography, differed with their gestational age and did not appear to correlate well with PAP. Our data also suggest that AT:RVET(c) values may not be a good predictor of the subsequent occurrence of CLD in VLBW infants.

  2. Pulmonary arterial hypertension

    PubMed Central

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role

  3. Pulmonary arterial hypertension.

    PubMed

    Montani, David; Günther, Sven; Dorfmüller, Peter; Perros, Frédéric; Girerd, Barbara; Garcia, Gilles; Jaïs, Xavier; Savale, Laurent; Artaud-Macari, Elise; Price, Laura C; Humbert, Marc; Simonneau, Gérald; Sitbon, Olivier

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role

  4. Transcatheter closure of high pulmonary artery pressure persistent ductus arteriosus with the Amplatzer muscular ventricular septal defect occluder

    PubMed Central

    Thanopoulos, B D; Tsaousis, G S; Djukic, M; Al Hakim, F; Eleftherakis, N G; Simeunovic, S D

    2002-01-01

    Background: The design of devices currently used for closure of persistent ductus arteriosus (PDA) with high pulmonary artery pressure is not ideal and there is a risk of embolisation into the aorta. Objective: To investigate the use of the Amplatzer muscular ventricular septal defect occluder (AMVSDO) for treatment of PDA with high pulmonary artery pressure. Patients and design: Seven patients, aged 5–12 years, with large PDAs and systemic or near systemic pulmonary artery pressure underwent attempted transcatheter closure using the AMVSDO. The device consists of two low profile disks made of a nitinol wire mesh with a 7 mm connecting waist. Balloon occlusion of the duct was performed before closure from the venous side, and prosthesis size was chosen according to the measured diameter of the occluding balloon. A 7 French sheath was used to deliver the device. All patients underwent a complete haemodynamic and angiographic study one year after occlusion. Results: The mean (SD) angiographic PDA diameter was 9.8 (1.7) mm (range 7–13 mm) and the mean AMVSDO diameter was 11.4 (1.8) mm (range 9–16 mm). Qp/Qs ranged from 1.9–2.2 (mean 2.0 (0.1)). Successful device delivery and complete closure occurred in all patients (100% occlusion rate, 95% confidence interval 59.04% to 100.00%). Mean systolic pulmonary artery pressures were as follows: before balloon occlusion, 106 (13) mm Hg; during occlusion, 61 (6) mm Hg; immediately after the procedure, 57 (5) mm Hg; and at the one year follow up catheterisation, 37 (10) mm Hg. Fluoroscopy time was 10.4 (4.3) min (range 7–18 min). No complications occurred. Conclusions: AMVSDO is an important adjunct for closure of large PDAs associated with high pulmonary artery pressure. Further studies are required to document its efficacy, safety, and long term results in a larger number of patients. PMID:11847167

  5. Pulmonary arterial hypertension in primary amyloidosis

    PubMed Central

    Emerson, Lyska L.; Bull, David A.; Hatton, Nathan; Nativi-Nicolai, Jose; Hildebrandt, Gerhard C.; Ryan, John J.

    2016-01-01

    Abstract Amyloidosis involves extravascular deposition of fibrillar proteins within tissues and organs. Primary light chain amyloidosis represents the most common form of systemic amyloidosis involving deposition of monoclonal immunoglobulin light chains. Although pulmonary amyloid deposition is common in primary amyloidosis, clinically significant pulmonary amyloidosis is uncommon, and elevated pulmonary artery pressures are rarely observed in the absence of other underlying etiologies for pulmonary hypertension, such as elevated filling pressures secondary to cardiac amyloid. In this case report, we present a patient with primary light chain amyloidosis and pulmonary arterial hypertension in the setting of pulmonary vascular and right ventricular myocardial amyloid deposition. PMID:27252852

  6. Patient positioning and the accuracy of pulmonary artery pressure measurements (180f).

    PubMed

    Shih, F J

    1999-12-01

    The measurement of pulmonary artery pressure (PAP) is a common nursing practice in hemodynamic monitoring of patients in the emergency room and intensive care unit. Several researchers have proposed that PAP should be measured with the patient in a supine position with legs horizontal in order to promote a relaxed state. The most widely used reference point is the phlebostatic axis, which is located at the intersection of the fourth intercostal space and the midchest level. However, this positioning requirement is in conflict with one of the goals of nursing care, which is to achieve comfortable positioning of the patient without compromising respiratory or cardiovascular function. In addition, since frequent readings are necessary, critically ill patients can lose valuable sleep time. The existing literature still fails to justify the validity of the phlebostatic axis as an external reference point for leveling the pressure transducer. In addition, findings on the accuracy of readings obtained in the supine, Fowler's and lateral recumbent positions are also in conflict. This paper reviewed research related to measurement of PAP in the supine, various Fowler's, and lateral positions in order to clarify the major factors which might have resulted in the conflicts in data on PAP measurements. Suggestions are also provided for nurse clinicians to obtain more accurate PAP measurements. PMID:10576120

  7. Acute effects of oxygen administration on transmural pulmonary artery pressure in obstructive sleep apnea.

    PubMed

    Marrone, O; Bellia, V; Pieri, D; Salvaggio, A; Bonsignore, G

    1992-04-01

    In order to investigate the role of hypoxia on the cyclic oscillation of transmural pulmonary artery pressure (PAP) in obstructive sleep apnea, oxygen was administered during one half of the night to six patients affected by obstructive sleep apnea syndrome during a nocturnal polysomnographic study. In each patient, transmural PAP measurements were performed on 15 randomly selected apneas recorded while breathing room air, and on 15 during O2 administration. During O2 administration in all patients, apneas were associated with a higher oxyhemoglobin saturation (SaO2), a smaller SaO2 swing, and a higher transcutaneous PCO2. The mean highest level of transmural PAP in the apneic episodes, commonly reached at their end, was significantly lower than while breathing room air in only two patients; however, due to a decrease in the mean lowest PAP level (at the beginning of apneas), the extent of the PAP increase within apneas did not differ between air and O2 breathing; these patients showed the smallest increase in transcutaneous PCO2 in our sample. End-apneic transmural PAP during O2 administration was significantly higher in one subject (for systolic values) and was not significantly different in the remaining three subjects. The extent of the increase in transmural PAP within apneas was greater in one patient; it was smaller in another one, but only for the diastolic values; and it did not differ significantly with respect to the value observed while breathing room air in all of the other subjects. The results suggest that hypoxia in obstructive apneas, at least in some patients, may lead to a steady increase in PAP, detectable both at the beginning and at the end of the episodes; conversely, the increase in PAP within apneas does not seem to be influenced by the simultaneous decrease in SaO2. PMID:1555416

  8. Pulmonary hypertension and pulmonary artery dissection

    PubMed Central

    Corrêa, Ricardo de Amorim; Silva, Luciana Cristina dos Santos; Rezende, Cláudia Juliana; Bernardes, Rodrigo Castro; Prata, Tarciane Aline; Silva, Henrique Lima

    2013-01-01

    Pulmonary artery dissection is a fatal complication of long-standing pulmonary hypertension, manifesting as acute, stabbing chest pain, progressive dyspnea, cardiogenic shock, or sudden death. Its incidence has been underestimated, and therapeutic options are still scarce. In patients with pulmonary hypertension, new chest pain, acute chest pain, or cardiogenic shock should raise the suspicion of pulmonary artery dissection, which can result in sudden death. PMID:23670510

  9. An Update on Pulmonary Arterial Hypertension

    PubMed Central

    Wapner, Joanna; Matura, Lea Ann

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a progressive disease that ultimately leads to right heart failure and death. PAH is defined as a mean pulmonary arterial pressure ≥ 25 mm Hg with a pulmonary capillary wedge pressure ≤ 15 mm Hg at rest. The diagnosis of PAH is one of exclusion; diagnostics include an extensive history, serology, chest radiograph, pulmonary function tests, ventilation/perfusion scan, transthoracic echocardiogram, and right heart catheterization. Treatment and care of patients with PAH can be complex. Therefore, the nurse practitioner is an integral member of the healthcare team caring for PAH patients, helping to ensure seamless care and support. PMID:25954140

  10. Exercise physiology and pulmonary arterial hypertension.

    PubMed

    Waxman, Aaron B

    2012-01-01

    The lungs are the only organ that receives the entire cardiac output with every stroke. The pulmonary circulation is normally a high-flow, low-resistance, low-pressure system that carries blood into the pulmonary microcirculation. In pulmonary artery hypertension (PAH)vascular remodeling contributes to a sustained elevation of pulmonary vascular resistance (PVR) and pulmonary artery pressure (PAP) as a result of vascular remodeling characterized largely by vascular smooth muscle cell proliferation and medial hypertrophy, and endothelial cell proliferation resulting in lumen obliteration. The loss of pulmonary arterial compliance and development of elevated PVR puts an excessive burden on the right ventricle due to the increased workload necessary to overcome the downstream pressure, ultimately leading to right-sided heart failure. The functional status of the pulmonary circulation and the levels of PVR and PAP ultimately determine the outcome of patients with PAH. Study of the pressure-flow relationships in the pulmonary vascular bed will provide an improved appreciation of the pathophysiology of pulmonary hypertension.

  11. The Impact of Pulmonary Arterial Pressure on Exercise Capacity in Mild-to-Moderate Cystic Fibrosis: A Case Control Study

    PubMed Central

    Manika, Katerina; Pitsiou, Georgia G.; Boutou, Afroditi K.; Tsaoussis, Vassilis; Chavouzis, Nikolaos; Antoniou, Marina; Fotoulaki, Maria; Stanopoulos, Ioannis; Kioumis, Ioannis

    2012-01-01

    Background. Pulmonary hypertension (PH) is an often complication of severe cystic fibrosis (CF); however, data on the presence and impact of pulmonary vasculopathy in adult CF patients with milder disease, is very limited. Aim. To investigate, for the first time, the impact of systolic pulmonary arterial pressure (PASP) on maximal exercise capacity in adults with mild-to-moderate cystic fibrosis, without PH at rest. Methods. This is a Case Control study. Seventeen adults with mild-to-moderate CF, without PH at rest (cases) and 10 healthy, nonsmoking, age, and height matched controls were studied. All subjects underwent maximal cardiopulmonary exercise testing and echocardiography before and within 1 minute after stopping exercise. Results. Exercise ventilation parameters were similar in the two groups; however, cases, compared to controls, had higher postexercise PASP and decreased exercise capacity, established with lower peak work rate, peak O2 uptake, anaerobic threshold, and peak O2 pulse. Furthermore, the change in PASP values before and after exercise was strongly correlated to the parameters of exercise capacity among cases but not among controls. Conclusions. CF adults with mild-to-moderate disease should be screened for the presence of pulmonary vasculopathy, since the elevation of PASP during exercise might contribute to impaired exercise capacity. PMID:22900167

  12. Investigating Cardiac MRI Based Right Ventricular Contractility As A Novel Non-Invasive Metric of Pulmonary Arterial Pressure

    PubMed Central

    Menon, Prahlad G; Adhypak, Srilakshmi M; Williams, Ronald B; Doyle, Mark; Biederman, Robert WW

    2014-01-01

    BACKGROUND We test the hypothesis that cardiac magnetic resonance (CMR) imaging-based indices of four-dimensional (4D) (three dimensions (3D) + time) right ventricle (RV) function have predictive values in ascertaining invasive pulmonary arterial systolic pressure (PASP) measurements from right heart catheterization (RHC) in patients with pulmonary arterial hypertension (PAH). METHODS We studied five patients with idiopathic PAH and two age and sex-matched controls for RV function using a novel contractility index (CI) for amplitude and phase to peak contraction established from analysis of regional shape variation in the RV endocardium over 20 cardiac phases, segmented from CMR images in multiple orientations. RESULTS The amplitude of RV contractility correlated inversely with RV ejection fraction (RVEF; R2 = 0.64, P = 0.03) and PASP (R2 = 0.71, P = 0.02). Phase of peak RV contractility also correlated inversely to RVEF (R2 = 0.499, P = 0.12) and PASP (R2 = 0.66, P = 0.04). CONCLUSIONS RV contractility analyzed from CMR offers promising non-invasive metrics for classification of PAH, which are congruent with invasive pressure measurements. PMID:25624777

  13. Dynamic Changes of Pulmonary Arterial Pressure and Ductus Arteriosus in Human Newborns From Birth to 72 Hours of Age

    PubMed Central

    Kang, Chunmiao; Zhao, Enfa; Zhou, Yinghua; Zhao, Huayun; Liu, Yunyao; Gao, Ningning; Huang, Xiaoxin; Liu, Baomin

    2016-01-01

    Abstract Normal pulmonary artery pressure and pulmonary hypertension assessment of newborns is rarely reported. The aim of the study is to explore dynamic changes of pulmonary arterial pressure and ductus arteriosus in human newborns from birth to 72 h of age with echocardiography. A total of 76 cases of normal newborns were prospectively detected by echocardiography after birth of 2 h, 6 h, 12 h, 24 h, 48 h, and 72 h, respectively. Ductus arteriosus diameter, blood shunt direction, blood flow velocity, and pressure gradient were recorded. The brachial artery blood pressure were measured to estimate the pulmonary artery systolic pressure (PASP) and pulmonary artery diastolic pressure (PADP) using patent ductus arteriosus pressure gradient method. The mean pulmonary artery pressure (PAMP) were calculated by equation of PAMP = PADP + 1/3(PASP-PADP). (1) There were 76 cases of normal newborns. Among them, 29 cases (38%) ductus arteriosus closed within 24 h, 59 cases (78%) closed within 48 h, 72 cases (95%) closed within 72 h, and 4 cases (5%) ductus arteriosus not closed within 72 h. (2) The ductus arteriosus diameter of 2 h, 6 h, 12 h, 24 h, 48 h, and 72 h after birth was 4.60 ± 0.59 mm, 3.37 ± 0.59 mm, 2.47 ± 0.49 mm, 1.89 ± 0.41 mm, 1.61 ± 0.35 mm, and 1.20 ± 0.24 mm, respectively. Compared all of the ductus arteriosus diameter of the above time periods, there were statistically differences with P < 0.05, respectively. (3) The mean PASP in 2 h, 6 h, 12 h, 24 h, 48 h, 72 h after birth were 76.58 ± 7.28 mm Hg, 65.53 ± 9.25mm Hg, 52.51 ± 9.07 mm Hg, 43.83 ± 7.90 mm Hg, 38.07 ± 8.26 mm Hg, and 36 ± 6.48 mm Hg, respectively. The PADP of the above time period were 37.88 ± 5.56 mm Hg, 29.93 ± 7.91 mm Hg, 23.43 ± 7.37 mm Hg, 19.70 ± 8.51 mm Hg, 13.85 ± 5.58 mm Hg, 13.25 ± 6.18 mm Hg, respectively. The PAMP of the

  14. Molecular Mechanisms of Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension

    PubMed Central

    Leopold, Jane A.; Maron, Bradley A.

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease that is precipitated by hypertrophic pulmonary vascular remodeling of distal arterioles to increase pulmonary artery pressure and pulmonary vascular resistance in the absence of left heart, lung parenchymal, or thromboembolic disease. Despite available medical therapy, pulmonary artery remodeling and its attendant hemodynamic consequences result in right ventricular dysfunction, failure, and early death. To limit morbidity and mortality, attention has focused on identifying the cellular and molecular mechanisms underlying aberrant pulmonary artery remodeling to identify pathways for intervention. While there is a well-recognized heritable genetic component to PAH, there is also evidence of other genetic perturbations, including pulmonary vascular cell DNA damage, activation of the DNA damage response, and variations in microRNA expression. These findings likely contribute, in part, to dysregulation of proliferation and apoptosis signaling pathways akin to what is observed in cancer; changes in cellular metabolism, metabolic flux, and mitochondrial function; and endothelial-to-mesenchymal transition as key signaling pathways that promote pulmonary vascular remodeling. This review will highlight recent advances in the field with an emphasis on the aforementioned molecular mechanisms as contributors to the pulmonary vascular disease pathophenotype. PMID:27213345

  15. [Serotonin hypothesis and pulmonary artery hypertension].

    PubMed

    Kloza, Monika; Baranowska-Kuczko, Marta; Pędzińska-Betiuk, Anna; Jackowski, Konrad; Kozłowska, Hanna

    2014-06-06

    Pulmonary arterial hypertension (PAH) is a progressive, complex disease leading to the right ventricular failure and premature death. PAH is characterized by increased pulmonary arterial pressure, increased vascular resistance, pulmonary vascular remodeling and endothelial dysfunction. Pathomechanism of this disease is still unknown. It has been suggested, that endothelial dysfunction is caused by unbalance between vasodilators and vasoconstrictors e.g. serotonin (5-HT). Previously, serotonin hypothesis was linked to the anorexigens, derivatives of fenfluramine, which are serotonin transporter (SERT) substrates. Nowadays, it has been proved that all elements of serotonergic system within pulmonary circulation participate in the developement of PAH. The tryptophan hydroxylase 1 (Tph-1) catalyses synthesis of 5-HT from tryptophan in the pulmonary arterial endothelial cells. 5-HT mediates contraction of pulmonary vessels via 5-HT1B and 5-HT2A receptors. 5-HT is also transported into pulmonary arterial smooth muscle cells via SERT and through activation of reactive oxygen species and Rho-kinase may contribute to contraction or/and, via stimulation of transcription factors, lead to proliferation and remodelling. There is also increasing number of evidence about functional interaction between 5-HT1B receptor and SERT in modulation of vasoconstriction and proliferation in pulmonary arteries. This review discusses the role of 5-HT in the development of PAH and highlights possible therapeutic targets within serotonergic system.

  16. Update on pulmonary arterial hypertension pharmacotherapy.

    PubMed

    Velayati, Arash; Valerio, Marcos G; Shen, Michael; Tariq, Sohaib; Lanier, Gregg M; Aronow, Wilbert S

    2016-06-01

    Pulmonary artery hypertension (PAH) refers to several subgroups of disease in which the mean pulmonary artery pressure (mPAP) is elevated to more than 25 mm Hg, pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg, and an elevated pulmonary vascular resistance (PVR) > 3 Wood units as confirmed by right heart catheterization. The prevalence and geographic distribution of PAH vary depending on the type and etiology of the disease. Despite enormous efforts in the research and development of therapeutic agents in the last twenty years, the disease remains relatively incurable and the overall prognosis remains guarded. Median survival for an untreated patient is 2.8 years. In the last three decades, there have been dramatic advances in understanding the molecular mechanisms and signaling pathways involved in the disease, resulting in emerging new treatment strategies. In the following pages, we will review currently approved treatments for PAH, as well as a new generation of investigational drugs. PMID:27232660

  17. Contribution of live heartworms harboring in pulmonary arteries to pulmonary hypertension in dogs with dirofilariasis.

    PubMed

    Kitagawa, H; Sasaki, Y; Ishihara, K; Hirano, Y

    1990-12-01

    To investigate whether adult heartworms harboring in the pulmonary arteries contribute to pulmonary hypertension, we determined the cardio-pulmonary values immediately before and after removal of heartworms from the pulmonary arteries and before and after insertion of live worms in their place. In 10 heartworm-infected dogs, 8 to 46 worms were removed. The mean pulmonary arterial pressure fell significantly from 24.5 +/- 7.9 mmHg to 16.3 +/- 4.9 mmHg (p less than 0.01) immediately after removal. The right cardiac output decreased in 7 of the 10 cases. The total pulmonary resistance and right ventricular stroke work index also decreased. At 24 hours after removal, live heartworms were put back into the pulmonary arteries of their host dog. The mean pulmonary arterial pressure elevated significantly (p less than 0.01) immediately after insertion. The right cardiac output further decreased in 7 of the 10 dogs, and the total pulmonary resistance and right ventricular stroke work index increased. Separate from this, 12 to 42 heartworms were transplanted into the pulmonary arteries of 5 heartworm-free dogs. Immediately after transplantation, the pulmonary arterial pressure did not show any significant change. However, the stroke volume decreased, and the total pulmonary resistance increased. These facts suggest a contribution of live heartworms to the pulmonary hypertension, although there is a complicated interaction among the presence of heartworms, the pulmonary lesions and the pulmonary hypertension.

  18. Pulmonary Arterial Pressure Response During Exercise in COPD: A Correlation with C-Reactive Protein (hsCRP)

    PubMed Central

    Varga, Janos; Palinkas, Attila; Lajko, Imre; Horváth, Ildikó; Boda, Krisztina; Somfay, Attila

    2016-01-01

    Background: The non-invasive assessment of pulmonary haemodynamics during exercise provides complementary data for the evaluation of exercise tolerance in patients with COPD. Methods: Exercise echocardiography in the semi-supine position was performed in 27 patients with COPD (C) with a forced expiratory volume in one second (FEV1) of 36±12% predicted and 13 age and gender-matched non-COPD subjects (NC). COPD patients also underwent cardiopulmonary exercise testing with gas exchange detection (CPET). Furthermore, serum high sensitive C-reactive protein (hsCRP), a marker of systemic inflammation, was also measured. Results: The maximal work rate (WRmax) and aerobic capacity (VO2peak) were significantly reduced (WRmax: 77±33 Watt, VO2peak: 50±14 %pred) in COPD. Pulmonary arterial systolic pressure (PAPs) was higher in COPD versus controls both at rest (39±5 vs. 31±2 mmHg, p<0.001), and at peak exercise (72±12 vs. 52±8 mmHg, p<0.001). In 19 (70%) COPD patients, the increase in PAPs was above 22 mmHg. The change in pressure (dPAPs) correlated with hsCRP (r2=0.53, p<0.0001) and forced vital capacity (FVC) (r2=0.18, p<0.001). Conclusion: PAPs at rest and during exercise were significantly higher in COPD patients and correlated with higher hsCRP. This may indicate a role for systemic inflammation and hyperinflation in the pulmonary vasculature in COPD. The study was registered at ClinicalTrials.gov webpage with NCT00949195 registration number. PMID:27019674

  19. The Effect of Tonsillectomy and Adenoidectomy on Right Ventricle Function and Pulmonary Artery Pressure by Using Doppler Echocardiography in Children

    PubMed Central

    Acar, Onur Çağlar; Üner, Abdurrahman; Garça, Mehmet Fatih; Ece, İbrahim; Epçaçan, Serdar; Turan, Mahfuz; Kalkan, Ferhat

    2016-01-01

    Objectives The purpose of the present study is to emphasize the efficacy of the myocardial performance index and tricuspid annular plane systolic excursion (TAPSE) in the determination of impaired cardiac functions and recovery period following the treatment in children with adenoid and/or tonsillar hypertrophy. Methods Fifty-three healthy children after routine laboratory, imaging and clinical examinations, with adenoid and/or tonsillar hypertrophy were evaluated before and 3 months after adenotonsillectomy for cardiac functions using M mode and Doppler echocardiography. Results The mean age of cases was 6.4±3.0 years, 34 (65%) were male, and 19 (35%) were female. Pulmonary hypertension was observed to be mild in 3 patients and moderate in 1 patient preoperatively. When the preoperative and postoperative echocardiographic measurements of the patients were compared, the tricuspid valve E wave velocity, the E/A ratio (E, early diastolic flow rate; A, late diastolic flow rate), and the TAPSE values were determined to be significantly higher postoperatively (P<0.05). The tricuspid valve deceleration time, the isovolumetric relaxation time and the systolic pulmonary artery pressure were found to be significantly lower compared to the preoperative values (P<0.05). Conclusion Adenoidectomy and/or tonsillectomy may prevent cardiac dysfunctions that can develop in the later periods due to adenoid and/or tonsil hypertrophy in children, before the appearance of the clinical findings of cardiac failure. PMID:27090272

  20. Regression of pulmonary artery hypertension due to development of a pulmonary arteriovenous malformation

    PubMed Central

    Hasan, Ashfaq; Sastry, B.K.S.; Aleem, M.A.; Reddy, Gokul; Mahmood, Syed

    2014-01-01

    Idiopathic Pulmonary Hypertension (IPAH) is characterized by elevated pulmonary arterial pressure in the absence of an identifiable underlying cause. The condition is usually relentlessly progressive with a short survival in the absence of treatment.1 We describe a patient of IPAH in whom the pulmonary artery pressures significantly abated with complete disappearance of symptoms, following spontaneous development of a pulmonary arterio-venous malformation (PAVM). PMID:25443608

  1. High estimated pulmonary artery systolic pressure predicts adverse cardiovascular outcomes in stage 2-4 chronic kidney disease.

    PubMed

    Bolignano, Davide; Lennartz, Simone; Leonardis, Daniela; D'Arrigo, Graziella; Tripepi, Rocco; Emrich, Insa E; Mallamaci, Francesca; Fliser, Danilo; Heine, Gunnar; Zoccali, Carmine

    2015-07-01

    High estimated pulmonary artery systolic pressure (ePASP) is an established risk factor for mortality and cardiovascular (CV) events in the general population. High ePASP predicts mortality in dialysis patients but such a relationship has not been tested in patients with early CKD. Here we estimated the prevalence and the risk factors of high ePASP in 468 patients with CKD stage 2-4 and determined its prognostic power for a combined end point including cardiovascular death, acute heart failure, coronary artery disease, and cerebrovascular and peripheral artery events. High ePASP (35 mm Hg and above) was present in 108 CKD patients. In a multivariate logistic regression model adjusted for age, diabetes, hemoglobin, left atrial volume (LAV/BSA), left ventricular mass (LVM/BSA), and history of CV disease, age (OR, 1.06; 95% CI, 12 1.04-1.09) and LAV/BSA (OR, 1.05; 95% CI, 1.03-1.07) were the sole significant independent predictors of high ePASP. Elevated ePASP predicted a significantly high risk for the combined cardiovascular end point both in unadjusted analyses (HR, 2.70; 95% CI, 1.68-4.32) and in analyses adjusting for age, eGFR, hemoglobin, LAV/BSA, LVM/BSA, and the presence of diabetes and CV disease (HR, 1.75; 95% CI, 1.05-2.91). High ePASP is relatively common in patients with stage 2-4 CKD and predicts adverse CV outcomes independent of established classical and CKD-specific risk factors. Whether high ePASP is a modifiable risk factor in patients with CKD remains to be determined in randomized clinical trials. PMID:25692957

  2. Targeted therapies in pulmonary arterial hypertension.

    PubMed

    Montani, David; Chaumais, Marie-Camille; Guignabert, Christophe; Günther, Sven; Girerd, Barbara; Jaïs, Xavier; Algalarrondo, Vincent; Price, Laura C; Savale, Laurent; Sitbon, Olivier; Simonneau, Gérald; Humbert, Marc

    2014-02-01

    Pulmonary arterial hypertension (PAH) is a rare disorder characterized by progressive obliteration of small pulmonary arteries that leads to elevated pulmonary arterial pressure and right heart failure. During the last decades, an improved understanding of the pathophysiology of the disease has resulted in the development of effective therapies targeting endothelial dysfunction (epoprostenol and derivatives, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors). These drugs allow clinical, functional and hemodynamic improvement. Even though, no cure exists for PAH and prognosis remains poor. Recently, several additional pathways have been suggested to be involved in the pathogenesis of PAH, and may represent innovative therapies. In this summary, we review conventional therapy, pharmacological agents currently available for the treatment of PAH and the benefit/risk ratio of potential future therapies. PMID:24134901

  3. The Warburg effect: A new story in pulmonary arterial hypertension.

    PubMed

    Peng, Hongyan; Xiao, Yunbin; Deng, Xicheng; Luo, Jingfei; Hong, Chenliang; Qin, Xuping

    2016-10-01

    Pulmonary arterial hypertension (PAH) is a rare yet fatal condition that is characterized by a continuous and notable elevation of pulmonary arterial pressure (PAP), resulting in right heart failure and death. Pulmonary arterial remodelling does not result from abnormal proliferation of pulmonary arterial vascular smooth muscle cells (PASMCs) but from pulmonary arterial endothelial cell (PAEC) dysfunction. However, the pathological mechanism of these two types of vascular cells in pulmonary artery remodelling is unclear. The Warburg effect describes aerobic glycolysis wherein cells commonly reprogram their energy metabolism to preferentially utilize glycolysis over oxidative phosphorylation for ATP production. Recent research has demonstrated that the Warburg effect plays a significant role in the development of PAH, which involves the abnormal proliferation of PASMCs and endothelial dysfunction. This review attempts to illustrate the functions of the Warburg effect in PAH, which may provide a new therapeutic target for PAH treatment.

  4. Usefulness of the Sum of Pulmonary Capillary Wedge Pressure and Right Atrial Pressure as a Congestion Index that Prognosticates Heart Failure Survival (from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness Trial).

    PubMed

    Ma, Tony S; Paniagua, David; Denktas, Ali E; Jneid, Hani; Kar, Biswajit; Chan, Wenyaw; Bozkurt, Biykem

    2016-09-15

    In the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial, use of a pulmonary artery catheter did not significantly affect advanced heart failure outcomes. However, the success of achieving the targeted hemodynamic goals of pulmonary capillary wedge pressure (PCWP) of 15 mm Hg and right atrial pressure (RAP) of 8 mm Hg and the association of these goals with clinical outcomes were not addressed. Furthermore, goals with 2 independent variables, PCWP and RAP, left room for uncertainties. We assessed the ability of a single hemodynamic target to achieve a threshold sum of PCWP and RAP as a predictor of all-cause mortality, death-or-transplantation (DT), or death-or-rehospitalization (DR) at 6 months in the pulmonary artery catheter-guided treatment arm of ESCAPE (n = 206). Patients with a posttreatment PCWP + RAP of <30 mm Hg had characteristics similar to those of the population who achieved the ESCAPE hemodynamic goals. This group had 8.7% mortality, 13.0% DT, and 58.7% DR at 6 months. The contrasting cohort with PCWP + RAP of ≥30 mm Hg had 45.3% mortality, 54.7% DT, and 84.9% DR at 6 months, with greater relative risk (RR) of death (RR 5.76), DT (RR 4.92), and DR (RR 1.80) and higher prevalence of jugular venous pulsation, edema, hepatomegaly, and ascites at admission and discharge. In conclusion, PCWP + RAP of 30 mm Hg posttreatment, obtained early in the index hospitalization, may represent as a simple congestion index that has prognostic value for heart failure survival and readmission rates at 6 months and as a warning signal for more aggressive intervention, thus warranting further validation.

  5. Usefulness of the Sum of Pulmonary Capillary Wedge Pressure and Right Atrial Pressure as a Congestion Index that Prognosticates Heart Failure Survival (from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness Trial).

    PubMed

    Ma, Tony S; Paniagua, David; Denktas, Ali E; Jneid, Hani; Kar, Biswajit; Chan, Wenyaw; Bozkurt, Biykem

    2016-09-15

    In the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial, use of a pulmonary artery catheter did not significantly affect advanced heart failure outcomes. However, the success of achieving the targeted hemodynamic goals of pulmonary capillary wedge pressure (PCWP) of 15 mm Hg and right atrial pressure (RAP) of 8 mm Hg and the association of these goals with clinical outcomes were not addressed. Furthermore, goals with 2 independent variables, PCWP and RAP, left room for uncertainties. We assessed the ability of a single hemodynamic target to achieve a threshold sum of PCWP and RAP as a predictor of all-cause mortality, death-or-transplantation (DT), or death-or-rehospitalization (DR) at 6 months in the pulmonary artery catheter-guided treatment arm of ESCAPE (n = 206). Patients with a posttreatment PCWP + RAP of <30 mm Hg had characteristics similar to those of the population who achieved the ESCAPE hemodynamic goals. This group had 8.7% mortality, 13.0% DT, and 58.7% DR at 6 months. The contrasting cohort with PCWP + RAP of ≥30 mm Hg had 45.3% mortality, 54.7% DT, and 84.9% DR at 6 months, with greater relative risk (RR) of death (RR 5.76), DT (RR 4.92), and DR (RR 1.80) and higher prevalence of jugular venous pulsation, edema, hepatomegaly, and ascites at admission and discharge. In conclusion, PCWP + RAP of 30 mm Hg posttreatment, obtained early in the index hospitalization, may represent as a simple congestion index that has prognostic value for heart failure survival and readmission rates at 6 months and as a warning signal for more aggressive intervention, thus warranting further validation. PMID:27474338

  6. An investigation into beef calf mortality on five high-altitude ranches that selected sires with low pulmonary arterial pressures for over 20 years.

    PubMed

    Neary, Joseph M; Gould, Daniel H; Garry, Franklyn B; Knight, Anthony P; Dargatz, David A; Holt, Timothy N

    2013-03-01

    Producer reports from ranches over 2,438 meters in southwest Colorado suggest that the mortality of preweaned beef calves may be substantially higher than the national average despite the selection of low pulmonary pressure herd sires for over 20 years. Diagnostic investigations of this death loss problem have been limited due to the extensive mountainous terrain over which these calves are grazed with their dams. The objective of the current study was to determine the causes of calf mortality on 5 high-altitude ranches in Colorado that have been selectively breeding sires with low pulmonary pressure (<45 mmHg) for over 20 years. Calves were followed from branding (6 weeks of age) in the spring to weaning in the fall (7 months of age). Clinical signs were recorded, and blood samples were taken from sick calves. Postmortem examinations were performed, and select tissue samples were submitted for aerobic culture and/or histopathology. On the principal study ranch, 9.6% (59/612) of the calves that were branded in the spring either died or were presumed dead by weaning in the fall. In total, 28 necropsies were performed: 14 calves (50%) had lesions consistent with pulmonary hypertension and right-sided heart failure, and 14 calves (50%) died from bronchopneumonia. Remodeling of the pulmonary arterial system, indicative of pulmonary hypertension, was evident in the former and to varying degrees in the latter. There is a need to better characterize the additional risk factors that complicate pulmonary arterial pressure testing of herd sires as a strategy to control pulmonary hypertension. PMID:23512918

  7. Pulmonary extramedullary hematopoiesis involving the pulmonary artery.

    PubMed

    Monga, Varun; Silverman, Margarida

    2015-02-24

    Extramedullary hematopoiesis (EMH) occurs as a complication of hematologic disorders such as myelofibrosis, sickle cell anemia and thalassemia. The extramedullary tissue usually involves liver, spleen and lymph nodes, less frequently the chest. We present a recent case of a man with myeloproliferative neoplasm who developed pulmonary hemorrhage secondary to EMH in the lung and pulmonary artery. Radiation therapy was considered the best approach, but it didn't work and the patient died a week after radiation therapy was completed. We also review herein the present literature. PMID:25852851

  8. Pulmonary Artery Sarcoma Masquerading as Chronic Pulmonary Thromboembolism

    PubMed Central

    Coskun, Ugur; Calpar, Ilknur; Yildizeli, Bedrettin; Yanartas, Mehmet; Filinte, Deniz; Kucukoglu, Mehmet Serdar

    2014-01-01

    We describe the case of a 60-year-old woman who presented with pulmonary artery sarcoma, a very rare tumor of the cardiovascular system. Her tumor was initially misdiagnosed as chronic pulmonary thromboembolism, and she underwent pulmonary endarterectomy. Early diagnosis of primary pulmonary artery sarcoma is crucial. That alternative should always be considered before settling on a diagnosis of pulmonary embolism. Suspicion should be aroused by the failure of anticoagulant treatment to alleviate pulmonary perfusion abnormalities and systemic symptoms. Surgical resection of the tumor—preferably by pulmonary endarterectomy, followed by reconstruction as needed—is currently the most promising treatment for pulmonary artery sarcoma. PMID:25425987

  9. Diagnostic enigma: primary pulmonary artery sarcoma

    PubMed Central

    Bhagwat, Krishna; Hallam, Jane; Antippa, Phillip; Larobina, Marco

    2012-01-01

    Primary angiosarcoma of pulmonary artery is a very rare lesion. We present a case of primary angiosarcoma that was initially misdiagnosed as a subacute massive pulmonary thromboembolism in a 30-year-old man. This rare disease is usually indistinguishable from acute or chronic thromboembolic disease of the pulmonary arteries. The clinical and radiological findings of pulmonary artery angiosarcoma are similar to those of pulmonary thromboembolism. Although the incidence of pulmonary artery angiosarcoma is very low, our case demonstrates that this disease entity should be included in the differential diagnosis of pulmonary thromboembolism. Patients with early identification can have curative potential with aggressive surgical intervention. PMID:22159261

  10. [Arterial CO2- and O2 partial pressure at rest and during exertion in pulmonary emphysema].

    PubMed

    Scherrer, M; Zeller, C; Bachofen, H

    1977-07-30

    In 83 patients with severe, largely irreversible bronchial obstruction (FEV1/VC less than 40% and FEV1 after orciprenaline inhalation less than 120% of the control value) and radiologie evidence of AD-emphysema, arterial PCO2 and PO2 were measured at rest in supine position and on the bicycle ergometer during a steady-state exercice of 5 min. Alveolar hypoventilation (PCO2 greater than 45 mm Hg) was most often observed in the cases with FEV1 less than 1.01 (in 22 patients [27%] at rest and in 26 patients [31%] during exercise). However, there was no significant correlation of the PCO2 increase with the degree of bronchial obstruction. In all patients there was a marked inhomogeneity of the alveolar ventilation or the alveolar-capillary O2 transfer in relation to alveolar blood perfusion. Indeed, the alveolar-arterial PO2 difference was increased (40 mm Hg at rest and 45 mm Hg during exercise). The additional increase of this gradient during exercise was due to an unequal distribution of alveolar O2 diffusing capacities in connection with the alveolar blood flow (preceding measurements of the N2 gradient between alveolar air and arterial blood revealed a mean fall from 18 at rest to 8 mm Hg during exercise). The observed deterioration of hypoxemia during exercise (without additional hypercapnia) is to a great extent related to the degree of bronchial obstruction measured by simple spirometry. Thus, measurements of PCO2 and PO2 at rest and during exercise appear to be a helpful adjuvant to routine spirometry in the diagnosis of subclinical emphysema.

  11. Definition, classification, and epidemiology of pulmonary arterial hypertension.

    PubMed

    Hoeper, Marius M

    2009-08-01

    Pulmonary arterial hypertension (PAH) is a distinct subgroup of pulmonary hypertension that comprises idiopathic PAH, familial/heritable forms, and PAH associated with connective tissue disease, congenital heart disease, portal hypertension, human immunodeficiency virus (HIV) infection, and some other conditions. The hemodynamic definition of PAH was recently revised: PAH is now defined by a mean pulmonary artery pressure at rest > or =25 mm Hg in the presence of a pulmonary capillary wedge pressure < or =15 mm Hg. The exercise criterion (mean pulmonary artery pressure > or =30 mm Hg during exercise) that was used in the old definition of PAH has been removed because there are no robust data that would allow defining an upper limit of normal for the pulmonary pressure during exercise. The revised classification of pulmonary hypertension still consists of five major groups: (1) PAH, (2) pulmonary hypertension due to left heart disease, (3) pulmonary hypertension due to chronic lung disease and/or hypoxia, (4) chronic thromboembolic pulmonary hypertension, and (5) miscellaneous forms. Modifications have been made in some of these groups, such as the addition of schistosomiasis-related pulmonary hypertension and pulmonary hypertension in patients with chronic hemolytic anemia to group 1.

  12. Novel biomarkers for pulmonary arterial hypertension.

    PubMed

    Anwar, Anjum; Ruffenach, Gregoire; Mahajan, Aman; Eghbali, Mansoureh; Umar, Soban

    2016-01-01

    Pulmonary arterial hypertension is a deadly disease characterized by elevated pulmonary arterial pressures leading to right ventricular hypertrophy and failure. The confirmatory gold standard test is the invasive right heart catheterization. The disease course is monitored by pulmonary artery systolic pressure measurement via transthoracic echocardiography. A simple non-invasive test to frequently monitor the patients is much needed. Search for a novel biomarker that can be detected by a simple test is ongoing and many different options are being studied. Here we review some of the new and unique pre-clinical options for potential pulmonary hypertension biomarkers. These biomarkers can be broadly categorized based on their association with endothelial cell dysfunction, inflammation, epigenetics, cardiac function, oxidative stress, metabolism,extracellular matrix, and volatile compounds in exhaled breath condensate. A biomarker that can be detected in blood, urine or breath condensate and correlates with disease severity, progression and response to therapy may result in significant cost reduction and improved patient outcomes. PMID:27439993

  13. Pulmonary Artery Intimal Sarcoma: A Case Report

    PubMed Central

    Kriz, Joseph P.; Munfakh, Nabil A.; King, Gregory S.; Carden, Juan O.

    2016-01-01

    Pulmonary artery intimal sarcomas are rare and lethal malignant tumors that typically affect larger vessels: the aorta, inferior vena cava, and pulmonary arteries. Since symptoms and imaging of pulmonary arterial intimal sarcomas mimic pulmonary thromboembolism, the differential diagnosis of a patient presenting with chest pain, dyspnea, and filling defect within the pulmonary arteries should include intimal sarcoma. Often right ventricular failure is observed due to pulmonary hypertension caused by the obstructive effect of the tumor and concomitant chronic thromboembolism. We report the case of a 72-year-old African-American male with arterial intimal sarcoma of the left and right pulmonary artery with extension through the right artery into the bronchus and right lung. PMID:27239183

  14. Pulmonary arterial hypertension secondary to chronic left-sided cardiac dysfunction in dogs.

    PubMed

    Stepien, Rebecca L

    2009-09-01

    Pulmonary arterial hypertension is a description of a physiological finding rather than a diagnosis. Pulmonary arterial pressure is the result of interactions among pulmonary blood flow (right ventricular cardiac output), pulmonary vascular impedance and post-capillary pressure (typically reflecting left atrial pressure). When elevations in pulmonary arterial pressure (systolic/diastolic pulmonary arterial pressure > approximately 30/19 mmHg at rest) are accompanied by increased left atrial pressure, pulmonary arterial hypertension may be considered secondary to left-heart failure. Introduction of Doppler methods to diagnose pulmonary arterial hypertension has increased the awareness of the prevalence and importance of pulmonary arterial hypertension dogs with left-heart failure. Increasing understanding of the mechanism of development of pulmonary venous hypertension and reactive pulmonary arterial hypertension in dogs with left-heart disease has led to the development of successful additive therapies for progressive clinical signs in the setting of chronic therapy for congestive heart failure due to left-sided valvular and myocardial dysfunction. Because effective therapies for pulmonary arterial hypertension secondary to chronic left-sided cardiac dysfunction are now available, screening for pulmonary arterial hypertension should be a regular part of the Doppler echocardiographic examination in a clinical setting of chronic therapy for left-sided congestive heart failure due to valvular or myocardial disease.

  15. Arterial Pressure Analog.

    ERIC Educational Resources Information Center

    Heusner, A. A.; Tracy, M. L.

    1980-01-01

    Describes a simple hydraulic analog which allows students to explore some physical aspects of the cardiovascular system and provides them with a means to visualize and conceptualize these basic principles. Simulates the behavior of arterial pressure in response to changes in heart rate, stroke volume, arterial compliance, and peripheral…

  16. Sodium hydrosulfide alleviates pulmonary artery collagen remodeling in rats with high pulmonary blood flow.

    PubMed

    Li, Xiaohui; Du, Junbao; Jin, Hongfang; Geng, Bin; Tang, Chaoshu

    2008-11-01

    This study aimed to explore the effect of sodium hydrosulfide (NaHS) on pulmonary artery collagen remodeling in rats with high pulmonary blood flow. Thirty-two Sprague-Dawley rats were randomly divided into a sham group, shunt group, sham + NaHS (an H2S donor) group, and shunt + NaHS group. After 11 weeks of shunting, mean pulmonary artery pressure (MPAP), relative median area (RMA) of pulmonary arteries, H2S concentration in lung tissues, plasma endothelin-1 (ET-1) levels, and ET-1 mRNA in lung tissues were investigated. Collagen I and collagen III were evaluated by immunohistochemistry. Hydroxyproline assay and Sirius-red staining were performed. Matrix metalloproteinase-13 (MMP-13), tissue inhibitor of metalloproteinase-1 (TIMP-1), and connective tissue growth factor (CTGF) were evaluated by immunohistochemistry. After 11 weeks of shunting, rats showed a significant pulmonary hypertension and pulmonary artery collagen remodeling in association with a decrease in lung tissue H2S content. After NaHS treatment for 11 weeks, lung tissue H(2)S content was increased, whereas MPAP was attenuated and RMA was reduced. Meanwhile, pulmonary artery collagen I and collagen III protein expressions of intra-acinar pulmonary arteries were inhibited, but MMP-13/TIMP-1 ratio was augmented with a decreased plasma ET-1 content and lung tissue ET-1mRNA and CTGF expressions. The downregulation of H(2)S is involved in the development of pulmonary artery collagen remodeling induced by high pulmonary blood flow.

  17. Pulmonary rehabilitation and exercise in pulmonary arterial hypertension: An underutilized intervention

    PubMed Central

    Sahni, Sonu; Capozzi, Barbara; Iftikhar, Asma; Sgouras, Vasiliki; Ojrzanowski, Marcin; Talwar, Arunabh

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a rare and devastating disease characterized by progressive increases in pulmonary arterial pressure and pulmonary vascular resistance which eventually leads to right ventricular failure and death. Early thought process was that exercise and increased physical activity may be detrimental to PAH patients however many small cohort trials have proven otherwise. In addition to the many pharmaceutical options, exercise and pulmonary rehabilitation have also been shown to increase exercise capacity as well as various aspects of psychosomatic health. As pulmonary and exercise rehabilitation become more widely used as an adjuvant therapy patient outcomes improve and physicians should consider this in the therapeutic algorithm along with pharmacotherapy. PMID:25960979

  18. Pulmonary arterial hypertension and pregnancy

    PubMed Central

    Terek, Demet; Kayikcioglu, Meral; Kultursay, Hakan; Ergenoglu, Mete; Yalaz, Mehmet; Musayev, Oktay; Mogulkoc, Nesrin; Gunusen, Ilkben; Akisu, Mete; Kultursay, Nilgun

    2013-01-01

    This is the case report of a pregnant woman who refused pregnancy termination when diagnosed with pulmonary arterial hypertension (PAH) functional class 2–3 at the 24th week of gestation and of her newborn. A pregnant woman with PAH functional class 2–3 was treated with inhaled prostacyclin analog (iloprost), oral sildenafil, oxygen, and low molecular weight heparin. She delivered at 32nd week by Cesarean section. The infant required oxygen up to 36th week postconceptional age and had a short steroid treatment. The mother needed close cardiovascular monitorization, intensive oxygen and pulmonary vasodilator therapy for 2 months and was discharged with oxygen and oral iloprost treatment. A multidisciplinary approach together with pulmonary vasodilator therapy may be succesful in such a high-risk pregnant woman. PMID:23900530

  19. Drugs induced pulmonary arterial hypertension.

    PubMed

    Seferian, Andrei; Chaumais, Marie-Camille; Savale, Laurent; Günther, Sven; Tubert-Bitter, Pascale; Humbert, Marc; Montani, David

    2013-09-01

    Pulmonary arterial hypertension (PAH) is a rare disorder characterized by progressive obliteration of the pulmonary microvasculature, resulting in elevated pulmonary vascular resistance and premature death. According to the current classification, PAH can be associated with exposure to certain drugs or toxins, particularly appetite suppressant drugs, such as aminorex, fenfluramine derivatives and benfluorex. These drugs have been confirmed to be risk factors for PAH and were withdrawn from the market. The supposed mechanism is an increase in serotonin levels, which was demonstrated to act as a growth factor for the pulmonary arterial smooth muscle cells. Amphetamines, phentermine and mazindol were less frequently used but are also considered as possible risk factors for PAH. Dasatinib, a dual Src/Abl kinase inhibitor, used in the treatment of chronic myelogenous leukaemia was associated with cases of severe PAH, in part reversible after its withdrawal. Recently several studies raised the potential endothelial dysfunction that could be induced by interferon, and few cases of PAH have been reported with interferon therapy. Other possible risk factors for PAH include: nasal decongestants, like phenylpropanolamine, dietary supplement - L-Tryptophan, selective serotonin reuptake inhibitors, pergolide and other drugs that could act on 5HT2B receptors. Interestingly, PAH remains a rare complication of these drugs, suggesting possible individual susceptibility and further studies are needed to identify patients at risk of drugs induced PAH. PMID:23972547

  20. Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats

    SciTech Connect

    Suzuki, Chihiro; Takahashi, Masafumi . E-mail: masafumi@sch.md.shinshu-u.ac.jp; Morimoto, Hajime; Izawa, Atsushi; Ise, Hirohiko; Hongo, Minoru; Hoshikawa, Yasushi; Ito, Takayuki; Miyashita, Hiroshi; Kobayashi, Eiji; Shimada, Kazuyuki; Ikeda, Uichi

    2006-10-20

    Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation of smooth muscle cells (SMCs), leading to occlusion of pulmonary arterioles, right ventricular (RV) hypertrophy, and death. We investigated whether mycophenolate mofetil (MMF), a potent immunosuppresssant, prevents the development of monocrotaline (MCT)-induced PAH in rats. MMF effectively decreased RV systolic pressure and RV hypertrophy, and reduced the medial thickness of pulmonary arteries. MMF significantly inhibited the number of proliferating cell nuclear antigen (PCNA)-positive cells, infiltration of macrophages, and expression of P-selectin and interleukin-6 on the endothelium of pulmonary arteries. The infiltration of T cells and mast cells was not affected by MMF. In vitro experiments revealed that mycophenolic acid (MPA), an active metabolite of MMF, dose-dependently inhibited proliferation of human pulmonary arterial SMCs. MMF attenuated the development of PAH through its anti-inflammatory and anti-proliferative properties. These findings provide new insight into the potential role of immunosuppressants in the treatment of PAH.

  1. Severe Pulmonary Arterial Hypertension: Comprehensive Evaluation by Magnetic Resonance Imaging

    PubMed Central

    Ibrahim, El-Sayed H.; Bajwa, Abubakr A.

    2015-01-01

    Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary artery (PA) pressure, which negatively affects the right ventricular (RV) function. This report shows a patient with severe PAH, on whom a comprehensive MRI exam was performed to evaluate both PA and RV. New imaging sequences were implemented for obtaining additional parameters about the patient's condition. The results show the capabilities of the developed exam of providing complete picture of the cardiovascular system in PAH, which helps the physician optimize treatment. PMID:26435871

  2. [Roentgenosemeiotics of thromboembolism of the pulmonary artery].

    PubMed

    Iablokov, E G; Kirienko, A I; Matiushenko, A A

    1985-12-01

    The study is based on data of radiopaque investigation of pulmonary vessels in 400 patients with pulmonary arterial thromboembolism. A retrospective assessment of noncontrast chest roentgenograms was carried out in 200 of those. Conventional pulmonary roentgenology was shown to be a fairly unreliable tool of the diagnosis of pulmonary embolism owing to low specificity of the symptoms. Only arterial filling defects and "amputations" may be regarded as specific angiographic signs of thromboembolism. The value of indirect angiographic symptoms was demonstrated. Angiographic semiotics of embolism was studied with reference to the duration of the affection. Vascular filling defects and stenoses are angiographic markers of prolonged presence of thromboemboli in pulmonary arteries.

  3. Recent Strategies in Treatment of Pulmonary Arterial Hypertension, A Review

    PubMed Central

    Fallah, Flora

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a disease characterized by an elevation in pulmonary artery pressure that can lead to right ventricular failure and death. The pulmonary circulation has to accommodate the entire cardiac output in each cardiac cycle and evolution has adapted to this by making it a low-pressure high-flow system. However, pathology can affect both the arterial and venous components of this system. Pulmonary venous hypertension mainly refers to diseases that result in elevated venous pressure and occurs mainly from mitral valve and left-sided heart disease. Standard treatment options include oral anticoagulation, diuretics, oxygen supplementation, and for a small percentage of patients, calcium channel blockers. Newer treatments include prostacyclin analogues, endothelin receptor antago¬nists, and phosphodiesterase type 5 inhibitors. This article reviews the current treatments strategies for PAH and provides guidelines for its management. PMID:25946920

  4. Inflammation in pulmonary arterial hypertension.

    PubMed

    Price, Laura C; Wort, S John; Perros, Frédéric; Dorfmüller, Peter; Huertas, Alice; Montani, David; Cohen-Kaminsky, Sylvia; Humbert, Marc

    2012-01-01

    Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling of the precapillary pulmonary arteries, with excessive proliferation of vascular cells. Although the exact pathophysiology remains unknown, there is increasing evidence to suggest an important role for inflammation. Firstly, pathologic specimens from patients with PAH reveal an accumulation of perivascular inflammatory cells, including macrophages, dendritic cells, T and B lymphocytes, and mast cells. Secondly, circulating levels of certain cytokines and chemokines are elevated, and these may correlate with a worse clinical outcome. Thirdly, certain inflammatory conditions such as connective tissue diseases are associated with an increased incidence of PAH. Finally, treatment of the underlying inflammatory condition may alleviate the associated PAH. Underlying pathologic mechanisms are likely to be "multihit" and complex. For instance, the inflammatory response may be regulated by bone morphogenetic protein receptor type 2 (BMPR II) status, and, in turn, BMPR II expression can be altered by certain cytokines. Although antiinflammatory therapies have been effective in certain connective-tissue-disease-associated PAH, this approach is untested in idiopathic PAH (iPAH). The potential benefit of antiinflammatory therapies in iPAH is of importance and requires further study. PMID:22215829

  5. Pulmonary arterial compliance: How and why should we measure it?

    PubMed Central

    Ghio, Stefano; Schirinzi, Sandra; Pica, Silvia

    2015-01-01

    The pulmonary circulation is a high-flow/low-pressure system, coupled with a flow generator chamber–the right ventricle–, which is relatively unable to tolerate increases in afterload. A right heart catheterization, using a fluid-filled, balloon-tipped Swan-Ganz catheter allows the measurement of all hemodynamic parameters characterizing the pulmonary circulation: the inflow pressure, an acceptable estimate the outflow pressure, and the pulmonary blood flow. However, the study of the pulmonary circulation as a continuous flow system is an oversimplification and a thorough evaluation of the pulmonary circulation requires a correct understanding of the load that the pulmonary vascular bed imposes on the right ventricle, which includes static and dynamic components. This is critical to assess the prognosis of patients with pulmonary hypertension or with heart failure. Pulmonary compliance is a measure of arterial distensibility and, either alone or in combination with pulmonary vascular resistance, gives clinicians the possibility of a good prognostic stratification of patients with heart failure or with pulmonary hypertension. The measurement of pulmonary arterial compliance should be included in the routine clinical evaluation of such patients. PMID:26779530

  6. Pulmonary arterial hypertension: a current review of pharmacological management.

    PubMed

    Sahni, Sonu; Ojrzanowski, Marcin; Majewski, Sebastian; Talwar, Arunabh

    2016-01-01

    Pulmonary hypertension (PHTN) is a rare and devastating disease characterized by progressive increases in pulmonary arterial pressure and pulmonary vascular resistance, which eventually leads to right ventricular failure and death. At present there is no cure for pulmonary arterial hypertension (PAH); however over the past decade targeted pharmaceutical options have become available for the treatment of PAH. Prior to evaluation for therapeutic options a definitive diagnosis of pulmonary arterial hypertension must be made via comprehensive physical exam and definitive diagnostic testing. Screening test of choice remains echocardiography and gold standard for definitive diagnosis is right heart catheterization. Once the establishment of a diagnosis of PAH is made therapeutic options may be a possibility based on a diagnostic algorithm and disease severity of the PAH patient. There are different classes of medications available with different mechanisms of actions which net a vasodilatory effect and improve exercise tolerance, quality of life as well and survival.

  7. Prevalence of coronary artery-pulmonary artery collaterals in patients with chronic thromboembolic pulmonary hypertension.

    PubMed

    Lee, Noel S; Blanchard, Daniel G; Knowlton, Kirk U; McDivit, Anna M; Pretorius, Victor; Madani, Michael M; Fedullo, Peter F; Kerr, Kim M; Kim, Nick H; Poch, David S; Auger, William R; Daniels, Lori B

    2015-06-01

    This study sought to determine the prevalence of coronary artery-pulmonary artery collaterals in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and to correlate their presence with the degree of clot burden. CTEPH is a treatable cause of severe pulmonary hypertension and right heart failure. Bronchopulmonary collateral vessels have been used as a supplementary diagnostic and prognostic tool for this disease. Coronary artery-pulmonary artery collaterals in this population have not been described. The coronary angiograms of 300 consecutive patients with CTEPH evaluated for pulmonary thromboendarterectomy (PTE) between January 1, 2007, and May 1, 2014, were examined. Of these patients, 259 (50% male; mean age, 58.3 ± 10.6 years) had cineangiographic images deemed adequate to definitively assess for the presence of coronary artery-pulmonary artery collaterals and were included in the final analyses. Pulmonary angiogram reports were reviewed for extent of pulmonary artery obstruction. The coronary angiograms of 259 age- and sex-matched control patients were also examined. Among 259 CTEPH patients with definitive imaging, 34 coronary artery-pulmonary artery collaterals were found in 28 patients (10.8%), versus 1 coronary artery-pulmonary artery collateral among control subjects (0.4%; P < 0.001). Compared with CTEPH patients without collaterals, patients with collaterals had a significantly higher prevalence of total occlusion of their right or left main pulmonary artery (P < 0.001) or lobar arteries (P < 0.001). In conclusion, the prevalence of coronary artery-pulmonary artery collaterals in CTEPH patients undergoing coronary angiography for possible PTE is approximately 11%. These vessels are associated with more severe pulmonary artery occlusion. PMID:26064456

  8. Changes in large pulmonary arterial viscoelasticity in chronic pulmonary hypertension.

    PubMed

    Wang, Zhijie; Lakes, Roderic S; Golob, Mark; Eickhoff, Jens C; Chesler, Naomi C

    2013-01-01

    Conduit pulmonary artery (PA) stiffening is characteristic of pulmonary arterial hypertension (PAH) and is an excellent predictor of mortality due to right ventricular (RV) overload. To better understand the impact of conduit PA stiffening on RV afterload, it is critical to examine the arterial viscoelastic properties, which require measurements of elasticity (energy storage behavior) and viscosity (energy dissipation behavior). Here we hypothesize that PAH leads to frequency-dependent changes in arterial stiffness (related to elasticity) and damping ratio (related to viscosity) in large PAs. To test our hypothesis, PAH was induced by the combination of chronic hypoxia and an antiangiogenic compound (SU5416) treatment in mice. Static and sinusoidal pressure-inflation tests were performed on isolated conduit PAs at various frequencies (0.01-20 Hz) to obtain the mechanical properties in the absence of smooth muscle contraction. Static mechanical tests showed significant stiffening of large PAs with PAH, as expected. In dynamic mechanical tests, structural stiffness (κ) increased and damping ratio (D) decreased at a physiologically relevant frequency (10 Hz) in hypertensive PAs. The dynamic elastic modulus (E), a material stiffness, did not increase significantly with PAH. All dynamic mechanical properties were strong functions of frequency. In particular, κ, E and D increased with increasing frequency in control PAs. While this behavior remained for D in hypertensive PAs, it reversed for κ and E. Since these novel dynamic mechanical property changes were found in the absence of changes in smooth muscle cell content or contraction, changes in collagen and proteoglycans and their interactions are likely critical to arterial viscoelasticity in a way that has not been previously described. The impact of these changes in PA viscoelasticity on RV afterload in PAH awaits further investigation. PMID:24223157

  9. Changes in Large Pulmonary Arterial Viscoelasticity in Chronic Pulmonary Hypertension

    PubMed Central

    Wang, Zhijie; Lakes, Roderic S.; Golob, Mark; Eickhoff, Jens C.; Chesler, Naomi C.

    2013-01-01

    Conduit pulmonary artery (PA) stiffening is characteristic of pulmonary arterial hypertension (PAH) and is an excellent predictor of mortality due to right ventricular (RV) overload. To better understand the impact of conduit PA stiffening on RV afterload, it is critical to examine the arterial viscoelastic properties, which require measurements of elasticity (energy storage behavior) and viscosity (energy dissipation behavior). Here we hypothesize that PAH leads to frequency-dependent changes in arterial stiffness (related to elasticity) and damping ratio (related to viscosity) in large PAs. To test our hypothesis, PAH was induced by the combination of chronic hypoxia and an antiangiogenic compound (SU5416) treatment in mice. Static and sinusoidal pressure-inflation tests were performed on isolated conduit PAs at various frequencies (0.01–20 Hz) to obtain the mechanical properties in the absence of smooth muscle contraction. Static mechanical tests showed significant stiffening of large PAs with PAH, as expected. In dynamic mechanical tests, structural stiffness (κ) increased and damping ratio (D) decreased at a physiologically relevant frequency (10 Hz) in hypertensive PAs. The dynamic elastic modulus (E), a material stiffness, did not increase significantly with PAH. All dynamic mechanical properties were strong functions of frequency. In particular, κ, E and D increased with increasing frequency in control PAs. While this behavior remained for D in hypertensive PAs, it reversed for κ and E. Since these novel dynamic mechanical property changes were found in the absence of changes in smooth muscle cell content or contraction, changes in collagen and proteoglycans and their interactions are likely critical to arterial viscoelasticity in a way that has not been previously described. The impact of these changes in PA viscoelasticity on RV afterload in PAH awaits further investigation. PMID:24223157

  10. Localised pulmonary metastatic calcification associated with pulmonary artery obstruction.

    PubMed Central

    Bloodworth, J; Tomashefski, J F

    1992-01-01

    BACKGROUND: Metastatic pulmonary calcification, a complication of uraemia and disordered calcium metabolism, may be diffuse or localised. The factors that determine calcium precipitation are complex, but tissue alkalosis is thought to be important. As obstruction of the pulmonary artery theoretically causes local alkalosis a retrospective necropsy study was carried out to examine the relation between metastatic pulmonary calcification and vascular obstruction. METHODS: Five patients with focal and two with diffuse metastatic calcification in the lungs were identified over eight years. Lungs were studied macroscopically and by light microscopy, haematoxylin and eosin and histochemical stains being used for calcium. RESULTS: Underlying risk factors for calcification in these patients included renal failure in six and disseminated malignancy in five. In the five patients with localised calcification obstruction of the pulmonary artery by thrombus or tumour was found proximal or adjacent to areas of calcium deposition. In two patients metastatic calcification was confined to a lung with unilateral pulmonary artery thromboembolic occlusion. Calcification was not specifically associated with infarction, pneumonia, or diffuse alveolar damage. Lesions of the pulmonary artery were not seen in the two patients with diffuse bilateral metastatic calcification. CONCLUSION: In this small series there was a spatial association between pulmonary artery obstruction and localised metastatic calcification. It is proposed that pulmonary artery obstruction alters the microchemical environment of the lung, favouring tissue alkalosis and thereby enhancing parenchymal calcification in patients predisposed to this condition. Images PMID:1519194

  11. [Treatment of pulmonary arterial hypertension].

    PubMed

    Roman, Antonio; López-Meseguer, Manuel; Domingo, Enric

    2015-06-22

    Treatment of pulmonary arterial hypertension has achieved significant progress over the past 20 years. Currently, 3 groups of drugs have proven useful for the treatment of this disease: endothelin receptor antagonist, phosphodiesterase inhibitors and prostacyclin and its analogues. It is recommended to initiate treatment with one of these drugs, the choice depending on the initial severity of patient disease and the preferences of the treating physician. When the patient does not have a satisfactory response, new drugs acting at a different pathway are most commonly added. At this time, considering referral for lung transplantation could be an alternative. Most experts recommend grouping maximum experience in what is known as expert centers. Treatment has led to better survival in these patients, but there is still a long way to cure this life-threatening disease.

  12. Breath Analysis in Pulmonary Arterial Hypertension

    PubMed Central

    Cikach, Frank S.; Tonelli, Adriano R.; Barnes, Jarrod; Paschke, Kelly; Newman, Jennie; Grove, David; Dababneh, Luma; Wang, Sihe

    2014-01-01

    Background: Pulmonary arterial hypertension (PAH) is a progressive and devastating condition characterized by vascular cell proliferation and is associated with several metabolic derangements. We hypothesized that metabolic derangements in PAH can be detected by measuring metabolic by-products in exhaled breath. Methods: We collected breath and blood samples from patients with PAH at the time of right-sided heart catheterization (n = 31) and from healthy control subjects (n = 34). Breath was analyzed by selected ion flow tube-mass spectrometry in predetermined training and validation cohorts. Results: Patients with PAH were 51.5 ± 14 years old, and 27 were women (85%). Control subjects were 38 ± 13 years old, and 22 were women (65%). Discriminant analysis in the training set identified three ion peaks (H3O+29+, NO+56+, and O2+98+) and the variable age that correctly classified 88.9% of the individuals. In an independent validation cohort, 82.8% of the individuals were classified correctly. The concentrations of the volatile organic compounds 2-propanol, acetaldehyde, ammonia, ethanol, pentane, 1-decene, 1-octene, and 2-nonene were different in patients with PAH compared with control subjects. Exhaled ammonia was higher in patients with PAH (median [interquartile range]: 94.7 parts per billion (ppb) [70-129 ppb] vs 60.9 ppb [46-77 ppb], P < .001) and was associated with right atrial pressure (ρ = 0.57, P < .001), mean pulmonary artery pressure (ρ = 0.43, P = .015), cardiac index by thermodilution (ρ = −0.39, P = .03), pulmonary vascular resistance (ρ = 0.40, P = .04), mixed venous oxygen (ρ = −0.59, P < .001), and right ventricular dilation (ρ = 0.42, P = .03). Conclusions: Breathprint is different between patients with PAH and healthy control subjects. Several specific compounds, including ammonia, were elevated in the breath of patients with PAH. Exhaled ammonia levels correlated with severity of disease. PMID:24091389

  13. Pulmonary arterial remodeling revealed by microfocal x-ray tomography

    NASA Astrophysics Data System (ADS)

    Karau, Kelly L.; Molthen, Robert C.; Johnson, Roger H.; Dhyani, Anita H.; Haworth, Steven T.; Dawson, Christopher A.

    2001-05-01

    Animal models and micro-CT imaging are useful for understanding the functional consequences of, and identifying the genes involved in, the remodeling of vascular structures that accompanies pulmonary vascular disease. Using a micro-CT scanner to image contrast-enhanced arteries in excised lungs from fawn hooded rats (a strain genetically susceptible to hypoxia induced pulmonary hypertension), we found that portions of the pulmonary arterial tree downstream from a given diameter were morphometrically indistinguishable. This 'self-consistency' property provided a means for summarizing the pulmonary arterial tree architecture and mechanical properties using a parameter vector obtained from measurements of the contiguous set of vessel segments comprising the longest (principal) pathway and its branches over a range of vascular pressures. This parameter vector was used to characterize the pulmonary vascular remodeling that occurred in rats exposed to a hypoxic (11.5% oxygen) environment and provided the input to a hemodynamic model relating structure to function. The major effect of the remodeling was a longitudinally (pulmonary artery to arterioles) uniform decrease in vessel distensibility that resulted in a 90% increase in arterial resistance. Despite the almost uniform change in vessel distensibility, over 50% of the resistance increase was attributable to vessels with unstressed diameters less than 125 microns.

  14. Ultrasound diagnosis of pulmonary sling with proximal stenosis of left pulmonary artery and patent arterial duct.

    PubMed

    Mądry, Wojciech; Karolczak, Maciej A

    2013-03-01

    Authors discuss methods of echocardiographic diagnosis of the pulmonary sling with stenosis and hypoplasia of the left pulmonary artery and patent arterial duct with massive left-to-right shunt, based on a case of the newborn with resistant to treatment heart failure, with initial diagnosis of patent ductus arteriosus, referred to surgical treatment. The optimal echocardiographic views permitting establish diagnosis of the pulmonary sling were suggested. The special attention was paid to high parasternal and suprasternal views visualizing vessels of the upper mediastinum as well as characteristic differences between the normal and pathologic picture. The typical features of the echocardiogram suggesting pulmonary sling, like the lack of the left pulmonary artery in its expected position, and the abnormal branching pattern of the right pulmonary artery were indicated. The greatest diagnostic difficulties in visualization of the abnormal route of the left pulmonary artery were related to the presence of air-containing tissues, like lungs and central airways between the ultrasound probe and area of interest. The other was the masking influence of the large patent arterial duct, that may mimic the left pulmonary artery arising from the pulmonary trunk. The other entities requiring differentiation with sling, like aplasia of the left lung, the direct or indirect aortic origin of the left pulmonary artery, were discussed. The role of other visualization technics, like computed 3D tomography, and magnetic nuclear resonance, as well as direct visualization of central airways with bronchoscopy in establishing precise diagnosis were stressed.

