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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. Diurnal variation of pulmonary artery pressure in chronic heart failure.

    PubMed Central

    Gibbs, J S; Cunningham, D; Shapiro, L M; Park, A; Poole-Wilson, P A; Fox, K M

    1989-01-01

    Variation in pulmonary artery pressure has important consequences for the interpretation of isolated pressure measurements in patients with chronic heart failure. To investigate the nature of diurnal variation in pulmonary artery pressure in chronic heart failure, eight angina-free men (aged 50-72 years) with treated chronic heart failure caused by ischaemic heart disease underwent continuous ambulatory pulmonary artery pressure recording by a transducer tipped catheter. The mean (1 SD) daytime pulmonary artery pressure was 29.6 (5.0) mm Hg systolic and 13.7 (5.6) mm Hg diastolic. The mean change in pressure from day to night was +5.1 (3.2) mm Hg systolic and +3.8 (1.7) mm Hg diastolic; and the mean change from standing to lying +9.3 (2.3) mm Hg systolic and +6.4 (2.1) mm Hg diastolic. In six of the eight patients there was considerable rise in pulmonary artery pressure at night, but in the two patients with the most severe symptoms there was no nocturnal rise. In patients with chronic heart failure, nocturnal pulmonary artery pressure is not determined by postural change alone. But interpretation of isolated pulmonary artery pressure measurements must take the posture of the patient into account. PMID:2757872

  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. 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

  5. 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

  6. 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. PMID:17652313

  7. 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. PMID:26922398

  8. Intraobserver variation in Doppler ultrasound assessment of pulmonary artery pressure.

    PubMed

    Subhedar, N V; Shaw, N J

    1996-07-01

    Intraobserver variation associated with the non-invasive assessment of pulmonary artery pressure (PAP), using measurement of pulmonary artery Doppler derived systolic time intervals, was investigated. Forty pairs of independent ultrasound examinations of the pulmonary artery were performed by a single observer in 20 preterm infants, median gestation 27 weeks (range 24-31 weeks). Median age at study was 17 days (range 1-47 days). paired measurements of acceleration time (AT), ratio between acceleration time and right ventricular ejection time (AT:RVET), corrected AT, and corrected AT:RVET were compared to assess intraobserver agreement. For the corrected AT:RVET ratio, the mean percentage difference between observations was -0.9% (95% confidence intervals -5.0 to 3.1%). The limits of agreement for the two measurements were -26.3 to 24.5%. The coefficient of repeatability was 25.4%. Variation for other indices was similar. Non-invasive assessment of PAP using Doppler derived systolic time intervals is associated with considerable intraobserver variation. PMID:8795360

  9. Impact of age on pulmonary artery systolic pressures at rest and with exercise

    PubMed Central

    Sachdev, Arun; Villarraga, Hector R; Ammash, Naser M; Oh, Jae K; McGoon, Michael D; Pellikka, Patricia A; McCully, Robert B

    2016-01-01

    Aim It is not well known if advancing age influences normal rest or exercise pulmonary artery pressures. The purpose of the study was to evaluate the association of increasing age with measurements of pulmonary artery systolic pressure at rest and with exercise. Subjects and methods A total of 467 adults without cardiopulmonary disease and normal exercise capacity (age range: 18–85 years) underwent symptom-limited treadmill exercise testing with Doppler measurement of rest and exercise pulmonary artery systolic pressure. Results There was a progressive increase in rest and exercise pulmonary artery pressures with increasing age. Pulmonary artery systolic pressures at rest and with exercise were 25±5mmHg and 33±9mmHg, respectively, in those <40 years, and 30±5mmHg and 41±12mmHg, respectively, in those ≥70 years. While elevated left-sided cardiac filling pressures were excluded by protocol design, markers of arterial stiffness associated with the age-dependent effects on pulmonary pressures. Conclusion These data demonstrate that in echocardiographically normal adults, pulmonary artery systolic pressure increases with advancing age. This increase is seen at rest and with exercise. These increases in pulmonary pressure occur in association with decreasing transpulmonary flow and increases in systemic pulse pressure, suggesting that age-associated blood vessel stiffening may contribute to these differences in pulmonary artery systolic pressure. PMID:27343212

  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. PMID:25755701

  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. The haemodynamic significance of asymptomatic ST segment depression assessed by ambulatory pulmonary artery pressure monitoring.

    PubMed Central

    Levy, R D; Shapiro, L M; Wright, C; Mockus, L J; Fox, K M

    1986-01-01

    A transducer-tipped catheter with simultaneous frequency modulated electrocardiograms and a miniaturised tape recorder was used to record ambulatory pulmonary artery pressure for 24-48 hours in 19 men (mean age 57.7) with clinical and angiographic evidence of coronary artery disease. Sixty seven episodes of ST segment depression (greater than 1 mm) were recorded. Thirty five were accompanied by pain of which six occurred at night; in 34 pulmonary artery diastolic pressure rose significantly. In all but two of the 32 episodes of painless ST segment depression (four of which were at night) there was a significant rise in pulmonary artery diastolic pressure. No such rise was found in six normal subjects during exertion. ST segment changes tended to occur before (24 episodes) or at the same time (27 episodes) as changes in pulmonary artery diastolic pressure. ST segment depression followed an increase in pulmonary artery diastolic pressure in only 13 episodes. The times to maximum ST depression and maximum pulmonary artery diastolic pressure rise were similar. Painful and painless ST segment depression could not be distinguished on the basis of the configuration of the ST segment or in terms of the changes in the pulmonary artery diastolic pressure. PMID:3801243

  14. The haemodynamic significance of asymptomatic ST segment depression assessed by ambulatory pulmonary artery pressure monitoring.

    PubMed

    Levy, R D; Shapiro, L M; Wright, C; Mockus, L J; Fox, K M

    1986-12-01

    A transducer-tipped catheter with simultaneous frequency modulated electrocardiograms and a miniaturised tape recorder was used to record ambulatory pulmonary artery pressure for 24-48 hours in 19 men (mean age 57.7) with clinical and angiographic evidence of coronary artery disease. Sixty seven episodes of ST segment depression (greater than 1 mm) were recorded. Thirty five were accompanied by pain of which six occurred at night; in 34 pulmonary artery diastolic pressure rose significantly. In all but two of the 32 episodes of painless ST segment depression (four of which were at night) there was a significant rise in pulmonary artery diastolic pressure. No such rise was found in six normal subjects during exertion. ST segment changes tended to occur before (24 episodes) or at the same time (27 episodes) as changes in pulmonary artery diastolic pressure. ST segment depression followed an increase in pulmonary artery diastolic pressure in only 13 episodes. The times to maximum ST depression and maximum pulmonary artery diastolic pressure rise were similar. Painful and painless ST segment depression could not be distinguished on the basis of the configuration of the ST segment or in terms of the changes in the pulmonary artery diastolic pressure. PMID:3801243

  15. Expert critical care nurses' use of pulmonary artery pressure monitoring.

    PubMed

    Aitken, L M

    2000-08-01

    Critical care nurses make numerous complex decisions during their day-to-day practice. General themes in previous decision-making studies have included the influence of knowledge and previous experience, the increasing complexity of decisions made and the change in decision-making processes used as the nurse progresses from a novice to an expert practitioner. This paper reports one component of a study which used a concept attainment framework to determine what data were used by eight expert critical care nurses in relation to haemodynamic monitoring. Results indicated that pulmonary artery pressure monitoring was used to attain the concepts of preload, cardiac output and blood pressure. In addition, participants used few clinical assessment attributes, but collected a large number of attributes which they arranged around three to five central concepts and took a broad view of haemodynamic assessment. One participant did not display many of the decision-making features normally associated with an expert practitioner. In conclusion, expert critical care nurses process an immense amount of data in a short space of time. However, they may not use all available data. Evidence suggests not all nurses who practise in the field for a lengthy period reach the level of an expert. PMID:10922186

  16. Accuracy of Doppler-Echocardiographic Mean Pulmonary Artery Pressure for Diagnosis of Pulmonary Hypertension

    PubMed Central

    Er, Fikret; Ederer, Stefan; Nia, Amir M.; Caglayan, Evren; Dahlem, Kristina M.; Semmo, Nasser; Gassanov, Natig

    2010-01-01

    Background The validity of Doppler echocardiographic (DE) measurement of systolic pulmonary artery pressure (sPAP) has been questioned. Recent studies suggest that mean pulmonary artery pressure (mPAP) might reflect more accurately the invasive pressures. Methodology/Principal Findings 241 patients were prospectively studied to evaluate the diagnostic accuracy of mPAP for the diagnosis of PH. Right heart catheterization (RHC) and DE were performed in 164 patients mainly for preoperative evaluation of heart valve dysfunction. The correlation between DE and RHC was better when mPAP (r = 0.93) and not sPAP (r = 0.81) was assessed. Bland-Altman analysis revealed a smaller variation of mPAP than sPAP. The following ROC analysis identified that a mPAP≥25.5 mmHg is useful for the diagnosis of PH. This value was validated in an independent cohort of patients (n = 50) with the suspicion of chronic-thromboembolic pulmonary hypertension. The calculated diagnostic accuracy was 98%, based on excellent sensitivity of 98% and specificity of 100%. The corresponding positive and negative predictive values were 100%, respectively 88%. Conclusion mPAP has been found to be highly accurate for the initial diagnosis of PH. A cut-off value of 25.5 mmHg might be helpful to avoid unnecessary RHC and select patients in whom RHC might be beneficial. PMID:21179417

  17. 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

  18. Increased Red Blood Cell Stiffness Increases Pulmonary Vascular Resistance and Pulmonary Arterial Pressure.

    PubMed

    Schreier, David A; Forouzan, Omid; Hacker, Timothy A; Sheehan, John; Chesler, Naomi

    2016-02-01

    Patients with sickle cell anemia (SCD) and pulmonary hypertension (PH) have a significantly increased risk of sudden death compared to patients with SCD alone. Sickled red blood cells (RBCs) are stiffer, more dense, more frequently undergo hemolysis, and have a sixfold shorter lifespan compared to normal RBCs. Here, we sought to investigate the impact of increased RBC stiffness, independent of other SCD-related biological and mechanical RBC abnormalities, on the hemodynamic changes that ultimately cause PH and increase mortality in SCD. To do so, pulmonary vascular impedance (PVZ) measures were recorded in control C57BL6 mice before and after ∼50 μl of blood (Hct = 45%) was extracted and replaced with an equal volume of blood containing either untreated RBCs or RBCs chemically stiffened with glutaraldehyde (Hct = 45%). Chemically stiffened RBCs increased mean pulmonary artery pressure (mPAP) (13.5 ± 0.6 mmHg at baseline to 23.2 ± 0.7 mmHg after the third injection), pulmonary vascular resistance (PVR) (1.23 ± 0.11 mmHg*min/ml at baseline to 2.24 ± 0.14 mmHg*min/ml after the third injection), and wave reflections (0.31 ± 0.02 at baseline to 0.43 ± 0.03 after the third injection). Chemically stiffened RBCs also decreased cardiac output, but did not change hematocrit, blood viscosity, pulmonary arterial compliance, or heart rate. The main finding of this study is that increased RBC stiffness alone affects pulmonary pulsatile hemodynamics, which suggests that RBC stiffness plays an important role in the development of PH in patients with SCD. PMID:26638883

  19. 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

  20. Transpulmonary pressure gradient verifies pulmonary hypertension is initiated by increased arterial resistance in broilers.

    PubMed

    Lorenzoni, A G; Anthony, N B; Wideman, R F

    2008-01-01

    Previous hemodynamic evaluations demonstrated that pulmonary arterial pressure (PAP) is higher in broilers that are susceptible to pulmonary hypertension syndrome (PHS, ascites) than in broilers that are resistant to PHS. We compared key pulmonary hemodynamic parameters in broilers from PHS-susceptible and PHS-resistant lines (selected for 12 generations under hypobaric hypoxia) and in broilers from a relaxed (control) line. In experiment 1 the PAP was measured in male broilers in which a flow probe positioned on one pulmonary artery permitted the determination of cardiac output and pulmonary vascular resistance (PVR). The PAP and relative PVR were higher in susceptible broilers than in relaxed and resistant broilers, whereas absolute and relative cardiac output did not differ between lines. In experiment 2 male and female broilers from the 3 lines were catheterized to measure pressures in the wing vein, right atrium, right ventricle, pulmonary artery, and pulmonary veins (WP, wedge pressure). The transpulmonary pressure gradient (TPG) was calculated as (PAP-WP), with PAP quantifying precapillary pressure and WP approximating postcapillary pulmonary venous pressure. When compared with resistant and relaxed broilers, PAP values in susceptible broilers were > or =10 mmHg higher, TPG values were > or =8 mmHg higher, and WP values were < or =2 mmHg higher, regardless of sex. The combined hemodynamic criteria (elevated PAP and PVR combined with a proportionally elevated TPG) demonstrate that susceptibility to PHS can be attributed primarily to pulmonary arterial hypertension associated with increased precapillary (arteriole) resistance rather than to pulmonary venous hypertension caused by elevated postcapillary (venous and left atrial) resistance. PMID:18079461

  1. 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

  2. Haemodynamic response to myocardial ischaemia during unrestricted activity, exercise testing, and atrial pacing assessed by ambulatory pulmonary artery pressure monitoring.

    PubMed

    Levy, R D; Shapiro, L M; Wright, C; Mockus, L; Fox, K M

    1986-07-01

    Ambulatory pulmonary artery pressure monitoring by means of a transducer tipped catheter with a simultaneous frequency modulated electrocardiogram and a miniaturised tape recorder was used to study the haemodynamic implications of ST segment depression in patients with coronary artery disease. Nineteen male patients (mean (SD) age 58 (11) years) with clinical and angiographic evidence of coronary artery disease were studied together with six controls. Changes in the ST segment and pulmonary artery diastolic pressure during treadmill exercise, atrial pacing, and unrestricted ambulant activity were analysed. During exercise, pulmonary artery diastolic pressure rose significantly in patients with coronary artery disease but not in the controls. One patient with ST depression greater than 1 mm did not have a rise in pulmonary artery diastolic pressure on exercise; two had a rise in pulmonary artery diastolic pressure with no ST segment change despite severe angina. The pulmonary artery diastolic pressure tended to rise before or simultaneously with the onset of ST segment depression. The haemodynamic response to atrial pacing was similar in normal controls and patients with coronary artery disease. During ambulatory monitoring there were 29 episodes of ST segment depression all of which were associated with a rise in pulmonary artery diastolic pressure and chest pain. The onset of ST segment depression occurred before a rise in pulmonary artery diastolic pressure in 11 episodes, was simultaneous with it in 11, and followed it in seven episodes. During exercise and ambulatory monitoring there was a correlation between the magnitude of ST segment depression and the rise in pulmonary artery diastolic pressure. Pain was a late feature during exercise, atrial pacing, and anginal episodes. This technique for the first time allows the relation between ST segment changes and haemodynamic alterations in left ventricular function to be assessed in ambulant patients with coronary

  3. 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

  4. 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

  5. The compliance of the porcine pulmonary artery depends on pressure and heart rate

    PubMed Central

    Kornet, L; Jansen, J R C; te Nijenhuis, F C A M; Langewouters, G J; Versprille, A

    1998-01-01

    The influence of mean pulmonary arterial pressure (mean Ppa) on dynamic (Cd) and pseudo-static compliance (Cps) of the pulmonary artery was studied at a constant and a changing heart rate. Cd is the change in cross-sectional area (CSA) relative to the change in Ppa throughout a heart cycle. Cps is the change in mean CSA relative to the change in mean Ppa. If Cd is known, pulmonary blood flow can be computed from the Ppa using a windkessel model. We investigated whether Cps can be interchanged with Cd. In nine anaesthetized pigs, we determined the mean CSA and Cd of the pulmonary artery at various Ppa levels, ranging from approximately 30 to 10 mmHg, established by bleeding. Two series of measurements were carried out, one series at a spontaneously changing heart rate (n = 9) and one series at a constant heart rate (n = 6). To determine CSA a conductance method was used. Cps depended on pressure. The mean CSA versus mean Ppa curves were sigmoid and steepest in the series with the increasing heart rate (established by bleeding). The CSA versus Ppa loop during a heart cycle, giving Cd, was approximately linear and almost closed. The Cdversus mean Ppa relationship was bell shaped. Its width was smaller if the heart rate increased during the series of measurements. The pressure, where Cd was maximum, was higher at higher heart rates. Furthermore, the maximum Cd was not affected by the heart rate. Because the pulmonary artery constricts with increasing heart rate, Cps will be overestimated during procedures where heart rate increases. Cd should be determined on a beat-to-beat basis to calculate flow because it changes with mean pulmonary arterial pressure and heart rate. PMID:9769432

  6. The compliance of the porcine pulmonary artery depends on pressure and heart rate.

    PubMed

    Kornet, L; Jansen, J R; Nijenhuis, F C; Langewouters, G J; Versprille, A

    1998-11-01

    1. The influence of mean pulmonary arterial pressure (mean Ppa) on dynamic (Cd) and pseudo-static compliance (Cps) of the pulmonary artery was studied at a constant and a changing heart rate. Cd is the change in cross-sectional area (CSA) relative to the change in Ppa throughout a heart cycle. Cps is the change in mean CSA relative to the change in mean Ppa. If Cd is known, pulmonary blood flow can be computed from the Ppa using a windkessel model. We investigated whether Cps can be interchanged with Cd. 2. In nine anaesthetized pigs, we determined the mean CSA and Cd of the pulmonary artery at various Ppa levels, ranging from approximately 30 to 10 mmHg, established by bleeding. Two series of measurements were carried out, one series at a spontaneously changing heart rate (n = 9) and one series at a constant heart rate (n = 6). To determine CSA a conductance method was used. 3. Cps depended on pressure. The mean CSA versus mean Ppa curves were sigmoid and steepest in the series with the increasing heart rate (established by bleeding). The CSA versus Ppa loop during a heart cycle, giving Cd, was approximately linear and almost closed. The Cd versus mean Ppa relationship was bell shaped. Its width was smaller if the heart rate increased during the series of measurements. The pressure, where Cd was maximum, was higher at higher heart rates. Furthermore, the maximum Cd was not affected by the heart rate. 4. Because the pulmonary artery constricts with increasing heart rate, Cps will be overestimated during procedures where heart rate increases. Cd should be determined on a beat-to-beat basis to calculate flow because it changes with mean pulmonary arterial pressure and heart rate. PMID:9769432

  7. A computational study of pressure wave reflections in the pulmonary arteries.

    PubMed

    Qureshi, M Umar; Hill, N A

    2015-12-01

    Experiments using wave intensity analysis suggest that the pulmonary circulation in sheep and dogs is characterized by negative or open-end type wave reflections, that reduce the systolic pressure. Since the pulmonary physiology is similar in most mammals, including humans, we test and verify this hypothesis by using a subject specific one-dimensional model of the human pulmonary circulation and a conventional wave intensity analysis. Using the simulated pressure and velocity, we also analyse the performance of the P-U loop and sum of squares techniques for estimating the local pulse wave velocity in the pulmonary arteries, and then analyse the effects of these methods on linear wave separation in the main pulmonary artery. P-U loops are found to provide much better estimates than the sum of squares technique at proximal locations, but both techniques accumulate progressive error at distal locations away from heart, particularly near junctions. The pulse wave velocity estimated using the sum of squares method also gives rise to an artificial early systolic backward compression wave. Finally, we study the influence of three types of pulmonary hypertension viz. pulmonary arterial hypertension, chronic thromboembolic pulmonary hypertension and pulmonary hypertension associated with hypoxic lung disease. Simulating these conditions by changing the relevant parameters in the model and then applying the wave intensity analysis, we observe that for each group the early systolic backward decompression wave reflected from proximal junctions is maintained, whilst the initial forward compression and the late systolic backward compression waves amplify with increasing pathology and contribute significantly to increases in systolic pressure. PMID:25754476

  8. Prognostic Value of the Pre-Transplant Diastolic Pulmonary Artery Pressure to Pulmonary Capillary Wedge Pressure Gradient (DPG) in Cardiac Transplant Recipients with Pulmonary Hypertension

    PubMed Central

    Tedford, Ryan J.; Beaty, Claude A.; Mathai, Stephen C.; Kolb, Todd M.; Damico, Rachel; Hassoun, Paul M.; Leary, Peter J.; Kass, David A.; Shah, Ashish S.

    2014-01-01

    Background Although the transpulmonary gradient (TPG) and pulmonary vascular resistance (PVR) are commonly used to differentiate heart failure patients with pulmonary vascular disease from those with passive pulmonary hypertension (PH), elevations in TPG and PVR may not always reflect pre-capillary PH. Recently, it has been suggested an elevated diastolic pulmonary artery pressure to pulmonary capillary wedge pressure gradient (DPG) may be better indicator of pulmonary vascular remodeling, and therefore, may be of added prognostic value in patients with PH being considered for cardiac transplantation. Methods Utilizing the United Network for Organ Sharing (UNOS) database, we retrospectively reviewed all primary adult (age >17 years) orthotropic heart transplant recipients between 1998–2011. All patients with available pre-transplant hemodynamic data and PH (mean pulmonary artery pressure ≥ 25mmHg were included (n=16,811). We assessed the prognostic value of DPG on post-transplant survival in patients with PH and an elevated TPG and PVR. Results In patients with PH and a TPG > 12mmHg (n=5,827), there was no difference in survival at up to 5 years post-transplant between high (defined as ≥3, ≥5, ≥7, or ≥10mmHg) and low DPG groups (<3, <5, <7, or <10mmHg). Similarly, there was no difference in survival between high and low DPG groups in those with a PVR > 3 wood units (n=6,270). Defining an elevated TPG as > 15mmHg (n=3,065) or an elevated PVR > 5 (n=1783) yielded similar results. Conclusions In the largest analysis to date investigating the prognostic value of DPG, an elevated DPG had no impact on post-transplant survival in patients with PH and an elevated TPG and PVR. PMID:24462554

  9. 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

  10. Continuous ambulatory pulmonary artery pressure monitoring. A new method using a transducer tipped catheter and a simple recording system.

    PubMed

    Levy, R D; Cunningham, D; Shapiro, L M; Wright, C; Mockus, L; Fox, K M

    1986-04-01

    A transducer tipped catheter and simple recording system were used for the continuous measurement of ambulatory pulmonary artery pressure. The pulmonary artery pressure was recorded on a miniaturised tape recorder and replayed via an optical writer. Pulmonary arterial systolic and diastolic pressures can be analysed on a beat to beat basis. Continuous ambulatory monitoring was performed for a total 288 hours in 13 patients who were undergoing routine investigation for coronary artery disease. There was less than 1% zero drift and 0.25% linearity error per full scale pressure. The frequency response of the entire system was flat to 8 Hz with a linear phase delay. The transducer tipped catheter and a conventional fluid-filled system were used to measure left ventricular and pulmonary artery end diastolic pressures in eight patients. The correlation between the results obtained by the two methods was excellent. This method could be used at any centre equipped for ambulatory electrocardiographic monitoring. PMID:3964499

  11. Remote telemonitoring for patients with heart failure: might monitoring pulmonary artery pressure become routine?

    PubMed

    Hutchinson, Kate; Pellicori, Pierpaolo; Dierckx, Riet; Cleland, John G F; Clark, Andrew L

    2014-08-01

    Heart failure is one of the most important medical problems facing societies in developed economies and its prevalence is predicted to rise inexorably in the next few decades as longevity increases. Worsening heart failure leading to hospitalization is associated with a poor prognosis and imposes a substantial burden on health care resources and budgets. Interventions that can stabilize patients should reduce the need for hospitalization and improve prognosis. This might be facilitated by frequent self-monitoring of clinical and physiological variables by patients themselves at home. Rising pulmonary artery pressure is an early sign of cardiac decompensation that may be more sensitive than conventional methods of patient assessment and thus allow early adjustment of medical therapy to avoid hospitalizations and improve patient outcomes. Remote monitoring of pulmonary artery pressure is now possible using devices that can be implanted percutaneously. This innovative technology could become a routine part of the management of heart failure in the next few decades. PMID:24984847

  12. The effects of hemolyzed blood on pulmonary and systemic arterial pressure and heart rate of the dog.

    PubMed Central

    McCrady, J D; Pendery, G B; Camp, B J; Clark, D R; Smith, B P; Davis, R H; Moody, G M

    1978-01-01

    The injection of hemolyzed blood into the venous system of the dog produced a rise in the pulmonary arterial pressure and a fall in the systemic arterial pressure. There were variable changes in the heart rate. Comparison with serotonin injections indicated that the above responses were produced by factors other than serotonin. Images Fig. 1. PMID:647460

  13. 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

  14. Effects of physical training on pulmonary arterial pressure during exercise under hypobaric hypoxia in rats

    NASA Astrophysics Data System (ADS)

    Kashimura, Osamu; Sakai, Akio

    1991-12-01

    In this investigation, we assessed the effects of physical training on exercise-induced systemic and pulmonary hemodynamic changes under hypobaric hypoxia in catheter-implanted rats. We made continuous measurements of pulmonary and systemic arterial pressures during progressive treadmill exercises under hypobaric hypoxia (equivalent to altitudes of 2500 and 5500 m) in 46 control and 41 trained rats. Trained rats were exercised on two running schedules: 4 weeks (4-trained) and 6 weeks (6-trained). Both these groups of trained rats were exercised for the same length of running time each day. The increase in resting mean pulmonary arterial pressure(overline {P_{pa} } ) with increasing equivalent altitude was lower in the two trained groups than in the control group. The increase in(overline {P_{pa} } ) with progressive intensity of exercise was lower in the 6-trained than in the 4-trained and control groups at 610 and 2500 m. The 6-trained rats showed higher pH, P a CO 2 and O2 saturation in their blood than did the control group, whereas the P a O 2 was less. Lung tissue cyclic AMP concentration at rest was higher in the 6-trained than in the control group. Finally, it may be noted that exercise-induced lung tissue vasodilator responses seem to be enhanced in well-trained rats under both normobaric normoxia and hypobaric hypoxia. This study indicates that exercise training may be useful in preventing pulmonary hypertension resulting from both hypoxia and exercise.

  15. 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

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

    PubMed

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

    2016-06-30

    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

  17. 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

  18. Elevated pulmonary artery pressure and brain natriuretic peptide in high altitude pulmonary edema susceptible non-mountaineers

    PubMed Central

    Gupta, Rajinder K.; Himashree, G.; Singh, Krishan; Soree, Poonam; Desiraju, Koundinya; Agrawal, Anurag; Ghosh, Dishari; Dass, Deepak; Reddy, Prassana K.; Panjwani, Usha; Singh, Shashi Bala

    2016-01-01

    Exaggerated pulmonary pressor response to hypoxia is a pathgonomic feature observed in high altitude pulmonary edema (HAPE) susceptible mountaineers. It was investigated whether measurement of basal pulmonary artery pressure (Ppa) and brain natriuretic peptide (BNP) could improve identification of HAPE susceptible subjects in a non-mountaineer population. We studied BNP levels, baseline hemodynamics and the response to hypoxia (FIo2 = 0.12 for 30 min duration at sea level) in 11 HAPE resistant (no past history of HAPE, Control) and 11 HAPE susceptible (past history of HAPE, HAPE-S) subjects. Baseline Ppa (19.31 ± 3.63 vs 15.68 ± 2.79 mm Hg, p < 0.05) and plasma BNP levels (52.39 ± 32.9 vs 15.05 ± 9.6 pg/ml, p < 0.05) were high and stroke volume was less (p < 0.05) in HAPE-S subjects compared to control. Acute hypoxia produced an exaggerated increase in heart rate (p < 0.05), mean arterial pressure (p < 0.05) and Ppa (28.2 ± 5.8 vs 19.33 ± 3.74 mm Hg, p < 0.05) and fall in peripheral oxygen saturation (p < 0.05) in HAPE-S compared to control. Receiver operating characteristic (ROC) curves showed that Ppa response to acute hypoxia was the best variable to identify HAPE susceptibility (AUC 0.92) but BNP levels provided comparable information (AUC 0.85). BNP levels are easy to determine and may represent an important marker for the determination of HAPE susceptibility. PMID:26892302

  19. Elevated pulmonary artery pressure and brain natriuretic peptide in high altitude pulmonary edema susceptible non-mountaineers.

    PubMed

    Gupta, Rajinder K; Himashree, G; Singh, Krishan; Soree, Poonam; Desiraju, Koundinya; Agrawal, Anurag; Ghosh, Dishari; Dass, Deepak; Reddy, Prassana K; Panjwani, Usha; Singh, Shashi Bala

    2016-01-01

    Exaggerated pulmonary pressor response to hypoxia is a pathgonomic feature observed in high altitude pulmonary edema (HAPE) susceptible mountaineers. It was investigated whether measurement of basal pulmonary artery pressure (Ppa) and brain natriuretic peptide (BNP) could improve identification of HAPE susceptible subjects in a non-mountaineer population. We studied BNP levels, baseline hemodynamics and the response to hypoxia (FIo2 = 0.12 for 30 min duration at sea level) in 11 HAPE resistant (no past history of HAPE, Control) and 11 HAPE susceptible (past history of HAPE, HAPE-S) subjects. Baseline Ppa (19.31 ± 3.63 vs 15.68 ± 2.79 mm Hg, p < 0.05) and plasma BNP levels (52.39 ± 32.9 vs 15.05 ± 9.6 pg/ml, p < 0.05) were high and stroke volume was less (p < 0.05) in HAPE-S subjects compared to control. Acute hypoxia produced an exaggerated increase in heart rate (p < 0.05), mean arterial pressure (p < 0.05) and Ppa (28.2 ± 5.8 vs 19.33 ± 3.74 mm Hg, p < 0.05) and fall in peripheral oxygen saturation (p < 0.05) in HAPE-S compared to control. Receiver operating characteristic (ROC) curves showed that Ppa response to acute hypoxia was the best variable to identify HAPE susceptibility (AUC 0.92) but BNP levels provided comparable information (AUC 0.85). BNP levels are easy to determine and may represent an important marker for the determination of HAPE susceptibility. PMID:26892302

  20. 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 ...

  1. Left Ventricular Mass Index and Pulmonary Artery Pressure in Patients with the Obstructive Sleep Apnea Syndrome

    PubMed Central

    Sezavar, Seyed Hashem; Hajsadeghi, Shokoufeh; Hejrati, Maral; Ghaleh Bandi, Mir Farhad

    2016-01-01

    Background: Sleep apnea is accompanied by some cardiovascular complications. It has even been hypothesized that sleep apnea, itself, can induce some of these complications. Given such controversies, we assessed the left ventricular mass index (LVMI) and systolic pulmonary artery pressure in patients with sleep apnea. Methods: Through convenience sampling, 56 patients with the obstructive sleep apnea syndrome (OSAS) were included in the present descriptive cross-sectional study. Patients with any past history of hypertension and diabetes mellitus were excluded. The apnea severity was assessed via the polysomnography-derived apnea-hypopnea index (AHI). All the patients underwent transthoracic echocardiography. In this cross-sectional study - data regarding age, gender, smoking, systolic and diastolic blood pressures, polysomnographic parameters (AHI, severity of disease, mean heart rate, mean oxygen saturation [SaO2], lowest SaO2, and duration of SaO2 below 90% [d.SaO2 < 90%]), and echocardiographic parameters (systolic pulmonary artery pressure and LVMI) were accumulated and processed. Results: Fifty-two men and 14 women at a mean age of 49.29 ± 11.79 years participated in this study. Systolic and was significantly high in the severe group compared with the mild group (128.21 ± 9.73 mmHg vs. 119.23 ± 12.5 mmHg; p value = 0.007). The LVMI was increased parallel to an increase in the severity of the OSAS, but that increase was not statistically significant (p value = 0.161). The d.SaO2 < 90% was positively correlated with the LVMI, and this relationship remained true after adjustment for the body mass index (r = 0.27; p value = 0.042). Conclusion: Severe OSAS was accompanied by a higher blood pressure. The LVMI did not differ significantly between the patients with the OSAS and those who did not suffer from other risk factors of cardiac diseases. PMID:27403184

  2. Longitudinal follow up of elevated pulmonary artery pressures in children with sickle cell disease.

    PubMed

    Pashankar, Farzana D; Carbonella, Judith; Bazzy-Asaad, Alia; Friedman, Alan

    2009-03-01

    Elevated pulmonary artery pressures (PAP) occur in approximately 30% of children with sickle cell disease. In adults, pulmonary hypertension is significantly associated with mortality. There are no data on the long term significance in children. Nineteen children with SS/Sbeta(0) thalassaemia had elevated PAP, defined as tricuspid regurgitant jet velocity (TRV) > or =2.5 m/s on screening echocardiograms. They were prospectively followed for 23 months (range 19-31 months). Patients with initial TRV > or = 3 or TRV > or = 2.5 m/s on repeat echocardiogram had cardiopulmonary evaluation and were offered treatment with hydroxyurea. Associated conditions like asthma and obstructive sleep apnea were treated. 18/19 patients had follow-up echocardiograms. These showed normalization of TRV in 8 patients. Risk factors associated with persistent elevation were higher TRV on initial echocardiogram (P = 0.01), lower haemoglobin (P = 0.003) and lower oxygen saturation (P = 0.03). Five patients with persistently elevated PAP were treated with hydroxyurea. Mean right ventricular pressure dropped from 40.16 to 29.26 (P = 0.017) after 3-6 months and to 23.6 mmHg (P = 0.002) after 9-12 months on treatment. In conclusion (i) At borderline elevation of TRV there is intrapatient variability and echocardiograms should be repeated for confirmation. (ii) Elevated PAP are reversible in children with early detection and treatment with hydroxyurea. PMID:19055665

  3. 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

  4. 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...

  5. 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

  6. 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

  7. 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

  8. 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

  9. Pulmonary arterial hypertension in primary amyloidosis.

    PubMed

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

    2016-06-01

    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

  10. The Endothelial Prolyl-4-Hydroxylase Domain 2/Hypoxia-Inducible Factor 2 Axis Regulates Pulmonary Artery Pressure in Mice.