  15. Increased cardiac output, not pulmonary artery systolic pressure, increases intrapulmonary shunt in healthy humans breathing room air and 40% O2

    PubMed Central

    Elliott, Jonathan E; Duke, Joseph W; Hawn, Jerold A; Halliwill, John R; Lovering, Andrew T

    2014-01-01

    Blood flow through intrapulmonary arteriovenous anastomoses (IPAVAs) has been demonstrated to increase in healthy humans during a variety of conditions; however, whether or not this blood flow represents a source of venous admixture (/) that impairs pulmonary gas exchange efficiency (i.e. increases the alveolar-to-arterial difference (A–aDO2)) remains controversial and unknown. We hypothesized that blood flow through IPAVAs does provide a source of /. To test this, blood flow through IPAVAs was increased in healthy humans at rest breathing room air and 40% O2: (1) during intravenous adrenaline (epinephrine) infusion at 320 ng kg−1 min−1 (320 ADR), and (2) with vagal blockade (2 mg atropine), before and during intravenous adrenaline infusion at 80 ng kg−1 min−1 (ATR + 80 ADR). When breathing room air the A–aDO2 increased by 6 ± 2 mmHg during 320 ADR and by 5 ± 2 mmHg during ATR + 80 ADR, and the change in calculated / was +2% in both conditions. When breathing 40% O2, which minimizes contributions from diffusion limitation and alveolar ventilation-to-perfusion inequality, the A–aDO2 increased by 12 ± 7 mmHg during 320 ADR, and by 9 ± 6 mmHg during ATR + 80 ADR, and the change in calculated / was +2% in both conditions. During 320 ADR cardiac output () and pulmonary artery systolic pressure (PASP) were significantly increased; however, during ATR + 80 ADR only was significantly increased, yet blood flow through IPAVAs as detected with saline contrast echocardiography was not different between conditions. Accordingly, we suggest that blood flow through IPAVAs provides a source of intrapulmonary shunt, and is mediated primarily by increases in rather than PASP. PMID:25085889

  16. Diffuse Pulmonary Arteriovenous Fistulas With Pulmonary Arterial Hypertension: Case Report and Review.

    PubMed

    Jiang, Rong; Gong, Su-Gang; Pudasaini, Bigyan; Zhao, Qin-Hua; Wang, Lan; He, Jing; Liu, Jin-Ming

    2016-04-01

    Pulmonary arteriovenous fistulas (PAVFs) are rare. Diffuse type PAVFs with pulmonary arterial hypertension (PAH) are even rarer and can elude anatomy imaging like a plain chest film or a computed tomography. The rapid blood flow that ensues due to lack of a capillary bed leads to various degrees of ischemia depending on the number and size of the PAVF. This is a case report of diffuse PAVF in a patient with PAH.This case report describes a patient with recurrent hemoptysis and chest pain. Systemic examination was unremarkable except for P2 attenuation on auscultation. Echocardiograghy showed confirmed pulmonary hypertension with mild dilation of right atrium and ventricle and a tricuspid regurgitation pressure gradient of 40 mm Hg and ruled out congenital heart diseases. Right heart catheterization revealed precapillary PAH with mean pulmonary arterial pressure of 88 mm Hg. Pulmonary angiography showed enlarged pulmonary arterial trunk and diffuse spiral tortuous pulmonary arterial branches indicting diffuse PAVFs. The patient was diagnosed as PAH and began treatment of 25 mg tid of sildenafil.The case highlights a rare and unique presentation of PAH.

  17. Diffuse Pulmonary Arteriovenous Fistulas With Pulmonary Arterial Hypertension: Case Report and Review.

    PubMed

    Jiang, Rong; Gong, Su-Gang; Pudasaini, Bigyan; Zhao, Qin-Hua; Wang, Lan; He, Jing; Liu, Jin-Ming

    2016-04-01

    Pulmonary arteriovenous fistulas (PAVFs) are rare. Diffuse type PAVFs with pulmonary arterial hypertension (PAH) are even rarer and can elude anatomy imaging like a plain chest film or a computed tomography. The rapid blood flow that ensues due to lack of a capillary bed leads to various degrees of ischemia depending on the number and size of the PAVF. This is a case report of diffuse PAVF in a patient with PAH.This case report describes a patient with recurrent hemoptysis and chest pain. Systemic examination was unremarkable except for P2 attenuation on auscultation. Echocardiograghy showed confirmed pulmonary hypertension with mild dilation of right atrium and ventricle and a tricuspid regurgitation pressure gradient of 40 mm Hg and ruled out congenital heart diseases. Right heart catheterization revealed precapillary PAH with mean pulmonary arterial pressure of 88 mm Hg. Pulmonary angiography showed enlarged pulmonary arterial trunk and diffuse spiral tortuous pulmonary arterial branches indicting diffuse PAVFs. The patient was diagnosed as PAH and began treatment of 25 mg tid of sildenafil.The case highlights a rare and unique presentation of PAH. PMID:27057843

  18. Hemodynamic, Functional, and Clinical Responses to Pulmonary Artery Denervation in Patients With Pulmonary Arterial Hypertension of Different Causes

    PubMed Central

    Zhang, Hang; Xie, Du-Jiang; Zhang, Juan; Zhou, Ling; Rothman, Alexander M.K.

    2015-01-01

    Background— The mechanisms underlying pulmonary arterial hypertension (PAH) are multifactorial. The efficacy of pulmonary artery denervation (PADN) for idiopathic PAH treatment has been evaluated. This study aimed to analyze the hemodynamic, functional, and clinical responses to PADN in patients with PAH of different causes. Methods and Results— Between April 2012 and April 2014, 66 consecutive patients with a resting mean pulmonary arterial pressure ≥25 mm Hg treated with PADN were prospectively followed up. Target drugs were discontinued after the PADN procedure. Hemodynamic response and 6-minute walk distance were repeatedly measured within the 1 year post PADN follow-up. The clinical end point was the occurrence of PAH-related events at the 1-year follow-up. There were no PADN-related complications. Hemodynamic success (defined as the reduction in mean pulmonary arterial pressure by a minimal 10% post PADN) was achieved in 94% of all patients, with a mean absolute reduction in systolic pulmonary arterial pressure and mean pulmonary arterial pressure within 24 hours of −10 mm Hg and −7 mm Hg, respectively. The average increment in 6-minute walk distance after PADN was 94 m. Worse PAH-related events occurred in 10 patients (15%), mostly driven by the worsening of PAH (12%). There were 8 (12%) all-cause deaths, with 6 (9%) PAH-related deaths. Conclusions— PADN was safe and feasible for the treatment of PAH. The PADN procedure was associated with significant improvements in hemodynamic function, exercise capacity, and cardiac function and with less frequent PAH-related events and death at 1 year after PADN treatment. Further randomized studies are required to confirm the efficacy of PADN for PAH. Clinical Trial Registration— URL: http://www.chictr.trc.com.cn. Unique identifier: chiCTR-ONC-12002085. PMID:26553699

  19. Medical treatment update on pulmonary arterial hypertension.

    PubMed

    Enderby, Cher Y; Burger, Charles

    2015-09-01

    Pulmonary arterial hypertension is a chronic, progressive disease of the pulmonary vasculature resulting in poor outcomes if left untreated. The management of group 1 pulmonary arterial hypertension has included the use of prostanoids, phosphodiesterase-5 inhibitors, and endothelin receptor antagonists targeting the prostacyclin, endothelin-1, and nitric oxide pathways. Three new medications have been approved by the US Food and Drug Administration over the past couple of years. Macitentan is the newest endothelin receptor antagonist, riociguat is a soluble guanylate cyclase stimulator, and treprostinil diolamine is the first oral prostanoid. This review will focus on the key trials leading to their approval, special considerations for each medication, and their potential place in therapy. The use of combination therapy as initial therapy in pulmonary arterial hypertension will also be discussed.

  20. Medical treatment update on pulmonary arterial hypertension

    PubMed Central

    Burger, Charles

    2015-01-01

    Pulmonary arterial hypertension is a chronic, progressive disease of the pulmonary vasculature resulting in poor outcomes if left untreated. The management of group 1 pulmonary arterial hypertension has included the use of prostanoids, phosphodiesterase-5 inhibitors, and endothelin receptor antagonists targeting the prostacyclin, endothelin-1, and nitric oxide pathways. Three new medications have been approved by the US Food and Drug Administration over the past couple of years. Macitentan is the newest endothelin receptor antagonist, riociguat is a soluble guanylate cyclase stimulator, and treprostinil diolamine is the first oral prostanoid. This review will focus on the key trials leading to their approval, special considerations for each medication, and their potential place in therapy. The use of combination therapy as initial therapy in pulmonary arterial hypertension will also be discussed. PMID:26336595

  1. Interim prostacyclin therapy for an isolated disconnected pulmonary artery: a case report

    PubMed Central

    2010-01-01

    Introduction Disconnected pulmonary arteries are unusual and may result in pulmonary hypertension with acute right heart failure. Case presentation We report a case of a three-month-old Asian girl who presented with heart failure and severe pulmonary hypertension due to a disconnected right pulmonary artery. An epoprostenol (prostacyclin) infusion was instrumental in lowering pulmonary artery pressures and stabilizing the child prior to surgery. Conclusions This is, to the best of our knowledge, the first report of successful prostacyclin usage in such a situation. PMID:20525186

  2. Potassium channels in pulmonary arterial hypertension.

    PubMed

    Boucherat, Olivier; Chabot, Sophie; Antigny, Fabrice; Perros, Frédéric; Provencher, Steeve; Bonnet, Sébastien

    2015-10-01

    Pulmonary arterial hypertension (PAH) is a devastating cardiopulmonary disorder with various origins. All forms of PAH share a common pulmonary arteriopathy characterised by vasoconstriction, remodelling of the pre-capillary pulmonary vessel wall, and in situ thrombosis. Although the pathogenesis of PAH is recognised as a complex and multifactorial process, there is growing evidence that potassium channels dysfunction in pulmonary artery smooth muscle cells is a hallmark of PAH. Besides regulating many physiological functions, reduced potassium channels expression and/or activity have significant effects on PAH establishment and progression. This review describes the molecular mechanisms and physiological consequences of potassium channel modulation. Special emphasis is placed on KCNA5 (Kv1.5) and KCNK3 (TASK1), which are considered to play a central role in determining pulmonary vascular tone and may represent attractive therapeutic targets in the treatment of PAH. PMID:26341985

  3. Bradykinin actively modulates pulmonary vascular pressure-cardiac index relationships.

    PubMed

    Nyhan, D P; Clougherty, P W; Goll, H M; Murray, P A

    1987-07-01

    Our objectives were to investigate the pulmonary vascular effects of exogenously administered bradykinin at normal and reduced levels of cardiac index in intact conscious dogs and to assess the extent to which the pulmonary vascular response to bradykinin is the result of either cyclooxygenase pathway activation or reflex activation of sympathetic beta-adrenergic and -cholinergic receptors. Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed during normoxia in conscious dogs by step-wise constriction of the thoracic inferior vena cava to reduce Q. In intact dogs, bradykinin (2 micrograms X kg-1 X min-1 iv) caused systemic vasodilation, i.e., systemic arterial pressure was slightly decreased (P less than 0.05), Q was markedly increased (P less than 0.01), and mixed venous PO2 and oxygen saturation (SO2) were increased (P less than 0.01). Bradykinin decreased (P less than 0.01) the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure) over the entire range of Q studied (140-60 ml X min-1 X kg-1) in intact dogs. During cyclooxygenase pathway inhibition with indomethacin, bradykinin again decreased (P less than 0.05) pulmonary arterial pressure-pulmonary capillary wedge pressure at every level of Q, although the magnitude of the vasodilator response was diminished at lower levels of Q (60 ml X min-1 X kg-1). Following combined administration of sympathetic beta-adrenergic and -cholinergic receptor antagonists, bradykinin still decreased (P less than 0.01) pulmonary arterial pressure-pulmonary capillary wedge pressure over the range of Q from 160 to 60 ml X min-1 X kg-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3114215

  4. [Roll repair of nonconfluent pulmonary artery].

    PubMed

    Komiya, T; Yamazaki, K; Kohchi, K; Kanzaki, Y

    1995-11-01

    We reviewed the repair of nonconfluent pulmonary artery using a roll to clarify indication of this operation, operative technique (especially the material and the size of conduit) and possibility of total correction. Eleven patients (mean age: five years) and 13 operations including two reoperations were reviewed. The material of the roll was xenopericardium in nine and artificial graft in four operations. No operative death and late death occurred. Five patients required reoperations from three occlusion and two severe stenosis of the roll. Three of nine xenopericardial roll needed reoperations and in two reoperated cases, the roll had been placed behind the aorta. In contrast, one artificial graft needed reoperation. The diameter of the roll was compared with that of normal pulmonary artery estimated from the body surface area. If the roll was too large (more than 125% normal) or too small (less than 100% normal), the luminal diameter of the roll became significantly smaller than appropriate-sized roll (p = 0.002). The size of nonconfluent side of the pulmonary artery also affect the result of repair. In occluded or stenotic cases, the unilateral PA index was significantly smaller than good patent cases (p = 0.014). Total correction was possible in eight cases (73%) including four Rastelli operation, two right ventricular outflow patch enlargement, and two modified Fontan operations without operative death. Thus preoperative evaluation of the pulmonary artery size and anatomy, selection of roll material and size matching seemed to be important for successful roll repair of nonconfluent pulmonary artery.

  5. Arterial pulse wave pressure transducer

    NASA Technical Reports Server (NTRS)

    Kim, C.; Gorelick, D.; Chen, W. (Inventor)

    1974-01-01

    An arterial pulse wave pressure transducer is introduced. The transducer is comprised of a fluid filled cavity having a flexible membrane disposed over the cavity and adapted to be placed on the skin over an artery. An arterial pulse wave creates pressure pulses in the fluid which are transduced, by a pressure sensitive transistor in direct contact with the fluid, into an electric signal. The electrical signal is representative of the pulse waves and can be recorded so as to monitor changes in the elasticity of the arterial walls.

  6. [Management of Pulmonary Blood Flow for a Patient with Congenital Pulmonary Vein Stenosis Undergoing Pulmonary Venous Obstruction Release and Pulmonary Artery Banding].

    PubMed

    Ideno, Satoshi; Yamamoto, Shinichi; Oda, Fujiko; Wakamiya, Rie; Ozawa, Kana; Kaneko, Haruka; Matsuoka, Taku; Shinto, Atsushi; Mikasa, Hiromi; Miyazawa, Noriko

    2015-02-01

    Congenital pulmonary vein stenosis (CPVS) is a rare fetal congenital heart disease with a prevalence of 1.7 per 100,000 children younger than two years of age. Because of the difficulty of maintaining the pulmonary blood flow, CPVS is associated with a 50% survival rate within five years of diagnosis. We describe a successful management of pulmonary blood flow for a 4-month-old-girl with CPVS, combined with atrial septal defect and ventricular septal defect, undergoing pulmonary vein obstruction release (PVOR). In this case, CPVS was the only cause for pulmonary hypertension because there was no significant pressure gradient between each pulmonary capillary wedge pressure and the paired pulmonary vein pressure, indicating the normal pulmonary vascular structure prior to pulmonary vein stenosis. As pulmonary blood flow was estimated to be high after PVOR, pulmonary artery banding was also performed. Management of pulmonary blood flow is the most important issue for anesthesia of this surgery, especially in postcardiopulmonary bypass period, when the pulmonary vasoconstriction is induced by endothelial dysfuncion.

  7. Management of pulmonary arterial hypertension.

    PubMed

    McLaughlin, Vallerie V; Shah, Sanjiv J; Souza, Rogerio; Humbert, Marc

    2015-05-12

    Pulmonary hypertension (PH) is common and may result from a number of disorders, including left heart disease, lung disease, and chronic thromboembolic disease. Pulmonary arterial hypertension (PAH) is an uncommon disease characterized by progressive remodeling of the distal pulmonary arteries, resulting in elevated pulmonary vascular resistance and, eventually, in right ventricular failure. Over the past decades, knowledge of the basic pathobiology of PAH and its natural history, prognostic indicators, and therapeutic options has exploded. A thorough evaluation of a patient is critical to correctly characterize the PH. Cardiac studies, including echocardiography and right heart catheterization, are key elements in the assessment. Given the multitude of treatment options currently available for PAH, assessment of risk and response to therapy is critical in long-term management. This review also underscores unique situations, including perioperative management, intensive care unit management, and pregnancy, and highlights the importance of collaborative care of the PAH patient through a multidisciplinary approach.

  8. Pulmonary arterial hypertension: a clot in question.

    PubMed

    Patel, Bhavin; Pakala, Aneesh; Aronson, Willard; Magharyous, Hany; Brown, Brent

    2014-07-01

    Pulmonary arterial hypertension (PAH) is a group of disorders characterized by a progressive increase in pulmonary vascular resistance leading to right heart failure and premature death. We present an unusual case of PAH diagnosed initially as Idiopathic PAH (IPAH) after secondary causes were excluded which was successfully managed for a number of years with vasodilators and anticoagulation. Over the months after stopping anticoagulation (because of recurring small bowel hemorrhaging) patient developed progressive findings of right heart failure, which failed to respond to escalating doses of prostacyclin. The patient died and an autopsy revealed the surprising finding of extensive organized central pulmonary artery thrombi as is seen in patients with chronic thromboembolic pulmonary hypertension (CTEPH). We discuss the question of whether these thrombi are generally embolic or develop in situ and recommend that clinicians have a high index of suspicion for central thrombi in patients with IPAH were anticoagulation is contraindicated. PMID:25223151

  9. [Successful pregnancy in a patient with idiopathic pulmonary arterial hypertension. Case report].

    PubMed

    Szenczi, Orsolya; Karlócai, Kristóf; Bucsek, László; Rigó, János

    2016-04-10

    Idiopathic pulmonary arterial hypertension is characterized by progressive increase in pulmonary arterial pressure and pulmonary vascular resistance which lead to right ventricular failure and death. Pregnancy in patients with idiopathic pulmonary arterial hypertension is contraindicated because of the high maternal and fetal mortality. The authors present a case of successful pregnancy and delivery of a patient with idiopathic pulmonary arterial hypertension in Hungary for the first time. The aim of the report was to demonstrate that management and treatment of idiopathic pulmonary arterial hypertension in a pregnant woman is a complex and multidisciplinary task that should involve obstetrician, cardiologist and anesthesiologist. Those patients who become pregnant and do not wish to terminate the pregnancy must be referred to obstetric centers where a multidiciplinary approach is taken.

  10. MRI of absent left pulmonary artery.

    PubMed

    Debatin, J F; Moon, R E; Spritzer, C E; MacFall, J; Sostman, H D

    1992-01-01

    Unilateral absence of a pulmonary artery, more accurately referred to as unilateral proximal interruption of a pulmonary artery, is a rare congenital anomaly that may occur as an isolated lesion or in association with other congenital cardiovascular abnormalities. Diagnosis of associated lesions is imperative as early detection and intervention may significantly improve the patient's prognosis. We present the case of an adult patient who had come to our attention after suffering neurological decompression illness related to scuba diving. The patient's cardiopulmonary anatomy was evaluated using MRI gated spin echo, cine, and breath-held fast spoiled recalled echo sequences.

  11. Pulmonary Arterial Hypertension Associated with Congenital Portosystemic Shunts Treated with Transcatheter Embolization and Pulmonary Vasodilators.

    PubMed

    Sato, Haruka; Miura, Masanobu; Yaoita, Nobuhiro; Yamamoto, Saori; Tatebe, Shunsuke; Aoki, Tatsuo; Satoh, Kimio; Ota, Hideki; Takase, Kei; Sugimura, Koichiro; Shimokawa, Hiroaki

    2016-01-01

    Cardiopulmonary abnormalities are often present in patients with liver diseases. We herein report a case of congenital portosystemic shunts complicated by hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PoPH). A 57-year-old woman complained of dyspnea and was subsequently diagnosed with HPS and PoPH caused by congenital portosystemic shunts. Although shunt closure by transcatheter embolization was successfully performed, her dyspnea worsened and pulmonary artery pressure and pulmonary vascular resistance elevated. Conventional vasodilator therapy was started, resulting in an improvement of pulmonary hypertension (PH). In some patients with congenital portosystemic shunts, shunt closure could exacerbate PH, and vasodilator therapy may be effective. PMID:27580545

  12. Influence of bidirectional superior cavopulmonary anastomosis on pulmonary arterial growth.

    PubMed

    Slavik, Z; Webber, S A; Lamb, R K; Horvath, P; LeBlanc, J G; Keeton, B R; Monro, J L; Tax, P; Tuma, S; Reich, O

    1995-11-15

    Right-sided BSCA provides for satisfactory pulmonary arterial growth in infants and children with complex congenital heart defects, and it could enhance the growth of a small right pulmonary artery. The growth of the left pulmonary artery, particularly in younger patients, needs close attention to confirm the safe role of BSCA in long-term palliation. PMID:7484871

  13. Right Ventricular Dysfunction in Systemic Sclerosis Associated Pulmonary Arterial Hypertension

    PubMed Central

    Tedford, Ryan J.; Mudd, James O.; Girgis, Reda E.; Mathai, Stephen C.; Zaiman, Ari L.; Housten-Harris, Traci; Boyce, Danielle; Kelemen, Benjamin W.; Bacher, Anita C.; Shah, Ami A.; Hummers, Laura K.; Wigley, Fredrick M.; Russell, Stuart D.; Saggar, Rajeev; Saggar, Rajan; Maughan, W. Lowell; Hassoun, Paul M.; Kass, David A.

    2013-01-01

    Background Systemic sclerosis associated pulmonary artery hypertension (SScPAH) has a worse prognosis compared to idiopathic pulmonary arterial hypertension (IPAH), with a median survival of 3 years after diagnosis often due to right ventricular (RV) failure. We tested if SScPAH or systemic sclerosis related pulmonary hypertension with interstitial lung disease (SSc-ILD-PH) imposes a greater pulmonary vascular load than IPAH and/or leads to worse RV contractile function. Methods and Results We analyzed pulmonary artery pressures and mean flow in 282 patients with pulmonary hypertension (166 SScPAH, 49 SSc-ILD-PH, 67 IPAH). An inverse relation between pulmonary resistance (RPA) and compliance (CPA) was similar for all three groups, with a near constant resistance × compliance product. RV pressure-volume loops were measured in a subset, IPAH (n=5) and SScPAH (n=7) as well as SSc without PH (SSc-no-PH, n=7) to derive contractile indexes (end-systolic elastance [Ees] and preload recruitable stroke work [Msw]), measures of right ventricular load (arterial elastance [Ea]), and RV-pulmonary artery coupling (Ees/Ea). RV afterload was similar in SScPAH and IPAH (RPA=7.0±4.5 vs. 7.9±4.3 Wood units; Ea=0.9±0.4 vs. 1.2±0.5 mmHg/mL; CPA=2.4±1.5 vs. 1.7±1.1 mL/mmHg; p>0.3 for each). Though SScPAH did not have greater vascular stiffening compared to IPAH, RV contractility was more depressed (Ees=0.8±0.3 vs. 2.3±1.1, p<0.01; Msw=21±11 vs. 45±16, p=0.01), with differential RV-PA uncoupling (Ees/Ea=1.0±0.5 vs. 2.1±1.0, p=.03). This ratio was higher in SSc-no-PH (Ees/Ea = 2.3±1.2, p=0.02 vs. SScPAH). Conclusions RV dysfunction is worse in SScPAH compared to IPAH at similar afterload, and may be due to intrinsic systolic function rather than enhanced pulmonary vascular resistive and/or pulsatile loading. PMID:23797369

  14. Fontan hemodynamics: Importance of pulmonary artery diameter

    PubMed Central

    Dasi, Lakshmi P.; KrishnankuttyRema, Resmi; Kitajima, Hiroumi D.; Pekkan, Kerem; Sundareswaran, Kartik S.; Fogel, Mark; Sharma, Shiva; Whitehead, Kevin; Kanter, Kirk; Yoganathan, Ajit P.

    2010-01-01

    Objective We quantify the geometric and hemodynamic characteristics of extracardiac and lateral tunnel Fontan surgical options and correlate certain anatomic characteristics with their hemodynamic efficiency and patient cardiac index. Methods and Results The study was conducted retrospectively on 22 patients undergoing Fontan operations (11 extracardiac and 11 lateral tunnel operations). Total cavopulmonary connection geometric parameters such as vessel areas, curvature, and offsets were quantified using a skeletonization method. Energy loss at the total cavopulmonary connection junction was available from previous in vitro experiments and computational fluid dynamic simulations for 5 and 9 patients, respectively. Cardiac index data were available for all patients. There was no significant difference in the mean and minimum cross-sectional vessel areas of the pulmonary artery between the extracardiac and lateral tunnel groups. The indexed energy dissipation within the total cavopulmonary connection was strongly correlated to minimum cross-sectional area of the pulmonary arteries (R2 value of 0.90 and P < .0002), whereas all other geometric features, including shape characteristics, had no significant correlation. Finally, cardiac index significantly correlated with the minimum pulmonary artery area (P = .006), suggesting that total cavopulmonary connection energy losses significantly affect resting cardiac output. Conclusions The minimum outlet size of the total cavopulmonary connection (ie, minimum cross section of pulmonary artery) governs the energy loss characteristics of the total cavopulmonary connection more strongly than variations in the shapes corresponding to extracardiac and lateral tunnel configurations. Differences in pulmonary artery sizes must be accounted for when comparing energy losses between extracardiac and lateral tunnel geometries. PMID:19258065

  15. [Pulmonary arterial hypertension: a flavor of autoimmunity].

    PubMed

    Perros, Frédéric; Humbert, Marc; Cohen-Kaminsky, Sylvia

    2013-01-01

    It is admitted that autoimmunity results from a combination of risks such as genetic background, environmental triggers, and stochastic events. Pulmonary arterial hypertension (PAH) shares with the so-called prototypic autoimmune diseases, genetic risk factors, female predominance and sex hormone influence, association with other chronic inflammatory and autoimmune diseases, defects in regulatory T cells function, and presence of autoantibodies. Case reports have been published indicating the beneficial effect of some immunosuppressive and anti-inflammatory therapies in PAH, supporting the potential role of immune mechanisms in the pathophysiology of the disease. In this review, we discuss the current knowledge on autoimmune mechanisms operating in PAH, especially mounting a local autoimmune response inside the pulmonary tissue, namely pulmonary lymphoid neogenesis. A better understanding of the role of autoimmunity in pulmonary vascular remodelling may help develop targeted immunomodulatory strategies in PAH. PMID:23859515

  16. A case of left main pulmonary artery aneurysm associated with valvular pulmonary stenosis in a child.

    PubMed

    Lee, Ran; Son, Jae Sung; Park, Yong Mean

    2011-10-01

    Aneurysm of the main pulmonary artery is a rare clinical entity that can be congenital or acquired. Most cases occur in association with other congenital malformations, severe pulmonary hypertension, vasculitides, infectious agents, or collagen vascular disorders. We report here a pediatric case of left pulmonary artery aneurysm associated with valvular pulmonary stenosis and a hypoplastic right pulmonary artery, which we confirmed via multidetector computed tomography angiography.

  17. Unusual Systemic Artery to Pulmonary Artery Malformation Without Evidence of Systemic Disease, Trauma or Surgery

    SciTech Connect

    Geyik, Serdar; Yavuz, Kivilcim; Keller, Frederick S.

    2006-10-15

    Connections between the systemic and pulmonary arterial systems are rare conditions that can be due to either congenital or acquired diseases such as anomalous systemic arterial supply to normal lung, pulmonary sequestration, and systemic supply to pulmonary arteriovenous malformations. Herein, a unique case of systemic artery to pulmonary arterial malformation and its endovascular treatment in a patient with no history of the usual etiologies is reported.

  18. Wave reflections in the pulmonary arteries analysed with the reservoir-wave model.

    PubMed

    Bouwmeester, J Christopher; Belenkie, Israel; Shrive, Nigel G; Tyberg, John V

    2014-07-15

    Conventional haemodynamic analysis of pressure and flow in the pulmonary circulation yields incident and reflected waves throughout the cardiac cycle, even during diastole. The reservoir-wave model provides an alternative haemodynamic analysis consistent with minimal wave activity during diastole. Pressure and flow in the main pulmonary artery were measured in anaesthetized dogs and the effects of hypoxia and nitric oxide, volume loading and positive end-expiratory pressure were observed. The reservoir-wave model was used to determine the reservoir contribution to pressure and flow and once subtracted, resulted in 'excess' quantities, which were treated as wave-related. Wave intensity analysis quantified the contributions of waves originating upstream (forward-going waves) and downstream (backward-going waves). In the pulmonary artery, negative reflections of incident waves created by the right ventricle were observed. Overall, the distance from the pulmonary artery valve to this reflection site was calculated to be 5.7 ± 0.2 cm. During 100% O2 ventilation, the strength of these reflections increased 10% with volume loading and decreased 4% with 10 cmH2O positive end-expiratory pressure. In the pulmonary arterial circulation, negative reflections arise from the junction of lobar arteries from the left and right pulmonary arteries. This mechanism serves to reduce peak systolic pressure, while increasing blood flow.

  19. Pulmonary stenosis development and reduction of pulmonary arterial hypertension in atrioventricular septal defect: a case report

    PubMed Central

    Barth, Emeline; Bouvaist, Hélène; Marlière, Stéphanie; Ninet, Gérard; Vanzetto, Gérald

    2009-01-01

    A 24-year-old patient was admitted for dyspnoea and syncope. He had a previous history of complete atrio-ventricular septal defect and trisomy 21. At the age of 6 months, in 1984, cardiac catheterization revealed a quasi-systemic pulmonary arterial hypertension with a bidirectional shunt corresponding to an Eisenmenger syndrome. Corrective cardiac surgery was not performed at this time because surgical risk was considered too high. Until the age of 20 years old, he showed few symptoms while under medical treatment. But since 2006, his functional status became worse with an increased dyspnoea, syncopes, and severe cyanosis. In these conditions, haemodynamic parameters have been re-evaluated in 2006 and 2008. They highlighted a late and progressive development of a valvular and infundibular pulmonary stenosis leading to a normalisation of pulmonary arterial pressures. At the age of 24 , the patient underwent corrective cardiac surgery which was successful. Late development of both infundibular and valvular pulmonary stenosis have not been described before in non operated congenital ventricular septal defects, but development of one or the other abnormality would be found in 8% of patients. The physiopathological mechanism of this obstruction is unclear. Nevertheless, in unoperated congenital cardiac shunt lesions, reversibility of severe pulmonary arterial hypertension should be reconidered and re-assessed during follow up. PMID:19758423

  20. Pulmonary Artery Cement Embolism after a Vertebroplasty

    PubMed Central

    Nooh, Anas; Abduljabbar, Fahad H.; Abduljabbar, Ahmed H.; Jarzem, Peter

    2015-01-01

    Background Context. Vertebroplasty is a minimally invasive procedure most commonly used for the treatment of vertebral compression fractures. Although it is relatively safe, complications have been reported over time. Among those complications, massive cement pulmonary embolism is considered a rare complication. Here we report a case of massive diffuse cement pulmonary embolism following percutaneous vertebroplasty for a vertebral compression fracture. Study Design. Case report. Methods. This is a 70-year-old female who underwent vertebroplasty for T11 and T12 vertebral compression fracture. Results. CT-scan revealed an incidental finding of cement embolism in the pulmonary trunk and both pulmonary arteries. Since the patient was asymptomatic, she was monitored closely and she did not need any intervention. Conclusion. Vertebroplasty is a minimally invasive procedure used for treatment of vertebral compression fracture. Despite the low rate of complications, a pulmonary cement embolism can occur. The consequences of cement embolism range widely from being asymptomatic to embolism that can cause paralysis, radiculopathy, or a fatal pulmonary embolism. PMID:26221556

  1. Computational Simulation of the Pulmonary Arteries and its Role in the Study of Pediatric Pulmonary Hypertension

    PubMed Central

    Hunter, Kendall S.; Feinstein, Jeffrey A.; Ivy, D. Dunbar; Shandas, Robin

    2010-01-01

    The hemodynamic state of the pulmonary arteries is challenging to routinely measure in children due to the vascular circuit's position in the lungs. The resulting relative scarcity of quantitative clinical diagnostic and prognostic information impairs management of diseases such as pulmonary hypertension, or high blood pressure of the pulmonary circuit, and invites new techniques of measurement. Here we examine recent applications of macro-scale computational mechanics methods for fluids and solids – traditionally used by engineers in the design and virtual testing of complex metal and composite structures – applied to study the pulmonary vasculature, both in healthy and diseased states. In four subject areas, we briefly outline advances in computational methodology and provide examples of clinical relevance. PMID:21499523

  2. Histopathologic Characteristics of a Coronary-pulmonary Artery Fistula with a Coronary Artery Aneurysm

    PubMed Central

    Sakata, Noriyuki; Minematsu, Noritoshi; Morishige, Noritsugu; Tashiro, Tadashi; Imanaga, Yoshinobu

    2011-01-01

    Here, we report a case of a 59-year-old woman with a coronary-pulmonary artery fistula with a concomitant coronary artery aneurysm, which comprised an anomalous coronary artery originating at the right coronary cusp, an aberrant branch of the left anterior descending artery, and a coronary artery aneurysm draining into the main pulmonary artery. Histopathologically, non-dilated anomalous coronary artery showed the preservation of internal elastic lamina and medial smooth muscle cell phenotype which lacked in the aneurysmal wall. Thus, the disrupted internal elastic lamina and phenotypic change of medial smooth muscle cells might contribute to aneurysm formation in a coronary-pulmonary arterial fistula. PMID:23555427

  3. [Novel immunopathological approaches to pulmonary arterial hypertension].

    PubMed

    Perros, Frédéric; Montani, David; Dorfmüller, Peter; Huertas, Alice; Chaumais, Marie-Camille; Cohen-Kaminsky, Sylvia; Humbert, Marc

    2011-04-01

    Inflammation is important for the initiation and the maintenance of vascular remodeling in the most commun animal models of pulmonary hypertension (PH), and its therapeutical targeting blocks PH development in these models. In human, pulmonary vascular lesions of PH are also the source of an intense chemokine production, linked to inflammatory cell recruitment. However, arteritis is uncommon in PH patients. Of note, current PH treatments have immunomodulatory properties. In addition, some studies have shown a correlation between levels of circulating inflammatory mediators and patients' survival. The study of autoimmunity in the pathophysiology of pulmonary arterial hypertension is becoming an area of intense investigation. New immunopathological approaches to PH should allow the development of innovative treatments for this very severe condition. PMID:21536178

  4. Recurrent ischemia resulting from left internal mammary artery-to-pulmonary artery fistula.

    PubMed

    Madu, E C; Hanumanthu, S K; Kim, C; Prudoff, A

    2001-03-01

    This report describes a case series of recurrent ischemia after coronary artery bypass grafting resulting from left internal mammary artery-to-pulmonary artery fistula. An angiographic demonstration of this fistula is presented.

  5. Serum VEGF levels are related to the presence of pulmonary arterial hypertension in systemic sclerosis

    PubMed Central

    Papaioannou, Andriana I; Zakynthinos, Epaminondas; Kostikas, Konstantinos; Kiropoulos, Theodoros; Koutsokera, Angela; Ziogas, Athanasios; Koutroumpas, Athanasios; Sakkas, Lazaros; Gourgoulianis, Konstantinos I; Daniil, Zoe D

    2009-01-01

    Background The association between systemic sclerosis and pulmonary arterial hypertension (PAH) is well recognized. Vascular endothelial growth factor (VEGF) has been reported to play an important role in pulmonary hypertension. The aim of the present study was to examine the relationship between systolic pulmonary artery pressure, clinical and functional manifestations of the disease and serum VEGF levels in systemic sclerosis. Methods Serum VEGF levels were measured in 40 patients with systemic sclerosis and 13 control subjects. All patients underwent clinical examination, pulmonary function tests and echocardiography. Results Serum VEGF levels were higher in systemic sclerosis patients with sPAP ≥ 35 mmHg than in those with sPAP < 35 mmHg (352 (266, 462 pg/ml)) vs (240 (201, 275 pg/ml)) (p < 0.01), while they did not differ between systemic sclerosis patients with sPAP < 35 mmHg and controls. Serum VEGF levels correlated to systolic pulmonary artery pressure, to diffusing capacity for carbon monoxide and to MRC dyspnea score. In multiple linear regression analysis, serum VEGF levels, MRC dyspnea score, and DLCO were independent predictors of systolic pulmonary artery pressure. Conclusion Serum VEGF levels are increased in systemic sclerosis patients with sPAP ≥ 35 mmHg. The correlation between VEGF levels and systolic pulmonary artery pressure may suggest a possible role of VEGF in the pathogenesis of PAH in systemic sclerosis. PMID:19426547

  6. Recapitulation of developing artery muscularization in pulmonary hypertension.

    PubMed

    Sheikh, Abdul Q; Lighthouse, Janet K; Greif, Daniel M

    2014-03-13

    Excess smooth muscle accumulation is a key component of many vascular disorders, including atherosclerosis, restenosis, and pulmonary artery hypertension, but the underlying cell biological processes are not well defined. In pulmonary artery hypertension, reduced pulmonary artery compliance is a strong independent predictor of mortality, and pathological distal arteriole muscularization contributes to this reduced compliance. We recently demonstrated that embryonic pulmonary artery wall morphogenesis consists of discrete developmentally regulated steps. In contrast, poor understanding of distal arteriole muscularization in pulmonary artery hypertension severely limits existing therapies that aim to dilate the pulmonary vasculature but have modest clinical benefit and do not prevent hypermuscularization. Here, we show that most pathological distal arteriole smooth muscle cells, but not alveolar myofibroblasts, derive from pre-existing smooth muscle. Furthermore, the program of distal arteriole muscularization encompasses smooth muscle cell dedifferentiation, distal migration, proliferation, and then redifferentiation, thereby recapitulating many facets of arterial wall development. PMID:24582963

  7. Pulmonary artery aneurysm in an adult patient with idiopathic dilatation of the pulmonary artery

    PubMed Central

    Betkier-Lipińska, Katarzyna; Czarkowski, Sebastian; Hendzel, Piotr; Cwetsch, Andrzej

    2015-01-01

    Idiopathic dilatation of the pulmonary artery (IDPA) is a rare congenital heart disease. It has been described for almost one hundred years, and numerous definitions have been proposed. The IDPA diagnostic criteria have not been updated for years. Secondary to primary disease, pulmonary artery aneurism was recognised as a lethal defect; however, long-term follow-up of patients with IDPA has not been well researched. Thus, indications to medical or surgical treatment are not evidence based. Here, we present a rare case of a 54-year-old patient with IDPA, who remained under observation for 36 years without surgical intervention. PMID:26855651

  8. Quantification of pulmonary arterial wall distensibility using parameters extracted from volumetric micro-CT images

    NASA Astrophysics Data System (ADS)

    Johnson, Roger H.; Karau, Kelly L.; Molthen, Robert C.; Dawson, Christopher A.

    1999-09-01

    Stiffening, or loss of distensibility, of arterial vessel walls is among the manifestations of a number of vascular diseases including pulmonary arterial hypertension. We are attempting to quantify the mechanical properties of vessel walls of the pulmonary arterial tree using parameters derived from high-resolution volumetric x-ray CT images of rat lungs. The pulmonary arterial trees of the excised lungs are filled with a contrast agent. The lungs are imaged with arterial pressures spanning the physiological range. Vessel segment diameters are measured from the inlet to the periphery, and distensibilities calculated from diameters as a function of pressure. The method shows promise as an adjunct to other morphometric techniques such as histology and corrosion casting. It possesses the advantages of being nondestructive, characterizing the vascular structures while the lungs are imaged rapidly and in a near-physiological state, and providing the ability to associate mechanical properties with vessel location in the intact tree hierarchy.

  9. Pulmonary arterial hypertension: a comparison between children and adults.

    PubMed

    Barst, R J; Ertel, S I; Beghetti, M; Ivy, D D

    2011-03-01

    The characteristics of pulmonary arterial hypertension (PAH), including pathology, symptoms, diagnosis and treatment are reviewed in children and adults. The histopathology seen in adults is also observed in children, although children have more medial hypertrophy at presentation. Both populations have vascular and endothelial dysfunction. Several unique disease states are present in children, as lung growth abnormalities contribute to pulmonary hypertension. Although both children and adults present at diagnosis with elevations in pulmonary vascular resistance and pulmonary artery pressure, children have less heart failure. Dyspnoea on exertion is the most frequent symptom in children and adults with PAH, but heart failure with oedema occurs more frequently in adults. However, in idiopathic PAH, syncope is more common in children. Haemodynamic assessment remains the gold standard for diagnosis, but the definition of vasoreactivity in adults may not apply to young children. Targeted PAH therapies approved for adults are associated with clinically meaningful effects in paediatric observational studies; children now survive as long as adults with current treatment guidelines. In conclusion, there are more similarities than differences in the characteristics of PAH in children and adults, resulting in guidelines recommending similar diagnostic and therapeutic algorithms in children (based on expert opinion) and adults (evidence-based).

  10. Extracellular matrix protein gene expression in atherosclerotic hypertensive pulmonary arteries.

    PubMed Central

    Botney, M. D.; Kaiser, L. R.; Cooper, J. D.; Mecham, R. P.; Parghi, D.; Roby, J.; Parks, W. C.

    1992-01-01

    Lobar pulmonary arteries from patients with unexplained pulmonary hypertension were obtained at the time of single-lung transplantation to determine the response of large elastic vessels to increased intraluminal pressure. Specifically, human pulmonary arteries were examined to determine if remodeling remained active at the time of surgery and whether remodeling was similar to previously reported remodeling observed in several animal models. Grossly, the hypertensive vessels appeared atherosclerotic. Histochemical stains revealed a thick, diffuse neointima in hypertensive vessels compared with normal vessels. Immunohistochemistry demonstrated elastin protein in the neointima and in situ hybridization studies demonstrated tropoelastin mRNA largely in the neointima. Similarly, immunohistochemistry and in situ hybridization detected cellular fibronectin, thrombospondin and type I collagen protein and mRNA within the thickened intima from hypertensive vessels. These studies provide evidence that hypertensive vessels in patients with severe chronic pulmonary hypertension are actively remodeling but that the pattern of remodeling is different from previously described animal models. Images Figure 1 Figure 2 Figure 3 PMID:1739129

  11. [Clinical and instrumental characteristics of primary high altitude arterial pulmonary hypertension].

    PubMed

    Mirrakhimov, M M; Rudenko, R I; Murataliev, T M; Khamzamulin, R O

    1976-10-01

    The clinical pattern of primary high altitude pulmonary arterial hypertension observed in permanent residents of mountain regions is described. The diagnostic value of some non-invasive instrumental methods in primary high altitude pulmonary artery hypertension is analysed: electro- and vectorcardiography, rheopulmonography, and indirect pulmonary artery pressure determination. It is suggested to distinguish the labile, stable and decompensated forms of the disease on the basis of its clinical and functional peculiarities. The criterion for the initial two forms consists in the persistence of the pulmonary artery pressure elevation, while the latter form is established when the high altitude cor pulmonale gets decompensated. Functional vasoconstriction of the pulmonary resistive vessels was shown to play an important role in the genesis of the disease: the administration of 0.5 mg of nitroglycerine and a 5-minute oxygen inhalation caused a positive dynamics in the indices of the pulmonary rheogramme and a reduction of the pulmonary artery pressure, which did not reach the level of the plane inhabitants, though.

  12. Liposomal Fasudil, a Rho-Kinase Inhibitor, for Prolonged Pulmonary Preferential Vasodilation in Pulmonary Arterial Hypertension

    PubMed Central

    Gupta, Vivek; Gupta, Nilesh; Shaik, Imam H.; Mehvar, Reza; McMurtry, Ivan F.; Oka, Masahiko; Nozik-Grayck, Eva; Komatsu, Masanobu; Ahsan, Fakhrul

    2013-01-01

    Current pharmacological interventions for pulmonary arterial hypertension (PAH) require continuous infusions, multiple inhalations, or oral administration of drugs that act on various pathways involved in the pathogenesis of PAH. However, invasive methods of administration, short duration of action, and lack of pulmonary selectivity result in noncompliance and poor patient outcomes. In this study, we tested the hypothesis that encapsulation of an investigational anti-PAH molecule fasudil (HA-1077), a Rho-kinase inhibitor, into liposomal vesicles results in prolonged vasodilation in distal pulmonary arterioles. Liposomes were prepared by hydration and extrusion method and fasudil was loaded by ammonium sulfate-induced transmembrane electrochemical gradient. Liposomes were then characterized for various physicochemical properties. Optimized formulations were tested for pulmonary absorption and their pharmacological efficacy in a monocrotaline (MCT) induced rat model of PAH. The entrapment efficiency of optimized liposomal fasudil formulations was between 68.1±0.8% and 73.6±2.3%, and the cumulative release at 37°C was 98–99% over a period of 5 days. Compared to intravenous (IV) fasudil, a ~10 fold increase in the terminal plasma half-life was observed when liposomal fasudil was administered as aerosols. The t1/2 of IV fasudil was 0.39±0.12 h. and when given as liposomes via pulmonary route, the t1/2 extended to 4.71±0.72 h. One h after intratracheal instillation of liposomal fasudil, mean pulmonary arterial pressure (MPAP) was reduced by 37.6±5.7% and continued to decrease for about 3 h, suggesting that liposomal formulations produced pulmonary preferential vasodilation in MCT induced PAH rats. Overall, this study established the proof-of-principle that aerosolized liposomal fasudil is a feasible option for a non-invasive, controlled release and pulmonary preferential treatment of PAH. PMID:23353807

  13. Stream tube and velocity profile analysis of pulmonary arterial angiograms

    NASA Astrophysics Data System (ADS)

    Clough, Anne V.; Haworth, Steven T.; Manuel, Albert J.; Dawson, Christopher A.

    1999-05-01

    The distribution of blood transit times within the pulmonary arterial tree has important implications with regards to overall lung function. Previously, we showed that the pulmonary arterial tree imparts little dispersion to an injected bolus, so that the bolus arrives at downstream arteries with a time delay, but little increase in variance. Furthermore, the arterial time delay is nearly the same for all pathways to arteries of the same diameter, independent of their pathway length. This small amount of dispersion was observed despite the velocity profile within the arterial tree and the substantial variation in arterial pathway lengths. Thus, we have begun to ask why velocity profile effects and pathway length heterogeneity within the pulmonary arterial tree have so little influence on bolus dispersion. X-ray angiography studies were used to visualize streamtube pathways within the pulmonary arterial tree. Full bolus injections were used to visualize all flow streamlines within the tree, while 'streamtube' injections labeled only about 1% of the inlet arterial cross-section. By changing the injector position within the arterial cross-section, different streamtubes were traced and found to remain intact downstream to vessels less than 200 micrometer in diameter. Thus, it appears that lower velocity streamtubes tend to peel off from the full velocity profile at arterial bifurcations, while flow streamtubes with higher average velocity travel down the main arterial trunk. The net result is that dispersive velocity profile effects are mitigated by the interaction between the distributed velocity profile and the branching pattern of the pulmonary arterial tree.

  14. A case of pulmonary artery sarcoma presented as cavitary pulmonary lesions.

    PubMed

    Min, Daniel; Lee, Ji-Hyun; Jeong, Hye-Cheol; Kim, Jung-Hyun; Shin, Suk-Pyo; Kim, Hong-Min; Han, Kyu Hyun; Jeong, Hye Yun; Kim, Eun-Kyung

    2014-03-01

    Pulmonary artery sarcoma (PAS) is a rare, poorly differentiated malignancy arising from the intimal layer of the pulmonary artery. Contrast-enhanced chest computed tomography (CT) is a good diagnostic modality that shows a low-attenuation filling defect of the pulmonary artery in PAS patients. An 18-year-old man was referred to our hospital for the evaluation and management of cavitary pulmonary lesions that did not respond to treatment. A contrast-enhanced CT of the chest was performed, which showed a filling defect within the right interlobar pulmonary artery. The patient underwent a curative right pneumonectomy after confirmation of PAS. Although lung parenchymal lesions of PAS are generally nonspecific, it can be presented as cavities indicate pulmonary infarcts. Clinicians must consider the possibility of PAS as well as pulmonary thromboembolism in patients with pulmonary infarcts. So, we report the case with PAS that was diagnosed during the evaluation of cavitary pulmonary lesions and reviewed the literatures. PMID:24734102

  15. Coanda effect on ductal flow in the pulmonary artery.

    PubMed

    Guntheroth, W; Miyaki-Hull, C

    1999-03-01

    The Coanda effect (the tendency of a jet stream to adhere to a boundary wall), and the relevant anatomy, may explain the location of ductal jets within the main pulmonary artery. With the usual insertion of the duct close to the left pulmonary artery, during right ventricular ejection, the ductal jet adheres to the left wall of the main pulmonary artery. When right ventricular ejection is absent in pulmonary atresia, the ductal jet streams down the right wall of the pulmonary artery to the pulmonary valve, reverses, and maintains a parallel column back toward the bifurcation. If the reversed flow is mistaken for ejection from the right ventricle, the diagnosis of pulmonary atresia may be missed. PMID:10082354

  16. Intraoperative Monitoring of Pulmonary Artery Physiology With Transesophageal Echocardiography in a Patient With an Extensive Pulmonary Aneurysm Undergoing Partial Nephrectomy.

    PubMed

    Plakke, Michael J; Maxwell, Cory D; Bottiger, Brandi A

    2016-09-01

    Surgical patients with pulmonary hypertension present a significant challenge to the anesthesiologist. Continuous perioperative monitoring of pulmonary artery (PA) pressure is recommended and most often accomplished with a PA catheter. Placement of a PA catheter may be difficult or contraindicated, and in these cases, transesophageal echocardiography is a useful alternative to monitor dynamic PA physiology. In this case, we used intraoperative transesophageal echocardiography to detect changes in peak PA pressure and guide clinical treatment in a patient with pulmonary hypertension and an extensive PA aneurysm undergoing partial nephrectomy. PMID:27580409

  17. [Pulmonary artery aneurysm. A case report].

    PubMed

    Palma Nieto, J C; Sciaccaluga Morelli, C; Antón Martínez, J; Ramos del Amo, V M

    1999-02-01

    The pulmonary artery aneurysm is a rare clinical entity that presents a low incidence and prevalence, of difficult diagnosis to be presented with poorly specific symptoms or also without symptoms, being detected in radiological studies as a widening or mediastinal mass. It can be uni or bilateral and presenting itself isolated or in the context of other sicknesses. The diagnosis of certainty is based in the realization of Echo-Doppler and other studies as a tomography or a magnetic resonance, the therapeutic option being so difficult, and according to cases, by an expectant or aggressive attitude. PMID:10073101

  18. Pulmonary artery endothelium resident endothelial colony-forming cells in pulmonary arterial hypertension

    PubMed Central

    Duong, Heng T.; Comhair, Suzy A.; Aldred, Micheala A.; Mavrakis, Lori; Savasky, Benjamin M.; Erzurum, Serpil C.; Asosingh, Kewal

    2011-01-01

    Proliferative pulmonary vascular remodeling is the pathologic hallmark of pulmonary arterial hypertension (PAH) that ultimately leads to right heart failure and death. Highly proliferative endothelial cells known as endothelial colony-forming cells (ECFC) participate in vascular homeostasis in health as well as in pathological angiogenic remodeling in disease. ECFC are distinguished by the capacity to clonally proliferate from a single cell. The presence of ECFC in the human pulmonary arteries and their role in PAH pathogenesis is largely unknown. In this study, we established a simple technique for isolating and growing ECFC from cultured pulmonary artery endothelial cells (PAEC) to test the hypothesis that ECFC reside in human pulmonary arteries and that the proliferative vasculopathy of PAH is related to greater numbers and/or more proliferative ECFC in the pulmonary vascular wall. Flow cytometric forward and side scatter properties and aggregate correction were utilized to sort unmanipulated, single PAEC to enumerate ECFC in primary PAEC cultures derived from PAH and healthy lungs. After 2 weeks, wells were assessed for ECFC formation. ECFC derived from PAH PAEC were more proliferative than control. A greater proportion of PAH ECFC formed colonies following subculturing, demonstrating the presence of more ECFC with high proliferative potential among PAH PAEC. Human androgen receptor assay showed clonality of progeny, confirming that proliferative colonies were single cell-derived. ECFC expressed CD31, von Willebrand factor, endothelial nitric oxide synthase, caveolin-1 and CD34, consistent with an endothelial cell phenotype. We established a simple flow cytometry method that allows ECFC quantification using unmanipulated cells. We conclude that ECFC reside among PAEC and that PAH PAEC contain ECFC that are more proliferative than ECFC in control cultures, which likely contributes to the proliferative angiopathic process in PAH. PMID:22530103

  19. [Anesthetic Management for Non-cardiac Surgery in a Patient with Severe Pulmonary Arterial Hypertension].

    PubMed

    Ohno, Sho; Niiyama, Yukitoshi; Murouchi, Takeshi; Yamakage, Michiaki

    2016-05-01

    Severe pulmonary arterial hypertension is a significant risk factor for anesthetic management in patients undergoing even non-cardiac surgery. A 64-year-old female patient with severe pulmonary arterial hypertension was scheduled to undergo inguinal hernioplasty. Preoperative systolic pulmonary arterial pressure was 115 mmHg. We selected monitored anesthesia care with 0.2-0.5 μg x kg(-1) x hr(-1) dexmedetomidine and ultrasound-guided iliohypogastric block. Thereafter, LiDCOrapid was used to acquire the hemodynamic responses during surgery. Continuous iliohypogastric block produced postoperative pain relief and the supplemental analgesic was not needed. The monitored anesthesia care by dexmedetomidine and ultrasound guided continuous iliohypogastric block would be a safe procedure for patients with severe pulmonary arterial hypertension undergoing non-cardiac surgery. LiDCO rapid could be low invasive and useful as a hemodaynamic monitor in such a case. PMID:27319099

  20. Changes in the structure and mechanical properties of pulmonary arteries of rats exposed to cigarette smoke.

    PubMed

    Liu, S Q; Fung, Y C

    1993-09-01

    The effect of cigarette smoke on the structure and mechanical properties of pulmonary arteries was studied in 2- and 3-month smoke-exposed rats. The animals were exposed to cigarette smoke in a smoke-generating system 10 times per day with one cigarette each time. The smoke density and the puffing duration and frequency of the system were regulated in accordance with reference values measured from human smokers. The volume fractions of the cells, including smooth muscle cells and fibroblasts, and extracellular matrix components, including collagen, elastin, and remainder (components not specified in this study), of the pulmonary arteries of approximately 450 microns in external diameter (at zero pressure) were determined in smoke-exposed and control rats by using an electron microscopic method. It was found that the volume fractions of the fibroblasts, the collagenous bundles, and the elastic laminae of the pulmonary arteries were increased significantly, whereas those of the smooth muscle cells and the remainder were decreased significantly in both the 2- and 3-month smoke-exposed rats in comparison with those of the corresponding control rats. The mechanical properties of the pulmonary arteries were determined based on the in vitro dimensional measurement of the vessels at various inflation pressures and zero-stress state. An increase in the stiffness of the pulmonary arteries was found in both the 2- and 3-month smoke-exposed rats. We conclude that cigarette smoke can induce structural and mechanical remodeling in the pulmonary arteries of rats. PMID:8368648

  1. Pulmonary blood flow distribution after banding of pulmonary artery.

    PubMed Central

    Samánek, M; Fiser, B; Ruth, C; Tůma, S; Hucín, B

    1975-01-01

    Radioisotope lung scanning was used to investigate the distribution of pulmonary blood flow after banding of the pulmonary artery in children with a left-to-right shunt and pulmonary hypertension. An abnormal distribution of blood flow in the lung on the side of the operation approach was observed in all patients in the first three weeks following surgery. Abnormalities were still observed in 17 of 21 children 10 months to more than 8 years after the banding operation. There was no significant relation between the occurrence of these abnormalities and time after surgery. Diminished flow to the zones of the right lung was observed less frequently. The incidence of abnormalities in flow distribution was also high preoperatively. Respiratory complications in infants with large left-to-right shunts were considered to be responsible for most of the abnormal blood flow distributions observed. Radioactive lung scanning was found to be a valuable diagnostic method in the early and late postoperative period in infants and small children. It was more sensitive than the other techniques used in revealing deviation of blood flow from one lung in those cases with shifting of the applied band. Images PMID:1111558

  2. Main pulmonary arterial wall shear stress correlates with invasive hemodynamics and stiffness in pulmonary hypertension

    PubMed Central

    Kheyfets, Vitaly O.; Schroeder, Joyce D.; Dunning, Jamie; Shandas, Robin; Buckner, J. Kern; Browning, James; Hertzberg, Jean; Hunter, Kendall S.; Fenster, Brett E.

    2016-01-01

    Abstract Pulmonary hypertension (PH) is associated with proximal pulmonary arterial remodeling characterized by increased vessel diameter, wall thickening, and stiffness. In vivo assessment of wall shear stress (WSS) may provide insights into the relationships between pulmonary hemodynamics and vascular remodeling. We investigated the relationship between main pulmonary artery (MPA) WSS and pulmonary hemodynamics as well as markers of stiffness. As part of a prospective study, 17 PH patients and 5 controls underwent same-day four-dimensional flow cardiac magnetic resonance imaging (4-D CMR) and right heart catheterization. Streamwise velocity profiles were generated in the cross-sectional MPA in 45° increments from velocity vector fields determined by 4-D CMR. WSS was calculated as the product of hematocrit-dependent viscosity and shear rate generated from the spatial gradient of the velocity profiles. In-plane average MPA WSS was significantly decreased in the PH cohort compared with that in controls (0.18 ± 0.07 vs. 0.32 ± 0.08 N/m2; P = 0.01). In-plane MPA WSS showed strong inverse correlations with multiple hemodynamic indices, including pulmonary resistance (ρ = −0.74, P < 0.001), mean pulmonary pressure (ρ = −0.64, P = 0.006), and elastance (ρ = −0.70, P < 0.001). In addition, MPA WSS had significant associations with markers of stiffness, including capacitance (ρ = 0.67, P < 0.001), distensibility (ρ = 0.52, P = 0.013), and elastic modulus (ρ = −0.54, P = 0.01). In conclusion, MPA WSS is decreased in PH and is significantly associated with invasive hemodynamic indices and markers of stiffness. 4-D CMR–based assessment of WSS may represent a novel methodology to study blood-vessel wall interactions in PH. PMID:27076906

  3. [Patterns, predictors, and personalization in pulmonary arterial hypertension].

    PubMed

    Kawut, Steven M

    2014-06-01

    Epidemiologic patterns of pulmonary arterial hypertension differ by era and region and may shed light on the pathophysiology and treatment of the disease. New efforts to target one or more of the recently studied therapies could establish personalized medicine as standard care in pulmonary arterial hypertension. PMID:25164214

  4. Heterogeneous mechanics of the mouse pulmonary arterial network.

    PubMed

    Lee, Pilhwa; Carlson, Brian E; Chesler, Naomi; Olufsen, Mette S; Qureshi, M Umar; Smith, Nicolas P; Sochi, Taha; Beard, Daniel A

    2016-10-01

    Individualized modeling and simulation of blood flow mechanics find applications in both animal research and patient care. Individual animal or patient models for blood vessel mechanics are based on combining measured vascular geometry with a fluid structure model coupling formulations describing dynamics of the fluid and mechanics of the wall. For example, one-dimensional fluid flow modeling requires a constitutive law relating vessel cross-sectional deformation to pressure in the lumen. To investigate means of identifying appropriate constitutive relationships, an automated segmentation algorithm was applied to micro-computerized tomography images from a mouse lung obtained at four different static pressures to identify the static pressure-radius relationship for four generations of vessels in the pulmonary arterial network. A shape-fitting function was parameterized for each vessel in the network to characterize the nonlinear and heterogeneous nature of vessel distensibility in the pulmonary arteries. These data on morphometric and mechanical properties were used to simulate pressure and flow velocity propagation in the network using one-dimensional representations of fluid and vessel wall mechanics. Moreover, wave intensity analysis was used to study effects of wall mechanics on generation and propagation of pressure wave reflections. Simulations were conducted to investigate the role of linear versus nonlinear formulations of wall elasticity and homogeneous versus heterogeneous treatments of vessel wall properties. Accounting for heterogeneity, by parameterizing the pressure/distention equation of state individually for each vessel segment, was found to have little effect on the predicted pressure profiles and wave propagation compared to a homogeneous parameterization based on average behavior. However, substantially different results were obtained using a linear elastic thin-shell model than were obtained using a nonlinear model that has a more

  5. Heterogeneous mechanics of the mouse pulmonary arterial network.

    PubMed

    Lee, Pilhwa; Carlson, Brian E; Chesler, Naomi; Olufsen, Mette S; Qureshi, M Umar; Smith, Nicolas P; Sochi, Taha; Beard, Daniel A

    2016-10-01

    Individualized modeling and simulation of blood flow mechanics find applications in both animal research and patient care. Individual animal or patient models for blood vessel mechanics are based on combining measured vascular geometry with a fluid structure model coupling formulations describing dynamics of the fluid and mechanics of the wall. For example, one-dimensional fluid flow modeling requires a constitutive law relating vessel cross-sectional deformation to pressure in the lumen. To investigate means of identifying appropriate constitutive relationships, an automated segmentation algorithm was applied to micro-computerized tomography images from a mouse lung obtained at four different static pressures to identify the static pressure-radius relationship for four generations of vessels in the pulmonary arterial network. A shape-fitting function was parameterized for each vessel in the network to characterize the nonlinear and heterogeneous nature of vessel distensibility in the pulmonary arteries. These data on morphometric and mechanical properties were used to simulate pressure and flow velocity propagation in the network using one-dimensional representations of fluid and vessel wall mechanics. Moreover, wave intensity analysis was used to study effects of wall mechanics on generation and propagation of pressure wave reflections. Simulations were conducted to investigate the role of linear versus nonlinear formulations of wall elasticity and homogeneous versus heterogeneous treatments of vessel wall properties. Accounting for heterogeneity, by parameterizing the pressure/distention equation of state individually for each vessel segment, was found to have little effect on the predicted pressure profiles and wave propagation compared to a homogeneous parameterization based on average behavior. However, substantially different results were obtained using a linear elastic thin-shell model than were obtained using a nonlinear model that has a more

  6. MDCT-based quantification of porcine pulmonary arterial morphometry and self-similarity of arterial branching geometry.

    PubMed

    Lee, Yik Ching; Clark, Alys R; Fuld, Matthew K; Haynes, Susan; Divekar, Abhay A; Hoffman, Eric A; Tawhai, Merryn H

    2013-05-01

    The pig is frequently used as an experimental model for studies of the pulmonary circulation, yet the branching and dimensional geometry of the porcine pulmonary vasculature remains poorly defined. The purposes of this study are to improve the geometric definition of the porcine pulmonary arteries and to determine whether the arterial tree exhibits self-similarity in its branching geometry. Five animals were imaged using thin slice spiral computed tomography in the prone posture during airway inflation pressure at 25 cmH2O. The luminal diameter and distance from the inlet of the left and right pulmonary arteries were measured along the left and right main arterial pathway in each lung of each animal. A further six minor pathways were measured in a single animal. The similarity in the rate of reduction of diameter with distance of all minor pathways and the two main pathways, along with similarity in the number of branches arising along the pathways, supports self-similarity in the arterial tree. The rate of reduction in diameter with distance from the inlet was not significantly different among the five animals (P > 0.48) when normalized for main pulmonary artery diameter and total main artery pathlength, which supports intersubject similarity. Other metrics to quantify the tree geometry are strikingly similar to those from airways of other quadrupeds, with the exception of a significantly larger length to diameter ratio, which is more appropriate for the vascular tree. A simplifying self-similar model for the porcine pulmonary arteries is proposed to capture the important geometric features of the arterial tree. PMID:23449941

  7. Adaptive response of pulmonary arterial smooth muscle to length change.

    PubMed

    Syyong, Harley; Cheung, Christine; Solomon, Dennis; Seow, Chun Y; Kuo, Kuo H

    2008-04-01

    Hypervasoconstriction is associated with pulmonary hypertension and dysfunction of the pulmonary arterial smooth muscle (PASM) is implicated. However, relatively little is known about the mechanical properties of PASM. Recent advances in our understanding of plastic adaptation in smooth muscle may shed light on the disease mechanism. In this study, we determined whether PASM is capable of adapting to length changes (especially shortening) and regain its contractile force. We examined the time course of length adaptation in PASM in response to step changes in length and to length oscillations mimicking the periodic stretches due to pulsatile arterial pressure. Rings from sheep pulmonary artery were mounted on myograph and stimulated using electrical field stimulation (12-16 s, 20 V, 60 Hz). The length-force relationship was determined at L(ref) to 0.6 L(ref), where L(ref) was a reference length close to the in situ length of PASM. The response to length oscillations was determined at L(ref), after the muscle was subjected to length oscillation of various amplitudes for 200 s at 1.5 Hz. Release (or stretch) of resting PASM from L(ref) to 0.6 (and vice versa) was followed by a significant force recovery (73 and 63%, respectively), characteristic of length adaptation. All recoveries of force followed a monoexponential time course. Length oscillations with amplitudes ranging from 5 to 20% L(ref) caused no significant change in force generation in subsequent contractions. It is concluded that, like many smooth muscles, PASM possesses substantial capability to adapt to changes in length. Under pathological conditions, this could contribute to hypervasoconstriction in pulmonary hypertension. PMID:18218913

  8. Imatinib in pulmonary arterial hypertension: c-Kit inhibition.

    PubMed

    Farha, Samar; Dweik, Raed; Rahaghi, Franck; Benza, Raymond; Hassoun, Paul; Frantz, Robert; Torres, Fernando; Quinn, Deborah A; Comhair, Suzy; Erzurum, Serpil; Asosingh, Kewal

    2014-09-01

    Pulmonary arterial hypertension (PAH) is a progressive disease characterized by severe remodeling of the pulmonary artery resulting in increased pulmonary artery pressure and right ventricular hypertrophy and, ultimately, failure. Bone marrow-derived progenitor cells play a critical role in vascular homeostasis and have been shown to be involved in the pathogenesis of PAH. A proliferation of c-Kit(+) hematopoietic progenitors and mast cells has been noted in the remodeled vessels in PAH. Imatinib, a tyrosine kinase inhibitor that targets c-Kit, has been shown to be beneficial for patients with PAH. Here we hypothesize that the clinical benefit of imatinib in PAH could be related to c-Kit inhibition of progenitor cell mobilization and maturation into mast cells. As a corollary to the phase 3 study using imatinib in PAH, blood samples were collected from 12 patients prior to starting study drug (baseline) and while on treatment at weeks 4 and 24. Eight were randomized to imatinib and 4 to placebo. Circulating c-Kit(+) and CD34(+)CD133(+) hematopoietic progenitors as well as biomarkers of mast cell numbers and activation were measured. Circulating CD34(+)CD133(+) and c-Kit(+) progenitor cells as well as c-Kit(+)/CD34(+)CD133(+) decreased with imatinib therapy (all P < 0.05). In addition, total tryptase, a marker of mast cell load, dropped with imatinib therapy (P = 0.02) and was related to pulmonary vascular resistance (R = 0.7, P = 0.02). The findings support c-Kit inhibition as a potential mechanism of action of imatinib in PAH and suggest that tryptase is a potential biomarker of response to therapy. PMID:25621158

  9. Noninvasive pulmonary artery wave intensity analysis in pulmonary hypertension.

    PubMed

    Quail, Michael A; Knight, Daniel S; Steeden, Jennifer A; Taelman, Liesbeth; Moledina, Shahin; Taylor, Andrew M; Segers, Patrick; Coghlan, Gerry J; Muthurangu, Vivek

    2015-06-15

    Pulmonary wave reflections are a potential hemodynamic biomarker for pulmonary hypertension (PH) and can be analyzed using wave intensity analysis (WIA). In this study we used pulmonary vessel area and flow obtained using cardiac magnetic resonance (CMR) to implement WIA noninvasively. We hypothesized that this method could detect differences in reflections in PH patients compared with healthy controls and could also differentiate certain PH subtypes. Twenty patients with PH (35% CTEPH and 75% female) and 10 healthy controls (60% female) were recruited. Right and left pulmonary artery (LPA and RPA) flow and area curves were acquired using self-gated golden-angle, spiral, phase-contrast CMR with a 10.5-ms temporal resolution. These data were used to perform WIA on patients and controls. The presence of a proximal clot in CTEPH patients was determined from contemporaneous computed tomography/angiographic data. A backwards-traveling compression wave (BCW) was present in both LPA and RPA of all PH patients but was absent in all controls (P = 6e(-8)). The area under the BCW was associated with a sensitivity of 100% [95% confidence interval (CI) 63-100%] and specificity of 91% (95% CI 75-98%) for the presence of a clot in the proximal PAs of patients with CTEPH. In conclusion, WIA metrics were significantly different between patients and controls; in particular, the presence of an early BCW was specifically associated with PH. The magnitude of the area under the BCW showed discriminatory capacity for the presence of proximal PA clot in patients with CTEPH. We believe that these results demonstrate that WIA could be used in the noninvasive assessment of PH. PMID:25659483

  10. Endobronchial ultrasound for the detection of chronic pulmonary artery thrombus.

    PubMed

    Dhillon, Samjot Singh; Harris, Kassem

    2016-01-01

    Endobronchial ultrasound (EBUS) has been shown to be able to successfully identify acute/subacute pulmonary thromboembolism (PE). Most reported cases have required confirmation by computerized tomography (CT) angiography. This report demonstrates a case where CT angiography was not conclusive and the EBUS was useful in clarifying the chronic process inside the pulmonary artery compatible with clinical diagnosis of chronic pulmonary artery thrombosis. PMID:27503162

  11. Fontan Operation in a Patient with Severe Hypoplastic Right Pulmonary Artery, Single Ventricle, and Heterotaxy Syndrome

    PubMed Central

    Pan, Jun-Yen; Lin, Chu-Chuan; Chang, Jen-Ping

    2016-01-01

    Assessment of the pulmonary circulation status including pressure, resistance, size, and absence of anatomical distortion, is crucial to the successful Fontan operation. Most patients are found to have acceptable pulmonary arteries after previous palliation, although some degree of distortion is not uncommon. However, in rare instances, some patients have only one functioning lung with another pulmonary artery seriously hypoplastic or atretic. For theses patients, completion of a Fontan operation will be challenging. We reported a 17-year-old girl with a single ventricle and heterotaxy syndrome and only her left lung functioning, who underwent one-lung Fontan operation with a satisfactory result. PMID:27713611

  12. Pulmonary artery dilatation: an overlooked mechanism for angina pectoris.

    PubMed

    Ginghina, Carmen; Popescu, Bogdan A; Enache, Roxana; Ungureanu, Catalina; Deleanu, Dan; Platon, Pavel

    2008-07-01

    Dilatation of the pulmonary artery may lead to the compression of adjacent structures. Of those, the extrinsic compression of the left main coronary artery is the most worrisome. We present the case of a 48-year-old woman who was diagnosed with pulmonary artery dilatation due to severe, thromboembolic pulmonary hypertension. She also had angina and coronary angiography revealed a 70% ostial stenosis of the left main coronary artery. The presence of this isolated lesion in a young woman without risk factors for atherosclerosis suggests extrinsic compression of the left main coronary artery by the dilated pulmonary artery as the likely mechanism. The patient underwent direct stenting of the left main coronary stenosis with a good result.

  13. Peripheral airways obstruction in idiopathic pulmonary artery hypertension (primary).

    PubMed

    Fernandez-Bonetti, P; Lupi-Herrera, E; Martinez-Guerra, M L; Barrios, R; Seoane, M; Sandoval, J

    1983-05-01

    The mechanical properties of the lung were studied in ten nonsmokers with idiopathic pulmonary artery hypertension (IPAH) (mean pulmonary artery pressure 65.7 +/- 30 mm Hg). In the routine lung test, residual volume was found to be abnormal (greater than 120 percent of the predicted) in seven patients, and measured airway resistance was normal in eight out of the ten patients. A decreased FEF 75-85 percent, abnormal values for the helium-air flow ratios and increased closing capacities were documented in eight of ten patients in whom lung elastic recoil was normal (six of ten) or increased (four of ten). These features suggest peripheral airways obstruction (PAO) which was also supported by histopathologic findings in three cases (one biopsy and two necropsies). The observed changes in lung compliance could be related to the behavior of the coupling of the air-space and vascular compartments. The etiology of PAO in IPAH patients is not known, but our results indicate that both the peripheral airways and the pulmonary circulation are affected. The knowledge of PAO in IPAH patients could help to better understand the observed V/Q inequality in this entity. PMID:6839814

  14. Prostanoid therapies in the management of pulmonary arterial hypertension

    PubMed Central

    LeVarge, Barbara L

    2015-01-01

    Prostacyclin is an endogenous eicosanoid produced by endothelial cells; through actions on vascular smooth-muscle cells, it promotes vasodilation. Pulmonary arterial hypertension (PAH) is characterized by elevated mean pulmonary artery pressure due to a high pulmonary vascular resistance state. A relative decrease in prostacyclin presence has been associated with PAH; this pathway has thus become a therapeutic target. Epoprostenol, the synthetic equivalent of prostacyclin, was first utilized as short-term or bridging therapy in the 1980s. Further refinement of its long-term use via continuous intravenous infusion followed. A randomized controlled trial by Barst et al in 1996 demonstrated functional, hemodynamic, and mortality benefits of epoprostenol use. This work was a groundbreaking achievement in the management of PAH and initiated a wave of research that markedly altered the dismal prognosis previously associated with PAH. Analogs of prostacyclin, including iloprost and treprostinil, exhibit increased stability and allow for an extended array of parenteral and non-parenteral (inhaled and oral) therapeutic options. This review further examines the pharmacology and clinical use of epoprostenol and its analogs in PAH. PMID:25848300

  15. Complex inheritance in Pulmonary Arterial Hypertension patients with several mutations.

    PubMed

    Pousada, Guillermo; Baloira, Adolfo; Valverde, Diana

    2016-01-01

    Pulmonary Arterial Hypertension (PAH) is a rare and progressive disease with low incidence and prevalence, and elevated mortality. PAH is characterized by increased mean pulmonary artery pressure. The aim of this study was to analyse patients with combined mutations in BMPR2, ACVRL1, ENG and KCNA5 genes and to establish a genotype-phenotype correlation. Major genes were analysed by polymerase chain reaction (PCR) and direct sequencing. Genotype-phenotype correlation was performed. Fifty-seven (28 idiopathic PAH, 29 associated PAH group I) were included. Several mutations in different genes, classified as pathogenic by in silico analysis, were present in 26% of PAH patients. The most commonly involved gene was BMPR2 (12 patients) followed by ENG gene (9 patients). ACVRL1 and KCNA5 genes showed very low incidence of mutations (5 and 1 patients, respectively). Genotype-phenotype correlation showed statistically significant differences for gender (p = 0.045), age at diagnosis (p = 0.035), pulmonary vascular resistance (p = 0.030), cardiac index (p = 0.035) and absence of response to treatment (p = 0.011). PAH is consequence of a heterogeneous constellation of genetic arrangements. Patients with several pathogenic mutations seem to display a more severe phenotype. PMID:27630060

  16. Complex inheritance in Pulmonary Arterial Hypertension patients with several mutations

    PubMed Central

    Pousada, Guillermo; Baloira, Adolfo; Valverde, Diana

    2016-01-01

    Pulmonary Arterial Hypertension (PAH) is a rare and progressive disease with low incidence and prevalence, and elevated mortality. PAH is characterized by increased mean pulmonary artery pressure. The aim of this study was to analyse patients with combined mutations in BMPR2, ACVRL1, ENG and KCNA5 genes and to establish a genotype-phenotype correlation. Major genes were analysed by polymerase chain reaction (PCR) and direct sequencing. Genotype-phenotype correlation was performed. Fifty-seven (28 idiopathic PAH, 29 associated PAH group I) were included. Several mutations in different genes, classified as pathogenic by in silico analysis, were present in 26% of PAH patients. The most commonly involved gene was BMPR2 (12 patients) followed by ENG gene (9 patients). ACVRL1 and KCNA5 genes showed very low incidence of mutations (5 and 1 patients, respectively). Genotype-phenotype correlation showed statistically significant differences for gender (p = 0.045), age at diagnosis (p = 0.035), pulmonary vascular resistance (p = 0.030), cardiac index (p = 0.035) and absence of response to treatment (p = 0.011). PAH is consequence of a heterogeneous constellation of genetic arrangements. Patients with several pathogenic mutations seem to display a more severe phenotype. PMID:27630060

  17. Response of pulmonary veins to increased intracranial pressure and pulmonary air embolization

    SciTech Connect

    Peterson, B.T.; Grauer, S.E.; Hyde, R.W.; Ortiz, C.; Moosavi, H.; Utell, M.J.

    1980-01-01

    To see whether air emboli to the lungs rather than brain compression caused these findings, anesthetized dogs received intravenous air infusions, subdural air infusions, or brain compression from balloons inflated in the subdural space. Subdural air and intravenous air resulted in similar vascular responses. Pulmonary artery pressure (Ppa) increased 160% (P < 0.01) and pulmonary venous pressure transiently rose 13 +- 5 Torr (P < 0.05) without an increase in left atrial pressure or cardiac output (Q). The end-tidal PCP/sub 2/ fell 55% (P < 0.01) and the postmortem weight of the lungs increased 55% (P < 0.05). Brain compression with a subdural balloon instead of air only caused a 20% rise in Ppa and Q without pulmonary edema. Thus, pulmonary air emboli rather than brain compression accounts for the edema and pulmonary hypertension caused by subdural air. Catheters in pulmonary veins and the left atrium showed that air emboli cause transient pulmonary venous hypertension as well as a reproducible form of noncardiogenic pulmonary edema.

  18. Electrocardiogram-Gated 320-Slice Multidetector Computed Tomography for the Measurement of Pulmonary Arterial Distensibility in Chronic Thromboembolic Pulmonary Hypertension

    PubMed Central

    Kasai, Hajime; Sugiura, Toshihiko; Tanabe, Nobuhiro; Sakurai, Yoriko; Yahaba, Misuzu; Matsuura, Yukiko; Shigeta, Ayako; Kawata, Naoko; Sakao, Seiichiro; Kasahara, Yasunori; Tatsumi, Koichiro

    2014-01-01

    Background We aimed to study whether pulmonary arterial distensibility (PAD) correlates with hemodynamic parameters in chronic thromboembolic pulmonary hypertension (CTEPH) using electrocardiogram (ECG)-gated 320-slice multidetector computed tomography (MDCT). Methods and Findings ECG-gated 320-slice MDCT and right heart catheterization (RHC) was performed in 53 subjects (60.6±11.4 years old; 37 females) with CTEPH. We retrospectively measured the minimum and maximum values of the cross sectional area (CSA) of the main pulmonary artery (mainPA), right pulmonary artery (rtPA), and left pulmonary artery (ltPA) during one heartbeat. PAD was calculated using the following formula: PAD = [(CSAmaximum−CSAminimum)/CSAmaximum]×100(%). The correlation between hemodynamic parameters and PAD was assessed. Mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) were 40.8±8.7 mmHg and 8.3±3.0 wood units, respectively. PAD values were as follows: mainPA (14.0±5.0%), rtPA (12.8±5.6%), and ltPA (9.7±4.6%). Good correlations existed between mainPAD, with mPAP (r = −0.594, p<0.001) and PVR (r = −0.659, p<0.001). The correlation coefficients between rtPAD and ltPAD with pulmonary hemodynamics were all lower or equal than for mainPAD. Conclusions PAD measured using ECG-gated 320-slice MDCT correlates with pulmonary hemodynamics in subjects with CTEPH. The mainPA is suitable for PAD measurement. PMID:25365168

  19. 4-Phenylbutyric Acid Induces Protection against Pulmonary Arterial Hypertension in Rats

    PubMed Central

    Long, Mei; Wang, Jie; Liu, Fen; Gai, Min-Tao; Aierken, Alidan; Li, Ming-Yuan; Li, Qian; Wu, Lei-Qi; Ma, Yi-Tong; Hujiaaihemaiti, Minawaer

    2016-01-01

    Background Endoplasmic reticulum (ER) stress has been implicated in the pathophysiology of various pulmonary diseases via the activation of the unfolded protein response. However, the role of ER stress in pulmonary arterial hypertension (PAH) remains unclear. The well-known chemical chaperone 4-phenylbutyric acid (4-PBA) inhibits ER stress signaling. We hypothesized that known chemical chaperones, including 4-PBA, would inhibit the activation of ER stress and prevent and/or reverse PAH. Methods and Results Male Wistar rats were randomly divided into four groups: a normal control group (NORMAL group), a PAH group, and two PAH model plus 4-PBA treatment groups. The latter two groups included rats receiving 4-PBA by gavage each day as a preventive measure (the PRE group, with PBA starting on the day of PAH induction and continuing for 4 weeks) or as a reversal measure (the REV group, with PBA starting on the third week of PAH induction and continuing for 2 weeks). The PAH model was induced by intraperitoneally administering monocrotaline. The mean pulmonary artery pressure and mean right ventricular pressure were lower in the REV and PRE groups than in the NORMAL group. Furthermore, 4-PBA improved pulmonary arterial remodeling and suppressed the expression of ER stress indicators. Conclusion Our findings indicate that PAH induces ER stress and provokes pulmonary arterial and right ventricular remodeling. Additionally, we show that attenuation of ER stress has the potential to be an effective therapeutic strategy for protecting pulmonary arteries. PMID:27304885

  20. Stiffening of the Extrapulmonary Arteries From Rats in Chronic Hypoxic Pulmonary Hypertension.

    PubMed

    Drexler, E S; Bischoff, J E; Slifka, A J; McCowan, C N; Quinn, T P; Shandas, R; Ivy, D D; Stenmark, K R

    2008-01-01

    Changes in the compliance properties of large blood vessels are critical determinants of ventricular afterload and ultimately dysfunction. Little is known of the mechanical properties of large vessels exhibiting pulmonary hypertension, particularly the trunk and right main artery. We initiated a study to investigate the influence of chronic hypoxic pulmonary hypertension on the mechanical properties of the extrapulmonary arteries of rats. One group of animals was housed at the equivalent of 5000 m elevation for three weeks and the other held at ambient conditions of ~1600 m. The two groups were matched in age and gender. The animals exposed to hypobaric hypoxia exhibited signs of pulmonary hypertension, as evidenced by an increase in the RV/(LV+S) heart weight ratio. The extrapulmonary arteries of the hypoxic animals were also thicker than those of the control population. Histological examination revealed increased thickness of the media and additional deposits of collagen in the adventitia. The mechanical properties of the trunk, and the right and left main pulmonary arteries were assessed; at a representative pressure (7 kPa), the two populations exhibited different quantities of stretch for each section. At higher pressures we noted less deformation among the arteries from hypoxic animals as compared with controls. A four-parameter constitutive model was employed to fit and analyze the data. We conclude that chronic hypoxic pulmonary hypertension is associated with a stiffening of all the extrapulmonary arteries. PMID:27096124

  1. [Drug therapy of pulmonary arterial hypertension in 2014].

    PubMed

    Aschermann, Michael; Jansa, Pavel

    2014-04-01

    Pulmonary arterial hypertension (PAH) is a primary pulmonary arteriolar disease, characterized by a progressive increase in pulmonary vascular resistance and pressure in the pulmonary circulation. It progressively leads to hypertrophy of the right ventricle and with no treatment to its failure and patient´s death. Etiology of pulmonary hypertension (PH) has been reclassified repeatedly, most recently during the 4th World Symposium on Pulmonary Hypertension held in 2008 [1]. Currently, the first group contains PAH with either unknown or known cause (systemic connective tissue disease, liver disease, congenital heart disease, HIV infection, abuse of anorexic agents). Current drug therapy of PAH is divided into conventional (anticoagulant therapy, calcium channel blockers, therapy of chronic heart failure) and specific (prostanoids, endothelium receptor antagonists, phosphodiesterase 5 inhibitors). Patients with positive vasodilator test are indicated for the high doses treatment of calcium channel blockers. Patients with negative vasodilator test are indicated for chronic anticoagulant therapy and specific drug therapy either as mono-therapy, or as combined therapy. Recent years have brought a wide range of new treatments modalities, especially in the field of pharmacotherapy. In addition, other treatment modalities have been tested, for example application of stem cells. Drugs in research include several groups: 1. vasodilators: fasudil, adrenonedullin, activators and stimulators of guanylate cyclase, vasoactive intestinal peptide (VIP); 2. Anti-inflammatory agents: inhibitor of elastase, antagonist of B cells, immunosuppressive agents, inhibitor of HDAC1; 3. agents affecting metabolism: nitrites, PPAR antagonists, antioxidants, serotonin receptor antagonist and serotonin transporter blockers, statins, inhibitors of Rho-kinase; 4. apoptosis inductors of smooth muscle cells: tyrosine-kinase inhibitors, elastase inhibitors; 5. agents influencing vascular regeneration

  2. Why there is a need to discuss pulmonary hypertension other than pulmonary arterial hypertension?

    PubMed Central

    Papathanasiou, Athanasios; Nakos, George

    2015-01-01

    Pulmonary hypertension (PH) is a condition characterized by the elevation of the mean pulmonary artery pressure above 25 mmHg and the pulmonary vascular resistance above 3 wood units. Pulmonary arterial hypertension (PAH) is an uncommon condition with severe morbidity and mortality, needing early recognition and appropriate and specific treatment. PH is frequently associated with hypoxemia, mainly chronic obstructive pulmonary disease and DPLD and/or left heart diseases (LHD), mainly heart failure with reduced or preserved ejection fraction. Although in the majority of patients with PH the cause is not PAH, a significant number of published studies are still in regard to group I PH, leading to a logical assumption that PH due to other causes is not such an important issue. So, is there a reason to discuss PH other than PAH? Chronic lung diseases, mainly chronic obstructive lung disease and DPLD, are associated with a high incidence of PH which is linked to exercise limitations and a worse prognosis. Although pathophysiological studies suggest that specific PAH therapy may benefit such patients, the results presented from small studies in regard to the safety and effectiveness of the specific PAH therapy are discouraging. PH is a common complication of left heart disease and is related to disease severity, especially in patients with reduced ejection fraction. There are two types of PH related to LHD based on diastolic pressure difference (DPD, defined as diastolic pulmonary artery pressure - mean PAWP): Isolated post-capillary PH, defined as PAWP > 15 mmHg and DPD < 7 mmHg, and combined post-capillary PH and pre-capillary PH, defined as PAWP > 15 mmHg and DPD ≥ 7 mmHg. The potential use of PAH therapies in patients with PH related to left heart disease is based on a logical pathobiological rationale. In patients with heart failure, endothelial dysfunction has been proposed as a cause of PH and hence as a target for treatment, supported by the presence of

  3. Pulmonary arterial hypertension: a review in pharmacotherapy.

    PubMed

    Patel, Bhaumik B; Feng, Ying; Cheng-Lai, Angela

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a progressive disease that remains incurable. The past 2 decades have witnessed many advances in PAH-directed therapies. More recently, 3 new oral agents have become available in the United States within the past 2 years. Treprostinil is now available in extended-release oral tablets. Macitentan is the third endothelin receptor antagonist approved for use, demonstrating benefits on morbidity and mortality among patients with PAH in an event-driven study. Riociguat is the first soluble guanylate cyclase stimulator that has been approved for use in the United States. This article reviews the clinical efficacy and safety of these 3 agents and the roles they play in the management of PAH. Additionally, we review the limitations of using surrogate markers such as change in 6-minute walk distance to assess disease progression.

  4. Unintended Pulmonary Artery Ligation during PDA Ligation.

    PubMed

    Kim, Dohun; Kim, Si-Wook; Shin, Hong-Ju; Hong, Jong-Myeon; Lee, Ji Hyuk; Han, Heon-Seok

    2016-01-01

    A 10-day-old boy was transferred to our hospital due to tachypnea. Patent ductus arteriosus (PDA), 4.8 mm in diameter, with small ASD was diagnosed on echocardiography. Surgical ligation of the ductus was performed after failure of three cycles of ibuprofen. However, the ductus remained open on routine postoperative echocardiography on the second postoperative day, and chest CT revealed inadvertent ligation of the left pulmonary artery (LPA) rather than the PDA. Emergent operation successfully reopened the clipped LPA and ligated the ductus on the same (second postoperative) day.Mechanical ventilator support was weaned on postoperative day 21, and the baby was discharged on postoperative day 47 with a normal left lung shadow. PMID:27585199

  5. Reconstruction of the bronchus and pulmonary artery

    PubMed Central

    D’Andrilli, Antonio; Venuta, Federico; Rendina, Erino Angelo

    2016-01-01

    Bronchovascular reconstructive procedures employed in order to avoid pneumonectomy (PN) in patients functionally unsuitable have provided, over time, excellent results, similar or even better than those obtained by PN. In recent years, new successful techniques have been developed that pertain in particular the prevention of major complications and the reconstruction of the pulmonary artery (PA). Encouraging data from increasing number of published experiences support the choice of parenchymal sparing procedures for lung cancer also in patients with good functional reserve. This is even more true if considering trials published in the last 10 years, thus indicating that improved outcome can be achieved with increased experience in reconstructive techniques and perioperative management. This article discusses the main technical aspects and results of literature. PMID:26981268

  6. Effects of baicalin on collagen Ι and collagen ΙΙΙ expression in pulmonary arteries of rats with hypoxic pulmonary hypertension

    PubMed Central

    LIU, PANPAN; YAN, SHUANGQUAN; CHEN, MAYUN; CHEN, ALI; YAO, DAN; XU, XIAOMEI; CAI, XUEDING; WANG, LIANGXING; HUANG, XIAOYING

    2015-01-01

    The synthesis and accumulation of collagen play an important role in the formation and progression of hypoxic pulmonary hypertension. Baicalin has been reported to prevent bleomycin-induced pulmonary fibrosis. However, the role of baicalin in the treatment of pulmonary hypertension remains unknown. A disintegrin and metalloprotease with thrombospondin type-1 motif (ADAMTS-1) is a secreted enzyme that acts on a wide variety of extracellular matrix (ECM) substrates associated with vascular diseases. In this study, we aimed to investigate the effects of baicalin on the synthesis of collagen I in rats with pulmonary hypertension induced by hypoxia and the changes in ADAMTS-1 expression. A total of 24 Sprague Dawley rats were randomly assigned to 3 groups as follows: the control group (C), the hypoxia group (H) and the hypoxia + baicalin group (B). The rats in groups H and B were kept in a normobaric hypoxic chamber for 4 weeks, and the rats in group C were exposed to room air. We measured the hemodynamic indexes, including mean pulmonary artery pressure (mPAP), mean systemic (carotid) artery pressure (mSAP), and then calculated the mass ratio of right ventricle to left ventricle plus septum [RV/(LV + S)] to reflect the extent of right ventricular hypertrophy. We measured the mRNA and protein expression levels of type I collagen, type III collagen and ADAMTS-1 by hybridization in situ, and immunohistochemistry and western blot analysis, respectively. The results revealed that treatment with baicalin significantly reduced pulmonary artery pressure and attenuated the remodeling of the pulmonary artery under hypoxic conditions by increasing the expression of ADAMTS-1, so that the synthesis of type I collagen and its mRNA expression were inhibited. In conclusion, baicalin effectively inhibits the synthesis of collagen I in pulmonary arteries and this is associated with an increase in the expression of ADAMTS-1. Thus, treatment with baicalin may be an effective method for

  7. Epistatic interactions in idiopathic pulmonary arterial hypertension

    PubMed Central

    Vadapalli, Shivani; Satyanarayana, M. L.; Chaitra, K. L.; Rani, H. Surekh; Sastry, B.K.S.; Nallari, Pratibha

    2012-01-01

    BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) is a poorly understood complex disorder, which results in progressive remodeling of the pulmonary artery that ultimately leads to right ventricular failure. A two-hit hypothesis has been implicated in pathogenesis of IPAH, according to which the vascular abnormalities characteristic of PAH are triggered by the accumulation of genetic and/or environmental insults in an already existing genetic background. The multifactor dimensionality reduction (MDR) analysis is a statistical method used to identify gene–gene interaction or epistasis and gene–environment interactions that are associated with a particular disease. The MDR method collapses high-dimensional genetic data into a single dimension, thus permitting interactions to be detected in relatively small sample sizes. AIM: To identify and characterize polymorphisms/genes that increases the susceptibility to IPAH using MDR analysis. MATERIALS AND METHODS: A total of 77 IPAH patients and 100 controls were genotyped for eight polymorphisms of five genes (5HTT, EDN1, NOS3, ALK-1, and PPAR-γ2). MDR method was adopted to determine gene–gene interactions that increase the risk of IPAH. RESULTS: With MDR method, the single-locus model of 5HTT (L/S) polymorphism and the combination of 5HTT(L/S), EDN1(K198N), and NOS3(G894T) polymorphisms in the three-locus model were attributed to be the best models for predicting susceptibility to IPAH, with a P value of 0.05. CONCLUSION: MDR method can be useful in understanding the role of epistatic and gene–environmental interactions in pathogenesis of IPAH. PMID:22754222

  8. Pulmonary artery segmentation and quantification in sickle cell associated pulmonary hypertension

    NASA Astrophysics Data System (ADS)

    Linguraru, Marius George; Mukherjee, Nisha; Van Uitert, Robert L.; Summers, Ronald M.; Gladwin, Mark T.; Machado, Roberto F.; Wood, Bradford J.

    2008-03-01

    Pulmonary arterial hypertension is a known complication associated with sickle-cell disease; roughly 75% of sickle cell disease-afflicted patients have pulmonary arterial hypertension at the time of death. This prospective study investigates the potential of image analysis to act as a surrogate for presence and extent of disease, and whether the size change of the pulmonary arteries of sickle cell patients could be linked to sickle-cell associated pulmonary hypertension. Pulmonary CT-Angiography scans from sickle-cell patients were obtained and retrospectively analyzed. Randomly selected pulmonary CT-Angiography studies from patients without sickle-cell anemia were used as negative controls. First, images were smoothed using anisotropic diffusion. Then, a combination of fast marching and geodesic active contours level sets were employed to segment the pulmonary artery. An algorithm based on fast marching methods was used to compute the centerline of the segmented arteries. From the centerline, the diameters at the pulmonary trunk and first branch of the pulmonary arteries were measured automatically. Arterial diameters were normalized to the width of the thoracic cavity, patient weight and body surface. Results show that the pulmonary trunk and first right and left pulmonary arterial branches at the pulmonary trunk junction are significantly larger in diameter with increased blood flow in sickle-cell anemia patients as compared to controls (p values of 0.0278 for trunk and 0.0007 for branches). CT with image processing shows great potential as a surrogate indicator of pulmonary hemodynamics or response to therapy, which could be an important tool for drug discovery and noninvasive clinical surveillance.

  9. Pulmonary Atresia with Ventricular Septal Defect and Major Aortopulmonary Collaterals Associated with Left Pulmonary Artery Interruption

    PubMed Central

    Mun, Da-Na; Park, Chun Soo; Kim, Young-Hwue; Goo, Hyun Woo

    2016-01-01

    A multistage plan and multidisciplinary approach are the keys to successful repair in patients with pulmonary atresia (PA) with ventricular septal defect (VSD) and major aortopulmonary collateral arteries (MAPCAs). In this article, we present a multidisciplinary approach adopted to treat a patient with PA with VSD and MAPCAs associated with left pulmonary artery interruption. PMID:27733998

  10. A Contemporary Approach to Pulmonary Arterial Hypertension.

    PubMed

    Krishnan, Udhay; Horn, Evelyn M

    2016-09-01

    In recent years, there have been major changes in the landscape of pulmonary arterial hypertension therapy with the introduction of novel agents and innovative treatment strategies for this progressive disease. The aim of this review is to discuss the evolution in trial design in this field and highlight the salient features of recently published studies. We also summarize our approach to therapy selection in this chronic disease and identify areas for future exploration. The therapeutic armamentarium now includes 13 approved therapies. While most of these agents have been studied in small, short-term trials using the 6-min walk distance as a primary endpoint, there has been a shift in recent years toward larger, long-term, event-driven trials that utilize combined morbidity and mortality endpoints. The SERAPHIN and GRIPHON trials were two such studies, which led to the approval of the dual endothelin-receptor antagonist macitentan and the selective prostacyclin receptor antagonist selexipag, respectively. Other event-driven trials, like AMBITION and COMPASS-2, have provided valuable insight into the use of combined oral therapies in symptomatic patients. In conclusion, despite being a more manageable disease in the modern treatment era, pulmonary hypertension is still associated with considerable morbidity and much more work remains to be done in this field. Important questions remain about the most optimal way to manage patients and conduct trials going forward. PMID:27491673

  11. Inflammation and immunity in the pathogenesis of pulmonary arterial hypertension.

    PubMed

    Rabinovitch, Marlene; Guignabert, Christophe; Humbert, Marc; Nicolls, Mark R

    2014-06-20

    This review summarizes an expanding body of knowledge indicating that failure to resolve inflammation and altered immune processes underlie the development of pulmonary arterial hypertension. The chemokines and cytokines implicated in pulmonary arterial hypertension that could form a biomarker platform are discussed. Pre-clinical studies that provide the basis for dysregulated immunity in animal models of the disease are reviewed. In addition, we present therapies that target inflammatory/immune mechanisms that are currently enrolling patients, and discuss others in development. We show how genetic and metabolic abnormalities are inextricably linked to dysregulated immunity and adverse remodeling in the pulmonary arteries. PMID:24951765

  12. Optical coherence tomography of the pulmonary arteries: A systematic review.

    PubMed

    Jorge, Elisabete; Baptista, Rui; Calisto, João; Faria, Henrique; Monteiro, Pedro; Pan, Manuel; Pêgo, Mariano

    2016-01-01

    Optical coherence tomography (OCT) is an imaging technique extensively used for visualizing the coronary circulation, where it assists clinical decision-making. Along with the new interventional procedures being introduced for pulmonary vascular disease, there is an increasing need for intravascular imaging of the pulmonary arteries. Additionally, measurements of the wall thickness of the pulmonary arteries of patients with various types of pulmonary hypertension (PH) may provide relevant diagnostic and prognostic information. The aim of this review is to summarize all the available evidence on the use of OCT for imaging the pulmonary bed and to describe a simple protocol for OCT image acquisition. We conducted a systematic review of the literature using electronic reference databases through February 2015 (MEDLINE, Cochrane Library, Web of Knowledge, and references cited in other studies) and the search terms "optical coherence tomography," "pulmonary hypertension," and "pulmonary arteries." Studies in which OCT was used to image the pulmonary vessels were considered for inclusion. We identified 14 studies reporting OCT imaging data from the pulmonary arteries. OCT was able to identify intravascular thrombi in patients with chronic thromboembolic PH (CTEPH), and an increase in vessel wall thickness was found in most patients with PH, compared with the controls. OCT has also been reported to be useful for the selection of balloon size in the setting of balloon pulmonary angioplasty for CTEPH. The main limitations include lack of standardization, little data on outcomes, cost, and the technical limitations involved in visualizing small-diameter (<1mm) pulmonary vessels. OCT has become a potential tool for the in vivo study of vascular changes in the pulmonary arteries, and may provide additional information in the assessment of patients with PH. Prospective high-quality studies assessing the safety, validity, and clinical impact of OCT imaging for pulmonary vessels

  13. [Stent dilatation of pulmonary artery stenosis in the adult patient with congenital heart disease].

    PubMed

    Benito, F; Oliver, J M

    2000-04-01

    Stents have been previously used to resolve stenoses of branch pulmonary arteries in children. We report 3 patients, with mean age of 22.7 +/- 4.7 years and pulmonary artery stenosis after palliative surgery in whom we implanted seven stents in four procedures. Six P308 Palmaz, overlapped two by two, were implanted by venous femoral approach in two patients, receiving four in the first case and the other two in the third case. In the second case, a NIR type stent was implanted through femoral artery in the right pulmonary artery. Stenosis diameter enlarged from 5.3 +/- 2.3 to 14.4 +/- 4.2 mm and the pressure gradient through stenosis fell from 40.6 +/- 15.3 to 6. 5 +/- 5 mmHg. All stents are well deployed and there are two patients waiting for total correction (previously not feasible) during a follow-up of 30.6 +/- 6.1 months.

  14. Developments in pulmonary arterial hypertension-targeted therapy for chronic thromboembolic pulmonary hypertension.

    PubMed

    Hadinnapola, Charaka; Pepke-Zaba, Joanna

    2015-10-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease characterised by the presence of organised chronic thromboembolic material occluding the proximal pulmonary arteries and a vasculopathy in the distal pulmonary arterial tree. Pulmonary endarterectomy (PEA) is a potential cure for many patients with CTEPH. However, PEA is not suitable for patients with a significant distal distribution of chronic thromboembolic material or with significant comorbidities. Also, a proportion of patients are left with residual CTEPH post PEA. Until recently, pulmonary arterial hypertension-targeted therapies have been used off licence to treat patients with inoperable or residual CTEPH. The CHEST1 study investigated the use of riociguat and was the first randomised controlled trial to show efficacy in inoperable or residual CTEPH. In this review, we explore the pathophysiology of CTEPH and review the current trial evidence for pulmonary arterial hypertension-targeted therapies. We also include a discussion of physiological considerations that require further investigation.

  15. A Pulmonary Sequestered Segment with an Aberrant Pulmonary Arterial Supply: A Case of Unique Anomaly

    PubMed Central

    Kim, Minchul; An, Jin Kyung; Jung, Yoon Young; Choi, Yun Sun

    2016-01-01

    We presented a rare case of a 64-year-old man with a combined anomaly of the bronchus and pulmonary artery that was detected incidentally. Computed tomography showed a hyperlucent, aerated sequestered segment of the right lower lung with an independent ectopic bronchus, which had no connection to the other airway. The affected segment was supplied by its own aberrant pulmonary artery branch from the right pulmonary trunk. This anomaly cannot be classified with any of the previously reported anomalies. PMID:26957918

  16. Transcatheter Embolization of Pulmonary Artery False Aneurysm Associated with Primary Pulmonary Hypertension

    SciTech Connect

    Hiraki, T. Kanazawa, S.; Mimura, H.; Yasui, K.; Okumura, Y.; Dendo, S.; Yoshimura, K.; Takahara, M.; Hiraki, Y.

    2004-03-15

    A 29-year-old woman with primary pulmonary hypertension presented with recurrent hemoptysis. Contrast-enhanced CT of the chest demonstrated the enhanced mass surrounded by consolidation related to parenchymal hemorrhage. Pulmonary angiography suggested that the mass was a pulmonary artery false aneurysm. After a microcatheter was superselectively inserted into the parent artery of the falseaneurysm, the false aneurysm was successfully treated by transcatheterembolization with coils. Her hemoptysis has never recurred.

  17. Genetics Home Reference: pulmonary arterial hypertension

    MedlinePlus

    ... Primary pulmonary hypertension 2 Primary pulmonary hypertension 3 Primary pulmonary hypertension 4 ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific articles on PubMed (1 link) PubMed OMIM (4 links) ...

  18. Comparative Effectiveness of Oral Medications for Pulmonary Arterial Hypertension.

    PubMed

    Igarashi, Ataru; Inoue, Sachie; Ishii, Tomonori; Tsutani, Kiichiro; Watanabe, Hiroshi

    2016-07-27

    Pulmonary arterial hypertension (PAH) is a disease that imposes a significant burden on patients. Although multiple treatment options for PAH are available, head-to-head comparisons are difficult to conduct. Network meta-analysis (NMA) can be a useful alternative for direct comparison to estimate the relative effectiveness of multiple treatments. The objective of the present study was to conduct a systematic review and NMA to evaluate the relative effectiveness among oral PAH medications.Data collection was performed by searching the Cochrane Central Register of Controlled Trials (CENTRAL) and Ichushi-Web. Randomized controlled trials (RCTs) assessing at least 1 of the following 3 outcome measurements; 6-minute walk distance test (6MWD), WHO functional class (WHOFC), and mean pulmonary artery pressure (mPAP) were included (PROSPERO registration number: CRD42015016557). Outcomes were evaluated by estimating the differences in the mean change from baseline or by estimating the odds ratios. Analyses were performed using WinBUGS 1.4.3.Seven double-blind RCTs were eligible. NMA results showed similar improvements in 6MWD for all medications assessed. Bosentan and sildenafil caused a statistically significant improvement in WHOFC compared to other medications.The relative effectiveness of oral PAH medications could be compared using NMA, which suggested the superiority of bosentan and sildenafil in the improvement of WHOFC. PMID:27385603

  19. Pulmonary artery perfusion versus no pulmonary perfusion during cardiopulmonary bypass in patients with COPD: a randomised clinical trial

    PubMed Central

    Buggeskov, Katrine B; Sundskard, Martin M; Jonassen, Thomas; Andersen, Lars W; Secher, Niels H; Ravn, Hanne B; Steinbrüchel, Daniel A; Jakobsen, Janus C; Wetterslev, Jørn

    2016-01-01

    Introduction Absence of pulmonary perfusion during cardiopulmonary bypass (CPB) may be associated with reduced postoperative oxygenation. Effects of active pulmonary artery perfusion were explored in patients with chronic obstructive pulmonary disease (COPD) undergoing cardiac surgery. Methods 90 patients were randomised to receive pulmonary artery perfusion during CPB with either oxygenated blood (n=30) or histidine-tryptophan-ketoglutarate (HTK) solution (n=29) compared with no pulmonary perfusion (n=31). The coprimary outcomes were the inverse oxygenation index compared at 21 hours after starting CPB and longitudinally in a mixed-effects model (MEM). Secondary outcomes were tracheal intubation time, serious adverse events, mortality, days alive outside the intensive care unit (ICU) and outside the hospital. Results 21 hours after starting CPB patients receiving pulmonary artery perfusion with normothermic oxygenated blood had a higher oxygenation index compared with no pulmonary perfusion (mean difference (MD) 0.94; 95% CI 0.05 to 1.83; p=0.04). The blood group had also a higher oxygenation index both longitudinally (MEM, p=0.009) and at 21 hours (MD 0.99; CI 0.29 to 1.69; p=0.007) compared with the HTK group. The latest result corresponds to a difference in the arterial partial pressure of oxygen of 23 mm Hg with a median fraction of inspired oxygen of 0.32. Yet the blood or HTK groups did not demonstrate a longitudinally higher oxygenation index compared with no pulmonary perfusion (MEM, p=0.57 and 0.17). Similarly, at 21 hours there was no difference in the oxygenation index between the HTK group and those no pulmonary perfusion (MD 0.06; 95% CI −0.73 to 0.86; p=0.87). There were no statistical significant differences between the groups for the secondary outcomes. Discussion Pulmonary artery perfusion with normothermic oxygenated blood during cardiopulmonary bypass appears to improve postoperative oxygenation in patients with COPD undergoing

  20. Pulmonary artery perfusion versus no pulmonary perfusion during cardiopulmonary bypass in patients with COPD: a randomised clinical trial

    PubMed Central

    Buggeskov, Katrine B; Sundskard, Martin M; Jonassen, Thomas; Andersen, Lars W; Secher, Niels H; Ravn, Hanne B; Steinbrüchel, Daniel A; Jakobsen, Janus C; Wetterslev, Jørn

    2016-01-01

    Introduction Absence of pulmonary perfusion during cardiopulmonary bypass (CPB) may be associated with reduced postoperative oxygenation. Effects of active pulmonary artery perfusion were explored in patients with chronic obstructive pulmonary disease (COPD) undergoing cardiac surgery. Methods 90 patients were randomised to receive pulmonary artery perfusion during CPB with either oxygenated blood (n=30) or histidine-tryptophan-ketoglutarate (HTK) solution (n=29) compared with no pulmonary perfusion (n=31). The coprimary outcomes were the inverse oxygenation index compared at 21 hours after starting CPB and longitudinally in a mixed-effects model (MEM). Secondary outcomes were tracheal intubation time, serious adverse events, mortality, days alive outside the intensive care unit (ICU) and outside the hospital. Results 21 hours after starting CPB patients receiving pulmonary artery perfusion with normothermic oxygenated blood had a higher oxygenation index compared with no pulmonary perfusion (mean difference (MD) 0.94; 95% CI 0.05 to 1.83; p=0.04). The blood group had also a higher oxygenation index both longitudinally (MEM, p=0.009) and at 21 hours (MD 0.99; CI 0.29 to 1.69; p=0.007) compared with the HTK group. The latest result corresponds to a difference in the arterial partial pressure of oxygen of 23 mm Hg with a median fraction of inspired oxygen of 0.32. Yet the blood or HTK groups did not demonstrate a longitudinally higher oxygenation index compared with no pulmonary perfusion (MEM, p=0.57 and 0.17). Similarly, at 21 hours there was no difference in the oxygenation index between the HTK group and those no pulmonary perfusion (MD 0.06; 95% CI −0.73 to 0.86; p=0.87). There were no statistical significant differences between the groups for the secondary outcomes. Discussion Pulmonary artery perfusion with normothermic oxygenated blood during cardiopulmonary bypass appears to improve postoperative oxygenation in patients with COPD undergoing

  1. Pulmonary artery aneurysm in Behcet's disease: a case report.

    PubMed

    Kasikcioglu, Erdem; Akhan, Hulya; Cuhadaroglu, Caglar; Erkan, Feyza

    2004-05-01

    The pulmonary artery is the second most common site of arterial involvement in Behcet's disease. A 32-year-old man presented with bilateral ankle edema, abdominal discomfort, and hemoptysis. He had a history of recurrent oral and genital aphthous ulcerations for 1 year. The diagnosis of Behcet's disease was made on the basis of the criteria published by the International Study Group for Behcet's Disease. His chest X-ray revealed left hilar enlargement. A helical computed tomography (CT) scan showed a pulmonary aneurysm with intramural thrombosis in the left pulmonary artery and enlarged hepatic veins. Treatment with colchicine and cyclophosphamide was given for 24 months, and helical thoracic CT was performed again. Helical CT showed that the pulmonary aneurysm was reduced by treatment. Helical CT could be used in Behcet's disease for the diagnosis and follow-up of pulmonary involvement.

  2. Direct communication between right pulmonary artery and left atrium.

    PubMed

    Alva, C; Jiménez Arteaga, S; Gómez, F D; Sánchez Soberanes, A; Ortegón, J; Campos, M; Ledesma, M; Argüero, R

    2000-01-01

    A case of direct communication between right pulmonary artery and left atrium is reported. The diagnosis was made before surgical correction. A surgical ligation of the fistula resolved the cyanosis of the patient. Selective angiocardiogram of the right pulmonary artery 4 months after surgery revealed no residual shunt. This very rare malformation should be considered in the clinical setting of unexplained cyanosis. This is the number 50 case reported in the literature.

  3. Proximal Interruption of the Pulmonary Artery: A Case Series.

    PubMed

    Anand, S H; Jasper, Anitha; Mani, Sunithi Elizabeth; Joseph, Elizabeth; Mathai, John

    2015-12-01

    We present a few cases of Proximal Interruption of the Pulmonary Artery, an uncommon developmental anomaly associated with congenital heart disease. The cases had varied clinical presentations. Chest radiograph showed a hypoplastic lung with an ipsilateral small hilum on the side of the interruption and hyperinflation of the contralateral lung. Contrast CT confirmed the diagnosis, demonstrating non-visualization of the left or right pulmonary artery, and other related findings. PMID:26816968

  4. Isolated large vessel pulmonary vasculitis as a cause of chronic obstruction of the pulmonary arteries

    PubMed Central

    Hagan, Guy; Gopalan, Deepa; Church, Colin; Rassl, Doris; Mukhtyar, Chetan; Wistow, Trevor; Lang, Chim; Sivasothy, Pasupathy; Stewart, Susan; Jayne, David; Sheares, Karen; Tsui, Steven; Jenkins, David P.; Pepke-Zaba, Joanna

    2011-01-01

    Isolated pulmonary artery involvement by large vessel vasculitis is rare. This case report describes two patients with large vessel pulmonary vasculitis initially thought to have chronic thromboembolic pulmonary hypertension who had their diagnosis revised following pulmonary endarterectomy surgery. Advances in imaging techniques such as positron emission tomography and magnetic resonance imaging have permitted complementary radiological methods of diagnosis and follow up of large vessel disease and these are discussed in conjunction with the immunosuppressive and operative management of these patients. PMID:22140633

  5. [Pulmonary artery sling and single ventricle treated with a simultaneous operation of slide tracheoplasty, left pulmonary artery reimplantation, and bidirectional cavo-pulmonary shunt].

    PubMed

    Kawahito, Tomohisa; Takano, Shinji; Egawa, Yoshiyasu; Iwamura, Yoshinobu; Nakahara, Yasuo; Nii, Akira; Ohnishi, Tatsuya; Miyagi, Yuhichi; Terada, Kazuya; Ohta, Akira

    2013-07-01

    Pulmonary artery sling is frequently combined with tracheal stenosis, and occasionally combined with congenital heart defects. However, there are few reports of successfully treated cases that were combined with single ventricle. In this article, we report a successfully treated case of pulmonary artery sling combined with tracheal stenosis, single ventricle, pulmonary atresia, vascular ring, and bilateral superior vena cava. A male infant was referred to our hospital for central cyanosis, and was diagnosed with single ventricle (tricuspid stenosis, multiple ventricular septal defect, and hypoplastic right ventricle)with pulmonary atresia by echocardiogram. Tracheal stenosis was shown at cardiac catheterization. Pulmonary artery sling and tracheal diverticulum were diagnosed by computed tomography (CT) and magnetic resonance imaging(MRI)examination. Furthermore, the patient was complicated by vascular ring, which consisted of right aortic arch, an aberrant left subclavian artery, and patent ductus arteriosus, and this ductus arteriosus was connected to the left subclavian artery and pulmonary arterial trunk. After 6 months of medical treatment, including continuous infusion of prostaglandin, re-evaluation was performed by cardiac catheterization. We considered that bidirectional cavo-pulmonary shunt was appropriate for the patient since his pulmonary vasculature had matured well. An operation was performed under the use of cardio-pulmonary bypass. Release of vascular ring by division of the ductus, bilateral bidirectional cavo-pulmonary shunt, and a slide tracheoplasty for tracheal stenosis were performed simultaneously. His recovery was uneventful, and he is currently waiting to receive a Fontan-type operation.

  6. Sublingual Microcirculation in Pulmonary Arterial Hypertension

    PubMed Central

    Dababneh, Luma; Cikach, Frank; Alkukhun, Laith; Dweik, Raed A.

    2014-01-01

    Rationale: Pulmonary arterial hypertension (PAH) is a pulmonary vasculopathy that leads to failure of the right ventricle and premature death. Objectives: To determine whether the sublingual microcirculation is affected in patients with PAH compared with healthy age- and sex-matched control subjects. Methods: Using the CapiScope Handheld Video Capillaroscope we measured the sublingual microvasculature density, flow index, tortuosity, and curvature. Videos were acquired immediately after right heart catheterization, and determinations were made off-line by investigators blinded to the group assignment or hemodynamics. Measurements and Main Results: In this cross-sectional pilot study, we included 26 patients with PAH (age, mean ± SD, 56.7 ± 10 yr; 77% women) and 14 healthy control subjects (age, 53.1 ± 12 yr; 71% women). Sublingual microvasculature flow index was lower (2 ± 0.66 vs. 2.7 ± 0.37, P < 0.001) with higher heterogeneity index (0.63 ± 0.63 vs. 0.25 ± 0.25, P = 0.04) in patients with PAH than control subjects. Microvasculature density was similar between the groups, but tortuosity was more pronounced in patients than control subjects (tort 0: 45 ± 19 vs. 23.6 ± 12, P = 0.001 and tort 1: 0.2 ± 0.16 vs. 0.06 ± 0.04, P < 0.001). Conclusions: Patients with PAH showed lower sublingual microvasculature flow index and higher tortuosity compared with healthy age- and sex-matched control subjects. Further investigations are needed to assess whether this methodology can provide information on disease prognosis and/or response to therapy in this condition. PMID:24601682

  7. Prognostic Role of Pulmonary Arterial Capacitance in Advanced Heart Failure

    PubMed Central

    Dupont, Matthias; Mullens, Wilfried; Skouri, Hadi N.; Abrahams, Zuheir; Wu, Yuping; Taylor, David O.; Starling, Randall C.; Tang, W. H. Wilson

    2012-01-01

    Background RV dysfunction frequently occurs and independently prognosticates in left-sided HF. It is not clear which right ventricular (RV) afterload measure has the greatest impact on RV function and prognosis. We examined the determinants, prognostic role and response to treatment of pulmonary arterial capacitance (PAC, ratio of stroke volume over pulmonary pulse pressure), in relation to pulmonary vascular resistance (PVR) in heart failure (HF). Methods and Results We reviewed 724 consecutive patients with HF who underwent right heart catheterization between 2000 and 2005. Changes in PAC were explored in an independent cohort of 75 subjects treated for acute decompensated HF. PAC showed a strong inverse relation with PVR (r=−0.64) and wedge pressure (r=−0.73), and provides stronger prediction of significant RV failure than PVR (AUC ROC 0.74 vs 0.67 respectively, p = 0.003). During a mean follow-up of 3.2 ± 2.2 years, both lower PAC (p<0.0001) and higher PVR (p<0.0001) portend more adverse clinical events (all-cause mortality and cardiac transplantation). In multivariate analysis, PAC (but not PVR) remains an independent predictor (Hazard ratio =0.92 [95% confidence interval: 0.84–1.0, p=0.037]). Treatment of HF resulted in a decrease in PVR (270±165 to 211±88 dynes·sec·cm−5, p=0.002), a larger increase in PAC (1.65±0.64 to 2.61±1.42 ml/mmHg, p<0.0001), leading to an increase in pulmonary arterial time constant (PVR × PAC) (0.29±0.12 to 0.37±0.15 sec, p<0.0001). Conclusions PAC bundles the effects of PVR and left sided filling pressures on RV afterload, explaining its strong relation with RV dysfunction, poor long-term prognosis, and response to therapy. PMID:23087402

  8. Notch3 signaling promotes the development of pulmonary arterial hypertension.

    PubMed

    Li, Xiaodong; Zhang, Xiaoxue; Leathers, Robin; Makino, Ayako; Huang, Chengqun; Parsa, Pouria; Macias, Jesus; Yuan, Jason X-J; Jamieson, Stuart W; Thistlethwaite, Patricia A

    2009-11-01

    Notch receptor signaling is implicated in controlling smooth muscle cell proliferation and in maintaining smooth muscle cells in an undifferentiated state. Pulmonary arterial hypertension is characterized by excessive vascular resistance, smooth muscle cell proliferation in small pulmonary arteries, leading to elevation of pulmonary vascular resistance, right ventricular failure and death. Here we show that human pulmonary hypertension is characterized by overexpression of NOTCH3 in small pulmonary artery smooth muscle cells and that the severity of disease in humans and rodents correlates with the amount of NOTCH3 protein in the lung. We further show that mice with homozygous deletion of Notch3 do not develop pulmonary hypertension in response to hypoxic stimulation and that pulmonary hypertension can be successfully treated in mice by administration of N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), a gamma-secretase inhibitor that blocks activation of Notch3 in smooth muscle cells. We show a mechanistic link from NOTCH3 receptor signaling through the Hairy and enhancer of Split-5 (HES-5) protein to smooth muscle cell proliferation and a shift to an undifferentiated smooth muscle cell phenotype. These results suggest that the NOTCH3-HES-5 signaling pathway is crucial for the development of pulmonary arterial hypertension and provide a target pathway for therapeutic intervention. PMID:19855400

  9. Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery in Adulthood: Challenges and Outcomes

    PubMed Central

    Kothari, Jignesh; Lakhia, Ketav; Solanki, Parth; Parmar, Divyakant; Boraniya, Hiren; Patel, Sanjay

    2016-01-01

    Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is an extremely rare, potentially fatal, congenital anomaly with a high mortality rate in the first year of life. It occurs rarely in adulthood and may appear with malignant ventricular a rrhythmia or sudden death. We report a case of a 49-year-old woman with ALCAPA who presented with dyspnea on exertion. Management was coronary artery bypass grafting to the left anterior descending artery and obtuse marginal arteries, closure of the left main coronary artery ostium, and reestablishment of the dual coronary artery system. PMID:27734000

  10. Aortic homograft for pulmonary artery augmentation in single lung transplantation.

    PubMed

    Rueda, Pablo; Morales, Jose; Guzman, Enrique; Tellez, Jose L; Niebla, Benito A; Avalos, Alejandro; Patiño, Hilda

    2005-06-01

    We present a case of unilateral lung transplantation in which a segment of the donor's descending aorta was used as a homograft for pulmonary artery augmentation in the donor lung. This technique can be used when the donor's lung artery has been cut at the base of the hilum during the harvesting procedure.

  11. CD133+ cells in pulmonary arterial hypertension.

    PubMed

    Foris, Vasile; Kovacs, Gabor; Marsh, Leigh M; Bálint, Zoltán; Tötsch, Martin; Avian, Alexander; Douschan, Philipp; Ghanim, Bahil; Klepetko, Walter; Olschewski, Andrea; Olschewski, Horst

    2016-08-01

    Circulating mononuclear cells may play an important role for the vascular remodelling in pulmonary arterial hypertension (PAH), but studies addressing multiple progenitor populations are rare and inconsistent.We used a comprehensive fluorescence-activated cell sorting analysis of circulating mononuclear cells in 20 PAH patients and 20 age- and sex-matched controls, and additionally analysed CD133(+) cells in the lung tissue of five PAH transplant recipients and five healthy controls (donor lungs).PAH patients were characterised by increased numbers of circulating CD133(+) cells and lymphopenia as compared with control. In PAH, CD133(+) subpopulations positive for CD117 or CD45 were significantly increased, whereas CD133(+)CD309(+), CD133(+)CXCR2(+) and CD133(+)CD31(+) cells were decreased. In CD133(+) cells, SOX2, Nanog, Ki67 and CXCR4 were not detected, but Oct3/4 mRNA was present in both PAH and controls. In the lung tissue, CD133(+) cells included three main populations: type 2 pneumocytes, monocytes and undifferentiated cells without significant differences between PAH and controls.In conclusion, circulating CD133(+) progenitor cells are elevated in PAH and consist of phenotypically different subpopulations that may be up- or downregulated. This may explain the inconsistent results in the literature. CD133(+) type 2 pneumocytes in the lung tissue are not associated with circulating CD133(+) mononuclear cells. PMID:27103380

  12. Updated treatment algorithm of pulmonary arterial hypertension.

    PubMed

    Galiè, Nazzareno; Corris, Paul A; Frost, Adaani; Girgis, Reda E; Granton, John; Jing, Zhi Cheng; Klepetko, Walter; McGoon, Michael D; McLaughlin, Vallerie V; Preston, Ioana R; Rubin, Lewis J; Sandoval, Julio; Seeger, Werner; Keogh, Anne

    2013-12-24

    The demands on a pulmonary arterial hypertension (PAH) treatment algorithm are multiple and in some ways conflicting. The treatment algorithm usually includes different types of recommendations with varying degrees of scientific evidence. In addition, the algorithm is required to be comprehensive but not too complex, informative yet simple and straightforward. The type of information in the treatment algorithm are heterogeneous including clinical, hemodynamic, medical, interventional, pharmacological and regulatory recommendations. Stakeholders (or users) including physicians from various specialties and with variable expertise in PAH, nurses, patients and patients' associations, healthcare providers, regulatory agencies and industry are often interested in the PAH treatment algorithm for different reasons. These are the considerable challenges faced when proposing appropriate updates to the current evidence-based treatment algorithm.The current treatment algorithm may be divided into 3 main areas: 1) general measures, supportive therapy, referral strategy, acute vasoreactivity testing and chronic treatment with calcium channel blockers; 2) initial therapy with approved PAH drugs; and 3) clinical response to the initial therapy, combination therapy, balloon atrial septostomy, and lung transplantation. All three sections will be revisited highlighting information newly available in the past 5 years and proposing updates where appropriate. The European Society of Cardiology grades of recommendation and levels of evidence will be adopted to rank the proposed treatments. PMID:24355643

  13. Idiopathic pulmonary fibrosis and coronary artery disease.

    PubMed

    Cicchitto, Gaetano; Musella, Valentina; Acitorio, Maria; Capuano, Nicola; Fiorenzano, Giuseppe; Owen, Caroline A; Polverino, Mario; Polverino, Francesca

    2014-01-01

    Idiopathic pulmonary fibrosis (IPF) is defined as a chronic fibrosing interstitial disease of unknown cause, limited to the lungs, and associated with the histopathologic and/or radiologic pattern of usual interstitial pneumonia (UIP); it generally progresses into respiratory failure and death. Although progression of the disease is the most common cause of death, there are increasing reports of its association with other pathologies has been reported: e.g., IPF patients seem more susceptible to cardiovascular diseases. Therefore, other pathologies might also influence the natural course. In this paper, we describe a case of IPF and coronary artery disease (CAD). We emphasize the importance of cardiopulmonary exercise test (CPET) as a useful procedure to monitor disease progression in IPF patients. We also stress the importance of a careful analysis of variables measured for an accurate interpretation of the clinical picture and an improvement of the clinical management of patients. Moreover, we suggest that a careful assessment of CPET parameters may additionally help in the early detection of high cardiovascular ischemic risk.

  14. Incidentally detected unilateral pulmonary artery agenesis with pulmonary hypoplasia in a 67 year old woman

    PubMed Central

    Muthusami, Prakash; Ananthakrishnan, Ramesh; Elangovan, S.

    2010-01-01

    Unilateral pulmonary artery agenesis is commonly seen associated with other congenital cardiovascular defects, when it is detected early in life, but isolated absence of the pulmonary artery is a rare entity, usually detected in adulthood. The latter patients are usually asymptomatic or might present with varied non-specific manifestations such as respiratory tract infections and hemoptysis. This report describes the imaging findings of a 67 year old female with absence of the right pulmonary artery. The embryology and clinical manifestations of the condition are reviewed. PMID:22470700

  15. Preliminary Experience with GORE-TEX® Grafting for Right Ventricle-Pulmonary Artery Conduits

    PubMed Central

    Molina, J. Ernesto

    1986-01-01

    A consecutive series of 12 patients between the ages of 6½ and 37 years underwent implantation of venous ventricle-pulmonary artery conduits. GORE-TEX material without prosthetic valves was used. Four patients had L-transposition of the great vessels with ventricular septal defect (VSD) and pulmonary stenosis; four had tetralogy of Fallot with pulmonary atresia; and one had double outlet right ventricle, pulmonary stenosis, and a complete form of A-V canal. Two patients had D-transposition of the great arteries, VSD, and pulmonary stenosis; and one patient had L-transposition of the great arteries and isolated pulmonary stenosis. All patients had low pulmonary resistance and pressures. The technique for implanting this noncrimped type of prosthesis is described in detail. Follow-up ranged from 2 months to 5½ years. GORE-TEX offers a good choice of material for the construction of this type of conduit to prevent pseudointima formation and obstruction, which is often observed in woven Dacron grafts. PMID:15226844

  16. Pulmonary arterial hypertension due to pulmonary vascular amyloid deposition in a patient with multiple myeloma

    PubMed Central

    Hashimoto, Hirotsugu; Kurata, Atsushi; Mizuno, Hideaki; Nashiro, Tamaki; Hangaishi, Akira; Kuroda, Masahiko; Usuki, Kensuke; Horiuchi, Hajime

    2015-01-01

    Systemic amyloidosis is characterized by amyloid deposition throughout the body and subsequent dysfunction of various organs. Although pulmonary amyloidosis does occur, pulmonary hypertension (PH) caused by amyloidosis is extremely rare. In most of these cases, amyloid deposition occurred diffusely in alveolar septa, indicating that PH was due to lung disease and/or hypoxia. On the other hand, the mechanism of PH due to amyloid deposition in the pulmonary arteries has never been demonstrated. Here, we report the first case of PH due to amyloid deposition in pulmonary elastic arteries and muscular artery, which was complicated by multiple myeloma (MM). In the autopsy specimen of the patient, amyloid deposition was found mainly in the pulmonary arterial media, along with intimal thickening with luminal narrowing. PH thus appeared to be caused by marked decrease of pulmonary elasticity due to the amyloid deposition in the arterial media that resulted in stasis of the blood flow and subsequent luminal narrowing. Our present data demonstrates a new concept of PH caused by amyloidosis, namely, pulmonary arterial hypertension due to amyloidosis. PMID:26823900

  17. Unilateral absence of pulmonary artery associated with contralateral lung cancer

    PubMed Central

    Zhang, Liang-Ze; Ma, Wei-Guo; He, Jie

    2016-01-01

    Unilateral absence of a pulmonary artery (UAPA) is a rare congenital cardiac malformation that is often associated with other cardiovascular deformities. Surgical repair of this rare condition is usually performed only on the abnormal lung. The occurrence of lung cancer in association with UAPA is even rarer and clinical experience is very limited. This report aims to describe a case of unilateral absence of right pulmonary artery that was complicated by primary carcinoma of the contralateral lung. A left lower lobectomy was performed despite the absence of the right pulmonary artery and repeated decreases in the arterial oxygen saturation (SaO2) were encountered intraoperatively. The current case provides insights into the operative tolerability and the foreseeable ominous prognosis after excision of the normal lung in patients with UAPA and highlights the importance of the clinical awareness of this potentially lethal congenital anomaly in light of its extreme rarity, which may facilitate better diagnosis and treatment of such patients.

  18. RNA Sequencing Analysis Detection of a Novel Pathway of Endothelial Dysfunction in Pulmonary Arterial Hypertension

    PubMed Central

    Rhodes, Christopher J.; Im, Hogune; Cao, Aiqin; Hennigs, Jan K.; Wang, Lingli; Sa, Silin; Chen, Pin-I; Nickel, Nils P.; Miyagawa, Kazuya; Hopper, Rachel K.; Tojais, Nancy F.; Li, Caiyun G.; Gu, Mingxia; Spiekerkoetter, Edda; Xian, Zhaoying; Chen, Rui; Zhao, Mingming; Kaschwich, Mark; del Rosario, Patricia A.; Bernstein, Daniel; Zamanian, Roham T.; Wu, Joseph C.; Snyder, Michael P.

    2015-01-01

    Rationale: Pulmonary arterial hypertension is characterized by endothelial dysregulation, but global changes in gene expression have not been related to perturbations in function. Objectives: RNA sequencing was used to discriminate changes in transcriptomes of endothelial cells cultured from lungs of patients with idiopathic pulmonary arterial hypertension versus control subjects and to assess the functional significance of major differentially expressed transcripts. Methods: The endothelial transcriptomes from the lungs of seven control subjects and six patients with idiopathic pulmonary arterial hypertension were analyzed. Differentially expressed genes were related to bone morphogenetic protein type 2 receptor (BMPR2) signaling. Those down-regulated were assessed for function in cultured cells and in a transgenic mouse. Measurements and Main Results: Fold differences in 10 genes were significant (P < 0.05), four increased and six decreased in patients versus control subjects. No patient was mutant for BMPR2. However, knockdown of BMPR2 by siRNA in control pulmonary arterial endothelial cells recapitulated 6 of 10 patient-related gene changes, including decreased collagen IV (COL4A1, COL4A2) and ephrinA1 (EFNA1). Reduction of BMPR2-regulated transcripts was related to decreased β-catenin. Reducing COL4A1, COL4A2, and EFNA1 by siRNA inhibited pulmonary endothelial adhesion, migration, and tube formation. In mice null for the EFNA1 receptor, EphA2, versus control animals, vascular endothelial growth factor receptor blockade and hypoxia caused more severe pulmonary hypertension, judged by elevated right ventricular systolic pressure, right ventricular hypertrophy, and loss of small arteries. Conclusions: The novel relationship between BMPR2 dysfunction and reduced expression of endothelial COL4 and EFNA1 may underlie vulnerability to injury in pulmonary arterial hypertension. PMID:26030479

  19. The physcial properties of human pulmonary arteries and veins.

    PubMed

    Banks, J; Booth, F V; MacKay, E H; Rajagopalan, B; Lee, G D

    1978-11-01

    1. We have studied the extensibility of circumferential strips of main pulmonary artery and large pulmonary veins obtained at post mortem from patients of all ages, dying from conditions other than heart and lung disease. 2. The vessel strips were submitted to increasing loads in a tension balance. The pulmonary arteries were found to be readily extensible. This extensibility became less with increasing age. The pulmonary veins were virtually inextensible at all ages. 3. It is postulated that the large extraparenchymal pulmonary veins have a capacitative role in supplying blood from the lungs to the left atrium. This may be accomplished by their collapsible nature, as they have little capability of distension. PMID:720001

  20. 5-Hydroxytryptamine receptors mediating vasoconstriction in pulmonary arteries from control and pulmonary hypertensive rats.

    PubMed Central

    MacLean, M. R.; Sweeney, G.; Baird, M.; McCulloch, K. M.; Houslay, M.; Morecroft, I.

    1996-01-01

    1. We investigated 5-hydroxytryptamine (5-HT)-receptor mediated vasoconstriction in the main, first branch and resistance pulmonary arteries removed from control and pulmonary hypertensive rats. Contractile responses to 5-HT, 5-carboxamidotryptamine (5-CT, non-selective 5-HT1 agonist), and sumatriptan (5-HT1D-like receptor agonist) were studied. The effects of methiothepin (non-selective 5-HT1 + 2-receptor antagonist) and ketanserin (5-HT2A receptor antagonist) and GR55562 (a novel selective 5-HT1D receptor antagonist) on 5-HT-mediated responses were also studied. Basal levels of adenosine 3':5'-cyclic monophosphate ([cyclic AMP]i) and guanosine 3':5'-cyclic monophosphate ([cyclic GMP]i) were determined and we assessed the degree of inherent tone in the vessels under study. 2. 5-HT was most potent in the resistance arteries. pEC50 values were 5.6 +/- 0.1, 5.3 +/- 0.1, 5.0 +/- 0.2 in the resistance arteries, pulmonary branch and main pulmonary artery, respectively (n = at least 5 from 5 animals). The sensitivity to, and maximum response of, 5-HT was increased in all the arteries removed from the chronic hypoxic (CH) rats. In CH rats the pEC50 values were 5.9 +/- 0.2, 6.3 +/- 0.2, 6.4 +/- 0.2 and the increase in the maximum response was 35%, 51% and 41% in the resistance arteries, pulmonary branch and main pulmonary artery, respectively. Sumatriptan did not contract any vessel from the control rats whilst 5-CT did contract the resistance arteries. In the CH rats, however, they both contracted the resistance arteries (responses to sumatriptan were small) (pEC50: 5-CT; 5.4 +/- 0.2) and the pulmonary artery branches (pEC50: sumatriptan, 5.4 +/- 0.2; 5-CT, 5.4 +/- 0.2). 5-CT also caused a contraction in the main pulmonary artery (pEC50: 6.0 +/- 0.3). 3. Ketanserin (1 nM-1 microM) caused a competitive antagonism of the 5-HT response in all vessels tested. In control rats, the estimated pKb values for ketanserin in resistance arteries, pulmonary branches and main pulmonary

  1. Hemodynamics and right-ventricle functional characteristics of a swine carotid artery-jugular vein shunt model of pulmonary arterial hypertension: An 18-month experimental study.

    PubMed

    Wu, Ji; Luo, Xiaoju; Huang, Yuanyuan; He, Yun; Li, Zhixian

    2015-10-01

    The continuous changes in pulmonary hemodynamic properties and right ventricular (RV) function in pulmonary arterial hypertension (PAH) have not been fully characterized in large animal model of PAH induced by a carotid artery-jugular vein shunt. A minipig model of PAH was induced by a surgical anastomosis between the left common carotid artery and the left jugular vein. The model was validated by catheter examination and pathologic analyses, and the hemodynamic features and right-ventricle functional characteristics of the model were continuously observed by Doppler echocardiography. Of the 45 minipigs who received the surgery, 27 survived and were validated as models of PAH, reflected by mean pulmonary artery pressure ≥25 mmHg, and typical pathologic changes of pulmonary arterial remodeling and RV fibrosis. Non-invasive indices of pulmonary hemodynamics (pulmonary artery accelerating time and its ratio to RV ventricular ejection time) were temporarily increased, then reduced later, similar to changes in tricuspid annular displacement. The Tei index of the RV was elevated, indicating a progressive impairment in RV function. Surgical anastomosis between carotid artery and jugular vein in a minipig is effective to establish PAH, and non-invasive hemodynamic and right-ventricle functional indices measured by Doppler echocardiography may be used as early indicators of PAH. PMID:25595189

  2. Hemodynamics and right-ventricle functional characteristics of a swine carotid artery-jugular vein shunt model of pulmonary arterial hypertension: An 18-month experimental study.

    PubMed

    Wu, Ji; Luo, Xiaoju; Huang, Yuanyuan; He, Yun; Li, Zhixian

    2015-10-01

    The continuous changes in pulmonary hemodynamic properties and right ventricular (RV) function in pulmonary arterial hypertension (PAH) have not been fully characterized in large animal model of PAH induced by a carotid artery-jugular vein shunt. A minipig model of PAH was induced by a surgical anastomosis between the left common carotid artery and the left jugular vein. The model was validated by catheter examination and pathologic analyses, and the hemodynamic features and right-ventricle functional characteristics of the model were continuously observed by Doppler echocardiography. Of the 45 minipigs who received the surgery, 27 survived and were validated as models of PAH, reflected by mean pulmonary artery pressure ≥25 mmHg, and typical pathologic changes of pulmonary arterial remodeling and RV fibrosis. Non-invasive indices of pulmonary hemodynamics (pulmonary artery accelerating time and its ratio to RV ventricular ejection time) were temporarily increased, then reduced later, similar to changes in tricuspid annular displacement. The Tei index of the RV was elevated, indicating a progressive impairment in RV function. Surgical anastomosis between carotid artery and jugular vein in a minipig is effective to establish PAH, and non-invasive hemodynamic and right-ventricle functional indices measured by Doppler echocardiography may be used as early indicators of PAH.

  3. Endovascular covered stent repair of an iatrogenic subclavian artery-to-pulmonary artery fistula and pseudoaneurysm.

    PubMed

    Wheeler, Shane C; Zinn, Kenneth M; Hughes, Terence W

    2007-06-01

    An iatrogenic fistula and consequent pseudoaneurysm developed between the right subclavian artery and right pulmonary artery as a result of misplacement of a hemodialysis access catheter. The patient, who was considered to be at high risk for surgical repair, successfully underwent endovascular treatment that involved insertion of two nitinol stents covered with expanded polytetrafluoroethylene (stent-grafts), one into the right subclavian artery and the other into a right upper lobe pulmonary artery. Multi-detector row computed tomographic angiography played an integral role in the evaluation of the patient's vascular injury and treatment planning. PMID:17538141

  4. 17β-Estradiol Attenuates Conduit Pulmonary Artery Mechanical Property Changes With Pulmonary Arterial Hypertension.