    PubMed

    Kapitsinou, Pinelopi P; Rajendran, Ganeshkumar; Astleford, Lindsay; Michael, Mark; Schonfeld, Michael P; Fields, Timothy; Shay, Sheila; French, Jaketa L; West, James; Haase, Volker H

    2016-05-15

    Hypoxia-inducible factors 1 and 2 (HIF-1 and -2) control oxygen supply to tissues by regulating erythropoiesis, angiogenesis and vascular homeostasis. HIFs are regulated in response to oxygen availability by prolyl-4-hydroxylase domain (PHD) proteins, with PHD2 being the main oxygen sensor that controls HIF activity under normoxia. In this study, we used a genetic approach to investigate the endothelial PHD2/HIF axis in the regulation of vascular function. We found that inactivation of Phd2 in endothelial cells specifically resulted in severe pulmonary hypertension (∼118% increase in right ventricular systolic pressure) but not polycythemia and was associated with abnormal muscularization of peripheral pulmonary arteries and right ventricular hypertrophy. Concurrent inactivation of either Hif1a or Hif2a in endothelial cell-specific Phd2 mutants demonstrated that the development of pulmonary hypertension was dependent on HIF-2α but not HIF-1α. Furthermore, endothelial HIF-2α was required for the development of increased pulmonary artery pressures in a model of pulmonary hypertension induced by chronic hypoxia. We propose that these HIF-2-dependent effects are partially due to increased expression of vasoconstrictor molecule endothelin 1 and a concomitant decrease in vasodilatory apelin receptor signaling. Taken together, our data identify endothelial HIF-2 as a key transcription factor in the pathogenesis of pulmonary hypertension. PMID:26976644

  11. 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

  12. Spatial Orientation and Morphology of the Pulmonary Artery: Relevance to Optimising Design and Positioning of a Continuous Pressure Monitoring Device.

    PubMed

    Lee, Su-Lin; Aguib, Heba; Chapron, Julien; Bahmanyar, Reza; Borghi, Alessandro; Murphy, Olive; McLeod, Chris; ElGuindy, Ahmed; Yacoub, Magdi

    2016-06-01

    Personalised treatment of heart disease requires an understanding of the patient-specific characteristics, which can vary over time. A newly developed implantable surface acoustic wave pressure sensor, capable of continuous monitoring of the left ventricle filling pressure, is a novel device for personalised management of patients with heart disease. However, a one-size-fits-all approach to device sizing will affect its positioning within the pulmonary artery and its relationship to the interrogating device on the chest wall on a patient-specific level. In this paper, we analyse the spatial orientation and morphology of the pulmonary artery and its main branches in patients who could benefit from the device and normal controls. The results could optimise the design of the sensor, its stent, and importantly its placement, ensuring long-term monitoring in patient groups. PMID:27075735

  13. Echocardiographic Assessment of Estimated Right Atrial Pressure and Size Predicts Mortality in Pulmonary Arterial Hypertension

    PubMed Central

    Austin, Christopher; Alassas, Khadija; Burger, Charles; Safford, Robert; Pagan, Ricardo; Duello, Katherine; Kumar, Preetham; Zeiger, Tonya

    2015-01-01

    BACKGROUND: Elevated mean right atrial pressure (RAP) measured by cardiac catheterization is an independent risk factor for mortality. Prior studies have demonstrated a modest correlation with invasive and noninvasive echocardiographic RAP, but the prognostic impact of estimated right atrial pressure (eRAP) has not been previously evaluated in patients with pulmonary arterial hypertension (PAH). METHODS: A retrospective analysis of 121 consecutive patients with PAH based on right-sided heart catheterization and echocardiography was performed. The eRAP was calculated by inferior vena cava diameter and collapse using 2005 and 2010 American Society of Echocardiography (ASE) definitions. Accuracy and correlation of eRAP to RAP was assessed. Kaplan-Meier survival analysis by eRAP, right atrial area, and Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry) risk criteria as well as univariate and multivariate analysis of echocardiographic findings was performed. RESULTS: Elevation of eRAP was associated with decreased survival time compared with lower eRAP (P < .001, relative risk = 7.94 for eRAP > 15 mm Hg vs eRAP ≤ 5 mm Hg). Univariate analysis of echocardiographic parameters including eRAP > 15 mm Hg, right atrial area > 18 cm2, presence of pericardial effusion, right ventricular fractional area change < 35%, and at least moderate tricuspid regurgitation was predictive of poor survival. However, multivariate analysis revealed that eRAP > 15 mm Hg was the only echocardiographic risk factor that was predictive of mortality (hazard ratio = 2.28, P = .037). CONCLUSIONS: Elevation of eRAP by echocardiography at baseline assessment was strongly associated with increased risk of death or transplant in patients with PAH. This measurement may represent an important prognostic component in the comprehensive echocardiographic evaluation of PAH. PMID:25211049

  14. Diagnosis and Management of Pulmonary Arterial Hypertension

    PubMed Central

    Houtchens, Jeanne; Martin, Douglas; Klinger, James R.

    2011-01-01

    Pulmonary arterial hypertension is a rare disease, which requires a high index of suspicion to diagnose when patients initially present. Initial symptoms can be nonspecific and include complaints such as fatigue and mild dyspnea. Once the disease is suspected, echocardiography is used to estimate the pulmonary arterial (PA) pressure and to exclude secondary causes of elevated PA pressures such as left heart disease. Right heart catheterization with vasodilator challenge is critical to the proper assessment of pulmonary hemodynamics and to determine whether patients are likely to benefit from vasodilator therapy. Pathologically, the disease is characterized by deleterious remodeling of the distal pulmonary arterial and arteriolar circulation, which results in increased pulmonary vascular resistance. In the last fifteen years, medications from three different classes have been approved for the treatment of pulmonary arterial hypertension. These include the prostanoids, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors. PMID:21941650

  15. Non-invasive monitoring of pulmonary artery pressure from timing information by EIT: experimental evaluation during induced hypoxia.

    PubMed

    Proença, Martin; Braun, Fabian; Solà, Josep; Adler, Andy; Lemay, Mathieu; Thiran, Jean-Philippe; Rimoldi, Stefano F

    2016-06-01

    Monitoring of pulmonary artery pressure (PAP) in pulmonary hypertensive patients is currently limited to invasive solutions. We investigate a novel non-invasive approach for continuous monitoring of PAP, based on electrical impedance tomography (EIT), a safe, low-cost and non-invasive imaging technology. EIT recordings were performed in three healthy subjects undergoing hypoxia-induced PAP variations. The pulmonary pulse arrival time (PAT), a timing parameter physiologically linked to the PAP, was automatically calculated from the EIT signals. Values were compared to systolic PAP values from Doppler echocardiography, and yielded strong correlation scores ([Formula: see text]) for all three subjects. Results suggest the feasibility of non-invasive, unsupervised monitoring of PAP. PMID:27212013

  16. 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

  17. Prognostic Implications of Elevated Pulmonary Artery Pressure After ST-Segment Elevation Myocardial Infarction.

    PubMed

    Haeck, Marlieke L A; Hoogslag, Georgette E; Boden, Helèn; Velders, Matthijs A; Katsanos, Spyridon; Al Amri, Ibtihal; Debonnaire, Philippe; Schalij, Martin J; Vliegen, Hubert W; Bax, Jeroen J; Marsan, Nina Ajmone; Delgado, Victoria

    2016-08-01

    Elevated systolic pulmonary artery pressure (SPAP) after ST-segment elevation myocardial infarction (STEMI) has been associated with adverse outcome. However, little is known about the development of increased SPAP after STEMI treated with primary percutaneous coronary intervention. The aims of this study were to investigate the incidence and determinants of elevated SPAP (SPAP ≥36 mm Hg at 12 months) after first STEMI and to analyze its prognostic implications. A total of 705 patients (60 ± 12 years; 75% men; left ventricular ejection fraction [LVEF] 47 ± 9%) with first STEMI treated with primary percutaneous coronary intervention were evaluated. Two-dimensional echocardiography was available at baseline and 12-month follow-up. Data on all-cause mortality were collected at long-term follow-up. Incident elevated SPAP was present in 5% (n = 38) of patients. Patients with incident elevated SPAP were older (66 ± 12 vs 60 ± 11 years, p = 0.001), had more systemic hypertension (58% vs 30%, p <0.001) and lower LVEF (43 ± 9% vs 48 ± 8%, p <0.001) than their counterparts. Left atrial volume was larger (23 ± 11 vs 18 ± 6 ml/m(2), p = 0.006), and moderate to severe mitral regurgitation was more prevalent in patients with incident elevated SPAP (16% vs 7%, p = 0.05). Independent correlates of incident elevated SPAP at 12-month follow-up were age (odds ratio [OR] 1.04, 95% CI 1.01 to 1.08, p = 0.01), hypertension (OR 2.52, 95% CI 1.23 to 5.14, p = 0.01), baseline LVEF (OR 0.94, 95% CI 0.90 to 0.98, p = 0.003), and baseline left atrial volume (OR 1.08, 95% CI 1.03 to 1.12, p = 0.001). Incident elevated SPAP was independently associated with all-cause mortality (hazard ratio 3.84, 95% CI 1.76 to 8.39, p = 0.001). In conclusion, although the incidence of elevated SPAP after STEMI is low, its presence is independently associated with increased risk of all-cause mortality at follow-up. PMID:27265675

  18. Mean pulmonary arterial pressures in Angus steers increase from cow-calf to feedlot-finishing phases.

    PubMed

    Neary, J M; Garry, F B; Holt, T N; Thomas, M G; Enns, R M

    2015-08-01

    Pulmonary arterial hypertension due to hypoxia-induced pulmonary vascular remodeling is the predominant cause of right-sided congestive heart failure (CHF) in cattle. Historically, heart failure was problematic only at altitudes over 2,134 m. However, anecdotal reports suggest that the incidence of heart failure is increasing in feedlot cattle at moderate altitude (800 to 1,600 m), with late-fed, or fat, cattle at greatest risk. The goal of this study was to evaluate pulmonary arterial pressures (PAP) in a cohort of male Angus calves from suckling to finishing to better understand why heart failure is particularly problematic in fat cattle. It was hypothesized that mean PAP would increase through the feeding period and that the calves with the greatest pressures at high altitude would have the greatest pressures as fat cattle. A total of 362 PAP measurements were obtained from 153 calves. Calves were tested at altitudes of 2,170 (4 and 6 mo old), 1,560 (13 mo old), and 1,300 m (13 and 18 mo old). Mean PAP were greater in 18-mo-old steers than any other age group (mean = 50.3 mm Hg; 95% confidence interval 48.2 to 52.4; < 0.05). Calves that had the greatest mean pressure at 6 mo of age tended to have the greatest mean pressures at 18 mo of age ( = 0.45, < 0.001). The increase in mean PAP with increasing age and adiposity likely predisposed the steers to an increased risk of CHF during the finishing phase. PMID:26440165

  19. Idiopathic pulmonary arterial hypertension.

    PubMed

    Souza, Rogerio; Jardim, Carlos; Humbert, Marc

    2013-10-01

    Idiopathic pulmonary arterial hypertension (IPAH), formerly called primary pulmonary hypertension, is a rare disease (incidence and prevalence rates of approximately one and six cases per million inhabitants, respectively) with different clinical phenotypes. A group of diverse conditions manifest pulmonary arterial hypertension (PAH) and share similar pathological and/or clinical findings with IPAH. By definition, IPAH is diagnosed only after alternative diagnoses have been ruled out. Extensive investigation is needed to determine if PAH is associated with thyroid diseases, infectious diseases, autoimmune conditions, exposure to certain drugs (particularly anorexigens), certain genetic mutations, and so on. The presence of genetic abnormalities and risk factors (such as specific drug exposures) reinforces the "multiple hit" concept for the development of pulmonary hypertension. Fortunately, within the past two decades, therapeutic options have become available for IPAH, resulting in improved survival and clinical outcomes. At least seven different compounds have been registered for PAH treatment. However, even with aggressive PAH-specific therapy, mortality rates remain high (∼40% at 5 years). Given the high mortality rates, the use of combinations of agents that work by different pathways has been advocated (either as "add-on" therapy or initial "up front" therapy). Further, new therapeutic agents and treatment strategies are on the near horizon, aiming to further improve survival from the remarkable progress already seen. PMID:24037625

  20. Pulmonary Arterial Hypertension: The Clinical Syndrome

    PubMed Central

    Lai, Yen-Chun; Potoka, Karin C.; Champion, Hunter C.; Mora, Ana L.; Gladwin, Mark T.

    2014-01-01

    Pulmonary arterial hypertension (PAH) is a progressive disorder in which endothelial dysfunction and vascular remodeling obstruct small pulmonary arteries, resulting in increased pulmonary vascular resistance and pulmonary pressures. This leads to reduced cardiac output, right heart failure, and ultimately death. In this review, we attempt to answer some important questions commonly asked by patients diagnosed with PAH pertaining to the disease, and aim to provide an explanation in terms of classification, diagnosis, pathophysiology, genetic etiologies, demographics, and prognostic factors. Furthermore, important molecular pathways that are central to the pathogenesis of PAH are reviewed, including nitric oxide, prostacyclin, endothelin-1, reactive oxygen species, and endothelial and smooth muscle proliferation. PMID:24951762

  1. 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

  2. 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

  3. Adenoviral gene transfer of endothelial nitric-oxide synthase (eNOS) partially restores normal pulmonary arterial pressure in eNOS-deficient mice

    PubMed Central

    Champion, Hunter C.; Bivalacqua, Trinity J.; Greenberg, Stanley S.; Giles, Thomas D.; Hyman, Albert L.; Kadowitz, Philip J.

    2002-01-01

    It has been shown that mice deficient in the gene coding for endothelial nitric-oxide synthase (eNOS) have increased pulmonary arterial pressure and pulmonary vascular resistance. In the present study, the effect of transfer to the lung of an adenoviral vector encoding the eNOS gene (AdCMVeNOS) on pulmonary arterial pressure and pulmonary vascular resistance was investigated in eNOS-deficient mice. One day after intratracheal administration of AdCMVeNOS to eNOS−/− mice, there was an increase in eNOS protein, cGMP levels, and calcium-dependent conversion of l-arginine to l-citrulline in the lung. The increase in eNOS protein and activity in eNOS−/− mice was associated with a reduction in mean pulmonary arterial pressure and pulmonary vascular resistance when compared with values in eNOS-deficient mice treated with vehicle or a control adenoviral vector coding for β-galactosidase, AdCMVβgal. These data suggest that in vivo gene transfer of eNOS to the lung in eNOS−/− mice can increase eNOS staining, eNOS protein, calcium-dependent NOS activity, and cGMP levels and partially restore pulmonary arterial pressure and pulmonary vascular resistance to near levels measured in eNOS+/+ mice. Thus, the major finding in this study is that in vivo gene transfer of eNOS to the lung in large part corrects a genetic deficiency resulting from eNOS deletion and may be a useful therapeutic intervention for the treatment of pulmonary hypertensive disorders in which eNOS activity is reduced. PMID:12237402

  4. 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

  5. Nicorandil Prevents Right Ventricular Remodeling by Inhibiting Apoptosis and Lowering Pressure Overload in Rats with Pulmonary Arterial Hypertension

    PubMed Central

    Yu, Yan-Zhe; Wang, Hui; Bi, Li-Qing; Xie, Wei-Ping; Wang, Hong

    2012-01-01

    Background Most of the deaths among patients with severe pulmonary arterial hypertension (PAH) are caused by progressive right ventricular (RV) pathological remodeling, dysfunction, and failure. Nicorandil can inhibit the development of PAH by reducing pulmonary artery pressure and RV hypertrophy. However, whether nicorandil can inhibit apoptosis in RV cardiomyocytes and prevent RV remodeling has been unclear. Methodology/Principal Findings RV remodeling was induced in rats by intraperitoneal injection of monocrotaline (MCT). RV systolic pressure (RVSP) was measured at the end of each week after MCT injection. Blood samples were drawn for brain natriuretic peptide (BNP) ELISA analysis. The hearts were excised for histopathological, ultrastructural, immunohistochemical, and Western blotting analyses. The MCT-injected rats exhibited greater mortality and less weight gain and showed significantly increased RVSP and RV hypertrophy during the second week. These worsened during the third week. MCT injection for three weeks caused pathological RV remodeling, characterized by hypertrophy, fibrosis, dysfunction, and RV mitochondrial impairment, as indicated by increased levels of apoptosis. Nicorandil improved survival, weight gain, and RV function, ameliorated RV pressure overload, and prevented maladaptive RV remodeling in PAH rats. Nicorandil also reduced the number of apoptotic cardiomyocytes, with a concomitant increase in Bcl-2/Bax ratio. 5-hydroxydecanoate (5-HD) reversed these beneficial effects of nicorandil in MCT-injected rats. Conclusions/Significance Nicorandil inhibits PAH-induced RV remodeling in rats not only by reducing RV pressure overload but also by inhibiting apoptosis in cardiomyocytes through the activation of mitochondrial ATP-sensitive K+ (mitoKATP) channels. The use of a mitoKATP channel opener such as nicorandil for PAH-associated RV remodeling and dysfunction may represent a new therapeutic strategy for the amelioration of RV remodeling during

  6. 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

  7. Continuous cardiac output and left atrial pressure monitoring by long time interval analysis of the pulmonary artery pressure waveform: proof of concept in dogs.

    PubMed

    Xu, Da; Olivier, N Bari; Mukkamala, Ramakrishna

    2009-02-01

    We developed a technique to continuously (i.e., automatically) monitor cardiac output (CO) and left atrial pressure (LAP) by mathematical analysis of the pulmonary artery pressure (PAP) waveform. The technique is unique to the few previous related techniques in that it jointly estimates the two hemodynamic variables and analyzes the PAP waveform over time scales greater than a cardiac cycle wherein wave reflections and inertial effects cease to be major factors. First, a 6-min PAP waveform segment is analyzed so as to determine the pure exponential decay and equilibrium pressure that would eventually result if cardiac activity suddenly ceased (i.e., after the confounding wave reflections and inertial effects vanish). Then, the time constant of this exponential decay is computed and assumed to be proportional to the average pulmonary arterial resistance according to a Windkessel model, while the equilibrium pressure is regarded as average LAP. Finally, average proportional CO is determined similar to invoking Ohm's law and readily calibrated with one thermodilution measurement. To evaluate the technique, we performed experiments in five dogs in which the PAP waveform and accurate, but highly invasive, aortic flow probe CO and LAP catheter measurements were simultaneously recorded during common hemodynamic interventions. Our results showed overall calibrated CO and absolute LAP root-mean-squared errors of 15.2% and 1.7 mmHg, respectively. For comparison, the root-mean-squared error of classic end-diastolic PAP estimates of LAP was 4.7 mmHg. On future successful human testing, the technique may potentially be employed for continuous hemodynamic monitoring in critically ill patients with pulmonary artery catheters. PMID:19057003

  8. 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. PMID:2287128

  9. 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

  10. Pharmacotherapeutic management of pulmonary arterial hypertension.

    PubMed

    Anderson, Joe R; Nawarskas, James J

    2010-01-01

    Pulmonary arterial hypertension (PAH) is a disabling chronic disorder of the pulmonary vasculature, which is characterized by increased pulmonary artery pressure as a result of increased pulmonary vascular resistance. The pathology of PAH is characterized by pulmonary vascular vasoconstriction, smooth muscle cell proliferation, and thrombosis. These changes are a result of an imbalance between vasodilators (prostacyclin, nitric oxide, vasoactive intestinal peptide) and vasoconstrictors (thromboxane A2, endothelin, serotonin), growth inhibitors and mitogenic factors, and antithrombotic and prothrombotic factors. Recent advances in treatment are directed at restoring the balance between these systems. Endothelin receptor antagonists (bosentan, ambrisentan, sitaxsentan), phosphodiesterase type 5 inhibitors (sildenafil, tadalafil), and prostacylin (epoprostenol, iloprost, treprostinil, beraprost) represent the different classes of medications that are currently used in monotherapy and in combination to treat PAH. The purpose of this drug highlight is to provide the reader with an update of the pharmacotherapeutic treatment of PAH. PMID:20395700

  11. 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

  12. Iranian Pulmonary Arterial Hypertension Registry

    PubMed Central

    Fahimi, Fanak; Sharif-Kashani, Babak; Malek Mohammad, Majid; Saliminejad, Leila; Monjazebi, Fateme

    2015-01-01

    Background: Idiopathic pulmonary arterial hypertension (IPAH) is a fatal disorder with a prevalence of 8.6 per million. We introduce a registry website for IPAH and PAH patients ( www.IPAH.ir) for access and efficient delivery of government-aided and subsidized antihypertensive medications. Materials and Methods: The IPAH registry was opened in November 2009. Information of IPAH and PAH patients with a username and password were uploaded in the site. Data entry was possible only via the physicians and healthcare organizations via internet that were given a personalized username and password for entry. Following the patients’ profile submission, a scientific committee composed of a cardiologist and a pulmonologist who were selected by the Ministry of Health of Iran (MOH), evaluated the data. The eligibility of the patient to receive the medications was confirmed after evaluation. If the patient was eligible, 82% of the Bosentan cost was paid by MOH. Results: To date, one hundred and sixteen patients (82 females, 34 males) have been registered. The mean pulmonary artery pressure by right heart catheterization was 69.24±17 mmHg (ranging from 35 to 110 mmHg). Conclusion: The first online Iranian registry program for IPAH and PAH patients is believed to supply essential information for health care providers in the field. PMID:26528365

  13. Pulmonary artery agenesis associated with coronary collaterals among adults.

    PubMed

    Darwazah, Ahmad K; Alhaddad, Imad A

    2016-01-01

    Unilateral agenesis of the pulmonary artery is a rare congenital anomaly, which commonly involves the right side. Cases are associated with systemic collaterals, that may also rarely arise from the coronary arteries.Two adult patients are presented with a right pulmonary artery agenesis associated with collaterals from the right coronary artery. The implications of such an anomaly on pulmonary artery pressure and lung pathology differs among both cases. The association of coronary collaterals is rare and its implication is variable among various patients. PMID:27422770

  14. 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

  15. Effect of blood pH on pulmonary artery pressure, left atrial pressure and fluid filtration rate in isolated rabbit lung.

    PubMed

    Pinto-Plata, V M; Pozo-Parilli, J C; Baum-Agay, A; Curiel, C; Sánchez de León, R

    1995-09-01

    To determine the effects of pH changes on Pulmonary Artery Pressure (PAP), 18 isolated rabbit lung preparations, perfused with autologous blood mixture and constant PaCO2 have been studied. Each preparation was studied under 3 conditions: Baseline: 30 minutes equilibration period. Acidosis: pH was decreased by 0.2 N HCl infusion, the ventilatory rate was changed and different CO2 mixtures were used to maintain the PCO2 within the initial parameters. Compensated Acidosis (CA): pH was returned to normal values by 0.7 N NaHCO3 infusion maintaining PCO2 in its initial values. The decrease in pH (acidosis) from 7.36 +/- 0.05 to 7.18 +/- 0.06 at constant PCO2, generated a significant increase in PAP (13.6 +/- 3.2 cm H2O to 18.8 +/- 5.2 cm H2O, p < 0.01). The pH increase (CA) from 7.18 +/- 0.06 to 7.40 +/- 0.09 caused the PAP to decrease (18.8 +/- 5.2 cm H2O to 15.9 +/- 4.2 cm H2O); the fluid filtration rate remained unchanged during the whole experiment. It is concluded that blood pH changes at constant PCO2 result in significant changes of PAP. Acidemia produces pulmonary vasoconstriction, which may be a contributing factor in the genesis of pulmonary hypertension in clinical conditions with increased hydrogen ion concentration [H+]. PMID:8606988

  16. 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

  17. Arterial pulmonary hypertension in noncardiac intensive care unit

    PubMed Central

    Tsapenko, Mykola V; Tsapenko, Arseniy V; Comfere, Thomas BO; Mour, Girish K; Mankad, Sunil V; Gajic, Ognjen

    2008-01-01

    Pulmonary artery pressure elevation complicates the course of many complex disorders treated in a noncardiac intensive care unit. Acute pulmonary hypertension, however, remains underdiagnosed and its treatment frequently begins only after serious complications have developed. Significant pathophysiologic differences between acute and chronic pulmonary hypertension make current classification and treatment recommendations for chronic pulmonary hypertension barely applicable to acute pulmonary hypertension. In order to clarify the terminology of acute pulmonary hypertension and distinguish it from chronic pulmonary hypertension, we provide a classification of acute pulmonary hypertension according to underlying pathophysiologic mechanisms, clinical features, natural history, and response to treatment. Based on available data, therapy of acute arterial pulmonary hypertension should generally be aimed at acutely relieving right ventricular (RV) pressure overload and preventing RV dysfunction. Cases of severe acute pulmonary hypertension complicated by RV failure and systemic arterial hypotension are real clinical challenges requiring tight hemodynamic monitoring and aggressive treatment including combinations of pulmonary vasodilators, inotropic agents and systemic arterial vasoconstrictors. The choice of vasopressor and inotropes in patients with acute pulmonary hypertension should take into consideration their effects on vascular resistance and cardiac output when used alone or in combinations with other agents, and must be individualized based on patient response. PMID:19183752

  18. 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

  19. Anticoagulation in Pulmonary Arterial Hypertension.

    PubMed

    Robinson, Jeffrey C; Pugliese, Steven C; Fox, Daniel L; Badesch, David B

    2016-06-01

    Pulmonary arterial hypertension (PAH) is characterized by molecular and pathologic alteration to the pulmonary circulation, resulting in increased pulmonary vascular resistance, right ventricular failure, and eventual death. Pharmacologic treatment of PAH consists of use of a multitude of pulmonary vasodilators, sometimes in combination. PAH has been associated with increased thrombosis and disrupted coagulation and fibrinolysis, making anticoagulation an attractive and frequently employed therapeutic modality. Observational studies have provided some insight into the therapeutic potential of anticoagulation in idiopathic PAH, but there is a distinct lack of well-controlled prospective trials. Due to the conflicting evidence, there is a large amount of heterogeneity in the application of therapeutic anticoagulation in PAH and further well-controlled prospective trials are needed to clarify its role in treating PAH. PMID:27137522

  20. Pulse propagation in the pulmonary arteries

    NASA Astrophysics Data System (ADS)

    Hill, Nicholas; Vaughan, Gareth; Olufsen, Mette; Johnson, Martin; Sainsbury, Christopher

    2007-11-01

    The model of Olufsen [1,2] has been extended to study pulse propagation in the pulmonary circulation. The pulmonary arteries are treated as a bifurcating tree of compliant and tapering vessels. The model is divided into two coupled parts: the larger and smaller arteries. Blood flow and pressure in the larger arteries are predicted from a nonlinear 1D cross-sectional area-averaged model for a Newtonian fluid in an elastic tube. The initial cardiac output is obtained from magnetic resonance measurements. The smaller blood vessels are modelled as an asymmetric structured tree with specified area and asymmetry ratios between the parent and daughter arteries. Womersley's theory gives the wave equation in the frequency domain for the 1D flow in these smaller vessels, resulting in a linear system. The impedances of the smallest vessels are set to a constant and then back-calculation gives the required outflow boundary condition for the Navier-Stokes equations in the larger vessels. The number of generations of blood vessels, and the compliance of the arterial wall are shown to affect both the systolic and diastolic pressures. [1] Olufsen MS et al. Ann Biomed Eng. 2000;28:1281-99. [2] Olufsen MS. Am J Physiol. 1999;276:H257-68.

  1. 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…

  2. Pulmonary arterial remodeling in chronic obstructive pulmonary disease is lobe dependent.

    PubMed

    Wrobel, Jeremy P; McLean, Catriona A; Thompson, Bruce R; Stuart-Andrews, Christopher R; Paul, Eldho; Snell, Gregory I; Williams, Trevor J

    2013-09-01

    Abstract Pulmonary arterial remodeling has been demonstrated in patients with severe chronic obstructive pulmonary disease (COPD), but it is not known whether lobar heterogeneity of remodeling occurs. Furthermore, the relationship between pulmonary hypertension (PH) and pulmonary arterial remodeling in COPD has not been established. Muscular pulmonary arterial remodeling in arteries 0.10-0.25 mm in diameter was assessed in COPD-explanted lungs and autopsy controls. Remodeling was quantified as the percentage wall thickness to vessel diameter (%WT) using digital image analysis. Repeat measures mixed-effects remodeling for %WT was performed according to lobar origin (upper and lower), muscular pulmonary arterial size (small, medium, and large), and echocardiography-based pulmonary arterial pressure (no PH, mild PH, and moderate-to-severe PH). Lobar perfusion and emphysema indices were determined from ventilation-perfusion and computed tomography scans, respectively. Overall, %WT was greater in 42 subjects with COPD than in 5 control subjects ([Formula: see text]). Within the COPD group, %WT was greater in the upper lobes ([Formula: see text]) and in the small muscular pulmonary arteries ([Formula: see text]). Lobar differences were most pronounced in medium and large arteries. Lobar emphysema index was not associated with arterial remodeling. However, there was a significant positive relationship between the lobar perfusion index and pulmonary arterial remodeling ([Formula: see text]). The presence of PH on echocardiography showed only a trend to a small effect on lower lobe remodeling. The pattern of pulmonary arterial remodeling in COPD is complicated and lobe dependent. Differences in regional blood flow partially account for the lobar heterogeneity of pulmonary arterial remodeling in COPD. PMID:24618551

  3. Mechanical properties of porcine intralobar pulmonary arteries.

    PubMed

    Ohtaka, H; Hogg, J C; Moreno, R H; Paré, P D; Schellenberg, R R

    1988-04-01

    The isobaric and isovolumetric properties of intrapulmonary arteries were evaluated by placing a highly compliant balloon inside arterial segments. The passive pressure-volume (P-V) curve was obtained by changing volume (0.004 ml/s) and measuring pressure. The isobaric active volume change (delta V) or isovolumetric active pressure change (delta P) generated by submaximal histamine was measured at four different transmural pressures (Ptm's) reached by balloon inflation. The maximal delta P = 11.2 +/- 0.6 cmH2O (mean +/- SE) was achieved at 30.8 +/- 1.2 cmH2O Ptm and maximal delta V = 0.20 +/- 0.02 ml at 16.7 +/- 1.7 cmH2O Ptm. The P-V relationships were similar when volume was increased after either isobaric or isovolumetric contraction. The calculated length-tension (L-T) relationship showed that the active tension curve was relatively flat and that the passive tension at the optimal length was 149 +/- 11% of maximal active tension. These data show that 1) a large elastic component operates in parallel with the smooth muscle in intralobar pulmonary arteries, and 2) the change in resistance associated with vascular expansion of the proximal arteries is independent of the type of contraction that occurs in the more distal arterial segments. PMID:3378988

  4. Endovascular treatment of isolated arterial pulmonary malinosculation

    PubMed Central

    Mammen, Suraj; Keshava, Shyamkumar N; Moses, Vinu; Chiramel, George Koshy; Irodi, Aparna; Gnanamuthu, Birla Roy

    2015-01-01

    We report the endovascular management of a series of four cases of isolated systemic supply to normal lung or isolated arterial pulmonary malinosculation of the left lung. In these cases, the basal segments of the left lung lacked normal pulmonary arterial supply and instead received systemic arterial blood from the descending thoracic aorta. The relevant anatomy and literature are also reviewed. PMID:26288517

  5. 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

  6. 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.

  7. Bifurcating stents in the pulmonary arteries: A novel technique to relieve bilateral branch pulmonary artery obstruction.

    PubMed

    Narayan, Hari K; Glatz, Andrew C; Rome, Jonathan J

    2015-10-01

    Balloon angioplasty and stent placement in close proximity to the bifurcation of the branch pulmonary arteries can be challenging. Multiple approaches have been previously described, though none of these approaches both treats bilateral proximal branch pulmonary artery stenosis and provides an anchor for a transcatheter pulmonary valve replacement. We report a novel approach that involves serial stent placement and balloon dilation through the struts of the stent in each pulmonary artery, along with balloon expansion of the proximal portion of the stents to the diameter of the main pulmonary artery. In the two cases we describe, this strategy resulted in significant relief of branch pulmonary artery obstruction without compromising the anatomy of the main pulmonary artery segment. This technique can be an effective way to alleviate stenoses of the bilateral proximal branch pulmonary arteries and provides a landing zone for a future transcatheter pulmonary valve. PMID:26256829

  8. 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

  9. Niflumic Acid Attenuated Pulmonary Artery Tone and Vascular Structural Remodeling of Pulmonary Arterial Hypertension Induced by High Pulmonary Blood Flow In Vivo.