    PubMed

    Liu, Aiping; Tian, Lian; Golob, Mark; Eickhoff, Jens C; Boston, Madison; Chesler, Naomi C

    2015-11-01

    Pulmonary arterial hypertension (PAH), a rapidly fatal vascular disease, strikes women more often than men. Paradoxically, female PAH patients have better prognosis and survival rates than males. The female sex hormone 17β-estradiol has been linked to the better outcome of PAH in females; however, the mechanisms by which 17β-estradiol alters PAH progression and outcomes remain unclear. Because proximal pulmonary arterial (PA) stiffness, one hallmark of PAH, is a powerful predictor of mortality and morbidity, we hypothesized that 17β-estradiol attenuates PAH-induced changes in mechanical properties in conduit proximal PAs, which imparts hemodynamic and energetic benefits to right ventricular function. To test this hypothesis, female mice were ovariectomized and treated with 17β-estradiol or placebo. PAH was induced in mice using SU5416 and chronic hypoxia. Extra-lobar left PAs were isolated and mechanically tested ex vivo to study both static and frequency-dependent mechanical behaviors in the presence or absence of smooth muscle cell activation. Our static mechanical test showed significant stiffening of large PAs with PAH (P<0.05). 17β-Estradiol restored PA compliance to control levels. The dynamic mechanical test demonstrated that 17β-estradiol protected the arterial wall from the PAH-induced frequency-dependent decline in dynamic stiffness and loss of viscosity with PAH (P<0.05). As demonstrated by the in vivo measurement of PA hemodynamics via right ventricular catheterization, modulation by 17β-estradiol of mechanical proximal PAs reduced pulsatile loading, which contributed to improved ventricular-vascular coupling. This study provides a mechanical mechanism for delayed disease progression and better outcome in female PAH patients and underscores the therapeutic potential of 17β-estradiol in PAH. PMID:26418020

  5. Sodium hydrosulfide prevents hypoxia-induced pulmonary arterial hypertension in broilers.

    PubMed

    Yang, Y; Zhang, B K; Liu, D; Nie, W; Yuan, J M; Wang, Z; Guo, Y M

    2012-01-01

    1. The aim of the study was to determine if H(2)S is involved in the development of hypoxia-induced pulmonary hypertension in broilers, a condition frequently observed in a variety of cardiac and pulmonary diseases. 2. Two-week-old broilers were reared under normoxic conditions or exposed to normobaric hypoxia (6 h/day) with tissue levels of H(2)S adjusted by administering sodium hydrosulfide (NaHS, 10 µmol/kg body weight/day). Mean pulmonary arterial pressure, right ventricular mass, plasma and tissue H(2)S levels, the expression of cystathionine-β-synthase (CSE) and vascular remodeling were determined at 35 d of age. 3. Exposure to hypoxia-induced pulmonary arterial hypertension was characterized by elevated pulmonary pressure, right ventricular hypertrophy and vascular remodeling. This was accompanied by decreased expression of CSE and decreased concentrations of plasma and tissue H(2)S. 4. Hypoxia-induced pulmonary hypertension was significantly reduced by administration of NaHS but this protective effect was largely abolished by D, L-propargylglycerine, an inhibitor of CSE. 5. The results indicate that H(2)S is involved in the development of hypoxia-induced pulmonary hypertension. Supplementing NaHS or H(2)S could be a strategy for reducing hypoxia-induced hypertension in broilers.

  6. Pulmonary artery bullet embolism—Case report and review

    PubMed Central

    Fernandez-Ranvier, Gustavo G.; Mehta, Pratik; Zaid, Usama; Singh, Kamalpreet; Barry, Maged; Mahmoud, Ahmed

    2013-01-01

    INTRODUCTION Bullet embolism, an uncommon but serious complication of penetrating vascular trauma, poses a unique clinical challenge for the trauma physician. Migration of bullets can lead to infection, thrombosis, ischemia, hemorrhage and death. PRESENTATION OF CASE We report a patient in whom a bullet embolized from the left femoral vein to the right pulmonary artery, a situation ultimately managed by observation alone. DISCUSSION Bullet embolism should be suspected when the number of penetrating entry wounds exceeds the number of exit wounds. Patients with radiographic studies showing a bullet outside the established trajectory require further evaluation. Most bullet emboli are arterial, and are generally symptomatic presenting with early signs of ischemia. Venous emboli are less common, and they are generally asymptomatic. Most venous bullet emboli travel in the direction of the blood flow and may lodge in the pulmonary arterial tree causing serious complications. Management of bullet emboli in the pulmonary arterial tree remains controversial and specific guidelines have not been clearly established. However, the available data in the literature suggest that pulmonary artery embolism can be observed in the asymptomatic patient. CONCLUSION Symptomatic pulmonary bullet emboli should be managed with endovascular retrieval when available or operative therapy. Asymptomatic intravascular bullet emboli may be managed conservatively as seen in our patient. PMID:23567547

  7. Treatment of Acute Low Pressure Pulmonary Edema in Dogs

    PubMed Central

    Prewitt, R. M.; McCarthy, J.; Wood, L. D. H.

    1981-01-01

    Severe pulmonary edema sometimes develops despite normal pulmonary capillary wedge pressure (Ppw). The equation describing net transvascular flux of lung liquid predicts decreased edema when hydrostatic pressure is reduced or when colloid osmotic pressure is increased in the pulmonary vessels. We tested these predictions in a model of pulmonary capillary leak produced in 35 dogs by intravenous oleic acid. 1 h later, the dogs were divided into five equal groups and treated for 4 h in different ways: (a) not treated, to serve as the control group (Ppw = 11.1 mm Hg); (b) given albumin to increase colloid osmotic pressure by 5 mm Hg (Ppw = 10.6 mm Hg); (c) ventilated with 10 cm H2O positive end-expiratory pressure (Peep) (transmural Ppw = 10.4 mm Hg); (d) phlebotomized to reduce Ppw to 6 mm Hg; (e) infused with nitroprusside, which also reduced Ppw to 6 mm Hg. Phlebotomy and nitroprusside reduced the edema in excised lungs by 50% (P< 0.001), but Peep and albumin did not affect the edema. Pulmonary shunt decreased on Peep and increased on nitroprusside, and lung compliance was not different among the treatment groups, demonstrating that these variables are poor indicators of changes in edema. Cardiac output decreased during the treatment period in all but the nitroprusside group, where Ppw decreased and cardiac output did not. We conclude that canine oleic acid pulmonary edema is reduced by small reductions in hydrostatic pressure, but not by increased colloid osmotic pressure, because the vascular permeability to liquid and protein is increased. These results suggest that low pressure pulmonary edema may be reduced by seeking the lowest Ppw consistent with adequate cardiac output enhanced by vasoactive agents like nitroprusside. Further, colloid infusions and Peep are not helpful in reducing edema, so they may be used in the lowest amount that provides adequate circulating volume and arterial O2 saturation on nontoxic inspired O2. Until these therapeutic principles

  8. Isorhynchophylline protects against pulmonary arterial hypertension and suppresses PASMCs proliferation

    SciTech Connect

    Guo, Haipeng; Zhang, Xin; Cui, Yuqian; Deng, Wei; Xu, Dachun; Han, Hui; Wang, Hao; Chen, Yuguo; Li, Yu; Wu, Dawei

    2014-07-18

    Highlights: • We focus on PASMCs proliferation in the pathogenesis of PAH. • Isorhynchophylline inhibited PASMCs proliferation and alleviated PAH. • IRN blocked PDGF-Rβ phosphorylation and its downstream signal transduction. • IRN regulated cyclins and CDKs to arrest cell cycle in the G0/G1 phase. • We reported IRN has the potential to be a candidate for PAH treatment. - Abstract: Increased pulmonary arterial smooth muscle cells (PASMCs) proliferation is a key pathophysiological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). Isorhynchophylline (IRN) is a tetracyclic oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla. It has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether IRN can influence the development of PAH. Here we examined the effect of IRN on monocrotaline (MCT) induced PAH in rats. Our data demonstrated that IRN prevented MCT induced PAH in rats, as assessed by right ventricular (RV) pressure, the weight ratio of RV to (left ventricular + septum) and RV hypertrophy. IRN significantly attenuated the percentage of fully muscularized small arterioles, the medial wall thickness, and the expression of smooth muscle α-actin (α-SMA) and proliferating cell nuclear antigen (PCNA). In vitro studies, IRN concentration-dependently inhibited the platelet-derived growth factor (PDGF)-BB-induced proliferation of PASMCs. Fluorescence-activated cell-sorting analysis showed that IRN caused G0/G1 phase cell cycle arrest. IRN-induced growth inhibition was associated with downregulation of Cyclin D1 and CDK6 as well as an increase in p27Kip1 levels in PDGF-BB-stimulated PASMCs. Moreover, IRN negatively modulated PDGF-BB-induced phosphorylation of PDGF-Rβ, ERK1/2, Akt/GSK3β, and signal transducers and activators of transcription 3 (STAT3). These results demonstrate that IRN could inhibit PASMCs proliferation and

  9. A Surgical Case of Bronchial Artery Aneurysm Directory Connecting with Pulmonary Artery

    PubMed Central

    Sano, Fumitoshi; Hayashi, Shoko; Suzuki, Kosuke; Uematsu, Shugo; Suzuki, Takashi; Saeki, Noriyuki

    2015-01-01

    We present a surgical case of bronchial artery aneurysm (BAA) connecting pulmonary artery accompanied with racemose hemangioma. This is a third surgical case report of BAA directly connecting pulmonary artery in the English literature. A 63-year-old female was found a BAA, 2 cm in diameter, connecting right A4 pulmonary artery. The patient underwent two attempts for embolization. However, due to extensive collaterals, there was persistent flow in the aneurysm. Standard lateral thoracotomy was performed. A BAA was located between A4 and A5 PA. A small branch of A4 PA was separated, and the small vessel connecting to the BAA could be ligated. A5 PA was separated similarly, however BAA was ruptured not to identify the other small vessel connecting to the BAA. After a clamp of the BAA, middle lobe lobectomy was performed. We removed the aneurysm with dilated bronchial artery connecting to the aneurysm. The postoperative course was uneventful. PMID:26050595

  10. Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery: Diagnosis with CT Angiography

    PubMed Central

    Oncel, Guray; Oncel, Dilek

    2013-01-01

    Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly. It is associated with early infant mortality and sudden death in adults. Traditionally, ALCAPA has been diagnosed by angiography or autopsy; however, the development of cardiac computed tomography (CT) and magnetic resonance imaging (MRI) has allowed noninvasive evaluation of the coronary anatomy by direct visualization of the origin of the left coronary artery (LCA) from the pulmonary artery. We report a case of 10-year-old girl who has been on follow up for dilated cardiomyopathy for 4 years. The definitive diagnosis of ALCAPA is reached by multislice computed tomography (MSCT). The MSCT scan showed an anomalous origin of LCA from the pulmonary trunk, with a tortuous and dilated right coronary artery and right-to-left collateralization. Consequently, the patient was successfully treated with surgery. PMID:23607073

  11. Pulmonary Artery Aneurysm Thrombosis with Combined Pulmonary Fibrosis and Emphysema: A Case Report.

    PubMed

    Agrawal, Mitali Bharat; Awad, Nilkant Tukaram

    2016-05-01

    We report a rare case of Pulmonary Artery Aneurysm (PAA) thrombosis with Combined Pulmonary Fibrosis and Emphysema (CPFE) with pulmonary hypertension. A 75-year-old male presented with haemoptysis, dyspnoea, clubbing and bilateral fine end inspiratory rales on examination. He was diagnosed to have PAA thrombosis with CPFE on the basis of computed tomographical angiography and high resolution computed tomography. He was then managed conservatively with pirfenidone for the interstitial lung disease. PMID:27437277

  12. Pulmonary Artery Aneurysm Thrombosis with Combined Pulmonary Fibrosis and Emphysema: A Case Report

    PubMed Central

    Awad, Nilkant Tukaram

    2016-01-01

    We report a rare case of Pulmonary Artery Aneurysm (PAA) thrombosis with Combined Pulmonary Fibrosis and Emphysema (CPFE) with pulmonary hypertension. A 75-year-old male presented with haemoptysis, dyspnoea, clubbing and bilateral fine end inspiratory rales on examination. He was diagnosed to have PAA thrombosis with CPFE on the basis of computed tomographical angiography and high resolution computed tomography. He was then managed conservatively with pirfenidone for the interstitial lung disease. PMID:27437277

  13. Pulmonary arterial hypertension in rats due to age-related arginase activation in intermittent hypoxia.

    PubMed

    Nara, Akina; Nagai, Hisashi; Shintani-Ishida, Kaori; Ogura, Sayoko; Shimosawa, Tatsuo; Kuwahira, Ichiro; Shirai, Mikiyasu; Yoshida, Ken-ichi

    2015-08-01

    Pulmonary arterial hypertension (PAH) is prevalent in patients with obstructive sleep apnea syndrome (OSAS). Aging induces arginase activation and reduces nitric oxide (NO) production in the arteries. Intermittent hypoxia (IH), conferred by cycles of brief hypoxia and normoxia, contributes to OSAS pathogenesis. Here, we studied the role of arginase and aging in the pathogenesis of PAH in adult (9-mo-old) and young (2-mo-old) male Sprague-Dawley rats subjected to IH or normoxia for 4 weeks and analyzed them with a pressure-volume catheter inserted into the right ventricle (RV) and by pulsed Doppler echocardiography. Western blot analysis was conducted on arginase, NO synthase isoforms, and nitrotyrosine. IH induced PAH, as shown by increased RV systolic pressure and RV hypertrophy, in adult rats but not in young rats. IH increased expression levels of arginase I and II proteins in the adult rats. IH also increased arginase I expression in the pulmonary artery endothelium and arginase II in the pulmonary artery adventitia. Furthermore, IH reduced pulmonary levels of nitrate and nitrite but increased nitrotyrosine levels in adult rats. An arginase inhibitor (N(ω)-hydroxy-nor-1-arginine) prevented IH-induced PAH and normalized nitrite and nitrate levels in adult rats. IH induced arginase up-regulation and PAH in adult rats, but not in young rats, through reduced NO production. Our findings suggest that arginase inhibition prevents or reverses PAH. PMID:25490411

  14. Hemodynamics and right-ventricle functional characteristics of a swine carotid artery-jugular vein shunt model of pulmonary arterial hypertension: An 18-month experimental study

    PubMed Central

    Luo, Xiaoju; Huang, Yuanyuan; He, Yun; Li, Zhixian

    2015-01-01

    The continuous changes in pulmonary hemodynamic properties and right ventricular (RV) function in pulmonary arterial hypertension (PAH) have not been fully characterized in large animal model of PAH induced by a carotid artery–jugular vein shunt. A minipig model of PAH was induced by a surgical anastomosis between the left common carotid artery and the left jugular vein. The model was validated by catheter examination and pathologic analyses, and the hemodynamic features and right-ventricle functional characteristics of the model were continuously observed by Doppler echocardiography. Of the 45 minipigs who received the surgery, 27 survived and were validated as models of PAH, reflected by mean pulmonary artery pressure ≥25 mmHg, and typical pathologic changes of pulmonary arterial remodeling and RV fibrosis. Non-invasive indices of pulmonary hemodynamics (pulmonary artery accelerating time and its ratio to RV ventricular ejection time) were temporarily increased, then reduced later, similar to changes in tricuspid annular displacement. The Tei index of the RV was elevated, indicating a progressive impairment in RV function. Surgical anastomosis between carotid artery and jugular vein in a minipig is effective to establish PAH, and non-invasive hemodynamic and right-ventricle functional indices measured by Doppler echocardiography may be used as early indicators of PAH. PMID:25595189

  15. Pressure Change in an Arterial Constriction

    ERIC Educational Resources Information Center

    Mungan, Carl E.

    2015-01-01

    Consider the following ConcepTest. A platelet is drifting with the blood flowing through a horizontal artery. As the platelet enters a constriction, does the blood pressure increase, decrease, or stay the same?

  16. Pressure Change in an Arterial Constriction

    NASA Astrophysics Data System (ADS)

    Mungan, Carl E.

    2015-12-01

    Consider the following ConcepTest. A platelet is drifting with the blood flowing through a horizontal artery. As the platelet enters a constriction, does the blood pressure increase, decrease, or stay the same?

  17. [Coronary artery fistula between pulmonary trunk and left descending coronary artery--description of two cases].

    PubMed

    Dytfeld, Dominik; Sarnowski, Wojciech

    2002-07-01

    Fistulas connecting coronary arteries with trunk of pulmonary artery are the most common congenital defects of coronary arteries. Depending on the size of fistula they cause IHD symptoms of different intensification (Coronary Steal Phenomenon). The symptoms appear very often in advanced age. In this study two patients with coronary-pulmonary artery fistula accompanied by another heart defects (VSD or stenosis of aortic valve), but with no IHD-symptoms, are presented. To find possible coronary arteries malformations, it seems to be useful to perform the catheterization of coronary arteries in all patients, who are qualified for surgical procedure because of heart's disease. It also concerns younger patients with VSD (under 35) in whom coronarography is not a routine procedure. PMID:12362509

  18. Macitentan in pulmonary arterial hypertension: The SERAPHIN trial.

    PubMed

    Said, Karim

    2014-01-01

    Major limitations of pulmonary arterial hypertension (PAH) drug trials include the small number of enrolled patients, short term follow up (12-16 weeks), and lack of morbidity and mortality primary endpoints. The recently published SERAPHIN (Study with an Endothelin Receptor Antagonist in Pulmonary arterial Hypertension to Improve cliNical outcome) trial represents an important landmark in the history of clinical trials in PAH being the largest and longest clinical study conducted thus far in PAH patients with morbidity and mortality events as primary endpoint. SERAPHIN trial investigated whether long-term treatment with the new endothelin receptor antagonist macitentan would reduce the risk of mortality and morbidity in PAH patients.

  19. Use of pulmonary arterial hypertension–specific therapy in overweight or obese patients with obstructive sleep apnea and pulmonary hypertension

    PubMed Central

    2014-01-01

    Abstract Pulmonary hypertension (PH) in overweight or obese patients with obstructive sleep apnea (OSA) may be multifactorial. The effect of pulmonary artery hypertension (PAH)–specific drugs on PH and exercise capacity in such patients is unknown. We performed a retrospective review of overweight or obese patients with OSA and PH who were treated with PAH-specific therapy in our PH clinic. We identified 9 female and 2 male patients. The mean age ± SD was 54.9 ± 9.3 years. The mean pulmonary artery pressure at the time of diagnosis of PH was 39.8 ± 16.1 mmHg. The right atrial pressure was 11.1 ± 4.5 mmHg, the pulmonary artery wedge pressure was 14.1 ± 2.9 mmHg, the cardiac index was 2.6 ± 0.5 L/min/m2, and the pulmonary vascular resistance index was 10.6 ± 7.1 Wood units/m2. The indications for use of PAH-specific therapy were dyspnea in association with right heart failure (n = 4), persistent PH despite compliance with nocturnal positive airway pressure (PAP) therapy (n = 4), or inability to tolerate PAP therapy (n = 3). PH was treated with an endothelin receptor antagonist (n = 8) or a phosphodiesterase-5 inhibitor (n = 3). The 6-minute walk distance (6MWD) improved significantly, from 234 ± 49.7 to 258 ± 54.6 m (24 m [95% confidence interval (CI): 6.5–341.5 m]; P = 0.014) over a period of 4.4 ± 1.8 months (n = 8) and from 241.7 ± 48.5 to 289.9 ± 91 m (48 m [95% CI: 5.5–90.8 m]; P = 0.033) in those with a longer follow-up period of 12.1 ± 6.4 months (n = 7). The systolic pulmonary artery pressure dropped significantly, from 64 ± 25.2 to 42 ± 10.4 mmHg (22 mmHg [95% CI: 4–40 mmHg]; P = 0.024) over a period of 6.1 ± 4.1 months (n = 7). In conclusion, PAH-specific therapy resulted in significant improvement in both PH and 6MWD. PMID:25006443

  20. Measurement of regional pulmonary blood volume in patients with increased pulmonary blood flow or pulmonary arterial hypertension

    SciTech Connect

    Wollmer, P.; Rozcovek, A.; Rhodes, C.G.; Allan, R.M.; Maseri, A.

    1984-01-01

    The effects of chronic increase in pulmonary blood flow and chronic pulmonary hypertension on regional pulmonary blood volume was measured in two groups of patients. One group of patients had intracardiac, left-to-right shunts without appreciable pulmonary hypertension, and the other consisted of patients with Eisenmenger's syndrome or primary pulmonary hypertension, i.e. patients with normal or reduced blood flow and severe pulmonary hypertension. A technique based on positron tomography was used to measure lung density (by transmission scanning) and regional pulmonary blood volume (after inhalation of /sup 11/CO). The distribution of pulmonary blood volume was more uniform in patients with chronic increase in pulmonary blood flow than in normal subjects. There were also indications of an absolute increase in intrapulmonary blood volume by about 15%. In patients with chronic pulmonary arterial hypertension, the distribution of pulmonary blood volume was also abnormally uniform. There was, however, no indication that overall intrapulmonary blood volume was substantially different from normal subjects. The abnormally uniform distribution of pulmonary blood volume can be explained by recruitment and/or dilatation of vascular beds. Intrapulmonary blood volume appears to be increased in patients with intracardiac, left-to-right shunts. With the development of pulmonary hypertension, intrapulmonary blood volume falls, which may be explained by reactive changes in the vasculature and/or obliteration of capillaries.

  1. Renal responses of normal and preascitic broilers to systemic hypotension induced by unilateral pulmonary artery occlusion.

    PubMed

    Forman, M F; Wideman, R F

    1999-12-01

    During the pathophysiological progression of pulmonary hypertension syndrome (PHS; ascites), broilers concurrently develop systemic hypotension (low mean systemic arterial pressure) that may initiate renal retention of water and solute, contributing to fluid accumulation in the abdominal cavity (ascites). In male Single Comb White Leghorns, glomerular filtration is autoregulated over a systemic arterial pressure range of 110 to 60 mm Hg, and corresponding reductions in urine flow are attributed to a phenomenon known as pressure natriuresis. Acute unilateral pulmonary artery occlusion was used in the present study to reduce systemic arterial pressure toward the lower autoregulatory limit for glomerular filtration, and to evaluate kidney function in normal and preascitic broilers. Preascitic broilers characteristically exhibited lower (P < or = 0.05) values for mean systemic arterial pressure (91 vs 100 mm Hg) and percentage saturation of hemoglobin with oxygen (73 vs 84%), higher hematocrits (35 vs 30%), heavier right ventricles (3.44 vs 2.32 g), and higher right:total ventricular weight ratios (0.32 vs 0.24) than normal broilers. Body weights (2,445 vs 2,429 g, respectively), left ventricle plus septum weights (7.16 vs 7.19 g), and heart rates (349 vs 341 beats/min) were similar. Preascitic broilers exhibited larger (P < or = 0.05) dependent reductions in glomerular filtration, urine flow, osmolal clearance, and solute excretion and had a higher free water clearance than normal broilers in response to pulmonary artery occlusion. The differences observed between normal and preascitic broilers demonstrate that systemic hypotension can trigger renal mechanisms contributing to fluid and solute retention during development of PHS.

  2. Arterial and pulmonary arterial hemodynamics and oxygen delivery/extraction in normal humans exposed to hyperbaric air and oxygen.

    PubMed

    Weaver, Lindell K; Howe, Steve; Snow, Gregory L; Deru, Kayla

    2009-07-01

    Divers and hyperbaric chamber attendants breathe hyperbaric air routinely. Hyperbaric oxygen (HBO(2)) is used therapeutically frequently. Although much is understood about the hemodynamic physiology and gas exchange effects during hyperbaric air and HBO(2) exposure, arterial and pulmonary arterial (PA) catheter data, including blood gas values during hyperbaric air and HBO(2) exposure of normal humans, have not been reported. We exposed 10 healthy volunteers instrumented with arterial and PA catheters to air at 0.85, 3.0, 2.5, 2.0, 1.3 (decompression stop), 1.12 (decompression stop), and 0.85 atm abs (our altitude) and then at identical pressures breathing O(2) followed by atmospheric pressure air while we measured arterial and PA pressures (PAP), cardiac output (Q), and blood gas measurements from both arterial and PA catheters. Although hemodynamic changes occurred during exposure to both hyperbaric air and HBO(2), we observed a greater magnitude of change under HBO(2) conditions: heart rate changes ranged from -9 to -19% (air to O(2)), respiratory rate from -12 to -17%, Q from -7 to -18%, PAP from -18 to -19%, pulmonary vascular resistance from -38 to -48%, and right-to-left shunt fraction from -87 to -107%. Mixed venous CO(2) fell 8% from baseline during HBO(2) despite mixed venous O(2) tensions of several hundred Torr. The stroke volume, O(2) delivery, and O(2) consumption did not change across exposures. The arterial and mixed venous partial pressures of O(2) and contents were elevated, as predicted. O(2) extraction increased 37% during HBO(2).

  3. Comparison of approaches to quantify arterial damping capacity from pressurization tests on mouse conduit arteries.

    PubMed

    Tian, Lian; Wang, Zhijie; Lakes, Roderic S; Chesler, Naomi C

    2013-05-01

    Large conduit arteries are not purely elastic, but viscoelastic, which affects not only the mechanical behavior but also the ventricular afterload. Different hysteresis loops such as pressure-diameter, pressure-luminal cross-sectional area (LCSA), and stress-strain have been used to estimate damping capacity, which is associated with the ratio of the dissipated energy to the stored energy. Typically, linearized methods are used to calculate the damping capacity of arteries despite the fact that arteries are nonlinearly viscoelastic. The differences in the calculated damping capacity between these hysteresis loops and the most common linear and correct nonlinear methods have not been fully examined. The purpose of this study was thus to examine these differences and to determine a preferred approach for arterial damping capacity estimation. Pressurization tests were performed on mouse extralobar pulmonary and carotid arteries in their physiological pressure ranges with pressure (P) and outer diameter (OD) measured. The P-inner diameter (ID), P-stretch, P-Almansi strain, P-Green strain, P-LCSA, and stress-strain loops (including the Cauchy and Piola-Kirchhoff stresses and Almansi and Green strains) were calculated using the P-OD data and arterial geometry. Then, the damping capacity was calculated from these loops with both linear and nonlinear methods. Our results demonstrate that the linear approach provides a reasonable approximation of damping capacity for all of the loops except the Cauchy stress-Almansi strain, for which the estimate of damping capacity was significantly smaller (22 ± 8% with the nonlinear method and 31 ± 10% with the linear method). Between healthy and diseased extralobar pulmonary arteries, both methods detected significant differences. However, the estimate of damping capacity provided by the linear method was significantly smaller (27 ± 11%) than that of the nonlinear method. We conclude that all loops except the Cauchy stress

  4. Temporary clamping of branch pulmonary artery for pulmonary hemorrhage after endarterectomy.

    PubMed

    Reddy, Srinivasa; Rajanbabu, Balram Babu; Kumar, Nalkunda Kyathaplar Sunil; Rajani, Indira

    2013-10-01

    A 49-year-old man underwent pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension. A massive pulmonary hemorrhage developed, which was identified to be from the right lower lobe, when weaning off cardiopulmonary bypass was attempted. He was managed by temporary overnight clamping of the right pulmonary artery, after the upper lobe branch. The next morning the clamp was removed, the bleeding had stopped completely, and his chest was closed. The patient was discharged on the 21st day. At 14 months' follow-up, he is in New York Heart Association functional class I. In suitable patients, temporary clamping of branch pulmonary artery can be a useful salvage measure, as in this patient. PMID:24088460

  5. Pulmonary Arterial Stent Implantation in an Adult with Williams Syndrome

    SciTech Connect

    Reesink, Herre J.; Henneman, Onno D. F.; Delden, Otto M. van; Biervliet, Jules D.; Kloek, Jaap J.; Reekers, Jim A.; Bresser, Paul

    2007-07-15

    We report a 38-year-old patient who presented with pulmonary hypertension and right ventricular dysfunction due to pulmonary artery stenoses as a manifestation of Williams syndrome, mimicking chronic thromboembolic pulmonary hypertension. The patient was treated with balloon angioplasty and stent implantation. Short-term follow-up showed a good clinical result with excellent patency of the stents but early restenosis of the segments in which only balloon angioplasty was performed. These stenoses were subsequently also treated successfully by stent implantation. Stent patency was observed 3 years after the first procedure.

  6. Visualization of the Spinal Artery by CT During Embolization for Pulmonary Artery Pseudoaneurysm

    PubMed Central

    Maki, Hiroyuki; Shimohira, Masashi; Hashizume, Takuya; Kawai, Tatsuya; Nakagawa, Motoo; Ozawa, Yoshiyuki; Sakurai, Keita; Shibamoto, Yuta

    2016-01-01

    Summary Background Spinal artery ischemia is a rare but serious complication of embolization for treatment of hemoptysis. When the spinal artery is visualized at angiography, embolization should not be performed. However, it has been reported that spinal artery feeders are not visible on angiography in patients with developing spinal infarction. Case Report A 70-year-old man with a history of pulmonary aspergillosis had hemoptysis and underwent contrast-enhanced CT, revealing a pulmonary artery pseudoaneurysm (PAP) in the left upper lobe. Systemic angiography from the fifth left intercostal artery showed the PAP at the distal site, but the access route to the PAP was very tortuous and long. Although the spinal branch could not be observed with that angiography, CT during angiography was performed, and it visualized the posterior spinal artery obviously. Thus, the artery distal and proximal to the PAP was then successfully coil-embolized from the pulmonary artery. Conclusions CT during angiography may be useful to confirm the presence of the spinal artery for treatment of hemoptysis by embolization.

  7. Visualization of the Spinal Artery by CT During Embolization for Pulmonary Artery Pseudoaneurysm

    PubMed Central

    Maki, Hiroyuki; Shimohira, Masashi; Hashizume, Takuya; Kawai, Tatsuya; Nakagawa, Motoo; Ozawa, Yoshiyuki; Sakurai, Keita; Shibamoto, Yuta

    2016-01-01

    Summary Background Spinal artery ischemia is a rare but serious complication of embolization for treatment of hemoptysis. When the spinal artery is visualized at angiography, embolization should not be performed. However, it has been reported that spinal artery feeders are not visible on angiography in patients with developing spinal infarction. Case Report A 70-year-old man with a history of pulmonary aspergillosis had hemoptysis and underwent contrast-enhanced CT, revealing a pulmonary artery pseudoaneurysm (PAP) in the left upper lobe. Systemic angiography from the fifth left intercostal artery showed the PAP at the distal site, but the access route to the PAP was very tortuous and long. Although the spinal branch could not be observed with that angiography, CT during angiography was performed, and it visualized the posterior spinal artery obviously. Thus, the artery distal and proximal to the PAP was then successfully coil-embolized from the pulmonary artery. Conclusions CT during angiography may be useful to confirm the presence of the spinal artery for treatment of hemoptysis by embolization. PMID:27617047

  8. Superior Vena Cava Stent Migration into the Pulmonary Artery Causing Fatal Pulmonary Infarction

    SciTech Connect

    Anand, Girija Lewanski, Conrad R.; Cowman, Steven A.; Jackson, James E.

    2011-02-15

    Migration of superior vena cava (SVC) stents is a well-recognised complication of their deployment, and numerous strategies exist for their retrieval. To our knowledge, only three cases of migration of an SVC stent to the pulmonary vasculature have previously been reported. None of these patients developed complications that resulted in death. We report a case of SVC stent migration to the pulmonary vasculature with delayed pulmonary artery thrombosis and death from pulmonary infarction. We conclude that early retrieval of migrated stents should be performed to decrease the risk of serious complications.

  9. Small pulmonary arteries in some natives of La Paz, Bolivia.

    PubMed Central

    Heath, D; Smith, P; Rios Dalenz, J; Williams, D; Harris, P

    1981-01-01

    A histological study was made of the small pulmonary blood vessels in pieces of lung obtained at necropsy from 19 long-term residents of La Paz, Bolivia (3800 m). There was variation in the response of the pulmonary vasculature of these subjects to the chronic hypoxia of high altitude. The most characteristic finding, seen in seven of the 16 cases beyond infancy, was distal extension of vascular smooth muscle into pulmonary arterioles as small as 20 micrometer in diameter. Medial hypertrophy of the muscular pulmonary arteries occurred in only three of these seven subjects. Intimal fibrosis was seen in eight of the 19 cases and was ascribed to age; such fibrotic proliferation may affect the reversibility of hypoxic pulmonary hypertension and associated vascular changes in highlanders. Images PMID:7314035

  10. Novel Strategies in the Treatment of Pulmonary Arterial Hypertension.

    PubMed

    Madonna, Rosalinda; Cocco, Nino

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a pathophysiological condition characterized by increased pulmonary vascular resistance (PVR), initially due to abnormal pulmonary vasoconstriction in response to endothelial injury. Recent studies confirmed the key role of endothelin (ET)-1 in the vasoconstriction and remodeling of pulmonary microcirculation during PAH. In responders patients, classical treatments for PAH are prostanoids, phosphodiesterase (PDE)-5 inhibitors and endothelin receptor antagonists (ERAs), which target prostaglandin I2, nitric oxide and endothelin pathways, respectively. Randomised, placebo-controlled trials have shown that ERAs improves haemodynamic parameters of the pulmonary circulation, functional capacity and clinical outcome in patients affected by PAH. Here, we will review the definition, classification and pathophysiology of PH. Furthermore, we will provide an up-to-date overview of currently recommended diagnostic and therapeutic work-up in PAH. PMID:26201488

  11. Pulmonary artery smooth muscle cell endothelin-1 expression modulates the pulmonary vascular response to chronic hypoxia

    PubMed Central

    Kim, Francis Y.; Barnes, Elizabeth A.; Ying, Lihua; Chen, Chihhsin; Lee, Lori; Alvira, Cristina M.

    2014-01-01

    Endothelin-1 (ET-1) increases pulmonary vascular tone through direct effects on pulmonary artery smooth muscle cells (PASMC) via membrane-bound ET-1 receptors. Circulating ET-1 contributes to vascular remodeling by promoting SMC proliferation and migration and inhibiting SMC apoptosis. Although endothelial cells (EC) are the primary source of ET-1, whether ET-1 produced by SMC modulates pulmonary vascular tone is unknown. Using transgenic mice created by crossbreeding SM22α-Cre mice with ET-1 flox/flox mice to selectively delete ET-1 in SMC, we tested the hypothesis that PASMC ET-1 gene expression modulates the pulmonary vascular response to hypoxia. ET-1 gene deletion and selective activity of SM22α promoter-driven Cre recombinase were confirmed. Functional assays were performed under normoxic (21% O2) or hypoxic (5% O2) conditions using murine PASMC obtained from ET-1+/+ and ET-1−/− mic and in human PASMC (hPASMC) after silencing of ET-1 using siRNA. Under baseline conditions, there was no difference in right ventricular systolic pressure (RVSP) between SM22α-ET-1−/− and SM22α-ET-1+/+ (control) littermates. After exposure to hypoxia (10% O2, 21–24 days), RVSP was and vascular remodeling were less in SM22α-ET-1−/− mice compared with control littermates (P < 0.01). Loss of ET-1 decreased PASMC proliferation and migration and increased apoptosis under normoxic and hypoxic conditions. Exposure to selective ET-1 receptor antagonists had no effect on either the hypoxia-induced hPASMC proliferative or migratory response. SMC-specific ET-1 deletion attenuates hypoxia-induced increases in pulmonary vascular tone and structural remodeling. The observation that loss of ET-1 inhibited SMC proliferation, survival, and migration represents evidence that ET-1 derived from SMC plays a previously undescribed role in modulating the response of the pulmonary circulation to hypoxia. Thus PASMC ET-1 may modulate vascular tone independently of ET-1 produced by EC

  12. Computerized axial tomography of the chest for visualization of ''absent'' pulmonary arteries

    SciTech Connect

    Sondheimer, H.M.; Oliphant, M.; Schneider, B.; Kavey, R.E.W.; Blackman, M.S.; Parker, F.B. Jr.

    1982-05-01

    To expand the search for central pulmonary arteries in six patients with absence of cardiac-pulmonary continuity, computerized axial tomography (CAT) of the chest was performed. The CAT scans were compared with previous arteriograms and pulmonary vein wedge angiograms. Three patients with type IV truncus arteriosus were studied, and none had a central, right or left pulmonary artery on CAT scan. However, two patients with tetralogy of Fallot with pulmonary atresia and a patent ductus arteriosus to the right lung demonstrated the presence of a left pulmonary artery. In addition, one child with truncus arteriosus with ''absent'' left pulmonary artery demonstrated a left pulmonary artery on the CAT scan. The CAT scan may therefore enhance our ability to search for disconnected pulmonary arteries in children with complex cyanotic congenital heart disease.

  13. The effect of ACE inhibition on the pulmonary vasculature in combined model of chronic hypoxia and pulmonary arterial banding in Sprague Dawley rats

    NASA Astrophysics Data System (ADS)

    Clarke, Shanelle; Baumgardt, Shelley; Molthen, Robert

    2010-03-01

    Microfocal CT was used to image the pulmonary arterial (PA) tree in rodent models of pulmonary hypertension (PH). CT images were used to measure the arterial tree diameter along the main arterial trunk at several hydrostatic intravascular pressures and calculate distensibility. High-resolution planar angiographic imaging was also used to examine distal PA microstructure. Data on pulmonary artery tree morphology improves our understanding of vascular remodeling and response to treatments. Angiotensin II (ATII) has been identified as a mediator of vasoconstriction and proliferative mitotic function. ATII has been shown to promote vascular smooth muscle cell hypertrophy and hyperplasia as well as stimulate synthesis of extracellular matrix proteins. Available ATII is targeted through angiotensin converting enzyme inhibitors (ACEIs), a method that has been used in animal models of PH to attenuate vascular remodeling and decrease pulmonary vascular resistance. In this study, we used rat models of chronic hypoxia to induce PH combined with partial left pulmonary artery occlusion (arterial banding, PLPAO) to evaluate effects of the ACEI, captopril, on pulmonary vascular hemodynamic and morphology. Male Sprague Dawley rats were placed in hypoxia (FiO2 0.1), with one group having underwent PLPAO three days prior to the chronic hypoxia. After the twenty-first day of hypoxia exposure, treatment was started with captopril (20 mg/kg/day) for an additional twenty-one days. At the endpoint, lungs were excised and isolated to examine: pulmonary vascular resistance, ACE activity, pulmonary vessel morphology and biomechanics. Hematocrit and RV/LV+septum ratio was also measured. CT planar images showed less vessel dropout in rats treated with captopril versus the non-treatment lungs. Distensibility data shows no change in rats treated with captopril in both chronic hypoxia (CH) and CH with PLPAO (CH+PLPAO) models. Hemodynamic measurements also show no change in the pulmonary vascular

  14. Calculated mean arterial pressure in the posterior tibial and radial artery pressure wave in newborn infants.

    PubMed

    Gevers, M; Hack, M W; van Genderingen, H R; Lafeber, H N; Westerhof, N

    1995-01-01

    Mean arterial pressure (MAP) is the area under the pressure wave averaged over the cardiac cycle, and therefore depends on pressure wave contour. A generally used rule of thumb to estimate MAP of peripheral arteries in adults is adding one-third of the arterial pulse pressure (PP) to diastolic arterial pressure (DAP). As peripheral pressure wave forms in neonates do not resemble adult peripheral wave forms, it may be expected that this rule of thumb does not hold for neonates. Previously, we found that MAP can be calculated by adding 50% PP to DAP in radial artery waves in neonates. In the present study, we investigated in neonates how MAP in the posterior tibial artery depends on systolic and diastolic pressure and we compared these findings to those found in the radial artery. Forty infants admitted for intensive care were studied. We analyzed 5000 invasively and accurately obtained blood pressure waves in the posterior tibial artery of 20 neonates and another 5000 waves similarly obtained from the radial artery in another group of 20 neonates. We found that MAP in posterior tibial artery waves is well approximated by adding 41.5 +/- 2.0% of PP to DAP, whereas MAP in radial artery waves can be calculated by adding 46.7 +/- 1.7% of PP to DAP. These values are significantly different (p < 0.0001). In conclusion, the rule of thumb as used in the adult to find MAP, where 33% PP is added to DAP, does not hold for the newborn. We recommend to calculate MAP in the tibial artery by adding 40% of PP to DAP and in the radial artery by adding 50% of PP to DAP.

  15. Activation of AMPK Prevents Monocrotaline-Induced Extracellular Matrix Remodeling of Pulmonary Artery

    PubMed Central

    Li, Shaojun; Han, Dong; Zhang, Yonghong; Xie, Xinming; Ke, Rui; Zhu, Yanting; Liu, Lu; Song, Yang; Yang, Lan; Li, Manxiang

    2016-01-01

    Background The current study was performed to investigate the effect of adenosine monophosphate (AMP) – activated protein kinase (AMPK) activation on the extracellular matrix (ECM) remodeling of pulmonary arteries in pulmonary arterial hypertension (PAH) and to address its potential mechanisms. Material/Methods PAH was induced by a single intraperitoneal injection of monocrotaline (MCT) into Sprague-Dawley rats. Metformin (MET) was administered to activate AMPK. Immunoblotting was used to determine the phosphorylation and expression of AMPK and expression of tissue inhibitor of metalloproteinase-1 (TIMP-1). Gelatin zymography was performed to determine the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9. Results Activation of AMPK by MET significantly reduced the right ventricle systolic pressure and the right ventricular hypertrophy in MCT-induced rat PAH model, and partially inhibited the ECM remodeling of pulmonary arteries. These effects were coupled with the decrease of MMP-2/9 activity and TIMP-1 expression. Conclusions This study suggests that activation of AMPK benefits PAH by inhibiting ECM remodeling of pulmonary arteries. Enhancing AMPK activity might have potential value in clinical treatment of PAH. PMID:26978596

  16. Recent advances in targeting the prostacyclin pathway in pulmonary arterial hypertension.

    PubMed

    Lang, Irene M; Gaine, Sean P

    2015-12-01

    Pulmonary arterial hypertension (PAH) is a severe disease characterised by increased pulmonary vascular resistance, which leads to restricted pulmonary arterial blood flow and elevated pulmonary arterial pressure. In patients with PAH, pulmonary concentrations of prostacyclin, a prostanoid that targets several receptors including the IP prostacyclin receptor, are reduced. To redress this balance, epoprostenol, a synthetic prostacyclin, or analogues of prostacyclin have been given therapeutically. These therapies improve exercise capacity, functional class and haemodynamic parameters. In addition, epoprostenol improves survival among patients with PAH. Despite their therapeutic benefits, treatments that target the prostacyclin pathway are underused. One key factor is their requirement for parenteral administration: continuous intravenous administration can lead to embolism and thrombosis; subcutaneous administration is associated with infusion-site pain; and inhalation is time consuming, requiring multiple daily administrations. Nevertheless, targeting the prostacyclin pathway is an important strategy for the management of PAH. The development of oral therapies for this pathway, as well as more user-friendly delivery devices, may alleviate some of the inconveniences. Continued improvements in therapeutic options will enable more patients with PAH to receive medication targeting the prostacyclin pathway.

  17. Simultaneous pulmonary and systemic blood pressure and ECG Interval measurement in conscious, freely moving rats.

    PubMed

    Rey, Markus; Weber, Edgar W; Hess, Patrick D

    2012-03-01

    Here we evaluated the ability of a new, dual blood-pressure telemetry transmitter to simultaneously measure pulmonary and systemic blood pressure and the electrocardiogram in rats. The transmitter was implanted in normotensive and monocrotaline-induced pulmonary hypertensive Wistar rats, with sensing catheters placed in the pulmonary artery (channel 1) and descending aorta (channel 2). Biopotential electrodes were positioned to record an apex-based lead II electrocardiogram. Pulmonary and systemic arterial blood pressure and electrocardiographic waveforms were recorded between 2 and 12 wk after implantation of the transmitter. During this period, pulmonary arterial pressure progressively increased in monocrotaline-treated compared with saline-treated rats. The pharmacologic response of rats to reference compounds was measured by using the transmitter to validate the technique and to evaluate the ability of the device to transmit changes in blood pressure and the electrocardiogram. Validation against 2 Millar high-fidelity blood-pressure catheters confirmed the accuracy of the blood pressure data recorded with the transmitter. In addition, local tolerance of the associated catheters was confirmed by histologic examination. PMID:22776124

  18. [Pulmonary arterial hypertension associated to human immunodeficiency virus].

    PubMed

    Sandoval-Gutiérrez, José Luis; Santos-Martínez, Luis Efren; Rodríguez-Silverio, Juan; Baranda-Tovar, Francisco Martín; Rivera-Rosales, Rosa María; Flores-Murrieta, Francisco Javier

    2015-01-01

    From the advent of the highly effective antiretroviral treatment, the life expectancy of patients with human immunodeficiency virus has increased significantly. At present, the causes of death are non-infectious complications. Between them, the pulmonary arterial hypertension has a special importance. It is important early detection to establish the therapeutic, with the objective of preventing a fatal outcome to future. PMID:25577549

  19. [Clinical utility of inhaled iloprost in pulmonary arterial hypertension].

    PubMed

    Santos-Martínez, Luis Efren; Moreno-Ruiz, Luis Antonio; Jiménez-Santos, Moisés; Olmos-Temois, Sergio Gabriel; Bojorquez-Guerrero, Luis Armando; Baranda-Tovar, Francisco Martín

    2014-01-01

    Inhaled iloprost is a drug from the group of prostacyclins used in the treatment of pulmonary arterial hypertension. Its efficacy and safety have allowed its use as monotherapy and combination therapy. This review describes the product characteristics, amenable to treatment groups, and updated clinical evidence of drug use.

  20. [Pulmonary arterial hypertension associated to human immunodeficiency virus].

    PubMed

    Sandoval-Gutiérrez, José Luis; Santos-Martínez, Luis Efren; Rodríguez-Silverio, Juan; Baranda-Tovar, Francisco Martín; Rivera-Rosales, Rosa María; Flores-Murrieta, Francisco Javier

    2015-01-01

    From the advent of the highly effective antiretroviral treatment, the life expectancy of patients with human immunodeficiency virus has increased significantly. At present, the causes of death are non-infectious complications. Between them, the pulmonary arterial hypertension has a special importance. It is important early detection to establish the therapeutic, with the objective of preventing a fatal outcome to future.

  1. Material coefficients of the strain energy function of pulmonary arteries in normal and cigarette smoke-exposed rats.

    PubMed

    Liu, S Q; Fung, Y C

    1993-11-01

    The effect of cigarette smoke on the stress-strain relationship of pulmonary arteries was studied in 2- and 3-month smoke-exposed rats. The animals were exposed to cigarette smoke in a smoke-generating system 10 times daily with one cigarette each time. The smoke density and the puffing duration and frequency of the system were regulated in accordance with reference values measured from human smokers. The mechanical properties of the pulmonary arteries about 450 microns in external diameter (at zero pressure) were determined in vitro by inflation and deflation tests. The average stress and middle-wall strain of the selected pulmonary arteries were determined on the basis of experimental data including inflation and deflation pressures during loading and unloading processes, respectively, and vessel diameter and length at various pressure levels, and vessel circumferential and longitudinal lengths at zero-stress state. A constitutive equation for the pulmonary arteries was derived from an energy function depending on circumferential and longitudinal Green's strains. The coefficients of the strain energy function of the pulmonary arteries were determined in both the smoke-exposed and control rats by fitting the experimental stress-strain data with the constitutive equation. It was found that the wall stress of the pulmonary arteries at a given strain and most of the coefficients of the strain energy function were increased in both the 2- and 3-month smoke-exposed rats in comparison with those in the corresponding controls. These results indicated that cigarette smoke induced an increase in the wall stiffness of the pulmonary arteries in the rats. PMID:8262988

  2. Diagnosis of pulmonary hypertension from radiographic estimates of pulmonary arterial size.

    PubMed Central

    Bush, A; Gray, H; Denison, D M

    1988-01-01

    The reported accuracy of radiographic measurements in predicting pulmonary hypertension is very variable. Measurements of right and left descending pulmonary artery diameter have been reported to provide a correct diagnosis in as many as 98% of patients. A study was carried out to determine the predictive value of measurements made from the chest radiographs of 50 normal subjects and of 27 patients undergoing right heart catheterisation for cardiac or pulmonary vascular disease, taking account of radiographic magnification. After such corrections a right descending pulmonary artery diameter over 16.7 mm or a left descending pulmonary artery diameter of over 16.9 mm distinguished 12 of 23 pulmonary hypertensive subjects, with no false positive results. The diameter was then arbitrarily squared (any differences between patients and control subjects being exaggerated) and the product was divided by either predicted or actual lung volume in an attempt to correct for body size. The new index distinguished 19 of 23 patients with pulmonary hypertension, with one false positive, when the divisor was actual lung volume; when predicted lung volume was used 18 of 23 patients were distinguished, again with one false positive result. PMID:3353884

  3. Constitutively active form of natriuretic peptide receptor 2 ameliorates experimental pulmonary arterial hypertension

    PubMed Central

    Nawa, Nobutoshi; Ishida, Hidekazu; Katsuragi, Shinichi; Baden, Hiroki; Takahashi, Kunihiko; Higeno, Ryota; Torigoe, Fumiko; Mihara, Seiko; Narita, Jun; Miura, Kohji; Nakamura, Kazufumi; Kogaki, Shigetoyo; Ozono, Keiichi

    2016-01-01

    We recently found a constitutively active mutant of natriuretic peptide receptor 2 (caNPR2; V883M), which synthesizes larger amounts of cyclic guanosine monophosphate (cGMP) intracellularly without any ligand stimulation than existing drugs. The aim of this study was to investigate the therapeutic effects of gene transduction using caNPR2 for pulmonary arterial hypertension (PAH). In vitro gene transduction into human pulmonary arterial smooth muscle cells using Sendai virus (SeV) vectors carrying caNPR2 induced 10,000-fold increases in the synthesis of cGMP without ligand stimulation, and the proliferation of caNPR2-expressing cells was significantly attenuated. The PAH model rats generated by hypoxia and the administration of SU5416 were then treated with SeV vectors through a direct injection into the left pulmonary artery. Right ventricular systolic pressure was significantly decreased 2 weeks after the treatment, while systemic blood pressure remained unchanged. Histological analyses revealed that the medial wall thickness and occlusion rate of pulmonary arterioles were significantly improved in caNPR2-treated lungs. Neither the systemic integration of virus vectors nor side effects were observed. The massive stimulation of cGMP synthesis by gene therapy with caNPR2 was safe and effective in a PAH rat model and, thus, has potential as a novel therapy for patients with severe progressive PAH. PMID:27419193

  4. Fatal Pulmonary Embolus After Uterine Artery Fibroid Embolisation

    SciTech Connect

    Hamoda, Haitham; Tait, P.; Edmonds, D. K.

    2009-09-15

    We report a 44-year-old woman who developed a fatal pulmonary embolus after uterine artery fibroid embolisation (UAE). Bilateral UAE was carried out through a single right-femoral artery puncture. The largest fibroid in the anterior fundal wall measured 4.5 cm, and the largest fibroid in the posterior fundal wall measured 6 cm. The appearances after UAE were satisfactory, and the procedure was apparently uneventful. No immediate complications were noted. The patient developed sudden-onset shortness of breath and went into cardiac arrest 19 h after the procedure. Postmortem autopsy confirmed that the cause of a death was a pulmonary embolism. To our knowledge this is the first reported case in the United Kingdom in which death occurred from a pulmonary embolus after UAE.

  5. Loss of alveolar membrane diffusing capacity and pulmonary capillary blood volume in pulmonary arterial hypertension

    PubMed Central

    2013-01-01

    Background Reduced gas transfer in patients with pulmonary arterial hypertension (PAH) is traditionally attributed to remodeling and progressive loss of pulmonary arterial vasculature that results in decreased capillary blood volume available for gas exchange. Methods We tested this hypothesis by determination of lung diffusing capacity (DL) and its components, the alveolar capillary membrane diffusing capacity (Dm) and lung capillary blood volume (Vc) in 28 individuals with PAH in comparison to 41 healthy individuals, and in 19 PAH patients over time. Using single breath simultaneous measure of diffusion of carbon monoxide (DLCO) and nitric oxide (DLNO), DL and Dm were respectively determined, and Vc calculated. Dm and Vc were evaluated over time in relation to standard clinical indicators of disease severity, including brain natriuretic peptide (BNP), 6-minute walk distance (6MWD) and right ventricular systolic pressure (RVSP) by echocardiography. Results Both DLCO and DLNO were reduced in PAH as compared to controls and the lower DL in PAH was due to loss of both Dm and Vc (all p < 0.01). While DLCO of PAH patients did not change over time, DLNO decreased by 24 ml/min/mmHg/year (p = 0.01). Consequently, Dm decreased and Vc tended to increase over time, which led to deterioration of the Dm/Vc ratio, a measure of alveolar-capillary membrane functional efficiency without changes in clinical markers. Conclusions The findings indicate that lower than normal gas transfer in PAH is due to loss of both Dm and Vc, but that deterioration of Dm/Vc over time is related to worsening membrane diffusion. PMID:23339456

  6. Right Pulmonary Artery Distensibility Index (RPAD Index). A field study of an echocardiographic method to detect early development of pulmonary hypertension and its severity even in the absence of regurgitant jets for Doppler evaluation in heartworm-infected dogs.

    PubMed

    Venco, Luigi; Mihaylova, Liliya; Boon, June A

    2014-11-15

    Despite the term "heartworm disease" Dirofilaria immitis infection in dogs should be considered a pulmonary arterial disease that might only involve the right heart structures in its late stage. Chronic infection by adult heartworms in dogs results in proliferative endoarteritis leading to progressively increasing pulmonary artery pressure due to reduced elasticity. Elasticity allows the pulmonary arteries to stretch in response to each pulse and helps maintain a relatively constant pressure in the arteries despite the pulsating nature of the blood flow. Pulmonary artery distensibility for both acute and chronic pulmonary hypertension has been investigated in humans using MRI and has been correlated with the severity of hypertension and its outcome and treatment response. The aim of the present study was to investigate whether echocardiographic measurement of the percentage change in diameter of the right pulmonary artery in systole and diastole (distensibility) may be of value in assessing the presence and severity of pulmonary hypertension in heartworm-infected dogs. The Right Pulmonary Artery Distensibility Index (RPAD Index) (which is calculated as the difference in diameter of the right pulmonary artery in systole and diastole) was calculated in healthy and naturally infected heartworm-positive dogs. The right pulmonary artery was chosen because it is usually affected earlier and to a greater degree. Data were obtained from healthy heartworm-free dogs without any clinical, radiographic, or echocardiographic signs of pulmonary hypertension; naturally infected heartworm-positive dogs in different stages of the disease in which pulmonary pressure could be measured by Doppler echocardiography (using tricuspid and or pulmonary regurgitation velocity and pressure gradient); and naturally infected heartworm-positive dogs in different stages of the disease (with or without tricuspid and or pulmonary regurgitation) in which the pulmonary pressure was measured

  7. Altered artery mechanics and structure in monocrotaline pulmonary hypertension.

    PubMed

    Langleben, D; Szarek, J L; Coflesky, J T; Jones, R C; Reid, L M; Evans, J N

    1988-11-01

    Pulmonary hypertension in rats, induced by an injection of monocrotaline, is associated with changes in the wall structure of the pulmonary arterial bed. We have studied the effects of this remodeling on mechanical properties of cylindrical pulmonary artery segments from rats 21 days after monocrotaline (MCT) injection. Resting and active (KCl induced) circumference-tension relationships were established for segments of extrapulmonary and intrapulmonary arteries isolated from the hilum and the fifth lateral branch from the axial pathway (all preacinar). The thicknesses of the vessel wall, the media, and adventitia were measured at several positions around the circumference of the artery by computerized analysis of histological cross sections of the segments fixed at a standard circumference. Resting and active stress were also calculated. The study shows that active circumferential tension and active stress are reduced in vessels from MCT-treated rats. Based on our findings, it is unlikely that altered contractile function of preacinar arteries contributes significantly to the increased vascular resistance seen in this model. PMID:3145283

  8. Therapeutic effect of low-dose imatinib on pulmonary arterial hypertension in dogs.

    PubMed

    Arita, Shinji; Arita, Noboru; Hikasa, Yoshiaki

    2013-03-01

    This was a pilot study to determine the effectiveness of low-dose imatinib therapy for hemodynamic disturbances, including pulmonary arterial hypertension (PAH), and clinical manifestations caused by chronic heart failure in dogs. Six client-owned dogs with PAH were administered imatinib mesylate orally, 3 mg/kg body weight q24h, for 30 d. Physical examination, blood biochemical tests, radiography, and Doppler echocardiography were performed prior to imatinib administration and again 30 days after administration. Clinical scores were significantly reduced after imatinib treatment. Systolic pulmonary arterial pressure, heart rate, maximum tricuspid regurgitation velocity, left atrium/aorta ratio, right and left ventricular Tei indexes, early diastolic transmitral flow wave/mitral annulus velocity ratio, and plasma atrial natriuretic peptide concentration decreased significantly after therapy. Diastolic blood pressure, stroke volume, cardiac output, and left ventricular fractional shortening increased significantly after therapy. These results indicate that low-dose imatinib therapy was effective for heart failure in dogs with PAH.

  9. Therapeutic effect of low-dose imatinib on pulmonary arterial hypertension in dogs

    PubMed Central

    Arita, Shinji; Arita, Noboru; Hikasa, Yoshiaki

    2013-01-01

    This was a pilot study to determine the effectiveness of low-dose imatinib therapy for hemodynamic disturbances, including pulmonary arterial hypertension (PAH), and clinical manifestations caused by chronic heart failure in dogs. Six client-owned dogs with PAH were administered imatinib mesylate orally, 3 mg/kg body weight q24h, for 30 d. Physical examination, blood biochemical tests, radiography, and Doppler echocardiography were performed prior to imatinib administration and again 30 days after administration. Clinical scores were significantly reduced after imatinib treatment. Systolic pulmonary arterial pressure, heart rate, maximum tricuspid regurgitation velocity, left atrium/aorta ratio, right and left ventricular Tei indexes, early diastolic transmitral flow wave/mitral annulus velocity ratio, and plasma atrial natriuretic peptide concentration decreased significantly after therapy. Diastolic blood pressure, stroke volume, cardiac output, and left ventricular fractional shortening increased significantly after therapy. These results indicate that low-dose imatinib therapy was effective for heart failure in dogs with PAH. PMID:23997262

  10. Controlled Release Inhalable Polymeric Microspheres for Treatment of Pulmonary Arterial Hypertension.

    PubMed

    Saigal, Aparna; Ng, Wai Kiong; Tan, Reginald B H; Chan, Sui Yung

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a chronic ailment of the lungs, exhibiting elevated arterial pressure and vascular resistance; with a mean arterial pressure above 25 mmHg at rest and above 30 mmHg during exercise. It is associated with poor prognosis, and its prevalence is estimated to be 15 cases per one million. The current treatment options for PAH are discussed with the prostanoid class of drugs being the most effective. The latter drugs act by dilating systemic and pulmonary arterial vascular beds and, with sustained long-term usage, altering pulmonary remodelling. They are administered as IV infusions or inhalation solutions. Despite their clinical effectiveness, prostanoids have short half-lives requiring frequent administration of 6-9 times daily and thus suffer from poor compliance. Controlled release inhalation delivery systems for treatment of PAH, ranging from liposomes, biodegradable nano- and microparticles, formation of co-precipitates and complexation with cyclodextrins, are explored. Arising from these formulation strategies, we developed novel polymeric microspheres for inhalation to reduce dosing frequency and improve medication compliance. These microspheres are designed with release modifiers, to reside in the lung which is the site of drug action for a longer duration so as to release the drug slowly and consistently over a prolonged period. This could lead to the development of the first commercially available controlled release inhalation product. PMID:26446472

  11. Systemic Artery to Pulmonary Artery Fistula Associated with Mitral Regurgitation: Successful Treatment with Endovascular Embolization

    SciTech Connect

    Iwazawa, Jin; Nakamura, Kenji; Hamuro, Masao; Nango, Mineyoshi; Sakai, Yukimasa; Nishida, Norifumi

    2008-07-15

    We present the case of a 60-year-old woman with symptomatic mitral regurgitation caused by a left-to-right shunt via anastomoses consisting of microfistulae, most likely of inflammatory origin, between the right subclavian artery and the right pulmonary artery. The three arteries responsible for fistulous formation, including the internal mammary, thyrocervical, and lateral thoracic arteries, were successfully occluded by transcatheter embolization using superabsorbent polymer microsphere (SAP-MS) particles combined with metallic coils. No complications have been identified following treatment with SAP-MS particles. This approach significantly reduced the patient's mitral regurgitation and she has remained asymptomatic for more than 4 years.

  12. 17β-estradiol attenuates conduit pulmonary artery mechanical property changes with pulmonary arterial hypertension

    PubMed Central

    Liu, Aiping; Tian, Lian; Golob, Mark; Eickhoff, Jens C.; Boston, Madison; Chesler, Naomi C.

    2015-01-01

    Pulmonary arterial hypertension (PAH), a rapidly fatal vascular disease, strikes women more often than men. Paradoxically, female PAH patients have better prognosis and survival rates than males. The female sex hormone 17β-estradiol has been linked to the better outcome of PAH in females; however, the mechanisms by which 17β-estradiol alters PAH progression and outcomes remain unclear. Since proximal PA stiffness, one hallmark of PAH, is a powerful predictor of mortality and morbidity, we hypothesized that 17β-estradiol attenuates PAH-induced changes in mechanical properties in conduit proximal PAs, which imparts hemodynamic and energetic benefits to RV function. To test this hypothesis, female mice were ovariectomized and treated with 17β-estradiol or placebo. PAH was induced in mice using SU5416 and chronic hypoxia (SuHx). Extra-lobar left PAs were isolated and mechanically tested ex vivo to study both static and frequency-dependent mechanical behaviors in the presence or absence of SMC activation. Our static mechanical test showed significant stiffening of large PAs with PAH (P < 0.05). 17β-estradiol restored PA compliance to control levels. The dynamic mechanical test demonstrated that 17β-estradiol protected the arterial wall from the PAH-induced frequency-dependent decline in dynamic stiffness and loss of viscosity with PAH (P<0.05). As demonstrated by the in vivo measurement of PA hemodynamics via RV catheterization, modulation by 17β-estradiol of mechanical proximal PAs reduced pulsatile loading, which contributed to improved ventricular-vascular coupling. This study provides a mechanical mechanism for delayed disease progression and better outcome in female PAH patients and underscores the therapeutic potential of 17β-estradiol in PAH. PMID:26418020

  13. Effects of altered left atrial pressure on pulmonary vascular pressure-flow relationships.

    PubMed

    Ducas, J; Schick, U; Girling, L; Prewitt, R M

    1988-07-01

    We studied the effects of changes in pulmonary capillary wedge pressure (PCWP) on the slope (incremental resistance) and the extrapolated pressure intercept (PI) of the mean pulmonary artery pressure (PAP)-cardiac output (CO) relationship. Multipoint plots of PAP against CO were obtained in intact anesthetized dogs. Group 1 consisted of six dogs entirely in West zone 3 and group 2 of four dogs with mixed West zone 2-3. The four conditions studied were the following: 1) fixed low PCWP, 2) fixed high PCWP, 3) variable PCWP, and 4) time-control repeat of condition 1. The PI significantly exceeded PCWP at fixed low PCWP (group 1, 9.3 vs. 11.1 mmHg, group 2, 6.6 vs. 3.9 mmHg). PI became identical to PCWP only at fixed high PCWP in group 1 (19 +/- 2.0 vs. 19 +/- 1.1 mmHg). Thus PCWP reflects the effective vascular outflow pressure when PCWP is fixed and high. For both groups of dogs in condition 3, when PCWP was varied with CO, the slope of the resulting PAP-CO plot was significantly greater than when PCWP was constant. Also in 9 of 10 dogs, PI was less than PCWP when PCWP was varied. These findings demonstrate that when changes in PCWP are allowed to occur during the generation of a pulmonary artery pressure-flow plot, the resulting slope and intercept, as defined by a Starling resistor model, do not accurately represent the incremental resistance and outflow pressure of the pulmonary vasculature. PMID:3293470

  14. Rare case of truncus arteriosus with anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA) and unilateral left pulmonary artery agenesis.

    PubMed

    Mittal, Kartik; Dey, Amit K; Gadewar, Rohit; Sharma, Rajaram; Pandit, Nilesh; Rajput, Priya; Hira, Priya

    2015-04-01

    The incidence of congenital heart disease (CHD) is 2.4-3.8/1000 live births. Up to 70.7 % of all cases of CHD are reported to be benign; complex heart anomalies are extremely rare. Our case is extremely rare, as we report three very rare findings-truncus arteriosus, anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA), and unilateral left pulmonary artery agenesis-in a single patient. Congenital complex cardiac abnormalities are very rare, and two-dimensional echocardiography screening should be supported by cardiac computed tomography (CT). We report a case of truncus arteriosus associated with ARCAPA and left pulmonary artery agenesis diagnosed by cardiac computed tomography; we believe that such an unusual case with all three of these entities has never been reported before. PMID:25731755

  15. Vascular pressures and passage of gas emboli through the pulmonary circulation

    NASA Technical Reports Server (NTRS)

    Butler, B. D.; Katz, J.

    1988-01-01

    Doppler technique was used to measure the pulmonary vascular pressure gradients in dogs that received venous air emboli (VAE) at the rate of 0.35 ml/kg per min, at which the spillover of bubbles into the systemic arteries occur. It was found that, in 60 percent of dogs, venous bubbles spilled over into the arterial circulation at the pulmonary vascular pressure gradient of about 34.7 mm Hg. When the pulmonary vascular pressure gradient was raised to about 52 mm Hg, the spillover of venous bubbles occurred 100 percent of time. It is concluded that venous bubbles can cross the lungs of anesthetized dogs when the driving pressures are sufficient to overcome the normal filtering function.

  16. [Pulmonary arterial hypertension, bone marrow, endothelial cell precursors and serotonin].

    PubMed

    Ayme-Dietrich, Estelle; Banas, Sophie M; Monassier, Laurent; Maroteaux, Luc

    2016-01-01

    Serotonin and bone-marrow-derived stem cells participate together in triggering pulmonary hypertension. Our work has shown that the absence of 5-HT2B receptors generates permanent changes in the composition of the blood and bone-marrow in the myeloid lineages, particularly in endothelial cell progenitors. The initial functions of 5-HT2B receptors in pulmonary arterial hypertension (PAH) are restricted to bone-marrow cells. They contribute to the differentiation/proliferation/mobilization of endothelial progenitor cells from the bone-marrow. Those bone-marrow-derived cells have a critical role in the development of pulmonary hypertension and pulmonary vascular remodeling. These data indicate that bone-marrow derived endothelial progenitors play a key role in the pathogenesis of PAH and suggest that interactions involving serotonin and bone morphogenic protein type 2 receptor (BMPR2) could take place at the level of the bone-marrow. PMID:27687599

  17. Pulmonary artery denervation for treatment of a patient with pulmonary hypertension secondary to left heart disease

    PubMed Central

    2016-01-01

    Abstract Pulmonary hypertension (PH) predicts poor outcome in patients with left heart disease. A 62-year-old man was referred for heart failure associated with ischemic cardiomyopathy. He received a diagnosis of combined postcapillary and precapillary PH secondary to left heart disease on the basis of hemodynamic parameters. After the pulmonary artery denervation procedure was performed, hemodynamic parameters were markedly improved, which resulted in a significant increase in functional capacity. PMID:27252851

  18. Treatment of an Iatrogenic Left Internal Mammary Artery to Pulmonary Artery Fistula with a Bovine Pericardium Covered Stent

    SciTech Connect

    Heper, Gulumser Barcin, Cem; Iyisoy, Atila; Tore, Hasan F.

    2006-10-15

    We report a case with an acquired fistula between the left internal mammary artery and the pulmonary artery following coronary bypass surgery treated with a bovine pericardium covered stent. We also reviewed similar cases reported previously.