    PubMed

    Wang, Kai; Ma, Jianfa; Pang, Yusheng; Lao, Jinquan; Pan, Xuanren; Tang, Qiaoyun; Zhang, Feng; Su, Danyan; Qin, Suyuan; Shrestha, Arnav Prasad

    2015-10-01

    Calcium-activated chloride channels (CaCCs) play a vital role in regulating pulmonary artery tone during pulmonary arterial hypertension (PAH) induced by high blood flow. The role of CaCCs inhibitor niflumic acid (NFA) in vivo during this process requires further investigation. We established the PAH model by abdominal shunt surgery and treated with NFA in vivo. Fifty rats were randomly divided into normal, sham, shunt, NFA group 1 (0.2 mg/kg), and NFA group 2 (0.4 mg/kg). Pathological changes, right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter were analyzed. Then contraction reactions of pulmonary arteries were measured. Finally, the electrophysiological characteristics of pulmonary arterial smooth muscle cells were investigated using patch-clamp technology. After 11 weeks of shunting, PAH developed, accompanied with increased right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter. In the NFA treatment groups, the pressure and pathological changes were alleviated. The pulmonary artery tone in the shunt group increased, whereas it decreased after NFA treatment. The current density of CaCC was higher in the shunt group, and it was decreased in the NFA treatment groups. In conclusion, NFA attenuated pulmonary artery tone and structural remodeling in PAH induced by high pulmonary blood flow in vivo. CaCCs were involved and the augmented current density was alleviated by NFA treatment. PMID:26132368

  10. 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

  11. Arrhythmias in pulmonary arterial hypertension.

    PubMed

    Rajdev, Archana; Garan, Hasan; Biviano, Angelo

    2012-01-01

    Cardiac arrhythmias are important contributors to morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Such patients manifest a substrate resulting from altered autonomics, repolarization abnormalities, and ischemia. Supraventricular arrhythmias such as atrial fibrillation and flutter are associated with worsened outcomes, and maintenance of sinus rhythm is a goal. Sudden death is a relatively common issue, though the contribution of malignant ventricular arrhythmias versus bradyarrhythmias differs from non-PAH patients. Congenital heart disease patients with PAH benefit from catheter ablation of medically refractory arrhythmias. Clinical studies of defibrillator/pacemaker therapy for primary prevention against sudden death in PAH patients are lacking. PMID:23009914

  12. Arrhythmias in Pulmonary Arterial Hypertension

    PubMed Central

    Rajdev, Archana; Garan, Hasan; Biviano, Angelo

    2013-01-01

    Cardiac arrhythmias are important contributors to morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Such patients manifest a substrate resulting from altered autonomics, repolarization abnormalities, and ischemia. Supraventricular arrhythmias such as atrial fibrillation and flutter are associated with worsened outcomes, and maintenance of sinus rhythm is a goal. Sudden death is a relatively common issue, though the contribution of malignant ventricular arrhythmias versus bradyarrhythmias differs from non-PAH patients. Congenital heart disease patients with PAH benefit from catheter ablation of medically refractory arrhythmias. Clinical studies of defibrillator/pacemaker therapy for primary prevention against sudden death in PAH patients are lacking. PMID:23009914

  13. Transcatheter Treatment of “Pulmonary Artery Hypertension” due to Patent Ductus Arteriosus and Pulmonary Artery Stenosis

    PubMed Central

    Gaio, Gianpiero; Santoro, Giuseppe; D'Alto, Michele; Palladino, Maria Teresa; Russo, Maria Giovanna; Caianiello, Giuseppe; Calabrò, Raffaele

    2006-01-01

    The association between large, left-sided patent ductus arteriosus and severe, peripheral, right pulmonary artery stenosis with no other cardiac malformation is an unreported condition that might be misdiagnosed as pulmonary hypertension due to long-standing ductal shunt. A 57-year-old man with supposed hypertensive patent ductus arteriosus underwent confirmatory cardiac catheterization. At angiography, a severe pre-hilar right pulmonary artery stenosis (peak pressure gradient, 65 mmHg) was found to complicate the hemodynamic picture of a moderate-to-large patent ductus arteriosus (QP/QS, 1.7:1), by causing pulmonary hypertension (mean pressure, 65 mmHg) and left-to-right pulmonary flow imbalance. Both lesions were treated in a single procedure of right pulmonary artery stenting and patent ductus arteriosus closure, after which the pulmonary artery pressure significantly decreased (mean, 35 mmHg). In our opinion, a thorough hemodynamic evaluation followed by pulmonary angiography should be mandatory before proceeding to patent ductus arteriosus closure in the adult patient who has “hypertensive” ductus, in whom possible associated malformations can be missed due to a poor echocardiographic window. PMID:17041703

  14. 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. PMID:26693827

  15. 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

  16. PULMONARY ARTERY ACCELERATED FLOW REVEALING HODGKIN'S LYMPHOMA.

    PubMed

    Ibrahim, Tony; Chehab, Ghassan; Saliba, Zakhia; Smayra, Tarek; Baz, Maria; Abdo, Lynn; Haddad, Fady; Abdel-Massih, Tony

    2016-01-01

    We present a case in which transthoracic echocardiography was the first diagnostic tool to suspect mediastinal Hodgkin's lymphoma by revealing a change in the hemodynamic of left pulmonary artery flow, and it was used as a follow-up method for monitoring treatment efficacy by demonstrating a normalization of pulmonary artery hemodynamics. PMID:27169170

  17. Pathophysiology and clinical implications of pulmonary arterial enlargement in COPD

    PubMed Central

    Wells, J Michael; Dransfield, Mark T

    2013-01-01

    Chronic obstructive pulmonary disease (COPD) is a complex condition defined by progressive airflow limitation in response to noxious stimuli, inflammation, and vascular changes. COPD exacerbations are critical events in the natural history of the disease, accounting for the majority of disease burden, cost, and mortality. Pulmonary vascular disease is an important risk factor for disease progression and exacerbation risk. Relative pulmonary artery enlargement on computed tomography scan, defined by a pulmonary artery to aortic (PA:A) ratio >1, has been evaluated as a marker of pulmonary vascular disease. The PA:A ratio can be measured reliably independent of electrocardiographic gating or the use of contrast, and in healthy patients a PA:A ratio >0.9 is considered to be abnormal. The PA:A ratio has been compared with invasive hemodynamic parameters, primarily mean pulmonary artery pressure in various disease conditions and is more strongly correlated with mean pulmonary artery pressure in obstructive as compared with interstitial lung disease. In patients without known cardiac or pulmonary disease, the PA:A ratio is predictive of mortality, while in COPD, an elevated PA:A ratio is correlated with increased exacerbation risk, outperforming other well established predictors of these events. Future studies should be aimed at determining the stability of the metric over time and evaluating the utility of the PA:A ratio in guiding specific therapies. PMID:24235822

  18. Effective arterial elastance as an index of pulmonary vascular load.

    PubMed

    Morimont, Philippe; Lambermont, Bernard; Ghuysen, Alexandre; Gerard, Paul; Kolh, Philippe; Lancellotti, Patrizio; Tchana-Sato, Vincent; Desaive, Thomas; D'Orio, Vincent

    2008-06-01

    The aim of this study was to test whether the simple ratio of right ventricular (RV) end-systolic pressure (Pes) to stroke volume (SV), known as the effective arterial elastance (Ea), provides a valid assessment of pulmonary arterial load in case of pulmonary embolism- or endotoxin-induced pulmonary hypertension. Ventricular pressure-volume (PV) data (obtained with conductance catheters) and invasive pulmonary arterial pressure and flow waveforms were simultaneously recorded in two groups of six pure Pietran pigs, submitted either to pulmonary embolism (group A) or endotoxic shock (group B). Measurements were obtained at baseline and each 30 min after injection of autologous blood clots (0.3 g/kg) in the superior vena cava in group A and after endotoxin infusion in group B. Two methods of calculation of pulmonary arterial load were compared. On one hand, Ea provided by using three-element windkessel model (WK) of the pulmonary arterial system [Ea(WK)] was referred to as standard computation. On the other hand, similar to the systemic circulation, Ea was assessed as the ratio of RV Pes to SV [Ea(PV) = Pes/SV]. In both groups, although the correlation between Ea(PV) and Ea(WK) was excellent over a broad range of altered conditions, Ea(PV) systematically overestimated Ea(WK). This offset disappeared when left atrial pressure (Pla) was incorporated into Ea [Ea * (PV) = (Pes - Pla)/SV]. Thus Ea * (PV), defined as the ratio of RV Pes minus Pla to SV, provides a convenient, useful, and simple method to assess the pulmonary arterial load and its impact on the RV function. PMID:18424634

  19. 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

  20. 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

  1. [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. PMID:25070518

  2. Nitric Oxide, Oxidative Stress and Inflammation in Pulmonary Arterial Hypertension

    PubMed Central

    Crosswhite, Patrick; Sun, Zhongjie

    2010-01-01

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease characterized by a persistent elevation of pulmonary artery pressure accompanied by right ventricular hypertrophy (RVH). The current treatment for pulmonary hypertension is limited and only provides symptomatic relief due to unknown etiology and pathogenesis of the disease. Both vasoconstriction and structural remodeling (enhanced proliferation of VSMC) of the pulmonary arteries contribute to the progressive course of PAH, irrespective of different underlying causes. The exact molecular mechanism of PAH, however, is not fully understood. The purpose of this review is to provide recent advances in the mechanistic investigation of PAH. Specifically, this review focuses on nitric oxide (NO), oxidative stress and inflammation and how these factors contribute to the development and progression of PAH. This review also discusses recent and potential therapeutic advancements for the treatment of PAH. PMID:20051913

  3. Increasing pulmonary artery pulsatile flow improves hypoxic pulmonary hypertension in piglets.

    PubMed

    Courboulin, Audrey; Kang, Chantal; Baillard, Olivier; Bonnet, Sebastien; Bonnet, Pierre

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a disease affecting distal pulmonary arteries (PA). These arteries are deformed, leading to right ventricular failure. Current treatments are limited. Physiologically, pulsatile blood flow is detrimental to the vasculature. In response to sustained pulsatile stress, vessels release nitric oxide (NO) to induce vasodilation for self-protection. Based on this observation, this study developed a protocol to assess whether an artificial pulmonary pulsatile blood flow could induce an NO-dependent decrease in pulmonary artery pressure. One group of piglets was exposed to chronic hypoxia for 3 weeks and compared to a control group of piglets. Once a week, the piglets underwent echocardiography to assess PAH severity. At the end of hypoxia exposure, the piglets were subjected to a pulsatile protocol using a pulsatile catheter. After being anesthetized and prepared for surgery, the jugular vein of the piglet was isolated and the catheter was introduced through the right atrium, the right ventricle and the pulmonary artery, under radioscopic control. Pulmonary artery pressure (PAP) was measured before (T0), immediately after (T1) and 30 min after (T2) the pulsatile protocol. It was demonstrated that this pulsatile protocol is a safe and efficient method of inducing a significant reduction in mean PAP via an NO-dependent mechanism. These data open up new avenues for the clinical management of PAH. PMID:25993379

  4. Calcium antagonist verapamil prevented pulmonary arterial hypertension in broilers with ascites by arresting pulmonary vascular remodeling.

    PubMed

    Yang, Ying; Qiao, Jian; Wang, Huiyu; Gao, Mingyu; Ou, Deyuan; Zhang, Jianjun; Sun, Maohong; Yang, Xin; Zhang, Xiaobo; Guo, Yuming

    2007-04-30

    Calcium signaling has been reported to be involved in the pathogenesis of hypertension. Verapamil, one of the calcium antagonists, is used to characterize the role of calcium signaling in the development of pulmonary arterial hypertension syndrome in broilers. The suppression effect of verapamil on pulmonary arterial hypertension and pulmonary vascular remodeling was examined in broilers, from the age of 16 days to 43 days. Our results showed that oral administration of lower dose of verapamil (5 mg/kg body weight every 12 h) prevented the mean pulmonary arterial pressure, the ascites heart index and the erythrocyte packed cell volume of birds at low temperature from increasing, the heart rate from decreasing, and pulmonary arteriole median from thickening, and no pulmonary arteriole remodeling in broilers treated with the two doses of verapamil at low temperature was observed. Our results indicated that calcium signaling was involved in the development of broilers' pulmonary arterial hypertension, which leads to the development of ascites, and we suggest that verapamil may be used as a preventive agent to reduce the occurrence and development of pulmonary arterial hypertension in broilers. PMID:17320074

  5. Vascular Leiomyoma of the Pulmonary Artery.

    PubMed

    Klotz, Laura V; Morresi-Hauf, Alicia; Hatz, Rudolf A; Lindner, Michael

    2016-01-01

    Leiomyoma of the pulmonary artery represents a curiosity in the literature. We describe a case of a 54-year-old female patient who presented with recurrent cough of a few weeks' duration. Computed tomography of the thorax located a smooth, limited tumor in the left thorax near the interlobar space. Thoracoscopic exploration showed a tumor mass, fused with the pulmonary artery. After anterolateral thoracotomy, a complete resection of the tumor was performed. The histopathologic examination showed the presence of a vascular leiomyoma of the tunica media of the pulmonary artery. PMID:26694272

  6. 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

  7. MR and CT imaging of the structural and functional changes of pulmonary arterial hypertension

    PubMed Central

    Schiebler, Mark L.; Bhalla, Sanjeev; Runo, James; Jarjour, Nizar; Roldan, Alejandro; Chesler, Naomi; François, Christopher J.

    2013-01-01

    The current Dana Point classification system (2009) divides elevation of pulmonary artery pressure into Pulmonary Arterial Hypertension (PAH) and Pulmonary Hypertension (PH). Fortunately, pulmonary arterial hypertension (PAH) is not a common disease. However, with the aging of the first world’s population, heart failure is now an important cause of pulmonary hypertension with up to 9% of the population involved. PAH is usually asymptomatic until late in the disease process. While there are indirect features of PAH found on noninvasive imaging studies, the diagnosis and management still requires right heart catheterization. Imaging features of PAH include: 1. Enlargement of the pulmonary trunk and main pulmonary arteries, 2. Decreased pulmonary arterial compliance, 3. Tapering of the peripheral pulmonary arteries, 4. Enlargement of the inferior vena cava, and 5. Increased mean transit time. The chronic requirement to generate high pulmonary arterial pressures measurably affects the right heart and main pulmonary artery. This change in physiology causes the following structural and functional alterations that have been shown to have prognostic significance: Relative area change of the pulmonary trunk, RVSVindex, RVSV, RVEDVindex, LVEDVindex, and baseline RVEF <35%. All of these variables can be quantified non-invasively and followed longitudinally in each patient using MRI to modify the treatment regimen. Untreated PAH frequently results in a rapid clinical decline and death within 3 years of diagnosis. Unfortunately, even with treatment, less than 1/2 of these patients are alive at four years. PMID:23612440

  8. 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.

  9. Origin of the right pulmonary artery from the ascending aorta.

    PubMed Central

    Fontana, G P; Spach, M S; Effmann, E L; Sabiston, D C

    1987-01-01

    Origin of the right pulmonary artery from the aorta is a congenital malformation usually associated with serious symptoms in the first year of life and characterized by a poor prognosis. Sixty-five patients with this disorder have been reviewed in the literature, and 95% presented during the first year with signs of congestive heart failure. All had cardiomegaly by radiographic and electrocardiographic examination. An accurate diagnosis was established by cineangiography, and associated cardiovascular anomalies were present in 85%. Origin of the right pulmonary artery from the ascending aorta is much more common than origin of the left pulmonary artery from this vessel (8 to 1). Twenty-three patients were managed without operation with a 30% 1-year survival rate. Among those patients managed surgically, the survival rate was 84% at 1 year. It is now clear that operation should be done as early as possible to prevent irreversible changes occurring in the pulmonary arterial vasculature since microscopic features of pulmonary hypertension have been seen during the first month of life. One patient was operated on at 5 months with correction of the deformity. The pulmonary arterial pressure decreased to normal after operation. This child is now asymptomatic and his 10-year postoperative follow-up is the longest found in the literature. Images Fig. 1. Fig. 2A. Fig. 2B. Fig. 2C. Fig. 3. Fig. 4A and B. Fig. 8. PMID:3606229

  10. Main pulmonary artery stenosis caused by fibrocalcified mass in a young infant.

    PubMed Central

    Han, Heon-Seok; Park, Jeong-Hyun; Kim, Deok Soo; Lee, Seog-Jae; Hong, Jang-Soo; Lee, Geon Kook

    2002-01-01

    We present a rare case of main pulmonary artery stenosis secondary to protruding fibrous material in the main pulmonary artery associated with patent ductus arteriosus. A 1-month-old baby boy manifested cardiac murmur. Echocardiogram showed circumferential high echogenic mass inside the main pulmonary artery with pressure gradient of 49 mmHg and patent ductus arteriosus. The mass did not regress during 3 months' follow-up period. Angiographic images showed that the circular filling defect was located at the main pulmonary artery distal to pulmonary valve, and pulmonary valve and both pulmonary arteries were normal. After surgical removal of the circumferential material and ductus ligation, the pressure gradient became negligible. The material was consisted of scarcely cellular fibrous tissue, abundant coagulum of fibrinous material and dense calcification. PMID:12172057

  11. Late Endovascular Pulmonary Artery Band Migration.

    PubMed

    Luciani, Giovanni Battista; Lucchese, Gianluca; Hoxha, Stiljan; Torre, Salvatore; Treviso, Oscar; Faggian, Giuseppe

    2016-01-01

    Here reported is an unusual case of pulmonary artery band migration with serendipitous clinical presentation late after neonatal palliation of single ventricle with aortic arch hypoplasia. The diagnostic and therapeutic implications are discussed. PMID:26694278

  12. Interaction between the Haptoglobin 2 Phenotype and Diabetes Mellitus on Systolic Pulmonary Arterial Pressure and Nitric Oxide Bioavailability in Hemodialysis Patients

    PubMed Central

    Dahan, Inbal; Farber, Evgeny; Thauho, Nadia; Nakhoul, Nakhoul; Francis, Adi; Awawde, Mohamad; Levy, Andrew P.; Kim-Shapiro, Daniel B.; Basu, Swati; Nakhoul, Farid

    2015-01-01

    Elevated systolic pulmonary artery pressure (s-PAP, ≥35 mmHg) serves as an independent predictor of mortality in hemodialysis (HD) and diabetic (DM) patients. A polymorphism in the antioxidant Haptoglobin (Hp) gene has been shown to regulate the bioavailability of nitric oxide (NO), a major mediator of pulmonary vascular tone. We therefore set out to test the hypothesis that the Hp polymorphism may be a determinant of developing elevated s-PAP specifically in the DM state due to a decreased bioavailability of NO. To test our hypothesis we Hp typed and performed transthoracic echocardiography on a series of HD patients and stratified them into elevated and normal s-PAP groups and then evaluated whether there was a significant association between the Hp type, elevated s-PAP, and decreased NO bioavailability as defined by low plasma nitrite. We found a statistically significant interaction between the Hp type and DM on the prevalence of elevated s-PAP and lower mean nitrite levels with the combination of elevated s-PAP and low nitrite levels being significantly more prevalent in Hp 2-2 DM individuals. We conclude that the Hp 2 type is associated with elevated s-PAP levels and low plasma nitrite levels in HD patients specifically in the DM state. PMID:26171400

  13. The role of pulmonary arterial stiffness in COPD

    PubMed Central

    Weir-McCall, Jonathan R.; Struthers, Allan D.; Lipworth, Brian J.; Houston, J. Graeme

    2015-01-01

    COPD is the second most common cause of pulmonary hypertension, and is a common complication of severe COPD with significant implications for both quality of life and mortality. However, the use of a rigid diagnostic threshold of a mean pulmonary arterial pressure (mPAP) of ≥25mHg when considering the impact of the pulmonary vasculature on symptoms and disease is misleading. Even minimal exertion causes oxygen desaturation and elevations in mPAP, with right ventricular hypertrophy and dilatation present in patients with mild to moderate COPD with pressures below the threshold for diagnosis of pulmonary hypertension. This has significant implications, with right ventricular dysfunction associated with poorer exercise capability and increased mortality independent of pulmonary function tests. The compliance of the pulmonary artery (PA) is a key component in decoupling the right ventricle from the pulmonary bed, allowing the right ventricle to work at maximum efficiency and protecting the microcirculation from large pressure gradients. PA stiffness increases with the severity of COPD, and correlates well with the presence of exercise induced pulmonary hypertension. A curvilinear relationship exists between PA distensibility and mPAP and pulmonary vascular resistance (PVR) with marked loss of distensibility before a rapid rise in mPAP and PVR occurs with resultant right ventricular failure. This combination of features suggests PA stiffness as a promising biomarker for early detection of pulmonary vascular disease, and to play a role in right ventricular failure in COPD. Early detection would open this up as a potential therapeutic target before end stage arterial remodelling occurs. PMID:26095859

  14. 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

  15. A Huge Thrombosed Pulmonary Artery Aneurysm without Pulmonary Hypertension in a Patient with Hepatosplenic Schistosomiasis

    PubMed Central

    Abo-Salem, Elsayed S.; Ramadan, Mahmoud M.

    2015-01-01

    Patient: Male, 55 Final Diagnosis: Thrombosed pulmonary artery aneurysm Symptoms: Cough productive • fever • shortness of breath Medication: — Clinical Procedure: Pericardiocentesis Specialty: Cardiology Objective: Rare disease Background: We herein report a case of huge pulmonary artery aneurysm in a 55-year-old male farmer from the Nile delta (Lower-Egypt), mostly due to infestation with Schistosoma mansoni, which is the parasite causing hepatosplenic schistosomiasis. Case Report: This male patient was admitted with a month-long history of progressive shortness of breath, 2-month history of fever, and a cough with mucoid sputum for 10 days. On examination, he had normal temperature and blood pressure, but he had tachypnea, tachycardia, and congested neck veins. Electrocardiography showed multifocal atrial tachycardia and right bundle branch block. Conclusions: The present case is unique in that it shows the presence of a huge pulmonary artery aneurysm despite the absence of pulmonary hypertension. PMID:25746428

  16. Acute pressure overload of the right ventricle. Comparison of two models of right-left shunt. Pulmonary artery to left atrium and right atrium to left atrium: experimental study

    PubMed Central

    2011-01-01

    Abtract Background In right ventricular failure (RVF), an interatrial shunt can relieve symptoms of severe pulmonary hypertension by reducing right ventricular preload and increasing systemic flow. Using a pig model to determine if a pulmonary artery - left atrium shunt (PA-LA) is better than a right atrial - left atrial shunt (RA-LA), we compared the hemodynamic effects and blood gases between the two shunts. Methods Thirty, male Large White pigs weighting in average 21.3 kg ± 0.7 (SEM) were divided into two groups (15 pigs per group): In group 1, banding of the pulmonary artery and a pulmonary artery to left atrium shunt with an 8 mm graft (PA-LA) was performed and in group 2 banding of the pulmonary artery and right atrial to left atrial shunt (RA-LA) with a similar graft was performed. Hemodynamic parameters and blood gases were measured from all cardiac chambers in 10 and 20 minutes, half and one hour interval from the baseline (30 min from the banding). Cardiac output and flow of at the left anterior descending artery was also monitored. Results In both groups, a stable RVF was generated. The PA-LA shunt compared to the RA-LA shunt has better hemodynamic performance concerning the decreased right ventricle afterload, the 4 fold higher mean pressure of the shunt, the better flow in left anterior descending artery and the decreased systemic vascular resistance. Favorable to the PA-LA shunt is also the tendency - although not statistically significant - in relation to central venous pressure, left atrial filling and cardiac output. Conclusion The PA-LA shunt can effectively reverse the catastrophic effects of acute RVF offering better hemodynamic characteristics than an interatrial shunt. PMID:22011551

  17. Longitudinal distribution of vascular resistance in the pulmonary arteries, capillaries, and veins

    PubMed Central

    Brody, Jerome S.; Stemmler, Edward J.; DuBois, Arthur B.

    1968-01-01

    A new method has been described for measuring the pressure and resistance to blood flow in the pulmonary arteries, capillaries, and veins. Studies were performed in dog isolated lung lobes perfused at constant flow with blood from a donor dog. Pulmonary artery and vein volume and total lobar blood volume were measured by the ether plethysmograph and dyedilution techniques. The longitudinal distribution of vascular resistance was determined by analyzing the decrease in perfusion pressure caused by a bolus of low viscosity liquid introduced into the vascular inflow of the lobe. The pulmonary arteries were responsible for 46% of total lobar vascular resistance, whereas the pulmonary capillaries and veins accounted for 34 and 20% of total lobar vascular resistance respectively. Vascular resistance was 322 dynes ·sec·cm-5/ml of vessel in the lobar pulmonary arteries, 112 dynes·sec·cm-5/ml in the pulmonary capillaries, and 115 dynes·sec·cm-5/ml in the lobar pulmonary veins. Peak vascular resistivity (resistance per milliliter of volume) was in an area 2 ml proximal to the capillary bed, but resistivity was high throughout the pulmonary arterial tree. The pulmonary arteries accounted for approximately 50% of vascular resistance upstream from the sluice point when alveolar pressure exceeded venous pressure. The method described provides the first measurements of pulmonary capillary pressure. Mid-capillary pressure averaged 13.3 cm H2O, pulmonary artery pressure averaged 20.4 cm H2O, and pulmonary vein pressure averaged 9.2 cm H2O. These techniques also provide a way of analyzing arterial, capillary, and venous responses to various pharmacologic and physiologic stimuli. PMID:4868032

  18. 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

  19. Sleep-disordered breathing is associated with depletion of circulating endothelial progenitor cells and elevation in pulmonary arterial pressure in patients with decompensated systolic heart failure

    PubMed Central

    Zhang, Han; Feng, Liu; Wan, Qi-Lin; Hong, Yan; Li, Yan-Ming; Cheng, Guan-Chang; Han, Xin-Qiang

    2015-01-01

    Background Sleep-disordered breathing (SDB) is known to occur frequently in and may predict worsening progression of patients with congestive heart failure (CHF). SDB is also known to play an important role in the development of idiopathic pulmonary arterial hypertension (PAH) via inducing endothelial dysfunction and vascular remodeling, a pathological process that can be significantly influenced by factors such as osteoprotegerin (OPG) and endothelial progenitor cells (EPCs). The objective of this study is to determine if CHF with SDB is associated with changes in OPG, EPCs, and PAH. Methods EPCs were isolated, cultured, and quantified from CHF patients with SDB (n = 52), or without SDB (n = 68). OPG and N-terminal pro-brain natriuretic peptide (NT-proBNP) from each group was analyzed and correlated with EPCs and the mean pulmonary artery pressure (mPAP) measured by right heart catheterization. Results A significant decrease in circulating EPCs (29.30 ± 9.01 vs. 45.17 ± 10.51 EPCs/× 200 field; P < 0.05) was found in CHF patients with SDB compared to those without SDB. Both OPG (789.83 ± 89.38 vs. 551.29 ± 42.12 pg/mL; P < 0.05) and NT-proBNP (5946.50 ± 1434.50 vs. 3028.60 ± 811.90 ng/mL; P < 0.05) were also significantly elevated in SDB CHF patients who also had significantly elevated mPAP (50.2 ± 9.5 vs. 36.4 ± 4.1 mm Hg; P < 0.05). EPC numbers correlated inversely with the episodes of apnea and hypopnea per hour (RDI, r = –0.45, P = 0.037) and blood level of OPG (r = –0.53, P = 0.011). Although NT-proBNP was also increased significantly in patients with SDB, it had no correlation with either EPCs or RDI. Conclusions SDB due to hypoxemia from decompensated CHF is associated with (1) OPG elevation, (2) EPC depletion, and (3) mPAP elevation. The inverse relationship of circulating OPG with EPCs suggests a likely mechanism for hypoxemia and OPG in the development of pulmonary vascular dysfunction via depleting EPCs, thus worsening prognosis of CHF. PMID

  20. A Novel Channelopathy in Pulmonary Arterial Hypertension

    PubMed Central

    Austin, Eric D.; Eyries, Mélanie; Sampson, Kevin S.; Soubrier, Florent; Germain, Marine; Trégouët, David-Alexandre; Borczuk, Alain; Rosenzweig, Erika Berman; Girerd, Barbara; Montani, David; Humbert, Marc; Loyd, James E.; Kass, Robert S.; Chung, Wendy K.

    2013-01-01

    BACKGROUND Pulmonary arterial hypertension is a devastating disease with high mortality. Familial cases of pulmonary arterial hypertension are usually characterized by autosomal dominant transmission with reduced penetrance, and some familial cases have unknown genetic causes. METHODS We studied a family in which multiple members had pulmonary arterial hypertension without identifiable mutations in any of the genes known to be associated with the disease, including BMPR2, ALK1, ENG, SMAD9, and CAV1. Three family members were studied with whole-exome sequencing. Additional patients with familial or idiopathic pulmonary arterial hypertension were screened for the mutations in the gene that was identified on whole-exome sequencing. All variants were expressed in COS-7 cells, and channel function was studied by means of patch-clamp analysis. RESULTS We identified a novel heterozygous missense variant c.608 G→A (G203D) in KCNK3 (the gene encoding potassium channel subfamily K, member 3) as a disease-causing candidate gene in the family. Five additional heterozygous missense variants in KCNK3 were independently identified in 92 unrelated patients with familial pulmonary arterial hypertension and 230 patients with idiopathic pulmonary arterial hypertension. We used in silico bioinformatic tools to predict that all six novel variants would be damaging. Electrophysiological studies of the channel indicated that all these missense mutations resulted in loss of function, and the reduction in the potassium-channel current was remedied by the application of the phospholipase inhibitor ONO-RS-082. CONCLUSIONS Our study identified the association of a novel gene, KCNK3, with familial and idiopathic pulmonary arterial hypertension. Mutations in this gene produced reduced potassium-channel current, which was successfully remedied by pharmacologic manipulation. (Funded by the National Institutes of Health.) PMID:23883380

  1. Pulmonary arterial hypertension (ascites syndrome) in broilers: a review.

    PubMed

    Wideman, R F; Rhoads, D D; Erf, G F; Anthony, N B

    2013-01-01

    Pulmonary arterial hypertension (PAH) syndrome in broilers (also known as ascites syndrome and pulmonary hypertension syndrome) can be attributed to imbalances between cardiac output and the anatomical capacity of the pulmonary vasculature to accommodate ever-increasing rates of blood flow, as well as to an inappropriately elevated tone (degree of constriction) maintained by the pulmonary arterioles. Comparisons of PAH-susceptible and PAH-resistant broilers do not consistently reveal differences in cardiac output, but PAH-susceptible broilers consistently have higher pulmonary arterial pressures and pulmonary vascular resistances compared with PAH-resistant broilers. Efforts clarify the causes of excessive pulmonary vascular resistance have focused on evaluating the roles of chemical mediators of vasoconstriction and vasodilation, as well as on pathological (structural) changes occurring within the pulmonary arterioles (e.g., vascular remodeling and pathology) during the pathogenesis of PAH. The objectives of this review are to (1) summarize the pathophysiological progression initiated by the onset of pulmonary hypertension and culminating in terminal ascites; (2) review recent information regarding the factors contributing to excessively elevated resistance to blood flow through the lungs; (3) assess the role of the immune system during the pathogenesis of PAH; and (4) present new insights into the genetic basis of PAH. The cumulative evidence attributes the elevated pulmonary vascular resistance in PAH-susceptible broilers to an anatomically inadequate pulmonary vascular capacity, to excessive vascular tone reflecting the dominance of pulmonary vasoconstrictors over vasodilators, and to vascular pathology elicited by excessive hemodynamic stress. Emerging evidence also demonstrates that the pathogenesis of PAH includes characteristics of an inflammatory/autoimmune disease involving multifactorial genetic, environmental, and immune system components. Pulmonary

  2. Recent trends in pulmonary arterial hypertension

    PubMed Central

    Natarajan, Rajagopalan

    2011-01-01

    Pulmonary hypertension is a serious and unrelenting pulmonary vascular disorder that affects the functional quality of patients and significantly decreases their life span. If diagnosed early, with the number of new therapeutic options that are available, a better quality of life can be provided for a protracted length of time. It is likely that the available treatment will change the natural course of the disease and perhaps prolong survival. As symptoms are often subtle in the early stages of the disease it is imperative that physicians are aware of the manifestations of this condition. A thorough investigation of patients suspected of this condition is essential so that appropriate treatment can be initiated promptly. The routine workup of a patient suspected to have pulmonary hypertension could easily be carried out in any well-equipped peripheral hospital in many affluent and advanced countries. However, it must be mentioned that in some less advanced countries the necessary work up can only be done in major teaching hospitals. Both pulmonologists and cardiologists should be aware of the pathophysiology of pulmonary arterial hypertension, the workup and the treatment options that are available. Patients with refractory pulmonary hypertension should be referred to these research centers for enrolment into any ongoing drug trials as well as for evaluation for heart–lung, single lung, or double lung transplantation. This paper is primarily aimed at pulmonologists and cardiologists taking care of these patients. Unless indicated otherwise this paper mainly deals with WHO group 1 pulmonary hypertension which is designated pulmonary arterial hypertension. Extensive review of the literature spanning the last 30 years was made through Medline using titles such as primary pulmonary hypertension, pulmonary arterial hypertension, secondary pulmonary hypertension, and pulmonary vascular diseases. PMID:21654985

  3. 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.

  4. [Candida albicans endocarditis after pulmonary artery banding].

    PubMed

    Talvard, M; Paranon, S; Dulac, Y; Mansir, T; Kreitmann, B; Acar, P

    2009-08-01

    Endocarditis is uncommon in infants and is exceptionally related to Candida albicans on pulmonary banding. We report on a case in a 7-month-old infant who had pulmonary artery banding for a ventricular septal defect and who presented with candidal endocarditis. Banding was chosen because of the patient's poor trophic and unstable status, which could be risky for surgery involving extracorporeal circulation. A few weeks after the banding, the patient developed systemic Candida infection, which was treated successfully. At 7 months, cardiac failure appeared without fever or inflammatory signs. Cardiac echography showed that the banding was not protective as well as a hyperechogenic image on the pulmonary bifurcation. The angioscan showed a hypodense thrombus. Emergency surgery was performed consisting of pulmonary artery exploration, thrombectomy, and ventricular septal defect closure. The exploration showed a pulmonary artery perforation caused by the infected pseudoaneurysm and the migration of the banding into the pulmonary artery. The anatomopathologic analysis of the vegetation identified multisensitive Candida albicans. After surgery and prolonged antifungal treatment, progression was satisfactory. PMID:19525096

  5. [Effect of changes in airway pressure and the inspiratory volume on the fluid filtration rate and pulmonary artery pressure in isolated rabbit lungs perfused with blood and acellular solution].