  19. Salvianolic acid A attenuates vascular remodeling in a pulmonary arterial hypertension rat model

    PubMed Central

    Chen, Yu-cai; Yuan, Tian-yi; Zhang, Hui-fang; Wang, Dan-shu; Yan, Yu; Niu, Zi-ran; Lin, Yi-huang; Fang, Lian-hua; Du, Guan-hua

    2016-01-01

    Aim: The current therapeutic approaches have a limited effect on the dysregulated pulmonary vascular remodeling, which is characteristic of pulmonary arterial hypertension (PAH). In this study we examined whether salvianolic acid A (SAA) extracted from the traditional Chinese medicine 'Dan Shen' attenuated vascular remodeling in a PAH rat model, and elucidated the underlying mechanisms. Methods: PAH was induced in rats by injecting a single dose of monocrotaline (MCT 60 mg/kg, sc). The rats were orally treated with either SAA (0.3, 1, 3 mg·kg−1·d−1) or a positive control bosentan (30 mg·kg−1·d−1) for 4 weeks. Echocardiography and hemodynamic measurements were performed on d 28. Then the hearts and lungs were harvested, the organ indices and pulmonary artery wall thickness were calculated, and biochemical and histochemical analysis were conducted. The levels of apoptotic and signaling proteins in the lungs were measured using immunoblotting. Results: Treatment with SAA or bosentan effectively ameliorated MCT-induced pulmonary artery remodeling, pulmonary hemodynamic abnormalities and the subsequent increases of right ventricular systolic pressure (RVSP). Furthermore, the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium, parenchymal injury and collagen deposition in the lungs. Moreover, the treatments attenuated MCT-induced apoptosis and fibrosis in the lungs. The treatments partially restored MCT-induced reductions of bone morphogenetic protein type II receptor (BMPRII) and phosphorylated Smad1/5 in the lungs. Conclusion: SAA ameliorates the pulmonary arterial remodeling in MCT-induced PAH rats most likely via activating the BMPRII-Smad pathway and inhibiting apoptosis. Thus, SAA may have therapeutic potential for the patients at high risk of PAH. PMID:27180980

  20. CT-Base Pulmonary Artery Measurementin the Detection of Pulmonary Hypertension

    PubMed Central

    Shen, Yongchun; Wan, Chun; Tian, Panwen; Wu, Yanqiu; Li, Xiaoou; Yang, Ting; An, Jing; Wang, Tao; Chen, Lei; Wen, Fuqiang

    2014-01-01

    Abstract To summarize the performance of CT-based main pulmonary artery diameter or pulmonary artery to aorta ratio (PA:A ratio) measurement in detection of pulmonary hypertension by a systematic review and meta-analysis. A comprehensive literature search was performed to identify studies determining diagnostic accuracy of main pulmonary artery diameter or PA:A ratio measurement for pulmonary hypertension. The Quality Assessment of Diagnostic Accuracy Studies tool was used to assess the quality of the included studies. A bivariate random-effects model was used to pool sensitivity, specificity, positive/negative likelihood ratio (PLR/NLR), and diagnostic odds ratio (DOR). Summary receiver operating characteristic (SROC) curves and area under the curve (AUC) were used to summarize overall diagnostic performance. This meta-analysis included 20 publications involving 2134 subjects. Summary estimates for main pulmonary artery diameter measurement in the diagnosis of pulmonary hypertension were as follows: sensitivity, 0.79 (95% CI 0.72–0.84); specificity, 0.83 (95% CI 0.75–0.89); PLR, 4.68 (95% CI 3.13–6.99); NLR, 0.26 (95% CI 0.20–0.33); DOR, 18.13 (95% CI 10.87–30.24); and AUC 0.87. The corresponding summary performance estimates for using the PA:A ratio were as follows: sensitivity, 0.74 (95% CI 0.66–0.80); specificity, 0.81 (95% CI 0.74–0.86); PLR, 3.83 (95% CI, 2.70–5.43); NLR, 0.33 (95% CI 0.24–0.44); DOR, 11.77 (95% CI 6.60–21.00); and AUC 0.84. Both main pulmonary artery diameter and PA:A ratio are helpful for diagnosing pulmonary hypertension. Nevertheless, the results of pulmonary artery measurement should be interpreted in parallel with the results of traditional tests such as echocardiography. PMID:25501096

  1. Peptide-Coated Liposomal Fasudil Enhances Site Specific Vasodilation in Pulmonary Arterial Hypertension

    PubMed Central

    2015-01-01

    This study sought to develop a liposomal delivery system of fasudil—an investigational drug for the treatment of pulmonary arterial hypertension (PAH)—that will preferentially accumulate in the PAH lungs. Liposomal fasudil was prepared by film-hydration method, and the drug was encapsulated by active loading. The liposome surface was coated with a targeting moiety, CARSKNKDC, a cyclic peptide; the liposomes were characterized for size, polydispersity index, zeta potential, and storage and nebulization stability. The in vitro drug release profiles and uptake by TGF-β activated pulmonary arterial smooth muscle cells (PASMC) and alveolar macrophages were evaluated. The pharmacokinetics were monitored in male Sprague–Dawley rats, and the pulmonary hemodynamics were studied in acute and chronic PAH rats. The size, polydispersity index (PDI), and zeta potential of the liposomes were 206–216 nm, 0.058–0.084, and −20–42.7 mV, respectively. The formulations showed minimal changes in structural integrity when nebulized with a commercial microsprayer. The optimized formulation was stable for >4 weeks when stored at 4 °C. Fasudil was released in a continuous fashion over 120 h with a cumulative release of 76%. Peptide-linked liposomes were taken up at a higher degree by TGF-β activated PASMCs; but alveolar macrophages could not engulf peptide-coated liposomes. The formulations did not injure the lungs; the half-life of liposomal fasudil was 34-fold higher than that of plain fasudil after intravenous administration. Peptide-linked liposomal fasudil, as opposed to plain liposomes, reduced the mean pulmonary arterial pressure by 35–40%, without influencing the mean systemic arterial pressure. This study establishes that CAR-conjugated inhalable liposomal fasudil offers favorable pharmacokinetics and produces pulmonary vasculature specific dilatation. PMID:25333706

  2. miR-223 reverses experimental pulmonary arterial hypertension.

    PubMed

    Meloche, Jolyane; Le Guen, Marie; Potus, François; Vinck, Jérôme; Ranchoux, Benoit; Johnson, Ian; Antigny, Fabrice; Tremblay, Eve; Breuils-Bonnet, Sandra; Perros, Frederic; Provencher, Steeve; Bonnet, Sébastien

    2015-09-15

    Pulmonary arterial hypertension (PAH) is a devastating disease affecting lung vasculature. The pulmonary arteries become occluded due to increased proliferation and suppressed apoptosis of the pulmonary artery smooth muscle cells (PASMCs) within the vascular wall. It was recently shown that DNA damage could trigger this phenotype by upregulating poly(ADP-ribose)polymerase 1 (PARP-1) expression, although the exact mechanism remains unclear. In silico analyses and studies in cancer demonstrated that microRNA miR-223 targets PARP-1. We thus hypothesized that miR-223 downregulation triggers PARP-1 overexpression, as well as the proliferation/apoptosis imbalance observed in PAH. We provide evidence that miR-223 is downregulated in human PAH lungs, distal PAs, and isolated PASMCs. Furthermore, using a gain and loss of function approach, we showed that increased hypoxia-inducible factor 1α, which is observed in PAH, triggers this decrease in miR-223 expression and subsequent overexpression of PARP-1 allowing PAH-PASMC proliferation and resistance to apoptosis. Finally, we demonstrated that restoring the expression of miR-223 in lungs of rats with monocrotaline-induced PAH reversed established PAH and provided beneficial effects on vascular remodeling, pulmonary resistance, right ventricle hypertrophy, and survival. We provide evidence that miR-223 downregulation in PAH plays an important role in numerous pathways implicated in the disease and restoring its expression is able to reverse PAH. PMID:26084306

  3. Anomalous origin of the left coronary artery from the pulmonary artery, scimitar syndrome, and aortic coarctation.

    PubMed

    Ilic, Slobodan; Hercog, Djordje; Vucicevic, Milan; Vulicevic, Irena; Mimic, Branko; Djukic, Milan; Jovanovic, Ida; Parezanovic, Vojislav; Ilisic, Tamara

    2014-02-01

    Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) represents one of the most common causes of myocardial ischemia in infants and if left untreated results in a high mortality rate. When ALCAPA coexists with other congenital malformations, particularly those associated with pulmonary hypertension, the initial presentation can be quite confusing and is often misinterpreted. We report an infant with ALCAPA associated with scimitar syndrome and aortic coarctation whose clinical course illustrates the complexities and difficulties of management with a successful outcome. PMID:24484819

  4. Apoptosis-based therapy to treat pulmonary arterial hypertension

    PubMed Central

    Suzuki, Yuichiro J.; Ibrahim, Yasmine F.; Shults, Nataliia V.

    2016-01-01

    Pulmonary arterial hypertension (PAH) is rare, but patients who are diagnosed with this disease still suffer from a lack of satisfactory treatment strategies to prolong survival. While currently approved drugs for PAH have some benefits, these vasodilators only have limited efficacy for eliminating pulmonary vascular remodeling and reducing mortality. Thus, our laboratory has been exploring the use of aggressive drugs, which are capable of causing apoptotic cell death, to treat PAH. We have so far found that three classes of anti-tumor agents, including anthracyclines, taxanes, and proteasome inhibitors, are capable of reducing pulmonary vascular thickness in rats with PAH. These drugs kill cells in remodeled pulmonary vessels without affecting the normal, healthy pulmonary vasculature, revealing that proliferating vascular cells in PAH patients are more sensitive to drug-induced apoptosis compared to the differentiated phenotype that is physiologically important for smooth muscle contraction. Since many apoptosis-inducing drugs cause cardiotoxicity in cancer patients, and because PAH patients already have a weakened heart, we focus on finding biological mechanisms that may reverse pulmonary vascular remodeling without promoting cardiotoxicity. We found two agents, dexrazoxane and pifithrin-α, that selectively inhibit cardiac muscle apoptosis without affecting the drug-induced apoptosis of the proliferating pulmonary vascular cells. Thus, we propose that the addition of apoptosis-inducing drugs and cardioprotectants to PAH therapies may be effective in treating patients and preventing right heart failure.

  5. Upregulation of Transient Receptor Potential Canonical Channels Contributes to Endotoxin-Induced Pulmonary Arterial Stenosis

    PubMed Central

    Chen, Gui-Lan; Jiang, Hongni; Zou, Fangdong

    2016-01-01

    Background Septic shock is a pathologic condition caused by endotoxin-producing bacteria, and often associated with severe pulmonary hypertension. Inflammation is a major systemic response to endotoxin; however, it is unknown whether endotoxin has a direct impact on pulmonary arteries that contributes to pathogenesis of pulmonary hypertension. Material/Methods Rat pulmonary arteries and primary pulmonary arterial smooth muscle cells (PASMCs) were cultured in vitro and treated with lipopolysaccharide (LPS) and blockers of transient receptor potential canonical (TRPC) channels. Neointimal growth and arterial stenosis were observed on cryosections of cultured pulmonary arteries. Proliferation of PASMCs was examined by a WST-1 (water-soluble tetrazolium salt) assay. Expression of TRPC genes in pulmonary arteries and PASMCs were detected and quantified by real-time polymerase chain reaction and Western blotting. Results LPS significantly induced neointimal growth and stenosis of pulmonary arteries and promoted proliferation of PASMCs. TRPC channel blockers 2-aminoethoxydiphenyl borate and SKF-96365 inhibited LPS-induced remodeling of pulmonary arteries and PASMC proliferation. Expression of TRPC1/3/4/6 was detected in pulmonary arteries and PASMCs. LPS treatment dramatically increased the expression of TRPC3 and TRPC4 at both messenger RNA and protein levels. Conclusions LPS stimulates stenosis of pulmonary arteries through enhancement of TRPC-mediated Ca2+ entry into PASMCs, which is caused by upregulation of TRPC3 and TRPC4 channels. PMID:27471122

  6. Liposomal nanoparticles encapsulating iloprost exhibit enhanced vasodilation in pulmonary arteries

    PubMed Central

    Jain, Pritesh P; Leber, Regina; Nagaraj, Chandran; Leitinger, Gerd; Lehofer, Bernhard; Olschewski, Horst; Olschewski, Andrea; Prassl, Ruth; Marsh, Leigh M

    2014-01-01

    Prostacyclin analogues are standard therapeutic options for vasoconstrictive diseases, including pulmonary hypertension and Raynaud’s phenomenon. Although effective, these treatment strategies are expensive and have several side effects. To improve drug efficiency, we tested liposomal nanoparticles as carrier systems. In this study, we synthesized liposomal nanoparticles tailored for the prostacyclin analogue iloprost and evaluated their pharmacologic efficacy on mouse intrapulmonary arteries, using a wire myograph. The use of cationic lipids, stearylamine, or 1,2-di-(9Z-octadecenoyl)-3-trimethylammonium-propane (DOTAP) in liposomes promoted iloprost encapsulation to at least 50%. The addition of cholesterol modestly reduced iloprost encapsulation. The liposomal nanoparticle formulations were tested for toxicity and pharmacologic efficacy in vivo and ex vivo, respectively. The liposomes did not affect the viability of human pulmonary artery smooth muscle cells. Compared with an equivalent concentration of free iloprost, four out of the six polymer-coated liposomal formulations exhibited significantly enhanced vasodilation of mouse pulmonary arteries. Iloprost that was encapsulated in liposomes containing the polymer polyethylene glycol exhibited concentration-dependent relaxation of arteries. Strikingly, half the concentration of iloprost in liposomes elicited similar pharmacologic efficacy as nonencapsulated iloprost. Cationic liposomes can encapsulate iloprost with high efficacy and can serve as potential iloprost carriers to improve its therapeutic efficacy. PMID:25045260

  7. Role of oxidized lipids in pulmonary arterial hypertension.

    PubMed

    Sharma, Salil; Ruffenach, Grégoire; Umar, Soban; Motayagheni, Negar; Reddy, Srinivasa T; Eghbali, Mansoureh

    2016-09-01

    Pulmonary arterial hypertension (PAH) is a multifactorial disease characterized by interplay of many cellular, molecular, and genetic events that lead to excessive proliferation of pulmonary cells, including smooth muscle and endothelial cells; inflammation; and extracellular matrix remodeling. Abnormal vascular changes and structural remodeling associated with PAH culminate in vasoconstriction and obstruction of pulmonary arteries, contributing to increased pulmonary vascular resistance, pulmonary hypertension, and right ventricular failure. The complex molecular mechanisms involved in the pathobiology of PAH are the limiting factors in the development of potential therapeutic interventions for PAH. Over the years, our group and others have demonstrated the critical implication of lipids in the pathogenesis of PAH. This review specifically focuses on the current understanding of the role of oxidized lipids, lipid metabolism, peroxidation, and oxidative stress in the progression of PAH. This review also discusses the relevance of apolipoprotein A-I mimetic peptides and microRNA-193, which are known to regulate the levels of oxidized lipids, as potential therapeutics in PAH. PMID:27683603

  8. Role of oxidized lipids in pulmonary arterial hypertension.

    PubMed

    Sharma, Salil; Ruffenach, Grégoire; Umar, Soban; Motayagheni, Negar; Reddy, Srinivasa T; Eghbali, Mansoureh

    2016-09-01

    Pulmonary arterial hypertension (PAH) is a multifactorial disease characterized by interplay of many cellular, molecular, and genetic events that lead to excessive proliferation of pulmonary cells, including smooth muscle and endothelial cells; inflammation; and extracellular matrix remodeling. Abnormal vascular changes and structural remodeling associated with PAH culminate in vasoconstriction and obstruction of pulmonary arteries, contributing to increased pulmonary vascular resistance, pulmonary hypertension, and right ventricular failure. The complex molecular mechanisms involved in the pathobiology of PAH are the limiting factors in the development of potential therapeutic interventions for PAH. Over the years, our group and others have demonstrated the critical implication of lipids in the pathogenesis of PAH. This review specifically focuses on the current understanding of the role of oxidized lipids, lipid metabolism, peroxidation, and oxidative stress in the progression of PAH. This review also discusses the relevance of apolipoprotein A-I mimetic peptides and microRNA-193, which are known to regulate the levels of oxidized lipids, as potential therapeutics in PAH.

  9. Role of oxidized lipids in pulmonary arterial hypertension

    PubMed Central

    Ruffenach, Grégoire; Umar, Soban; Motayagheni, Negar; Reddy, Srinivasa T.; Eghbali, Mansoureh

    2016-01-01

    Abstract Pulmonary arterial hypertension (PAH) is a multifactorial disease characterized by interplay of many cellular, molecular, and genetic events that lead to excessive proliferation of pulmonary cells, including smooth muscle and endothelial cells; inflammation; and extracellular matrix remodeling. Abnormal vascular changes and structural remodeling associated with PAH culminate in vasoconstriction and obstruction of pulmonary arteries, contributing to increased pulmonary vascular resistance, pulmonary hypertension, and right ventricular failure. The complex molecular mechanisms involved in the pathobiology of PAH are the limiting factors in the development of potential therapeutic interventions for PAH. Over the years, our group and others have demonstrated the critical implication of lipids in the pathogenesis of PAH. This review specifically focuses on the current understanding of the role of oxidized lipids, lipid metabolism, peroxidation, and oxidative stress in the progression of PAH. This review also discusses the relevance of apolipoprotein A-I mimetic peptides and microRNA-193, which are known to regulate the levels of oxidized lipids, as potential therapeutics in PAH. PMID:27683603

  10. Role of oxidized lipids in pulmonary arterial hypertension

    PubMed Central

    Ruffenach, Grégoire; Umar, Soban; Motayagheni, Negar; Reddy, Srinivasa T.; Eghbali, Mansoureh

    2016-01-01

    Abstract Pulmonary arterial hypertension (PAH) is a multifactorial disease characterized by interplay of many cellular, molecular, and genetic events that lead to excessive proliferation of pulmonary cells, including smooth muscle and endothelial cells; inflammation; and extracellular matrix remodeling. Abnormal vascular changes and structural remodeling associated with PAH culminate in vasoconstriction and obstruction of pulmonary arteries, contributing to increased pulmonary vascular resistance, pulmonary hypertension, and right ventricular failure. The complex molecular mechanisms involved in the pathobiology of PAH are the limiting factors in the development of potential therapeutic interventions for PAH. Over the years, our group and others have demonstrated the critical implication of lipids in the pathogenesis of PAH. This review specifically focuses on the current understanding of the role of oxidized lipids, lipid metabolism, peroxidation, and oxidative stress in the progression of PAH. This review also discusses the relevance of apolipoprotein A-I mimetic peptides and microRNA-193, which are known to regulate the levels of oxidized lipids, as potential therapeutics in PAH.

  11. Serotonin induces pulmonary artery smooth muscle cell migration

    PubMed Central

    Day, Regina M.; Agyeman, Abena S.; Segel, Michael J.; Chévere, Rubén D.; Angelosanto, Jill M.; Suzuki, Yuichiro J.; Fanburg, Barry L.

    2007-01-01

    The chronic phase of pulmonary arterial hypertension (PAH) is associated with vascular remodeling, especially thickening of the smooth muscle layer of large pulmonary arteries and muscularization of small pulmonary vessels, which normally have no associated smooth muscle. Serotonin (5-hydroxytryptamine, 5-HT) has been shown to induce proliferation and hypertrophy of pulmonary artery smooth muscle cells (PASMC), and may be important for in vivo pulmonary vascular remodeling. Here, we show that 5-HT stimulates migration of pulmonary artery PASMC. Treatment with 5-HT for 16 h increased migration of PASMC up to four-fold as monitored in a modified Boyden chamber assay. Increased migratory responses were associated with cellular morphological changes and reorganization of the actin cytoskeleton. 5-HT-induced alterations in morphology were previously shown in our laboratory to require cAMP [Lee SL, Fanburg BL. Serotonin produces a configurational change of cultured smooth muscle cells that is associated with elevation of intracellular cAMP. J Cell Phys 1992;150(2):396–405], and the 5-HT4 receptor was pharmacologically determined to be the primary activator of cAMP in bovine PASMC [Becker BN, Gettys TW, Middleton JP, Olsen CL, Albers FJ, Lee SL, et al. 8-Hydroxy-2-(di-n-propylamino)tetralin-responsive 5-hydroxytryptamine4-like receptor expressed in bovine pulmonary artery smooth muscle cells. Mol Pharmacol 1992;42(5):817–25]. We examined the role of the 5-HT4 receptor and cAMP in 5-HT-induced bovine PASMC migration. PASMC express 5-HT4 receptor mRNA, and a 5-HT4 receptor antagonist and a cAMP antagonist completely blocked 5-HT-induced cellular migration. Consistent with our previous report that a cAMP-dependent Cl− channel is required for 5-HT-induced morphological changes in PASMC, phenylanthranilic acid, a Cl− channel blocker, inhibited actin cytoskeletal reorganization and migration produced by 5-HT. We conclude that 5-HT stimulates PASMC migration and

  12. Pulmonary Artery Pseudoaneurysm Related to Radiofrequency Ablation of Lung Tumor

    SciTech Connect

    Sakurai, Jun Mimura, Hidefumi; Gobara, Hideo; Hiraki, Takao; Kanazawa, Susumu

    2010-04-15

    We describe a case of pulmonary artery (PA) pseudoaneurysm related to radiofrequency ablation (RFA) of lung tumor. We performed RFA for a pulmonary epithelioid hemangioendothelioma directly adjacent to a branch of the PA. Seventeen days later, the patient complained of hemoptysis. A chest CT image revealed PA pseudoaneurysm. Transcatheter coil embolization was performed 59 days after RFA. Although PA pseudoaneurysm is rare, with an incidence of 0.2% (1/538 sessions) at our institution, it should be recognized as a risk when treating lung tumors adjacent to a branch of the PA.

  13. Pulmonary Arterial Hypertension: A Focus on Infused Prostacyclins.

    PubMed

    Stewart, Traci

    2016-01-01

    Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and cell proliferation in the pulmonary vasculature. Guideline-driven interventions with infused prostacyclin treatment are the mainstay for patients with advanced symptoms. Infused prostacyclin therapy is complex. It is critical to manage prostacyclin therapy with precision because boluses or interruptions can be fatal. Education of patients and inpatient staff nurses is necessary to prevent negative outcomes. Nurses are an essential part of the multidisciplinary team caring for patients with PAH. The diagnostic evaluation and treatment of PAH are reviewed here, and challenges associated with the care of patients on prostacyclin therapy are discussed. PMID:27598071

  14. Reduced immunoreactivities of B-type natriuretic peptide in pulmonary arterial hypertension rats after ranolazine treatment.

    PubMed

    Lee, Jae Chul; Kim, Kwan Chang; Choe, Soo Young; Hong, Young Mi

    2016-03-01

    Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by sustained increase in the pulmonary arterial pressure and excessive thickening and remodeling of the distal small pulmonary arteries. During disease progression, structural remodeling of the right ventricular (RV) impairs pump function, creates pro-arrhythmic substrates and triggers for arrhythmias. Notably, RV failure and lethal arrhythmias are major contributors to cardiac death in PAH that are not directly addressed by currently available therapies. Ranolazine (RAN) is an anti-anginal, anti-ischemic drug that has cardioprotective effects of heart dysfunction. RAN also has anti-arrhythmic effects due to inhibition of the late sodium current in cardiomyocytes. Therefore, we hypothesized that RAN could reduce the mal-adaptive structural remodeling of the RV, and prevent triggered ventricular arrhythmias in the monocrotaline-induced rat model of PAH. RAN reduced ventricular hypertrophy, reduced levels of B-type natriuretic peptide, and decreased the expression of fibrosis. In addition, RAN prevented cardiovascular death in rat model of PAH. These results support the notion that RAN can improve the functional properties of the RV, highlighting its potential benefits in the setting of heart impairment. PMID:27051563

  15. Reduced immunoreactivities of B-type natriuretic peptide in pulmonary arterial hypertension rats after ranolazine treatment

    PubMed Central

    Lee, Jae Chul; Kim, Kwan Chang

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by sustained increase in the pulmonary arterial pressure and excessive thickening and remodeling of the distal small pulmonary arteries. During disease progression, structural remodeling of the right ventricular (RV) impairs pump function, creates pro-arrhythmic substrates and triggers for arrhythmias. Notably, RV failure and lethal arrhythmias are major contributors to cardiac death in PAH that are not directly addressed by currently available therapies. Ranolazine (RAN) is an anti-anginal, anti-ischemic drug that has cardioprotective effects of heart dysfunction. RAN also has anti-arrhythmic effects due to inhibition of the late sodium current in cardiomyocytes. Therefore, we hypothesized that RAN could reduce the mal-adaptive structural remodeling of the RV, and prevent triggered ventricular arrhythmias in the monocrotaline-induced rat model of PAH. RAN reduced ventricular hypertrophy, reduced levels of B-type natriuretic peptide, and decreased the expression of fibrosis. In addition, RAN prevented cardiovascular death in rat model of PAH. These results support the notion that RAN can improve the functional properties of the RV, highlighting its potential benefits in the setting of heart impairment. PMID:27051563

  16. A microstructurally driven model for pulmonary artery tissue.

    PubMed

    Kao, Philip H; Lammers, Steven R; Tian, Lian; Hunter, Kendall; Stenmark, Kurt R; Shandas, Robin; Qi, H Jerry

    2011-05-01

    A new constitutive model for elastic, proximal pulmonary artery tissue is presented here, called the total crimped fiber model. This model is based on the material and microstructural properties of the two main, passive, load-bearing components of the artery wall, elastin, and collagen. Elastin matrix proteins are modeled with an orthotropic neo-Hookean material. High stretch behavior is governed by an orthotropic crimped fiber material modeled as a planar sinusoidal linear elastic beam, which represents collagen fiber deformations. Collagen-dependent artery orthotropy is defined by a structure tensor representing the effective orientation distribution of collagen fiber bundles. Therefore, every parameter of the total crimped fiber model is correlated with either a physiologic structure or geometry or is a mechanically measured material property of the composite tissue. Further, by incorporating elastin orthotropy, this model better represents the mechanics of arterial tissue deformation. These advancements result in a microstructural total crimped fiber model of pulmonary artery tissue mechanics, which demonstrates good quality of fit and flexibility for modeling varied mechanical behaviors encountered in disease states. PMID:21599093

  17. A Microstructurally-Driven Model for Pulmonary Artery Tissue

    PubMed Central

    Kao, Philip H; Lammers, Steve; Tian, Lian; Hunter, Kendall; Stenmark, Kurt R.; Shandas, Robin; Qi, H. Jerry

    2011-01-01

    A new constitutive model for elastic, proximal pulmonary artery tissue is presented here, called the Total Crimped Fiber Model. This model is based on the material and micro-structural properties of the two main, passive, load-bearing components of the artery wall, elastin and collagen. Elastin matrix proteins are modeled with an orthotropic neo-Hookean material. High stretch behavior is governed by an orthotropic crimped fiber material, modeled as a planar sinusoidal linear elastic beam, which represents collagen fiber deformations. Collagen-dependent artery orthotropy is defined by a structure tensor representing the effective orientation distribution of collagen fiber bundles. Therefore, every parameter of the total crimped fiber model is correlated with either a physiologic structure or geometry or is a mechanically-measured material property of the composite tissue. Further, by incorporating elastin orthotropy, this model better represents the mechanics of arterial tissue deformation. These advancements result in a micro-structural total crimped fiber model of pulmonary artery tissue mechanics which demonstrates good quality of fit and flexibility for modeling varied mechanical behaviors encountered in disease states. PMID:21599093

  18. Acute pulmonary edema following inflation of arterial tourniquet.

    PubMed

    Santhosh, M C B; Pai, R B; Rao, R P

    2014-10-01

    Arterial tourniquets are used as one of the methods for reducing blood loss and for allowing blood free surgical field. A 20-year-old, 45 kg healthy female with a sphere shaped pendunculated hemangioma in the popliteal fossa of her left lower limb was applied with arterial tourniquet after exsanguination. The procedure was performed under general anesthesia. Soon after exsanguination and tourniquet inflation, the patient developed pulmonary edema which subsided after deflating the tourniquet. The clinical evolution, treatment and pathophysiology of this complication are described.

  19. Impairment of pulmonary vascular reserve and right ventricular systolic reserve in pulmonary arterial hypertension

    PubMed Central

    2014-01-01

    Background Exercise capacity is impaired in pulmonary arterial hypertension (PAH). We hypothesized that cardiovascular reserve abnormalities would be associated with impaired hemodynamic response to pharmacological stress and worse outcome in PAH. Methods Eighteen PAH patients (p) group 1 NYHA class II/III and ten controls underwent simultaneous right cardiac catheterization and intravascular ultrasound at rest and during low dose-dobutamine (10 mcg/kg/min) with trendelenburg (DST). We estimated cardiac output (CO), pulmonary vascular resistance (PVR) and capacitance (PC), and PA elastic modulus (EM). We concomitantly measured tricuspid annular plane systolic excursion (TAPSE), RV myocardial peak systolic velocity (Sm) and isovolumic myocardial acceleration (IVA) in PAH patients. Based on the rounded mean + 2 SD of the increase in mPAP in our healthy control group during DST (2.8 + 1.8 mm Hg), PAH p were divided into two groups according to mean PA pressure (mPAP) response during DST, 1: ΔmPAP > 5 mm Hg and 2: ΔmPAP ≤ 5 mm Hg. Cardiovascular reserve was estimated as the change (delta, Δ) during DST compared with rest, including ΔmPAP with respect to ΔCO (ΔmPAP/ΔCO). All patients were prospectively followed up for 2 years. Results PAH p showed significant lower heart rate and CO increase than controls during DST, with a significant mPAP and pulse PAP increase and higher ΔmPAP/ΔCO (p < 0.05). Neither hemodynamic, IVUS and echocardiographic data were different between both PAH groups at rest. In group 1, DST caused a higher ΔEM, ΔmPAP/ΔCO, ΔPVR, and ΔTAPSE than group 2, with a lower IVA increase and a negative ΔSV (p < 0.05). TAPSE correlated with mPAP and RVP (p < 0.05) and, IVA and Sm correlated with CO (p < 0.05). ΔEM correlated with ΔmPAP and ΔIVA with ΔCO (p < 0.05). There were two deaths/pulmonary transplantations in group 1 and one death in group 2 during the follow-up (p > 0.05). Conclusions

  20. [Towards new targets for the treatment of pulmonary arterial hypertension : Importance of cell-cell communications].

    PubMed

    Tu, Ly; Ghigna, Maria-Rosa; Phan, Carole; Bordenave, Jennifer; Le Hiress, Morane; Thuillet, Raphaël; Ricard, Nicolas; Huertas, Alice; Humbert, Marc; Guignabert, Christophe

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a disorder in which mechanical obstruction of the pulmonary vascular bed is largely responsible for the rise in mean pulmonary arterial pressure (mPAP), resulting in a progressive functional decline despite current available therapeutic options. There are multiple mechanisms predisposing to and/or promoting the aberrant pulmonary vascular remodeling in PAH, and these involve not only altered crosstalk between cells within the vascular wall but also sustained inflammation and dysimmunity, cell accumulation in the vascular wall and excessive activation of some growth factor-stimulated signaling pathways, in addition to the interaction of systemic hormones, local growth factors, cytokines, and transcription factors. Heterozygous germline mutations in the bone morphogenetic protein receptor, type-2 (BMPR2) gene, a gene encoding a receptor for the transforming growth factor (TGF)-β superfamily, can predispose to the disease. Although the spectrum of therapeutic options for PAH has expanded in the last 20 years, available therapies remain essentially palliative. Over the past decade, however, a better understanding of key regulators of this irreversible remodeling of the pulmonary vasculature has been obtained. New and more effective approaches are likely to emerge. The present article profiles the innovative research into novel pathways and therapeutic targets that may lead to the development of targeted agents in PAH. PMID:27687598

  1. Oxidative and nitrosative signalling in pulmonary arterial hypertension - Implications for development of novel therapies.

    PubMed

    Hansen, Thomas; Galougahi, Keyvan-Karimi; Celermajer, David; Rasko, Nathalie; Tang, Owen; Bubb, Kristen J; Figtree, Gemma

    2016-09-01

    Pulmonary arterial hypertension (PAH) is a syndrome characterised by an increase in pulmonary vascular resistance. This results in elevated resting pulmonary artery pressure and leads to progressive right ventricular (RV) failure, secondary to increased afterload. Although initially thought to be a disease driven primarily by endothelial dysfunction with a resultant vasoconstrictor versus vasodilator imbalance, it has become increasingly apparent that the rise in pulmonary vascular resistance that causes RV failure is also attributable to pulmonary vascular remodelling. This inflammatory, hyper-proliferative and anti-apoptotic phenotype is accompanied by a metabolic switch from physiological mitochondrial oxidative phosphorylation to aerobic glycolysis. The molecular pathways triggering this cellular metabolic shift have been the subject of extensive investigation, as their discovery will inevitably lead to new therapeutic targets. Reactive oxygen/nitrogen species (ROS/RNS) including hydrogen peroxide, superoxide and peroxynitrite are second messenger molecules that are involved in functional oxidative and nitrosative modification of proteins. Dysregulation of oxidative signalling caused by an excess of ROS and RNS relative to antioxidants has been heavily implicated in the underlying pathophysiology of PAH and likely participates in this metabolic reprogramming. This review will focus on the role of oxidative signalling and redox reactions to the molecular pathology of PAH. In addition, promising novel therapeutic agents targeting these pathways will be discussed.

  2. Chronic hypoxia does not cause wall thickening of intra-acinar pulmonary supernumerary arteries.

    PubMed

    Oshima, Kaori; McLendon, Jared M; Wagner, Wiltz W; McMurtry, Ivan F; Oka, Masahiko

    2016-02-01

    Chronic exposure to hypoxia causes pulmonary hypertension and pulmonary arterial remodeling. Although the exact mechanisms of this remodeling are unclear, there is evidence that it is dependent on hemodynamic stress, rather than on hypoxia alone. Pulmonary supernumerary arteries experience low hemodynamic stress as a consequence of reduced perfusion due to 90° branching angles, small diameters, and "valve-like" structures at their orifices. We investigated whether or not intra-acinar supernumerary arteries undergo structural remodeling during the moderate pulmonary hypertension induced by chronic hypoxia. Rats were exposed to either normoxia or hypoxia for 6 weeks. The chronically hypoxic rats developed pulmonary hypertension. For both groups, pulmonary arteries were selectively filled with barium-gelatin mixture, and the wall thickness of intra-acinar pulmonary arteries was measured in histological samples. Only thin-walled arteries were observed in normoxic lungs. In hypertensive lungs, we found both thin- and thick-walled pulmonary arteries with similar diameters. Disproportionate degrees of arterial wall thickening between parent and daughter branches were observed with supernumerary branching patterns. While parent arteries developed significant wall thickening, their supernumerary branches did not. Thus, chronic hypoxia-induced pulmonary hypertension did not cause wall thickening of intra-acinar pulmonary supernumerary arteries. These findings are consistent with the idea that hemodynamic stress, rather than hypoxia alone, is the cause of structural remodeling during chronic exposure to hypoxia.

  3. Pulmonary artery stenosis due to embryonal carcinoma with primary mediastinal location.

    PubMed

    Grzegorczyk, Franciszek; Dybowska, Małgorzata; Kuca, Paweł; Czajka, Cezary; Burakowski, Janusz; Langfort, Renata; Orłowski, Tadeusz; Tomkowski, Witold

    2015-01-01

    A 29-year old man was admitted to the intensive care unit after losing consciousness. On physical examination, a loud systolic murmur over the heart was found. Echocardiography revealed narrowing of pulmonary artery with high pressure gradient. Computed tomography of the chest revealed the presence of large tumour localised in the upper anterior mediastinum. Due to the risk of total closure of the pulmonary artery, interventional mediastinotomy was performed and diagnosis of carcinoma embryonale was established. Subsequent chemotherapy (BEP regimen) has brought regression of tumour and significant improvement in haemodynamic parameters (relief of pressure gradient in pulmonary artery). During the second surgery, the resection of all accessible tumour mass together with marginal resection of the right upper lobe was performed. No signs of cardiac or great vessels infiltration was found. Histopathologic examination revealed the necrotic masses and neoplastic foci diagnosed as teratoma immaturum. In a four-month follow-up the patient's condition remained good. The patient is still under the care of both oncological and cardiological specialists. Thus far he has not required further chemotherapy. Holter ECG monitoring revealed no arrhythmia, but the patient is still treated with mexiletine. The patient is planning to return to work. PMID:25754058

  4. Macitentan for the treatment of pulmonary arterial hypertension.

    PubMed

    Kholdani, Cyrus A; Fares, Wassim H; Trow, Terence K

    2014-01-01

    Macitentan is the most recently approved dual endothelin-receptor antagonist (ERA) for the treatment of symptomatic pulmonary arterial hypertension. Compared to other available ERAs, it demonstrates superior receptor-binding properties, with consequently improved tissue penetration, and a longer duration of action allowing for once-daily dosing. It has a favorable adverse-effect profile, with notably no demonstrable increase in the risk of hepatotoxicity or peripheral edema, but like other ERAs, it is potentially limited by significant anemia. Phase I data have demonstrated a favorable drug-drug interaction profile and no need for dose adjustment with hepatic and renal impairment. In the pivotal SERAPHIN study, treatment of symptomatic pulmonary arterial hypertension patients with macitentan led to statistically significant improvements in functional class, exercise tolerance, and hemodynamic parameters, in addition to a reduction in morbidity in an event-driven long-term trial.

  5. Macitentan for the treatment of pulmonary arterial hypertension

    PubMed Central

    Kholdani, Cyrus A; Fares, Wassim H; Trow, Terence K

    2014-01-01

    Macitentan is the most recently approved dual endothelin-receptor antagonist (ERA) for the treatment of symptomatic pulmonary arterial hypertension. Compared to other available ERAs, it demonstrates superior receptor-binding properties, with consequently improved tissue penetration, and a longer duration of action allowing for once-daily dosing. It has a favorable adverse-effect profile, with notably no demonstrable increase in the risk of hepatotoxicity or peripheral edema, but like other ERAs, it is potentially limited by significant anemia. Phase I data have demonstrated a favorable drug–drug interaction profile and no need for dose adjustment with hepatic and renal impairment. In the pivotal SERAPHIN study, treatment of symptomatic pulmonary arterial hypertension patients with macitentan led to statistically significant improvements in functional class, exercise tolerance, and hemodynamic parameters, in addition to a reduction in morbidity in an event-driven long-term trial. PMID:25473292

  6. Pulmonary arterial hypertension caused by treatment with dasatinib for chronic myeloid leukemia -critical alert-.

    PubMed

    Sano, Makoto; Saotome, Masao; Urushida, Tsuyoshi; Katoh, Hideki; Satoh, Hiroshi; Ohnishi, Kazunori; Hayashi, Hideharu

    2012-01-01

    We present a case of pulmonary arterial hypertension (PAH), which is potentially related to treatment with dasatinib (Sprycel(®)). A 61-year-old woman, who had been treated with dasatinib for 27 months for chronic myeloid leukemia (CML), visited our hospital complaining of dyspnea. In right heart catheterization, her mean pulmonary arterial pressure was 35 mmHg. After other possible etiologies to cause PAH were excluded, the patient was diagnosed as a dasatinib-related PAH. As notified by U.S. Food and Drug Administration (FDA) in October 2011, we recommend routine cardiopulmonary evaluation before and during treatment with dasatinib in CML patients in terms of the adverse effects of PAH. PMID:22975544

  7. Sphingosine-1-phosphate is involved in the occlusive arteriopathy of pulmonary arterial hypertension

    PubMed Central

    Joshi, Sachindra R.; Bastola, Mrigendra M.; McLendon, Jared M.; Oka, Masahiko; Fagan, Karen A.; McMurtry, Ivan F.

    2016-01-01

    Abstract Despite several advances in the pathobiology of pulmonary arterial hypertension (PAH), its pathogenesis is not completely understood. Current therapy improves symptoms but has disappointing effects on survival. Sphingosine-1-phosphate (S1P) is a lysophospholipid synthesized by sphingosine kinase 1 (SphK1) and SphK2. Considering the regulatory roles of S1P in several tissues leading to vasoconstriction, inflammation, proliferation, and fibrosis, we investigated whether S1P plays a role in the pathogenesis of PAH. To test this hypothesis, we used plasma samples and lung tissue from patients with idiopathic PAH (IPAH) and the Sugen5416/hypoxia/normoxia rat model of occlusive PAH. Our study revealed an increase in the plasma concentration of S1P in patients with IPAH and in early and late stages of PAH in rats. We observed increased expression of both SphK1 and SphK2 in the remodeled pulmonary arteries of patients with IPAH and PAH rats. Exogenous S1P stimulated the proliferation of cultured rat pulmonary arterial endothelial and smooth-muscle cells. We also found that 3 weeks of treatment of late-stage PAH rats with an SphK1 inhibitor reduced the increased plasma levels of S1P and the occlusive pulmonary arteriopathy. Although inhibition of SphK1 improved cardiac index and the total pulmonary artery resistance index, it did not reduce right ventricular systolic pressure or right ventricular hypertrophy. Our study supports that S1P is involved in the pathogenesis of occlusive arteriopathy in PAH and provides further evidence that S1P signaling may be a novel therapeutic target. PMID:27683614

  8. Sphingosine-1-phosphate is involved in the occlusive arteriopathy of pulmonary arterial hypertension.

    PubMed

    Gairhe, Salina; Joshi, Sachindra R; Bastola, Mrigendra M; McLendon, Jared M; Oka, Masahiko; Fagan, Karen A; McMurtry, Ivan F

    2016-09-01

    Despite several advances in the pathobiology of pulmonary arterial hypertension (PAH), its pathogenesis is not completely understood. Current therapy improves symptoms but has disappointing effects on survival. Sphingosine-1-phosphate (S1P) is a lysophospholipid synthesized by sphingosine kinase 1 (SphK1) and SphK2. Considering the regulatory roles of S1P in several tissues leading to vasoconstriction, inflammation, proliferation, and fibrosis, we investigated whether S1P plays a role in the pathogenesis of PAH. To test this hypothesis, we used plasma samples and lung tissue from patients with idiopathic PAH (IPAH) and the Sugen5416/hypoxia/normoxia rat model of occlusive PAH. Our study revealed an increase in the plasma concentration of S1P in patients with IPAH and in early and late stages of PAH in rats. We observed increased expression of both SphK1 and SphK2 in the remodeled pulmonary arteries of patients with IPAH and PAH rats. Exogenous S1P stimulated the proliferation of cultured rat pulmonary arterial endothelial and smooth-muscle cells. We also found that 3 weeks of treatment of late-stage PAH rats with an SphK1 inhibitor reduced the increased plasma levels of S1P and the occlusive pulmonary arteriopathy. Although inhibition of SphK1 improved cardiac index and the total pulmonary artery resistance index, it did not reduce right ventricular systolic pressure or right ventricular hypertrophy. Our study supports that S1P is involved in the pathogenesis of occlusive arteriopathy in PAH and provides further evidence that S1P signaling may be a novel therapeutic target. PMID:27683614

  9. Sphingosine-1-phosphate is involved in the occlusive arteriopathy of pulmonary arterial hypertension

    PubMed Central

    Joshi, Sachindra R.; Bastola, Mrigendra M.; McLendon, Jared M.; Oka, Masahiko; Fagan, Karen A.; McMurtry, Ivan F.

    2016-01-01

    Abstract Despite several advances in the pathobiology of pulmonary arterial hypertension (PAH), its pathogenesis is not completely understood. Current therapy improves symptoms but has disappointing effects on survival. Sphingosine-1-phosphate (S1P) is a lysophospholipid synthesized by sphingosine kinase 1 (SphK1) and SphK2. Considering the regulatory roles of S1P in several tissues leading to vasoconstriction, inflammation, proliferation, and fibrosis, we investigated whether S1P plays a role in the pathogenesis of PAH. To test this hypothesis, we used plasma samples and lung tissue from patients with idiopathic PAH (IPAH) and the Sugen5416/hypoxia/normoxia rat model of occlusive PAH. Our study revealed an increase in the plasma concentration of S1P in patients with IPAH and in early and late stages of PAH in rats. We observed increased expression of both SphK1 and SphK2 in the remodeled pulmonary arteries of patients with IPAH and PAH rats. Exogenous S1P stimulated the proliferation of cultured rat pulmonary arterial endothelial and smooth-muscle cells. We also found that 3 weeks of treatment of late-stage PAH rats with an SphK1 inhibitor reduced the increased plasma levels of S1P and the occlusive pulmonary arteriopathy. Although inhibition of SphK1 improved cardiac index and the total pulmonary artery resistance index, it did not reduce right ventricular systolic pressure or right ventricular hypertrophy. Our study supports that S1P is involved in the pathogenesis of occlusive arteriopathy in PAH and provides further evidence that S1P signaling may be a novel therapeutic target.

  10. Versican accumulates in vascular lesions in pulmonary arterial hypertension.

    PubMed

    Chang, Ya-Ting; Chan, Christina K; Eriksson, Inger; Johnson, Pamela Y; Cao, Xiaofang; Westöö, Christian; Norvik, Christian; Andersson-Sjöland, Annika; Westergren-Thorsson, Gunilla; Johansson, Staffan; Hedin, Ulf; Kjellén, Lena; Wight, Thomas N; Tran-Lundmark, Karin

    2016-09-01

    Pulmonary arterial hypertension (PAH) is a lethal condition for which there is no effective curative pharmacotherapy. PAH is characterized by vasoconstriction, wall thickening of pulmonary arteries, and increased vascular resistance. Versican is a chondroitin sulfate proteoglycan in the vascular extracellular matrix that accumulates following vascular injury and promotes smooth-muscle cell proliferation in systemic arteries. Here, we investigated whether versican may play a similar role in PAH. Paraffin-embedded lung sections from patients who underwent lung transplantation to treat PAH were used for immunohistochemistry. The etiologies of PAH in the subjects involved in this study were idiopathic PAH, scleroderma, and congenital heart disease (atrial septal defect) with left-to-right shunt. Independent of the underlying etiology, increased versican immunostaining was observed in areas of medial thickening, in neointima, and in plexiform lesions. Western blot of lung tissue lysates confirmed accumulation of versican in patients with PAH. Double staining for versican and CD45 showed only occasional colocalization in neointima of high-grade lesions and plexiform lesions. In vitro, metabolic labeling with [(35)S]sulfate showed that human pulmonary artery smooth-muscle cells (hPASMCs) produce mainly chondroitin sulfate glycosaminoglycans. In addition, hypoxia, but not cyclic stretch, was demonstrated to increase both versican messenger RNA expression and protein synthesis by hPASMCs. Versican accumulates in vascular lesions of PAH, and the amount of versican correlates more with lesion severity than with underlying etiology or inflammation. Hypoxia is a possible regulator of versican accumulation, which may promote proliferation of pulmonary smooth-muscle cells and vascular remodeling in PAH. PMID:27683612

  11. [Intralobar pulmonary sequestration with multiple arterial blood supply].

    PubMed

    Uroz Tristán, J; Mogueya, S A; Poenaru, D; Martínez Lagares, F; Arteaga García, R; Sanchís Solera, L; López-Pinto Ruiz, J

    1994-04-01

    We report the case of a 4 years old boy, who presented at our institution with reiterative neumonia affecting left basal lobe. Anomalous vascular appearance was detected in the chest x-ray. With the suspicion of pulmonary sequestration we carried on Digital Intravenous Angiography by Substraction (DIVAS) and aortogram. The anomalous systemic arterial supply was formed by 6 vessels coming from the thoracic aorta and going into the left lower lobe basal segment. Lobectomy was performed and previous diagnosis was confirmed pathologically.

  12. Pulmonary artery stump thrombosis developed during the late postoperative period

    PubMed Central

    Kaya, Seyda Ors; Samancilar, Ozgur; Ceylan, Kenan Can

    2016-01-01

    A 73-year-old man underwent left pneumonectomy for squamous cell lung carcinoma 3 years ago. The postoperative and follow-up periods were uneventful. A thrombus was detected in the left pulmonary artery stump during the last chest computed tomography (CT) scan. Anticoagulant treatment was applied: intravenous heparin for 3 days followed by oral warfarin. The follow-up chest CT examination revealed regression in the size of the thrombus.

  13. Versican accumulates in vascular lesions in pulmonary arterial hypertension

    PubMed Central

    Chan, Christina K.; Eriksson, Inger; Johnson, Pamela Y.; Cao, Xiaofang; Westöö, Christian; Norvik, Christian; Andersson-Sjöland, Annika; Westergren-Thorsson, Gunilla; Johansson, Staffan; Hedin, Ulf; Kjellén, Lena; Wight, Thomas N.; Tran-Lundmark, Karin

    2016-01-01

    Abstract Pulmonary arterial hypertension (PAH) is a lethal condition for which there is no effective curative pharmacotherapy. PAH is characterized by vasoconstriction, wall thickening of pulmonary arteries, and increased vascular resistance. Versican is a chondroitin sulfate proteoglycan in the vascular extracellular matrix that accumulates following vascular injury and promotes smooth-muscle cell proliferation in systemic arteries. Here, we investigated whether versican may play a similar role in PAH. Paraffin-embedded lung sections from patients who underwent lung transplantation to treat PAH were used for immunohistochemistry. The etiologies of PAH in the subjects involved in this study were idiopathic PAH, scleroderma, and congenital heart disease (atrial septal defect) with left-to-right shunt. Independent of the underlying etiology, increased versican immunostaining was observed in areas of medial thickening, in neointima, and in plexiform lesions. Western blot of lung tissue lysates confirmed accumulation of versican in patients with PAH. Double staining for versican and CD45 showed only occasional colocalization in neointima of high-grade lesions and plexiform lesions. In vitro, metabolic labeling with [35S]sulfate showed that human pulmonary artery smooth-muscle cells (hPASMCs) produce mainly chondroitin sulfate glycosaminoglycans. In addition, hypoxia, but not cyclic stretch, was demonstrated to increase both versican messenger RNA expression and protein synthesis by hPASMCs. Versican accumulates in vascular lesions of PAH, and the amount of versican correlates more with lesion severity than with underlying etiology or inflammation. Hypoxia is a possible regulator of versican accumulation, which may promote proliferation of pulmonary smooth-muscle cells and vascular remodeling in PAH.

  14. Versican accumulates in vascular lesions in pulmonary arterial hypertension

    PubMed Central

    Chan, Christina K.; Eriksson, Inger; Johnson, Pamela Y.; Cao, Xiaofang; Westöö, Christian; Norvik, Christian; Andersson-Sjöland, Annika; Westergren-Thorsson, Gunilla; Johansson, Staffan; Hedin, Ulf; Kjellén, Lena; Wight, Thomas N.; Tran-Lundmark, Karin

    2016-01-01

    Abstract Pulmonary arterial hypertension (PAH) is a lethal condition for which there is no effective curative pharmacotherapy. PAH is characterized by vasoconstriction, wall thickening of pulmonary arteries, and increased vascular resistance. Versican is a chondroitin sulfate proteoglycan in the vascular extracellular matrix that accumulates following vascular injury and promotes smooth-muscle cell proliferation in systemic arteries. Here, we investigated whether versican may play a similar role in PAH. Paraffin-embedded lung sections from patients who underwent lung transplantation to treat PAH were used for immunohistochemistry. The etiologies of PAH in the subjects involved in this study were idiopathic PAH, scleroderma, and congenital heart disease (atrial septal defect) with left-to-right shunt. Independent of the underlying etiology, increased versican immunostaining was observed in areas of medial thickening, in neointima, and in plexiform lesions. Western blot of lung tissue lysates confirmed accumulation of versican in patients with PAH. Double staining for versican and CD45 showed only occasional colocalization in neointima of high-grade lesions and plexiform lesions. In vitro, metabolic labeling with [35S]sulfate showed that human pulmonary artery smooth-muscle cells (hPASMCs) produce mainly chondroitin sulfate glycosaminoglycans. In addition, hypoxia, but not cyclic stretch, was demonstrated to increase both versican messenger RNA expression and protein synthesis by hPASMCs. Versican accumulates in vascular lesions of PAH, and the amount of versican correlates more with lesion severity than with underlying etiology or inflammation. Hypoxia is a possible regulator of versican accumulation, which may promote proliferation of pulmonary smooth-muscle cells and vascular remodeling in PAH. PMID:27683612

  15. Immune and Inflammatory Mechanisms in Pulmonary Arterial Hypertension

    PubMed Central

    El Chami, Hala; Hassoun, Paul M.

    2012-01-01

    Altered immunity and inflammation are increasingly recognized features of pulmonary arterial hypertension (PAH). This is suggested by infiltration of various inflammatory cells (e.g., macrophages, T and B lymphocytes), increased cytokine and growth factor (e.g., VEGF and PDGF) expression in remodeled pulmonary vessels, and the presence of circulating chemokines and cytokines. In certain diseases associated with PAH, increased expression of growth and transcriptional (e.g., Nuclear Factor of Activated T cells or NFAT) factors, and viral protein components (e.g., HIV-1 Nef), appear to contribute directly to recruitment of inflammatory cells in remodeled vessels, and may potentially serve as specific therapeutic targets. This section provides an overview of inflammatory pathways highlighting their potential role in pulmonary vascular remodeling in PAH and the possibility of future targeted therapy. PMID:23009917

  16. [Right heart adaptation to pulmonary arterial hypertension: physiology and pathobiology].

    PubMed

    Vonk-Noordegraaf, Anton; Haddad, François; Chin, Kelly M; Forfia, Paul R; Kawut, Steven M; Lumens, Joost; Naeije, Robert; Newman, John; Oudiz, Ronald J; Provencher, Steve; Torbicki, Adam; Voelkel, Norbert F; Hassoun, Paul M

    2014-10-01

    Survival in patients with pulmonary arterial hypertension (PAH) is closely related to right ventricular (RV) function. Although pulmonary load is an important determinant of RV systolic function in PAH, there remains a significant variability in RV adaptation to pulmonary hypertension. In this report, the authors discuss the emerging concepts of right heart pathobiology in PAH. More specifically, the discussion focuses on the following questions. 1) How is right heart failure syndrome best defined? 2) What are the uderlying molecular mechanisms of the failing right ventricle in PAH? 3) How are RV contractility and function and their prognostic implications best assessed? 4) What is the role of targeted RV therapy? Throughout the report, the authors highlight differences between right and left heart failure and outline key areas of future investigation. (J Am Coll Cardiol 2013;62:D22-33) a 2013 by the American College of Cardiology Foundation).

  17. Right heart adaptation to pulmonary arterial hypertension: physiology and pathobiology.

    PubMed

    Vonk-Noordegraaf, Anton; Haddad, François; Chin, Kelly M; Forfia, Paul R; Kawut, Steven M; Lumens, Joost; Naeije, Robert; Newman, John; Oudiz, Ronald J; Provencher, Steve; Torbicki, Adam; Voelkel, Norbert F; Hassoun, Paul M

    2013-12-24

    Survival in patients with pulmonary arterial hypertension (PAH) is closely related to right ventricular (RV) function. Although pulmonary load is an important determinant of RV systolic function in PAH, there remains a significant variability in RV adaptation to pulmonary hypertension. In this report, the authors discuss the emerging concepts of right heart pathobiology in PAH. More specifically, the discussion focuses on the following questions. 1) How is right heart failure syndrome best defined? 2) What are the underlying molecular mechanisms of the failing right ventricle in PAH? 3) How are RV contractility and function and their prognostic implications best assessed? 4) What is the role of targeted RV therapy? Throughout the report, the authors highlight differences between right and left heart failure and outline key areas of future investigation.

  18. Ascending aorta-right pulmonary artery anastomosis: Waterston's operation

    PubMed Central

    Alvarez-Díaz, F.; Brito, J. M.; Cordovilla, G.; De León, J. Pérez; Sanchez, P. A.; Bordiú, C. M.

    1973-01-01

    The results of 180 cases of congenital heart disease with diminished pulmonary flow operated upon with Waterston's technique are presented. It is considered that Waterston's operation is to be preferred in children under 2 years of age and in older children who have had a previous thrombotic or insufficient Blalock operation and in whom total correction is not indicated. The problem of pseudotruncus with hypoplastic pulmonary arteries is discussed. The convenience of the Waterston operation in these cases, and the importance of creating an anastomosis at the pulmonary bifurcation and as far back as possible in the aorta, is emphasized. The need to perform this technique in the correct way is stressed. This will avoid the kinking and pulling of the right pulmonary artery, which are causes of preferential blood flow to the right lung, as we have demonstrated experimentally. The possible complications caused by such a technical failure are discussed. The necessity for previous angiocardiographic study, in order properly to repair the defect during total correction, is also considered. Images PMID:4731106

  19. Mitochondrial Haplogroups and Risk of Pulmonary Arterial Hypertension.

    PubMed

    Farha, Samar; Hu, Bo; Comhair, Suzy; Zein, Joe; Dweik, Raed; Erzurum, Serpil C; Aldred, Micheala A

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a serious and often fatal disease. It is a panvasculopathy of the pulmonary microcirculation characterized by vasoconstriction and arterial obstruction due to vascular proliferation and remodeling and ultimately right ventricular failure. Mitochondrial dysfunction is a universal finding in pulmonary vascular cells of patients with PAH, and is mechanistically linked to disease origins in animal models of pulmonary hypertension. Mitochondria have their own circular DNA (mtDNA), which can be subgrouped into polymorphic haplogroup variants, some of which have been identified as at-risk or protective from cardiovascular and/or neurodegenerative diseases. Here, we hypothesized that mitochondrial haplogroups may be associated with PAH. To test this, mitochondrial haplogroups were determined in a cohort of PAH patients and controls [N = 204 Caucasians (125 PAH and 79 controls) and N = 46 African Americans (13 PAH and 33 controls)]. Haplogroup L was associated with a lower rate of PAH as compared to macrohaplogroups N and M. When haplogroups were nested based on ancestral inheritance and controlled for age, gender and race, haplogroups M and HV, JT and UK of the N macro-haplogroup had significantly higher rates of PAH compared to the ancestral L (L0/1/2 and L3) (all p ≤ 0.05). Overall, the findings suggest that mitochondrial haplogroups influence risk of PAH and that a vulnerability to PAH may have emerged under the selective enrichment of specific haplogroups that occurred with the migration of populations out of Africa. PMID:27224443

  20. Drug-induced pulmonary arterial hypertension: a recent outbreak.

    PubMed

    Montani, David; Seferian, Andrei; Savale, Laurent; Simonneau, Gérald; Humbert, Marc

    2013-09-01

    Pulmonary arterial hypertension (PAH) is a rare disorder characterised by progressive obliteration of the pulmonary microvasculature resulting in elevated pulmonary vascular resistance and premature death. According to the current classification PAH can be associated with exposure to certain drugs or toxins, particularly to appetite suppressant intake drugs, such as aminorex, fenfluramine derivatives and benfluorex. These drugs have been confirmed to be risk factors for PAH and were withdrawn from the market. The supposed mechanism is an increase in serotonin levels, which was demonstrated to act as a growth factor for the pulmonary artery smooth muscle cells. Amphetamines, phentermine and mazindol were less frequently used, but are considered possible risk factors, for PAH. Dasatinib, dual Src/Abl kinase inhibitor, used in the treatment of chronic myelogenous leukaemia was associated with cases of severe PAH, potentially in part reversible after dasatinib withdrawal. Recently, several studies have raised the issue of potential endothelial dysfunction that could be induced by interferon, and a few cases of PAH have been reported with interferon therapy. PAH remains a rare complication of these drugs, suggesting possible individual susceptibility, and further studies are needed to identify patients at risk of drug-induced PAH. PMID:23997051

  1. Mitochondrial Haplogroups and Risk of Pulmonary Arterial Hypertension

    PubMed Central

    Farha, Samar; Hu, Bo; Comhair, Suzy; Zein, Joe; Dweik, Raed

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a serious and often fatal disease. It is a panvasculopathy of the pulmonary microcirculation characterized by vasoconstriction and arterial obstruction due to vascular proliferation and remodeling and ultimately right ventricular failure. Mitochondrial dysfunction is a universal finding in pulmonary vascular cells of patients with PAH, and is mechanistically linked to disease origins in animal models of pulmonary hypertension. Mitochondria have their own circular DNA (mtDNA), which can be subgrouped into polymorphic haplogroup variants, some of which have been identified as at-risk or protective from cardiovascular and/or neurodegenerative diseases. Here, we hypothesized that mitochondrial haplogroups may be associated with PAH. To test this, mitochondrial haplogroups were determined in a cohort of PAH patients and controls [N = 204 Caucasians (125 PAH and 79 controls) and N = 46 African Americans (13 PAH and 33 controls)]. Haplogroup L was associated with a lower rate of PAH as compared to macrohaplogroups N and M. When haplogroups were nested based on ancestral inheritance and controlled for age, gender and race, haplogroups M and HV, JT and UK of the N macro-haplogroup had significantly higher rates of PAH compared to the ancestral L (L0/1/2 and L3) (all p ≤ 0.05). Overall, the findings suggest that mitochondrial haplogroups influence risk of PAH and that a vulnerability to PAH may have emerged under the selective enrichment of specific haplogroups that occurred with the migration of populations out of Africa. PMID:27224443

  2. Principles of pulmonary artery catheterization in the critically ill.

    PubMed

    Summerhill, Eleanor M; Baram, Michael

    2005-01-01

    The pulmonary artery catheter (PAC) may be helpful in determining the etiology of shock, lactic acidosis, pulmonary edema, oliguric renal failure, pulmonary hypertension, and a number of cardiac abnormalities. In addition, it may also be useful in guiding fluid and vasoactive therapy. However, although hemodynamic data from the pulmonary artery catheter (PAC) is widely used diagnostically and therapeutically in the care of critically ill patients, the use of the catheter has not been shown to provide outcomes benefit. In fact, there is some evidence to suggest that placement of the PAC may actually be detrimental. The reasons for this are unclear, but it has been shown that both physicians and nurses frequently misinterpret waveforms and other data obtained from the PAC. Presently, there are a number of ongoing randomized, controlled trials investigating the use of the PAC in specific clinical situations and/or patient populations as well as using specific treatment strategies. In the meantime, if any benefit is to be achieved, it is imperative that clinicians have a thorough understanding of the indications, contraindications, complications, and pitfalls of data interpretation prior to using the catheter. These are reviewed in this article. PMID:16078042

  3. Two rare conditions in an Eisenmenger patient: left main coronary artery compression and Ortner's syndrome due to pulmonary artery dilatation.

    PubMed

    Andjelkovic, Kristina; Kalimanovska-Ostric, Dimitra; Djukic, Milan; Vukcevic, Vladan; Menkovic, Nemanja; Mehmedbegovic, Zlatko; Topalovic, Mirko; Tesic, Milorad

    2013-01-01

    The left-main coronary artery extrinsic compression due to enlarged pulmonary artery has been described in several case series. Ortner's syndrome is also a rare condition in some cardiovascular disorders. There have been no reports about these two rare conditions in the same patient. Hence, we report a very rare case of an Eisenmenger patient with severe pulmonary hypertension and dilated pulmonary artery which has compressed the left main coronary artery, severely narrowing it, and the left laryngeal recurrent nerve with subsequent Ortner's syndrome and brief literature review. PMID:23831302

  4. Management of patients with pulmonary atresia, ventricular septal defect, hypoplastic pulmonary arteries and major aorto-pulmonary collaterals: Focus on the strategy of rehabilitation of the native pulmonary arteries.

    PubMed

    Fouilloux, Virginie; Bonello, Béatrice; Kammache, Issam; Fraisse, Alain; Macé, Loïc; Kreitmann, Bernard

    2012-12-01

    Pulmonary atresia with ventricular septal defect (VSD), hypoplastic native pulmonary arteries (PAs) and major aorto-pulmonary collateral arteries (MAPCAs) is a rare and complex congenital cardiac disease. In broad outline, two surgical approaches are available for patients with this condition. The first is characterized by one or several stages of complete unifocalization of the supplying MAPCAs, with or without incorporation of the native pulmonary arteries (PAs), connection of the right ventricle to the 'neo-Pas' and, if possible, concomitant or delayed closure of the VSD. The second strategy is based on rehabilitation of the native pulmonary arteries. The first step is a direct right ventricle to native PA connection, to promote the growth of native PAs. The establishment of antegrade flow also allows an easier approach for interventional catheterization, enabling dilatation or stenting of the stenosis and then closure of the communicant collaterals. When the development of the native PAs is satisfactory, the complete repair is performed. If it is necessary to suture a MAPCA to the PA ('unifocalization'), this is accomplished by connecting the collateral artery to an already developed native branch. Our team developed this multidisciplinary strategy with good results. Based on this experience as well as on the published literature, we describe this strategy of management of patients with pulmonary atresia, VSD, hypoplastic pulmonary arteries and major aorto-pulmonary collaterals (MAPCAs). PMID:23199622

  5. Severe pulmonary arterial hypertension in an adult patient with total anomalous pulmonary venous connection operated in infancy.

    PubMed

    Martinez-Quintana, Efrén; Rodríguez-González, Fayna

    2016-01-01

    The goal of total anomalous pulmonary venous connection repair is to obtain an unobstructed communication between the pulmonary veins and the left atrium and removing intracardiac shunting. However, pulmonary venous obstruction orstenosis may be seen in 5-10% of patients, is usually evident in the first 6 months following surgery and may lead to pulmonary congestion, pulmonary arterial hypertension, and late mortality. In such cases, early intervention may be indicated before irreversible secondary changes occur. We present the case and the therapeutic approach of an adolescent patient with total anomalous pulmonary venous drainage to the superior vena cava operated in infancy who developed pulmonary venous obstruction and secondary severe pulmonary arterial hypertension. PMID:27209841

  6. Arterial morphology responds differently to Captopril then N-acetylcysteine in a monocrotaline rat model of pulmonary hypertension

    NASA Astrophysics Data System (ADS)

    Molthen, Robert; Wu, Qingping; Baumgardt, Shelley; Kohlhepp, Laura; Shingrani, Rahul; Krenz, Gary

    2010-03-01

    Pulmonary hypertension (PH) is an incurable condition inevitably resulting in death because of increased right heart workload and eventual failure. PH causes pulmonary vascular remodeling, including muscularization of the arteries, and a reduction in the typically large vascular compliance of the pulmonary circulation. We used a rat model of monocrotaline (MCT) induced PH to evaluated and compared Captopril (an angiotensin converting enzyme inhibitor with antioxidant capacity) and N-acetylcysteine (NAC, a mucolytic with a large antioxidant capacity) as possible treatments. Twenty-eight days after MCT injection, the rats were sacrificed and heart, blood, and lungs were studied to measure indices such as right ventricular hypertrophy (RVH), hematocrit, pulmonary vascular resistance (PVR), vessel morphology and biomechanics. We implemented microfocal X-ray computed tomography to image the pulmonary arterial tree at intravascular pressures of 30, 21, 12, and 6 mmHg and then used automated vessel detection and measurement algorithms to perform morphological analysis and estimate the distensibility of the arterial tree. The vessel detection and measurement algorithms quickly and effectively mapped and measured the vascular trees at each intravascular pressure. Monocrotaline treatment, and the ensuing PH, resulted in a significantly decreased arterial distensibility, increased PVR, and tended to decrease the length of the main pulmonary trunk. In rats with PH induced by monocrotaline, Captopril treatment significantly increased arterial distensibility and decrease PVR. NAC treatment did not result in an improvement, it did not significantly increase distensibility and resulted in further increase in PVR. Interestingly, NAC tended to increase peripheral vascular density. The results suggest that arterial distensibility may be more important than distal collateral pathways in maintaining PVR at normally low values.

  7. Chronic intrauterine pulmonary hypertension increases main pulmonary artery stiffness and adventitial remodeling in fetal sheep

    PubMed Central

    Morgan, Matthew R.; Galambos, Csaba; Hunter, Kendall S.; Abman, Steven H.

    2014-01-01

    Persistent pulmonary hypertension of the newborn (PPHN) is a clinical syndrome that is characterized by high pulmonary vascular resistance due to changes in lung vascular growth, structure, and tone. PPHN has been primarily considered as a disease of the small pulmonary arteries (PA), but proximal vascular stiffness has been shown to be an important predictor of morbidity and mortality in other diseases associated with pulmonary hypertension (PH). The objective of this study is to characterize main PA (MPA) stiffness in experimental PPHN and to determine the relationship of altered biomechanics of the MPA with changes in extracellular matrix (ECM) content and orientation of collagen and elastin fibers. MPAs were isolated from control and PPHN fetal sheep model and were tested by planar biaxial testing to measure stiffness in circumferential and axial vessel orientations. Test specimens were fixed for histological assessments of the vascular wall ECM constituents collagen and elastin. MPAs from PPHN sheep had increased mechanical stiffness (P < 0.05) and altered ECM remodeling compared with control MPA. A constitutive mathematical model and histology demonstrated that PPHN vessels have a smaller contribution of elastin and a greater role for collagen fiber engagement compared with the control arteries. We conclude that exposure to chronic hemodynamic stress in late-gestation fetal sheep increases proximal PA stiffness and alters ECM remodeling. We speculate that proximal PA stiffness further contributes to increased right ventricular impedance in experimental PPHN, which contributes to abnormal transition of the pulmonary circulation at birth. PMID:25326575

  8. Pulmonary arterial responses to reactive oxygen species are altered in newborn piglets with chronic hypoxia-induced pulmonary hypertension

    PubMed Central

    Fike, Candice D.; Aschner, Judy L.; Slaughter, James C.; Kaplowitz, Mark R.; Zhang, Yongmei; Pfister, Sandra L.