    PubMed

    Crespo, Astrid; Novoa, Eva; Urich, Daniela; Trejo, Humberto; Pezzulo, Alejandro; Sznajder, Jacob I; Livia, Fernández; Sánchez-de León, Roberto

    2006-12-01

    It has been reported that ventilation with large tidal volumes causes pulmonary edema in rats by the stimulation and release of proinflammatory mediators. Our objective was to determine the level at which volutrauma induced by changes in Airway Pressure (PAW) and Inspiratory Volume (VI) produce significant changes on the Fluid Filtration Rate (FFR) and Pulmonary Artery Pressure (PAP) in lungs perfused with blood (cellular groups) or with a buffer-albumin solution (acellular groups), with a Positive End Expiratory Pressure (PEEP) 0 or 2 cmH2O and to study the effect of a vasodilator with antiinflammatory properties (fenoterol) in blood-perfused groups. Three experimental groups were used: the cellular groups studied the effect of increased PAW and IV in isolated lungs perfused with blood and PEEP 0 and 2; the acellular groups studied the increased PAW and IV in isolated lungs perfused with a buffer-albumin solution and PEEP 0 and 2; The fenoterol group studied the effect of increased PAW and IV in isolated lungs perfused with blood + fenoterol and PEEP 2. The results show that an increase of FFR is produced earlier in acellular groups than in cellular ones and that the damage in cellular groups is microscopically and macroscopically inferior when compared to acellular groups. Fenoterol did not inhibit edema formation, and that PEEP 2, both in the cellular and the acellular groups, has a protective effect. We propose the possible existence of mediators with protective effects against the formation of pulmonary edema in the blood. These data suggest that volutrauma induced pulmonary edema has a predominantly traumatic origin when the lungs are perfused with blood. PMID:17176901

  6. 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

  7. Urantide alleviates monocrotaline induced pulmonary arterial hypertension in Wistar rats.

    PubMed

    Mei, Yifang; Jin, Hong; Tian, Wei; Wang, Hao; Wang, Han; Zhao, Yanping; Zhang, Zhiyi; Meng, Fanchao

    2011-08-01

    Pulmonary arterial hypertension (PAH) is a serious disorder with poor prognosis. Urotensin II (UII) has been confirmed to be powerful vasoconstrictor than endothelin-1, which may play an important role in PAH development. The aim of this study is to observe the effects of urantide, a UII receptor antagonist, on monocrotaline (MCT) induced PAH in rats. 60 male Wistar rats were divided into six groups. For early treatment experiment, rats were divided into normal control group, MCT(4w) model group (MCT + saline × 3 wks from the 8th day of MCT injection) and urantide early treatment group (MCT + urantide 10 μg/kg/d × 3 wks, 1 week after MCT injection once). For late treatment experiment, rats were divided as controls, MCT(6w) model group (MCT + saline × 2 wks, 4 weeks after MCT injection once) and urantide late treatment group (MCT + urantide 10 μg/kg/d × 2 wks, 4 weeks after MCT injection once). At the end of experiments, mean pulmonary arterial pressures (mPAP) and mean blood pressure (MBP) of rats in each group were measured by catheterization. Right ventricular weight ratio was also weighed. Relaxation effects of urantide on intralobar pulmonary arterial rings of normal control and MCT(4w) model rats were investigated. Pulmonary artery remodeling was detected by hematoxylin and eosin (HE) staining and immunohistochemistry analysis. Serum nitric oxide (NO) levels in all six groups were assayed by ELISA kits. Urantide markedly reduced the mPAP levels of MCT induced PAH in both early and late treatment groups. It didn't change the MBP. Urantide dose-dependently relaxed the pulmonary arterial rings of normal control and MCT(4w) model rats. Moreover, N(G)-Nitro-l-arginine Methyl Ester (l-NAME) blocked the dilation response induced by urantide. In addition, urantide inhibited the pulmonary vascular remodeling remarkably. Serum NO level elevated in both early and late treatment rats with urantide infusion. These results suggest that urantide effectively alleviated

  8. The altitude at which a calf is born and raised influences the rate at which mean pulmonary arterial pressure increases with age.

    PubMed

    Neary, J M; Garry, F B; Holt, T N; Brown, R D; Stenmark, K R; Enns, R M; Thomas, M G

    2015-10-01

    Right heart failure secondary to pulmonary hypertension is a leading cause of mortality among suckling beef calves in the Rocky Mountain region. The objective of this study was to track changes in pulmonary arterial pressures (PAP) in healthy calves born and raised at altitudes ranging from 1,470 to 2,730 m. It was hypothesized that calves located at higher altitudes would show a greater increase in mean PAP (mPAP) with age than would be experienced by calves located at lower altitudes. The rationale is that high altitude hypobaric hypoxia causes a greater rate of vascular remodeling and, consequently, greater resistance to blood flow than calves located at lower altitudes. A prospective study was conducted on 5 cohorts of suckling calves from 4 herds located at altitudes of 1,470, 2,010, 2,170, and 2,730 m. In total, 470 PAP measurements were obtained from 258 calves. As hypothesized, calves located at altitudes ≥2,170 m showed a significant increase in mPAP with age ( ≤ 0.002) whereas calves at 1,470 m did not ( = 0.16). Except for calves at 2,170 m ( < 0.001), systolic PAP did not increase with age ( ≥ 0.16). Diastolic PAP increased with age at altitudes ≥ 2,170 m ( ≤ 0.09) but did not change in calves at 1,470 m ( = 0.20). In summary, mPAP and the rate at which mPAP increases with age are positively associated with the altitude at which calves are born and raised. PMID:26523564

  9. Initial experience with Tadalafil in Pediatric Pulmonary Arterial Hypertension

    PubMed Central

    Takatsuki, Shinichi; Calderbank, Michelle; Ivy, David Dunbar

    2012-01-01

    Summary Our objective was to investigate the safety, tolerability, and effects of tadalafil in children with pulmonary arterial hypertension after transition from sildenafil or receiving tadalafil as initial therapy. Thirty three pediatric patients with pulmonary arterial hypertension were retrospectively evaluated. Twenty nine of 33 patients were switched from sildenafil to tadalafil. The main reason for changing from sildenafil was once daily dosing. The average dose of sildenafil and tadalafil were 3.4+/−1.1 mg/kg/day and 1.0+/−0.4 mg/kg/day, respectively. In 14 of 29 patients undergoing repeat catheterization, statistically significant improvements were observed following transition from sildenafil to tadalafil, in mean pulmonary arterial pressure (mmHg) (53.2+/−18.3 versus 47.4+/−13.7, p<0.05) and pulmonary vascular resistance index (unitsxm2) (12.2+/−7.0 versus 10.6+/−7.2, p<0.05). In 4 patients treated with tadalafil as initial therapy, clinical improvement was noted. Side effect profiles were similar in patients who had transitioned from sildenafil to tadalafil and included headache, nausea, myalgia, nasal congestion, flushing, and allergic reaction. Two patients discontinued tadalafil due to migraine or an allergic reaction. One patient on sildenafil had no break through syncope after transition to tadalafil. Tadalafil can be safely used in pediatric patients with pulmonary arterial hypertension and may prevent disease progression. PMID:22402804

  10. Circulating Angiogenic Precursors in Idiopathic Pulmonary Arterial Hypertension

    PubMed Central

    Asosingh, Kewal; Aldred, Micheala A.; Vasanji, Amit; Drazba, Judith; Sharp, Jacqueline; Farver, Carol; Comhair, Suzy A.A.; Xu, Weiling; Licina, Lauren; Huang, Lan; Anand-Apte, Bela; Yoder, Mervin C.; Tuder, Rubin M.; Erzurum, Serpil C.

    2008-01-01

    Vascular remodeling in idiopathic pulmonary arterial hypertension (IPAH) involves hyperproliferative and apoptosis-resistant pulmonary artery endothelial cells. In this study, we evaluated the relative contribution of bone marrow-derived proangiogenic precursors and tissue-resident endothelial progenitors to vascular remodeling in IPAH. Levels of circulating CD34+CD133+ bone marrow-derived proangiogenic precursors were higher in peripheral blood from IPAH patients than in healthy controls and correlated with pulmonary artery pressure, whereas levels of resident endothelial progenitors in IPAH pulmonary arteries were comparable to those of healthy controls. Colony-forming units of endothelial-like cells (CFU-ECs) derived from CD34+CD133+ bone marrow precursors of IPAH patients secreted high levels of matrix metalloproteinase-2, had greater affinity for angiogenic tubes, and spontaneously formed disorganized cell clusters that increased in size in the presence of transforming growth factor-β or bone morphogenetic protein-2. Subcutaneous injection of NOD SCID mice with IPAH CFU-ECs within Matrigel plugs, but not with control CFU-ECs, produced cell clusters in the Matrigel and proliferative lesions in surrounding murine tissues. Thus, mobilization of high levels of proliferative bone marrow-derived proangiogenic precursors is a characteristic of IPAH and may participate in the pulmonary vascular remodeling process. PMID:18258847

  11. Crossed Pulmonary Arteries in a Patient With Persistent Truncus Arteriosus.

    PubMed

    Talwar, Sachin; Rajashekar, Palleti; Gupta, Saurabh Kumar; Gulati, Gurpreet Singh; Airan, Balram

    2016-06-01

    We report a 14-month-old child with persistent truncus arteriosus and crossed pulmonary arteries. The potential advantage of crossed pulmonary artery arrangement in achieving surgical correction is discussed. PMID:27211951

  12. 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

  13. MicroRNAs in Pulmonary Arterial Hypertension

    PubMed Central

    Zhou, Guofei; Chen, Tianji

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease without effective treatment. Despite decades of research and the development of novel treatments, PAH remains a fatal disease, suggesting an urgent need for better understanding of the pathogenesis of PAH. Recent studies suggest that microRNAs (miRNAs) are dysregulated in patients with PAH and in experimental pulmonary hypertension. Furthermore, normalization of a few miRNAs is reported to inhibit experimental pulmonary hypertension. We have reviewed the current knowledge about miRNA biogenesis, miRNA expression pattern, and their roles in regulation of pulmonary artery smooth muscle cells, endothelial cells, and fibroblasts. We have also identified emerging trends in our understanding of the role of miRNAs in the pathogenesis of PAH and propose future studies that might lead to novel therapeutic strategies for the treatment of PAH. PMID:25192340

  14. MicroRNAs in pulmonary arterial hypertension.

    PubMed

    Zhou, Guofei; Chen, Tianji; Raj, J Usha

    2015-02-01

    Pulmonary arterial hypertension (PAH) is a devastating disease without effective treatment. Despite decades of research and the development of novel treatments, PAH remains a fatal disease, suggesting an urgent need for better understanding of the pathogenesis of PAH. Recent studies suggest that microRNAs (miRNAs) are dysregulated in patients with PAH and in experimental pulmonary hypertension. Furthermore, normalization of a few miRNAs is reported to inhibit experimental pulmonary hypertension. We have reviewed the current knowledge about miRNA biogenesis, miRNA expression pattern, and their roles in regulation of pulmonary artery smooth muscle cells, endothelial cells, and fibroblasts. We have also identified emerging trends in our understanding of the role of miRNAs in the pathogenesis of PAH and propose future studies that might lead to novel therapeutic strategies for the treatment of PAH. PMID:25192340

  15. [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. PMID:27039998

  16. Video-assisted thoracoscopic bronchoplasty/pulmonary arterial angioplasty.

    PubMed

    Xu, Xin; Huang, Jun; Pan, Hui; Chen, Hanzhang; He, Jianxing

    2016-03-01

    Thoracoscopic bronchoplasty combined with pulmonary arterial angioplasty can be particularly challenging. In the past, it was often done by using a conventional incision or hybrid video-assisted small incision. In recent years, anecdotal articles have described the application of thoracoscopic bronchoplasty/pulmonary arterial angioplasty. This chapter will describe the details associated with thoracoscopic bronchoplasty/pulmonary arterial angioplasty. PMID:27076953

  17. Video-assisted thoracoscopic bronchoplasty/pulmonary arterial angioplasty

    PubMed Central

    Xu, Xin; Huang, Jun; Pan, Hui; Chen, Hanzhang

    2016-01-01

    Thoracoscopic bronchoplasty combined with pulmonary arterial angioplasty can be particularly challenging. In the past, it was often done by using a conventional incision or hybrid video-assisted small incision. In recent years, anecdotal articles have described the application of thoracoscopic bronchoplasty/pulmonary arterial angioplasty. This chapter will describe the details associated with thoracoscopic bronchoplasty/pulmonary arterial angioplasty. PMID:27076953

  18. 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

  19. Pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: pathophysiology.

    PubMed

    Humbert, M

    2010-03-01

    Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are two of the key subgroups of pulmonary hypertension. They are characterised by different risk factors. PAH can be associated with mutations in the gene encoding bone morphogenetic protein receptor type II (BMPR2), HIV infection, congenital heart disease, connective tissue disease (such as systemic sclerosis), and exposure to particular drugs and toxins including fenfluramine derivatives. In contrast, CTEPH can be associated with anti-phospholipid antibodies, splenectomy and the presence of a ventriculo-atrial shunt or an infected pacemaker. The first-line therapies used to treat PAH and CTEPH also differ. While medical therapy tends to be used for patients with PAH, pulmonary endarterectomy is the treatment of choice for patients with CTEPH. However, there are possible common mechanisms behind the two diseases, including endothelial cell dysfunction and distal pulmonary artery remodelling. Further research into these similarities is needed to assist the development of targeted pharmacological therapies for patients with inoperable CTEPH and patients who have persistent pulmonary hypertension after endarterectomy. PMID:20956167

  20. An inadequate pulmonary vascular capacity and susceptibility to pulmonary arterial hypertension in broilers.

    PubMed

    Wideman, R F; Chapman, M E; Hamal, K R; Bowen, O T; Lorenzoni, A G; Erf, G F; Anthony, N B

    2007-05-01

    Broilers are susceptible to pulmonary hypertension syndrome (PHS; ascites syndrome) when their pulmonary vascular capacity is anatomically or functionally inadequate to accommodate the requisite cardiac output without an excessive elevation in pulmonary arterial pressure. The consequences of an inadequate pulmonary vascular capacity have been demonstrated experimentally and include elevated pulmonary vascular resistance (PVR) attributable to noncompliant, fully engorged vascular channels; sustained pulmonary arterial hypertension (PAH); systemic hypoxemia and hypercapnia; specific right ventricular hypertrophy, and right atrioventricular valve failure (regurgitation), leading to central venous hypertension and hepatic cirrhosis. Pulmonary vascular capacity is broadly defined to encompass anatomical constraints related to the compliance and effective volume of blood vessels, as well as functional limitations related to the tone (degree of constriction) maintained by the primary resistance vessels (arterioles) within the lungs. Surgical occlusion of 1 pulmonary artery halves the anatomical pulmonary vascular capacity, doubles the PVR, triggers PAH, eliminates PHS-susceptible broilers, and reveals PHS-resistant survivors whose lungs are innately capable of handling sustained increases in pulmonary arterial pressure and cardiac output. We currently are using i.v. microparticle injections to increase the PVR and trigger PAH sufficient in magnitude to eliminate PHS-susceptible individuals while allowing PHS-resistant individuals to survive as progenitors of robust broiler lines. The microparticles obstruct pulmonary arterioles and cause local tissues and responding leukocytes to release vasoactive substances, including the vasodilator NO and the highly effective vasoconstrictors thromboxane A(2) and serotonin [5-hydroxytryptamine (5-HT)]. Nitric oxide is the principal vasodilator responsible for modulating (attenuating) the PAH response and ensuing mortality triggered by

  1. 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

  2. [Anesthetic Management for Lobectomy in a Patient with Pulmonary Arterial Hypertension].

    PubMed

    Imajo, Yukihiro; Komasawa, Nobuyasu; Kusaka, Yusuke; Kido, Haruki; Minami, Toshiaki

    2016-02-01

    Pulmonary arterial hypertension (PAH) is a known risk factor of perioperative complications, but the risks for non-cardiac operations have not yet been examined sufficiently. We report a case of a right lower lobectomy in a patient with PAH. A 73-year-old woman with Sjögren's syndrome was scheduled for right lowr lobectomy for primary lung cancer under general anesthesia. She was diagnosed with symptomatic PAH (estimated mean pulmonary arterial pressure, 40 mmHg) and medicated with ambrisentan. After induction of general anesthesia with propofol and fentanyl, a pulmonary artery catheter was placed to measure pulmonary artery pressure. The Pp/Ps was roughly 0.4 and the pulmonary artery clamp elevated it to 0.5. Milrinone administration gradually improved the Pp/Ps to 0.3. To avoid pulmonary artery pressure elevation during emergence of anesthesia, continuous dexmedetomidine was administered. The double-lumen tracheal tube was extubated uneventfully with minimal elevation in pulmonary arterial pressure. PMID:27017766

  3. An unexpected pulmonary arterial aneurysm in a COPD patient.

    PubMed

    Karkoulias, K; Lykouras, D; Nanopoulou, M; Tsiamita, M; Iliopoulos, P; Spiropoulos, K

    2011-01-01

    We present a case of an idiopathic pulmonary artery aneurysm in an asymptomatic patient who was treated for an irrelevant medical condition. Pulmonary artery aneurysms (PAA) are quite rare and can either be congenital or acquired. Congenital aneurysms are usually associated with cardiac malformations leading to pulmonary hypertension. Acquired aneurysms can be idiopathic or associated with infections (tuberculosis, syphilis), trauma, pulmonary valvular stenosis, or collagen diseases. Pulmonary artery aneurysms are not common and an idiopathic pulmonary artery aneurysm is a rare finding that could be diagnosed incidentally. PMID:22145274

  4. Endothelin receptor antagonists in pulmonary arterial hypertension.

    PubMed

    Channick, Richard N; Sitbon, Olivier; Barst, Robyn J; Manes, Alessandra; Rubin, Lewis J

    2004-06-16

    Endothelin receptor antagonism has emerged as an important therapeutic strategy in pulmonary arterial hypertension (PAH). Laboratory and clinical investigations have clearly shown that endothelin (ET)-1 is overexpressed in several forms of pulmonary vascular disease and likely plays a significant pathogenetic role in the development and progression of pulmonary vasculopathy. Oral endothelin receptor antagonists (ERAs) have been shown to improve pulmonary hemodynamics, exercise capacity, functional status, and clinical outcome in several randomized placebo-controlled trials. Bosentan, a dual-receptor antagonist, is approved by the U.S. Food and Drug Administration for class III and IV patients with PAH, based on two phase III trials. In addition to its efficacy as sole therapy, bosentan may have a role as part of a combination of drugs such as a prostanoid or sildenafil. The selective endothelin receptor-A antagonists sitaxsentan and ambrisentan are currently undergoing investigation. PMID:15194180

  5. Metabolomic Heterogeneity of Pulmonary Arterial Hypertension

    PubMed Central

    Zhao, Yidan; Peng, Jenny; Lu, Catherine; Hsin, Michael; Mura, Marco; Wu, Licun; Chu, Lei; Zamel, Ricardo; Machuca, Tiago; Waddell, Thomas; Liu, Mingyao; Keshavjee, Shaf; Granton, John; de Perrot, Marc

    2014-01-01

    Although multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH), the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to increased ATP synthesis for the vascular remodeling process in severe pulmonary hypertension. These identified metabolites may serve as potential biomarkers for the diagnosis of PAH. By profiling metabolomic alterations of the PAH lung, we reveal new pathogenic mechanisms of PAH, opening an avenue of exploration for therapeutics that target metabolic pathway alterations in the progression of PAH. PMID:24533144

  6. Management of Pulmonary Arterial Hypertension During Pregnancy

    PubMed Central

    Thomas, Shibu; Safdar, Zeenat; Torres, Fernando; Pacheco, Luis D.; Feldman, Jeremy; deBoisblanc, Bennet

    2013-01-01

    Background: Pulmonary arterial hypertension (PAH) is a rare disease with a predilection for young women that is associated with right ventricular failure and premature death. PAH can complicate pregnancy with hemodynamic instability or sudden death during parturition and postpartum. Our aim was to examine the impact of PAH on pregnancy outcomes in the modern era. Methods: We conducted a retrospective evaluation of pregnant patients with PAH managed between 1999 and 2009 at five US medical centers. Patient demographics, medical therapies, hemodynamic measurements, manner of delivery, anesthetic administration, and outcomes were assessed. Results: Among 18 patients with PAH, 12 continued pregnancy and six underwent pregnancy termination. Right ventricular systolic pressure in patients managed to parturition was 82 ± 5 mm Hg and in patients with pregnancy termination was 90 ± 16 mm Hg. Six patients underwent pregnancy termination at mean gestational age of 13 ± 1.0 weeks with no maternal deaths or complications. Twelve patients elected to continue their pregnancy and were hospitalized at 29 ± 1.4 weeks. PAH-specific therapy was administered to nine (75%) at time of delivery consisting of sildenafil, IV prostanoids, or combination therapy. All parturients underwent Cesarean section at 34 weeks with one in-hospital death and one additional death 2 months postpartum for maternal mortality of 16.7%. Conclusions: Compared with earlier reports, maternal morbidity and mortality among pregnant women with PAH was reduced, yet maternal complications remain significant and patients should continue to be counseled to avoid pregnancy. PMID:23100080

  7. 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.

  8. Mitochondrial Dynamics in Pulmonary Arterial Hypertension

    PubMed Central

    Ryan, John; Dasgupta, Asish; Huston, Jessica; Chen, Kuang-Huieh; Archer, Stephen L.

    2015-01-01

    Pulmonary arterial hypertension (PAH) is an idiopathic cardiopulmonary disease characterized by obstruction of small pulmonary arteries by excessive proliferation and apoptosis-resistance of vascular cells, as well as inflammation, thrombosis and vasoconstriction. Vascular obstruction increases the afterload faced by the right ventricle (RV), leading to RV failure. The proliferative, obstructive vasculopathy of PAH shares several mitochondrial abnormalities with cancer, notably a shift to aerobic glycolysis and mitochondrial fragmentation. Mitochondria in the pulmonary artery smooth muscle cell (PASMC) normally serve as oxygen sensors. In PAH, acquired mitochondrial abnormalities, including epigenetic silencing of superoxide dismutase (SOD2), disrupt oxygen sensing creating a pseudo-hypoxic environment characterized by normoxic activation of Hypoxia-Inducible Factor-1α (HIF-1α). The resulting metabolic shift to aerobic glycolysis (the Warburg phenomenon) reflects inhibition of pyruvate dehydrogenase by pyruvate dehydrogenase kinases. In addition, altered mitochondrial dynamics result in mitochondrial fragmentation. The molecular basis of this structural change includes upregulation and activation of fission mediators, notably dynamin-related protein 1 (DRP-1), and downregulation of fusion mediators, especially mitofusin-2 (MFN2). These pathogenic mitochondrial abnormalities offer new therapeutic targets. Inhibition of mitotic fission or enhancement of fusion in PAH PASMC slows cell proliferation, causes cell cycle arrest, and induces apoptosis. DRP-1 inhibition or MFN2 gene therapy can regress PAH in experimental models of PAH. This review focuses on the etiology of mitochondrial fragmentation in PAH and explores the therapeutic implications of mitochondrial dynamics in the pulmonary vasculature and RV. PMID:25672499

  9. Pulmonary veno-occlusive disease presenting with thrombosis of pulmonary arteries.

    PubMed Central

    Katz, D. S.; Scalzetti, E. M.; Katzenstein, A. L.; Kohman, L. J.

    1995-01-01

    Pulmonary veno-occlusive disease is a rare cause of pulmonary hypertension. An unusual case presenting with thrombosis of the right pulmonary artery and serological evidence of autoimmunity is reported. Images PMID:7638821

  10. Pulmonary artery pseudoaneurysm after a left upper sleeve lobectomy

    PubMed Central

    2013-01-01

    A 55-year-old man was re-admitted for persistent hemoptysis and high fever three weeks after an initial left upper sleeve lobectomy for a central squamous lung cancer tumor. Pulmonary artery pseudoaneurysm and pulmonary infection were confirmed by multidetector computed tomography angiography and subsequent emergency completion pneumonectomy. The development of pulmonary artery pseudoaneurysm, secondary to post-operative pulmonary infection and pulmonary vascular manipulation, is rare and prompt surgical manipulation is mandatory. PMID:24119497

  11. Neonatal pulmonary artery thrombosis presenting as persistent pulmonary hypertension of the newborn.

    PubMed

    Sawyer, Taylor; Antle, Amanda; Studer, Matthew; Thompson, Mark; Perry, Stanton; Mahnke, C Becket

    2009-05-01

    Pulmonary artery thrombosis in neonates occurs rarely. This report describes the case of a term infant with a pulmonary artery thrombosis presenting as persistent pulmonary hypertension of the newborn. The risk factors identified in the case included maternal diabetes and heterozygous factor V Leiden deficiency. The pulmonary thrombus was successfully treated with percutaneous catheter-based embolectomy. PMID:19052800

  12. Human Immunodeficiency Virus and Pulmonary Arterial Hypertension

    PubMed Central

    Ali, Alaa M.

    2013-01-01

    Human immunodeficiency virus- (HIV-) related pulmonary arterial hypertension (PAH) is a rare complication of HIV infection. The pathophysiology of HIV-related PAH is complex, with viral proteins seeming to play the major role. However, other factors, such as coinfection with other microorganisms and HIV-related systemic inflammation, might also contribute. The clinical presentation of HIV-related PAH and diagnosis is similar to other forms of pulmonary hypertension. Both PAH-specific therapies and HAART are important in HIV-related PAH management. Future studies investigating the pathogenesis are needed to discover new therapeutic targets and treatments. PMID:24027641

  13. 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

  14. Molecular pathogenesis of pulmonary arterial hypertension

    PubMed Central

    Rabinovitch, Marlene

    2012-01-01

    Recent clinical and experimental studies are redefining the cellular and molecular bases of pulmonary arterial hypertension (PAH). The genetic abnormalities first identified in association with the idiopathic form of PAH — together with a vast increase in our understanding of cell signaling, cell transformation, and cell-cell interactions; gene expression; microRNA processing; and mitochondrial and ion channel function — have helped explain the abnormal response of vascular cells to injury. Experimental and clinical studies now converge on the intersection and interactions between a genetic predisposition involving the BMPR2 signaling pathway and an impaired metabolic and chronic inflammatory state in the vessel wall. These deranged processes culminate in an exuberant proliferative response that occludes the pulmonary arterial (PA) lumen and obliterates the most distal intraacinar vessels. Here, we describe emerging therapies based on preclinical studies that address these converging pathways. PMID:23202738

  15. 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

  16. Erythropoietin upregulation in pulmonary arterial hypertension.

    PubMed

    Karamanian, Vanesa A; Harhay, Michael; Grant, Gregory R; Palevsky, Harold I; Grizzle, William E; Zamanian, Roham T; Ihida-Stansbury, Kaori; Taichman, Darren B; Kawut, Steven M; Jones, Peter L

    2014-06-01

    The pathophysiologic alterations of patients with pulmonary arterial hypertension (PAH) are diverse. We aimed to determine novel pathogenic pathways from circulating proteins in patients with PAH. Multianalyte profiling (MAP) was used to measure 90 specifically selected antigens in the plasma of 113 PAH patients and 51 control patients. Erythropoietin (EPO) functional activity was assessed via in vitro pulmonary artery endothelial cell networking and smooth muscle cell proliferation assays. Fifty-eight patients had idiopathic PAH, whereas 55 had other forms of PAH; 5 had heritable PAH, 18 had connective tissue disease (15 with scleroderma and 3 with lupus erythematosis), 13 had portopulmonary hypertension, 6 had PAH associated with drugs or toxins, and 5 had congenital heart disease. The plasma-antigen profile of PAH revealed increased levels of several novel biomarkers, including EPO. Immune quantitative and histochemical studies revealed that EPO not only was significantly elevated in the plasma of PAH patients but also promoted pulmonary artery endothelial cell network formation and smooth muscle cell proliferation. MAP is a hypothesis-generating approach to identifying novel pathophysiologic pathways in PAH. EPO is upregulated in the circulation and lungs of patients with PAH and may affect endothelial and smooth muscle cell proliferation. PMID:25006446

  17. 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

  18. Inhaled treprostinil for the treatment of pulmonary arterial hypertension.

    PubMed

    Poms, Abby; Kingman, Martha

    2011-12-01

    Pulmonary arterial hypertension is a progressive disease characterized by vascular proliferation and vasoconstriction of the small pulmonary arteries that eventually leads to right-sided heart failure and death. Patients often initially have symptoms such as shortness of breath, fatigue, and edema; later in the disease, presyncope and syncope are common. Patients with progressive pulmonary arterial hypertension despite oral therapy and/or with severe disease typically require treatment with a prostanoid. Inhaled treprostinil (Tyvaso) is a prostacyclin analog indicated for the treatment of pulmonary arterial hypertension to increase walk distance in patients with symptoms classified as New York Heart Association functional class III. Inhaled treprostinil was approved by the Food and Drug Administration in July 2009. This article provides a brief overview of the pathophysiology of pulmonary arterial hypertension and reviews the mechanism of action, key clinical data, and the practical management of inhaled treprostinil in patients with pulmonary arterial hypertension. PMID:22135338

  19. 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

  20. Hemodynamic Characterization of Rodent Models of Pulmonary Arterial Hypertension.

    PubMed

    Ma, Zhiyuan; Mao, Lan; Rajagopal, Sudarshan

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a rare disease of the pulmonary vasculature characterized by endothelial cell apoptosis, smooth muscle proliferation and obliteration of pulmonary arterioles. This in turn results in right ventricular (RV) failure, with significant morbidity and mortality. Rodent models of PAH, in the mouse and the rat, are important for understanding the pathophysiology underlying this rare disease. Notably, different models of PAH may be associated with different degrees of pulmonary hypertension, RV hypertrophy and RV failure. Therefore, a complete hemodynamic characterization of mice and rats with PAH is critical in determining the effects of drugs or genetic modifications on the disease. Here we demonstrate standard procedures for assessment of right ventricular function and hemodynamics in both rat and mouse PAH models. Echocardiography is useful in determining RV function in rats, although obtaining standard views of the right ventricle is challenging in the awake mouse. Access for right heart catheterization is obtained by the internal jugular vein in closed-chest mice and rats. Pressures can be measured using polyethylene tubing with a fluid pressure transducer or a miniature micromanometer pressure catheter. Pressure-volume loop analysis can be performed in the open chest. After obtaining hemodynamics, the rodent is euthanized. The heart can be dissected to separate the RV free wall from the left ventricle (LV) and septum, allowing an assessment of RV hypertrophy using the Fulton index (RV/(LV+S)). Then samples can be harvested from the heart, lungs and other tissues as needed. PMID:27167679

  1. Tricuspid annular plane systolic excursion and pulmonary arterial systolic pressure relationship in heart failure: an index of right ventricular contractile function and prognosis.

    PubMed

    Guazzi, M; Bandera, F; Pelissero, G; Castelvecchio, S; Menicanti, L; Ghio, S; Temporelli, P L; Arena, R

    2013-11-01

    Echo-derived pulmonary arterial systolic pressure (PASP) and right ventricular (RV) tricuspid annular plane systolic excursion (TAPSE; from the end of diastole to end-systole) are of basic relevance in the clinical follow-up of heart failure (HF) patients, carrying two- to threefold increase in cardiac risk when increased and reduced, respectively. We hypothesized that the relationship between TAPSE (longitudinal RV fiber shortening) and PASP (force generated by the RV) provides an index of in vivo RV length-force relationship, with their ratio better disclosing prognosis. Two hundred ninety-three HF patients with reduced (HFrEF, n = 247) or with preserved left ventricular (LV) ejection fraction (HFpEF, n = 46) underwent echo-Doppler studies and N-terminal pro-brain-type natriuretic peptide assessment and were tracked for adverse events. The median follow-up duration was 20.8 mo. TAPSE vs. PASP relationship showed a downward regression line shift in nonsurvivors who were more frequently presenting with higher PASP and lower TAPSE. HFrEF and HFpEF patients exhibited a similar distribution along the regression line. Given the TAPSE, PASP, and TAPSE-to-PASP ratio (TAPSE/PASP) collinearity, separate Cox regression and Kaplan-Meier analyses were performed: one with TAPSE and PASP as individual measures, and the other combining them in ratio form. Hazard ratios for variables retained in the multivariate regression were as follows: TAPSE/PASP

  2. Pulmonary Artery Perforation Repair During Thrombectomy Using Microcoil Embolization

    SciTech Connect

    Tajima, Hiroyuki Murata, Satoru; Kumazaki, Tatsuo; Abe, Yutaka; Takano, Teruo

    2006-02-15

    A distal pulmonary artery perforation was successfully occluded by percutaneous microcoil embolization via a microcatheter. Microcoil embolization is a reasonable alternative therapeutic approach for this rare complication of pulmonary interventional procedures.

  3. 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

  4. 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.

  5. Afferent fibres from pulmonary arterial baroreceptors in the left cardiac sympathetic nerve of the cat

    PubMed Central

    Nishi, K.; Sakanashi, M.; Takenaka, F.

    1974-01-01

    1. Afferent discharges were recorded from the left cardiac sympathetic nerve or the third sympathetic ramus communicans of anaesthetized cats. Twenty-one single units with baroreceptor activity were obtained. 2. The receptors of each unit were localized to the extrapulmonary part of the pulmonary artery, determined by direct mechanical probing of the wall of the pulmonary artery after death of the animals. Conduction velocity of the fibres ranged from 2·5 to 15·7 m/sec. 3. Afferent discharges occurred irregularly under artificial ventilation. The impulse activity was increased when pulmonary arterial pressure was raised by an intravenous infusion of Locke solution, or by occlusion of lung roots, and decreased by bleeding the animal from the femoral artery. 4. Above a threshold pressure, discharges occurred synchronously with the systolic pressure pulse in the pulmonary artery. A progressive further rise in pressure did not produce an increase in the number of impulses per heart beat. Occlusion of lung roots initially elicited a burst of discharges but the number of impulses for each cardiac cycle gradually decreased. 5. The receptors responded to repetitive mechanical stimuli up to a frequency of 10/sec, but failed to respond to stimuli delivered at 20/sec. 6. The results provide further evidence for the presence of afferent fibres in the cardiac sympathetic nerve. These afferent fibres are likely to provide the spinal cord with specific information only on transient changes in pulmonary arterial pressure. PMID:4850456

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

    PubMed Central

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

    2011-01-01

    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). PMID:21357924

  7. Medical therapies for pulmonary arterial hypertension.

    PubMed

    Pulido, Tomas; Zayas, Nayeli; de Mendieta, Maitane Alonso; Plascencia, Karen; Escobar, Jennifer

    2016-05-01

    Pulmonary Arterial hypertension (PAH) is a chronic and progressive disease characterized by an increase in pulmonary vascular resistance due to severe remodeling of the small pulmonary arteries. In PAH, the endothelial cells fail to maintain their homeostatic balance, with the consequent impaired production of vasodilators and over-expression of vasoconstrictors and proliferators. Current treatment of PAH is based on the discovery of three main pathways of endothelial dysfunction (prostacyclin, nitric oxide and endothelin-1), and includes drugs such as prostacyclin analogs, phosphodiesterase-5 inhibitors and endothelin receptor antagonists (ERAs). Recently approved drugs that act through these classic pathways include riociguat (cyclic GMP stimulator) and macitentan (a tissue specific dual ERA). However, several new drugs and new pathways are under study. New targeted therapies include tyrosine kinase inhibitors, Rho kinase inhibitors and serotonin receptor blockers. There are now ten drugs approved for the treatment of PAH that, alone or in combination, have changed the natural history of this disease. The new drugs will allow us to further modified the patients' life expectancy and move towards a cure. PMID:26791159

  8. 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

  9. Pulmonary vascular pressure profiles in broilers selected for susceptibility to pulmonary hypertension syndrome: age and sex comparisons.

    PubMed

    Wideman, R F; Eanes, M L; Hamal, K R; Anthony, N B

    2010-09-01

    Broilers that are susceptible to pulmonary hypertension syndrome (PHS, ascites) have an elevated pulmonary arterial pressure (PAP) when compared with PHS-resistant broilers. Two distinctly different syndromes, pulmonary arterial hypertension and pulmonary venous hypertension (PVH), both are associated with increases in PAP. Pulmonary arterial hypertension occurs when the right ventricle must elevate the PAP to overcome increased resistance to flow through restrictive pulmonary arterioles upstream from the pulmonary capillaries. In contrast, PVH is commonly caused by increased downstream (postcapillary) resistance. The sites of resistance to pulmonary blood flow are deduced by making contemporaneous measurements of the PAP and the wedge pressure (WP) and calculating the transpulmonary pressure gradient (TPG) (TPG = PAP - WP). We obtained PAP and WP values from 8-, 12-, 16-, 20-, and 24-wk-old anesthetized male and female broilers from a PHS-susceptible line. Pressures were recorded as a catheter was advanced through a wing vein to the pulmonary artery and onward until the WP was obtained. In addition to sex and age comparisons of vascular pressure gradients, the data also were pooled to obtain 3 cohorts for broilers having the lowest PAP values (n = 52; range: 12 to 22.9 mmHg), intermediate PAP values (n = 63; range: 23 to 32.9 mmHg), and highest PAP values (n = 62; range: 33 to 62 mmHg) independent of age or sex. Within each of the age, sex, and PAP cohort comparisons, broilers with elevated PAP consistently exhibited the hemodynamic characteristics of pulmonary arterial hypertension (elevated PAP and TPG combined with a normal WP) and not PVH (elevated PAP and WP combined with a normal or reduced TPG). Susceptibility to PHS can be attributed primarily to pulmonary arterial hypertension associated with increased precapillary (arteriole) resistance. PMID:20709965

  10. Interruption of pulmonary arterial flow with inadequate ventilation leads to pulmonary infection.

    PubMed

    Urano; Shibayama, Y; Fukunshi, K; Nariyama, K; Ohsawa, N

    1996-03-01

    We examined the effect of interruption of pulmonary arterial flow and inadequate ventilation on the development of pulmonary infarction in rats. Pulmonary arterial flow was blocked by the injection of agar into the inferior vena cava and inadequate ventilation was produced by obstructing the left main bronchus with a polypropylene tip. Histological and angiographic examination of the lung demonstrated that: pulmonary artery embolism alone does not induce pulmonary infarction; obstruction of a bronchus does not induce significant changes, but that pulmonary infarction develops when pulmonary artery embolism and obstruction of a bronchus occur simultaneously. It has been thought that pulmonary infarction is caused by acute obstruction of a pulmonary artery, however, the alveolar walls are supplied with oxygen by both the pulmonary circulation and by ventilation. Interruption of pulmonary arterial flow alone is probably not sufficient to induce pulmonary infarction, which is probably caused by deficiency of oxygen supply to the alveolar walls by a synergy between interruption of pulmonary arterial flow and inadequate ventilation. PMID:8605572

  11. Advances in Pediatric Pulmonary Arterial Hypertension

    PubMed Central

    Ivy, Dunbar

    2012-01-01

    Purpose of Review Pulmonary arterial hypertension (PAH) is an important cause of morbidity and mortality in children. Approved medications for the treatment of adult PAH have been used to treat children but evidence based treatment algorithms for children are lacking. Recent Findings Pediatric PAH registries have begun to define the incidence and prevalence of idiopathic PAH and PAH associated with congenital heart disease. A pediatric specific classification of pulmonary hypertensive vascular disease has been proposed. Furthermore, the first randomized placebo-controlled trial of type-5 phosphodiesterase therapy in treatment naïve children with PAH has been completed and reported. This trial highlights the importance of the difficulties of performing clinical trials children with targeted PAH therapy as well as the importance of long-term follow-up of adverse events. Summary Classification, clinical trials, and therapy for children with PAH must take into account the unique aspects of PAH in children. PMID:22274573

  12. Management of pulmonary arterial hypertension associated with congenital heart disease.

    PubMed

    Togănel, Rodica; Benedek, I; Suteu, Carmen; Blesneac, Cristina

    2007-01-01

    Congenital heart diseases are the most common congenital malformations and account for about eight cases per 1000 births and are often associated with pulmonary arterial hypertension. Increased shear stress and the excess flow through the pulmonary vascular bed due to a systemic-to-pulmonary shunt lead to the development of pulmonary vascular disease and an increase in pulmonary vascular resistance. Without surgical repair approximately 30% of patients develop pulmonary vascular disease. Eisenmenger syndrome represents the extreme end of pulmonary arterial hypertension with congenital heart disease. We summarized the current therapeutic options for pulmonary arterial hypertension; conventional treatments including calcium channel blockers, anticoagulation, digitalis, diuretics, and new treatment: prostacyclin, bosentan, sildenafil, ambrisentan. Preliminary data of new therapies are encouraging with disease significantly improved natural history, but there is need for more evidence-based data. PMID:18333354

  13. [SURGERY FOR SARCOMA OF THE PULMONARY ARTERY].

    PubMed

    Parshin, V D; Motus, I Ya; Belov, Yu V; Chernyavsky, A M; Neretin, A V; Rusinov, V V

    2015-01-01

    Sarcoma of the pulmonary artery is a rare tumor. At present the literature describes single cases. However the number of publications increases in recent time due to improved diagnostics. There are appeared papers, which provide a series of observations of surgical treatment for this kind of tumor exceeded more than 10 cases. It can be assumed that today the number of these cases in the literature contains several hundreds. Thus despite the rarity of this tumor there is a certain understanding of the clinical picture of this disease and treatment that we tried to do in this paper being studied the available literature and bringing four of our observation. PMID:26242161

  14. Pericardial effusion in pulmonary arterial hypertension

    PubMed Central

    2013-01-01

    Abstract Pulmonary arterial hypertension (PAH) is a serious condition that can lead to right heart failure and death. Pericardial effusion in PAH is associated with significant morbidity and mortality, and its pathogenesis is complex and poorly understood. There are few data on the prevalence of pericardial effusion in PAH, and more importantly, the management of pericardial effusion is controversial. Current literature abounds with case reports, case series, and retrospective studies that have limited value for assessing this association. Hence, we summarize the available evidence on this ominous association and identify areas for future research. PMID:24618534

  15. "Nocturnal seizures" in idiopathic pulmonary arterial hypertension.

    PubMed

    Izzo, Anthony; McSweeney, Julia; Kulik, Thomas; Khatwa, Umakanth; Kothare, Sanjeev V

    2013-10-15

    The usual differential diagnoses of nocturnal events in children include parasomnias, nocturnal seizures, nocturnal reflux (Sandifer syndrome), hypnic jerks, periodic limb movements of sleep, and sleep disordered breathing. We report a previously healthy young girl who presented to the sleep clinic for evaluation of nocturnal events which were diagnosed as medically refractory nocturnal seizures. It was not until a syncopal event occurred in the daytime, which prompted referral for cardiac evaluation, the diagnosis of idiopathic pulmonary arterial hyper-tension (IPAH) was made. Sleep physicians should consider IPAH in the differential diagnosis of nocturnal events in children. PMID:24127156

  16. [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

  17. 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

  18. [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

  19. 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

  20. 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

  1. Isolated Congenital Unilateral Agenesis of the Left Pulmonary Artery with Left Lung Hypoplasia in an Asymptomatic Adult Patient

    PubMed Central

    Emren, Sadık Volkan; Tülüce, Selcen Yakar; Tülüce, Kamil

    2015-01-01

    The congenital unilateral agenesis of pulmonary artery is a congenital cardiovascular anomaly rarely seen in adulthood. A 21-year-old asymptomatic male was admitted to our hospital to obtain a routine health report to accompany a job application. Posteroanterior chest radiograph revealed a mediastinal shift to the left, with increased radiopacity in the left lung and increased radiolucency in the right lung. Thoracoabdominal computed tomography revealed hypoplasia of the left pulmonary artery. Transthoracic echocardiography excluded any accompanying cardiac abnormalities. Pulmonary angiography was undertaken and confirmed diffuse hypoplasia of the left pulmonary artery while right pulmonary artery was significantly enlarged. The patient’s pulmonary artery pressure was within the normal limits, after which he decided to be carefully followed-up. PMID:27122926

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

    PubMed

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

    2016-03-01

    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/m(2); 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. 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

  4. Non-congenital heart disease associated pediatric pulmonary arterial hypertension.

    PubMed

    Ivy, D D; Feinstein, J A; Humpl, T; Rosenzweig, E B

    2009-12-01

    Recognition of causes of pulmonary hypertension other than congenital heart disease is increasing in children. Diagnosis and treatment of any underlying cause of pulmonary hypertension is crucial for optimal management of pulmonary hypertension. This article discusses the available knowledge regarding several disorders associated with pulmonary hypertension in children: idiopathic pulmonary arterial hypertension (IPAH), pulmonary capillary hemangiomatosis, pulmonary veno-occlusive disease, hemoglobinopathies, hepatopulmonary syndrome, portopulmonary hypertension and HIV. Three classes of drugs have been extensively studied for the treatment of IPAH in adults: prostanoids (epoprostenol, treprostinil, iloprost, beraprost), endothelin receptor antagonists (bosentan, sitaxsentan, ambrisentan), and phosphodiesterase inhibitors (Sildenafil, tadalafil). These medications have been used in treatment of children with pulmonary arterial hypertension, although randomized clinical trial data is lacking. As pulmonary vasodilator therapy in certain diseases may be associated with adverse outcomes, further study of these medications is needed before widespread use is encouraged. PMID:21852894

  5. Non-congenital heart disease associated pediatric pulmonary arterial hypertension

    PubMed Central

    Ivy, D. D.; Feinstein, J. A.; Humpl, T.; Rosenzweig, E. B.

    2011-01-01

    Recognition of causes of pulmonary hypertension other than congenital heart disease is increasing in children. Diagnosis and treatment of any underlying cause of pulmonary hypertension is crucial for optimal management of pulmonary hypertension. This article discusses the available knowledge regarding several disorders associated with pulmonary hypertension in children: idiopathic pulmonary arterial hypertension (IPAH), pulmonary capillary hemangiomatosis, pulmonary veno-occlusive disease, hemoglobinopathies, hepatopulmonary syndrome, portopulmonary hypertension and HIV. Three classes of drugs have been extensively studied for the treatment of IPAH in adults: prostanoids (epoprostenol, treprostinil, iloprost, beraprost), endothelin receptor antagonists (bosentan, sitaxsentan, ambrisentan), and phosphodiesterase inhibitors (Sildenafil, tadalafil). These medications have been used in treatment of children with pulmonary arterial hypertension, although randomized clinical trial data is lacking. As pulmonary vasodilator therapy in certain diseases may be associated with adverse outcomes, further study of these medications is needed before widespread use is encouraged. PMID:21852894

  6. An unusual cause of pulmonary artery pseudoaneurysm: acrylate embolism.

    PubMed

    Mourin, Giséle; Badia, Alain; Cazes, Aurélie; Planquette, Benjamin

    2012-12-01

    Sclerotherapy is commonly used to manage bleeding from oesophageal varices. In a patient with cirrhosis of the liver, sclerotherapy with bucrylate was followed by a pulmonary embolism and then by a decline in general health. A chest radiograph taken 5 months later disclosed a left perihilar opacity, surrounding and invading the pulmonary artery. Despite moderate fixation by positron emission tomography and inconclusive bronchoscopy findings, an upper left lobectomy was deemed in order. A left pulmonary artery pseudoaneurysm was found during the surgery. The pseudoaneurysm ruptured during dissection, requiring a left pneumonectomy. The pathological examination showed shredding of the left pulmonary artery, which contained foreign material. At points of contact with this material, destruction and severe polymorphic inflammation of the pulmonary parenchyma were noted. There was no evidence of tumour or infection. These findings strongly suggested an iatrogenic pulmonary artery pseudoaneurysm related to a bucrylate embolism through porto-systemic vascular shunts. We are not aware of previously reported cases. PMID:22990635

  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. Pulmonary Vascular Pressure Profiles in Broilers Selected for Susceptibility to Pulmonary Hypertension Syndrome: Age and Gender Comparisons

    PubMed Central

    Wideman, R. F.; Eanes, M. L.; Hamal, K. R.; Anthony, N. B.

    2011-01-01

    Broilers that are susceptible to pulmonary hypertension syndrome (PHS, ascites) have an elevated pulmonary arterial pressure (PAP) when compared with PHS-resistant broilers. Two distinctly different syndromes, pulmonary arterial hypertension (PAH) and pulmonary venous hypertension (PVH), both are associated with increases in PAP. Pulmonary arterial hypertension occurs when the right ventricle must elevate the PAP to overcome increased resistance to flow through restrictive pulmonary arterioles upstream from the pulmonary capillaries. In contrast, PVH is commonly caused by increased downstream (post-capillary) resistance. The sites of resistance to pulmonary blood flow are deduced by making contemporaneous measurements of the PAP and the wedge pressure (WP), and calculating the trans-pulmonary pressure gradient (TPG = PAP-WP). We obtained PAP and WP values from 8, 12, 16, 20 and 24 wk old anesthetized male and female broilers from a PHS-susceptible line. Pressures were recorded as a catheter was advanced through a wing vein to the pulmonary artery and onward until the WP was obtained. In addition to gender and age comparisons of vascular pressure gradients, the data also were pooled to obtain three cohorts for broilers having the lowest PAP values (n = 52; range: 12 to 22.9 mmHg), intermediate PAP values (n = 63; range: 23 to 32.9 mmHg), and highest PAP values (n = 62; range: 33 to 62 mmHg) independent of age or gender. Within each of the age, gender and PAP cohort comparisons, broilers with elevated PAP consistently exhibited the hemodynamic characteristics of PAH (elevated PAP and TPG combined with a normal WP) and not PVH (elevated PAP and WP combined with a normal or reduced TPG). Susceptibility to PHS can be attributed primarily to pulmonary arterial hypertension associated with increased pre-capillary (arteriole) resistance. PMID:20709965

  10. Symptomatic aorto-pulmonary collaterals early after arterial switch operation.

    PubMed

    Santoro, Giuseppe; Carrozza, Marianna; Russo, Maria Giovanna; Calabrò, Raffaele

    2008-07-01

    Enlarged bronchial arteries and/or systemic-to-pulmonary collaterals have been frequently demonstrated in association with transposition of the great arteries. They are usually clinically silent, although they might be large enough to cause accelerated pulmonary vascular obstructive disease or symptomatic cardiac volume overload after surgical repair. We report on a low-weight neonate with transposition of the great arteries and intact ventricular septum who showed a stormy postoperative course because of multiple aorto-pulmonary collaterals early after a successful arterial switch operation. Percutaneous coil embolization of these anomalous vessels resulted in sudden weaning from mechanical ventilation and hospital discharge in a few weeks. PMID:18185950

  11. Noninvasive pulmonary artery wave intensity analysis in pulmonary hypertension

    PubMed Central

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

    2015-01-01

    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

  12. 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

  13. 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

  14. An Experimental Method for Measuring Mechanical Properties of Rat Pulmonary Arteries Verified With Latex

    PubMed Central

    Drexler, E. S.; Slifka, A. J.; Wright, J. E.; McCowan, C. N.; Finch, D. S.; Quinn, T. P.; McColskey, J. D.; Ivy, D. D.; Shandas, R.

    2003-01-01

    This paper describes a test method for measuring the mechanical properties of small, nonlinear membrane samples from a rat model for pulmonary hypertension. The size and nonlinearity of the pulmonary artery samples poses a challenge for developing a test method that will generate quality, reproducible data in the pressure range experienced by the hypertensive pulmonary artery. The experimental method described here has sufficient precision to yield a combined relative standard uncertainty of 4 %. The method is calibrated against 75 µm thick latex and the data agree well with the neo-Hookian model.

  15. 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

  16. Novel Approaches to Treat Experimental Pulmonary Arterial Hypertension: A Review

    PubMed Central

    Umar, S.; Steendijk, P.; Ypey, D. L.; Atsma, D. E.; van der Wall, E. E.; Schalij, M. J.; van der Laarse, A.

    2010-01-01

    Background. Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by an increase in pulmonary artery pressure leading to right ventricular (RV) hypertrophy, RV failure, and ultimately death. Current treatments can improve symptoms and reduce severity of the hemodynamic disorder but gradual deterioration in their condition often necessitates a lung transplant. Methods and Results. In experimental models of PAH, particularly the model of monocrotaline-induced pulmonary hypertension, efficacious treatment options tested so far include a spectrum of pharmacologic agents with actions such as anti-mitogenic, proendothelial function, proangiogenic, antiinflammatory and antioxidative. Emerging trends in PAH treatment are gene and cell therapy and their combination, like (progenitor) cells enriched with eNOS or VEGF gene. More animal data should be collected to investigate optimal cell type, in vitro cell transduction, route of administration, and number of cells to inject. Several recently discovered and experimentally tested interventions bear potential for therapeutic purposes in humans or have been shown already to be effective in PAH patients leading to improved life expectation and better quality of life. Conclusion. Since many patients remain symptomatic despite therapy, we should encourage research in animal models of PAH and implement promising treatments in homogeneous groups of PAH patients. PMID:20339474

  17. 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

  18. Treatment of pulmonary arterial hypertension in connective tissue disease.

    PubMed

    Grünig, Ekkehard

    2012-05-28

    Pulmonary arterial hypertension (PAH) is a group of distinct disorders that includes idiopathic PAH (IPAH), familial PAH and PAH associated with other conditions (APAH) such as connective tissue disease (CTD-APAH) or congenital heart disease. PAH is characterized by increased pulmonary arterial pressure and pulmonary vascular resistance. If left untreated, PAH can lead to right heart failure and premature death. CTD-APAH represents an important clinical subgroup of APAH that has a higher risk of death than IPAH. The European treatment guidelines advocate the use of PAH-targeted therapies including bosentan, ambrisentan, sildenafil, inhaled iloprost, intravenous epoprostenol (I-A recommendations), tadalafil or treprostinil (I-B recommendations) for patients in WHO functional class II-III. Not all randomized clinical studies of the approved PAH-targeted therapies have included patients with CTD-APAH. The purpose of this review is to describe the clinical characteristics of CTD-APAH and discuss the approved pharmacological treatments, with a focus on data specific to this subgroup where possible. PMID:22621693

  19. Prevalence of coronary artery–pulmonary artery collaterals in patients with chronic thromboembolic pulmonary hypertension

    PubMed Central

    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.

    2015-01-01

    Abstract 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

  20. The effect of CO sub 2 on pulmonary artery pressure (P sub pa ) over time in the isolated perfused rabbit lung

    SciTech Connect

    Reynolds, P.; Shayevitz, J. )

    1991-03-11

    The isolated perfused rabbit lung model is used in studies of pulmonary hemodynamics, structure, and function under conditions closely resembling those which occur in living animals. The purpose of this study is to observe changes in P{sub pa} in response to differing concentrations of CO{sub 2} over time. After rapid exsanguination a tracheostomy was performed. Cannulas were secured in the main pulmonary artery and the left atrium. The lungs were perfused with Krebs-Henseleit buffer mixed with blood at a rate of 120 ml/min with recirculation. The temperature of the perfusate was maintained between 35 and 38C. The lungs were then ventilated with 5% CO{sub 2} in air with a tidal volume of 10 ml/kg at 20 breaths/min. CO{sub 2} was altered randomly by ventilating the lungs 2, 5 or 10% CO{sub 2} in air. Metabolic acidosis was corrected with NaHCO{sub 3}. In the first two hour period after lung perfusion was begun, the model was allowed to stabilize at each CO{sub 2} concentration, and pH, pCO{sub 2}, pO{sub 2}, and base excess were determined at each P{sub pa}. All measurements were repeated in the second period beginning two hours after lung perfusion was started. P{sub pa} was plotted against pH for each animal in both early and late phases, and simple regression analysis was performed. The slopes and the y intercepts for the data sets in both groups were compared using one factor ANOVA, and were found to be significantly different, implying a statistical difference between regression lines. In the early phase this model behaves like the in vivo lung, i.e. hypercarbia appears to increase, while hypocarbia decreases, P{sub pa}. During the late phase of lung perfusion the opposite occurs.

  1. 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

  2. Peptide-micelle hybrids containing fasudil for targeted delivery to the pulmonary arteries and arterioles to treat pulmonary arterial hypertension.

    PubMed

    Gupta, Nilesh; Ibrahim, Hany M; Ahsan, Fakhrul

    2014-11-01

    This study investigates the respirability and efficacy of peptide-micelle hybrid nanoparticles as carriers for inhalational therapy of pulmonary arterial hypertension (PAH). CARSKNKDC (CAR), a cell-penetrating and lung-homing peptide, conjugated polyethylene glycol-distearoyl-phosphoethanolamine micelles containing fasudil, an investigational anti-PAH drug, were prepared by solvent evaporation method and characterized for various physicochemical properties. The pharmacokinetics and pharmacological efficacy of hybrid particles containing fasudil were evaluated in healthy rats and monocrotaline-induced PAH rats. CAR micelles containing fasudil had an entrapment efficiency of approximately 58%, showed controlled release of the drug, and were monodispersed with an average size of approximately 14 nm. Nuclear magnetic resonance scan confirmed the drug's presence in the core of peptide-micelle hybrid particles. Compared with plain micelles, CAR peptide increased the cellular uptake by approximately 1.7-fold and extended the drug half-life by approximately fivefold. The formulations were more prone to accumulate in the pulmonary vasculature than in the peripheral blood, which is evident from the ratio of the extent of reduction of pulmonary and systemic arterial pressures. On the whole, this study demonstrates that peptide-polymer hybrid micelles can serve as inhalational carriers for PAH therapy. PMID:25266507

  3. Effects of Different Pulmonary Vasodilators on Arterial Saturation in a Model of Pulmonary Hypertension

    PubMed Central

    Becker, Eva Maria; Stasch, Johannes-Peter; Bechem, Martin; Keldenich, Jörg; Klipp, Alexandra; Schaefer, Katja; Ulbrich, Hannes-Friedrich; Truebel, Hubert

    2013-01-01

    Background Approved therapies for pulmonary arterial hypertension can induce oxygen desaturation when administered to patients with secondary forms of pulmonary hypertension (PH), probably due to an increase in ventilation/perfusion mismatch. Thus, so far these treatments have largely failed in secondary forms of PH. Methods We established an animal model of heterogeneous lung ventilation to evaluate the desaturation potential of mechanistically distinct vasoactive drugs launched or currently in clinical development for the treatment of PH. Single-lung ventilation was induced in five groups (N = 6) of anesthetized minipigs (7 weeks, 4 to 5 kg BW), and their hemodynamic parameters were monitored before and after intravenous injection of control (vehicle only), endothelin antagonist (bosentan; 0.3, 1, 3, 10 mg/kg), phosphodiesterase type 5 inhibitor (sildenafil; 3, 10, 30, 100 µg/kg), and soluble guanylate cyclase stimulators (BAY 41–8543 and riociguat; 1, 3, 10, 30 µg/kg). Cumulative doses were administered before successive unilateral ventilation cycles. The doses were chosen to achieve equal effect on blood pressure by the different pharmacologic principles. Results Single-lung ventilation resulted in transient increases in mean pulmonary artery pressure (mPAP) and desaturation. In contrast to control, all drugs dose-dependently decreased hypoxic mPAP (a positive treatment effect) and increased area under the arterial hemoglobin saturation curve (unwanted desaturation effect). Riociguat and bosentan reduced hypoxic mPAP to the greatest extent, while the soluble guanylate cyclase stimulators riociguat and BAY 41–8543 lowered arterial oxygen saturation of hemoglobin the least. Conclusions Future investigations will be required to confirm these findings in clinical settings. PMID:24015306

  4. 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

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

    PubMed Central

    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

  6. Serum levels of soluble ICAM-1 in children with pulmonary artery hypertension.

    PubMed

    Oguz, Melahat Melek; Oguz, Ayse Deniz; Sanli, Cihat; Cevik, Ayhan

    2014-04-01

    This prospective cross-sectional study attempted to determine both the usefulness of the serum intercellular adhesion molecule-1 (ICAM-1) as a biomarker for pulmonary artery hypertension secondary to congenital heart disease and the nature of this marker's association with catheter angiographic findings. Our study included a total of 70 male and female children, comprising 30 patients with both pulmonary artery hypertension and congenital heart disease, 20 patients with congenital heart disease alone, and 20 healthy control subjects. Levels of ICAM-1 in plasma samples from all groups were measured by the enzyme-linked immunosorbent assay method. Cardiac catheterization was also performed in all patients. The mean serum ICAM-1 levels in pediatric patients who had congenital heart disease with and without pulmonary artery hypertension were 349.6 ± 72.9 ng/mL and 312.3 ± 69.5 ng/mL, respectively (P=0.002). In healthy control subjects, the mean serum ICAM-1 level was 231.4 ± 60.4 ng/mL. According to the results of this study, the ICAM-1 level of the pulmonary artery hypertension group was significantly higher than those of the congenital heart disease group and the healthy control group. Correlation analysis showed that ICAM-1 level was correlated with systolic and mean pulmonary artery pressures (r=0.62, P=0.001; r=0.57, P=0.001)-which are 2 important values used in diagnosis of pulmonary artery hypertension. Moreover, receiver operating characteristic analysis yielded consistent results for the prediction of pulmonary artery hypertension. Therefore, we conclude that ICAM-1 has potential use as a biomarker for the diagnosis and follow-up of pulmonary artery hypertension. PMID:24808775

  7. Serum Levels of Soluble ICAM-1 in Children with Pulmonary Artery Hypertension

    PubMed Central

    Oguz, Melahat Melek; Oguz, Ayse Deniz; Sanli, Cihat; Cevik, Ayhan

    2014-01-01

    This prospective cross-sectional study attempted to determine both the usefulness of the serum intercellular adhesion molecule-1 (ICAM-1) as a biomarker for pulmonary artery hypertension secondary to congenital heart disease and the nature of this marker's association with catheter angiographic findings. Our study included a total of 70 male and female children, comprising 30 patients with both pulmonary artery hypertension and congenital heart disease, 20 patients with congenital heart disease alone, and 20 healthy control subjects. Levels of ICAM-1 in plasma samples from all groups were measured by the enzyme-linked immunosorbent assay method. Cardiac catheterization was also performed in all patients. The mean serum ICAM-1 levels in pediatric patients who had congenital heart disease with and without pulmonary artery hypertension were 349.6 ± 72.9 ng/mL and 312.3 ± 69.5 ng/mL, respectively (P=0.002). In healthy control subjects, the mean serum ICAM-1 level was 231.4 ± 60.4 ng/mL. According to the results of this study, the ICAM-1 level of the pulmonary artery hypertension group was significantly higher than those of the congenital heart disease group and the healthy control group. Correlation analysis showed that ICAM-1 level was correlated with systolic and mean pulmonary artery pressures (r=0.62, P=0.001; r=0.57, P=0.001)—which are 2 important values used in diagnosis of pulmonary artery hypertension. Moreover, receiver operating characteristic analysis yielded consistent results for the prediction of pulmonary artery hypertension. Therefore, we conclude that ICAM-1 has potential use as a biomarker for the diagnosis and follow-up of pulmonary artery hypertension. PMID:24808775

  8. Cytoskeletal defects in Bmpr2-associated pulmonary arterial hypertension

    PubMed Central

    Johnson, Jennifer A.; Hemnes, Anna R.; Perrien, Daniel S.; Schuster, Manfred; Robinson, Linda J.; Gladson, Santhi; Loibner, Hans; Bai, Susan; Blackwell, Tom R.; Tada, Yuji; Harral, Julie W.; Talati, Megha; Lane, Kirk B.; Fagan, Karen A.

    2012-01-01

    The heritable form of pulmonary arterial hypertension (PAH) is typically caused by a mutation in bone morphogenic protein receptor type 2 (BMPR2), and mice expressing Bmpr2 mutations develop PAH with features similar to human disease. BMPR2 is known to interact with the cytoskeleton, and human array studies in PAH patients confirm alterations in cytoskeletal pathways. The goal of this study was to evaluate cytoskeletal defects in BMPR2-associated PAH. Expression arrays on our Bmpr2 mutant mouse lungs revealed cytoskeletal defects as a prominent molecular consequence of universal expression of a Bmpr2 mutation (Rosa26-Bmpr2R899X). Pulmonary microvascular endothelial cells cultured from these mice have histological and functional cytoskeletal defects. Stable transfection of different BMPR2 mutations into pulmonary microvascular endothelial cells revealed that cytoskeletal defects are common to multiple BMPR2 mutations and are associated with activation of the Rho GTPase, Rac1. Rac1 defects are corrected in cell culture and in vivo through administration of exogenous recombinant human angiotensin-converting enzyme 2 (rhACE2). rhACE2 reverses 77% of gene expression changes in Rosa26-Bmpr2R899X transgenic mice, in particular, correcting defects in cytoskeletal function. Administration of rhACE2 to Rosa26-Bmpr2R899X mice with established PAH normalizes pulmonary pressures. Together, these findings suggest that cytoskeletal function is central to the development of BMPR2-associated PAH and that intervention against cytoskeletal defects may reverse established disease. PMID:22180660

  9. Molecular mechanisms of hypoxia-inducible factor-induced pulmonary arterial smooth muscle cell alterations in pulmonary hypertension.

    PubMed

    Veith, Christine; Schermuly, Ralph T; Brandes, Ralf P; Weissmann, Norbert

    2016-03-01

    Oxygen (O2) is essential for the viability and function of most metazoan organisms and thus is closely monitored at both the organismal and the cellular levels. However, alveoli often encounter decreased O2 levels (hypoxia), leading to activation of physiological or pathophysiological responses in the pulmonary arteries. Such changes are achieved by activation of transcription factors. The hypoxia-inducible factors (HIFs) are the most prominent hypoxia-regulated transcription factors in this regard. HIFs bind to hypoxia-response elements (HREs) in the promoter region of target genes, whose expression and translation allows the organism, amongst other factors, to cope with decreased environmental O2 partial pressure (pO2). However, prolonged HIF activation can contribute to major structural alterations, especially in the lung, resulting in the development of pulmonary hypertension (PH). PH is characterized by a rise in pulmonary arterial pressure associated with pulmonary arterial remodelling, concomitant with a reduced intravascular lumen area. Patients with PH develop right heart hypertrophy and eventually die from right heart failure. Thus, understanding the molecular mechanisms of HIF regulation in PH is critical for the identification of novel therapeutic strategies. This review addresses the relationship of hypoxia and the HIF system with pulmonary arterial dysfunction in PH. We particularly focus on the cellular and molecular mechanisms underlying the HIF-driven pathophysiological processes. PMID:26228924

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

    PubMed

    Papathanasiou, Athanasios; Nakos, George

    2015-11-01

    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

  11. 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

  12. Sildenafil in pediatric pulmonary arterial hypertension

    PubMed Central

    Dhariwal, AK; Bavdekar, SB

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a life-threatening disease of varied etiologies. Although PAH has no curative treatment, a greater understanding of pathophysiology, technological advances resulting in early diagnosis, and the availability of several newer drugs have improved the outlook for patients with PAH. Sildenafil is one of the therapeutic agents used extensively in the treatment of PAH in children, as an off-label drug. In 2012, the United States Food and Drug Administration (USFDA) issued a warning regarding the of use high-dose sildenafil in children with PAH. This has led to a peculiar situation where there is a paucity of approved therapies for the management of PAH in children and the use of the most extensively used drug being discouraged by the regulator. This article provides a review of the use of sildenafil in the treatment of PAH in children. PMID:26119438

  13. Pulmonary arterial hypertension in connective tissue diseases.

    PubMed

    Goldberg, Avram

    2010-01-01

    Pulmonary arterial hypertension (PAH) is an entity that is known to complicate connective tissue diseases (CTD). PAH in CTD is a very important diagnosis which greatly affects treatment and prognosis. The most commonly affected CTD is scleroderma, although lupus, inflammatory myopathies such as poly and dermatomyositis, and mixed CTD are also associated with PAH. The manifestations of PAH have both similarities and differences when occurring in the setting of CTD as compared with idiopathic PAH. These differences are most notable in scleroderma. In this section we will discuss the features of PAH as they appear in CTDs, and in particular, scleroderma. The focus of this article is an approach to the diagnosis and treatment of PAH in CTD, and how this setting might differ from idiopathic and other forms of PAH. PMID:20160534

  14. [Pulmonary arterial hypertension: changing approaches to management].

    PubMed

    Sidorenko, B A; Preobrazhenskiĭ, D V; Batyraliev, T A; Belenkov, Iu N

    2011-01-01

    The review is devoted to different aspects of pulmonary arterial hypertension (PAH); new classification of PAH is published in 2010. There are idiopathic PAH and PAH associated with other diseases. Current guidelines recommend to treat PAH only after the verification of diagnosis with right heart catheterization and acute tests with vasodilators. Patients-reactors should be treated with calcium antagonists. The following drugs related to one of three categories should be used in PAH: (1) prostanoids (epoprostenol, iloprost et al.); (2) blockers of endothelin receptors (bosentan, ambrisentan, sitaxsentan); (3) phosphodiesterase 5 type inhibitors (sildenafil, tadalafil et al.) In majority of cases the combined treatment is used, usually the combination of bosentan and sildenafil is used. PMID:21626809

  15. 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

  16. Exercise intolerance in pulmonary arterial hypertension.

    PubMed

    Fowler, Robin M; Gain, Kevin R; Gabbay, Eli

    2012-01-01

    Pulmonary arterial hypertension (PAH) is associated with symptoms of dyspnea and fatigue, which contribute to exercise limitation. The origins and significance of dyspnea and fatigue in PAH are not completely understood. This has created uncertainly among healthcare professionals regarding acceptable levels of these symptoms, on exertion, for patients with PAH. Dysfunction of the right ventricle (RV) contributes to functional limitation and mortality in PAH; however, the role of the RV in eliciting dyspnea and fatigue has not been thoroughly examined. This paper explores the contribution of the RV and systemic and peripheral abnormalities to exercise limitation and symptoms in PAH. Further, it explores the relationship between exercise abnormalities and symptoms, the utility of the cardiopulmonary exercise test in identifying RV dysfunction, and offers suggestions for further research. PMID:22737582

  17. Exercise Intolerance in Pulmonary Arterial Hypertension

    PubMed Central

    Fowler, Robin M.; Gain, Kevin R.; Gabbay, Eli

    2012-01-01

    Pulmonary arterial hypertension (PAH) is associated with symptoms of dyspnea and fatigue, which contribute to exercise limitation. The origins and significance of dyspnea and fatigue in PAH are not completely understood. This has created uncertainly among healthcare professionals regarding acceptable levels of these symptoms, on exertion, for patients with PAH. Dysfunction of the right ventricle (RV) contributes to functional limitation and mortality in PAH; however, the role of the RV in eliciting dyspnea and fatigue has not been thoroughly examined. This paper explores the contribution of the RV and systemic and peripheral abnormalities to exercise limitation and symptoms in PAH. Further, it explores the relationship between exercise abnormalities and symptoms, the utility of the cardiopulmonary exercise test in identifying RV dysfunction, and offers suggestions for further research. PMID:22737582

  18. 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

  19. 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

  20. 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.