    2011-01-01

    Reactive oxygen species (ROS) have been implicated in the pathogenesis of pulmonary hypertension. ROS might mediate vascular responses, at least in part, by stimulating prostanoid production. Our goals were to determine if the effect of ROS on vascular tone is altered in resistance pulmonary arteries (PRA) of newborn piglets with chronic hypoxia-induced pulmonary hypertension and the role, if any, of prostanoids in ROS-mediated responses. In cannulated, pressurized PRA, ROS generated by xanthine (X) plus xanthine oxidase (XO) had minimal effect on vascular tone in control piglets but caused significant vasoconstriction in hypoxic piglets. Both cyclooxygenase inhibition with indomethacin and thromboxane synthase inhibition with dazoxiben significantly blunted constriction to X+XO in hypoxic PRA. X+XO increased prostacyclin production (70±8%) by a greater degree than thromboxane production (50±6%) in control PRA; this was not the case in hypoxic PRA where the increases in prostacyclin and thromboxane production were not statistically different (78±13% versus 216±93%, respectively). Thromboxane synthase expression was increased in PRA from hypoxic piglets while prostacyclin synthase expression was similar in PRA from hypoxic and control piglets. Under conditions of chronic hypoxia, altered vascular responses to ROS may contribute to pulmonary hypertension by a mechanism that involves the prostanoid vasoconstrictor, thromboxane. PMID:21516056

  9. Anomalous origin of the left coronary artery from the pulmonary artery presenting as dilated cardiomyopathy: a case report

    PubMed Central

    2014-01-01

    Introduction Anomalous origin of the left coronary artery from the pulmonary artery is a rare congenital anomaly and one of the causes of myocardial ischemia. The usual clinical course is severe left-sided heart failure and mitral valve insufficiency presenting during the first months of life. Case presentation We report the case of a 6-month-old Tunisian girl who presented with dilated cardiomyopathy. Echocardiography suspected anomalous origin of the left coronary artery. The definitive diagnosis of anomalous origin of the left coronary artery from the pulmonary artery was reached by multislice computed tomography and coronary angiography. Conclusion In cases of dilated cardiomyopathy, anomalous origin of the left coronary artery from the pulmonary artery syndrome has to be kept in mind as a surgically correctable cause. PMID:24885797

  10. Arterial desaturation due to pulmonary arteriovenous malformations after the Kawashima Operation.

    PubMed

    Loomba, Rohit S

    2016-01-01

    Arterial desaturation may occur after the Kawashima procedure and, in the absence of venovenous collaterals is usually due to pulmonary arteriovenous malformations. Stenting of the pulmonary arteries, oxygen therapy, and pulmonary vasodilators such as sildenafil have not been able to resolve the arterial desaturation and the only way to do this has been Fontan completion. The time course of the formation of these malformations after the Kawashima and the progression of cyanosis and its resolution after the Fontan has only been demonstrated in case reports and small case series. We pool the available data to model arterial saturations in patients with pulmonary arteriovenous malformations after the Kawashima procedure. PMID:27011689

  11. Neonatal Repair in a Patient With Heterotaxy, Truncus Arteriosus, Pulmonary Artery Sling, and Tracheal Stenosis.

    PubMed

    Anagnostopoulos, Petros V; Kenny, Eugene C; Peterson, Amy L H; Hagen, Scott A; McMurray, J Scott

    2015-12-01

    We present a newborn with heterotaxy features, multiple congenital anomalies, truncus arteriosus with long segment tracheal stenosis, and a left pulmonary artery sling. The patient had complete neonatal repair with slide tracheoplasty and repair of the left pulmonary artery sling with anterior translocation of the pulmonary artery. The truncus was repaired with a transventricular ventricular septal defect closure with a patch and right ventricle to pulmonary artery conduit. Complete repair of complex cardiac neonatal lesions with critical tracheal stenosis is feasible and should be the strategy of choice in these complex patients. PMID:26652536

  12. Calorie Restriction Attenuates Monocrotaline-induced Pulmonary Arterial Hypertension in Rats.

    PubMed

    Ding, Mingge; Lei, Jingyi; Qu, Yinxian; Zhang, Huan; Xin, Weichuan; Ma, Feng; Liu, Shuwen; Li, Zhichao; Jin, Faguang; Fu, Enqing

    2015-06-01

    Calorie restriction (CR) is one of the most effective nonpharmacological interventions protecting against cardiovascular disease, such as hypertension in the systemic circulation. However, whether CR could attenuate pulmonary arterial hypertension (PAH) is largely unknown. The PAH model was developed by subjecting the rats to a single subcutaneous injection of monocrotaline. CR lowered mean pulmonary arterial pressure (mPAP) and reduced vascular remodeling and right ventricular hypertrophy in PAH rats. Meanwhile, CR attenuated endothelial dysfunction as evidenced by increased relaxation in response to acetylcholine. The beneficial effects of CR were associated with restored sirtuin-1 (SIRT1) expression and endothelial nitric oxide synthase (eNOS) phosphorylation and reduced eNOS acetylation in pulmonary arteries of PAH rats. To further clarify the role of SIRT1 in the protective effects of CR, adenoviral vectors for overexpression of SIRT1 were administered intratracheally at 1 day before monocrotaline injection. Overexpression of SIRT1 exhibited similar beneficial effects on mPAP and endothelial function, and increased eNOS phosphorylation and reduced eNOS acetylation in the absence of CR. Moreover, SIRT1 overexpression attenuated the increase in mPAP in hypoxia-induced PAH animals. Overall, the present data demonstrate that CR may serve as an effective treatment of PAH, and targeting the SIRT1/eNOS pathway may improve treatment of PAH. PMID:25636073

  13. Pulmonary arterial hypertension associated with bronchopulmonary dysplasia and congenital heart disease in preterm infants. A case report of a preterm infant with recurrent pulmonary hypertension after corrective cardiac surgery and review of the literature.

    PubMed

    Muneuchi, Jun; Kuraoka, Ayako; Watanabe, Mamie; Ochiai, Yoshie; Joo, Kunitaka

    2015-01-01

    In preterm infants with congenital heart disease, concomitant bronchopulmonary dysplasia (BPD) is associated with relatively poor clinical outcomes because of the increased pulmonary vascular resistance and adverse effects of inflammation on the damaged lungs, even after surgery. We present herein a 1-year-old female who developed recurrent pulmonary arterial hypertension 6 months after closure of a ventricular septal defect. She was born at 26 weeks of gestation (birth weight, 470 g), and developed BPD requiring oxygen supplementation. Her systemic-to-pulmonary blood flow ratio was 2.1 preoperatively and 1.0 postoperatively, pulmonary arterial pressure was 61/15 (mean 39) mmHg preoperatively and 41/17 (mean 24) mmHg postoperatively, and pulmonary vascular resistance was 4.2 mmHg/L·minute·m(2) preoperatively and 3.6 mmHg/L·minute·m(2) postoperatively. At 1 year of age, echocardiography showed an increase in her estimated right ventricular pressure, indicating worsening pulmonary hypertension. After 3 years of treatment with oxygen supplementation, prostacyclin, and bosentan, her pulmonary arterial pressure improved to the normal range. The pathophysiology of pulmonary arterial hypertension is heterogeneous in preterm infants with congenital heart disease and concomitant BPD. Careful management of these patients is warranted even after corrective cardiac surgery.

  14. Digital subtraction angiography of the pulmonary arteries for the diagnosis of pulmonary embolism

    SciTech Connect

    Ludwig, J.W.; Verhoeven, L.A.J.; Kersbergen, J.J.; Overtoom, T.T.C.

    1983-06-01

    A comparative study of radionuclide scanning (perfusion studies in all 18 patients and ventilation studies in 9) and digital subtraction angiography (DSA) was performed in 18 patients with suspected pulmonary thromboembolism. In 17 patients good visualization of the arteries was obtained with DSA; 10 of these patients had no pre-existing lung disease, and 7 had chronic obstructive pulmonary disease (COPD). The information provided by DSA in this small group was equal to or better than that of scintigraphy, especially in patients with COPD, and the reliability of DSA was superior to that of the radionuclide scintigraphy. Methods for preventing motion artifacts with DSA are also described.

  15. TEVAR for Flash Pulmonary Edema Secondary to Thoracic Aortic Aneurysm to Pulmonary Artery Fistula.

    PubMed

    Bornak, Arash; Baqai, Atif; Li, Xiaoyi; Rey, Jorge; Tashiro, Jun; Velazquez, Omaida C

    2016-01-01

    Enlarging aneurysms in the thoracic aorta frequently remain asymptomatic. Fistulization of thoracic aortic aneurysms (TAA) to adjacent structures or the presence of a patent ductus arteriosus and TAA may lead to irreversible cardiopulmonary sequelae. This article reports on a large aneurysm of the thoracic aorta with communication to the pulmonary artery causing pulmonary edema and cardiorespiratory failure. The communication was ultimately closed after thoracic endovascular aortic aneurysm repair allowing rapid symptom resolution. Early diagnosis and closure of such communication in the presence of TAA are critical for prevention of permanent cardiopulmonary damage.

  16. Riociguat as a treatment regime for pulmonary arterial hypertension: a review.

    PubMed

    Narang, Bawneet K; Roy, Subhajit; Sharma, Rajiv; Singh, Virender; Rawal, Ravindra K

    2015-01-01

    Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition distinguished by elevated pressure of pulmonary arteries and increased vascular resistance. The management of patients with PAH and CTEPH has advanced rapidly over last decade but despite the progress in the treatment, the survival of suffering patients remain unsatisfactory and there is no cure for the diseases. However, surgery is not a first choice for patients. Furthermore, some patients who undergo surgery have persistent pulmonary hypertension (HTN) as a side effect after surgery. Therefore, the search for an "ideal" therapy still goes on and it lead to the approval of riociguat as a potential agent for the treatment. It acts directly on soluble guanylate cyclase, exciting the enzyme, and elevating sensitivity to lower levels of NO. Riociguat, therefore, has potential as a novel therapy for PAH and CTEPH. This review is focused on various aspects of the recently approved "riociguat" including its efficacy and safety profiles with the clinical data highlighting its importance in the present scenario.

  17. Anomalous origin of left coronary artery from pulmonary artery in adults.

    PubMed

    Murala, John S K; Sankar, Madhu N; Agarwal, Ravi; Golla, Prasad N; Nayar, Pradeep G; Cherian, Kotturathu M

    2006-02-01

    Various techniques have been described for management of anomalous origin of the left coronary artery from the pulmonary artery presenting in adults. Three patients, 1 male and 2 females, aged 27-37 years, underwent transpulmonary pericardial patch closure with concomitant left internal thoracic artery anastomosis to the left anterior descending artery, under standard cardiopulmonary bypass, thus creating a two-coronary system. One patient had concomitant mitral valve repair. All 3 survived the operation. Postoperative angiography in 2 patients revealed good antegrade flow with decreased collaterals in one and competitive inhibition with increased collaterals in the other. This procedure is considered to be the safest and simplest in this subset of patients. PMID:16432117

  18. The limits of oral therapy in pulmonary arterial hypertension management

    PubMed Central

    Liu, Qian-Qian; Jing, Zhi-Cheng

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease in which remodeling of the small pulmonary arteries leads to a progressive increase in pulmonary vascular resistance and right-sided heart failure. Over the past decade, new treatments for PAH, such as the use of ERAs, PDE-5 inhibitors and prostacyclin analogs, have brought about dramatic improvements in clinical outcomes. Epoprostenol infusion therapy has been shown to improve hemodynamics, functional status, and survival, and it remains the gold standard for treatment of patients with severe PAH. Many agents, approved for PAH are always delivered in pill form. Although oral therapy occupies an important position, it has some drawbacks and limitations in PAH management. For patients in World Health Organization functional class IV and with severe right heart failure, there are few data on the long-term survival of patients treated with oral medications. Further research, exploration, and clinical experience with oral therapy in severe PAH and combination therapy will redefine its position in PAH management. PMID:26648729

  19. The limits of oral therapy in pulmonary arterial hypertension management.

    PubMed

    Liu, Qian-Qian; Jing, Zhi-Cheng

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease in which remodeling of the small pulmonary arteries leads to a progressive increase in pulmonary vascular resistance and right-sided heart failure. Over the past decade, new treatments for PAH, such as the use of ERAs, PDE-5 inhibitors and prostacyclin analogs, have brought about dramatic improvements in clinical outcomes. Epoprostenol infusion therapy has been shown to improve hemodynamics, functional status, and survival, and it remains the gold standard for treatment of patients with severe PAH. Many agents, approved for PAH are always delivered in pill form. Although oral therapy occupies an important position, it has some drawbacks and limitations in PAH management. For patients in World Health Organization functional class IV and with severe right heart failure, there are few data on the long-term survival of patients treated with oral medications. Further research, exploration, and clinical experience with oral therapy in severe PAH and combination therapy will redefine its position in PAH management. PMID:26648729

  20. Left ventricular thrombus formation after repair of anomalous left coronary artery from the pulmonary artery.

    PubMed

    Freud, Lindsay R; Koenig, Peter R; Russell, Hyde M; Patel, Angira

    2014-04-01

    Although thrombus formation following myocardial infarction in adults is well known, intracardiac thrombosis in children is uncommon. We report the case of a large left ventricular thrombus in an infant with ischemic cardiomyopathy secondary to anomalous origin of the left coronary artery from the pulmonary artery. Given its mobility and protrusion across the aortic valve, the patient underwent urgent thrombus removal through a transaortic approach. There were no embolic or neurologic complications. This case highlights that thrombectomy may be performed safely and successfully in critically ill pediatric patients.

  1. Echocardiographic presentation of anomalous origin of the left coronary artery from the pulmonary artery.

    PubMed

    Silverman, Norman H

    2015-12-01

    In the 1970s, diagnosing anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) was often uncertain using imaging alone; however, with the advances in high-frequency transducers, advanced image processing, and other ultrasound modalities such as Doppler colour flow imaging, tissue Doppler imaging, and speckle tracking to asses regional wall motion abnormalities, modern echocardiography now permits accurate diagnosis of ALCAPA with greater certainty. Although many consider ultrasound to be the only imaging test necessary if there is a question as to the diagnosis, other imaging modalities such as MRI, CT, and cardiac catheterisation with angiography remain valuable complementary tests, especially in older patients.

  2. Echocardiographic presentation of anomalous origin of the left coronary artery from the pulmonary artery.

    PubMed

    Silverman, Norman H

    2015-12-01

    In the 1970s, diagnosing anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) was often uncertain using imaging alone; however, with the advances in high-frequency transducers, advanced image processing, and other ultrasound modalities such as Doppler colour flow imaging, tissue Doppler imaging, and speckle tracking to asses regional wall motion abnormalities, modern echocardiography now permits accurate diagnosis of ALCAPA with greater certainty. Although many consider ultrasound to be the only imaging test necessary if there is a question as to the diagnosis, other imaging modalities such as MRI, CT, and cardiac catheterisation with angiography remain valuable complementary tests, especially in older patients. PMID:26675598

  3. 2014 Guidelines of Taiwan Society of Cardiology (TSOC) for the Management of Pulmonary Arterial Hypertension

    PubMed Central

    Hsu, Chih-Hsin; Ho, Wan-Jing; Huang, Wei-Chun; Chiu, Yu-Wei; Hsu, Tsu-Shiu; Kuo, Ping-Hung; Hsu, Hsao-Hsun; Chang, Jia-Kan; Cheng, Chin-Chang; Lai, Chao-Lun; Liang, Kae-Woei; Lin, Shoa-Lin; Sung, Hsao-Hsun; Tsai, Wei-Chuan; Weng, Ken-Pen; Hsieh, Kai-Sheng; Yin, Wei-Hsian; Lin, Shing-Jong; Wang, Kuo-Yang

    2014-01-01

    Pulmonary hypertension (PH) is a hemodynamic and pathophysiologic condition, defined as a mean pulmonary arterial pressure exceeding 25 mmHg at rest. According to the recent classifications, it is grouped into pulmonary arterial hypertension (PAH), heart-related, lung-related, thromboembolic, and miscellaneous PH. In the past two decades, tremendous advances have occurred in the field of PH. These include (1) development of clinical diagnostic algorithm and a monitoring strategy dedicated to PAH, (2) defining strong rationales for screening at-risk populations, (3) advent of pulmonary specific drugs which makes PAH manageable, (4) recognition of needs of having proper strategy of combining existing pulmonary specific drugs, and/or potential novel drugs, (5) pursuit of clinical trials with optimal surrogate endpoints and study durations, (6) recognition of critical roles of PH/right ventricular function, as well as interdependence of ventricles in different conditions, especially those with various phenotypes of heart failure, and (7) for rare diseases, putting equal importance on carefully designed observation studies, various registries, etc., besides double blind randomized studies. In addition, ongoing basic and clinical research has led to further understanding of relevant physiology, pathophysiology, epidemiology and genetics of PH/PAH. This guidelines from the working group of Pulmonary Hypertension of the Taiwan Society of Cardiology is to provide updated guidelines based on the most recent international guidelines as well as Taiwan’s domestic research on PH. The guidelines are mainly for the management of PAH (Group 1) ; however the majority of content can be helpful for managing other types of PH. PMID:27122817

  4. Biomarkers and prognostic indicators in pulmonary arterial hypertension.

    PubMed

    Jardim, Carlos; Souza, Rogerio

    2015-06-01

    Our understanding of the pathophysiology of pulmonary arterial hypertension (PAH) has increased substantially in the past decades. More accurate diagnosis and increased options for treatment have given researchers the opportunity to better explore the response to medical therapy and prognosis. As a result, the use of biomarkers and prognostic indicators for this devastating disease has been widely investigated. Biomarkers and prognostic indicators have also been more frequently incorporated into the design of new clinical trials. This approach has helped the pulmonary hypertension (PH) community step forward in the search for effective treatments for PAH. However, no single biomarker has shown significant superiority in predicting prognosis or patient response and an integrative approach is necessary to understand which combination of markers should be used in each of the clinical scenarios that characterize the management of PAH.

  5. Transcriptome Analysis and Gene Identification in the Pulmonary Artery of Broilers with Ascites Syndrome

    PubMed Central

    Xiao, Qingyang; Guo, Xiaoquan; Zhuang, Yu; Zhang, Caiying; Wang, Tiancheng; Lin, Huayuan; Song, Yalu; Hu, Guoliang; Liu, Ping

    2016-01-01

    Background Pulmonary arterial hypertension, also known as Ascites syndrome (AS), remains a clinically challenging disease with a large impact on both humans and broiler chickens. Pulmonary arterial remodeling presents a key step in the development of AS. The precise molecular mechanism of pulmonary artery remodeling regulating AS progression remains unclear. Methodology/Principal Findings We obtained pulmonary arteries from two positive AS and two normal broilers for RNA sequencing (RNA-seq) analysis and pathological observation. RNA-seq analysis revealed a total of 895 significantly differentially expressed genes (DEGs) with 437 up-regulated and 458 down-regulated genes, which were significantly enriched to 12 GO (Gene Ontology) terms and 4 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways (Padj<0.05) regulating pulmonary artery remodeling and consequently occurrence of AS. These GO terms and pathways include ribosome, Jak-STAT and NOD-like receptor signaling pathways which regulate pulmonary artery remodeling through vascular smooth cell proliferation, inflammation and vascular smooth cell proliferation together. Some notable DEGs within these pathways included downregulation of genes like RPL 5, 7, 8, 9, 14; upregulation of genes such as IL-6, K60, STAT3, STAT5 Pim1 and SOCS3; IKKα, IkB, P38, five cytokines IL-6, IL8, IL-1β, IL-18, and MIP-1β. Six important regulators of pulmonary artery vascular remodeling and construction like CYP1B1, ALDH7A1, MYLK, CAMK4, BMP7 and INOS were upregulated in the pulmonary artery of AS broilers. The pathology results showed that the pulmonary artery had remodeled and become thicker in the disease group. Conclusions/Significance Our present data suggested some specific components of the complex molecular circuitry regulating pulmonary arterial remodeling underlying AS progression in broilers. We revealed some valuable candidate genes and pathways that involved in pulmonary artery remodeling further contributing to the AS

  6. Dietary sodium intake and arterial blood pressure.

    PubMed

    Dumler, Francis

    2009-01-01

    We sought to summarize major recent studies in the field of dietary sodium intake and arterial blood pressure, and discuss the following trials. INTERSALT: Sodium intake correlates with the rise in blood pressure with age, but not with the prevalence of hypertension. The population study identified a minimal impact of sodium intake on blood pressure (0.9 mm Hg/10 mmol difference in salt intake). DASH: This diet induced significant reductions in blood pressure compared with the control diet. Further decreases were observed with DASH and a 50 mmol/day sodium intake. VANGUARD: Blood pressure was inversely related to urinary potassium, calcium and magnesium but not to sodium excretion. TONE: Cardiovascular events were highest in the usual care group (83%) and lowest in the sodium reduction-plus-weight loss group (56%). META-ANALYSIS: A systematic review of 11 long-term controlled randomized trials reported a small decrease (1.1 mm Hg) in median systolic but not diastolic blood pressure with a reduced dietary sodium intake. In conclusion, (1) sodium restriction in hypertensive patients reduces blood pressure, and (2) the long-term impact of reduced salt intake on blood pressure, mortality, and morbidity remains to be defined.

  7. Characterization of optimal resting tension in human pulmonary arteries

    PubMed Central

    Hussain, Azar; Bennett, Robert T; Chaudhry, Mubarak A; Qadri, Syed S; Cowen, Mike; Morice, Alyn H; Loubani, Mahmoud

    2016-01-01

    AIM To determine the optimum resting tension (ORT) for in vitro human pulmonary artery (PA) ring preparations. METHODS Pulmonary arteries were dissected from disease free sections of the resected lung in the operating theatre and tissue samples were directly sent to the laboratory in Krebs-Henseleit solution (Krebs). The pulmonary arteries were then cut into 2 mm long rings. PA rings were mounted in 25 mL organ baths or 8 mL myograph chambers containing Krebs compound (37 °C, bubbled with 21% O2: 5% CO2) to measure changes in isometric tension. The resting tension was set at 1-gram force (gf) with vessels being left static to equilibrate for duration of one hour. Baseline contractile reactions to 40 mmol/L KCl were obtained from a resting tension of 1 gf. Contractile reactions to 40 mmol/L KCl were then obtained from stepwise increases in resting tension (1.2, 1.4, 1.6, 1.8 and 2.0 gf). RESULTS Twenty PA rings of internal diameter between 2-4 mm were prepared from 4 patients. In human PA rings incrementing the tension during rest stance by 0.6 gf, up to 1.6 gf significantly augmented the 40 mmol/L KCl stimulated tension. Further enhancement of active tension by 0.4 gf, up to 2.0 gf mitigate the 40 mmol/L KCl stimulated reaction. Both Myograph and the organ bath demonstrated identical conclusions, supporting that the radial optimal resting tension for human PA ring was 1.61 g. CONCLUSION The radial optimal resting tension in our experiment is 1.61 gf (15.78 mN) for human PA rings. PMID:27721938

  8. Definition and classification of pulmonary hypertension.

    PubMed

    Humbert, Marc; Montani, David; Evgenov, Oleg V; Simonneau, Gérald

    2013-01-01

    Pulmonary hypertension is defined as an increase of mean pulmonary arterial pressure ≥25 mmHg at rest as assessed by right heart catheterization. According to different combinations of values of pulmonary wedge pressure, pulmonary vascular resistance and cardiac output, a hemodynamic classification of pulmonary hypertension has been proposed. Of major importance is the pulmonary wedge pressure which allows to distinguish pre-capillary (pulmonary wedge pressure ≤15 mmHg) and post-capillary (pulmonary wedge pressure >15 mmHg) pulmonary hypertension. Pre-capillary pulmonary hypertension includes the clinical groups 1 (pulmonary arterial hypertension), 3 (pulmonary hypertension due to lung diseases and/or hypoxia), 4 (chronic thrombo-embolic pulmonary hypertension) and 5 (pulmonary hypertension with unclear and/or multifactorial mechanisms). Post-capillary pulmonary hypertension corresponds to the clinical group 2 (pulmonary hypertension due to left heart diseases).

  9. Pulmonary artery involvement in aorto-arteritis. An analysis of DSA.

    PubMed

    He, N S; Liu, F; Wu, E H; Zhang, C L; Yang, J G; Tan, J; Gao, S; Yang, L C; Zhou, Y B

    1990-08-01

    Angiographic features of the pulmonary artery were studied in 24 patients with aortoarteritis (Takayasu's arteritis) by digital subtraction angiography. The pulmonary artery involvement was found in nine cases (37.5%). The right side was involved in eight and the left side in five cases. The right pulmonary artery was involved in two cases, the lobar artery in six, the segmental artery in six, and subsegmental as well as peripheral branches in four. The angiographic features were stenosis and/or occlusion as were the changes of the systemic arteries in aorto-arteritis. The aorta and its main branches were involved in all nine patients, but the severity of pulmonary vascular changes was not always related to the systemic vascular changes. Bronchial angiography demonstrated enlarged and tortuous bronchial arteries in four cases. Lung ECT revealed abnormalities in four cases. PMID:1978705

  10. Pregnancy as a possible trigger for heritable pulmonary arterial hypertension.

    PubMed

    Limoges, Maude; Langleben, David; Fox, Benjamin D; Shear, Roberta; Wieczorek, Paul; Rudski, Lawrence G; Hirsch, Andrew M; Schlesinger, Robert D; Lesenko, Lyda

    2016-09-01

    It is unclear whether pregnancy is a trigger or accelerant for idiopathic pulmonary arterial hypertension (PAH). Alternatively, its frequency close to the onset of symptoms and diagnosis in the idiopathic PAH population may represent a coincidence in a disease that predominates in young women. We describe a carrier of a BMPR2 gene mutation who had an uneventful first pregnancy but had aggressive PAH during her second pregnancy and now has ongoing heritable PAH. The possible role of pregnancy as a trigger in this vulnerable patient is discussed. Databases of patients with heritable PAH should be explored to see whether pregnancy is related to overt manifestation of the disease. PMID:27683615

  11. Macitentan for the treatment of pulmonary arterial hypertension.

    PubMed

    Spikes, L; Williamson, T; Satterwhite, L

    2014-06-01

    Macitentan is a novel, dual endothelin receptor antagonist recently approved for the treatment of WHO Group I pulmonary arterial hypertension. Its pharmacologic mechanism of action as well as the pharmacokinetics, pharmacodynamics and potential drug-drug interactions have been demonstrated in multiple phase I and II trials. The pivotal randomized, placebo-controlled, event-driven clinical trial revealed a significant reduction in morbidity. The most common adverse events were rarely clinically significant, nor did they result in a high rate of discontinuation. Of note, macitentan is contraindicated in pregnant women due to embryo-fetal toxicity.

  12. Pregnancy as a possible trigger for heritable pulmonary arterial hypertension

    PubMed Central

    Langleben, David; Fox, Benjamin D.; Shear, Roberta; Wieczorek, Paul; Rudski, Lawrence G.; Hirsch, Andrew M.; Schlesinger, Robert D.; Lesenko, Lyda

    2016-01-01

    Abstract It is unclear whether pregnancy is a trigger or accelerant for idiopathic pulmonary arterial hypertension (PAH). Alternatively, its frequency close to the onset of symptoms and diagnosis in the idiopathic PAH population may represent a coincidence in a disease that predominates in young women. We describe a carrier of a BMPR2 gene mutation who had an uneventful first pregnancy but had aggressive PAH during her second pregnancy and now has ongoing heritable PAH. The possible role of pregnancy as a trigger in this vulnerable patient is discussed. Databases of patients with heritable PAH should be explored to see whether pregnancy is related to overt manifestation of the disease. PMID:27683615

  13. Pulmonary arterial hypertension associated with neurofibromatosis type 1.

    PubMed

    Carrascosa, Miguel F; Larroque, Isabel Celemín; Rivero, Juan-Luis García; García, José-Antonio Saiz-Quevedo; Hoz, Marta Cano; Ares, Miguel Ares; López, Xabier Arrastio; Caviedes, José-Ramón Salcines

    2010-01-01

    The authors report a case of severe pulmonary arterial hypertension (PAH) in a 75-year-old woman who had received a diagnosis of neurofibromatosis type 1 (NF1) 23 years before. She presented with progressive dyspnoea and recurrent syncope. Even though the patient initially improved after starting supportive and specific treatment for PAH, she then deteriorated and died from respiratory failure 11 months after the diagnosis of PAH. Prompt recognition of such an unusual association between PAH and NF1 and appropriate therapeutic intervention could ameliorate quality of life and prolong survival in this patient population. PMID:22798089

  14. [Intralobar pulmonary sequestration with multiple arterial blood supply].

    PubMed

    Uroz Tristán, J; Mogueya, S A; Poenaru, D; Martínez Lagares, F; Arteaga García, R; Sanchís Solera, L; López-Pinto Ruiz, J

    1994-04-01

    We report the case of a 4 years old boy, who presented at our institution with reiterative neumonia affecting left basal lobe. Anomalous vascular appearance was detected in the chest x-ray. With the suspicion of pulmonary sequestration we carried on Digital Intravenous Angiography by Substraction (DIVAS) and aortogram. The anomalous systemic arterial supply was formed by 6 vessels coming from the thoracic aorta and going into the left lower lobe basal segment. Lobectomy was performed and previous diagnosis was confirmed pathologically. PMID:8086288

  15. Pulmonary Artery and Intestinal Temperatures during Heat Stress and Cooling

    PubMed Central

    Pearson, James; Ganio, Matthew S; Seifert, Thomas; Overgaard, Morten; Secher, Niels H; Crandall, Craig G

    2011-01-01

    Introduction/Purpose In humans, whole body heating and cooling are used to address physiological questions where core temperature is central to the investigated hypotheses. Core temperature can be measured in various locations throughout the human body. The measurement of intestinal temperature is increasingly used in laboratory settings as well as in athletics. However, it is unknown whether intestinal temperature accurately tracks pulmonary artery blood temperature, the gold standard, during thermal stimuli in resting humans, which is the investigated hypothesis. Methods This study compared pulmonary artery blood temperature (via thermistor in a pulmonary artery catheter) with intestinal temperature (telemetry pill) during whole-body heat stress (n=8), followed by whole-body cooling in healthy humans (mean ± SD age 24 ± 3 yrs; height 183 ± 8 cm; mass 78.1 ± 8.2 kg). Heat stress and subsequent cooling were performed by perfusing warm followed by cold water through a tube-lined suit worn by each subject. Results Prior to heat stress blood temperature (36.69 ± 0.25°C) was less than intestinal temperature (36.96 ± 0.21°C, P = 0.004). The increase in blood temperature after 20 min of heat stress was greater than intestinal temperature (0.70 ± 0.24 vs. 0.47 ± 0.18; P = 0.001). However, the increase in temperatures at the end of heat stress were similar between sites (blood Δ = 1.32 ± 0.20°C vs. intestinal Δ = 1.21 ± 0.36°C; P = 0.30). Subsequent cooling decreased blood temperature (Δ = −1.03 ± 0.34°C) to a greater extent than intestinal temperature (Δ = −0.41 ± 0.30°C, P = 0.04). Conclusion In response to the applied thermal provocations, early temperature changes in the intestine are less than the temperature changes in pulmonary artery blood. PMID:22015711

  16. Pregnancy as a possible trigger for heritable pulmonary arterial hypertension

    PubMed Central

    Langleben, David; Fox, Benjamin D.; Shear, Roberta; Wieczorek, Paul; Rudski, Lawrence G.; Hirsch, Andrew M.; Schlesinger, Robert D.; Lesenko, Lyda

    2016-01-01

    Abstract It is unclear whether pregnancy is a trigger or accelerant for idiopathic pulmonary arterial hypertension (PAH). Alternatively, its frequency close to the onset of symptoms and diagnosis in the idiopathic PAH population may represent a coincidence in a disease that predominates in young women. We describe a carrier of a BMPR2 gene mutation who had an uneventful first pregnancy but had aggressive PAH during her second pregnancy and now has ongoing heritable PAH. The possible role of pregnancy as a trigger in this vulnerable patient is discussed. Databases of patients with heritable PAH should be explored to see whether pregnancy is related to overt manifestation of the disease.

  17. Depression in pulmonary arterial hypertension: An undertreated comorbidity

    PubMed Central

    Verma, Sameer; Sahni, Sonu; Vijayan, Vannan K; Talwar, Arunabh

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a debilitating condition leading to progressive decline in functional capacity. As a result, PAH can lead to psychological impairment that can impact the overall disease status. The medical community has developed several screening questionnaires in order to assess depression in their patients allowing physicians to be at the forefront of recognizing clinical depression. There is a suggestion that depression symptomatology is more prevalent in the PAH population. The aim of this article is to review the current thought process about diagnosis and management of depression in PAH patients. PMID:26933309

  18. Multiplane transesophageal echocardiography in diagnosis of anomalous origin of the left coronary artery from the pulmonary artery: a case report.

    PubMed

    Hsu, S Y; Lin, F C; Chang, H J; Yeh, S J; Wu, D

    1998-06-01

    Anomalous origin of the left coronary artery from the pulmonary artery in adults is difficult to identify reliably by transthoracic echocardiography (TTE). We describe a 32-year-old woman with this coronary anomaly mimicking a coronary artery fistula on conventional TTE study. This anomaly was suggested by multiplane transesophageal echocardiography (TEE) and subsequently confirmed by coronary angiography. Multiplane TEE thus may serve as a first-line diagnostic tool for detecting anomalous origin of coronary arteries.

  19. Stress-shielding, growth and remodeling of pulmonary artery reinforced with copolymer scaffold and transposed into aortic position.

    PubMed

    Nappi, Francesco; Carotenuto, Angelo Rosario; Di Vito, Donato; Spadaccio, Cristiano; Acar, Cristophe; Fraldi, Massimiliano

    2016-10-01

    Ross operation, i.e., the use of autologous pulmonary artery to replace diseased aortic valve, has been recently at the center of a vivid debate regarding its unjust underuse in the surgical practice. Keystone of the procedure regards the use of an autologous biologically available graft which would preserve the anticoagulative and tissue homeostatic functions normally exerted by the native leaflets and would harmoniously integrate in the vascular system, allowing for progressive somatic growth of aortic structures. With this respect, recently, some of the authors have successfully pioneered a large animal model of transposition of pulmonary artery in systemic pressure load in order to reproduce the clinical scenario in which this procedure might be applied and allow for the development and testing of different devices or techniques to improve the pulmonary autograft (PA) performance, by testing a bioresorbable mesh for PA reinforcement. In the present work, to support and supplement the in vivo animal experimentation, a mathematical model is developed in order to simulate the biomechanical changes in pulmonary artery subjected to systemic pressure load and reinforced with a combination of resorbable and auxetic synthetic materials. The positive biological effects on vessel wall remodeling, the regional somatic growth phenomena and prevention of dilatative degeneration have been analyzed. The theoretical outcomes show that a virtuous biomechanical cooperation between biological and synthetic materials takes place, stress-shielding guiding the physiological arterialization of vessel walls, consequently determining the overall success of the autograft system.

  20. Obstruction of the Aorta and Left Pulmonary Artery After Gianturco Coil Occlusion of Patent Ductus Arteriosus

    SciTech Connect

    Kuo, H.-Cg; Ko, Sheung-Fat; Wu, Yu-Tsun; Huang, Chien-Fu; Chien, Shao-Ju; Tiao, Mao-Meng; Liang, Chi-Di

    2005-01-15

    We report an unusual case of simultaneous obstruction of the left pulmonary artery and descending thoracic aorta after Gianturco coil occlusion in a 15-month-old boy. The diagnosis was made by echocardiography and cardiac angiography. At surgery, thrombi coating on the protruded parts of the Gianturco coil in the pulmonary artery and aorta were found.

  1. Severe pulmonary arterial hypertension due to Angiostrongylosus vasorum in a dog.

    PubMed

    Nicolle, Audrey P; Chetboul, Valérie; Tessier-Vetzel, Dominique; Carlos Sampedrano, Carolina; Aletti, Edouard; Pouchelon, Jean-Louis

    2006-08-01

    A dog was presented with a history of dyspnea, coughing, and ascites. Angiostrongylosis and severe pulmonary arterial hypertension (PAH) were found, as well as a marked discordance between the electrical and mechanical events of the heart. Pulmonary arterial hypertension related to Angiostrongylus vasorum has rarely been reported.

  2. A pulmonary artery false aneurysm after right middle lobectomy: a case report

    PubMed Central

    Shaaban, Hossam; Sharma, Hemant; Rao, Jagan; Clark, Stephen

    2007-01-01

    Pulmonary artery false aneurysm is a rare condition, reported to complicate interventional procedures. We report a case of a false aneurysm of the interlobar pulmonary artery following a right middle lobectomy for lung cancer. This is probably the first reported case. PMID:17718925

  3. Compression of the left main coronary artery by a pulmonary artery aneurysm in a patient with tetralogy of Fallot and an absent pulmonary valve.

    PubMed

    Khante, Vishal; Agarwal, Saket; Satyarthi, Subodh; Upretti, Lalendra; Satsangi, Deepak K

    2011-05-01

    A case of a 16-year-old female with tetralogy of Fallot and absent pulmonary valve is presented, who on coronary angiography and computerized tomography (CT) angiography had severe compression of the left main coronary artery by the dilated main pulmonary artery. The patient was successfully managed by surgical correction of the intracardiac defect, with right ventricular outflow tract reconstruction by the Contegra(®) bovine jugular vein conduit.  PMID:21447083

  4. An alternative technique for direct implantation of an anomalous left coronary artery arising from the pulmonary artery with complex coronary arteries

    PubMed Central

    Ishimaru, Kazuhiko; Araki, Kanta; Nakamura, Tsuneyuki; Sawa, Yoshiki

    2016-01-01

    A 2-month-old patient with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) underwent an alternative repair involving coronary transfer with the bay window technique because of the very short left main coronary trunk. This procedure is a clinically relevant and feasible technique for ALCAPA with such a delicate coronary artery anomaly. PMID:27656197

  5. An alternative technique for direct implantation of an anomalous left coronary artery arising from the pulmonary artery with complex coronary arteries.

    PubMed

    Ishimaru, Kazuhiko; Araki, Kanta; Nakamura, Tsuneyuki; Sawa, Yoshiki

    2016-01-01

    A 2-month-old patient with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) underwent an alternative repair involving coronary transfer with the bay window technique because of the very short left main coronary trunk. This procedure is a clinically relevant and feasible technique for ALCAPA with such a delicate coronary artery anomaly. PMID:27656197

  6. An alternative technique for direct implantation of an anomalous left coronary artery arising from the pulmonary artery with complex coronary arteries

    PubMed Central

    Ishimaru, Kazuhiko; Araki, Kanta; Nakamura, Tsuneyuki; Sawa, Yoshiki

    2016-01-01

    A 2-month-old patient with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) underwent an alternative repair involving coronary transfer with the bay window technique because of the very short left main coronary trunk. This procedure is a clinically relevant and feasible technique for ALCAPA with such a delicate coronary artery anomaly.

  7. Right Ventricular Outflow Tract Tumor Mimicking a Thrombus in the Main Pulmonary Artery.

    PubMed

    Amuchastegui, Luis M.; Marani, Leandro P.; Caeiro, Andres

    1997-11-01

    Primary sarcomas of the pulmonary artery and right ventricle are rare, and their presentation is unusual in clinical practice; therefore, their diagnosis is often missed or delayed. The progression of the obstruction from the outflow tract of the right ventricle to the pulmonary artery resembles massive pulmonary embolism. We present a case of one of these tumors which mimicked transesophageal echocardiography (TEE), a massive pulmonary embolism. We conclude that TEE represents a noninvasive method of diagnosis and evaluation when the suspicion is massive pulmonary thromboembolism or a heart tumor.

  8. Ultrasonic Estimation of Mechanical Properties of Pulmonary Arterial Wall Under Normoxic and Hypoxic Conditions

    NASA Astrophysics Data System (ADS)

    Waters, Kendall R.; Mukdadi, Osama M.

    2005-04-01

    Secondary pediatric pulmonary hypertension is a disease that could benefit from improved ultrasonic diagnostic techniques. We perform high-frequency in vitro ultrasound measurements (25 MHz to 100 MHz) on fresh and fixed pulmonary arterial walls excised from normoxic and hypoxic Long-Evans rat models. Estimates of the elastic stiffness coefficients are determined from measurements of the speed of sound. Preliminary results indicate that hypoxia leads to up to increase of 20 % in stiffening of the pulmonary arterial wall.

  9. Connective tissue disease-associated pulmonary arterial hypertension

    PubMed Central

    Howard, Luke S.

    2015-01-01

    Although rare in its idiopathic form, pulmonary arterial hypertension (PAH) is not uncommon in association with various associated medical conditions, most notably connective tissue disease (CTD). In particular, it develops in approximately 10% of patients with systemic sclerosis and so these patients are increasingly screened to enable early detection. The response of patients with systemic sclerosis to PAH-specific therapy appears to be worse than in other forms of PAH. Survival in systemic sclerosis-associated PAH is inferior to that observed in idiopathic PAH. Potential reasons for this include differences in age, the nature of the underlying pulmonary vasculopathy and the ability of the right ventricle to cope with increased afterload between patients with systemic sclerosis-associated PAH and idiopathic PAH, while coexisting cardiac and pulmonary disease is common in systemic sclerosis-associated PAH. Other forms of connective tissue-associated PAH have been less well studied, however PAH associated with systemic lupus erythematosus (SLE) has a better prognosis than systemic sclerosis-associated PAH and likely responds to immunosuppression. PMID:25705389

  10. [NEGATIVE IMPACT OF CHROMOSOME 22Q11 MICRODELETION ON RESULTS OF TREATMENT IN PATIENTS, SUFFERING CONONTRUNCAL FAILURES OF HEART AND MAIN AORTO-PULMONARY COLLATERAL ARTERIES].

    PubMed

    Bablyak, O D; Yalynska, T A; Skorokhod, I M

    2015-05-01

    Dependence of results of surgical treatment in 42 patients, suffering conotruncal failures and main aorto-pulmonary collateral arteries from presence of the chromosome 22q11 deletion syndrome, was analyzed. While presence of the chromosome 22q11 deletion syndrome duration of treatment of patients in intensive therapy unit and artificial pulmonary ventilation are longer, pressure in a pulmonary artery system after radical operative failures correction is higher, general lethality is bigger, than while the chromosome 22q11 deletion syndrome absence. The data obtained must be taken into account while determining tactics of treatment in patients with confirmed diagnosis of the chromosome 22q11 deletion syndrome.

  11. Increased Mutagen Sensitivity and DNA Damage in Pulmonary Arterial Hypertension

    PubMed Central

    Federici, Chiara; Drake, Kylie M.; Rigelsky, Christina M.; McNelly, Lauren N.; Meade, Sirena L.; Comhair, Suzy A. A.; Erzurum, Serpil C.

    2015-01-01

    Rationale: Pulmonary arterial hypertension (PAH) is a serious lung condition characterized by vascular remodeling in the precapillary pulmonary arterioles. We and others have demonstrated chromosomal abnormalities and increased DNA damage in PAH lung vascular cells, but their timing and role in disease pathogenesis is unknown. Objectives: We hypothesized that if DNA damage predates PAH, it might be an intrinsic cell property that is present outside the diseased lung. Methods: We measured DNA damage, mutagen sensitivity, and reactive oxygen species (ROS) in lung and blood cells from patients with Group 1 PAH, their relatives, and unrelated control subjects. Measurements and Main Results: Baseline DNA damage was significantly elevated in PAH, both in pulmonary artery endothelial cells (P < 0.05) and peripheral blood mononuclear cells (PBMC) (P < 0.001). Remarkably, PBMC from unaffected relatives showed similar increases, indicating this is not related to PAH treatments. ROS levels were also higher (P < 0.01). DNA damage correlated with ROS production and was suppressed by antioxidants (P < 0.001). PBMC from patients and relatives also showed markedly increased sensitivity to two chemotherapeutic drugs, bleomycin and etoposide (P < 0.001). Results were consistent across idiopathic, heritable, and associated PAH groups. Conclusions: Levels of baseline and mutagen-induced DNA damage are intrinsically higher in PAH cells. Similar results in PBMC from unaffected relatives suggest this may be a genetically determined trait that predates disease onset and may act as a risk factor contributing to lung vascular remodeling following endothelial cell injury. Further studies are required to fully characterize mutagen sensitivity, which could have important implications for clinical management. PMID:25918951

  12. Clinical utility of tadalafil in the treatment of pulmonary arterial hypertension: an evidence-based review

    PubMed Central

    Henrie, Adam M; Nawarskas, James J; Anderson, Joe R

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a chronic and disabling condition characterized by an elevated pulmonary vascular resistance and an elevated mean pulmonary arterial pressure. Despite recent improvements in treatment availability, PAH remains challenging to treat, burdensome for patients, and ultimately incurable. Tadalafil is a phos-phodiesterase-5 inhibitor that is administered once daily by mouth for the treatment of PAH. Current treatment guidelines recommend tadalafil as an option for patients with World Health Organization functional class II or III PAH. In a placebo-controlled clinical trial, patients taking tadalafil demonstrated significantly improved exercise capacity as measured by the 6-minute walk distance. Patients also experienced decreased incidence of clinical worsening, increased quality of life, and improved cardiopulmonary hemodynamics. Uncontrolled studies and smaller trials have indicated a possible role for tadalafil as a suitable alternative to sildenafil and as a beneficial add-on option when used in combination with other treatments for PAH. Tadalafil is generally safe and well tolerated. Adverse events are typically mild-to-moderate in intensity, and discontinuation rates are usually low. The purpose of this review is to provide an evidence-based evaluation of the clinical utility of tadalafil in the treatment of PAH. PMID:26587013

  13. Anomalous Origins of Coronary Arteries From the Pulmonary Artery: A Comprehensive Review of Literature and Surgical Options.

    PubMed

    Karimi, Mohsen; Kirshbom, Paul M

    2015-10-01

    Anomalous origins of coronary arteries from the pulmonary artery are rare malformations in which the coronary arteries originate from pulmonary artery sinuses or branches. The consequences are variable although, in most cases, these anomalies lead to severe coronary hypoperfusion and ventricular dysfunction. Surgical correction is indicated once the diagnosis is established due to high early mortality associated with the disease. In nearly all cases, the anomalous artery can be excised from its pulmonary origin, mobilized, and reimplanted directly into the ascending aorta using different surgical techniques. In rare circumstances, technical modifications must be used to restore a normal dual coronary perfusion. The emphasis of this article is to provide a collective review of surgical options published in the literature.

  14. Arterial blood pressure wave forms in radial and posterior tibial arteries in critically ill newborn infants.

    PubMed

    Gevers, M; Hack, W W; Ree, E F; Lafeber, H N; Westerhof, N

    1993-04-01

    The aim of this study was to document arterial blood pressure wave forms at two sites along the arterial tree of the neonate: in the radial and posterior tibial arteries. Using a high-fidelity catheter tip-transducer system, peripheral arterial blood pressure wave forms in 26 critically newborn infants were studied. In 14 infants the radial artery and in 12 infants the posterior tibial artery was cannulated. Radial artery blood pressure waves resembled those of proximal aortic rather than those of the radial artery in adults. Quantitative analysis of the waves was performed to reassure this finding. Blood pressure waves obtained from posterior tibial artery resembled those of femoral artery rather than those of posterior tibial artery waves in adults. We conclude that radial and posterior tibial artery wave forms in neonates appear to have a central appearance. This phenomenon might be explained by the close proximity of the radial and posterior tibial artery to the central aorta and femoral artery respectively, due to the small and short limbs of the neonate. The finding allows an "easy central pressure look" at both ends of the neonatal aorta.

  15. Copper Dependence of Angioproliferation in Pulmonary Arterial Hypertension in Rats and Humans

    PubMed Central

    Mizuno, Shiro; Guignabert, Christophe; Al Hussaini, Aysar A.; Farkas, Daniela; Ruiter, Gerrina; Kraskauskas, Donatas; Fadel, Elie; Allegood, Jeremy C.; Humbert, Marc; Noordegraaf, Anton Vonk; Spiegel, Sarah; Farkas, Laszlo; Voelkel, Norbert F.

    2012-01-01

    Obliteration of the vascular lumen by endothelial cell growth is a hallmark of many forms of severe pulmonary arterial hypertension. Copper plays a significant role in the control of endothelial cell proliferation in cancer and wound-healing. We sought to determine whether angioproliferation in rats with experimental pulmonary arterial hypertension and pulmonary microvascular endothelial cell proliferation in humans depend on the proangiogenic action of copper. A copper-depleted diet prevented, and copper chelation with tetrathiomolybdate reversed, the development of severe experimental pulmonary arterial hypertension. The copper chelation–induced reopening of obliterated vessels was caused by caspase-independent apoptosis, reduced vessel wall cell proliferation, and a normalization of vessel wall structure. No evidence was found for a role of super oxide–1 inhibition or lysyl–oxidase–1 inhibition in the reversal of angioproliferation. Tetrathiomolybdate inhibited the proliferation of human pulmonary microvascular endothelial cells, isolated from explanted lungs from control subjects and patients with pulmonary arterial hypertension. These data suggest that the inhibition of endothelial cell proliferation by a copper-restricting strategy could be explored as a new therapeutic approach in pulmonary arterial hypertension. It remains to be determined, however, whether potential toxicity to the right ventricle is offset by the beneficial pulmonary vascular effects of antiangiogenic treatment in patients with pulmonary arterial hypertension. PMID:22162909

  16. The role of collagen in extralobar pulmonary artery stiffening in response to hypoxia-induced pulmonary hypertension.

    PubMed

    Ooi, Chen Yen; Wang, Zhijie; Tabima, Diana M; Eickhoff, Jens C; Chesler, Naomi C

    2010-12-01

    Hypoxic pulmonary hypertension (HPH) causes extralobar pulmonary artery (PA) stiffening, which potentially impairs right ventricular systolic function. Changes in the extracellular matrix proteins collagen and elastin have been suggested to contribute to this arterial stiffening. We hypothesized that vascular collagen accumulation is a major cause of extralobar PA stiffening in HPH and tested our hypothesis with transgenic mice that synthesize collagen type I resistant to collagenase degradation (Col1a1(R/R)). These mice and littermate controls that have normal collagen degradation (Col1a1(+/+)) were exposed to hypoxia for 10 days; some were allowed to recover for 32 days. In vivo PA pressure and isolated PA mechanical properties and collagen and elastin content were measured for all groups. Vasoactive studies were also performed with U-46619, Y-27632, or calcium- and magnesium-free medium. Pulmonary hypertension occurred in both mouse strains due to chronic hypoxia and resolved with recovery. HPH caused significant PA mechanical changes in both mouse strains: circumferential stretch decreased, and mid-to-high-strain circumferential elastic modulus increased (P < 0.05 for both). Impaired collagen type I degradation prevented a return to baseline mechanical properties with recovery and, in fact, led to an increase in the low and mid-to-high-strain moduli compared with hypoxia (P < 0.05 for both). Significant changes in collagen content were found, which tended to follow changes in mid-to-high-strain elastic modulus. No significant changes in elastin content or vasoactivity were observed. Our results demonstrate that collagen content is important to extralobar PA stiffening caused by chronic hypoxia. PMID:20852040

  17. The role of collagen in extralobar pulmonary artery stiffening in response to hypoxia-induced pulmonary hypertension

    PubMed Central

    Ooi, Chen Yen; Wang, Zhijie; Tabima, Diana M.; Eickhoff, Jens C.

    2010-01-01

    Hypoxic pulmonary hypertension (HPH) causes extralobar pulmonary artery (PA) stiffening, which potentially impairs right ventricular systolic function. Changes in the extracellular matrix proteins collagen and elastin have been suggested to contribute to this arterial stiffening. We hypothesized that vascular collagen accumulation is a major cause of extralobar PA stiffening in HPH and tested our hypothesis with transgenic mice that synthesize collagen type I resistant to collagenase degradation (Col1a1R/R). These mice and littermate controls that have normal collagen degradation (Col1a1+/+) were exposed to hypoxia for 10 days; some were allowed to recover for 32 days. In vivo PA pressure and isolated PA mechanical properties and collagen and elastin content were measured for all groups. Vasoactive studies were also performed with U-46619, Y-27632, or calcium- and magnesium-free medium. Pulmonary hypertension occurred in both mouse strains due to chronic hypoxia and resolved with recovery. HPH caused significant PA mechanical changes in both mouse strains: circumferential stretch decreased, and mid-to-high-strain circumferential elastic modulus increased (P < 0.05 for both). Impaired collagen type I degradation prevented a return to baseline mechanical properties with recovery and, in fact, led to an increase in the low and mid-to-high-strain moduli compared with hypoxia (P < 0.05 for both). Significant changes in collagen content were found, which tended to follow changes in mid-to-high-strain elastic modulus. No significant changes in elastin content or vasoactivity were observed. Our results demonstrate that collagen content is important to extralobar PA stiffening caused by chronic hypoxia. PMID:20852040

  18. [Intrapericardial lipoma with stenosis of the left bronchus and pulmonary artery].

    PubMed

    Nemoto, S; Fujimura, M; Nishiya, Y; Hamawaki, M; Miwa, A; Takabatake, S

    1992-02-01

    In a 1-year-6 month-old girl with asthma, a chest magnetic resonance imaging revealed an intrapericardial lipoma at the site of the transverse sinus behind the great arteries. The tumor compressed the left bronchus and pulmonary artery resulting in the stenosis. Under cardiopulmonary bypass, the tumor was successfully removed. The stenosis of the left bronchus and pulmonary artery were released. PMID:1593168

  19. A fractal continuum model of the pulmonary arterial tree.

    PubMed

    Krenz, G S; Linehan, J H; Dawson, C A

    1992-06-01

    The extant morphometric data from the intrapulmonary arteries of dog, human, and cat lungs produce graphs of the log of the vessel number, (N) or length (l) in each level vs. the log of the mean diameter (D) in each level that are sufficiently linear to suggest that a scale-independent self-similar or fractal structure may underlie the observed relationships. These data can be correlated by the following formulas: Nj = a1Dj-beta 1, and lj = a2Dj beta 2, where j denotes the level (order or generation) number measured from the largest vessel at the entrance to the arterial tree to the smallest vessel at the entrance to the capillary bed. With the hemodynamic resistance (R) represented by Rj = 128 microliterj/(Nj pi Dj4) and the vascular volume (Q) by Qj = Nj pi Dj2lj/4, the continuous cumulative distribution of vascular resistance (Rcum) vs. cumulative vascular volume (Qcum) (where Rcum and Qcum represent the total resistance or volume, respectively, upstream from the jth level) can be calculated from [formula: see text] where r = Dj/Dj+1 is a constant independent of j. Analogous equations are developed for the inertance and compliance distributions, providing simple formulas to represent the hemodynamic consequences of the pulmonary arterial tree structure. PMID:1629077

  20. Mesenchymal stem cells suppress CaN/NFAT expression in the pulmonary arteries of rats with pulmonary hypertension

    PubMed Central

    LIU, JUNFENG; HAN, ZHIBO; HAN, ZHONGCHAO; HE, ZHIXU

    2015-01-01

    Inflammation and hyperproliferation of pulmonary artery smooth muscle cells (PASMCs) is considered the primary pathological feature of pulmonary hypertension (PH). The present study determined that mesenchymal stem cells (MSCs) suppress the expression of calcineurin (CaN) and nuclear factor of activated T-cells (NFAT) in the pulmonary arteries of rats, and this may exert a therapeutic effect on PH. The potential therapeutic effects of MSCs on PH were assessed via the transplantation of human umbilical cord-derived MSCs, which were cultured in serum-free medium, into a monocrotaline (MCT)-induced PH rat model. Subsequently, the expression levels of tumor necrosis factor (TNF)-α in lung tissue and plasma, and of CaN and NFATc2 in pulmonary arteries were assessed. In the rat model of MCT-induced PH, investigated in the present study, TNF-α expression levels were detected in the lung tissue, and the levels of TNF-α in the plasma were increased. Furthermore, in addition to hemodynamic changes and the evident medial hypertrophy of the pulmonary muscular arterioles, CaN and NFATc2 expression levels were significantly upregulated in the pulmonary arteries. In the present study, the transplantation of MSCs, cultured in serum-free medium, decreased the levels of TNF-α in the lung tissue and plasma of rats, and downregulated CaN and NFATc2 expression in the pulmonary arteries. Furthermore, hemodynamic abnormalities and medial hypertrophy of the pulmonary muscular arterioles were notably improved. Therefore, the results of the present study may suggest that the administration of MSCs in PH may suppress the production of TNF-α, and downregulate the expression of CaN and NFATc2 in pulmonary arteries, which may provide an effective treatment for PH by suppressing the pathological proliferation of PASMCs. PMID:26640533

  1. [Myocardial ischemia secondary to a bilateral coronary fistula with drainage into the pulmonary artery trunk].

    PubMed

    Castelo, V; González-Juanatey, J R; Amaro, A; Iglesias, C; Rubio, J; Gil, M

    1994-07-01

    A case of bilateral coronary artery fistula into main pulmonary artery which courses with crisis of angina and subepicardial ischaemic changes in anterolateral leads is presented. The interest of the case reported is based on the peculiar anatomy of the fistula; there is only an unique collector to the pulmonary artery for both fistula and they present a completely different way of emerging: an unique vessel from the right coronary artery and several vessels from the anterior descending coronary artery. Ligation of the fistula was performed successfully and postoperative course was uneventful.

  2. Automated 3D Volumetry of the Pulmonary Arteries based on Magnetic Resonance Angiography Has Potential for Predicting Pulmonary Hypertension

    PubMed Central

    Rengier, Fabian; Wörz, Stefan; Melzig, Claudius; Ley, Sebastian; Fink, Christian; Benjamin, Nicola; Partovi, Sasan; von Tengg-Kobligk, Hendrik; Rohr, Karl; Kauczor, Hans-Ulrich; Grünig, Ekkehard

    2016-01-01

    Purpose To demonstrate feasibility of automated 3D volumetry of central pulmonary arteries based on magnetic resonance angiography (MRA), to assess pulmonary artery volumes in patients with pulmonary hypertension compared to healthy controls, and to investigate the potential of the technique for predicting pulmonary hypertension. Methods MRA of pulmonary arteries was acquired at 1.5T in 20 patients with pulmonary arterial hypertension and 21 healthy normotensive controls. 3D model-based image analysis software was used for automated segmentation of main, right and left pulmonary arteries (MPA, RPA and LPA). Volumes indexed to vessel length and mean, minimum and maximum diameters along the entire vessel course were assessed and corrected for body surface area (BSA). For comparison, diameters were also manually measured on axial reconstructions and double oblique multiplanar reformations. Analyses were performed by two cardiovascular radiologists, and by one radiologist again after 6 months. Results Mean volumes of MPA, RPA and LPA for patients/controls were 5508 ± 1236/3438 ± 749, 3522 ± 934/1664 ± 468 and 3093 ± 692/1812 ± 474 μl/(cm length x m2 BSA) (all p<0.001). Mean, minimum and maximum diameters along the entire vessel course were also significantly increased in patients compared to controls (all p<0.001). Intra- and interobserver agreement were excellent for both volume and diameter measurements using 3D segmentation (intraclass correlation coefficients 0.971–0.999, p<0.001). Area under the curve for predicting pulmonary hypertension using volume was 0.998 (95% confidence interval 0.990–1.0, p<0.001), compared to 0.967 using manually measured MPA diameter (95% confidence interval 0.910–1.0, p<0.001). Conclusions Automated MRA-based 3D volumetry of central pulmonary arteries is feasible and demonstrated significantly increased volumes and diameters in patients with pulmonary arterial hypertension compared to healthy controls. Pulmonary artery

  3. DNA Microarray and Signal Transduction Analysis in Pulmonary Artery Smooth Muscle Cells From Heritable and Idiopathic Pulmonary Arterial Hypertension Subjects

    PubMed Central

    Yu, Jun; Wilson, Jamie; Taylor, Linda; Polgar, Peter

    2015-01-01

    Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular smooth muscle contraction and proliferation. Here, we analyze genome-wide mRNA expression in human pulmonary arterial smooth muscle cells (HPASMC) isolated from three control, three hereditary (HPAH), and three idiopathic PAH (IPAH) subjects using the Affymetrix Human Gene ST 1.0 chip. The microarray analysis reveals the expression of 537 genes in HPAH and 1024 genes in IPAH changed compared with control HPASMC. Among those genes, 227 genes show similar directionality of expression in both HPAH and IPAH HPASMC. Ingenuity™ Pathway Analysis (IPA) suggests that many of those genes are involved in cellular growth/proliferation and cell cycle regulation and that signaling pathways such as the mitotic activators, polo-like kinases, ATM signaling are activated under PAH conditions. Furthermore, the analysis demonstrates downregulated mRNA expression of certain vasoactive receptors such as bradykinin receptor B2 (BKB2R). Using real time PCR, we verified the downregulated BKB2R expression in the PAH cells. Bradykinin-stimulated calcium influx is also decreased in PAH PASMC. IPA also identified transcriptional factors such p53 and Rb as downregulated, and FoxM1 and Myc as upregulated in both HPAH and IPAH HPASMC. The decreased level of phospho-p53 in PAH cells was confirmed with a phospho-protein array; and we experimentally show a dysregulated proliferation of both HPAH and IPAH PASMC. Together, the microarray experiments and bioinformatics analysis highlight an aberrant proliferation and cell cycle regulation in HPASMC from PAH subjects. These newly identified pathways may provide new targets for the treatment of both hereditary and idiopathic PAH. PMID:25290246

  4. Pulmonary Hypertension

    MedlinePlus

    Pulmonary hypertension (PH) is high blood pressure in the arteries to your lungs. It is a serious condition. If you have ... and you can develop heart failure. Symptoms of PH include Shortness of breath during routine activity, such ...

  5. Calculated mean arterial blood pressure in critically ill neonates.

    PubMed

    Gevers, M; Hack, W W; Ree, E F; Lafeber, H N; Westerhof, N

    1993-01-01

    Mean arterial pressure (MAP) is the area under the pressure wave form averaged over the cardiac cycle. A widely used rule of thumb to estimate MAP of peripheral arterial pressure waves in adults is adding one-third of the pulse pressure (PP) to diastolic arterial pressure (DAP). However, radial artery pressure waves in newborns differ from those in adults and resemble proximal aortic pressure waves, so that the above-mentioned calculation of MAP may not be correct. The present study was set up to obtain an arithmetical approximation to derive MAP from blood pressure waves measured in the radial artery of the neonate. We accurately recorded about 300 invasively obtained blood pressure curves in the radial artery of 10 neonates admitted for intensive care. We found that MAP in the radial artery in these neonates can be well approximated by adding 46.6% PP to DAP (range 43.0-50.1%). We suggest that the rule of thumb to derive MAP from radial artery waves in the neonate to be approximately the average of systolic and diastolic pressure, as opposed to adding one-third of the pulse pressure to the diastolic value in the adult.

  6. Pulmonary vascular disease in mice xenografted with human BM progenitors from patients with pulmonary arterial hypertension

    PubMed Central

    Farha, Samar; Lichtin, Alan; Graham, Brian; George, Deepa; Aldred, Micheala; Hazen, Stanley L.; Loyd, James; Tuder, Rubin

    2012-01-01

    Hematopoietic myeloid progenitors released into the circulation are able to promote vascular remodeling through endothelium activation and injury. Endothelial injury is central to the development of pulmonary arterial hypertension (PAH), a proliferative vasculopathy of the pulmonary circulation, but the origin of vascular injury is unknown. In the present study, mice transplanted with BM-derived CD133+ progenitor cells from patients with PAH, but not from healthy controls, exhibited morbidity and/or death due to features of PAH: in situ thrombi and endothelial injury, angioproliferative remodeling, and right ventricular hypertrophy and failure. Myeloid progenitors from patients with heritable and/or idiopathic PAH all produced disease in xenografted mice. Analyses of hematopoietic transcription factors and colony formation revealed underlying abnormalities of progenitors that skewed differentiation toward the myeloid-erythroid lineage. The results of the present study suggest a causal role for hematopoietic stem cell abnormalities in vascular injury, right ventricular hypertrophy, and morbidity associated with PAH. PMID:22745307

  7. Porcine radial artery decellularization by high hydrostatic pressure.

    PubMed

    Negishi, Jun; Funamoto, Seiichi; Kimura, Tsuyoshi; Nam, Kwangoo; Higami, Tetsuya; Kishida, Akio

    2015-11-01

    Many types of decellularized tissues have been studied and some have been commercially used in clinics. In this study, small-diameter vascular grafts were made using HHP to decellularize porcine radial arteries. One decellularization method, high hydrostatic pressure (HHP), has been used to prepare the decellularized porcine tissues. Low-temperature treatment was effective in preserving collagen and collagen structures in decellularized porcine carotid arteries. The collagen and elastin structures and mechanical properties of HHP-decellularized radial arteries were similar to those of untreated radial arteries. Xenogeneic transplantation (into rats) was performed using HHP-decellularized radial arteries and an untreated porcine radial artery. Two weeks after transplantation into rat carotid arteries, the HHP-decellularized radial arteries were patent and without thrombosis. In addition, the luminal surface of each decellularized artery was covered by recipient endothelial cells and the arterial medium was fully infiltrated with recipient cells.

  8. Automated measurement of pulmonary artery in low-dose non-contrast chest CT images

    NASA Astrophysics Data System (ADS)

    Xie, Yiting; Liang, Mingzhu; Yankelevitz, David F.; Henschke, Claudia I.; Reeves, Anthony P.

    2015-03-01

    A new measurement of the pulmonary artery diameter is obtained where the artery may be robustly segmented between the heart and the artery bifurcation. An automated algorithm is presented that can make this pulmonary artery measurement in low-dose non-contrast chest CT images. The algorithm uses a cylinder matching method following geometric constraints obtained from other adjacent organs that have been previously segmented. This new measurement and the related ratio of pulmonary artery to aortic artery measurement are compared to traditional manual approaches for pulmonary artery characterization. The algorithm was qualitatively evaluated on 124 low-dose and 223 standard-dose non-contrast chest CT scans from two public datasets; 324 out of the 347 cases had good segmentations and in the other 23 cases there was significant boundary inaccuracy. For quantitative evaluation, the comparison was to manually marked pulmonary artery boundary in an axial slice in 45 cases; the resulting average Dice Similarity Coefficient was 0.88 (max 0.95, min 0.74). For the 45 cases with manual markings, the correlation between the automated pulmonary artery to ascending aorta diameter ratio and manual ratio at pulmonary artery bifurcation level was 0.81. Using Bland-Altman analysis, the mean difference of the two ratios was 0.03 and the limits of agreement was (-0.12, 0.18). This automated measurement may have utility as an alternative to the conventional manual measurement of pulmonary artery diameter at the bifurcation level especially in the context of noisy low-dose CT images.

  9. Bidirectional Glenn with interruption of antegrade pulmonary blood flow: Which is the preferred option: Ligation or division of the pulmonary artery?

    PubMed

    Chowdhury, Ujjwal Kumar; Kapoor, Poonam Malhotra; Rao, Keerthi; Gharde, Parag; Kumawat, Mukesh; Jagia, Priya

    2016-01-01

    We report a rare complication of massive aneurysm of the proximal ligated end of the main pulmonary artery which occurred in the setting of a patient with a functionally univentricular heart and increased pulmonary blood flow undergoing superior cavopulmonary connection. Awareness of this possibility may guide others to electively transect the pulmonary artery in such a clinical setting. PMID:27397472

  10. 4,4′-Methylenedianiline Alters Serotonergic Transport in a Novel, Sex-Specific Model of Pulmonary Arterial Hypertension in Rats

    PubMed Central

    Carroll-Turpin, Michelle; Hebert, Valeria; Chotibut, Tanya; Wensler, Heather; Krentzel, Dallas; Varner, Kurt James; Burn, Brendan R.; Chen, Yi-Fan; Abreo, Fleurette; Dugas, Tammy Renee

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a cardiovascular disorder characterized by elevated pulmonary artery pressure as a result of arterial wall thickening. Patients are 3–4 times more likely to be women than men. This gender discrepancy demonstrates a need for an animal model with similar sex differences. 4,4′-Methylenedianiline (DAPM) is an aromatic amine used industrially in the synthesis of polyurethanes. Chronic, intermittent treatment of male and female rats with DAPM resulted in medial hyperplasia of pulmonary arterioles, exclusively in females, coupled to increases in pulmonary arterial pressures. Significant increases in plasma levels of endothelin-1 (ET-1) and serotonin, but decreases in nitrite (NO2−), were observed in females treated with DAPM. A decrease was observed in the serum ratio of the estrogen metabolites 2-hydroxyestradiol (2-OHE1)/16α-hydroxyestrogen (16α-OHE1). In females, ET-1,NO2− , and 2-OHE1/16α-OHE1 were significantly correlated with peak pressure gradient, an indirect measure of pulmonary arterial pressure. Expression of the serotonin transport protein (SERT) was significantly higher in the arteries of DAPM-treated females. In vitro, DAPM induced human pulmonary vascular smooth muscle cell proliferation and serotonin uptake, both of which were inhibited by treatment with the estrogen receptor antagonist ICI 182,780 or the selective serotonin reuptake inhibitor fluoxetine. DAPM also induced the release of serotonin from human pulmonary endothelial cells in culture, which is blocked by ICI 182,780. Taken together, this suggests that DAPM-mediated dysregulation of serotonin transport is estrogen-receptor dependent. Thus, DAPM-induced PAH pathology may be a new tool to clarify the sex selectivity of PAH disease pathogenesis. PMID:26116029

  11. Micro-CT image-derived metrics quantify arterial wall distensibility reduction in a rat model of pulmonary hypertension

    NASA Astrophysics Data System (ADS)

    Johnson, Roger H.; Karau, Kelly L.; Molthen, Robert C.; Haworth, Steven T.; Dawson, Christopher A.

    2000-04-01

    We developed methods to quantify arterial structural and mechanical properties in excised rat lungs and applied them to investigate the distensibility decrease accompanying chronic hypoxia-induced pulmonary hypertension. Lungs of control and hypertensive (three weeks 11% O2) animals were excised and a contrast agent introduced before micro-CT imaging with a special purpose scanner. For each lung, four 3D image data sets were obtained, each at a different intra-arterial contrast agent pressure. Vessel segment diameters and lengths were measured at all levels in the arterial tree hierarchy, and these data used to generate features sensitive to distensibility changes. Results indicate that measurements obtained from 3D micro-CT images can be used to quantify vessel biomechanical properties in this rat model of pulmonary hypertension and that distensibility is reduced by exposure to chronic hypoxia. Mechanical properties can be assessed in a localized fashion and quantified in a spatially-resolved way or as a single parameter describing the tree as a whole. Micro-CT is a nondestructive way to rapidly assess structural and mechanical properties of arteries in small animal organs maintained in a physiological state. Quantitative features measured by this method may provide valuable insights into the mechanisms causing the elevated pressures in pulmonary hypertension of differing etiologies and should become increasingly valuable tools in the study of complex phenotypes in small-animal models of important diseases such as hypertension.

  12. Pulmonary artery aneurysm with patent arterial duct: resection of aneurysm and ductal division.

    PubMed

    Tefera, Endale; Teodori, Michael

    2013-10-01

    Congenital or acquired aneurysm of the pulmonary artery (PA) is rare. Although aneurysms are described following surgical treatment of patent ductus arteriosus (PDA), occurrence of this lesion in association with PDA without previous surgery is extremely uncommon. An eight-year-old patient with PDA and aneurysm of the main PA is described in this report. Clinical diagnosis of PDA was made upon presentation. Diagnosis of PA aneurysm was suspected on chest x-ray and was confirmed on transthoracic echocardiography. Successful surgical resection of the aneurysm and division of the duct were performed under cardiopulmonary bypass. The patient did well on follow-up both from clinical and echocardiographic point of view.

  13. The role of endothelin-1 in pulmonary arterial hypertension

    PubMed Central

    Chester, Adrian H.; Yacoub, Magdi H.

    2014-01-01

    Pulmonary arterial hypertension (PAH) is a rare but debilitating disease, which if left untreated rapidly progresses to right ventricular failure and eventually death. In the quest to understand the pathogenesis of this disease differences in the profile, expression and action of vasoactive substances released by the endothelium have been identified in patients with PAH. Of these, endothelin-1 (ET-1) is of particular interest since it is known to be an extremely powerful vasoconstrictor and also involved in vascular remodelling. Identification of ET-1 as a target for pharmacological intervention has lead to the discovery of a number of compounds that can block the receptors via which ET-1 mediates its effects. This review sets out the evidence in support of a role for ET-1 in the onset and progression of the disease and reviews the data from the various clinical trials of ET-1 receptor antagonists for the treatment of PAH. PMID:25405182

  14. Psychosocial Burdens of Pulmonary Arterial Hypertension: A Discussion Paper.

    PubMed

    Doyle-Cox, Carolyn; Brousseau, Carolynne; Tulloch, Heather; Mielniczuk, Lisa M; Davies, Ross A; Sherrard, Heather; Clark, Lorraine

    2016-01-01

    Pulmonary arterial hypertension is an uncommon and devastating chronic illness with no known cure. Little is known about the disease, and even less about the psychosocial burdens. While it is important to create awareness about the physical aspects of the disease, it is equally important to create awareness about the psychosocial burdens patients and their families face. We reviewed the literature to better understand these psychosocial burdens, which include impact from physical limitations, emotional strains, financial burdens, social isolation, lack of intimacy in relationships, and an overall lack of information. The findings can be used to assist health care providers to understand the psychosocial challenges that are being experienced by patients and families in order to better provide supportive care. The creation of a standardized tool to assess the psychosocial burdens at each clinic visit can benefit health care providers by addressing challenges faced and facilitate subsequent referral to appropriate specialists.

  15. Macitentan for the treatment of pulmonary arterial hypertension.

    PubMed

    DuBrock, Hilary M; Channick, Richard N

    2014-08-01

    Macitentan is a novel dual endothelin receptor antagonist recently approved for the treatment of symptomatic pulmonary arterial hypertension (PAH). Compared to other endothelin receptor antagonists, in vitro and in vivo studies have demonstrated that macitentan has improved tissue targeting, a longer duration of action and an improved safety profile. Macitentan is available as a once daily oral medication and has been well tolerated in clinical trials. The recently published Study with an Endothelin Receptor Antagonist in PAH to Improve cliNical Outcomes (SERAPHIN), which was the first event-driven trial ever done in PAH, also demonstrated the benefit of macitentan on reducing the likelihood of a composite endpoint of morbidity and mortality events without a significant difference in mortality.

  16. Macitentan (Opsumit) for the treatment of pulmonary arterial hypertension.

    PubMed

    Clarke, Megan; Walter, Claire; Agarwal, Richa; Kanwar, Manreet; Benza, Raymond L

    2014-07-01

    The endothelin pathway is a key pathway for the pathogenesis of pulmonary arterial hypertension (PAH). Antagonism of this pathway is recommended as initial therapy in low-risk patient with PAH to inhibit fibrosis, cell proliferation, and inflammation caused by endothelin. Prior to October 2013, ambrisentan, a selective ETA receptor antagonist and bosentan, a dual ETA/ETB antagonist, were the only currently available agents for PAH targeting the endothelin pathway. Based on the results of the SERAPHIN trial, macitentan (brand name Opsumit®), a new ETA/ETB antagonist, has been US FDA approved to delay disease progression and reduce hospitalizations for PAH. SERAPHIN is the first ERA trial to use an event-driven strategy with a composite primary end point of morbidity or mortality. Previous trials have focused on short-term outcomes, such as improved 6-min walk distance and WHO functional class.

  17. Connective tissue disease-related pulmonary arterial hypertension.

    PubMed

    Thakkar, Vivek; Lau, Edmund M T

    2016-02-01

    Over the past two decades, there have been several advances in the assessment and management of connective tissue disease-related pulmonary arterial hypertension (CTD-PAH) that improved outcomes of the treatment of this lethal disease, and this will be the focus of this study. Systemic sclerosis is the leading cause of CTD-PAH, followed by systemic lupus erythematosus, mixed connective tissue disease, idiopathic inflammatory myositis, rheumatoid arthritis, and Sjogren's syndrome. Clinical registries have been invaluable in informing about the burden of disease, risk and prognostic factors, and temporal trends with respect to treatment and outcome in CTD-PAH. The major advances have centered on improved disease classification and diagnostic criteria, screening and early diagnosis, the emergence of evidence-based therapies including combination goal-orientated treatment strategies, and the establishment of centers with expertise in PAH.

  18. Connective tissue disease-related pulmonary arterial hypertension.

    PubMed

    Thakkar, Vivek; Lau, Edmund M T

    2016-02-01

    Over the past two decades, there have been several advances in the assessment and management of connective tissue disease-related pulmonary arterial hypertension (CTD-PAH) that improved outcomes of the treatment of this lethal disease, and this will be the focus of this study. Systemic sclerosis is the leading cause of CTD-PAH, followed by systemic lupus erythematosus, mixed connective tissue disease, idiopathic inflammatory myositis, rheumatoid arthritis, and Sjogren's syndrome. Clinical registries have been invaluable in informing about the burden of disease, risk and prognostic factors, and temporal trends with respect to treatment and outcome in CTD-PAH. The major advances have centered on improved disease classification and diagnostic criteria, screening and early diagnosis, the emergence of evidence-based therapies including combination goal-orientated treatment strategies, and the establishment of centers with expertise in PAH. PMID:27421214

  19. New trial designs and potential therapies for pulmonary artery hypertension.

    PubMed

    Gomberg-Maitland, Mardi; Bull, Todd M; Saggar, Rajeev; Barst, Robyn J; Elgazayerly, Amany; Fleming, Thomas R; Grimminger, Friedrich; Rainisio, Maurizio; Stewart, Duncan J; Stockbridge, Norman; Ventura, Carlo; Ghofrani, Ardeschir H; Rubin, Lewis J

    2013-12-24

    A greater understanding of the epidemiology, pathogenesis, and pathophysiology of pulmonary artery hypertension (PAH) has led to significant advances, but the disease remains fatal. Treatment options are neither universally available nor always effective, underscoring the need for development of novel therapies and therapeutic strategies. Clinical trials to date have provided evidence of efficacy, but were limited in evaluating the scope and duration of treatment effects. Numerous potential targets in varied stages of drug development exist, in addition to novel uses of familiar therapies. The pursuit of gene and cell-based therapy continues, and device use to help acute deterioration and chronic management is emerging. This rapid surge of drug development has led to multicenter pivotal clinical trials and has resulted in novel ethical and global clinical trial concerns. This paper will provide an overview of the opportunities and challenges that await the development of novel treatments for PAH.

  20. Optical studies of oxidative stress in pulmonary artery endothelial cells

    NASA Astrophysics Data System (ADS)

    Ghanian, Zahra; Sepehr, Reyhaneh; Eis, Annie; Kondouri, Ganesh; Ranji, Mahsa

    2015-03-01

    Reactive oxygen species (ROS) play an essential role in facilitating signal transduction processes within the cell and modulating the injuries. However, the generation of ROS is tightly controlled both spatially and temporally within the cell, making the study of ROS dynamics particularly difficult. This study present a novel protocol to quantify the dynamic of the mitochondrial superoxide as a precursor of reactive oxygen species. To regulate the mitochondrial superoxide level, metabolic perturbation was induced by administration of potassium cyanide (KCN). The presented method was able to monitor and measure the superoxide production rate over time. Our results demonstrated that the metabolic inhibitor, potassium cyanide (KCN) induced a significant increase in the rate of superoxide production in mitochondria of fetal pulmonary artery endothelial cells (FPAEC). Presented method sets the stage to study different ROS mediated injuries in vitro.

  1. Psychosocial Burdens of Pulmonary Arterial Hypertension: A Discussion Paper.

    PubMed

    Doyle-Cox, Carolyn; Brousseau, Carolynne; Tulloch, Heather; Mielniczuk, Lisa M; Davies, Ross A; Sherrard, Heather; Clark, Lorraine

    2016-01-01

    Pulmonary arterial hypertension is an uncommon and devastating chronic illness with no known cure. Little is known about the disease, and even less about the psychosocial burdens. While it is important to create awareness about the physical aspects of the disease, it is equally important to create awareness about the psychosocial burdens patients and their families face. We reviewed the literature to better understand these psychosocial burdens, which include impact from physical limitations, emotional strains, financial burdens, social isolation, lack of intimacy in relationships, and an overall lack of information. The findings can be used to assist health care providers to understand the psychosocial challenges that are being experienced by patients and families in order to better provide supportive care. The creation of a standardized tool to assess the psychosocial burdens at each clinic visit can benefit health care providers by addressing challenges faced and facilitate subsequent referral to appropriate specialists. PMID:27159936

  2. Baseline Characteristics of the Korean Registry of Pulmonary Arterial Hypertension.

    PubMed

    Chung, Wook-Jin; Park, Yong Bum; Jeon, Chan Hong; Jung, Jo Won; Ko, Kwang-Phil; Choi, Sung Jae; Seo, Hye Sun; Lee, Jae Seung; Jung, Hae Ok

    2015-10-01

    Despite recent advances in understanding of the pathobiology and targeted treatments of pulmonary arterial hypertension (PAH), epidemiologic data from large populations have been limited to western countries. The aim of the Korean Registry of Pulmonary Arterial Hypertension (KORPAH) was to examine the epidemiology and prognosis of Korean patients with PAH. KORPAH was designed as a nationwide, multicenter, prospective data collection using an internet webserver from September 2008 to December 2011. A total of 625 patients were enrolled. The patients' mean age was 47.6 ± 15.7 yr, and 503 (80.5%) were women. The diagnostic methods included right heart catheterization (n = 249, 39.8%) and Doppler echocardiography (n = 376, 60.2%). The etiologies, in order of frequency, were connective tissue disease (CTD), congenital heart disease, and idiopathic PAH (IPAH) (49.8%, 25.4%, and 23.2%, respectively). Patients with WHO functional class III or IV at diagnosis were 43.4%. In total, 380 (60.8%) patients received a single PAH-specific treatment at the time of enrollment, but only 72 (18.9%) patients received combination therapy. Incident cases during the registry represented 297 patients; therefore, the incidence rate of PAH was 1.9 patients/yr/million people. The 1st-, 2nd-, and 3rd-yr estimated survival rates were 90.8%, 87.8%, and 84.4%, respectively. Although Korean PAH patients exhibited similar age, gender, and survival rate compared with western registries, they showed relatively more CTD-PAH in the etiology and also systemic lupus erythematosus among CTD-PAH. The data suggest that earlier diagnosis and more specialized therapies should be needed to improve the survival of PAH patients.

  3. Frequency of supraventricular arrhythmias in patients with idiopathic pulmonary arterial hypertension.

    PubMed

    Wen, Li; Sun, Ming-Li; An, Pei; Jiang, Xin; Sun, Kai; Zheng, Lu; Liu, Qian-Qian; Wang, Lan; Zhao, Qin-Hua; He, Jing; Jing, Zhi-Cheng

    2014-11-01

    Supraventricular arrhythmias (SVA) may be risk factors of prognosis in patients with pulmonary arterial hypertension. SVA are increasingly reported in patients with pulmonary hypertension, but little is known about their incidence and outcomes for patients with idiopathic pulmonary arterial hypertension (IPAH) in a large cohort. In this 6-year prospective multicenter study, 280 patients with IPAH were enrolled to investigate the incidence of SVA and assess risk factors, clinical manifestation, management, and impact on survival. The cumulative 6-year incidence of SVA was 15.8%. The most common types of SVA were atrial fibrillation (n = 16) and atrial flutter (n = 13), followed by atrial tachycardia (n = 11). Most episodes of SVA were associated with significant clinical deterioration and right-sided cardiac failure. Sinus rhythm was successfully restored in most patients, resulting in clinical recovery. Increased right ventricular diameter, left atrial area, and higher right atrial pressure and pulmonary vascular resistance were associated with increased risk for experiencing SVA. SVA predicted a greater risk for mortality in a stepwise forward Cox analysis (hazard ratio 4.757, 95% confidence interval 2.695 to 8.397, p <0.001). Kaplan-Meier survival curves showed that patients with SVA, mainly permanent SVA, had a lower survival rate than those who did not develop SVA (p = 0.008). In conclusion, SVA often lead to clinical deterioration and may be associated with an increased risk for death in a large cohort of patients with IPAH. Restoration and maintenance of sinus rhythm are important treatment goals in patients with IPAH.

  4. IREB2 and GALC are associated with pulmonary artery enlargement in chronic obstructive pulmonary disease.

    PubMed

    Lee, Jin Hwa; Cho, Michael H; Hersh, Craig P; McDonald, Merry-Lynn N; Wells, J Michael; Dransfield, Mark T; Bowler, Russell P; Lynch, David A; Lomas, David A; Crapo, James D; Silverman, Edwin K

    2015-03-01

    Pulmonary hypertension is associated with advanced chronic obstructive pulmonary disease (COPD), although pulmonary vascular changes occur early in the course of the disease. Pulmonary artery (PA) enlargement (PAE) measured by computed tomography correlates with pulmonary hypertension and COPD exacerbation frequency. Genome-wide association studies of PAE in subjects with COPD have not been reported. To investigate whether genetic variants are associated with PAE within subjects with COPD, we investigated data from current and former smokers from the COPDGene Study and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study. The ratio of the diameter of the PA to the diameter of the aorta (A) was measured using computed tomography. PAE was defined as PA/A greater than 1. A genome-wide association study for COPD with PAE was performed using subjects with COPD without PAE (PA/A ≤ 1) as a control group. A secondary analysis used smokers with normal spirometry as a control group. Genotyping was performed on Illumina platforms. The results were summarized using fixed-effect meta-analysis. Both meta-analyses revealed a genome-wide significant locus on chromosome 15q25.1 in IREB2 (COPD with versus without PAE, rs7181486; odds ratio [OR] = 1.32; P = 2.10 × 10(-8); versus smoking control subjects, rs2009746; OR = 1.42; P = 1.32 × 10(-9)). PAE was also associated with a region on 14q31.3 near the GALC gene (rs7140285; OR = 1.55; P = 3.75 × 10(-8)). Genetic variants near IREB2 and GALC likely contribute to genetic susceptibility to PAE associated with COPD. This study provides evidence for genetic heterogeneity associated with a clinically important COPD vascular subtype.

  5. IREB2 and GALC Are Associated with Pulmonary Artery Enlargement in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Lee, Jin Hwa; Cho, Michael H.; Hersh, Craig P.; McDonald, Merry-Lynn N.; Wells, J. Michael; Dransfield, Mark T.; Bowler, Russell P.; Lynch, David A.; Lomas, David A.; Crapo, James D.

    2015-01-01

    Pulmonary hypertension is associated with advanced chronic obstructive pulmonary disease (COPD), although pulmonary vascular changes occur early in the course of the disease. Pulmonary artery (PA) enlargement (PAE) measured by computed tomography correlates with pulmonary hypertension and COPD exacerbation frequency. Genome-wide association studies of PAE in subjects with COPD have not been reported. To investigate whether genetic variants are associated with PAE within subjects with COPD, we investigated data from current and former smokers from the COPDGene Study and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study. The ratio of the diameter of the PA to the diameter of the aorta (A) was measured using computed tomography. PAE was defined as PA/A greater than 1. A genome-wide association study for COPD with PAE was performed using subjects with COPD without PAE (PA/A ≤ 1) as a control group. A secondary analysis used smokers with normal spirometry as a control group. Genotyping was performed on Illumina platforms. The results were summarized using fixed-effect meta-analysis. Both meta-analyses revealed a genome-wide significant locus on chromosome 15q25.1 in IREB2 (COPD with versus without PAE, rs7181486; odds ratio [OR] = 1.32; P = 2.10 × 10−8; versus smoking control subjects, rs2009746; OR = 1.42; P = 1.32 × 10−9). PAE was also associated with a region on 14q31.3 near the GALC gene (rs7140285; OR = 1.55; P = 3.75 × 10−8). Genetic variants near IREB2 and GALC likely contribute to genetic susceptibility to PAE associated with COPD. This study provides evidence for genetic heterogeneity associated with a clinically important COPD vascular subtype. PMID:25101718

  6. Association of physical examination with pulmonary artery catheter parameters in acute lung injury*

    PubMed Central

    Grissom, Colin K.; Morris, Alan H.; Lanken, Paul N.; Ancukiewicz, Marek; Orme, James F.; Schoenfeld, David A.; Thompson, B. Taylor

    2016-01-01

    Objective To correlate physical examination findings, central venous pressure, fluid output, and central venous oxygen saturation with pulmonary artery catheter parameters. Design Retrospective study. Setting Data from the multicenter Fluid and Catheter Treatment Trial of the National Institutes of Health Acute Respiratory Distress Syndrome Network. Patients Five hundred thirteen patients with acute lung injury randomized to treatment with a pulmonary artery catheter. Interventions Correlation of physical examination findings (capillary refill time >2 secs, knee mottling, or cool extremities), central venous pressure, fluid output, and central venous oxygen saturation with parameters from a pulmonary artery catheter. Measurements We determined association of baseline physical examination findings and on-study parameters of central venous pressure and central venous oxygen saturation with cardiac index <2.5 L/min/m2 and mixed venous oxygen saturation <60%. We determined correlation of baseline central venous oxygen saturation and mixed venous oxygen saturation and predictive value of a low central venous oxygen saturation for a low mixed venous oxygen saturation. Measurements and Main Results Prevalence of cardiac index <2.5 and mixed venous oxygen saturation <60% was 8.1% and 15.5%, respectively. Baseline presence of all three physical examination findings had low sensitivity (12% and 8%), high specificity (98% and 99%), low positive predictive value (40% and 56%), but high negative predictive value (93% and 86%) for cardiac index <2.5 and mixed venous oxygen saturation <60%, respectively. Central venous oxygen saturation <70% predicted a mixed venous oxygen saturation <60% with a sensitivity 84%, specificity 70%, positive predictive value 31%, and negative predictive value of 96%. Low cardiac index correlated with cool extremities, high central venous pressure, and low 24-hr fluid output; and low mixed venous oxygen saturation correlated with knee mottling and

  7. An international physician survey of pulmonary arterial hypertension management

    PubMed Central

    Hinzmann, Barbara; Heinz, Sabina; Gall, Henning; Jenkins, David; Kim, Nick H.; Lang, Irene

    2016-01-01

    Abstract We conducted an international study to evaluate practices in the diagnosis and management of pulmonary arterial hypertension (PAH) globally across different geographic regions. Between July and October 2012, PAH-treating physicians completed a 15-minute online questionnaire and provided patient record data for their 3 or 5 most recent patients with PAH. Overall, 560 physicians (Europe: 278; United States: 160; Argentina: 53; Japan: 69) completed the questionnaire and provided data for 2,618 patients. The proportion of physicians who described themselves as working in or affiliated with a specialized pulmonary hypertension center ranged from 13% in Argentina to 74% in the United States. At the time of diagnosis, patients’ New York Heart Association functional class differed significantly between regions. At the time of last assessment, functional class had improved overall, and differences between regions had largely disappeared. A large proportion of patients did not undergo right heart catheterization for the diagnosis of PAH (Europe: 7%–21%; United States: 21%; Japan: 19%; Argentina: 51%). Variations in management included greater use of phosphodiesterase 5 inhibitors in the United States than in Europe and Japan and greater use of triple or greater combination therapy in Japan than in other regions. Results from this study, which includes a global aspect of PAH care, demonstrate that there are significant differences in PAH management between regions and low adherence to guidelines recommending right heart catheterization for the diagnosis of PAH. PMID:27683611

  8. An international physician survey of pulmonary arterial hypertension management.

    PubMed

    Preston, Ioana R; Hinzmann, Barbara; Heinz, Sabina; Gall, Henning; Jenkins, David; Kim, Nick H; Lang, Irene

    2016-09-01

    We conducted an international study to evaluate practices in the diagnosis and management of pulmonary arterial hypertension (PAH) globally across different geographic regions. Between July and October 2012, PAH-treating physicians completed a 15-minute online questionnaire and provided patient record data for their 3 or 5 most recent patients with PAH. Overall, 560 physicians (Europe: 278; United States: 160; Argentina: 53; Japan: 69) completed the questionnaire and provided data for 2,618 patients. The proportion of physicians who described themselves as working in or affiliated with a specialized pulmonary hypertension center ranged from 13% in Argentina to 74% in the United States. At the time of diagnosis, patients' New York Heart Association functional class differed significantly between regions. At the time of last assessment, functional class had improved overall, and differences between regions had largely disappeared. A large proportion of patients did not undergo right heart catheterization for the diagnosis of PAH (Europe: 7%-21%; United States: 21%; Japan: 19%; Argentina: 51%). Variations in management included greater use of phosphodiesterase 5 inhibitors in the United States than in Europe and Japan and greater use of triple or greater combination therapy in Japan than in other regions. Results from this study, which includes a global aspect of PAH care, demonstrate that there are significant differences in PAH management between regions and low adherence to guidelines recommending right heart catheterization for the diagnosis of PAH.

  9. [Phosphodiesterase-5 inhibitors for the treatment of pulmonary arterial hypertension].

    PubMed

    Beltrán-Gámez, Miguel E; Sandoval-Zárate, Julio; Pulido, Tomás

    2015-01-01

    In experimental and clinical cardiology, phosphodiesterase type 5 (PDE-5) inhibitors have brought scientific interest as a therapeutic tool in pulmonary arterial hypertension (PAH) management in recent years. Phosphodiesterases are a superfamily of enzymes that inactivate cyclic adenosine monophosphate and cyclic guanosine monophosphate, the second messengers of prostacyclin and nitric oxide. The rationale for the use of PDE-5 inhibitors in PAH is based on their capacity to overexpresss the nitric oxide pathway pursued inhibition of cyclic guanosine monophosphate hydrolysis. By increasing cyclic guanosine monophosphate levels it promotes vasodilation, antiproliferative and pro-apoptotic effects that may reverse pulmonary vascular remodeling. There is also evidence that these drugs may directly enhance right ventricular contractility through an increase in cyclic adenosine monophosphate mediated by the inhibition of the cyclic guanosine monophosphate -sensitive PDE-3. Sildenafil, tadalafil and vardenafil are 3 specific PDE-5 inhibitors in current clinical use, which share similar mechanisms of action but present some significant differences regarding potency, selectivity for PDE-5 and pharmacokinetic properties. Sildenafil received approval in 2005 by the Food and Drug Administration and the European Medicines Agency and tadalafil in 2009 by the Food and Drug Administration and the European Medicines Agency for the treatment of PAH in patients classified as NYHA/WHO functional class II and III. In Mexico, sildenafil and tadalafil were approved by Comisión Federal de Protección contra Riesgos Sanitarios for this indication in 2010 and 2011, respectively. PMID:26047999

  10. [Phosphodiesterase-5 inhibitors for the treatment of pulmonary arterial hypertension].

    PubMed

    Beltrán-Gámez, Miguel E; Sandoval-Zárate, Julio; Pulido, Tomás

    2015-01-01

    In experimental and clinical cardiology, phosphodiesterase type 5 (PDE-5) inhibitors have brought scientific interest as a therapeutic tool in pulmonary arterial hypertension (PAH) management in recent years. Phosphodiesterases are a superfamily of enzymes that inactivate cyclic adenosine monophosphate and cyclic guanosine monophosphate, the second messengers of prostacyclin and nitric oxide. The rationale for the use of PDE-5 inhibitors in PAH is based on their capacity to overexpresss the nitric oxide pathway pursued inhibition of cyclic guanosine monophosphate hydrolysis. By increasing cyclic guanosine monophosphate levels it promotes vasodilation, antiproliferative and pro-apoptotic effects that may reverse pulmonary vascular remodeling. There is also evidence that these drugs may directly enhance right ventricular contractility through an increase in cyclic adenosine monophosphate mediated by the inhibition of the cyclic guanosine monophosphate -sensitive PDE-3. Sildenafil, tadalafil and vardenafil are 3 specific PDE-5 inhibitors in current clinical use, which share similar mechanisms of action but present some significant differences regarding potency, selectivity for PDE-5 and pharmacokinetic properties. Sildenafil received approval in 2005 by the Food and Drug Administration and the European Medicines Agency and tadalafil in 2009 by the Food and Drug Administration and the European Medicines Agency for the treatment of PAH in patients classified as NYHA/WHO functional class II and III. In Mexico, sildenafil and tadalafil were approved by Comisión Federal de Protección contra Riesgos Sanitarios for this indication in 2010 and 2011, respectively.

  11. An international physician survey of pulmonary arterial hypertension management

    PubMed Central

    Hinzmann, Barbara; Heinz, Sabina; Gall, Henning; Jenkins, David; Kim, Nick H.; Lang, Irene

    2016-01-01

    Abstract We conducted an international study to evaluate practices in the diagnosis and management of pulmonary arterial hypertension (PAH) globally across different geographic regions. Between July and October 2012, PAH-treating physicians completed a 15-minute online questionnaire and provided patient record data for their 3 or 5 most recent patients with PAH. Overall, 560 physicians (Europe: 278; United States: 160; Argentina: 53; Japan: 69) completed the questionnaire and provided data for 2,618 patients. The proportion of physicians who described themselves as working in or affiliated with a specialized pulmonary hypertension center ranged from 13% in Argentina to 74% in the United States. At the time of diagnosis, patients’ New York Heart Association functional class differed significantly between regions. At the time of last assessment, functional class had improved overall, and differences between regions had largely disappeared. A large proportion of patients did not undergo right heart catheterization for the diagnosis of PAH (Europe: 7%–21%; United States: 21%; Japan: 19%; Argentina: 51%). Variations in management included greater use of phosphodiesterase 5 inhibitors in the United States than in Europe and Japan and greater use of triple or greater combination therapy in Japan than in other regions. Results from this study, which includes a global aspect of PAH care, demonstrate that there are significant differences in PAH management between regions and low adherence to guidelines recommending right heart catheterization for the diagnosis of PAH.

  12. An international physician survey of pulmonary arterial hypertension management.

    PubMed

    Preston, Ioana R; Hinzmann, Barbara; Heinz, Sabina; Gall, Henning; Jenkins, David; Kim, Nick H; Lang, Irene

    2016-09-01

    We conducted an international study to evaluate practices in the diagnosis and management of pulmonary arterial hypertension (PAH) globally across different geographic regions. Between July and October 2012, PAH-treating physicians completed a 15-minute online questionnaire and provided patient record data for their 3 or 5 most recent patients with PAH. Overall, 560 physicians (Europe: 278; United States: 160; Argentina: 53; Japan: 69) completed the questionnaire and provided data for 2,618 patients. The proportion of physicians who described themselves as working in or affiliated with a specialized pulmonary hypertension center ranged from 13% in Argentina to 74% in the United States. At the time of diagnosis, patients' New York Heart Association functional class differed significantly between regions. At the time of last assessment, functional class had improved overall, and differences between regions had largely disappeared. A large proportion of patients did not undergo right heart catheterization for the diagnosis of PAH (Europe: 7%-21%; United States: 21%; Japan: 19%; Argentina: 51%). Variations in management included greater use of phosphodiesterase 5 inhibitors in the United States than in Europe and Japan and greater use of triple or greater combination therapy in Japan than in other regions. Results from this study, which includes a global aspect of PAH care, demonstrate that there are significant differences in PAH management between regions and low adherence to guidelines recommending right heart catheterization for the diagnosis of PAH. PMID:27683611

  13. Robotic-Assisted Endovascular Pulmonary Artery Foreign Body Retrieval: A Case Report.

    PubMed

    Wolujewicz, Michael

    2016-04-01

    As intravascular robotics technology continues to evolve, so do the potential applications. The present case describes the use of the Magellan Robotic System within the pulmonary artery. A 61-year-old female was referred for retrieval of a transected port catheter, which had embolized into the pulmonary artery. After a failed attempt using a conventional technique, retrieval was ultimately successful with assistance of the Magellan system. The unique navigational capabilities and stability of the system may make it a valuable tool in pulmonary artery interventions.

  14. Coil Embolization Treatment in Pulmonary Artery Branch Rupture During Swan-Ganz Catheterization

    SciTech Connect

    Gottwalles, Yannick; Wunschel-Joseph, Marie-Eve; Hanssen, Michel

    2000-11-15

    Rupture of the pulmonary artery or one of its branches during Swan-Ganz catheterization is a complication that is rare but remains fatal in almost 50% of cases. The risk factors and mechanisms involved in the pathogenesis of this accident have been widely reported. Management is twofold: resuscitation procedures and specific medical or even surgical treatment. We report a case of pulmonary artery rupture occurring during Swan-Ganz catheterization that was treated by coil embolization. This technique, which is quick and simple to use, would appear to be very promising. This is the first case of successful emergency treatment of pulmonary artery rupture using an endovascular technique.

  15. Endovascular Treatment of Hemoptysis by Abnormal Systemic Pulmonary Artery Supply

    SciTech Connect

    Munoz, J.J. Garcia, J.A.; Bentabol, M.; Padin, M.I.; Serrano, F.

    2008-03-15

    We report the case of a 29-year-old man with hemoptysis. The patient came to the emergency department, where a laboratory test and chest radiograph were reported as normal. The following day the patient again had hemoptysis, though less than previously. He reported no chest pain, dyspnea, fever, catarrh, changes in urine or feces, contact with patients with bacillus disease or constitutional symptoms. Doppler ultrasound of the chest showed right basal parenchymatous condensation containing a vessel with arterial flow (in the opposite direction to the aortic flow) compatible with an aberrant vessel, possibly a sequestration, leaving the aorta above the celiac trunk. Because of the findings of the chest echogram and magnetic resonance study, thoracoabdominal computed tomography angiography was undertaken; this showed right basal condensation and an anomalous vessel originating 1 cm above the celiac trunk, supplying the right lower lobe. An aortic and pulmonary arteriogram via an arterial and right femoral vein approach confirmed the findings. The patient was treated successfully with percutaneous embolization with coils. The relevant literature is reviewed.

  16. Duplicated left pulmonary artery: an unknown disease? Three case reports and review of the literature.

    PubMed

    Giudici, Valentina; Kanani, Mazyar; Muthialu, Nagarajan; Carr, Michelle; Calder, Alistair D; Owens, Catherine M; Cook, Andrew C; Marek, Jan

    2016-02-01

    We report three cases of an abnormal finding of duplicated left pulmonary artery: two of these occurring in children with Kabuki syndrome and configuring the setting of a pseudo-pulmonary sling without any clinical or cardiac cross-sectional evidence of tracheal compression. The other case instead represents duplicated left pulmonary artery with pulmonary sling caused by the retro-tracheal course of the lower left pulmonary artery associated with "Christmas Tree" arrangement of the tracheo-bronchial system. In both patients with pseudo-pulmonary sling and Kabuki syndrome, the abnormal finding was incidental during echocardiographic examination and neither of the patients required surgical repair for the condition. To the best of our knowledge, they represent the third and fourth cases in which such an anomaly of the pulmonary artery branches not forming a sling is seen in association with Kabuki syndrome. Another case represents our second experience and the second case reported in literature with duplicated left pulmonary artery in the setting of a complex tracheal anatomy. In this symptomatic patient, surgical repair of atrial septal defect and relief of the vascular ring were indicated, and the surgical repair was performed successfully at the age of 3 years.

  17. Can echocardiographically estimated pulmonary arterial elastance be a non-invasive predictor of pulmonary vascular resistance?

    PubMed Central

    Sinha, Neeraj; Devabhaktuni, Srikala; Kadambi, Aparna; McClung, John A.; Lehrman, Stuart G.

    2014-01-01

    Introduction Measurement of pulmonary vascular resistance (PVR) is essential in evaluating a patient with pulmonary hypertension. Material and methods Data from right heart catheterization (RHC) and echocardiograms performed within 90 days of each other on 45 non-consecutive adult patients were reviewed in this retrospective study. Patients were recruited using an assortment of strategies to ensure the presence of patients with a wide range of PVR. Results The linear regression equation between RHC-derived PVR and echocardiographic pulmonary arterial elastance (PAE) was: PVR = (562.6 × PAE) – 38.9 (R = 0.56, p < 0.0001). An adjustment for echocardiographic PAE was made by multiplying it by hemoglobin (in g/dl) and (right atrial area)1.5 (in cm3). As RHC-derived PVR varies with blood hemoglobin, an adjustment for PVR was made for hemoglobin of 12 g/dl. Visualization of the XY scatter plot of adjusted PVR and adjusted PAE isolated a subset of patients with PVR higher than 8.8 Wood units, where a strong linear relationship existed (adjusted PVR = (0.89 × adjusted PAE) + 137.4, R = 0.89, p = 0.008). Conclusions The correlation coefficient of the regression equation connecting echocardiographic PAE and RHC-derived PVR was moderate. In a subset of patients with very high PVR and after appropriate adjustment, a strong linear relationship existed with an excellent correlation coefficient. PMID:25276152

  18. Soluble Guanylate Cyclase: A new therapeutic target for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension

    PubMed Central

    Das Gupta, Asish; Bowman, Lindsay; D’Arsigny, Christine L.; Archer, Stephen L.

    2014-01-01

    Nitric oxide (NO) activates soluble guanylate cyclase (sGC) by binding its prosthetic heme group, thereby catalyzing cyclic guanosine monophosphate (cGMP) synthesis. cGMP causes vasodilation and may inhibit smooth muscle cell proliferation and platelet aggregation. The NO-sGC-cGMP pathway is disordered in pulmonary arterial hypertension (PAH), a syndrome in which pulmonary vascular obstruction, inflammation, thrombosis, and constriction ultimately lead to death from right heart failure. Expression of sGC is increased in PAH but its function is reduced by decreased NO bioavailability, sGC oxidation and the related loss of sGC’s heme group. Two classes of sGC modulators offer promise in PAH. sGC stimulators (e.g. riociguat) require heme-containing sGC to catalyze cGMP production, whereas sGC activators (e.g. cinaciguat) activate heme-free sGC. Riociguat is approved for PAH and yields functional and hemodynamic benefits similar to other therapies. Its main serious adverse effect is dose-dependent hypotension Riociguat is also approved for inoperable chronic thromboembolic pulmonary hypertension. PMID:25670386

  19. Pulmonary artery balloon counterpulsation for right ventricular failure. An experimental evaluation.

    PubMed

    Jett, G K; Siwek, L G; Picone, A L; Applebaum, R E; Jones, M

    1983-09-01

    Right ventricular (RV) failure frequently occurs in patients undergoing correction of congenital cardiac defects, as well as in other clinical settings. RV hypertrophy was created in 10 neonatal lambs by pulmonary artery (PA) banding. Twelve months later RV hypertrophy was present (RV weight/body weight = 2.71 +/- 0.31 gm/kg); RV systolic pressures were elevated (65 +/- 9 mm Hg) and the average gradient across the PA band was 38 +/- 9 mm Hg. RV failure was produced in all animals by performing a right ventriculotomy. Four unassisted (control) animals died shortly after separation from bypass. Six experimental animals underwent pulmonary artery balloon counterpulsation (PABCP). A Dacron graft anastomosed to the proximal PA served as a reservoir for a 40 ml intra-aortic balloon pump system. PABCP effectively reversed RV failure, low cardiac output, and systemic arterial hypotension. Periods with PABCP on and off in each animal were compared. PABCP increased cardiac output from 1.45 +/- 0.16 to 2.03 +/- 0.13 L/min (p less than 0.0001) and increased aortic systolic pressure from 78 +/- 7 to 99 +/- 6 mm Hg (p less than 0.0004). PABCP produced a significant reduction in RV peak systolic pressure from 56 +/- 5 to 41 +/- 3 mm Hg (p less than 0.0001). PA peak pressure distal to the band increased from 31 +/- 2 to 40 +/- 1 mm Hg (p less than 0.0001). Right atrial pressure decreased from 14 +/- 1 to 11 +/- 1 mm Hg (p less than 0.0001) with PABCP, and RV end-diastolic pressure fell from 15 +/- 1 to 11 +/- 1 mm Hg (p less than 0.0001). RV stroke work index increased 49% from 0.081 +/- 0.011 to 0.121 +/- 0.017 gm X m/kg/beat (p less than 0.01), and RV systolic pressure time index decreased 38% from 1140 +/- 79 to 710 +/- 65 mm Hg sec/min (p less than 0.0001). Thus PABCP in the presence of RV dysfunction can produce substantial improvement in RV function and in overall cardiac function and may prove clinically useful in managing patients in refractory RV failure.

  20. Efficacy of Statin Therapy in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis

    PubMed Central

    Rysz-Górzynska, Magdalena; Gluba-Brzózka, Anna; Sahebkar, Amirhossein; Serban, Maria-Corina; Mikhailidis, Dimitri P.; Ursoniu, Sorin; Toth, Peter P.; Bittner, Vera; Watts, Gerald F.; Lip, Gregory Y. H.; Rysz, Jacek; Catapano, Alberico L.; Banach, Maciej

    2016-01-01

    Since the evidence regarding statin therapy in PAH has not been conclusive, we assessed the impact of statin therapy in PAH through a systematic review and meta-analysis of available studies. We searched selected databases up to August 1, 2015 to identify the studies investigating the effect of statin administration on PAH. Meta-analysis was performed using either a fixed-effects or random-effect model according to I2 statistic. Meta-analysis of 8 studies with 665 patients did not suggest any significant improvement in 6-min walking distance (6MWD) by statin therapy (weighed mean difference [WMD]: −6.08 m, 95% confidence interval [CI]: −25.66, 13.50, p = 0.543; Q = 8.41, I2 = 28.64%). Likewise, none of the other indices including pulmonary arterial pressure (WMD: −0.97 mmHg, 95%CI: −4.39, 2.44, p = 0.577; Q = 14.64, I2 = 79.51%), right atrial pressure (WMD: 1.01 mmHg, 95%CI: −0.93, 2.96, p = 0.307; Q = 44.88, I2 = 95.54%), cardiac index (WMD: 0.05 L/min/m2, 95%CI: −0.05, 0.15, p = 0.323; Q = 3.82, I2 = 21.42%), and pulmonary vascular resistance (WMD: −1.42 dyn*s/cm5, 95%CI: −72.11, 69.27, p = 0.969; Q = 0.69, I2 = 0%) was significantly altered by statin therapy. In conclusion, the results of the meta-analysis did not show a statistically significant effect of statin therapy in the improvement of 6MWD, pulmonary arterial pressure, right atrial pressure, cardiac index and pulmonary vascular resistance. PMID:27444125

  1. Efficacy of Statin Therapy in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis.

    PubMed

    Rysz-Górzynska, Magdalena; Gluba-Brzózka, Anna; Sahebkar, Amirhossein; Serban, Maria-Corina; Mikhailidis, Dimitri P; Ursoniu, Sorin; Toth, Peter P; Bittner, Vera; Watts, Gerald F; Lip, Gregory Y H; Rysz, Jacek; Catapano, Alberico L; Banach, Maciej

    2016-01-01

    Since the evidence regarding statin therapy in PAH has not been conclusive, we assessed the impact of statin therapy in PAH through a systematic review and meta-analysis of available studies. We searched selected databases up to August 1, 2015 to identify the studies investigating the effect of statin administration on PAH. Meta-analysis was performed using either a fixed-effects or random-effect model according to I(2) statistic. Meta-analysis of 8 studies with 665 patients did not suggest any significant improvement in 6-min walking distance (6MWD) by statin therapy (weighed mean difference [WMD]: -6.08 m, 95% confidence interval [CI]: -25.66, 13.50, p = 0.543; Q = 8.41, I(2) = 28.64%). Likewise, none of the other indices including pulmonary arterial pressure (WMD: -0.97 mmHg, 95%CI: -4.39, 2.44, p = 0.577; Q = 14.64, I(2) = 79.51%), right atrial pressure (WMD: 1.01 mmHg, 95%CI: -0.93, 2.96, p = 0.307; Q = 44.88, I(2) = 95.54%), cardiac index (WMD: 0.05 L/min/m(2), 95%CI: -0.05, 0.15, p = 0.323; Q = 3.82, I(2) = 21.42%), and pulmonary vascular resistance (WMD: -1.42 dyn*s/cm(5), 95%CI: -72.11, 69.27, p = 0.969; Q = 0.69, I(2) = 0%) was significantly altered by statin therapy. In conclusion, the results of the meta-analysis did not show a statistically significant effect of statin therapy in the improvement of 6MWD, pulmonary arterial pressure, right atrial pressure, cardiac index and pulmonary vascular resistance. PMID:27444125

  2. Pressure drops in a distensible model of end-to-side anastomosis in systemic-to-pulmonary shunts.

    PubMed

    Migliavacca, Francesco; Pennati, Giancarlo; Di Martino, Elena; Dubini, Gabriele; Pietrabissa, Riccardo

    2002-06-01

    The modified Blalock-Taussig shunt is a surgical procedure used as a palliation to treat complex congenital heart defects. It consists of an interposing prosthetic tube between the innominate/subclavian artery and the right pulmonary artery. Previous experience indicates that the pressure drop across the shunt is affected by the pulmonary pressure at the distal anastomosis combined with the distensibility of the anastomosis. In this study, a computational fluid-structure interaction approach is presented to investigate the haemodynamic behaviour. Steady-state fluid dynamics and structural analyses were carried out using commercial codes based on the finite element method (FIDAP and ABAQUS) coupled by means of a purposely-developed procedure to transfer boundary conditions. Both prosthetic tube and artery walls were characterised by non-linear material properties. Three different pulmonary pressures (2, 5 and 15 mmHg) and two volume flow rates (0.4 and 0.8 l/min) were investigated. Results indicate that the effects of distensibility at the distal anastomosis on the shunt pressure drop are relevant only when the distal anastomosis on the shunt pressure drop are relevant only when the distal anastomosis is not fully distended, which occurs when the pulmonary pressure is lower than 5 mmHg.

  3. Pulmonary artery catheter entrapment in cardiac surgery: a simple percutaneous solution.

    PubMed

    Divakaran, Vijay; Caldera, Angel; Stephens, Jack; Gonzalez, Rafael

    2015-10-01

    Pulmonary artery catheter entrapment is a reported complication after cardiac surgery from inadvertent suturing of the catheter to the vena-caval wall during surgery. This article reports a simple percutaneous technique to retrieve the trapped catheter.

  4. Acute right atrial and pulmonary artery bone cement mass emboli following vertebroplasty

    PubMed Central

    Diab, Amr; Dihmis, Walid; Diab, Samir

    2016-01-01

    Cardiac and pulmonary artery emboli are lethal complications following vertebroplasty. Clinicians should recognise these fatal complications immediately and surgical extraction is mandatory and provides the best outcome. PMID:27293775

  5. Implantable Ultralow Pulmonary Pressure Monitoring System for Fetal Surgery

    PubMed Central

    Etemadi, Mozziyar; Heller, J. Alex; Schecter, Samuel C.; Shue, Eveline H.; Miniati, Doug; Roy, Shuvo

    2015-01-01

    Congenital pulmonary hypoplasia is a devastating condition affecting fetal and newborn pulmonary physiology, resulting in great morbidity and mortality. The fetal lung develops in a fluid-filled environment. In this paper, we describe a novel, implantable pressure sensing and recording device which we use to study the pressures present in the fetal pulmonary tree throughout gestation. The system achieves 0.18 cm H2O resolution and can record for 21 days continuously at 256 Hz. Sample tracings of in vivo fetal lamb recordings are shown. PMID:22801521

  6. Dual left anterior descending artery with anomalous origin of long LAD from pulmonary artery - rare coronary anomaly detected on computed tomography coronary angiography

    PubMed Central

    Vohra, Aditi; Narula, Harneet

    2016-01-01

    Dual left anterior descending artery is a rare coronary artery anomaly showing two left anterior descending arteries. Short anterior descending artery usually arises from the left coronary artery, while long anterior descending artery has anomalous origin and course. Dual left anterior descending artery with origin of long anterior descending artery from the pulmonary artery (ALCAPA) is a very rare coronary artery anomaly which has not been reported previously in the literature. We present the computed tomography coronary angiographic findings of this rare case in a young female patient who presented with atypical chest pain. PMID:27413266

  7. Children with pulmonary arterial hypertension and prostanoid therapy: Long-term hemodynamics

    PubMed Central

    Siehr, Stephanie L.; Ivy, D. Dunbar; Miller-Reed, Kathleen; Ogawa, Michelle; Rosenthal, David N.; Feinstein, Jeffrey A.

    2013-01-01

    BACKGROUND Pediatric patients with severe pulmonary arterial hypertension (PAH) are treated with intravenous epoprostenol or intravenous or subcutaneous treprostinil. Little is known about longitudinal hemodynamics and outcomes of epoprostenol, treprostinil, and transitions from epoprostenol to treprostinil. METHODS This was retrospective study of 77 pediatric patients (47 idiopathic PAH, 24 congenital heart disease-PAH) receiving epoprostenol or treprostinil from 1992 to 2010 at 2 centers. Outcomes were defined as living vs dead/transplant. RESULTS Mean age at baseline was 7.7 ± 5.2 years, with follow-up of 4.3 ± 3.4 years. Thirty-seven patients were treated with epoprostenol, 20 with treprostinil, and 20 were transitioned from epoprostenol to treprostinil. Mean pulmonary-to-systemic vascular resistance ratio (Rp/Rs) for epoprostenol was 1.0 ± 0.4, 0.8 ± 0.4, 0.8 ± 0.4, 1.0 ± 0.4, and 1.2 ± 0.4, respectively, at baseline, 1, 2, 3, and 4 years. For treprostinil, Rp/Rs was 0.9 ± 0.3, 0.7 ± 0.3, 0.5 ± 0.2, (p < 0.01 vs baseline), and 1.1 ± 0.2, respectively, at baseline, 1, 2, and 3 to 4 years, respectively. There were similar changes in mean pulmonary artery pressure and pulmonary vascular resistance index. The Rp/Rs 1 year after epoprostenol to treprostinil transition increased from 0.6 to 0.8 (n = 7). Changes not statistically significant unless noted. Eight patients died or received a transplant within 2 years of baseline; compared with the rest of the cohort, mean baseline Rp/Rs, right atrial pressure, and pulmonary vascular resistance index were significantly worse in this group. Thirty-nine patients remain on prostanoids, 17 are off, 16 died, and 5 received heart-lung transplant. Kaplan-Meier 5-year transplant-free survival was 70% (95% confidence interval, 56%-80%). CONCLUSION There was improvement in Rp/Rs on both therapies at 1 to 2 years that was not sustained. The 5-year transplant-free survival was better than in similar adult studies. PMID

  8. Estimation of pulmonary arterial volume changes in the normal and hypertensive fawn-hooded rat from 3D micro-CT data

    NASA Astrophysics Data System (ADS)

    Molthen, Robert C.; Wietholt, Christian; Haworth, Steven T.; Dawson, Christopher A.

    2002-04-01

    In the study of pulmonary vascular remodeling, much can be learned from observing the morphological changes undergone in the pulmonary arteries of the rat lung when exposed to chronic hypoxia or other challenges which elicit a remodeling response. Remodeling effects include thickening of vessel walls, and loss of wall compliance. Morphometric data can be used to localize the hemodynamic and functional consequences. We developed a CT imaging method for measuring the pulmonary arterial tree over a range of pressures in rat lungs. X-ray micro-focal isotropic volumetric imaging of the arterial tree in the intact rat lung provides detailed information on the size, shape and mechanical properties of the arterial network. In this study, we investigate the changes in arterial volume with step changes in pressure for both normoxic and hypoxic Fawn-Hooded (FH) rats. We show that FH rats exposed to hypoxia tend to have reduced arterial volume changes for the same preload when compared to FH controls. A secondary objective of this work is to quantify various phenotypes to better understand the genetic contribution of vascular remodeling in the lungs. This volume estimation method shows promise in high throughput phenotyping, distinguishing differences in the pulmonary hypertensive rat model.

  9. Percutaneous retrieval of a radiolucent anchoring sleeve embolized in pulmonary artery during pacemaker implantation.

    PubMed

    Tokuda, Michifumi; Yamane, Teiichi; Sadaoka, Shunichi; Tokutake, Kenichi; Yokoyama, Kenichi; Hioki, Mika; Narui, Ryohsuke; Tanigawa, Shinichi; Inada, Keiichi; Matsuo, Seiichiro; Yoshimura, Michihiro

    2016-08-01

    An 85-year-old female presented to our institution with symptomatic sick sinus syndrome. During pacemaker implantation, an anchoring sleeve in the right ventricular lead was embolized in the left pulmonary artery. Although the anchoring sleeve was radiolucent, digital subtraction angiography revealed an angiographic filling defect in the lower branch of the left pulmonary artery, and a snare catheter enabled the anchoring sleeve to be grasped and extracted.

  10. [Intracranial Dural Arteriovenous Fistula Associated with Multiple Arterio-arterial Fistulas between the Systemic Arteries and the Pulmonary Artery:A Case Report].

    PubMed

    Miyamoto, Junichi; Niijima, Kyo

    2016-09-01

    An intracranial dural arteriovenous fistula(dAVF)was incidentally detected in a 39-year-old man during a medical checkup. Except for a mild episode of pneumonia at the age of 22 years, his medical history was unremarkable. He had no family history of hereditary hemorrhagic telangiectasia(HHT). The dAVF was treated radically via ligation of the fistula, without any complications. Postoperative angiography demonstrated that the dAVF had completely healed, but showed an aberrant, dilatated, and tortuous internal mammary artery. A contrast-enhanced computed tomography scan revealed multiple arterio-arterial fistulas between various systemic arteries and the pulmonary artery(an intercostal artery to the pulmonary artery fistula, an internal mammary artery to the pulmonary artery fistula, and an inferior phrenic artery to the pulmonary artery fistula). These thoracic lesions did not require additional treatment because they did not cause any symptoms, e.g., respiratory or cardiac failure. In most previous cases, such aberrant thoracic arterial fistulas were detected incidentally or based on the presence of minor clinical symptoms. However, in some cases, they caused severe respiratory or cardiac failure and were treated via the embolization of the responsible vessels. Therefore, the co-existence of thoracic arterial fistulas in patients with dAVF should be evaluated, even if the dAVF does not meet the criteria for HHT. Such thoracic lesions might cause a chest murmur that can be detected via a stethoscope or via a blunt costophrenic angle on chest radiography. PMID:27605480

  11. Pulmonary artery banding in the current era: Is it still useful?

    PubMed Central

    Dehaki, Maziar Gholampour; Tabaee, Ali Sadeghpour; Ahmadabadi, Changiz Azadi; Ghavidel, Alireza Alizadeh; Omra, Gholamreza

    2012-01-01

    Background: The objective of this study was to assess the results of the pulmonary artery (PA) banding in patients with congenital heart defects (CHD) and pulmonary hypertension (PH) in the current era. Methods: We analyzed data from 305 patients who underwent PA banding between April 2005 and April 2010 at our centre. All patients were approached through a left thoracotomy. Twenty percent of patients underwent PA banding based on Trusler's rule (Group 1), 55% of them underwent PA banding based on PA pressure measurement (Group 2), and the rest of them (25%) based on surgeon experience (Group 3). The follow-up period was 39 ± 20 month and 75% of patients (230 cases) had definitive repair at mean interval 23 ± 10 months. Results: The rate of anatomically and functionally effectiveness of PA banding in all groups was high (97% and 92%, respectively). There were no significant differences in anatomically and functionally efficacy rate between all groups (P=0.77, P=0.728, respectively). There was PA bifurcation stenosis in six cases (2%), and pulmonary valve injury in one case (0.3%). The mortality rate in PA banding was 2% and in definitive repair was 3%. Conclusions: We believe that PA banding still plays a role in management of patients with CHD, particularly for infants with medical problems such as sepsis, low body weight, intracranial hemorrhage and associated non cardiac anomalies. PA banding can be done safely with low morbidity and mortality. PMID:22529599

  12. Neurohormonal activation and pharmacological inhibition in pulmonary arterial hypertension and related right ventricular failure.

    PubMed

    Ameri, Pietro; Bertero, Edoardo; Meliota, Giovanni; Cheli, Martino; Canepa, Marco; Brunelli, Claudio; Balbi, Manrico

    2016-09-01

    During the last decade, hyperactivity of the sympathetic nervous and renin-angiotensin-aldosterone systems (SNS and RAAS, respectively) has repeatedly been related to the pathophysiology of pulmonary arterial hypertension (PAH) and PAH-related right ventricular failure (PAH-RVF), raising the question of whether neurohormonal inhibition may be indicated for these conditions. Experimental data indicate that the RAAS may be involved in pulmonary vascular remodeling, which is in fact halted by RAAS antagonism. Favorable actions of β-blockers on the pulmonary vasculature have also been described, even if information about β-adrenergic receptors in PAH is lacking. Furthermore, the available evidence suggests that stimulation of the pressure-overloaded RV by the SNS and RAAS is initially compensatory, but becomes maladaptive over time. Consistently, RV reverse remodeling has been shown in PAH animal models treated with either β-blockers or RAAS inhibitors, although important differences with human PAH may limit the translational value of these findings. Only few observational studies of neurohormonal antagonism in PAH and PAH-RVF have been published. Nonetheless, β-blockers on top of specific therapy appear to be safe and possibly also effective. The combination of mineralocorticoid receptor and endothelin-A receptor antagonists may result in an additive effect because of a positive pharmacodynamic interaction. While neurohormonal inhibitors cannot be recommended at present for treatment of PAH and PAH-RVF, they are worth being further investigated. PMID:27206576

  13. In vivo and in vitro measurements of pulmonary arterial stiffness: A brief review

    PubMed Central

    Tian, Lian; Chesler, Naomi C.

    2012-01-01

    During the progression of pulmonary hypertension (PH), proximal pulmonary arteries (PAs) undergo remodeling such that they become thicker and the elastic modulus increases. Both of these changes increase the vascular stiffness. The increase in pulmonary vascular stiffness contributes to increased right ventricular (RV) afterload, which causes RV hypertrophy and eventually failure. Studies have found that proximal PA stiffness or its inverse, compliance, is strongly related to morbidity and mortality in patients with PH. Therefore, accurate in vivo measurement of PA stiffness is useful for prognoses in patients with PH. It is also important to understand the structural changes in PAs that occur with PH that are responsible for stiffening. Here, we briefly review the most common parameters used to quantify stiffness and in vivo and in vitro methods for measuring PA stiffness in human and animal models. For in vivo approaches, we review invasive and noninvasive approaches that are based on measurements of pressure and inner or outer diameter or cross-sectional area. For in vitro techniques, we review several different testing methods that mimic one, two or several aspects of physiological loading (e.g., uniaxial and biaxial testing, dynamic inflation-force testing). Many in vivo and in vitro measurement methods exist in the literature, and it is important to carefully choose an appropriate method to measure PA stiffness accurately. Therefore, advantages and disadvantages of each approach are discussed. PMID:23372936

  14. Cardiac haemangioma with coronary-pulmonary artery fistula in one patient.

    PubMed

    Xu, Hongfei; Li, Weidong; Teng, Peng; Ni, Yiming

    2015-02-01

    Cardiac haemangioma and coronary-pulmonary artery fistula are both rare entities. We present the case of a 45-year-old symptomatic male patient with a rare cardiac cavernous haemangioma. During assessment, coronary-pulmonary artery fistula was diagnosed by computed tomographic angiography (CTA) of the coronary artery. As far as we know, this is the first case in which cardiac haemangioma has been found to co-exist with coronary-pulmonary artery fistula. Surgery remains the most effective form of therapy. Meanwhile, in patients with heart issues, CTA of the coronary artery has its particularly advantages that can reduce the risk of a second operation and missed diagnosis. We also performed an electronic search of the published literature in English on cases of cardiac haemangioma.

  15. Right ventricular free wall pacing improves cardiac pump function in severe pulmonary arterial hypertension: a computer simulation analysis.

    PubMed

    Lumens, Joost; Arts, Theo; Broers, Bernard; Boomars, Karin A; van Paassen, Pieter; Prinzen, Frits W; Delhaas, Tammo

    2009-12-01

    In pulmonary arterial hypertension (PAH), duration of myofiber shortening is prolonged in the right ventricular (RV) free wall (RVfw) compared with that in the interventricular septum and left ventricular free wall. This interventricular mechanical asynchrony eventually leads to right heart failure. We investigated by computer simulation whether, in PAH, early RVfw pacing may improve interventricular mechanical synchrony and, hence, cardiac pump function. A mathematical model of the human heart and circulation was used to simulate left ventricular and RV pump mechanics and myofiber mechanics. First, we simulated cardiovascular mechanics of a healthy adult at rest. Size and mass of heart and blood vessels were adapted so that mechanical tissue load was normalized. Second, compensated PAH was simulated by increasing mean pulmonary artery pressure to 32 mmHg while applying load adaptation. Third, decompensated PAH was simulated by increasing mean pulmonary artery pressure further to 79 mmHg without further adaptation. Finally, early RVfw pacing was simulated in severely decompensated PAH. Time courses of circumferential strain in the ventricular walls as simulated were similar to the ones measured in healthy subjects (uniform strain patterns) and in PAH patients (prolonged RVfw shortening). When simulating pacing in decompensated PAH, RV pump function was best upon 40-ms RVfw preexcitation, as evidenced by maximal decrease of RV end-diastolic volume, reduced RVfw myofiber work, and most homogeneous distribution of workload over the ventricular walls. Thus our simulations indicate that, in decompensated PAH, RVfw pacing may improve RV pump function and may homogenize workload over the ventricular walls.

  16. Pediatric Cardiopulmonary Bypass Adaptations for Long-Term Survival of Baboons Undergoing Pulmonary Artery Replacement

    PubMed Central

    Whittaker, Carrie; Grist, Gary; Bert, Arthur; Brasky, Kathleen; Neighbors, Stacy; McFall, Christopher; Hilbert, Stephen L.; Drake, William B.; Cromwell, Michael; Mueller, Barbara; Lofland, Gary K.; Hopkins, Richard A.

    2010-01-01

    Abstract: Cardiopulmonary bypass (CPB) protocols of the baboon (Papio cynocephalus anubis) are limited to obtaining experimental data without concern for long-term survival. In the evaluation of pulmonary artery tissue engineered heart valves (TEHVs), pediatric CPB methods are adapted to accommodate the animals’ unique physiology enabling survival up to 6 months until elective sacrifice. Aortic access was by a 14F arterial cannula and atrial access by a single 24F venous cannula. The CPB circuit includes a 3.3 L/min flow rated oxygenator, ¼″ × ⅜″ arterial-venous loop, ⅜″ raceway, and bubble trap. The prime contains 700 mL Plasma-Lyte, 700 units heparin, 5 mL of 50% dextrose, and 20 mg amiodarone. Heparinization (200 u/kg) targets an activated clotting time of 350 seconds. Normothermic CPB was initiated at a 2.5 L/m2/min cardiac index with a mean arterial pressure of 55–80 mmHg. Weaning was monitored with transesophageal echocardiogram. Post-CPB circuit blood was re-infused. Chest tubes were removed with cessation of bleeding. Extubation was performed upon spontaneous breathing. The animals were conscious and upright 3 hours post-CPB. Bioprosthetic valves or TEHVs were implanted as pulmonary replacements in 20 baboons: weight = 27.5 ± 5.6 kg, height = 73 ± 7 cm, body surface area = 0.77 m2 ± 0.08, mean blood flow = 1.973 ± .254 L/min, core temperature = 37.1 ± .1°C, and CPB time = 60 ± 40 minutes. No acidosis accompanied CPB. Sixteen animals survived, four expired. Three died of right ventricular failure and one of an anaphylactoid reaction. Surviving animals had normally functioning replacement valves and ventricles. Baboon CPB requires modifications to include high systemic blood pressure for adequate perfusion into small coronary arteries, careful CPB weaning to prevent ventricular distention, and drug and fluid interventions to abate variable venous return related to a muscularized spleno-splanchnic venous capacity. PMID:21114226

  17. Bronchial Artery Embolization in the Management of Pulmonary Parenchymal Endometriosis with Hemoptysis

    SciTech Connect

    Kervancioglu, Selim Andic, Cagatay; Bayram, Nazan; Telli, Cumali; Sarica, Akif; Sirikci, Akif

    2008-07-15

    Pulmonary parenchymal endometriosis is extremely rare and usually manifests itself with a recurrent hemoptysis associated with the menstrual cycle. The therapies proposed for women with endometriosis consist of medical treatments and surgery. Bronchial artery embolization has become a well-established and minimally invasive treatment modality for hemoptysis, and to the best of our knowledge, it has not been reported in pulmonary endometriosis. We report a case of pulmonary parenchymal endometriosis treated with embolotheraphy for hemoptysis.

  18. Impact of pulmonary arterial endothelial cells on duroquinone redox status.

    PubMed

    Merker, Marilyn P; Bongard, Robert D; Krenz, Gary S; Zhao, Hongtao; Fernandes, Viola S; Kalyanaraman, Balaraman; Hogg, Neil; Audi, Said H

    2004-07-01

    The study objective was to use pulmonary arterial endothelial cells to examine kinetics and mechanisms contributing to the disposition of the quinone 2,3,5,6-tetramethyl-1,4-benzoquinone (duroquinone, DQ) observed during passage through the pulmonary circulation. The approach was to add DQ, durohydroquinone (DQH2), or DQ with the cell membrane-impermeant oxidizing agent, ferricyanide (Fe(CN)6(3)-), to the cell medium, and to measure the medium concentrations of substrates and products over time. Studies were carried out under control conditions and with dicumarol, to inhibit NAD(P)H:quinone oxidoreductase 1 (NQO1), or cyanide, to inhibit mitochondrial electron transport. In control cells, DQH2 appears in the extracellular medium of cells incubated with DQ, and DQ appears when the cells are incubated with DQH2. Dicumarol blocked the appearance of DQH2 when DQ was added to the cell medium, and cyanide blocked the appearance of DQ when DQH2 was added to the cell medium, suggesting that the two electron reductase NQO1 dominates DQ reduction and mitochondrial electron transport complex III is the predominant route of DQH2 oxidation. In the presence of cyanide, the addition of DQ also resulted in an increased rate of appearance of DQH2 and stimulation of cyanide-insensitive oxygen consumption. As DQH2 does not autoxidize-comproportionate over the study time course, these observations suggest a cyanide-stimulated one-electron DQ reduction and durosemiquinone (DQ*-) autoxidation. The latter processes are apparently confined to the cell interior, as the cell membrane impermeant oxidant, ferricyanide, did not inhibit the DQ-stimulated cyanide-insensitive oxygen consumption. Thus, regardless of whether DQ is reduced via a one- or two-electron reduction pathway, the net effect in the extracellular medium is the appearance of DQH2. These endothelial redox functions and their apposition to the vessel lumen are consistent with the pulmonary endothelium being an important site of

  19. The unique heart sound signature of children with pulmonary artery hypertension.

    PubMed

    Elgendi, Mohamed; Bobhate, Prashant; Jain, Shreepal; Guo, Long; Kumar, Shine; Rutledge, Jennifer; Coe, Yashu; Zemp, Roger; Schuurmans, Dale; Adatia, Ian

    2015-12-01

    We hypothesized that vibrations created by the pulmonary circulation would create sound like the vocal cords during speech and that subjects with pulmonary artery hypertension (PAH) might have a unique sound signature. We recorded heart sounds at the cardiac apex and the second left intercostal space (2LICS), using a digital stethoscope, from 27 subjects (12 males) with a median age of 7 years (range: 3 months-19 years) undergoing simultaneous cardiac catheterization. Thirteen subjects had mean pulmonary artery pressure (mPAp) < 25 mmHg (range: 8-24 mmHg). Fourteen subjects had mPAp ≥ 25 mmHg (range: 25-97 mmHg). We extracted the relative power of the frequency band, the entropy, and the energy of the sinusoid formants from the heart sounds. We applied linear discriminant analysis with leave-one-out cross validation to differentiate children with and without PAH. The significance of the results was determined with a t test and a rank-sum test. The entropy of the first sinusoid formant contained within an optimized window length of 2 seconds of the heart sounds recorded at the 2LICS was significantly lower in subjects with mPAp ≥ 25 mmHg relative to subjects with mPAp < 25 mmHg, with a sensitivity of 93% and specificity of 92%. The reduced entropy of the first sinusoid formant of the heart sounds in children with PAH suggests the existence of an organized pattern. The analysis of this pattern revealed a unique sound signature, which could be applied to a noninvasive method to diagnose PAH. PMID:26697170

  20. Survival in systemic sclerosis-associated pulmonary arterial hypertension in the modern management era

    PubMed Central

    Launay, David; Sitbon, Olivier; Hachulla, Eric; Mouthon, Luc; Gressin, Virginie; Rottat, Laurence; Clerson, Pierre; Cordier, Jean-François; Simonneau, Gerald; Humbert, Marc

    2013-01-01

    Objective To assess the survival and prognostic factors in patients with newly diagnosed incident systemic sclerosis (SSc)–associated pulmonary arterial hypertension (PAH) in the modern management era. Methods Prospectively enrolled SSc patients in the French PAH Network between January 2006 and November 2009, with newly diagnosed PAH and no interstitial lung disease, were analysed (85 patients, mean age 64.9±12.2 years). Median follow-up after PAH diagnosis was 2.32 years. Results A majority of patients were in NYHA functional class III–IV (79%). Overall survival was 90% (95% CI 81% to 95%), 78% (95% CI 67% to 86%) and 56% (95% CI 42% to 68%) at 1, 2 and 3 years from PAH diagnosis, respectively. Age (HR: 1.05, 95% CI 1.01 to 1.09, p=0.012) and cardiac index (HR: 0.49, 95% CI 0.27 to 0.89, p=0.019) were significant predictors in the univariate analysis. We also observed strong trends for gender, SSc subtypes, New York Heart Association functional class, pulmonary vascular resistance and capacitance to be significant predictors in the univariate analysis. Conversely, six-min walk distance, mean pulmonary arterial and right atrial pressures were not significant predictors. In the multivariate model, gender was the only independent factor associated with survival (HR: 4.76, 95% CI 1.35 to 16.66, p=0.015 for male gender). Conclusions Incident SSc-associated PAH remains a devastating disease even in the modern management era. Age, male gender and cardiac index were the main prognosis factors in this cohort of patients. Early detection of less severe patients should be a priority. PMID:23178295

  1. Is early diagnosis of pulmonary arterial hypertension possible in inflammatory rheumatic diseases? Experience from a single center in Turkey

    PubMed Central

    Akdoğan, Ali; Okutucu, Sercan; Kılıç, Levent; Kaya, Barış; Evranos, Banu; Aytemir, Kudret; Çöplü, Lütfi; Ertenli, İhsan; Çalgüneri, Meral; Oto, Ali; Tokgözoğlu, Lale

    2015-01-01

    Objective Pulmonary arterial hypertension (PAH) is a devastating complication of inflammatory rheumatic diseases. The aim of this study was to determine the role of screening for the early diagnosis of pulmonary hypertension (PH) in inflammatory rheumatic diseases. Material and Methods Data of patients with inflammatory rheumatic diseases and PH who had no obvious cause of PH and who were evaluated by Working Group for Pulmonary Hypertension in Hacettepe University were investigated retrospectively. All patients with inflammatory disease were evaluated by right heart catheterization (RHC) to check if they had systolic pulmonary arterial pressure (sPAP) ≥40 mmHg and/or symptoms related to PH unless explained by other causes. Results RHC was performed in 47 patients with inflammatory rheumatic diseases and PH out of 50 patients who were to be evaluated by RHC based on clinical and Doppler echocardiographic findings. There was a positive correlation between sPAP estimated by Doppler echocardiography and sPAP determined by RHC in patients with inflammatory rheumatic diseases (r=0.66; p<0.001). The mean pulmonary arterial pressure (mPAP) was found to be <25 mmHg in 27.7% of the patients. New York Heart Association functional capacity (NYHA FC) was class III or IV in 79.0% of the patients with PAH. PAH was more frequent in patients with NYHA FC III–IV compared with patients with NYHA FC I–II [58.7% (15) patients vs. 19.0% (4) patients; p=0.009]. Conclusion In this study, approximately 80% of the patients with inflammatory disease-associated PAH were diagnosed late in NYHA FC III or IV. There are still unresolved issues in the diagnosis and treatment of PH in inflammatory diseases. Collaboration and multidisciplinary approach are the key points to overcome the challenges in this field. PMID:27708911

  2. Contributions of tidal lung inflation to human R-R interval and arterial pressure fluctuations.

    PubMed

    Koh, J; Brown, T E; Beightol, L A; Eckberg, D L

    1998-01-19

    We studied the effects of mechanical lung inflation on respiratory frequency R-R interval and arterial pressure fluctuations in nine healthy young adults undergoing elective orthopedic surgery. We conducted this research to define the contribution of pulmonary and thoracic stretch receptor input to respiratory sinus arrhythmia. We compared fast Fourier transform spectral power during three modes of ventilation: (1) spontaneous, frequency-controlled (0.25 Hz) breathing, (2) intermittent positive pressure ventilation (0.25 Hz, with a tidal volume of 8 ml/kg) and (3) high frequency jet ventilation (5.0 Hz, 2.5 kg/cm2), after sedation and vecuronium paralysis. Mean R-R intervals, arterial pressures and arterial blood gas levels were comparable during all three breathing conditions. Respiratory frequency systolic pressure spectral power was comparable during spontaneous breathing and conventional mechanical ventilation, but was significantly reduced during high frequency jet ventilation (P < 0.05). Respiratory frequency R-R interval spectral power (used as an index of respiratory sinus arrhythmia) declined dramatically with sedation and muscle paralysis (P < 0.05), but was greater during conventional mechanical, than high frequency jet ventilation (P < 0.05). These results suggest that although phasic inputs from pulmonary and thoracic stretch receptors make a statistically significant contribution to respiratory sinus arrhythmia, that contribution is small.