  1. Compression of adjacent anatomical structures by pulmonary artery dilation.

    PubMed

    Dakkak, Wael; Tonelli, Adriano R

    2016-06-01

    Pulmonary hypertension is the commonest condition leading to dilated pulmonary artery. We describe three different types of compression of adjacent anatomical structures by dilated pulmonary arteries. We included involvement of the left main coronary artery, left recurrent laryngeal nerve and tracheobronchial tree. Compression of these structures can cause major complications such as myocardial ischemia, hoarseness and major airway stenosis. We present a case for each scenario and review the literature for each of these complications, focusing on patients' characteristics and contemporary management. PMID:26898826

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

    PubMed

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

    2014-07-18

    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 attenuate pulmonary vascular remodeling after MCT induction. These beneficial effects were at least through the inhibition of PDGF-Rβ phosphorylation and its downstream signaling pathways. Therefore, IRN might be a potential candidate for the treatment of PAH. PMID:24950404

  3. 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

  4. New Concepts in the Invasive and Non Invasive Evaluation of Remodelling of the Right Ventricle and Pulmonary Vasculature in Pulmonary Arterial Hypertension

    PubMed Central

    Domingo, Enric; Aguilar, Rio; López-Meseguer, Manuel; Teixidó, Gisela; Vazquez, Manuel; Roman, Antonio

    2009-01-01

    Pulmonary arterial hypertension (PAH) is a rare fatal disease defined as a sustained elevation of pulmonary arterial pressure to more than 25 mmHg at rest, with a mean pulmonary-capillary wedge pressure and left ventricular enddiastolic pressure of less than 15 mmHg at rest. Histopathology of PAH is founded on structural modifications on the vascular wall of small pulmonary arteries characterized by thickening of all its layers. These changes, named as vascular remodelling, include vascular proliferation, fibrosis, and vessel obstruction. In clinical practice the diagnosis of PAH relies on measurements of pulmonary vascular pressure and cardiac output, and calculation of pulmonary vascular resistances. Direct evaluation of pulmonary vascular structure is not routinely performed in pulmonary hypertension since current imaging techniques are limited and since little is known about the relationship between structural changes and functional characteristics of the pulmonary vasculature. Intravascular ultrasound studies in patients with pulmonary hypertension have shown a thicker middle layer, increased wall-thickness ratio and diminished pulsatility than in control patients. Optical Coherence Tomography, a new high resolution imaging modality that has proven its superiority over intravascular ultrasound (IVUS) for the detection and characterization of coronary atherosclerotic plaque composition, may potentially be a useful technique for the in vivo study of the pulmonary arterial wall. In addition current progress in Echo Doppler technique will quantify right ventricular function with parameters independent of loading conditions and not requiring volumetric approximations of the complex geometry of the right ventricle. This would allow the in vivo study of right ventricular and pulmonary artery remodelling in PAH. PMID:19452037

  5. Are Hemodynamics Surrogate Endpoints in Pulmonary Arterial Hypertension?

    PubMed Central

    Ventetuolo, Corey E.; Gabler, Nicole B.; Fritz, Jason S.; Smith, K. Akaya; Palevsky, Harold I.; Klinger, James R.; Halpern, Scott D.; Kawut, Steven M.

    2014-01-01

    Background While frequently assessed in trials and clinical practice, hemodynamic response to therapy has never been validated as a surrogate endpoint for clinical events in pulmonary arterial hypertension (PAH). Methods and Results We performed a patient-level pooled analysis of four randomized placebo-controlled trials to determine if treatment-induced changes in hemodynamic values at 12 weeks accounted for the relationship between treatment assignment and the probability of early clinical events (death, lung transplantation, atrial septostomy, PAH hospitalization, withdrawal for clinical worsening, escalation in PAH therapy). We included 1119 subjects with PAH. The median (interquartile range) age was 48 (37 – 59), and 23% were men. 656 (59%) received active therapy (101 [15%] iloprost, 118 [18%] sitaxsentan, 204 [31%] sildenafil, and 233 [36%] subcutaneous treprostinil). Active treatment significantly lowered right atrial pressure (RAP), mean pulmonary artery pressure (mPAP), and pulmonary vascular resistance and increased cardiac output and index (p < 0.01 for all). Changes in hemodynamic values (except for RAP and mPAP) were significantly associated with the risk of a clinical event (p ≤ 0.01 for all). While active treatment approximately halved the odds of a clinical event compared to placebo (p < 0.001), changes in hemodynamics accounted for only 1.2 – 13.9% of the overall treatment effect. Conclusions Treatment-induced changes in hemodynamics at 12 weeks only partially explain the impact of therapy on the probability of early clinical events in PAH. These findings suggest that resting hemodynamics are not valid surrogate endpoints for short-term events in PAH clinical trials. PMID:24951771

  6. Endovascular Treatment of a Coronary Artery Bypass Graft to Pulmonary Artery Fistula with Coil Embolization

    SciTech Connect

    Nielson, Jeffery L. Kang, Preet S.

    2006-04-15

    Fistula formation between a coronary artery bypass graft (CABG)and the pulmonary arterial circulation represents a rare cause of recurrent angina in patients following bypass grafting. Therapy has traditionally involved surgical ligation by open thoracotomy. We describe a case of left internal mammary artery-left upper lobe pulmonary artery fistula presenting as early recurrent angina following CABG. The fistula was embolized using platinum coils, resulting in symptomatic relief and improvement in myocardial perfusion on cardiac perfusion scintigraphy. Coil embolization should be considered a therapeutic option in patients with coronary-pulmonary steal syndrome.

  7. Does pulmonary rehabilitation reduce peripheral blood pressure in patients with chronic obstructive pulmonary disease?

    PubMed

    Canavan, Jane L; Kaliaraju, Djeya; Nolan, Claire M; Clark, Amy L; Jones, Sarah E; Kon, Samantha S C; Polkey, Michael I; Man, William D-C

    2015-08-01

    Pulmonary rehabilitation (PR) can improve aerobic exercise capacity, health-related quality of life and dyspnoea in patients with chronic obstructive pulmonary disease (COPD). Recent studies have suggested that exercise training may improve blood pressure and arterial stiffness, albeit in small highly selected cohorts. The aim of the study was to establish whether supervised outpatient or unsupervised home PR can reduce peripheral blood pressure. Resting blood pressure was measured in 418 patients with COPD before and after outpatient PR, supervised by a hospital-based team (HOSP). Seventy-four patients with COPD undergoing an unsupervised home-based programme acted as a comparator group (HOME). Despite significant improvements in mean (95% confidence interval) exercise capacity in the HOSP group (56 (50-60) m, p < 0.001) and HOME group (30 (17-42) m, p < 0.001) systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP) did not change in either the HOSP (SBP: p = 0.47; DBP: p = 0.06; MAP: p = 0.38) or HOME group (SBP: p = 0.67; DBP: p = 0.38; MAP: p = 0.76). Planned subgroup analysis of HOSP patients with known hypertension and/or cardiovascular disease showed no impact of PR upon blood pressure. PR is unlikely to reduce blood pressure, and by implication, makes a mechanism of action in which arterial stiffness is reduced, less likely. PMID:26015460

  8. 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.

  9. 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

  10. Pulmonary haemorrhage due to an aortopulmonary collateral artery after arterial switch.

    PubMed

    Sugimoto, Ai; Ota, Noritaka; Sakamoto, Kisaburo

    2016-03-01

    A neonate with transposition of the great arteries and intact ventricular septum presented without pulmonary over-circulation, and subsequently developed pulmonary haemorrhage after corrective surgery. Postoperative CT revealed an aortopulmonary collateral artery arising from the descending aorta, and we performed successful embolisation on postoperative day 9. Aggressive imaging modalities such as angiography and/or CT imaging with contrast can detect unexpected extra-pulmonary blood supply and guide further management. PMID:26144860

  11. 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) ...

  12. 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

  13. Functional Prostacyclin Synthase Promoter Polymorphisms. Impact in Pulmonary Arterial Hypertension

    PubMed Central

    Cornelius, Amber R.; Lu, Xiao; Conklin, David S.; Del Rosario, Mark J.; Lowe, Anita M.; Elos, Mihret T.; Fettig, Lynsey M.; Wong, Randall E.; Hara, Naoko; Cogan, Joy D.; Phillips, John A.; Taylor, Matthew R.; Graham, Brian B.; Tuder, Rubin M.; Loyd, James E.; Geraci, Mark W.

    2014-01-01

    Rationale: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by elevated pulmonary artery pressure, vascular remodeling, and ultimately right ventricular heart failure. PAH can have a genetic component (heritable PAH), most often through mutations of bone morphogenetic protein receptor 2, and idiopathic and associated forms. Heritable PAH is not completely penetrant within families, with approximately 20% concurrence of inactivating bone morphogenetic protein receptor 2 mutations and delayed onset of PAH disease. Because one of the treatment options is using prostacyclin analogs, we hypothesized that prostacyclin synthase promoter sequence variants associated with increased mRNA expression may play a protective role in the bone morphogenetic protein receptor 2 unaffected carriers. Objectives: To characterize the range of prostacyclin synthase promoter variants and assess their transcriptional activities in PAH-relevant cell types. To determine the distribution of prostacyclin synthase promoter variants in PAH, unaffected carriers in heritable PAH families, and control populations. Methods: Polymerase chain reaction approaches were used to genotype prostacyclin synthase promoter variants in more than 300 individuals. Prostacyclin synthase promoter haplotypes’ transcriptional activities were determined with luciferase reporter assays. Measurements and Main Results: We identified a comprehensive set of prostacyclin synthase promoter variants and tested their transcriptional activities in PAH-relevant cell types. We demonstrated differences of prostacyclin synthase promoter activities dependent on their haplotype. Conclusions: Prostacyclin synthase promoter sequence variants exhibit a range of transcriptional activities. We discovered a significant bias for more active prostacyclin synthase promoter variants in unaffected carriers as compared with affected patients with PAH. PMID:24605778

  14. Long term combination treatment for severe idiopathic pulmonary arterial hypertension

    PubMed Central

    Affuso, Flora; Cirillo, Plinio; Ruvolo, Antonio; Carlomagno, Guido; Fazio, Serafino

    2010-01-01

    We report the long-term follow-up of 3 cases of severe idiopathic pulmonary arterial hypertension, in whom tadalafil plus sitaxentan combination therapy improved the clinical condition and exercise performance without any relevant adverse event. PMID:21160759

  15. Intimal pulmonary artery sarcoma presenting as dyspnea: case report

    PubMed Central

    Hsing, Jeff M; Thakkar, Snehal G; Borden, Ernest C; Budd, George T

    2007-01-01

    Background We report a case of pulmonary sarcoma which is a rare cause of the common symptom of dyspnea. Case presentation A fifty-one year old previously healthy male presented to the emergency room with complaints of dyspnea on exertion. A cardiac workup including an exercise stress test was negative but an echocardiography showed pulmonary stenosis. Cardiac MRI showed a large mass extending from the pulmonic valve to both the right and left pulmonary arteries suggestive of sarcoma. A complete resection and repair of the pulmonary artery was done and adjuvant chemotherapy with doxorubicin and ifosfamide was recommended. The patient is currently disease free after eighteen months. Conclusion Pulmonary artery sarcomas are a difficult diagnosis. The diagnosis may remain elusive for some time until the proper imaging techniques are utilized to make a diagnosis. Earlier and accurate diagnosis may lead to earlier interventions and improve survival. PMID:17603895

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

    PubMed Central

    Anand, S.H.; Mani, Sunithi Elizabeth; Joseph, Elizabeth; Mathai, John

    2015-01-01

    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

  17. 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

  18. Pulmonary hypertension

    MedlinePlus

    Pulmonary arterial hypertension; Sporadic primary pulmonary hypertension; Familial primary pulmonary hypertension; Idiopathic pulmonary arterial hypertension; Primary pulmonary hypertension; PPH; Secondary pulmonary ...

  19. A rare cause of pulmonary hypertension: congenital bilateral atresia of the superior pulmonary arteries and bilateral stenosis of the inferior pulmonary arteries.

    PubMed

    Ertem, Ahmet Goktug; Akdemir, Ramazan

    2014-02-01

    Bilateral absence (atresia) of the superior pulmonary arteries, combined with bilateral stenosis of the inferior pulmonary arteries, has not to our knowledge been reported before now. We report such a case in a 48-year-old woman, together with the medical and percutaneous catheter interventions used to treat her condition. PMID:24512407

  20. Arginine metabolic endotypes in pulmonary arterial hypertension

    PubMed Central

    Wedes, Samuel H.; Hsu, Jean W.; Bohren, Kurt M.; Comhair, Suzy A. A.; Jahoor, Farook; Erzurum, Serpil C.

    2015-01-01

    Abstract Decreased synthesis of nitric oxide (NO) by NO synthases (NOS) is believed to play an important role in the pathogenesis of pulmonary arterial hypertension (PAH). Multiple factors may contribute to decreased NO bioavailability, including increased activity of arginase, the enzyme that converts arginine to ornithine and urea, which may compete with NOS for arginine; inadequate de novo arginine production from citrulline; and increased concentration of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NOS. We hypothesized that PAH patients with the lowest arginine availability secondary to increased arginase activity and/or inadequate de novo arginine synthesis might have a slower rate of NO synthesis and greater pulmonary vascular resistance. Nine patients with group 1 PAH and 10 healthy controls were given primed, constant intravenous infusions of 15N2-arginine, 13C,2H4-citrulline, 15N2-ornithine, and 13C-urea in the postabsorptive state. The results showed that, compared with healthy controls, PAH patients had a tendency toward increased arginine clearance and ornithine flux but no difference in arginine and citrulline flux, de novo arginine synthesis, or NO synthesis. Arginine-to-ADMA ratio was increased in PAH patients. Two endotypes of patients with low and high arginase activity were identified; compared with the low-arginase group, the patients with high arginase had increased arginine flux, slower NO synthesis, and lower plasma concentrations of ADMA. These results demonstrate that increased breakdown of arginine by arginase occurs in PAH and affects NO synthesis. Furthermore, there is no compensatory increase in de novo arginine synthesis to overcome this increased utilization of arginine by arginase. PMID:25992277

  1. [Treatment algorithm for pulmonary arterial hypertension].

    PubMed

    Hoeper, Marius M

    2005-06-01

    During the last decade, we have witnessed substantial improvements in the therapeutic options for pulmonary arterial hypertension (PAH), including true innovations targeting some of the mechanisms involved in the pathogenesis of this devastating disease. Intravenous epoprostenol was the first drug to improve symptoms and survival of patients with PAH. Novel prostanoids including subcutaneous treprostinil and inhaled iloprost also have beneficial effects in many patients, although their long-term efficacy is less well known. Among the newer treatments for PAH, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors have reshaped clinical practice. The endothelin receptor antagonist bosentan has been approved in many parts of the world and most current guidelines recommend this drug as first-line treatment for PAH. Novel endothelin receptor antagonists such as sitaxsentan and ambrisentan are currently being investigated. The phosphodiesterase type 5 inhibitor sildenafil is also being intensively studied in patients with pulmonary hypertension, and most of the available data look promising, although approval for PAH is still pending. Other phosphodiesterase type 5 inhibitors have not yet undergone extensive study in PAH. However, PAH is a complex disorder and targeting a single pathway cannot be expected to be uniformly successful. Thus, combining substances with different modes of action is expected to improve symptoms, hemodynamics and survival in PAH patients, although combination therapy has yet to undergo the scrutiny of large randomized clinical trials.Based on the available data, several guidelines for the diagnostic and therapeutic approach to PAH have been published recently. These guidelines have incorporated treatment algorithms, which, fortunately, are virtually identical. The present review article summarizes the current guidelines to the management of patients with PAH. PMID:15965810

  2. Pulmonary Arterial Stiffness: Toward a New Paradigm in Pulmonary Arterial Hypertension Pathophysiology and Assessment.

    PubMed

    Schäfer, Michal; Myers, Cynthia; Brown, R Dale; Frid, Maria G; Tan, Wei; Hunter, Kendall; Stenmark, Kurt R

    2016-01-01

    Stiffening of the pulmonary arterial bed with the subsequent increased load on the right ventricle is a paramount feature of pulmonary hypertension (PH). The pathophysiology of vascular stiffening is a complex and self-reinforcing function of extracellular matrix remodeling, driven by recruitment of circulating inflammatory cells and their interactions with resident vascular cells, and mechanotransduction of altered hemodynamic forces throughout the ventricular-vascular axis. New approaches to understanding the cell and molecular determinants of the pathophysiology combine novel biopolymer substrates, controlled flow conditions, and defined cell types to recapitulate the biomechanical environment in vitro. Simultaneously, advances are occurring to assess novel parameters of stiffness in vivo. In this comprehensive state-of-art review, we describe clinical hemodynamic markers, together with the newest translational echocardiographic and cardiac magnetic resonance imaging methods, to assess vascular stiffness and ventricular-vascular coupling. Finally, fluid-tissue interactions appear to offer a novel route of investigating the mechanotransduction processes and disease progression. PMID:26733189

  3. Management of the patient with pulmonary arterial hypertension receiving intravenous prostacyclin: an expert nurse practical guide.

    PubMed

    Kingman, Martha S; Lombardi, Sandra

    2014-01-01

    Pulmonary arterial hypertension (PAH) is a severely disabling disorder characterized by elevated pulmonary artery pressure ultimately leading to right heart failure and death. Treatment options have significantly increased over the past decade. Intravenous prostacyclins remain the treatment of choice for advanced PAH, leading to long-term clinical benefits and improved survival. Their administration requires a high level of nursing competency and presents considerable challenges for patients and caregivers. This article reviews the characteristics of currently available intravenous prostacyclins and provides a practical guide for nurses who may have had limited exposure to intravenous prostacyclins and their unique dosing, side effects, and titration characteristics. PMID:25376321

  4. 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

  5. [Combination treatment in pulmonary arterial hypertension].

    PubMed

    Kramer, Mordechai R

    2011-04-01

    In recent years, there has been a marked improvement in the treatment of pulmonary arterial hypertension (PAH) due to the development of targeted therapies. There are now several treatment options available--oral, inhaled, and those delivered by subcutaneous or intravenous methods. These treatments have greatly improved patient survival, which in the past was 2.5 years on average. Efficient treatment choice generally proceeds from oral therapies--PDE-5 inhibitors (sildenafil) and endothelin receptor antagonists (bosentan or ambrisentan)--to inhaled prostanoids (iloprost) or subcutaneous (treprostinil). Intravenous prostacyclins are used in treating the more severe cases. The different pathways of action of each class of drugs allow a synergistic effect of combination therapy similar to malignancy or patients in congestive heart failure. The updated treatment algorithm includes combinations of therapies that target different pathways. This article will review the literature regarding combination therapy for the treatment of PAH. Combining PAH therapies that target different pathways is now a well-established treatment option, based on numerous international clinical trials, and offers new hope to patients suffering from this severe disease. PMID:22164922

  6. Endothelin receptor antagonists in pulmonary arterial hypertension.

    PubMed

    Dupuis, J; Hoeper, M M

    2008-02-01

    The endothelin (ET) system, especially ET-1 and the ET(A) and ET(B) receptors, has been implicated in the pathogenesis of pulmonary arterial hypertension (PAH). Together with prostanoids and phosphodiesterase 5 inhibitors, ET receptor antagonists have become mainstays in the current treatment of PAH. Three substances are currently available for the treatment of PAH. One of these substances, bosentan, blocks both ET(A) and ET(B) receptors, whereas the two other compounds, sitaxsentan and ambrisentan, are more selective blockers of the ET(A) receptor. There is ongoing debate as to whether selective or nonselective ET receptor blockade is advantageous in the setting of PAH, although there is no clear evidence that receptor selectivity is relevant with regard to the clinical effects of these drugs. For the time being, other features, such as safety profiles and the potential for pharmacokinetic interactions with other drugs used in the treatment of PAH, may be more important than selectivity or nonselectivity when selecting treatments for individual patients. PMID:18238950

  7. 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

  8. Surgical Technique for Repair of Peripheral Pulmonary Artery Stenosis and Other Complex Peripheral Reconstructions.

    PubMed

    Mainwaring, Richard D; Ibrahimiye, Ali N; Hanley, Frank L

    2016-08-01

    Surgical reconstruction of peripheral pulmonary artery stenosis is a technically challenging procedure due to the need to access all lobar and segmental branches. This paper describes our surgical approach that entails division of the main pulmonary and separation of the branch pulmonary arteries. This surgical approach can also be utilized for other complex peripheral pulmonary artery reconstructions. PMID:27449462

  9. Acute Pulmonary Vasodilator Testing With Inhaled Treprostinil in Children With Pulmonary Arterial Hypertension

    PubMed Central

    Takatsuki, Shinichi; Parker, Donna K.; Doran, Aimee K.; Friesen, Robert H.

    2012-01-01

    Acute pulmonary vasodilator testing (AVT) is essential to determining the initial therapy for children with pulmonary arterial hypertension (PAH). This study aimed to report the initial experience with inhaled treprostinil used for AVT in children with PAH and to evaluate the hemodynamic change after inhaled treprostinil compared with inhaled nitric oxide. This prospective cohort study was designed for 13 children who underwent AVT with inhaled treprostinil or oxygen plus inhaled nitric oxide (iNO) during catheterization. Inhaled treprostinil was delivered during cardiac catheterization by adapting the Optineb ultrasonic nebulizer via either a flow-inflating bag or the manual mode of the anesthesia system. The median age of the patients was 10 years (range 4–17 years). The etiologies of PAH included idiopathic PAH and associated PAH. All the patients tolerated inhaled treprostinil without marked clinical worsening and received six or nine breaths (36 or 54 µg) of treprostinil. The median of the total treprostinil doses was 1.53 µg/kg (range 0.71–2.89 µg/kg). Inhaled treprostinil was administrated via an endotracheal tube (n = 8), anesthesia mask (n = 3), or laryngeal mask airway (n = 2). Inhaled nitric oxide (iNO) and inhaled treprostinil significantly decreased the mean pulmonary artery pressure and the pulmonary vascular resistance index compared with baseline. Three adverse events were reported after inhaled treprostinil, including cough and mild to moderate hypotension with higher doses. All adverse events resolved without any intervention. This study report is the first to describe the use of inhaled treprostinil for AVT in children with PAH. In this small pediatric cohort, inhaled treprostinil was effectively delivered and well tolerated and may be useful for AVT. PMID:23184020

  10. Platelet-activating factor induces selective pulmonary arterial hyperreactivity in isolated perfused rabbit lungs.

    PubMed

    Ohar, J A; Waller, K S; Dahms, T E

    1993-07-01

    The role of vasoreactivity in PAF-induced pulmonary hypertension (PHT) was assessed in isolated, perfused rabbit lungs. We evaluated the steady-state pulmonary vascular response to five vasoconstrictors: PGF2 alpha, norepinephrine, angiotensin II, PAF, and KCl. Pulmonary arterial pressure and pulmonary vascular resistance (PVR) were significantly greater in lungs of rabbits treated with PAF for 28 days than in control rabbits in response to PGF2 alpha and norepinephrine. When resistance was partitioned by the vascular occlusion method, at baseline the vascular resistance was equally distributed between arterial and venous segments in both experimental groups. Arterial resistance accounted for approximately 76% of PVR during norepinephrine injection and 60% of PVR during PGF2 alpha injection in PAF-treated lungs. Whereas arterial resistance accounted for approximately 63% of PVR during norepinephrine injection and 52% of PVR during PGF2 alpha injection in control lungs, there was no significant difference in the response to angiotensin II, acute PAF, and KCl in lungs from chronic PAF-treated rabbits compared with responses in control rabbit lungs, though the pressor response to acute PAF tended to be blunted in PAF-treated lungs. Chronic PAF treatment results in enhanced pulmonary arterial reactivity to selected autacoids in isolated perfused lungs. PMID:8317792

  11. Lung effect on the hemodynamics in pulmonary artery

    NASA Astrophysics Data System (ADS)

    Tsai, S. F.; Sheu, Tony W. H.; Chang, T. M.

    2001-06-01

    The present study investigates blood flow in a pulmonary artery. The aim is to gain a better understanding of offset value in vascular circulation through a two-dimensional analysis of the Navier-Stokes equations. In this study, the hemodynamics in a blood vessel with truncated outlets at which constant pressure is specified is examined. To simplify the analysis, the vessel walls are regarded as being rigid. In quadratic elements, the streamline upwind Petrov-Galerkin finite element model is employed to simulate the incompressible Newtonian blood flow. The adopted finite element model introduces artificial damping terms solely in the streamline direction. With these terms added to the formulation, the discrete system is enhanced while solution accuracy is maintained without deterioration due to numerical diffusion errors. Copyright

  12. Extensive pulmonary sarcoid reaction in a patient with BMPR-2 associated idiopathic pulmonary arterial hypertension.

    PubMed

    Braam, Evelien A J E; Quanjel, Marian J R; Van Haren-Willems, Jolanda H G M; Van Oosterhout, Matthijs F M; Vink, Aryan; Heijdra, Yvonne F; Kwakkel-van Erp, Johanna M

    2016-01-01

    Pulmonary arterial hypertension is a progressive life-threatening disease characterized by vascular remodeling. There is evidence that varied immune mechanism play an important role in progression of pulmonary hypertension.  We describe a case of a 35-year-old woman with idiopathic pulmonary arterial hypertension (IPAH) and a novel BMPR2 mutation, who underwent a successful lung transplantation.  Extensive granulomatous inflammation was seen in the resected lungs. The granulomatous inflammation found in the histology supports  a sarcoid-like reaction due to pulmonary hypertension in the context of the BMPR2 mutation. PMID:27537724

  13. Hoarseness after pulmonary arterial stenting and occlusion of the arterial duct.

    PubMed

    Assaqqat, Mervat; Siblini, Ghassan; Fadley, Fadel Al

    2003-06-01

    We report a 12-year-old girl who had multiple congenital cardiac lesions, specifically an arterial duct, left pulmonary arterial stenosis, an atrial septal defect in the oval fossa, and mild Ebstein's malformation of the tricuspid valve. Therapeutic transcatheter intervention was performed to stent the left pulmonary artery, occlude the arterial duct with a coil, and place a device to close the atrial septal defect. Subsequent to the catheterization, she complained of hoarseness, which was shown to be due to entrapment of the left recurrent laryngeal nerve between the coil used to close the arterial duct and the stent placed in the left pulmonary artery. Laryngoscopy confirmed paralysis of the recurrent laryngeal nerve. PMID:12903881

  14. Pulmonary artery aneurysms in Behçet's disease.

    PubMed

    Yilmaz, Sema; Cimen, Kadriye Akar

    2010-08-01

    Behçet's disease is the most common cause of pulmonary artery aneurysms. Pulmonary artery aneurysms are rare, but they are life-threatening because of their high tendency to rupture. However, there is also a chance that the aneurysms may completely resolve with immunosuppressive therapy. A 30-year-old man was admitted with chest pain, painful oral and genital ulcers, skin rash, weakness, and intermittent hemoptysis. He had a history of Behçet's disease for 6 years. The chest radiography showed a round opacity superior part of hilus on right. The helical thoracic computed tomography (CT) angiography demonstrated pulmonary aneurysms associated with Behçet's disease. The patient was successfully treated with colchicine, corticosteroids, and cyclophosphamide. A discussion about pulmonary artery aneurysms associated with Behçet's disease is provided in this case. PMID:19693504

  15. A Novel Vascular Homing Peptide Strategy to Selectively Enhance Pulmonary Drug Efficacy in Pulmonary Arterial Hypertension

    PubMed Central

    Toba, Michie; Alzoubi, Abdallah; O’Neill, Kealan; Abe, Kohtaro; Urakami, Takeo; Komatsu, Masanobu; Alvarez, Diego; Järvinen, Tero A.H.; Mann, David; Ruoslahti, Erkki; McMurtry, Ivan F.; Oka, Masahiko

    2015-01-01

    A major limitation in the pharmacological treatment of pulmonary arterial hypertension (PAH) is the lack of pulmonary vascular selectivity. Recent studies have identified a tissue-penetrating homing peptide, CARSKNKDC (CAR), which specifically homes to hypertensive pulmonary arteries but not to normal pulmonary vessels or other tissues. Some tissue-penetrating vascular homing peptides have a unique ability to facilitate transport of co-administered drugs into the targeted cells/tissues without requiring physical conjugation of the drug to the peptide (bystander effect). We tested the hypothesis that co-administered CAR would selectively enhance the pulmonary vascular effects of i.v. vasodilators in Sugen5416/hypoxia/normoxia-exposed PAH rats. Systemically administered CAR was predominantly detected in cells of remodeled pulmonary arteries. Intravenously co-administered CAR enhanced pulmonary, but not systemic, effects of the vasodilators, fasudil and imatinib, in PAH rats. CAR increased lung tissue imatinib concentration in isolated PAH lungs without increasing pulmonary vascular permeability. Sublingual CAR was also effective in selectively enhancing the pulmonary vasodilation by imatinib and sildenafil. Our results suggest a new paradigm in the treatment of PAH, using an i.v./sublingual tissue-penetrating homing peptide to selectively augment pulmonary vascular effects of nonselective drugs without the potentially problematic conjugation process. CAR may be particularly useful as an add-on therapy to selectively enhance the pulmonary vascular efficacy of any ongoing drug treatment in patients with PAH. PMID:24401613

  16. A novel vascular homing peptide strategy to selectively enhance pulmonary drug efficacy in pulmonary arterial hypertension.

    PubMed

    Toba, Michie; Alzoubi, Abdallah; O'Neill, Kealan; Abe, Kohtaro; Urakami, Takeo; Komatsu, Masanobu; Alvarez, Diego; Järvinen, Tero A H; Mann, David; Ruoslahti, Erkki; McMurtry, Ivan F; Oka, Masahiko

    2014-02-01

    A major limitation in the pharmacological treatment of pulmonary arterial hypertension (PAH) is the lack of pulmonary vascular selectivity. Recent studies have identified a tissue-penetrating homing peptide, CARSKNKDC (CAR), which specifically homes to hypertensive pulmonary arteries but not to normal pulmonary vessels or other tissues. Some tissue-penetrating vascular homing peptides have a unique ability to facilitate transport of co-administered drugs into the targeted cells/tissues without requiring physical conjugation of the drug to the peptide (bystander effect). We tested the hypothesis that co-administered CAR would selectively enhance the pulmonary vascular effects of i.v. vasodilators in Sugen5416/hypoxia/normoxia-exposed PAH rats. Systemically administered CAR was predominantly detected in cells of remodeled pulmonary arteries. Intravenously co-administered CAR enhanced pulmonary, but not systemic, effects of the vasodilators, fasudil and imatinib, in PAH rats. CAR increased lung tissue imatinib concentration in isolated PAH lungs without increasing pulmonary vascular permeability. Sublingual CAR was also effective in selectively enhancing the pulmonary vasodilation by imatinib and sildenafil. Our results suggest a new paradigm in the treatment of PAH, using an i.v./sublingual tissue-penetrating homing peptide to selectively augment pulmonary vascular effects of nonselective drugs without the potentially problematic conjugation process. CAR may be particularly useful as an add-on therapy to selectively enhance the pulmonary vascular efficacy of any ongoing drug treatment in patients with PAH. PMID:24401613

  17. Relevance of width of right descending branch of pulmonary artery as a radiological sign of pulmonary hypertension

    PubMed Central

    Teichmann, V.; Ježek, V.; Herles, F.

    1970-01-01

    An enlargement of the diameter of the right descending branch (RDB) of the pulmonary artery in chest radiographs may serve as a sign of pulmonary arterial hypertension. We tried at first to establish exactly the normal values for men and women of different age, analysing the radiographs of 112 healthy subjects. There is a relationship of RDB diameter to sex and age. We compared the RDB diameters in 95 men suffering from chronic bronchitis with the pulmonary arterial pressure, flow, and resistance, and with the right ventricular work: a highly significant relationship of RDB diameter to all but the blood flow values was found. Considering (in men over 40 years of age) a diameter of the RDB of 18 mm. or more as pathological, the reliability of the diagnosis of pulmonary hypertension in chronic bronchitis was 72·2% with readable films, or 64·2% when not reliably readable chest films were included. Nevertheless, a similar comparison in patients with mitral stenosis indicates that the radiographic picture of pulmonary hypertension differs according to the initial disease. Here we discuss the factors which may influence the RDB diameter. Images PMID:5418015

  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. Anatomical considerations for the development of a new transcatheter aortopulmonary shunt device in patients with severe pulmonary arterial hypertension

    PubMed Central

    2013-01-01

    Abstract Morbidity from pulmonary arterial hypertension (PAH) ensues when the pulmonary pressure reaches suprasystemic levels. A transcatheter alternative to the Potts shunt would allow decompression of the right heart without the surgical risks. To aid development of a transcatheter aortopulmonary shunt (TAPS) device, we described the anatomic relationship between the left pulmonary artery (LPA) and the descending aorta (dAO) in adults with severe pulmonary hypertension. Adults with severe PAH (peak systolic pulmonary arterial pressure [PASP] ≥80 mmHg) who had computed tomography of the chest were enrolled. Measurements were taken on the axial plane at the level of the pulmonary artery bifurcation. Forty patients (male sex, 9 patients; median age ± standard deviation [SD], years; median PASP ± SD, mmHg) were identified. The mean distance (±SD) between the LPA and dAO was mm. The mean luminal dAO and LPA diameters (±SD) were mm and mm, respectively. The LPA and dAO approximated in 93% of patients, with 38% having aortic calcification at the contact site. The mean “landing zone” width and height (defining an area with distance <4 mm between the outer borders) of the two arteries were mm and mm, respectively, at a mean distance of mm from the main pulmonary artery bifurcation. This study shows that the landing zone is able to accommodate a TAPS device of up to 15 mm in diameter in the majority of patients with severe PAH. PMID:24618548

  20. 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

  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. [The effect of high-frequency ventilation of the lungs on the pulmonary and systemic circulations in microembolism of the pulmonary artery].

    PubMed

    Sanotskaia, N V; Vyzhigina, M A; Matsievskiĭ, D D; Luk'ianov, M V; Aleĭnikov, S O

    1993-11-01

    The linear and volumetric blood flow velocity in the ascending aorta and pulmonary artery conus, right-left ventricular ejection balance, pulmonary and femoral arterial blood pressures, pulmonary microcirculation in fat pulmonary microembolism induced during the routine and high-frequency jet lung ventilation (HFJLV) were studied by ultrasonic techniques in acute experiments on cats with open chest under nembutal narcosis. Pulmonary microembolism was shown to resulted in 487 and 252% increases in pulmonary vascular resistance during the routine and HFJLVs, respectively. There were also 167 and 127% increases in mean pulmonary pressure and 60 and 34% decreases in the volumetric velocity of pulmonary blood flow. The linear velocity of pulmonary blood flow was unchanged with routine lung ventilation, whereas it decreased by 68% with HFJLV. Microembolism impaired the balance between right and left ventricular ejections with blood being redistributed into the greater circulation. The imbalance lasted 5-7 min during HFJLV, while with the routine lung ventilation it was preserved up to the end of the experiment, and systemic blood pressure and total peripheral vascular resistance decreased. Alveolar edema developed in interstitial pulmonary edema. The animals' death occurred 40-60 min later. PMID:8312529

  3. 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

  4. 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. PMID:23281754

  5. Current Clinical Management of Pulmonary Arterial Hypertension

    PubMed Central

    Sung, Yon K; Perez, Vinicio de Jesus; Liu, Juliana; Spiekerkoetter, Edda

    2014-01-01

    Over the last 2 decades there has been a tremendous evolution in the evaluation and care of patients with pulmonary arterial hypertension (PAH). The introduction of targeted PAH therapy consisting of prostacyclin and its analogues, endothelin antagonists, phosphodiestase-5 inhibitors, and now a soluble guanylate cyclase activator have increased therapeutic options and potentially reduced morbidity and mortality, yet none of the current therapies have been curative. Current clinical management of PAH has become more complex given the focus on early diagnosis, an increased number of available therapeutics within each mechanistic class, as well as the emergence of clinically challenging scenarios such as perioperative care. Efforts to standardize the clinical care of PAH patients have led to the formation of multidisciplinary PAH tertiary care programs that strive to offer medical care based on peer-reviewed evidence-based and expert consensus guidelines. Furthermore, these tertiary PAH centers often support clinical and basic science research programs to gain novel insights into the pathogenesis of PAH with the goal to improve the clinical management of this devastating disease. In this manuscript, we discuss the clinical approach and management of PAH from the perspective of a single US-based academic institution. We provide an overview of currently available clinical guidelines, and offer some insight into how we approach current controversies in clinical management of certain patient subsets. We conclude with an overview of our program structure as well as a perspective on research and the role of a tertiary PAH center in contributing new knowledge to the field. PMID:24951763

  6. Coenzyme Q supplementation in pulmonary arterial hypertension

    PubMed Central

    Sharp, Jacqueline; Farha, Samar; Park, Margaret M.; Comhair, Suzy A.; Lundgrin, Erika L.; Tang, W.H. Wilson; Bongard, Robert D.; Merker, Marilyn P.; Erzurum, Serpil C.

    2014-01-01

    Mitochondrial dysfunction is a fundamental abnormality in the vascular endothelium and smooth muscle of patients with pulmonary arterial hypertension (PAH). Because coenzyme Q (CoQ) is essential for mitochondrial function and efficient oxygen utilization as the electron carrier in the inner mitochondrial membrane, we hypothesized that CoQ would improve mitochondrial function and benefit PAH patients. To test this, oxidized and reduced levels of CoQ, cardiac function by echocardiogram, mitochondrial functions of heme synthesis and cellular metabolism were evaluated in PAH patients (N=8) in comparison to healthy controls (N=7), at baseline and after 12 weeks oral CoQ supplementation. CoQ levels were similar among PAH and control individuals, and increased in all subjects with CoQ supplementation. PAH patients had higher CoQ levels than controls with supplementation, and a tendency to a higher reduced-to-oxidized CoQ ratio. Cardiac parameters improved with CoQ supplementation, although 6-minute walk distances and BNP levels did not significantly change. Consistent with improved mitochondrial synthetic function, hemoglobin increased and red cell distribution width (RDW) decreased in PAH patients with CoQ, while hemoglobin declined slightly and RDW did not change in healthy controls. In contrast, metabolic and redox parameters, including lactate, pyruvate and reduced or oxidized gluthathione, did not change in PAH patients with CoQ. In summary, CoQ improved hemoglobin and red cell maturation in PAH, but longer studies and/or higher doses with a randomized placebo-controlled controlled design are necessary to evaluate the clinical benefit of this simple nutritional supplement. PMID:25180165

  7. Plasma endothelin-1 levels in patients with systemic sclerosis: influence of pulmonary or systemic arterial hypertension.

    PubMed Central

    Morelli, S; Ferri, C; Di Francesco, L; Baldoncini, R; Carlesimo, M; Bottoni, U; Properzi, G; Santucci, A

    1995-01-01

    OBJECTIVES--To investigate the behaviour of circulating endothelin-1 (ET-1) in patients affected by systemic sclerosis and to elucidate the relationship between systemic and pulmonary plasma peptide and arterial pressure levels. METHODS--Plasma ET-1 concentrations were determined in 48 patients affected by systemic sclerosis (41 women, seven men; mean age 47.2 (SD 5.5) years) with or without systemic or pulmonary hypertension (or both). A group of 18 normal volunteers served as controls (15 women, three men; mean age 45.0 (10.1) years). RESULTS--Plasma ET-1 levels were significantly greater in patients affected by systemic sclerosis (1.65 (0.29) pg/ml) than in controls (0.63 (0.19) pg/ml) (p < 0.0001). Pulmonary artery systolic hypertension alone was present in 14 patients with systemic sclerosis (50.5 (8.49) mm Hg, range 37-67 mm Hg), and systemic hypertension alone (160.7 (5.9)/100.6 (3.2) mm Hg) was present in 11 patients. Both conditions were present in 12 patients, while 11 patients had systemic hypertension. There were no significant differences in plasma ET-1 levels between patients with pulmonary hypertension alone (1.62 (0.21) pg/ml) and those with systemic hypertension alone (1.65 (0.43) pg/ml). In particular, patients with normal pulmonary artery and systemic pressures (n = 11) had plasma ET-1 concentrations identical to those found in patients (n = 12) with both pulmonary and systemic hypertension (1.70 (0.15) v 1.64 (0.35) pg/ml, respectively). No correlations were observed between plasma ET-1 and either pulmonary or systemic pressures. CONCLUSION--Systemic sclerosis is characterised by increased plasma ET-1 levels, but neither pulmonary nor systemic hypertension are accompanied by further increase in plasma peptide levels. PMID:7495344

  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. Assessment of pulmonary arterial stiffness in obstructive sleep apnea.

    PubMed

    Ozkececi, Gulay; Ulasli, Sevinc Sarinc; Akci, Onder; Dural, İbrahim Ethem; Avsar, Alaettin; Unlu, Mehmet; Onrat, Ersel

    2016-05-01

    Pulmonary hypertension (PH) is one of the major complications of obstructive sleep apnea syndrome (OSAS). Pulmonary arterial stiffness (PAS) can be used in determination of PH. The aim of the present study was to evaluate the PAS and cardiac function of patients with OSAS and analyses the relationship between OSAS severity and PAS. Sixty newly diagnosed patients with OSAS (mean age 49.6 ± 11.7 years) and 30 healthy controls (mean age 46.4 ± 14 years) were enrolled. Right ventricle (RV) and left ventricle (LV) echocardiographic parameters and PAS values of study groups were compared. There were no significant differences in terms of LV ejection fraction, LV Tei-index and tricuspid annular plane systolic excursion. PAS, mean pulmonary arterial pressure (PAP) and RV Tei-index were significantly higher but tricuspid annulus early diastolic myocardial velocity was lower in patients with OSAS than control subjects (respectively p < 0.001, p < 0.001, p = 0.001, p = 0.001). Moreover, we found a higher PAS in OSAS patients without PH compared to controls (p < 0.001). When we investigated the relationship between polysomnographic variables and echocardiographic parameters, we found positive correlations between apnea hypopnea index and total oxygen desaturation with PAS and mean PAP (r = 0.384, p < 0.001; r = 0.404, p < 0.001; r = 0.36, p < 0.001; r = 0.349, p = 0.001 respectively). PAS and mean PAP were increased in patients with OSAS. Pulmonary vascular bed may be affected due to the fluctuation of PAP during day and night time. Therefore, assessment of PAS can be more useful than PAP in OSAS patients. PMID:26783146

  10. 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

  11. Arginase inhibition protects against hypoxia‑induced pulmonary arterial hypertension.

    PubMed

    Jiang, Wenjin; Sun, Bolin; Song, Xuepeng; Zheng, Yanbo; Wang, Ligang; Wang, Tao; Liu, Sheng

    2015-09-01

    The present study aimed to determine the role of arginase (Arg) in pulmonary arterial hypertension (PAH). In vitro, human pulmonary artery smooth muscle cells (HPASMCs) were cultured under hypoxic conditions with, or without, the Arg inhibitor, S‑(2‑boronoethyl)‑l‑cysteine (BEC), for 48 h, following which the proliferation of the HPASMCs was determined using MTT and cell counting assays. For the in vivo investigation, 30 male rats were randomly divided into the following three groups (n=10 per group): i) control group, ii) PAH group and iii) BEC group, in which the right ventricle systolic pressure (RVSP) of the rats was assessed. The levels of cyclin D1, cyclin‑dependent kinase (CDK)4 and p27 were measured in vitro and in vivo. The phosphorylation levels of Akt and extracellular‑related kinase (ERK) were also measured in HPASMCs. In vitro, compared with the hypoxia group, Arg inhibition reduced HPASMC proliferation and reduced the expression levels of cyclin D1, CDK4, phosphorylated (p‑)Akt and p‑ERK. By contrast, Arg inhibition increased the expression of p27. In vivo, compared with the control group, the expression levels of cyclin D1 and CDK4 were reduced in the PAH group, however, the expression of p27 and the RVSP increased. In the BEC group, the opposite effects were observed. Therefore, it was suggested that Arg inhibition may reduce the RVSP of PAH rats and reduce HPASMC proliferation by decreasing the expression levels of cyclin D1 and CDK4, increasing the expression of p27, and partly reducing the phosphorylation of Akt and ERK. PMID:26126810

  12. Changes in bronchial and pulmonary arterial blood flow with progressive tension pneumothorax.

    PubMed

    Carvalho, P; Hilderbrandt, J; Charan, N B

    1996-10-01

    We studied the effects of unilateral tension pneumothorax and its release on bronchial and pulmonary arterial blood flow and gas exchange in 10 adult anesthetized and mechanically ventilated sheep with chronically implanted ultrasonic flow probes. Right pleural pressure (Ppl) was increased in two steps from -5 to 10 and 25 cmH2O and then decreased to 10 and -5 cmH2O. Each level of Ppl was maintained for 5 min. Bronchial blood flow, right and left pulmonary arterial flows, cardiac output (QT), hemodynamic measurements, and arterial blood gases were obtained at the end of each period. Pneumothorax resulted in a 66% decrease in QT, bronchial blood flow decreased by 84%, and right pulmonary arterial flow decreased by 80% at Ppl of 25 cmH2O (P < 0.001). At peak Ppl, the majority of QT was due to blood flow through the left pulmonary artery. With resolution of pneumothorax, hemodynamic parameters normalized, although abnormalities in gas exchange persisted for 60-90 min after recovery and were associated with a decrease in total respiratory compliance. PMID:8904584

  13. Pathological function of Ca2+-sensing receptor in pulmonary arterial hypertension.

    PubMed

    Yamamura, Aya

    2014-01-01

    Pulmonary arterial hypertension (PAH) is defined as an intractable disease characterized by a progressive elevation of pulmonary vascular resistance (PVR) and pulmonary arterial pressure (PAP), leading to right heart failure and premature death. The five-year survival rate after diagnosis is approximately 57%. Although extensive research has identified some factors associated with the cause of PAH, the etiology and pathogenesis remain unclear. In addition to Ca(2+) channel blockers (nifedipine, diltiazem), three categories of drug have been developed for the treatment of PAH based on the pathological mechanisms: prostacyclin and its analogues (epoprostenol, treprostinil, iloprost), endothelin receptor antagonists (bosentan, ambrisentan), and phosphodiesterase type 5 inhibitors (sildenafil, tadalafil). However, screening of novel types of drug acting on the signal pathway associated with the pathological mechanism underlying PAH is ongoing. We recently found that the extracellular Ca(2+)-sensing receptor (CaSR), which belongs to family C of the G protein-coupled receptor (GPCR) superfamily, is upregulated in pulmonary arterial smooth muscle cells (PASMCs) from patients with idiopathic PAH (IPAH). The upregulated CaSR is necessary for the enhanced Ca(2+) signaling and the augmented cell proliferation in PASMCs from IPAH patients. Most importantly, blockage of CaSR with an antagonist, NPS2143, prevents the development of pulmonary hypertension and right ventricular hypertrophy in animal models of pulmonary hypertension. The use of calcilytics, antagonists of CaSR, may be a novel therapeutic approach for PAH patients. PMID:24770445

  14. 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

  15. [Pulmonary circulation in embolic pulmonary edema].

    PubMed

    Sanotskaia, N V; Polikarpov, V V; Matsievskiĭ, D D

    1989-02-01

    The ultrasonic method was used in acute experiments on cats with open chest under artificial lung ventilation to obtain blood flow in low-lobar pulmonary artery and vein, the blood pressure in pulmonary artery, as well as the left atrial pressure in fat (olive oil) and mechanical (Lycopodium spores) pulmonary embolism. It is shown that pulmonary embolism produces the decrease in the blood flow in pulmonary artery and vein, the increase of the pressure in pulmonary artery and left atria, the increase of lung vessels resistance. The decrease is observed of systemic arterial pressure, bradycardia, and extrasystole. After 5-10 min the restoration of arterial pressure and heart rhythm occur and partial restoration of blood flow in pulmonary artery and vein. In many experiments the blood flow in vein outdoes that in the artery--it allows to suppose the increase of the blood flow in bronchial artery. After 60-90 min there occur sudden decrease of systemic arterial pressure, the decrease of the blood flow in pulmonary artery and vein. The pressure in pulmonary artery and resistance of pulmonary vessels remain high. Pulmonary edema developed in all animals. The death occurs in 60-100 min after the beginning of embolism. PMID:2923969

  16. 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?

  17. 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?

  18. Port-a-cath embolisation to pulmonary artery.

    PubMed

    Bhatt, Vijaya Raj; Gupta, Shilpi; Lowry, Joseph; Dhar, Meekoo

    2011-01-01

    Intravascular embolisation of catheter, a relatively uncommon event associated with the use of totally implanted port devices, can have serious cardiovascular, pulmonary and septic complications with an overall mortality of 1.8%. Here, the authors report an asymptomatic patient with pulmonary artery catheter embolisation diagnosed incidentally in a positron emission tomography scan who underwent successful percutaneous extraction of the catheter in an attempt to avoid the possible dreadful complications. PMID:22689667

  19. Pulmonary function differences in patients with chronic right heart failure secondary to pulmonary arterial hypertension and chronic left heart failure

    PubMed Central

    Liu, Wei-Hua; Luo, Qin; Liu, Zhi-Hong; Zhao, Qing; Xi, Qun-Ying; Xue, Hai-Feng; Zhao, Zhi-Hui

    2014-01-01

    Background Pulmonary abnormalities are found in both chronic heart failure (CHF) and pulmonary arterial hypertension (PAH). The differences of pulmonary function in chronic left heart failure and chronic right heart failure are not fully understood. Material/Methods We evaluated 120 patients with stable CHF (60 with chronic left heart failure and 60 with chronic right heart failure). All patients had pulmonary function testing, including pulmonary function testing at rest and incremental cardiopulmonary exercise testing (CPX). Results Patients with right heart failure had a significantly lower end-tidal partial pressure of CO2 (PetCO2), higher end-tidal partial pressure of O2 (PetO2) and minute ventilation/CO2 production (VE/VCO2) at rest. Patients with right heart failure had a lower peak PetCO2, and a higher peak dead space volume/tidal volume (VD/VT) ratio, peak PetO2, peak VE/VCO2, and VE/VCO2 slope during exercise. Patients with right heart failure had more changes in ΔPetCO2 and ΔVE/VCO2, from rest to exercise. Conclusions Patients with right heart failure had worse pulmonary function at rest and exercise, which was due to severe ventilation/perfusion (V/Q) mismatching, severe ventilation inefficiency, and gas exchange abnormality. PMID:24916204

  20. A continuum model for pressure-flow relationship in human pulmonary circulation.

    PubMed

    Huang, Wei; Zhou, Qinlian; Gao, Jian; Yen, R T

    2011-06-01

    A continuum model was introduced to analyze the pressure-flow relationship for steady flow in human pulmonary circulation. The continuum approach was based on the principles of continuum mechanics in conjunction with detailed measurement of vascular geometry, vascular elasticity and blood rheology. The pulmonary arteries and veins were considered as elastic tubes and the "fifth-power law" was used to describe the pressure-flow relationship. For pulmonary capillaries, the "sheet-flow" theory was employed and the pressure-flow relationship was represented by the "fourth-power law". In this paper, the pressure-flow relationship for the whole pulmonary circulation and the longitudinal pressure distribution along the streamlines were studied. Our computed data showed general agreement with the experimental data for the normal subjects and the patients with mitral stenosis and chronic bronchitis in the literature. In conclusion, our continuum model can be used to predict the changes of steady flow in human pulmonary circulation. PMID:21608412

  1. Endothelin receptor antagonists in the treatment of pulmonary arterial hypertension.

    PubMed

    Langleben, David

    2007-03-01

    The recognition that endothelin-1 contributes to the pathogenesis of pulmonary arterial hypertension has led to the development of clinically useful endothelin receptor antagonists that improve symptoms and functional capacity and alter the natural history of the disease in a beneficial way. The antagonists have varying degrees of selectivity for the two classes of endothelin receptor, termed ETA and ETB, and the varying degrees may translate into clinical differences. Endothelin receptor antagonists have become an integral part of therapy for pulmonary arterial hypertension, and the indications for their use are expanding. PMID:17338931

  2. Bronchial‐pulmonary arterial fistula with primary racemose hemangioma

    PubMed Central

    Morio, Yoshiteru; Matsunaga, Takeshi; Shiraishi, Akihiko; Uekusa, Toshimasa; Takahashi, Kazuhisa

    2016-01-01

    Abstract Bronchial‐pulmonary arterial fistula (BPAF) is a rare vascular malformation complicated with racemose hemangioma. We report a case of a 65‐year‐old male with BPAF with primary racemose hemangioma. Bronchial arteriography demonstrated convolution, dilation, and aneurysm connected with pulmonary artery, suggesting the presence of BPAF, in the left upper lobe. Since a 20‐mm sized aneurysm of bronchial artery and BPAF coexisted, he underwent ligation of bronchial arterial aneurysm and left upper lobectomy to prevent hemoptysis. As neither history of prior illness nor histopathologic findings of vascular inflammation was seen, the present case demonstrated BPAF with primary racemose hemangioma. Establishment of non‐invasive treatment strategy for BPAF is urgently required. PMID:27081488

  3. Bronchial-pulmonary arterial fistula with primary racemose hemangioma.

    PubMed

    Kato, Miharu; Morio, Yoshiteru; Matsunaga, Takeshi; Shiraishi, Akihiko; Uekusa, Toshimasa; Takahashi, Kazuhisa

    2016-04-01

    Bronchial-pulmonary arterial fistula (BPAF) is a rare vascular malformation complicated with racemose hemangioma. We report a case of a 65-year-old male with BPAF with primary racemose hemangioma. Bronchial arteriography demonstrated convolution, dilation, and aneurysm connected with pulmonary artery, suggesting the presence of BPAF, in the left upper lobe. Since a 20-mm sized aneurysm of bronchial artery and BPAF coexisted, he underwent ligation of bronchial arterial aneurysm and left upper lobectomy to prevent hemoptysis. As neither history of prior illness nor histopathologic findings of vascular inflammation was seen, the present case demonstrated BPAF with primary racemose hemangioma. Establishment of non-invasive treatment strategy for BPAF is urgently required. PMID:27081488

  4. 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.

  5. Effects of pressure on arterial failure.

    PubMed

    Khamdaengyodtai, Pannathai; Vafai, Kambiz; Sakulchangsatjatai, Phrut; Terdtoon, Pradit

    2012-10-11

    A three-dimensional multilayer model of mechanical response for analyzing the effect of pressure on arterial failure is presented in this work. The multilayer arterial wall is considered to be composed of five different layers. The three-dimensional effects are incorporated within the five-concentric axisymmetric layers while incorporating the nonlinear elastic characteristics under combined extension and inflation. Constitutive equations for fiber-reinforced material are employed for three of the major layers, i.e., intima, media and adventitia and an isotropic material model is employed for the other two layers, i.e., endothelium and internal elastic lamina. Our own developed three-dimensional five-layer model has been utilized to model propagated rupture area of the arterial wall. Required parameters for each layer are obtained by using a nonlinear least square method fitted to in vivo non-invasive experimental data of human artery and the effects of pressure on arterial failure are examined. The solutions from our computational model are compared with previous studies and good agreements are observed. Local stresses and strain distributions across the deformed arterial wall are illustrated and consequently the rupture area is predicted by varying luminal pressure in the physiological range and beyond. The effects of pressure on the arterial failure have been interpreted based on this comprehensive three-dimensional five-layer arterial wall model. This is the first study which employs two constitutive equations and incorporates a five-layer arterial wall model in three-dimensions based on in vivo non-invasive experimental data for a human artery. PMID:22980577

  6. 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

  7. 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.

  8. Connective tissue disease-associated pulmonary arterial hypertension.

    PubMed

    Sung, Yon K; Chung, Lorinda

    2015-05-01

    Pulmonary arterial hypertension (PAH) is characterized by vascular remodeling of pulmonary arterioles that leads to increased pulmonary vascular resistance, right heart failure, and death. It is associated with connective tissue diseases, including systemic sclerosis, systemic lupus erythematosus, and mixed connective tissue disease. PAH is characterized by dyspnea on exertion and fatigue. Syncopal events suggest severe disease. Patients may present with signs of right heart failure. One- and 3-year survival rates are approximately 81% and 52%, respectively. Given the high prevalence and mortality, algorithms for screening are currently under investigation and will hopefully lead to earlier diagnosis and improved survival. PMID:25836644

  9. Improved survival in limited scleroderma-related pulmonary artery hypertension.

    PubMed

    Marini, Carlo; Formichi, Bruno; Bauleo, Carolina; Michelassi, Claudio; Pancani, Roberta; Prediletto, Renato; Miniati, Massimo; Catapano, Giosuè; Monti, Simonetta; Mannucci, Francesca; Tavoni, Antonio; D'Ascanio, Anna; Pastormerlo, Luigi Emilio; Giannoni, Alberto; Giuntini, Carlo

    2014-06-01

    Reportedly, patients with scleroderma-related pulmonary hypertension (SSc-PAH) respond poorly to new vasoactive drugs (NVD). Forty-nine SSc-PAH patients underwent right heart catheterization (RHC) and, according to NVD availability, divided as follows: Group 1 (n = 23, from 1999 to 2004, poor availability), and Group 2 (n = 26, from 2005 to 2010, good availability). Before diagnostic RHC, NVD had been given to 30 % of the patients in Group 1, and 58 % of those in Group 2 (p = 0.049). At diagnosis, patients in Group 1 had greater heart dilatation (p < 0.01), higher mean pulmonary artery pressure (p < 0.05), lower pulmonary artery capacitance (p < 0.05), and lower carbon monoxide lung diffusing capacity (DLco, p < 0.05) than those in Group 2. At a median follow-up time of 15.5 months, DLco further decreased in Group 1 (p < 0.05), whereas cardiac index increased in Group 2 (p < 0.05). At 36 months of follow-up, 72.4 % of the patients in Group 2 were still alive as opposed to 30.4 % in Group 1 (p = 0.02). In multivariate analysis, DLco and mixed venous oxygen saturation (SvO2) were independent predictors of survival. A value of DLco <7.2 mL/mmHg/min was associated with a hazard ratio (HR) of 5.3 (p < 0.001); for SvO2 <63.8 %, the HR was 3.7 (p < 0.01).NVD have beneficial effects in patients with SSc-PAH. Both DLco and SvO2 are predictors of survival and may assist in planning treatment. PMID:23361526

  10. 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.

  11. Use of Computed Tomography – Digital Subtraction Angiography in differentiating pulmonary thrombosis and pulmonary artery dissection in a large pulmonary artery aneurysm

    PubMed Central

    Rashid, Hashrul N.Z.; Lim, Andy K.; Lau, Kenneth K.

    2016-01-01

    70 year-old female with chronic obstructive pulmonary disease (COPD) presented with typical symptoms of an exacerbation of COPD. Management of COPD resolved her wheezing, but ongoing hypoxia and retrospective history of atypical chest pain prompted exclusion of a pulmonary embolus. A CT Pulmonary Angiogram (CTPA) with standard 64-slice CT revealed an extensive non-occlusive defect in a grossly dilated right pulmonary artery. Presence of circumferential cuff of soft tissue within sub-segmental pulmonary artery branch raised the possibility of pulmonary artery dissection (PAD). Exclusion of PAD was important as it precluded full anticoagulation. A dynamic CT-digital subtraction angiography (CT-DSA) with the 320-slice multidetector CT (Aquilion-one Vision, Toshiba) did not reveal any intimal flap or contrast extension into the pulmonary arterial wall, suggesting it is unlikely to be PAD. The patient was started on full anticoagulation and reported improvement of symptoms with reduction in pulmonary thrombus burden on repeat CTPA at 4 weeks. To our knowledge, this is the first reported use of dynamic CT-DSA in ruling out PAD. PMID:27144113

  12. Use of Computed Tomography - Digital Subtraction Angiography in differentiating pulmonary thrombosis and pulmonary artery dissection in a large pulmonary artery aneurysm.

    PubMed

    Rashid, Hashrul N Z; Lim, Andy K; Lau, Kenneth K

    2016-01-01

    70 year-old female with chronic obstructive pulmonary disease (COPD) presented with typical symptoms of an exacerbation of COPD. Management of COPD resolved her wheezing, but ongoing hypoxia and retrospective history of atypical chest pain prompted exclusion of a pulmonary embolus. A CT Pulmonary Angiogram (CTPA) with standard 64-slice CT revealed an extensive non-occlusive defect in a grossly dilated right pulmonary artery. Presence of circumferential cuff of soft tissue within sub-segmental pulmonary artery branch raised the possibility of pulmonary artery dissection (PAD). Exclusion of PAD was important as it precluded full anticoagulation. A dynamic CT-digital subtraction angiography (CT-DSA) with the 320-slice multidetector CT (Aquilion-one Vision, Toshiba) did not reveal any intimal flap or contrast extension into the pulmonary arterial wall, suggesting it is unlikely to be PAD. The patient was started on full anticoagulation and reported improvement of symptoms with reduction in pulmonary thrombus burden on repeat CTPA at 4 weeks. To our knowledge, this is the first reported use of dynamic CT-DSA in ruling out PAD. PMID:27144113

  13. 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.

  14. Idiopathic Pulmonary Arterial Hypertension: An Avian Model for Plexogenic Arteriopathy and Serotonergic Vasoconstriction

    PubMed Central

    Wideman, Robert F.; Hamal, Krishna R.

    2011-01-01

    Idiopathic pulmonary arterial hypertension (IPAH) is a disease of unknown cause that is characterized by elevated pulmonary arterial pressure and pulmonary vascular resistance attributable to vasoconstriction and vascular remodeling of small pulmonary arteries. Vascular remodeling includes hypertrophy and hyperplasia of smooth muscle (medial hypertrophy) accompanied in up to 80% of the cases by the formation of occlusive plexiform lesions (plexogenic arteriopathy). Patients tend to be unresponsive to vasodilator therapy and have a poor prognosis for survival when plexogenic arteriopathy progressively obstructs their pulmonary arteries. Research is needed to understand and treat plexogenic arteriopathy, but advances have been hindered by the absence of spontaneously developing lesions in existing laboratory animal models. Young domestic fowl bred for meat production (broiler chickens, broilers) spontaneously develop IPAH accompanied by semi-occlusive endothelial proliferation that progresses into fully developed plexiform lesions. Plexiform lesions develop in both females and male broilers, and lesion incidences (lung sections with lesions/lung sections examined) averaged approximately 40% in 8 to 52 week old birds. Plexiform lesions formed distal to branch points in muscular interparabronchial pulmonary arteries, and were associated with perivascular mononuclear cell infiltrates. Serotonin (5-hydroxytryptamine, 5-HT) is a potent vasoconstrictor and mitogen known to stimulate vascular endothelial and smooth muscle cell proliferation. Serotonin has been directly linked to the pathogenesis of IPAH in humans, including IPAH linked to serotonergic anorexigens that trigger the formation of plexiform lesions indistinguishable from those observed in primary IPAH triggered by other causes. Serotonin also plays a major role in the susceptibility of broilers to IPAH. This avian model of spontaneous IPAH constitutes a new animal model for biomedical research focused on the

  15. 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

  16. 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

  17. [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

  18. Pulmonary Arterial Hypertension-A Deadly Complication of Systemic Sclerosis

    PubMed Central

    Pankey, Edward A; Epps, Matthew; Nossaman, Bobby D; Hyman, Albert L; Kadowitz, Philip J

    2011-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease with limited therapeutic options. Moreover, when PAH occurs in patients diagnosed with systemic sclerosis, worse outcomes are observed. The purpose of this review is to discuss the etiologies of PAH found in the systemic sclerosis patient, limitations of current medical therapies, and, finally, potential therapies for patients with this combination. PMID:23626904

  19. Vascular leiomyoma of the lung arising from pulmonary artery.

    PubMed

    Terada, Tadashi

    2013-01-01

    Leiomyoma of the lung is extremely rare. The entity is not described in WHO blue book. Less than 100 cases of leiomyoma of the lung have been reported in the literature. However, vascular leiomyoma has not been reported in the literature, to the author's best knowledge. Herein reported is the first case of vascular leiomyoma of the lung arising from smooth muscles of the pulmonary artery. A 62-year-old woman (non-smoker) was found to have a small tumor in the upper lobe in the right lung in routine check. Imaging modalities including CT demonstrated no metastatic lesions. Although clinical cytology and biopsy revealed no malignant cell, right upper lobectomy was performed under the clinical diagnosis of lung carcinoma. Grossly, a white tumor of 1 x 0.8 cm was recognized in the lung. Microscopically, the tumor was connected to the pulmonary arteries. The tumor was composed of mature smooth muscles. Small pulmonary arteries are embedded in the tumor. No lymphatics were seen. Immunohistochemically, the tumor cells were poisitive for alpha-smooth muscle actin, vimentin and Ki-67 (labeling 2%). However, they were negative for cytokeratin (CK) AE1/3, CK CAM5.2, desmin, S100 protein, p53, CD34, KIT, HMB45, estrogen receptor, progesterone receptor, and myoglobin. A pathological diagnosis of primary vascular leiomyoma arising from the smooth muscle of pulmonary artery was made. The patient is now free from tumor, and is now alive 10 year after the operation. PMID:23236548

  20. 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

  1. 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

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

    PubMed

    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

  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. 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

  6. 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.

  7. 4,4'-Methylenedianiline Alters Serotonergic Transport in a Novel, Sex-Specific Model of Pulmonary Arterial Hypertension in Rats.

    PubMed

    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

    2015-09-01

    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 [Formula: see text], 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,[Formula: see text] , 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

  8. Interventional therapeutic strategy for hemoptysis originating from infectious pulmonary artery pseudoaneurysms.

    PubMed

    Tsukada, Jitsuro; Hasegawa, Ichiro; Torikai, Hideyuki; Sayama, Koichi; Jinzaki, Masahiro; Narimatsu, Yoshiaki

    2015-07-01

    This study reports 6 cases of hemoptysis originating from infectious pulmonary artery pseudoaneurysms (PAPs). Selective pulmonary angiography revealed PAPs in 5 cases, and segmental pulmonary artery embolization was performed using coils and gelatin sponge particles. Systemic arterial embolization also was performed in 5 cases because of inadequate initial control or for shunts from systemic to pulmonary arteries. At a median follow-up time of 9 months (range, 25 d to 25 mo), no recurrence occurred, although 2 patients died of respiratory failure. Segmental artery embolization combined with systemic artery embolization may be useful in patients with hemoptysis secondary to PAPs. PMID:26095272

  9. Invasive pulmonary mucormycosis with concomitant lung cancer presented with massive hemoptysis by huge pseudoaneurysm of pulmonary artery.

    PubMed

    Kim, Young Il; Kang, Hyo Cheol; Lee, Ho Sung; Choi, Jae Sung; Seo, Ki Hyun; Kim, Yong Hoon; Na, Juock

    2014-11-01

    Pulmonary mucormycosis is a rare opportunistic invasive fungal infection involving the pulmonary vasculature in immunocompromised patients. Pseudoaneurysm of pulmonary artery in mucormycosis is a rare fatal complication after invasion and rupture of a pulmonary artery. We report a patient with diabetes mellitus and incidental lung cancer who developed massive hemoptysis because of a huge pseudoaneurysm of the left pulmonary artery by mucormycosis. Although the patient had been managed by amphotericin B followed by left pneumonectomy for persistent hemoptysis, he died from septic shock and multiorgan failure after surgery. Histologic analysis of a surgical specimen revealed concomitant squamous cell lung cancer. PMID:25441799

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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

  16. A Case of Behcet’s Disease Combined with Pulmonary Artery Aneurysm in a Korean Female Patient

    PubMed Central

    Uh, Sootaek; Kim, Jin Oh; You, Yong Kyu; Moon, Seung Hyug; Park, Choon Sik

    1994-01-01

    Behcet’s disease (BD) is a systemic disorder of unknown process resulting from systemic vasculitis. The pulmonary involvements in BD are uncommon. Furthermore, in the female, involvement of the pulmonary artery is quite rare. There were a few cases of female patients with BD with pulmonary artery aneurysm confirmed by pulmonary artery angiogram. In this article, we report a case of BD, combined with pulmonary artery aneurysm, confirmed by pulmonary angiogram and treated by surgery in a Korean female patient. PMID:8038147

  17. [Emerging therapies for the treatment of pulmonary arterial hypertension].