  3. Contributions of tidal lung inflation to human R-R interval and arterial pressure fluctuations

    NASA Technical Reports Server (NTRS)

    Koh, J.; Brown, T. E.; Beightol, L. A.; Eckberg, D. L.

    1998-01-01

    We studied the effects of mechanical lung inflation on respiratory frequency R-R interval and arterial pressure fluctuations in nine healthy young adults undergoing elective orthopedic surgery. We conducted this research to define the contribution of pulmonary and thoracic stretch receptor input to respiratory sinus arrhythmia. We compared fast Fourier transform spectral power during three modes of ventilation: (1) spontaneous, frequency-controlled (0.25 Hz) breathing, (2) intermittent positive pressure ventilation (0.25 Hz, with a tidal volume of 8 ml/kg) and (3) high frequency jet ventilation (5.0 Hz, 2.5 kg/cm2), after sedation and vecuronium paralysis. Mean R-R intervals, arterial pressures and arterial blood gas levels were comparable during all three breathing conditions. Respiratory frequency systolic pressure spectral power was comparable during spontaneous breathing and conventional mechanical ventilation, but was significantly reduced during high frequency jet ventilation (P < 0.05). Respiratory frequency R-R interval spectral power (used as an index of respiratory sinus arrhythmia) declined dramatically with sedation and muscle paralysis (P < 0.05), but was greater during conventional mechanical, than high frequency jet ventilation (P < 0.05). These results suggest that although phasic inputs from pulmonary and thoracic stretch receptors make a statistically significant contribution to respiratory sinus arrhythmia, that contribution is small.

  4. The effect of exercise training on the pulmonary arterial system in patients with pulmonary hypertension.

    PubMed

    Arena, Ross; Cahalin, Lawrence P; Borghi-Silva, Audrey; Myers, Jonathan

    2015-01-01

    Given the unique and clinically ominous pathology associated with pulmonary arterial (PA) hypertension (PH) and its implications for the eventual deterioration of right ventricular function, exercise training (ET) was historically not recommended. More recently, a body of literature demonstrating the safety and efficacy of ET in PH has emerged. The primary focus of this review is to provide a synopsis of current evidence assessing the effects of ET on the PA system in patients with PH. The current body of evidence is relatively small and it is not clear if ET improves PA function or vessel characteristics. Nevertheless, studies have consistently found ET leads to numerous clinically relevant benefits including increased: 1) aerobic capacity, 2) muscle strength, 3) exercise tolerance, and 4) quality of life. Thus, ET, given its clinical benefits, is likely to enjoy increased utilization in patients with PH.

  5. Comparative Transcriptome Analysis Identifies CCDC80 as a Novel Gene Associated with Pulmonary Arterial Hypertension

    PubMed Central

    Sasagawa, Shota; Nishimura, Yuhei; Sawada, Hirofumi; Zhang, Erquan; Okabe, Shiko; Murakami, Soichiro; Ashikawa, Yoshifumi; Yuge, Mizuki; Kawaguchi, Koki; Kawase, Reiko; Mitani, Yoshihide; Maruyama, Kazuo; Tanaka, Toshio

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a heterogeneous disorder associated with a progressive increase in pulmonary artery resistance and pressure. Although various therapies have been developed, the 5-year survival rate of PAH patients remains low. There is thus an important need to identify novel genes that are commonly dysregulated in PAH of various etiologies and could be used as biomarkers and/or therapeutic targets. In this study, we performed comparative transcriptome analysis of five mammalian PAH datasets downloaded from a public database. We identified 228 differentially expressed genes (DEGs) from a rat PAH model caused by inhibition of vascular endothelial growth factor receptor under hypoxic conditions, 379 DEGs from a mouse PAH model associated with systemic sclerosis, 850 DEGs from a mouse PAH model associated with schistosomiasis, 1598 DEGs from one cohort of human PAH patients, and 4260 DEGs from a second cohort of human PAH patients. Gene-by-gene comparison identified four genes that were differentially upregulated or downregulated in parallel in all five sets of DEGs. Expression of coiled-coil domain containing 80 (CCDC80) and anterior gradient two genes was significantly increased in the five datasets, whereas expression of SMAD family member six and granzyme A was significantly decreased. Weighted gene co-expression network analysis revealed a connection between CCDC80 and collagen type I alpha 1 (COL1A1) expression. To validate the function of CCDC80 in vivo, we knocked out ccdc80 in zebrafish using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system. In vivo imaging of zebrafish expressing a fluorescent protein in endothelial cells showed that ccdc80 deletion significantly increased the diameter of the ventral artery, a vessel supplying blood to the gills. We also demonstrated that expression of col1a1 and endothelin-1 mRNA was significantly decreased in the ccdc80-knockout zebrafish. Finally, we examined Ccdc

  6. Comparative Transcriptome Analysis Identifies CCDC80 as a Novel Gene Associated with Pulmonary Arterial Hypertension.

    PubMed

    Sasagawa, Shota; Nishimura, Yuhei; Sawada, Hirofumi; Zhang, Erquan; Okabe, Shiko; Murakami, Soichiro; Ashikawa, Yoshifumi; Yuge, Mizuki; Kawaguchi, Koki; Kawase, Reiko; Mitani, Yoshihide; Maruyama, Kazuo; Tanaka, Toshio

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a heterogeneous disorder associated with a progressive increase in pulmonary artery resistance and pressure. Although various therapies have been developed, the 5-year survival rate of PAH patients remains low. There is thus an important need to identify novel genes that are commonly dysregulated in PAH of various etiologies and could be used as biomarkers and/or therapeutic targets. In this study, we performed comparative transcriptome analysis of five mammalian PAH datasets downloaded from a public database. We identified 228 differentially expressed genes (DEGs) from a rat PAH model caused by inhibition of vascular endothelial growth factor receptor under hypoxic conditions, 379 DEGs from a mouse PAH model associated with systemic sclerosis, 850 DEGs from a mouse PAH model associated with schistosomiasis, 1598 DEGs from one cohort of human PAH patients, and 4260 DEGs from a second cohort of human PAH patients. Gene-by-gene comparison identified four genes that were differentially upregulated or downregulated in parallel in all five sets of DEGs. Expression of coiled-coil domain containing 80 (CCDC80) and anterior gradient two genes was significantly increased in the five datasets, whereas expression of SMAD family member six and granzyme A was significantly decreased. Weighted gene co-expression network analysis revealed a connection between CCDC80 and collagen type I alpha 1 (COL1A1) expression. To validate the function of CCDC80 in vivo, we knocked out ccdc80 in zebrafish using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system. In vivo imaging of zebrafish expressing a fluorescent protein in endothelial cells showed that ccdc80 deletion significantly increased the diameter of the ventral artery, a vessel supplying blood to the gills. We also demonstrated that expression of col1a1 and endothelin-1 mRNA was significantly decreased in the ccdc80-knockout zebrafish. Finally, we examined Ccdc

  7. Updated Evidence-Based Treatment Algorithm in Pulmonary Arterial Hypertension

    PubMed Central

    Barst, Robyn J.; Gibbs, J. Simon; Ghofrani, Hossein A.; Hoeper, Marius M.; McLaughlin, Vallerie V.; Rubin, Lewis J.; Sitbon, Olivier; Tapson, Victor; Galiè, Nazzareno

    2009-01-01

    Uncontrolled and controlled clinical trials with different compounds and procedures are reviewed to define the risk-benefit profiles for therapeutic options in pulmonary arterial hypertension (PAH). A grading system for the level of evidence of treatments based on the controlled clinical trials performed with each compound is used to propose an evidence-based treatment algorithm. The algorithm includes drugs approved by regulatory agencies for the treatment of PAH and/or drugs available for other indications. The different treatments have been evaluated mainly in idiopathic PAH, heritable PAH, and in PAH associated with the scleroderma spectrum of diseases or with anorexigen use. Extrapolation of these recommendations to other PAH subgroups should be done with caution. Oral anticoagulation is proposed for most patients; diuretic treatment and supplemental oxygen are indicated in cases of fluid retention and hypoxemia, respectively. High doses of calcium channel blockers are indicated only in the minority of patients who respond to acute vasoreactivity testing. Nonresponders to acute vasoreactivity testing, or responders who remain in World Health Organization (WHO) functional class III, should be considered candidates for treatment with either an oral phosphodiesterase-5 inhibitor or an oral endothelin-receptor antagonist. Continuous intravenous administration of epoprostenol remains the treatment of choice in WHO functional class IV patients. Combination therapy is recommended for patients treated with PAH monotherapy who remain in New York Heart Association functional class III. Atrial septostomy and lung transplantation are indicated for refractory patients or where medical treatment is unavailable. PMID:19555861

  8. Development of macitentan for the treatment of pulmonary arterial hypertension.

    PubMed

    Selej, Mona; Romero, Alain J; Channick, Richard N; Clozel, Martine

    2015-11-01

    Pulmonary arterial hypertension (PAH) is a serious, chronic condition that, without early recognition and treatment, leads to progressive right heart failure and death. The dual endothelin receptor antagonist macitentan was designed through a deliberate discovery process to maximize endothelin-axis blockade while improving adverse-effect profiles compared with previous compounds. Macitentan's efficacy was demonstrated in an event-driven morbidity and mortality study of treatment-naive and background PAH therapy-treated symptomatic patients. Compared to placebo, 10 mg of macitentan significantly reduced the relative risk of morbidity and mortality by 45%, primarily by delaying PAH worsening, most prominently in World Health Organization (WHO) functional class II and III PAH patients. Macitentan reduced the incidence of the composite end point of PAH-related hospitalizations and mortality and improved WHO FC and exercise capacity (6-min walk distance). Furthermore, it significantly improved cardiopulmonary hemodynamics and quality of life, and had a favorable safety and tolerability profile. To date, this was the largest and longest prospective trial for PAH. Macitentan, currently the only approved oral PAH treatment shown to be safe and effective in delaying long-term progression and reducing PAH-related hospitalizations, has changed treatment paradigms from goal-directed to long-term outcome-oriented therapy.

  9. Epoprostenol sodium for treatment of pulmonary arterial hypertension

    PubMed Central

    Saito, Yukihiro; Nakamura, Kazufumi; Akagi, Satoshi; Sarashina, Toshihiro; Ejiri, Kentaro; Miura, Aya; Ogawa, Aiko; Matsubara, Hiromi; Ito, Hiroshi

    2015-01-01

    The release of endogenous prostacyclin (PGI2) is depressed in patients with pulmonary arterial hypertension (PAH). PGI2 replacement therapy by epoprostenol infusion is one of the best treatments available for PAH. Here, we provide an overview of the current clinical data for epoprostenol. Epoprostenol treatment improves symptoms, exercise capacity, and hemodynamics, and is the only treatment that has been shown to reduce mortality in patients with idiopathic PAH (IPAH) in randomized clinical trials. We have reported that high-dose epoprostenol therapy (>40 ng/kg/min) also results in marked hemodynamic improvement in some patients with IPAH. High-dose epoprostenol has a pro-apoptotic effect on PAH-PASMCs via the IP receptor and upregulation of Fas ligand (FasL) in vitro. However, long-term intravenous administration of epoprostenol is sometimes associated with catheter-related infections and leads to considerable inconvenience for the patient. In the future, the development of new routes of administration or the development of powerful PGI2 analogs, IP-receptor agonists, and gene and cell-based therapy enhancing PGI2 production with new routes of administration is required. PMID:25999730

  10. The molecular targets of approved treatments for pulmonary arterial hypertension

    PubMed Central

    Humbert, Marc; Ghofrani, Hossein-Ardeschir

    2016-01-01

    Until recently, three classes of medical therapy were available for the treatment of pulmonary arterial hypertension (PAH)—prostanoids, endothelin receptor antagonists and phosphodiesterase type 5 (PDE5) inhibitors. With the approval of the soluble guanylate cyclase stimulator riociguat, an additional drug class has become available targeting a distinct molecular target in the same pathway as PDE5 inhibitors. Treatment recommendations currently include the use of all four drug classes to treat PAH, but there is a lack of comparative data for these therapies. Therefore, an understanding of the mechanistic differences between these agents is critical when making treatment decisions. Combination therapy is often used to treat PAH and it is therefore important that physicians understand how the modes of action of these drugs may interact to work as complementary partners, or potentially with unwanted consequences. Furthermore, different patient phenotypes mean that patients respond differently to treatment; while a certain monotherapy may be adequate for some patients, for others it will be important to consider alternating or combining compounds with different molecular targets. This review describes how the four currently approved drug classes target the complex pathobiology of PAH and will consider the distinct target molecules of each drug class, their modes of action, and review the pivotal clinical trial data supporting their use. It will also discuss the rationale for combining drugs (or not) from the different classes, and review the clinical data from studies on combination therapy. PMID:26219978

  11. Epigenetic modulation as a therapeutic approach for pulmonary arterial hypertension

    PubMed Central

    Kim, Jun-Dae; Lee, Aram; Choi, Jihea; Park, Youngsook; Kang, Hyesoo; Chang, Woochul; Lee, Myeong-Sok; Kim, Jongmin

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a rare but progressive and currently incurable disease, which is characterized by vascular remodeling in association with muscularization of the arterioles, medial thickening and plexiform lesion formation. Despite our advanced understanding of the pathogenesis of PAH and the recent therapeutic advances, PAH still remains a fatal disease. In addition, the susceptibility to PAH has not yet been adequately explained. Much evidence points to the involvement of epigenetic changes in the pathogenesis of a number of human diseases including cancer, peripheral hypertension and asthma. The knowledge gained from the epigenetic study of various human diseases can also be applied to PAH. Thus, the pursuit of novel therapeutic targets via understanding the epigenetic alterations involved in the pathogenesis of PAH, such as DNA methylation, histone modification and microRNA, might be an attractive therapeutic avenue for the development of a novel and more effective treatment. This review provides a general overview of the current advances in epigenetics associated with PAH, and discusses the potential for improved treatment through understanding the role of epigenetics in the development of PAH. PMID:26228095

  12. The Characteristics of Treated Pulmonary Arterial Hypertension Patients in Ontario

    PubMed Central

    Vaid, Haris M.; Camacho, Ximena; Granton, John T.; Mamdani, Muhammad M.; Yao, Zhan; Singh, Samantha; Juurlink, David N.; Gomes, Tara

    2016-01-01

    Background. There are no Canadian prevalence studies on pulmonary arterial hypertension (PAH) to date. We described the characteristics of treated PAH patients and the healthcare utilization and costs associated with PAH in a population of public drug plan beneficiaries in Ontario, Canada. Methods. A retrospective cross-sectional analysis was conducted between April 2010 and March 2011 to identify treated PAH patients using population-based health administrative databases. We investigated demographic and clinical characteristics of treated PAH patients and conducted a cohort study to determine treatment patterns, healthcare utilization, and associated costs, over a one-year follow-up period (March 2012). Results. We identified 326 treated PAH cases in Ontario's publicly funded drug plan. Overall mean age was 59.4 years (±20.3 years) and over 77% of cases were women (n = 251). Combination therapy was used to treat 22.9% (n = 69) of cases, costing an average of $4,569 (SD $1,544) per month. Median monthly healthcare costs were $264 (IQR $96–$747) for those who survived and $2,021 (IQR $993–$6,399) for those who died over a one-year period, respectively (p < 0.01). Conclusions. PAH care in Ontario is complex and has high healthcare costs. This data may help guide towards improved patient management. PMID:27445555

  13. Redox biology in pulmonary arterial hypertension (2013 Grover Conference Series)

    PubMed Central

    2015-01-01

    Abstract Through detailed interrogation of the molecular pathways that contribute to the development of pulmonary arterial hypertension (PAH), the separate but related processes of oxidative stress and cellular metabolic dysfunction have emerged as being critical pathogenic mechanisms that are as yet relatively untargeted therapeutically. In this review, we have attempted to summarize some of the important existing studies, to point out areas of overlap between oxidative stress and metabolic dysfunction, and to do so under the unifying heading of redox biology. We discuss the importance of precision in assessing oxidant signaling versus oxidant injury and why this distinction matters. We endeavor to advance the discussion of carbon-substrate metabolism beyond a focus on glucose and its fate in the cell to encompass other carbon substrates and some of the murkiness surrounding our understanding of how they are handled in different cell types. Finally, we try to bring these ideas together at the level of the mitochondrion and to point out some additional points of possible cognitive dissonance that warrant further experimental probing. The body of beautiful science regarding the molecular and cellular details of redox biology in PAH points to a future that includes clinically useful therapies that target these pathways. To fully realize the potential of these future interventions, we hope that some of the issues raised in this review can be addressed proactively. PMID:26697167

  14. Redox biology in pulmonary arterial hypertension (2013 Grover Conference Series).

    PubMed

    Fessel, Joshua P; West, James D

    2015-12-01

    Through detailed interrogation of the molecular pathways that contribute to the development of pulmonary arterial hypertension (PAH), the separate but related processes of oxidative stress and cellular metabolic dysfunction have emerged as being critical pathogenic mechanisms that are as yet relatively untargeted therapeutically. In this review, we have attempted to summarize some of the important existing studies, to point out areas of overlap between oxidative stress and metabolic dysfunction, and to do so under the unifying heading of redox biology. We discuss the importance of precision in assessing oxidant signaling versus oxidant injury and why this distinction matters. We endeavor to advance the discussion of carbon-substrate metabolism beyond a focus on glucose and its fate in the cell to encompass other carbon substrates and some of the murkiness surrounding our understanding of how they are handled in different cell types. Finally, we try to bring these ideas together at the level of the mitochondrion and to point out some additional points of possible cognitive dissonance that warrant further experimental probing. The body of beautiful science regarding the molecular and cellular details of redox biology in PAH points to a future that includes clinically useful therapies that target these pathways. To fully realize the potential of these future interventions, we hope that some of the issues raised in this review can be addressed proactively.

  15. Epigenetic modulation as a therapeutic approach for pulmonary arterial hypertension.

    PubMed

    Kim, Jun-Dae; Lee, Aram; Choi, Jihea; Park, Youngsook; Kang, Hyesoo; Chang, Woochul; Lee, Myeong-Sok; Kim, Jongmin

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a rare but progressive and currently incurable disease, which is characterized by vascular remodeling in association with muscularization of the arterioles, medial thickening and plexiform lesion formation. Despite our advanced understanding of the pathogenesis of PAH and the recent therapeutic advances, PAH still remains a fatal disease. In addition, the susceptibility to PAH has not yet been adequately explained. Much evidence points to the involvement of epigenetic changes in the pathogenesis of a number of human diseases including cancer, peripheral hypertension and asthma. The knowledge gained from the epigenetic study of various human diseases can also be applied to PAH. Thus, the pursuit of novel therapeutic targets via understanding the epigenetic alterations involved in the pathogenesis of PAH, such as DNA methylation, histone modification and microRNA, might be an attractive therapeutic avenue for the development of a novel and more effective treatment. This review provides a general overview of the current advances in epigenetics associated with PAH, and discusses the potential for improved treatment through understanding the role of epigenetics in the development of PAH. PMID:26228095

  16. Pharmacologic Therapy for Pulmonary Arterial Hypertension in Adults

    PubMed Central

    Taichman, Darren B.; Chung, Lorinda; Klinger, James R.; Lewis, Sandra; Mandel, Jess; Palevsky, Harold I.; Rich, Stuart; Sood, Namita; Rosenzweig, Erika B.; Trow, Terence K.; Yung, Rex; Elliott, C. Gregory; Badesch, David B.

    2014-01-01

    OBJECTIVE: Choices of pharmacologic therapies for pulmonary arterial hypertension (PAH) are ideally guided by high-level evidence. The objective of this guideline is to provide clinicians advice regarding pharmacologic therapy for adult patients with PAH as informed by available evidence. METHODS: This guideline was based on systematic reviews of English language evidence published between 1990 and November 2013, identified using the MEDLINE and Cochrane Library databases. The strength of available evidence was graded using the Grades of Recommendations, Assessment, Development, and Evaluation methodology. Guideline recommendations, or consensus statements when available evidence was insufficient to support recommendations, were developed using a modified Delphi technique to achieve consensus. RESULTS: Available evidence is limited in its ability to support high-level recommendations. Therefore, we drafted consensus statements to address many clinical questions regarding pharmacotherapy for patients with PAH. A total of 79 recommendations or consensus statements were adopted and graded. CONCLUSIONS: Clinical decisions regarding pharmacotherapy for PAH should be guided by high-level recommendations when sufficient evidence is available. Absent higher level evidence, consensus statements based upon available information must be used. Further studies are needed to address the gaps in available knowledge regarding optimal pharmacotherapy for PAH. PMID:24937180

  17. The Characteristics of Treated Pulmonary Arterial Hypertension Patients in Ontario.

    PubMed

    Vaid, Haris M; Camacho, Ximena; Granton, John T; Mamdani, Muhammad M; Yao, Zhan; Singh, Samantha; Juurlink, David N; Gomes, Tara

    2016-01-01

    Background. There are no Canadian prevalence studies on pulmonary arterial hypertension (PAH) to date. We described the characteristics of treated PAH patients and the healthcare utilization and costs associated with PAH in a population of public drug plan beneficiaries in Ontario, Canada. Methods. A retrospective cross-sectional analysis was conducted between April 2010 and March 2011 to identify treated PAH patients using population-based health administrative databases. We investigated demographic and clinical characteristics of treated PAH patients and conducted a cohort study to determine treatment patterns, healthcare utilization, and associated costs, over a one-year follow-up period (March 2012). Results. We identified 326 treated PAH cases in Ontario's publicly funded drug plan. Overall mean age was 59.4 years (±20.3 years) and over 77% of cases were women (n = 251). Combination therapy was used to treat 22.9% (n = 69) of cases, costing an average of $4,569 (SD $1,544) per month. Median monthly healthcare costs were $264 (IQR $96-$747) for those who survived and $2,021 (IQR $993-$6,399) for those who died over a one-year period, respectively (p < 0.01). Conclusions. PAH care in Ontario is complex and has high healthcare costs. This data may help guide towards improved patient management. PMID:27445555

  18. Initial dual oral combination therapy in pulmonary arterial hypertension.

    PubMed

    Sitbon, Olivier; Sattler, Caroline; Bertoletti, Laurent; Savale, Laurent; Cottin, Vincent; Jaïs, Xavier; De Groote, Pascal; Chaouat, Ari; Chabannes, Céline; Bergot, Emmanuel; Bouvaist, Hélène; Dauphin, Claire; Bourdin, Arnaud; Bauer, Fabrice; Montani, David; Humbert, Marc; Simonneau, Gérald

    2016-06-01

    Treatment for pulmonary arterial hypertension (PAH) has been underpinned by single-agent therapy to which concomitant drugs are added sequentially when pre-defined treatment goals are not met.This retrospective analysis of real-world clinical data in 97 patients with newly diagnosed PAH (86% in New York Heart Association functional class III-IV) explored initial dual oral combination treatment with bosentan plus sildenafil (n=61), bosentan plus tadalafil (n=17), ambrisentan plus tadalafil (n=11) or ambrisentan plus sildenafil (n=8).All regimens were associated with significant improvements in functional class, exercise capacity, dyspnoea and haemodynamic indices after 4 months of therapy. Over a median follow-up period of 30 months, 75 (82%) patients were still alive, 53 (71%) of whom received only dual oral combination therapy. Overall survival rates were 97%, 94% and 83% at 1, 2 and 3 years, respectively, and 96%, 94% and 84%, respectively, for the patients with idiopathic PAH, heritable PAH and anorexigen-induced PAH. Expected survival rates calculated from the French equation for the latter were 86%, 75% and 66% at 1, 2 and 3 years, respectively.Initial combination of oral PAH-targeted medications may offer clinical benefits, especially in PAH patients with severe haemodynamic impairment. PMID:26989105

  19. Clinical and molecular genetic features of hereditary pulmonary arterial hypertension.

    PubMed

    Brenner, Laura; Chung, Wendy K

    2011-10-01

    Pulmonary arterial hypertension (PAH) is a rare disorder that may be hereditary (HPAH), idiopathic (IPAH), or associated with either drug-toxin exposures or other medical conditions. Familial cases have long been recognised and are usually due to mutations in the bone morphogenetic protein receptor type 2 gene (BMPR2), or, much less commonly, two other members of the transforming growth factor-β superfamily, activin-like kinase-type 1 (ALK1), and endoglin (ENG), which are associated with hereditary hemorrhagic telangiectasia. In addition, approximately 20% of patients with IPAH carry mutations in BMPR2. Clinical testing for BMPR2 mutations is available and may be offered to HPAH and IPAH patients but should be preceded by genetic counselling, since lifetime penetrance is only 10% to 20%, and there are currently no known effective preventative measures. Identification of a familial mutation can be valuable in reproductive planning and identifying family members who are not mutation carriers and thus will not require lifelong surveillance. With advances in genomic technology and with international collaborative efforts, genome-wide association studies will be conducted to identify additional genes for HPAH, genetic modifiers for BMPR2 penetrance, and genetic susceptibility to IPAH. In addition, collaborative studies of BMPR2 mutation carriers should enable identification of environmental modifiers, biomarkers for disease development and progression, and surrogate markers for efficacy end points in clinical drug development, thereby providing an invaluable resource for trials of PAH prevention.

  20. Pulmonary Artery Endothelial Cell Phenotypic Alterations in a Large Animal Model of Pulmonary Arteriovenous Malformations Following the Glenn Shunt

    PubMed Central

    Kavarana, Minoo N.; Mukherjee, Rupak; Eckhouse, Shaina R.; Rawls, William F.; Logdon, Christina; Stroud, Robert E.; Patel, Risha K.; Nadeau, Elizabeth K.; Spinale, Francis G.; Graham, Eric M.; Forbus, Geoffrey A.; Bradley, Scott M.; Ikonomidis, John S.; Jones, Jeffrey A.

    2014-01-01

    Background: Longevity of the superior cavopulmonary connection (SCPC) is limited by the development of pulmonary arteriovenous malformations (PAVM). The goal of this study was to determine whether phenotypic changes in pulmonary artery endothelial cells (PAEC) that favor angiogenesis occur with PAVM formation. Methods: A superior vena cava to right pulmonary artery connection was constructed in 5 pigs. Pulmonary arteries were harvested at 6-8 weeks following surgery to establish cultures of PAEC and smooth muscle cells, to determine cell proliferation, gene expression, and tubule formation. Abundance of proteins related to angiogenesis was measured in lung tissue. Results: Contrast echocardiography revealed right-to-left shunting, consistent with PAVM formation. While the proliferation of smooth muscle cells from the right pulmonary artery (RPA) (shunted side) and left pulmonary artery (LPA) (non- shunted side) were similar, right PAEC proliferation was significantly higher. Expression profiles of genes encoding cellular signaling proteins were higher in PAECs from the RPA vs. LPA. Protein abundance of angiopoietin-1, and Tie-2 (angiopoietin receptor) were increased in the right lung (both p<0.05). Tubule formation was increased in endothelial cells from the RPA compared to the LPA (404±16 vs. 199±71 tubules/mm2, respectively p<0.05). Conclusions: These findings demonstrate that PAVMs developed in a clinically relevant animal model of SCPC. This study found that PAVM development occurred concomitantly with differential changes in PAEC proliferative ability and phenotype. Moreover, there was a significant increase in the angiopoietin/Tie-2 complex in the right lung, which may provide novel therapeutic targets to attenuate PAVM formation following a SCPC. PMID:23968766

  1. Information experiences and needs in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension.

    PubMed

    Ivarsson, Bodil; Ekmehag, Björn; Sjöberg, Trygve

    2014-01-01

    Background. Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are fatal, noncurable, but treatable diseases that strongly affect the patients. Objective. To describe patients' experience of information relating to PAH or CTEPH. Methods. A qualitative method using content analysis was applied. Seventeen patients (thirteen women and four men) aged 28-73 years from a regional PAH centre were individually interviewed. Results. Three categories that describe patients' experiences of information emerged: handling of information, struggling with feelings that also affect others, and vulnerability associated with uncertainty. The patients would have welcomed more information to relatives from the healthcare professionals. Shortcomings on communicating a prognosis were experienced. The mediated information and knowledge gave the patients insight into physical or psychosocial problems. Mutual exchange of information between patients and healthcare professionals were marred by different experiences of attitudes, behaviour, and ownership. Conclusions. In the future, healthcare organizations must struggle to achieve a holistic healthcare by making it more person-centred, and they must also promote cooperation between PAH centres and local healthcare providers. It is essential to determine the most appropriate and valuable path of information and communication and, thereby, the most cost-effective management of PAH or CTEPH. PMID:25197567

  2. Coronary CT findings of coronary to bronchial arterial communication in chronic pulmonary disease.

    PubMed

    Byun, Sung Su; Park, Jae Hyung; Kim, Jeong Ho; Sung, Yon Mi; Kim, Yoon Kyung; Kim, Eun Young; Park, Eun Ah

    2015-06-01

    To describe the coronary CT findings of coronary-to-bronchial artery communication (CBAC) in chronic pulmonary disease. Coronary CT was performed in 15 patients with chronic pulmonary disease using 64-channel or greater multidetector CT. Among those patients, one or two CBACs were identified. A retrospective analysis of the CT findings was done to determine the originating artery, arterial course of the communications and other associated results. The main underlying pulmonary disease was bronchiectasis (n = 12). The origin of the CBAC was from the left atrial (n = 7) or sinoatrial (SA) nodal (n = 3) branch of the left circumflex artery in nine patients and the SA nodal branch of the right coronary artery in six patients. The CBAC was connected to the left bronchial artery in 11 patients and the right bronchial artery in five patients. The course of the CBAC passed through the interpulmonary venous bare area between reflections of the serous pericardium of the transverse and oblique sinuses in 13 patients. In three patients, it passed through the perivascular space around the left upper or lower pulmonary vein. In one patient, there were two communications-one through the interpulmonary venous bare area and the other through the perivascular space around the left lower pulmonary vein. There was no significant coronary arterial stenosis except in two patients. Bronchial arterial hypertrophy was found in all 15 patients. Detailed analysis of coronary CT can be a helpful guide for hemodynamic significance and clinical management including embolotherapy for CBAC in patients of chronic pulmonary disease with hemoptysis.

  3. Changes in the structure-function relationship of elastin and its impact on the proximal pulmonary arterial mechanics of hypertensive calves.

    PubMed

    Lammers, Steven R; Kao, Phil H; Qi, H Jerry; Hunter, Kendall; Lanning, Craig; Albietz, Joseph; Hofmeister, Stephen; Mecham, Robert; Stenmark, Kurt R; Shandas, Robin

    2008-10-01

    Extracellular matrix remodeling has been proposed as one mechanism by which proximal pulmonary arteries stiffen during pulmonary arterial hypertension (PAH). Although some attention has been paid to the role of collagen and metallomatrix proteins in affecting vascular stiffness, much less work has been performed on changes in elastin structure-function relationships in PAH. Such work is warranted, given the importance of elastin as the structural protein primarily responsible for the passive elastic behavior of these conduit arteries. Here, we study structure-function relationships of fresh arterial tissue and purified arterial elastin from the main, left, and right pulmonary artery branches of normotensive and hypoxia-induced pulmonary hypertensive neonatal calves. PAH resulted in an average 81 and 72% increase in stiffness of fresh and digested tissue, respectively. Increase in stiffness appears most attributable to elevated elastic modulus, which increased 46 and 65%, respectively, for fresh and digested tissue. Comparison between fresh and digested tissues shows that, at 35% strain, a minimum of 48% of the arterial load is carried by elastin, and a minimum of 43% of the change in stiffness of arterial tissue is due to the change in elastin stiffness. Analysis of the stress-strain behavior revealed that PAH causes an increase in the strains associated with the physiological pressure range but had no effect on the strain of transition from elastin-dominant to collagen-dominant behavior. These results indicate that mechanobiological adaptations of the continuum and geometric properties of elastin, in response to PAH, significantly elevate the circumferential stiffness of proximal pulmonary arterial tissue. PMID:18660454

  4. Detection of Heart Sounds in Children with and without Pulmonary Arterial Hypertension―Daubechies Wavelets Approach

    PubMed Central

    Elgendi, Mohamed; Kumar, Shine; Guo, Long; Rutledge, Jennifer; Coe, James Y.; Zemp, Roger; Schuurmans, Dale; Adatia, Ian

    2015-01-01

    Background Automatic detection of the 1st (S1) and 2nd (S2) heart sounds is difficult, and existing algorithms are imprecise. We sought to develop a wavelet-based algorithm for the detection of S1 and S2 in children with and without pulmonary arterial hypertension (PAH). Method Heart sounds were recorded at the second left intercostal space and the cardiac apex with a digital stethoscope simultaneously with pulmonary arterial pressure (PAP). We developed a Daubechies wavelet algorithm for the automatic detection of S1 and S2 using the wavelet coefficient ‘D6’ based on power spectral analysis. We compared our algorithm with four other Daubechies wavelet-based algorithms published by Liang, Kumar, Wang, and Zhong. We annotated S1 and S2 from an audiovisual examination of the phonocardiographic tracing by two trained cardiologists and the observation that in all subjects systole was shorter than diastole. Results We studied 22 subjects (9 males and 13 females, median age 6 years, range 0.25–19). Eleven subjects had a mean PAP < 25 mmHg. Eleven subjects had PAH with a mean PAP ≥ 25 mmHg. All subjects had a pulmonary artery wedge pressure ≤ 15 mmHg. The sensitivity (SE) and positive predictivity (+P) of our algorithm were 70% and 68%, respectively. In comparison, the SE and +P of Liang were 59% and 42%, Kumar 19% and 12%, Wang 50% and 45%, and Zhong 43% and 53%, respectively. Our algorithm demonstrated robustness and outperformed the other methods up to a signal-to-noise ratio (SNR) of 10 dB. For all algorithms, detection errors arose from low-amplitude peaks, fast heart rates, low signal-to-noise ratio, and fixed thresholds. Conclusion Our algorithm for the detection of S1 and S2 improves the performance of existing Daubechies-based algorithms and justifies the use of the wavelet coefficient ‘D6’ through power spectral analysis. Also, the robustness despite ambient noise may improve real world clinical performance. PMID:26629704

  5. Harmonics tracking of intracranial and arterial blood pressure waves.

    PubMed

    Shahsavari, Sima; McKelvey, Tomas

    2008-01-01

    Considering cardiorespiratory interaction and heart rate variability, a new approach is proposed to decompose intracranial pressure and arterial blood pressure to their different harmonics. The method is based on tracking the amplitudes of the harmonics by a Kalman filter based tracking algorithm. The algorithm takes benefit of combined frequency estimation technique which uses both Fast Fourier Transform and RR-interval detection. The result would be of use in intracranial pressure and arterial blood pressure waveform analysis as well as other investigations which need to estimate contribution of specific harmonic in above mentioned signals such as Pressure-Volume Compensatory Reserve assessment.

  6. Pulmonary vascular resistance and compliance relationship in pulmonary hypertension.

    PubMed

    Chemla, Denis; Lau, Edmund M T; Papelier, Yves; Attal, Pierre; Hervé, Philippe

    2015-10-01

    Right ventricular adaptation to the increased pulmonary arterial load is a key determinant of outcomes in pulmonary hypertension (PH). Pulmonary vascular resistance (PVR) and total arterial compliance (C) quantify resistive and elastic properties of pulmonary arteries that modulate the steady and pulsatile components of pulmonary arterial load, respectively. PVR is commonly calculated as transpulmonary pressure gradient over pulmonary flow and total arterial compliance as stroke volume over pulmonary arterial pulse pressure (SV/PApp). Assuming that there is an inverse, hyperbolic relationship between PVR and C, recent studies have popularised the concept that their product (RC-time of the pulmonary circulation, in seconds) is "constant" in health and diseases. However, emerging evidence suggests that this concept should be challenged, with shortened RC-times documented in post-capillary PH and normotensive subjects. Furthermore, reported RC-times in the literature have consistently demonstrated significant scatter around the mean. In precapillary PH, the true PVR can be overestimated if one uses the standard PVR equation because the zero-flow pressure may be significantly higher than pulmonary arterial wedge pressure. Furthermore, SV/PApp may also overestimate true C. Further studies are needed to clarify some of the inconsistencies of pulmonary RC-time, as this has major implications for our understanding of the arterial load in diseases of the pulmonary circulation.

  7. One-year follow-up of the effects of sildenafil on pulmonary arterial hypertension and veno-occlusive disease.

    PubMed

    Barreto, A C; Franchi, S M; Castro, C R P; Lopes, A A

    2005-02-01

    We hypothesized that chronic oral administration of the phosphodiesterase-5 inhibitor sildenafil could improve the exercise capacity and pulmonary hemodynamics in patients with pulmonary arterial hypertension (PAH) on the basis of previous short-term studies. We tested this hypothesis in 14 subjects with PAH, including seven patients with the idiopathic form and seven patients with atrial septal defects, but no other congenital heart abnormalities. Patients were subjected to a 6-min walk test and dyspnea was graded according to the Borg scale. Pulmonary flow and pressures were measured by Doppler echocardiography. Patients were given sildenafil, 75 mg orally three times a day, and followed up for 1 year. Sildenafil therapy resulted in the following changes: increase in the 6-min walk distance from a median value of 387 m (range 0 to 484 m) to 462 m (range 408 to 588 m; P < 0.01), improvement of the Borg dyspnea score from 4.0 (median value) to 3.0 (P < 0.01), and increased pulmonary flow (velocity-time integral) from a median value of 0.12 (range 0.08 to 0.25) to 0.23 (range 0.11 to 0.40; P < 0.01) with no changes in pulmonary pressures. In one patient with pulmonary veno-occlusive disease diagnosed by a lung biopsy, sildenafil had a better effect on the pulmonary wedge pressure than inhaled nitric oxide (15 and 29 mmHg, respectively, acute test). He walked 112 m at baseline and 408 m at one year. One patient died at 11 months of treatment. No other relevant events occurred. Thus, chronic administration of sildenafil improves the physical capacity of PAH patients and may be beneficial in selected cases of veno-occlusive disease.

  8. Novel dual endothelin receptor antagonist macitentan reverses severe pulmonary arterial hypertension in rats.

    PubMed

    Kunita-Takanezawa, Mutsumi; Abe, Kohtaro; Hirooka, Yoshitaka; Kuwabara, Yukimitsu; Hirano, Katsuya; Oka, Masahiko; Sunagawa, Kenji

    2014-11-01

    The efficacy of endothelin (ET) receptor antagonist bosentan in patients with severe pulmonary arterial hypertension (PAH) remains limited, partly because its higher doses for potential blockade of ET receptors have never been tested due to liver dysfunction. We hypothesized that rigorous blockade of ET receptors using the novel dual ET receptor antagonist macitentan would be effective in treating severe PAH without major side effects in a preclinical model appropriately representing the human disorder. In normal rats, 30 mg·kg·d of macitentan completely abolished big ET-1-induced increases in right ventricle (RV) systolic pressure. Adult male rats were injected with SU5416, a vascular endothelial growth factor blocker, and exposed to hypoxia for 3 weeks and then to normoxia for an additional 5 weeks (total 8 weeks). In intrapulmonary arterial rings isolated from rats with severe PAH, macitentan concentration dependently inhibited ET-1-induced contraction. Long-term treatment with macitentan (30 mg·kg·d, from week 3 to 8) reversed the high RV systolic pressure with preserved cardiac output. Development of RV hypertrophy, luminal occlusive lesions and medial wall thickening were also significantly improved without increasing serum levels of liver enzymes by macitentan. In conclusion, efficacious blockade of ET receptors with macitentan would reverse severe PAH without major adverse effects.

  9. Changes in pulmonary arterial wall mechanical properties and lumenal architecture with induced vascular remodeling

    NASA Astrophysics Data System (ADS)

    Molthen, Robert C.; Heinrich, Amy E.; Haworth, Steven T.; Dawson, Christopher A.

    2004-04-01

    To explore and quantify pulmonary arterial remodeling we used various methods including micro-CT, high-resolution 3-dimensional x-ray imaging, to examine the structure and function of intact pulmonary vessels in isolated rat lungs. The rat is commonly used as an animal model for studies of pulmonary hypertension (PH) and the accompanying vascular remodeling, where vascular remodeling has been defined primarily by changes in the vessel wall composition in response to hypertension inducing stimuli such as chronic hypoxic exposure (CHE) or monocrotaline (MCT) injection. Little information has been provided as to how such changes affect the vessel wall mechanical properties or the lumenal architecture of the pulmonary arterial system that actually account for the hemodynamic consequences of the remodeling. In addition, although the link between primary forms of pulmonary hypertension and inherited genetics is well established, the role that genetic coding plays in hemodynamics and vascular remodeling is not. Therefore, we are utilizing Fawn-Hooded (FH), Sprague-Dawley (SD) and Brown Norway (BN)rat strains along with unique imaging methods to parameterize both vessel distensibility and lumenal morphometry using a principal pulmonary arterial pathway analysis based on self-consistency. We have found for the hypoxia model, in addition to decreased body weight, increased hematocrit, increased right ventricular hypertrophy, the distensibility of the pulmonary arteries is shown to decrease significantly in the presence of remodeling.

  10. Measuring Arterial Blood Pressure. A Self-Contained Instructional Module.

    ERIC Educational Resources Information Center

    Schultz, Chris Ellen

    This self-contained instructional module is designed to help adult caregivers learn how to measure arterial blood pressure in the home. The module includes the following parts: objectives; pretest (with answers); four sections of instructional material covering (1) equipment, (2) cuff placement and locating the brachial artery, (3) measuring blood…

  11. Estimation of pressure gradients at renal artery stenoses

    NASA Astrophysics Data System (ADS)

    Yim, Peter J.; Cebral, Juan R.; Weaver, Ashley; Lutz, Robert J.; Vasbinder, G. Boudewijn C.

    2003-05-01

    Atherosclerotic disease of the renal artery can reduce the blood flow leading to renovascular hypertension and ischemic nephopathy. The kidney responds to a decrease in blood flow by activation of the renin-angiotensin system that increases blood pressure and can result in severe hypertension. Percutaneous translumenal angioplasty (PTA) may be indicated for treatment of renovascular hypertension (RVH). However, direct measurement of renal artery caliber and degree of stenosis has only moderate specificity for detection of RVH. A confounding factor in assessment of the proximal renal artery is that diffuse atherosclerotic disease of the distal branches of the renal artery can produce the same effect on blood-flow as atherosclerotic disease of the proximal renal artery. A methodology is proposed for estimation of pressure gradients at renal artery stenoses from magnetic resonance imaging that could improve the evaluation of renal artery disease. In the proposed methodology, pressure gradients are estimated using computational fluid dynamics (CFD) modeling. Realistic CFD models are constructed from images of vessel shape and measurements of blood-flow rates which are available from magnetic resonance angiography (MRA) and phase-contrast magnetic resonance (MR) imaging respectively. CFD measurement of renal artery pressure gradients has been validated in a physical flow-through model.

  12. Diagnostic Value of Transthoracic Echocardiography in Patients With Anomalous Origin of the Left Coronary Artery From the Pulmonary Artery.

    PubMed

    Li, Rong-Juan; Sun, Zhonghua; Yang, Jiao; Yang, Ya; Li, Yi-Jia; Leng, Zhao-Ting; Liu, Guo-Wen; Pu, Li-Hong

    2016-04-01

    Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital coronary abnormality associated with early infant mortality and sudden death in adults. Transthoracic echocardiography (TTE) plays an important role in early detection and diagnosis of ALCAPA as a noninvasive modality. However, its diagnostic value is not well studied. The purpose of this study is to determine the performance of TTE in the diagnostic assessment of ALCAPA as compared with coronary CT and invasive coronary angiography. A total of 22 patients (13 women and 9 men, mean age, 12.9 ± 19.5 years) with ALCAPA who underwent echocardiographic examination for clinical diagnosis were retrospectively reviewed and analyzed. Transthoracic echocardiographic features of ALCAPA were analyzed and its diagnostic value was compared with invasive coronary angiography and coronary CT angiography (CTA) with surgical findings serving as the gold standard. Surgery was performed in all of the patients to establish the dual coronary artery system. Five underwent the Takeuchi procedure and 17 had re-implantation of the anomalous left coronary artery. Of 20 patients, echocardiographic diagnoses were in good agreement with findings at surgery, resulting in the diagnostic accuracy of 90.9%. Two cases were misdiagnosed-one as the right coronary artery to pulmonary artery fistula and the other as rheumatic heart disease. The echocardiographic features of these patients with ALCAPA included: abnormal left coronary ostium arising from the pulmonary trunk with retrograde coronary artery flow in 20 patients; enlargement of the right coronary artery in 17 patients; abundant intercoronary septal collaterals in 17 patients; and moderate and significant mitral regurgitation in 14 patients. The diagnostic accuracy of invasive coronary angiography (in 17 patients) and coronary CTA (in 9 patients) was 100%. This study shows that TTE is an accurate, noninvasive imaging modality for

  13. 4D Flow Assessment of Pulmonary Artery Flow and Wall Shear Stress in Adult Pulmonary Arterial Hypertension: Results from Two Institutions

    PubMed Central

    Barker, Alex J; Roldán-Alzate, Alejandro; Entezari, Pegah; Shah, Sanjiv J.; Chesler, Naomi C; Wieben, Oliver; Markl, Michael; François, Christopher J

    2014-01-01

    Purpose To compare pulmonary artery flow using Cartesian and radially sampled four-dimensional flow sensitive (4D flow) magnetic resonance imaging at two institutions. Methods 19 healthy and 17 pulmonary arterial hypertension (PAH) subjects underwent a Cartesian 4D flow acquisition (institution 1) or a three-dimensional radial acquisition (institution 2). The diameter, peak systolic velocity (Vmax), peak flow (Qmax), stroke volume (SV), and wall shear stress (WSS) were computed in two-dimensional analysis planes at the main, right, and left pulmonary artery. Inter-observer variability, inter-institutional differences, flow continuity, and the hemodynamic measurements in healthy and PAH subjects were assessed. Results Vmax, Qmax, SV, and WSS at all locations were significantly lower (p<0.05) in PAH compared to healthy subjects. The limits of agreement were 0.16 m/s, 2.4 L/min, 10 mL, and 0.31 N/m2 for Vmax, Qmax, SV, and WSS, respectively. Differences between Qmax, and SV using Cartesian and radial sequences were not significant. Plane placement and acquisition exhibited isolated, site-based differences between Vmax and WSS. Conclusions 4D flow MRI was used to detect differences in pulmonary artery hemodynamics for PAH subjects. Flow and WSS in healthy and PAH subject cohorts were similar between Cartesian- and radial-based 4D flow MRI acquisitions with minimal inter-observer variability. PMID:24974951

  14. Heart and Artery Damage and High Blood Pressure

    MedlinePlus

    ... Resources Stroke More Heart and Artery Damage and High Blood Pressure Updated:Oct 22,2015 There are several harmful ... content was last reviewed on 08/04/2014. High Blood Pressure • Home • About High Blood Pressure (HBP) • Why HBP ...

  15. Arterial blood gases, pulmonary function and pathology in rats exposed to 0. 75 or 1. 0 ppM ozone

    SciTech Connect

    Pepelko, W.E.; Mattox, J.K.; Yang, Y.Y.

    1980-06-01

    Arterial blood gases, residual lung volume (RV), deflation pressure volume (PV) curves, pulmonary pathology and body weight changes were studied in rats exposed up to 14 days to either 0.75 or 1.0 ppM ozone. Arterial PO2 and body weights decreased progressively with length of exposure while PaCO2 and RV increased. The slope of the PV curve decreased in all groups exposed to ozone. Pathological changes in the lung increased in severity with concentration and length of exposure. The present findings have shown that arterial blood gas measurements represent a sensitive index of altered lung function in rats, a species very sensitive to ozone exposure.

  16. Single-trunk anomalous origin of both coronary arteries from the pulmonary artery. Diagnosis and surgical management

    SciTech Connect

    Goldblatt, E.; Adams, A.P.; Ross, I.K.; Savage, J.P.; Morris, L.L.

    1984-01-01

    The cases of two infants with heart failure and myocardial infarction because of single-trunk anomalous origin of both coronary arteries from the pulmonary artery are reported. Electrocardiography and thallium 201 imaging indicated preoperative myocardial infarction. The diagnosis was confirmed by cardiac catheterization and angiography in each case. To our knowledge these are the first reports of this diagnosis being made during life prior to attempts at surgical correction. Both patients underwent cardiac operations and the operative techniques used are described. Corrective operations for this abnormality have not been attempted previously. At autopsy radiopaque contrast material injected into the aorta confirmed flow from the aorta to the coronary arteries.

  17. A different kind of Christmas tree: anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA).

    PubMed

    Afolabi-Brown, Olayinka; Witzke, Christian; Moldovan, Raul; Pressman, Gregg

    2014-02-01

    Anomalous right coronary artery from the pulmonary artery (ARCAPA) is a rare congenital coronary anomaly that has an incidence of 0.002%. We report a case of a previously healthy female who presented to our hospital with pneumonia and was incidentally discovered to have ARCAPA. This was initially diagnosed on echocardiography by the unusual echocardiographic finding of multiple color flow Doppler signals around the right ventricular free wall and apex which were subsequently confirmed by angiography to be due to extensive collateral circulation between the left and right coronary arteries. This represents an unusual echocardiographic manifestation of this very rare condition.

  18. Carvacrol induces the apoptosis of pulmonary artery smooth muscle cells under hypoxia.

    PubMed

    Zhang, Qianlong; Fan, Kai; Wang, Peng; Yu, Juan; Liu, Ruxia; Qi, Hanping; Sun, Hongli; Cao, Yonggang

    2016-01-01

    The abnormal apoptosis of pulmonary artery smooth muscle cells (PASMCs) is an important pathophysiological process in pulmonary vascular remodeling and pulmonary arterial hypertension (PAH). Carvacrol, an essential oil compound from oregano and thyme, has displayed antimicrobial, antitumor, and antioxidant properties. Although carvacrol has pro-apoptosis properties in tumor cells, the underlying mechanisms of carvacrol in PASMC apoptosis remain unclear. Thus, in this study, we aim to investigate the role of carvacrol in pulmonary vascular remodeling and PASMC apoptosis in hypoxia. Right Ventricular Hypertrophy Measurements and pulmonary pathomorphology data show that the ratio of the heart weight/tibia length (HW/TL), the right ventricle/left ventricle plus septum (RV/LV+S) and the medial width of the pulmonary artery increased in chronic hypoxia and were reversed by carvacrol treatment under hypoxia. Additionally, carvacrol inhibited PASMC viability, attenuated oxidative stress, induced mitochondria membrane depolarization, increased the percentage of apoptotic cells, suppressed Bcl-2 expression, decreased procaspase-3 expression, promoted caspase-3 activation, and inhibited the ERK1/2 and PI3K/Akt pathway. Taken together, these findings suggest that carvacrol attenuates the pulmonary vascular remodeling and promotes PASMC apoptosis by acting on, at least in part, the intrinsic apoptotic pathway. This process might provide us new insight into the development of hypoxic pulmonary hypertension. PMID:26607464

  19. Clinical features of pulmonary artery sarcoma: A report of three cases

    PubMed Central

    Zhu, Guangfa; Pu, Xin; Guo, Hongjuang; Huang, Xiaoyong; Chen, Dong; Gan, Huili

    2016-01-01

    Pulmonary artery sarcoma (PAS) is a rare and highly malignant tumor of pulmonary artery origin. Since 1923, when the first case was reported, <300 cases have been reported worldwide. PAS has a poor prognosis, and early diagnosis with radical surgical resection offers patients with PAS the only chance of survival. However, due to its rarity and the non-specificity of its clinical manifestations and imaging presentation, PAS is frequently misdiagnosed as a pulmonary thromboembolic disease, including pulmonary thromboembolism (PTE) and chronic thromboembolic pulmonary hypertension (CTEPH). The present study reports three cases of PAS that were initially misdiagnosed as PTE or CTEPH, and were later shown to be PAS following surgery. In addition, the clinical features of these patients are examined in order to improve the differential diagnosis of PAS during the early stages of the disease, when the prognosis of patients with PAS is at its optimum. PMID:27446344

  20. Emergency Endovascular Management of Pulmonary Artery Aneurysms In Behcet's Disease: Report of Two Cases and a Review of the Literature

    SciTech Connect

    Cantasdemir, Murat; Kantarci, Fatih; Mihmanli, Ismail; Akman, Canan; Numan, Furuzan; Islak, Civan; Bozkurt, A. Kursat

    2002-12-15

    his report describes two patients with a known history of Behcet's disease in whom massive hemoptysis developed from rupture of pulmonary artery aneurysms. The high recurrence rate of complications related to pulmonary artery aneurysms and even the aneurysms themselves due to inadequacy of medical therapy and the disadvantages of surgical treatment make these aneurysms candidates for endovascular management.The pulmonary artery aneurysms reported here were successfully treated with endovascular embolization using n-butylcyanoacrylate. Pulmonary artery aneurysm embolization in Behcet's disease has been reviewed in the light of relevant literature.

  1. Hemodynamic analysis of arterial pressure oscillations in conscious rats.

    PubMed

    Julien, C; Zhang, Z Q; Cerutti, C; Barrès, C

    1995-01-01

    This study examined the contribution of rhythmic fluctuations of regional blood flow and vascular conductance to the genesis of low- (LF, 0.27-0.74 Hz) and high- (HF, 0.76-5 Hz) frequency oscillations of arterial pressure. In conscious 15-week-old male intact (n = 11), guanethidine-sympathectomized (n = 8) and chronically sinoaortic denervated (n = 7) rats, arterial pressure and regional blood flow velocities (pulsed Doppler probes) were simultaneously recorded. Indices of subdiaphragmatic aortic, hindquarters and superior mesenteric conductances were calculated on a beat-to-beat basis over a 60-min period. Spectral power was calculated in the LF and HF bands using a fast Fourier transform algorithm. Transfer function analysis was also performed to calculate coherence and phase between arterial pressure and regional flows and conductances. In the LF band, spectral power of arterial pressure was decreased by approx. 85% in sympathectomized and approx. 54% in sinoaortic denervated rats. In the HF band, spectral power did not differ between the groups. In the three groups of rats, relations between arterial pressure and blood flow were characterized by a significant coherence in the HF band with little or no phase delay (synchronous oscillations). Relations between arterial pressure and vascular conductance were characterized in intact rats by a significant coherence in the LF band and a phase delay tending to pi radians (opposite oscillations), whereas in both sympathectomized and sinoaortic denervated rats, coherence did not reach significance. It is concluded that LF oscillations of arterial pressure are mostly secondary to rhythmic fluctuations in the vasomotor sympathetic tone in several regional circulations. Part of these oscillations originate from the synchronizing influence of the baroreceptor reflex. The study also suggests that the respiratory (HF) oscillations of arterial pressure involve fluctuations in cardiac output of purely mechanical origin. PMID

  2. Responses of rabbit pulmonary arteries to hydrogen peroxide

    SciTech Connect

    Russell, J.A.; Gugino, S.F.; Giese, E.C. )

    1991-03-15

    The effects of hydrogen peroxide on isolated rabbit intrapulmonary arteries were investigated using tissue bath techniques. Exposure of resting vessels to 10{sup {minus}7}-10{sup {minus}5} M H{sub 2}O{sub 2} caused concentration-dependent contractions that were blocked by 10{sup {minus}5} M indomethacin, 3 {times} 10{sup {minus}6} M SQ 29548 or by removal of the endothelium. Addition of a single concentration of H{sub 2}O{sub 2} to resting vessels incubated with 3 {times} 10{sup {minus}6} M SQ 29548 caused slowly developing contractions that attained approximately 80% of the response to 118mM KCL. Late phase contractions were highly resistance to the inhibitory effects of 10{sup {minus}8}-10{sup {minus}5} M isoproterenol or 10{sup {minus}7}-10{sup {minus}5} M sodium nitroprusside and they persisted in calcium-free media, in vessels incubated with 5 {times} 10{sup {minus}5} M verapamil, and after removal of the endothelium. Pulmonary arteries incubated with 3 {times} 10{sup {minus}6} M SQ 29548 and contracted by 10{sup {minus}7} M phenylephrine relaxed in response to 10{sup {minus}7}-10{sup {minus}5} M H{sub 2}O{sub 2}. H{sub 2}O{sub 2}-induced relaxations were unaffected by 10{sup {minus}4} M N{omega}-nitro-L-arginine or 10{sup {minus}5}M indomethacin but were partially depressed by removal of the endothelium. The authors conclude that H{sub 2}O{sub 2} causes: an early phase contraction via release of thromboxane A2 from endothelial cells; a late-phase contraction that is endothelium-independent and probably results from the release of calcium from intracellular stores in smooth muscle cells; and an early phase relaxation that may be due to both endothelium-dependent and endothelium-independent mechanisms. The endothelium-derived relaxing factor does not appear to be nitric oxide or a dilator prostaglandin.

  3. Clinical Implications of Hemoptysis in Patients with Pulmonary Arterial Hypertension

    PubMed Central

    Cantu, Jose; Wang, Degang; Safdar, Zeenat

    2013-01-01

    Introduction Pulmonary arterial hypertension (PAH) is a disabling disease that may result in haemoptysis. Patients with congenital heart disease associated PAH (CHD-APAH) may have a survival advantage when compared with patients with other types of PAH presenting with haemoptysis. The effects of aetiology and sub-sequent management choice of haemoptysis in PAH patients is not well-defined. Methods We conducted outcome analysis in CHD-APAH vs. all other subtypes of PAH patients presenting with haemoptysis to The Methodist Hospital. Twenty-one patients were identified, thirteen patients in the CHD-APAH group and eight patients in the non-CHD group. We evaluated outcomes related to treatment (bronchial artery embolization vs. conservative management), hospital length of stay, mortality rates and survival in this cohort. Results The CHD-APAH and non-CHD groups had similar baseline demographic, haemodynamic and laboratory values except BMI was higher in the non-CHD group and haematocrit was higher in the CHD-APAH group. Twenty-eight-day mortality (0% vs. 31%) and 1-year mortality (0% vs. 54%) was lower in the CHD-APAH patients as compared with non-CHD group. A statistically significant difference was found in the survival rate in favour of CHD-APAH group for the total follow-up period (p = 0.02). Although not statistically significant, patients treated with BAE had shorter length of stay (4.0 days ± 4.0 vs. 13.7 days ± 22.5; p = 0.26). There was recurrent haemoptysis in 43% of patients treated with BAE. Conclusion Haemoptysis in PAH patients is a serious event with a high mortality rate. CHD-APAH seems to confer a survival advantage, independent of therapy utilised. Termination of haemoptysis with BAE is rapid with relatively few complications except for frequent re-bleeding episodes. Further studies are needed to determine the risk factors that may predispose PAH patients to excessive mortality from haemoptysis and to identify an optimal therapeutic modality. PMID

  4. Ambrisentan and Tadalafil Up-front Combination Therapy in Scleroderma-associated Pulmonary Arterial Hypertension

    PubMed Central

    Zamanian, Roham T.; Damico, Rachel; Lechtzin, Noah; Khair, Rubina; Kolb, Todd M.; Tedford, Ryan J.; Hulme, Olivia L.; Housten, Traci; Pisanello, Chiara; Sato, Takahiro; Pullins, Erica H.; Corona-Villalobos, Celia P.; Zimmerman, Stefan L.; Gashouta, Mohamed A.; Minai, Omar A.; Torres, Fernando; Girgis, Reda E.; Chin, Kelly; Mathai, Stephen C.

    2015-01-01

    Background: Scleroderma-associated pulmonary arterial hypertension (SSc-PAH) is a rare disease characterized by a very dismal response to therapy and poor survival. We assessed the effects of up-front combination PAH therapy in patients with SSc-PAH. Methods: In this prospective, multicenter, open-label trial, 24 treatment-naive patients with SSc-PAH received ambrisentan 10 mg and tadalafil 40 mg daily for 36 weeks. Functional, hemodynamic, and imaging (cardiac magnetic resonance imaging and echocardiography) assessments at baseline and 36 weeks included changes in right ventricular (RV) mass and pulmonary vascular resistance as co–primary endpoints and stroke volume/pulmonary pulse pressure ratio, tricuspid annular plane systolic excursion, 6-minute walk distance, and N-terminal pro-brain natriuretic peptide as secondary endpoints. Results: At 36 weeks, we found that treatment had resulted in significant reductions in median (interquartile range [IQR]) RV mass (28.0 g [IQR, 20.6–32.9] vs. 32.5 g [IQR, 23.2–41.4]; P < 0.05) and median pulmonary vascular resistance (3.1 Wood units [IQR, 2.0–5.7] vs. 6.9 Wood units [IQR, 4.0–12.9]; P < 0.0001) and in improvements in median stroke volume/pulmonary pulse pressure ratio (2.6 ml/mm Hg [IQR, 1.8–3.5] vs. 1.4 ml/mm Hg [IQR 8.9–2.4]; P < 0.0001) and mean ( ± SD) tricuspid annular plane systolic excursion (2.2 ± 0.12 cm vs. 1.65 ± 0.11 cm; P < 0.0001), 6-minute walk distance (395 ± 99 m vs. 343 ± 131 m; P = 0.001), and serum N-terminal pro-brain natriuretic peptide (647 ± 1,127 pg/ml vs. 1,578 ± 2,647 pg/ml; P < 0.05). Conclusions: Up-front combination therapy with ambrisentan and tadalafil significantly improved hemodynamics, RV structure and function, and functional status in treatment-naive patients with SSc-PAH and may represent a very effective therapy for this patient population. In addition, we identified novel hemodynamic and imaging biomarkers

  5. An Alternative Surgical Technique for Repair of Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery

    PubMed Central

    Kim, Young-su; Lee, Mina; Cho, Yang Hyun; Yang, Ji-Hyuk; Jun, Tae-Gook

    2014-01-01

    Background For the surgical management of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA), there have been various techniques that reduce the tension and kinking of the coronary artery during reimplantation to the aorta. The aim of this study is to describe the results of our modified technique of coronary reimplantation for the treatment of ALCAPA. Methods Between October 2003 and February 2011, seven patients underwent coronary reimplantation with the modified technique (tubing formation with the sinus wall of the pulmonary artery and trapdoor formation at the site of implantation in the aorta). The median follow-up duration was 52 months (range, 4 to 72 months). Clinical outcomes and serial echocardiographic data were reviewed. Results There was no mortality. One patient had a small amount of cerebral hemorrhage postoperatively and improved without any sequelae. Another patient had left diaphragm palsy and underwent diaphragm plication. Follow-up echocardiogram showed that all patients had normal ventricular function without chamber enlargement. Conclusion Our modified technique (tubing formation with the sinus wall of the pulmonary artery and trapdoor formation at the site of implantation in the aorta) demonstrated successful clinical outcomes. We conclude that this surgical technique can be a potential alternative for the treatment of ALCAPA. PMID:25207218

  6. Novel biomarkers for risk stratification in pulmonary arterial hypertension

    PubMed Central

    Zelniker, Thomas; Uhlmann, Lorenz; Spaich, Sebastian; Friedrich, Jörg; Preusch, Michael R.; Meyer, Franz J.; Katus, Hugo A.

    2015-01-01

    Risk stratification in pulmonary arterial hypertension (PAH) is paramount to identifying individuals at highest risk of death. So far, there are only limited parameters for prognostication in patients with PAH. 95 patients with confirmed PAH were included in the present analysis and followed for a total of 4 years. Blood samples were analysed for serum levels of N-terminal pro-brain natriuretic peptide, high-sensitivity troponin T (hsTnT), pro-atrial natriuretic peptide (proANP), growth differentiation factor 15, soluble fms-like tyrosine kinase 1 and placental growth factor. 27 (28.4%) patients died during a follow-up of 4 years. Levels of all tested biomarkers, except for placental growth factor, were significantly elevated in nonsurvivors compared with survivors. Receiver operating characteristic analyses demonstrated that cardiac biomarkers had the highest power in predicting mortality. In particular, proANP exhibited the highest area under the curve, followed by N-terminal pro-brain natriuretic peptide and hsTnT. Furthermore, proANP and hsTnT added significant additive prognostic value to the established markers in categorical and continuous net reclassification index. Moreover, after Cox regression, proANP (hazard ratio (HR) 1.91), hsTnT (HR 1.41), echocardiographic right ventricular impairment (HR 1.30) and 6-min walk test (HR 0.97 per 10 m) remained the only significant parameters in prognostication of mortality. Our data suggest benefits of the implementation of proANP and hsTnT as additive biomarkers for risk stratification in patients with PAH.

  7. The heart and pulmonary arterial hypertension in systemic sclerosis.

    PubMed

    Vandecasteele, Els H; De Pauw, Michel; Brusselle, Guy; Decuman, Saskia; Piette, Yves; De Keyser, Filip; Smith, V

    2016-02-01

    Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by vasculopathy and progressive fibrosis of the skin and visceral organs (gastrointestinal tract, heart, kidneys and lungs). Although the prevalence is low, SSc is a disease with high morbidity and mortality. Since pulmonary arterial hypertension (PAH) associated with SSc (SSc-PAH) and clinically evident cardiac involvement is associated with increased mortality, the cardiac complications and PAH in SSc are reviewed. Both diffuse cutaneous (DcSSc) and limited cutaneous (LcSSc) subgroups are at risk for cardiac involvement and SSc-PAH. Cardiac involvement can be divided in pericardial involvement, myocardial involvement and rhythm disturbances and mostly occurs asymptomatically. However, when symptomatic, it is associated with a poor prognosis. Screening for asymptomatic cardiac involvement should be considered in SSc in order to initiate treatment in an early stage. However, there are no randomized controlled trials on treatment options for cardiac involvement in SSc. SSc-PAH is a devastating complication of SSc, which can develop early in DcSSc and LcSSc. Screening for PAH should be performed since screening leads to earlier diagnosis and earlier treatment is associated with a better prognosis. Today, screening is performed by clinical judgement and echocardiography. Recently the DETECT algorithm, a 2-step screening algorithm is proposed in a SSc-subgroup at increased risk for PAH, but further validation is needed. Despite current treatment options with prostacyclins, endothelin-1 receptor antagonists and phosphodiesterase type-5 inhibitors, mortality remains high. Several promising new treatment options for PAH are evaluated in phase II and III clinical trials. PMID:27075793

  8. Phase I safety study of ranolazine in pulmonary arterial hypertension

    PubMed Central

    Schilz, Robert; Mediratta, Anuj; Addetia, Karima; Coslet, Sandra; Thomeas, Vasiliki; Gillies, Hunter; Oudiz, Ronald J.

    2015-01-01

    Abstract Pulmonary arterial hypertension (PAH) causes right ventricular ischemia, dysfunction, and failure. PAH patients may benefit from antianginal agents based on a shared pathophysiology with left ventricular ischemia. A single-center, randomized, placebo-controlled trial (1∶1) to assess the acute vasoreactivity and safety of ranolazine in PAH was conducted. Plasma samples for pharmacokinetic (PK) studies were drawn during hemodynamic measurements at 0, 60, 90, 120, 240, and 360 minutes from a Swan-Ganz catheter. All patients received 500-mg doses, uptitrated to 1,000 mg at week 4, monthly evaluations, and a complete objective assessment after 12 weeks, followed by an open-label extension. Thirteen patients were randomized and 12 enrolled (6 ranolazine, 6 placebo). All patients completed the acute phase; 10 completed the 12-week study. There were no acute changes in invasive hemodynamics. At 12 weeks ranolazine was well tolerated. Only 1 of the 5 patients on ranolazine had a serum concentration considered to be in the therapeutic range. Two serious adverse events required early withdrawal (both in the ranolazine group); gastrointestinal complaints were the most common adverse event. Efficacy measures did not demonstrate any differences between treatment groups. During the open-label trial, 2 additional patients reached a therapeutic concentration. Ranolazine in PAH appears safe, without acute hemodynamic effects after a 500-mg dose. Ranolazine administrated to PAH patients receiving background PAH therapies did not consistently reach therapeutic levels. Future studies should first perform PK analysis in PAH patients receiving PAH therapies and explore the safety and tolerability of the higher doses perhaps necessary to achieve therapeutic levels in PAH patients. (Trial registration: Clinicaltrials.gov identifier NCT01757808.) PMID:26697176

  9. Bisoprolol in idiopathic pulmonary arterial hypertension: an explorative study.

    PubMed

    van Campen, Jasmijn S J A; de Boer, Karin; van de Veerdonk, Mariëlle C; van der Bruggen, Cathelijne E E; Allaart, Cor P; Raijmakers, Pieter G; Heymans, Martijn W; Marcus, J Tim; Harms, Hendrik J; Handoko, M Louis; de Man, Frances S; Vonk Noordegraaf, Anton; Bogaard, Harm-Jan

    2016-09-01

    While beta-blockers are considered contraindicated in pulmonary arterial hypertension (PAH), the prognostic significance of sympathetic nervous system over-activity suggests a potential benefit of beta-blocker therapy. The aim of this randomised, placebo-controlled, crossover, single c