    PubMed

    Ghofrani, Hossein Ardeschir; Voswinckel, Robert; Reichenberger, Frank; Grimminger, Friedrich; Seeger, Werner

    2005-06-01

    Besides all progress in the therapy of pulmonary arterial hypertension over the past years, there is still no cure for this devastating disease. By introducing effective and nonparenteral medications (e. g., oral endothelin receptor antagonists [ERAs], inhaled prostanoids), quality of life, exercise tolerance and prognosis of patients have substantially improved. However, applicability of these therapies can be hampered by serious side effects and/or the necessity for elaborate application techniques. Whether selective ERAs--due to their specificity for the A-type receptor--have potential benefits over the nonselective ERA bosentan remains to be answered by the analysis of pivotal trials recently carried out with ambrisentan and sitaxsentan. Inhaled treprostinil can potentially have benefits over the already approved inhaled iloprost, related to its higher pulmonary selectivity as well as to the longer biological half-life. However, this has yet to be proven in long-term randomized controlled trials. In comparison to the previously mentioned substances, the selective phosphodiesterase-5 (PDE5) inhibitor sildenafil approached approval closest as new therapy for pulmonary arterial hypertension. Oral sildenafil has proven its efficacy as a selective pulmonary vasodilator in various forms of pulmonary hypertension. The results of the pivotal phase III trial have confirmed the strong efficacy and excellent tolerability of this substance. Combination therapies, despite all progress seen for single agents, can be regarded as the most promising therapeutic approach for the future. However, controlled randomized trials that are currently under consideration have to confirm this notion. PMID:15965806

  18. CT-Based Pulmonary Artery Measurements for the Assessment of Pulmonary Hypertension

    PubMed Central

    Corson, Neal; Armato, Samuel G.; Labby, Zacariah E.; Straus, Christopher; Starkey, Adam; Gomberg-Maitland, Mardi

    2014-01-01

    Rationale and Objectives Pulmonary hypertension (PH) is a complex and fatal disease that is difficult to diagnose non-invasively. This study evaluated previously published CT-based vessel measurement criteria and investigated the predictive power and diagnostic ability of the main pulmonary artery diameter (MPAD) and the ratio of MPAD to aorta diameter (rPA). Materials and Methods The database for this study consisted of 175 PH patients (for whom mean pulmonary artery pressure (mPAP) was known), 16 patients without PH but with known mPAP (non-PH patients), and 114 “normal” patients without known mPAP. The performance of previously published criteria, MPAD > 29 mm and rPA > 1, was determined. The relationship between vessel measurements and mPAP was evaluated through correlation and linear regression analysis. The ability of these measurements to discriminate between patients with and without PH was determined by receiver operating characteristic analysis. Results For discriminating between PH and “normal” patients, the sensitivity and specificity of the criterion MPAD>29mm were 0.89 (0.84-0.93) and 0.83 (0.76-0.90), respectively, and the sensitivity and specificity of the criterion rPA>1 were 0.89 (0.85-0.94) and 0.82 (0.74-0.89), respectively. At a specificity of 0.95 in the task of separating PH and “normal” patients, the sensitivity of MPAD was 0.81 (0.72-0.90) and the sensitivity of rPA was 0.76 (0.66-0.85), but the specificity for both decreased when non-PH patients were included. For the combined PH and non-PH patient groups, the correlation between the vessel measurements and mPAP was significant but low, and the ability of the vessel measurements to predict mPAP was limited. Conclusion This study found that the sensitivity of previously published vessel criteria for identifying PH patients is high but the specificity may not be high enough for routine use in a clinical patient population. PMID:24594422

  19. 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

  20. Fistulous connection between internal mammary graft and pulmonary vasculature after coronary artery bypass grafting: a rare cause of continuous murmur.

    PubMed

    Guray, Umit; Guray, Yesim; Ozbakir, Cemal; Yilmaz, M Birhan; Sasmaz, Hatice; Korkmaz, Sule

    2004-09-01

    A 58-year-old male who had undergone coronary artery bypass grafting (CABG) using left internal mammary artery and a sequential saphenous vein graft 2 years ago presented with new onset angina. His initial physical examination revealed an unexpected continuous murmur over the left sternal border, and two-dimensional echocardiography has failed to identy the cause. Cardiac catheterization then performed and revealed patent left internal mammary artery and saphenous vein grafts. Besides, selective injection of the left internal mammary artery graft also showed a fistula formation between left internal mammary artery graft and pulmonary vasculature of the left upper lobe. He was managed conservatively because of the severely diseased left anterior descending artery distal to internal mammary artery anastomosis and low pulmonary artery pressure. The development of fistulous connection between internal mammary artery and pulmonary vasculature is an extremely rare complication following CABG. Patients with such fistulae usually present with chest pain due to coronary steal syndrome. A new heart sound, especially a continuous murmur, may be detected during physical examination. Surgical correction is indicated in the event of refractory angina, growing fistula causing heart failure or endarteritis. Otherwise, a conservative approach with instruction of the patient for prophylactic precautions of subacute bacterial endocarditis may be recommended for asymptomatic patients. PMID:15301909

  1. Reflexes from pulmonary arterial baroreceptors in dogs: interaction with carotid sinus baroreceptors

    PubMed Central

    Moore, Jonathan P; Hainsworth, Roger; Drinkhill, Mark J

    2011-01-01

    Abstract In contrast to the reflex vasodilatation occurring in response to stimulation of baroreceptors in the aortic arch, carotid sinuses and coronary arteries, stimulation of receptors in the wall of pulmonary arteries results in reflex systemic vasoconstriction. It is rare for interventions to activate only one reflexogenic region, therefore we investigated how these two types of reflexes interact. In anaesthetized dogs connected to cardiopulmonary bypass, reflexogenic areas of the carotid sinuses, aortic arch and coronary arteries and the pulmonary artery were subjected to independently controlled pressures. Systemic perfusion pressure (SPP) measured in the descending aorta (constant flow) provided an index of systemic vascular resistance. In other experiments, sympathetic efferent neural activity was recorded in fibres dissected from the renal nerve (RSNA). Physiological increases in pulmonary arterial pressure (PAP) induced significant increases in SPP (+39.1 ± 10.4 mmHg) and RSNA (+17.6 ± 2.2 impulses s−1) whereas increases in carotid sinus pressure (CSP) induced significant decreases in SPP (−42.6 ± 10.8 mmHg) and RSNA (−42.8 ± 18.2 impulses s−1) (P < 0.05 for each comparison; paired t test). To examine possible interactions, PAP was changed at different levels of CSP in both studies. With CSP controlled at 124 ± 2 mmHg, the threshold, ‘set point’ and saturation pressures of the PAP–SPP relationship were higher than those with CSP at 60 ± 1 mmHg; this rightward shift was associated with a significant decrease in the reflex gain. Similarly, increasing CSP produced a rightward shift of the PAP–RSNA relationship, although the effect on reflex gain was inconsistent. Furthermore, the responses to changes in CSP were influenced by setting PAP at different levels; increasing the level of PAP from 5 ± 1 to 33 ± 3 mmHg significantly increased the set point and threshold pressures of the CSP–SPP relationship; the reflex gain was not

  2. 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

  3. 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

  4. Cell Permeable Peptide Conjugated Nanoerythrosomes of Fasudil Prolong Pulmonary Arterial Vasodilation in PAH Rats

    PubMed Central

    Gupta, Nilesh; Patel, Brijeshkumar; Nahar, Kamrun; Ahsan, Fakhrul

    2014-01-01

    In this study, we tested the hypothesis that a cell permeable peptide, CARSKNKDC (CAR), conjugated nanoerythrosomes (NERs) containing fasudil, a rho-kinase (ROCK) inhibitor, produces prolonged pulmonary preferential vasodilation. CAR conjugated NERs containing fasudil were prepared by hypotonic lysis and extrusion method, optimized for various physicochemical properties in-vitro. The formulations were then used to study the hemodynamic efficacy in a monocrotaline-induced rodent model of pulmonary arterial hypertension (PAH). CAR-NERs-Fasudil was spherical in shape with an average vesicle size and entrapment efficiency of 161.3±1.37nm and 48.81±1.96%, respectively. Formulations were stable for ~3 weeks when stored at 4°C and the drug was released in a controlled fashion for >48 hrs. The uptake of CAR-NERs-Fasudil by TGF-β activated pulmonary arterial smooth muscle cell was ~1.5 fold greater than the uptake of NERs-Fasudil. CAR-NERs-Fasudil inhibited ROCK activity and 5-hydroxytryptamine induced cell proliferation. In terms of reduction of pulmonary arterial pressure, intratracheal administration of CAR-NERs-Fasudil was ~2-fold more specific to the lungs compared with plain fasudil. Overall, CAR peptide grafted nanoerythrosomes offers a new platform for improving the therapeutic efficacy of a rho-kinase inhibitor, fasudil, without affecting peripheral vasodilation. PMID:25460151

  5. Rescue balloon pulmonary angioplasty under veno-arterial extracorporeal membrane oxygenation in a patient with acute exacerbation of chronic thromboembolic pulmonary hypertension.

    PubMed

    Nakamura, Makiko; Sunagawa, Osahiko; Tsuchiya, Hiroyuki; Miyara, Takafumi; Taba, Yoji; Touma, Takashi; Munakata, Hiroshi; Kugai, Tadao; Okita, Yutaka

    2015-01-01

    We describe a case of a 41-year-old woman with acute exacerbation of chronic thromboembolic pulmonary hypertension (CTEPH) complicated by rapidly progressive respiratory failure and right heart failure with cardiogenic shock. A computed tomography (CT) showed thrombi in the right main pulmonary artery and bilateral peripheral pulmonary arteries, and echocardiography showed right ventricular dilatation and tricuspid regurgitation, with an estimated pressure gradient of 80 mmHg. The patient was initially diagnosed with acute pulmonary thromboembolism, and thrombolytic therapy was administered. Her condition subsequently deteriorated, however, necessitating mechanical ventilation and veno-arterial extracorporeal membrane oxygenation (VA-ECMO). We performed emergency catheter-directed thrombectomy and thrombus aspiration. Pulmonary hypertension (PH) temporarily improved, but subsequently worsened, and the patient was diagnosed with CTEPH. Pulmonary endarterectomy (PEA) was performed. After PEA, we were unable to wean the patient off VA-ECMO, and rescue balloon pulmonary angioplasty (BPA) to the middle and inferior lobe branches of the right lung was performed. Five days after BPA, the patient was removed from VA-ECMO and on the 57th day of hospitalization, she was weaned off the ventilator. The patient was discharged after 139 days of hospitalization. Rescue BPA represents a useful intervention for improving PH and weaning off VA-ECMO in a patient with acute exacerbation of CTEPH. PMID:25742948

  6. 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

  7. Pulmonary arterial hypertension associated with congenital heart disease. Personal perspectives.

    PubMed

    Nakanishi, Toshio

    2015-01-01

    The management of patients with congenital heart disease (CHD) and pulmonary arterial hypertension (PAH) has changed dramatically with the development of targeted therapy with selective pulmonary vasodilators. The number of adult Japanese patients with PAH associated with CHD is increasing. It is important to develop evidence-based guidelines for the management of these patients, and to achieve this, a register of adult Japanese patients with PAH associated with CHD should be established. At the World Symposium in Nice, France, in 2013, the consensus was reached that patients with a pulmonary resistance of < 4 Wood Units (WU)·m(2) have operable disease, and patients with a pulmonary resistance of > 8 WU·m(2) have inoperable disease. However, these criteria are conservative. Some patients with a pulmonary resistance of > 8 WU·m(2) and a good response to a pulmonary vasodilator test have operable disease and a favorable clinical course long after repair of CHD. The criteria determining operability in patients with PAH associated with CHD in the era of pulmonary vasodilators should be established using data obtained from patient registers and/or multicenter studies. The optimal management of Eisenmenger syndrome should also be established using data obtained from patient registers. Prospective studies should be conducted to determine the life expectancy of patients with Eisenmenger syndrome in the era of targeted therapy. A relatively mild increase in pulmonary resistance may result in failure of a Fontan circulation. The effects of pulmonary vasodilators on the long-term prognosis of patients who have undergone the Fontan operation are still unclear. PMID:25787791

  8. Activation of Calpain-2 by Mediators in Pulmonary Vascular Remodeling of Pulmonary Arterial Hypertension.

    PubMed

    Kovacs, Laszlo; Han, Weihong; Rafikov, Ruslan; Bagi, Zsolt; Offermanns, Stefan; Saido, Takaomi C; Black, Stephen M; Su, Yunchao

    2016-03-01

    Calpain mediates collagen synthesis and cell proliferation and plays an important role in pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). In the present study, we investigated whether and how calpain is activated by PAH mediators in pulmonary artery smooth muscle cells (PASMCs). These data show that smooth muscle-specific knockout of calpain attenuated and knockout of calpastatin potentiated pulmonary vascular remodeling and pulmonary hypertension. Treatment of PASMCs with the PAH mediators platelet-derived growth factor (PDGF), serotonin, H2O2, endothelin-1, and IL-6 caused significant increases in calpain activity, cell proliferation, and collagen-I protein level without changes in protein levels of calpain-1 and -2. The calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxymethyl ester) (BAPTA/AM) did not affect calpain activation, but the extracellular signal-regulated kinase (ERK) 1/2 inhibitor PD98059 and knocking down of calpain-2 prevented calpain activation in PAH mediator-treated PASMCs. Mass spectrometry data showed that the phosphorylation of calpain-2 at serine (Ser) 50 was increased and the phosphorylation of calpain-2 at Ser369 was decreased in PDGF-treated PASMCs. The PDGF-induced increase in Ser50 phosphorylation of calpain-2 was prevented by PD98059, whereas dephosphorylation of calpain-2 at Ser369 was blocked by the protein phosphatase 2A inhibitor fostriecin. Furthermore, smooth muscle of pulmonary arteries in PAH animal models and patients with PAH showed higher levels of phospho-Ser50-calpain-2 (P-Ser50) and lower levels of phospho-Ser369-calpain-2 (P-Ser369). These data support that calpain modulates pulmonary vascular remodeling in PAH. PAH mediator-induced activation of calpain is caused by ERK1/2-dependent phosphorylation of calpain-2 at Ser50 and protein phosphatase 2A-dependent dephosphorylation of calpain-2 at Ser369 in pulmonary vascular remodeling of PAH. PMID:26248159

  9. 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. PMID:26811053

  10. Vasoreactivity to inhaled nitric oxide with oxygen predicts long-term survival in pulmonary arterial hypertension.

    PubMed

    Malhotra, Rajeev; Hess, Dean; Lewis, Gregory D; Bloch, Kenneth D; Waxman, Aaron B; Semigran, Marc J

    2011-04-01

    Pulmonary vasodilator testing is currently used to guide management of patients with pulmonary arterial hypertension (PAH). However, the utility of the pulmonary vascular response to inhaled nitric oxide (NO) and oxygen in predicting survival has not been established. Eighty patients with WHO Group I PAH underwent vasodilator testing with inhaled NO (80 ppm with 90% O(2) for 10 minutes) at the time of diagnosis. Changes in right atrial (RA) pressure, mean pulmonary artery pressure (mPAP), pulmonary capillary wedge pressure, Fick cardiac output, and pulmonary vascular resistance (PVR) were tested for associations to long-term survival (median follow-up 2.4 years). Five-year survival was 56%. Baseline PVR (mean±SD 850±580 dyne-sec/cm(5)) and mPAP (49±14 mmHg) did not predict survival, whereas the change in either PVR or mPAP while breathing NO and O(2) was predictive. Patients with a ≥30% reduction in PVR with inhaled NO and O(2) had a 53% relative reduction in mortality (Cox hazard ratio 0.47, 95% confidence interval (CI) 0.23-0.99, P=0.047), and those with a ≥12% reduction in mPAP with inhaled NO and O(2) had a 55% relative reduction in mortality (hazard ratio 0.45, 95% CI 0.22-0.96, P=0.038). The same vasoreactive thresholds predicted survival in the subset of patients who never were treated with calcium channel antagonists (n=66). Multivariate analysis showed that decreases in PVR and mPAP with inhaled NO and O(2) were independent predictors of survival. Reduction in PVR or mPAP during short-term administration of inhaled NO and O(2) predicts survival in PAH patients. PMID:22020367

  11. 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

  12. 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

  13. Changes in the composition and metabolism of arterial collagens during the development of pulmonary hypertension in rabbits.

    PubMed

    Bishop, J E; Guerreiro, D; Laurent, G J

    1990-02-01

    Increased pulmonary artery pressure is known to result in enhanced collagen deposition in the pulmonary artery. Here we investigate how changes in collagen metabolism may bring about this increased deposition in the pulmonary artery of animals with pulmonary hypertension induced by bleomycin. Rabbits were injected intratracheally with bleomycin sulfate or with saline. After 14 days the animals were injected with L-[U-14C]proline plus a "flooding" dose of unlabeled proline. Uptake into arterial collagens and release of labeled hydroxyproline were then measured after 2.5 h. The relative amounts of types I and III collagens were assessed from the levels of cyanogen-bromide-derived peptides alpha 1(I)CB8 and alpha 1(III)CB5, respectively, after sodium dodecyl sulfate polyacrylamide gel electrophoresis. Collagen synthesis rates of about 3%/day were found in the control pulmonary artery and aorta, and about one-half of the newly synthesized collagen was degraded rapidly. Fourteen days after bleomycin, there was a fivefold increase in collagen synthesis rate (p less than 0.01) and a marked decrease in the percentage of newly synthesized collagen degraded rapidly. There was no change in collagen metabolism in the aorta of these animals. Pulmonary artery collagen from control rabbits consisted of 26.5 +/- 1.0% type III collagen. There was no change in composition in bleomycin-treated animals. This study demonstrates quite rapid turnover rates for collagen in normal blood vessels. Our results also indicate that remodeling of arterial connective tissue matrix during pulmonary hypertension involves marked but commensurate increases in type I and III collagens brought about by changes in both synthesis and degradative processes. PMID:1689130

  14. Influence of Rho kinase inhibitor Fasudil on late endothelial progenitor cells in peripheral blood of COPD patients with pulmonary artery hypertension.

    PubMed

    Liu, Pei; Zhang, Hongmei; Tang, Yijun; Sheng, Chunfeng; Liu, Jianxin; Zeng, Yanjun

    2014-02-01

    The objective of our work was to investigate the influence of Fasudil, a Rho inhibitor on the number and function of the late endothelial progenitor cells in peripheral blood of chronic obstructive pulmonary diseases (COPD) patients with pulmonary artery hypertension. Eighty COPD patients with pulmonary artery hypertension were selected and divided into two groups: the treatment group and the control group, which had 40 patients respectively. The control group received routine treatment, including oxygen uptake, anti-infection and phlegm dissolving. The treatment group received the Fasudil in addition to the routine treatment. The changes on the number and function of the late endothelial progenitor cells in peripheral blood of the patients before and after the treatment were compared between the two groups. The changes on the pulmonary artery pressure were also compared. The number of the late endothelial progenitor cells in peripheral blood of the treatment group increased and the function was enhanced. The pulmonary artery pressure was reduced. The difference before and after the treatment and with the control group was statistically significant (p<0.05). The changes on the number and function of the late endothelial progenitor cells in peripheral blood and the pulmonary artery pressure before and after the treatment of the control group were not statistically significant (p>0.05). The Rho-kinase inhibitor Fasudil increased the number and enhanced the function of the late endothelial progenitor cells in peripheral blood of COPD patients with pulmonary artery hypertension. PMID:24579970

  15. Patient-specific computational modeling of blood flow in the pulmonary arterial circulation.

    PubMed

    Kheyfets, Vitaly O; Rios, Lourdes; Smith, Triston; Schroeder, Theodore; Mueller, Jeffrey; Murali, Srinivas; Lasorda, David; Zikos, Anthony; Spotti, Jennifer; Reilly, John J; Finol, Ender A

    2015-07-01

    Computational fluid dynamics (CFD) modeling of the pulmonary vasculature has the potential to reveal continuum metrics associated with the hemodynamic stress acting on the vascular endothelium. It is widely accepted that the endothelium responds to flow-induced stress by releasing vasoactive substances that can dilate and constrict blood vessels locally. The objectives of this study are to examine the extent of patient specificity required to obtain a significant association of CFD output metrics and clinical measures in models of the pulmonary arterial circulation, and to evaluate the potential correlation of wall shear stress (WSS) with established metrics indicative of right ventricular (RV) afterload in pulmonary hypertension (PH). Right Heart Catheterization (RHC) hemodynamic data and contrast-enhanced computed tomography (CT) imaging were retrospectively acquired for 10 PH patients and processed to simulate blood flow in the pulmonary arteries. While conducting CFD modeling of the reconstructed patient-specific vasculatures, we experimented with three different outflow boundary conditions to investigate the potential for using computationally derived spatially averaged wall shear stress (SAWSS) as a metric of RV afterload. SAWSS was correlated with both pulmonary vascular resistance (PVR) (R(2)=0.77, P<0.05) and arterial compliance (C) (R(2)=0.63, P<0.05), but the extent of the correlation was affected by the degree of patient specificity incorporated in the fluid flow boundary conditions. We found that decreasing the distal PVR alters the flow distribution and changes the local velocity profile in the distal vessels, thereby increasing the local WSS. Nevertheless, implementing generic outflow boundary conditions still resulted in statistically significant SAWSS correlations with respect to both metrics of RV afterload, suggesting that the CFD model could be executed without the need for complex outflow boundary conditions that require invasively obtained

  16. 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

  17. 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

  18. 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

  19. Continuous inhaled iloprost in a neonate with d-transposition of the great arteries and severe pulmonary arterial hypertension.

    PubMed

    Dykes, John C; Torres, Marilyn; Alexander, Plato J

    2016-03-01

    This report describes the case of a neonate with d-transposition of the great arteries and severe pulmonary arterial hypertension stabilised in the post-operative period with continuous iloprost nebulisation. To our knowledge, this is the first documented method of treating post-operative severe pulmonary arterial hypertension with continuous inhaled iloprost in a patient with complex CHD. We found this method of delivering the drug very effective in stabilising haemodynamic swings in the setting of severe pulmonary arterial hypertension. PMID:26220108

  20. SGLT inhibitors attenuate NO-dependent vascular relaxation in the pulmonary artery but not in the coronary artery.

    PubMed

    Han, Ying; Cho, Young-Eun; Ayon, Ramon; Guo, Rui; Youssef, Katia D; Pan, Minglin; Dai, Anzhi; Yuan, Jason X-J; Makino, Ayako

    2015-11-01

    Inhibitors of sodium-glucose cotransporter (SGLT)2 are a new class of oral drugs for type 2 diabetic patients that reduce plasma glucose levels by inhibiting renal glucose reabsorption. There is increasing evidence showing the beneficial effect of SGLT2 inhibitors on glucose control; however, less information is available regarding the impact of SGLT2 inhibitors on cardiovascular outcomes. The present study was designed to determine whether SGLT inhibitors regulate vascular relaxation in mouse pulmonary and coronary arteries. Phlorizin (a nonspecific SGLT inhibitor) and canagliflozin (a SGLT2-specific inhibitor) relaxed pulmonary arteries in a dose-dependent manner, but they had little or no effect on coronary arteries. Pretreatment with phlorizin or canagliflozin significantly inhibited sodium nitroprusside (SNP; a nitric oxide donor)-induced vascular relaxation in pulmonary arteries but not in coronary arteries. Phlorizin had no effect on cGMP-dependent relaxation in pulmonary arteries. SNP induced membrane hyperpolarization in human pulmonary artery smooth muscle cells, and pretreatment of cells with phlorizin and canagliflozin attenuated SNP-induced membrane hyperpolarization by decreasing K(+) activities induced by SNP. Contrary to the result observed in ex vivo experiments with SGLT inhibitors, SNP-dependent relaxation in pulmonary arteries was not altered by chronic administration of canagliflozin. On the other hand, canagliflozin administration significantly enhanced SNP-dependent relaxation in coronary arteries in diabetic mice. These data suggest that SGLT inhibitors differentially regulate vascular relaxation depending on the type of arteries, duration of the treatment, and health condition, such as diabetes. PMID:26361875

  1. HIV protease inhibitors in pulmonary hypertension: rationale and design of a pilot trial in idiopathic pulmonary arterial hypertension

    PubMed Central

    Li, Ying; Li, Xiao-hui; Yu, Zai-xin; Cai, Jing-jing; Billiar, Timothy R.; Chen, Alex F.; Lv, Ben; Chen, Zi-ying; Huang, Zhi-jun; Yang, Guo-ping; Song, Jie; Liu, Bin

    2015-01-01

    Abstract We propose an exploratory clinical study, the first of its kind to our knowledge, to determine the safety and potential clinical benefit of the combination of the HIV protease inhibitors (HIV-PIs) saquinavir and ritonavir (SQV+RIT) in patients with idiopathic pulmonary arterial hypertension (IPAH). This study is based on evidence that (1) HIV-PIs can improve pulmonary hemodynamics in experimental models; (2) both Toll-like receptor 4 and high-mobility group box 1 (HMGB1) participate in the pathogenesis of experimental pulmonary hypertension; and (3) a high-throughput screen for inhibitors of HMGB1-induced macrophage activation yielded HIV-PIs as potent inhibitors of HMGB1-induced cytokine production. In this proposed open-label, pre-post study, micro, low, and standard doses of SQV+RIT will be given to IPAH patients for 14 days. Patients will receive follow-up for the next 14 days. The primary outcome to be evaluated is change in HMGB1 level from baseline at 14 days. The secondary outcome is changes in tumor necrosis factor α, interleukin 1β, interleukin 6, C-reactive protein, pulmonary arterial pressure based on echocardiography parameters and New York Heart Association/World Health Organization functional class, and Brog dyspnea scale index from baseline at 14 days. Other secondary measurements will include N-terminal pro-brain natriuretic peptide, atrial natriuretic peptide, and 6-minute walk distance. We propose that SQV+RIT treatment will improve inflammatory disorders and pulmonary hemodynamics in IPAH patients. If the data support a potentially useful therapeutic effect and suggest that SQV+RIT is safe in IPAH patients, the study will warrant further investigation. (ClinicalTrials.gov identifier: NCT02023450.) PMID:26401255

  2. Surgical intervention for bilateral coronary artery fistulas to the pulmonary artery.

    PubMed

    Kainuma, Satoshi; Funatsu, Toshihiro; Sawa, Yoshiki; Taniguchi, Kazuhiro

    2016-05-01

    A 60-year old female was referred to our institution for surgical intervention to treat bilateral coronary artery fistulas to the pulmonary artery (PA). Multidetector computed tomography (MDCT) imaging showed two tortuous vessels with multiple aneurysmal dilatations originating from the right coronary artery and left anterior descending artery. Furthermore, oximetry revealed an oxygen step-up of 10% between the PA and the right ventricle, consistent with an estimated left-to-right shunt of 47.1%, indicating that the patient was a candidate for surgery. Under heart arrest, the main PA was longitudinally opened and a single efferent hole sized 10 mm in diameter located in the anterior sinus of the pulmonary trunk was closed. Thereafter, the two afferent vessels were individually ligated at their proximal origins. Postoperative MDCT demonstrated no evidence of abnormal vessel communication between the coronary arteries and the PA, as well as relatively dilated native coronary arteries when compared with the preoperative state. At the 6-month follow-up examination, the patient was asymptomatic and showed no complications. PMID:26503730

  3. Differential effects of Selexipag [corrected] and prostacyclin analogs in rat pulmonary artery.

    PubMed

    Morrison, Keith; Studer, Rolf; Ernst, Roland; Haag, Franck; Kauser, Katalin; Clozel, Martine

    2012-12-01

    {4-[(5,6-Diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}acetic acid (ACT-333679) is the main metabolite of the selective prostacyclin (PGI(2)) receptor (IP receptor) agonist selexipag. The goal of this study was to determine the influence of IP receptor selectivity on the vasorelaxant efficacy of ACT-333679 and the PGI(2) analog treprostinil in pulmonary artery under conditions associated with pulmonary arterial hypertension (PAH). Selexipag and ACT-333679 evoked full relaxation of pulmonary artery from control and monocrotaline (MCT)-PAH rats, and ACT-333679 relaxed normal pulmonary artery contracted with either endothelin-1 (ET-1) or phenylephrine. In contrast, treprostinil evoked weaker relaxation than ACT-333679 of control pulmonary artery and failed to induce relaxation of pulmonary artery from MCT-PAH rats. Treprostinil did not evoke relaxation of normal pulmonary artery contracted with either ET-1 or phenylephrine. Expression of prostaglandin E(3) (EP(3)) receptor mRNA was increased in pulmonary artery from MCT-PAH rats. In contraction experiments, the selective EP(3) receptor agonist sulprostone evoked significantly greater contraction of pulmonary artery from MCT-PAH rats compared with control rats. The presence of a threshold concentration of ET-1 significantly augmented the contractile response to sulprostone in normal pulmonary artery. ACT-333679 did not evoke direct contraction of rat pulmonary artery, whereas treprostinil evoked concentration-dependent contraction that was inhibited by the EP(3) receptor antagonist (2E)-3-(3',4'-dichlorobiphenyl-2-yl)-N-(2-thienylsulfonyl)acrylamide. Antagonism of EP(3) receptors also revealed a relaxant response to treprostinil in normal pulmonary artery contracted with ET-1. These data demonstrate that the relaxant efficacy of the selective IP receptor agonist selexipag and its metabolite ACT-333679 is not modified under conditions associated with PAH, whereas relaxation to treprostinil may be limited in the presence

  4. Hemoptysis due to a mycotic pulmonary artery aneurysm in an injecting drug user.

    PubMed

    Papaioannou, Vasilios; Mikroulis, Dimitrios; Chrysafis, Ioannis; Fotakis, Stelios; Pneumatikos, Ioannis

    2014-08-01

    Infected aneurysms of the pulmonary artery are a rare consequence of injected drug use. Hemoptysis of pulmonary arterial origin is also infrequent; however, the mortality is as high as 50%. We report here a case of hemoptysis in an intravenous drug user, caused by a pulmonary artery aneurysm due to septic microemboli, originating from a groin abscess. We highlight the importance of recognizing and treating thromboembolic complications associated with deep venous thrombosis in injecting drug users. PMID:23250844

  5. Structure and composition of pulmonary arteries, capillaries and veins

    PubMed Central

    2013-01-01

    The pulmonary vasculature is comprised of three anatomic compartments connected in series: the arterial tree, an extensive capillary bed, and the venular tree. Although in general this vasculature is thin-walled, structure is nonetheless complex. Contributions to structure (and thus potentially to function) from cells other than endothelial and smooth muscle cells as well as those from the extracellular matrix should be considered. This review is multifaceted, bringing together information regarding 1) classification of pulmonary vessels, 2) branching geometry in the pulmonary vascular tree, 3) a quantitative view of structure based on morphometry of the vascular wall, 4) the relationship of nerves, a variety of interstitial cells, matrix proteins, and striated myocytes to smooth muscle and endothelium in the vascular wall, 5) heterogeneity within cell populations and between vascular compartments, 6) homo- and heterotypic cell-cell junctional complexes, and 7) the relation of the pulmonary vasculature to that of airways. These issues for pulmonary vascular structure are compared, when data is available, across species from human to mouse and shrew. Data from studies utilizing vascular casting, light and electron microscopy, as well as models developed from those data, are discussed. Finally, the need for rigorous quantitative approaches to study of vascular structure in lung is highlighted. PMID:23606929

  6. Right Ventricular Adaptation and Failure in Pulmonary Arterial Hypertension

    PubMed Central

    Ryan, John J.; Huston, Jessica; Kutty, Shelby; Hatton, Nathan D.; Bowman, Lindsay; Tian, Lian; Herr, Julia E.; Johri, Amer M.; Archer, Stephen L.

    2015-01-01

    Pulmonary arterial hypertension (PAH) is an obstructive pulmonary vasculopathy, characterized by excess proliferation, apoptosis-resistance, inflammation, fibrosis and vasoconstriction. While PAH therapies target some of these vascular abnormalities (primarily vasoconstriction) most do not directly benefit the right ventricle (RV). This is suboptimal since a patient’s functional state and prognosis are largely determined by the success of the adaptation of the RV to the increased afterload. The RV initially hypertrophies but may ultimately decompensate, becoming dilated, hypokinetic and fibrotic. A number of pathophysiologic abnormalities have been identified in the PAH RV, including: ischemia and hibernation (partially reflecting RV capillary rarefaction), autonomic activation (due to GRK2-mediated down-regulation and desensitization of β-adrenergic receptors), mitochondrial-metabolic abnormalities (notably increased uncoupled glycolysis and glutaminolysis), and fibrosis. Many RV abnormalities are detectable by molecular imaging and may serve as biomarkers. Some molecular pathways, such as those regulating angiogenesis, metabolism and mitochondrial dynamics, are similarly deranged in the RV and pulmonary vasculature, offering the possibility of therapies that treat both the RV and pulmonary circulation. An important paradigm in PAH is that the RV and pulmonary circulation constitute a unified cardiopulmonary unit. Clinical trials of PAH pharmacotherapies should assess both components of the cardiopulmonary unit. PMID:25840092

  7. 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

  8. Anomalous origin of the left coronary artery from the pulmonary artery in an adult: tubular reconstruction of the left main coronary artery under coronary perfusion.

    PubMed

    Murashita, T; Kubota, T; Kanaoka, T; Zakaria, M; Yasuda, K

    1997-01-01

    A 38-year-old female with anomalous origin of the left coronary artery (LCA) from pulmonary artery was surgically corrected by tubular reconstruction of the left main coronary artery (LMCA) using the pulmonary artery wall, and this repair was performed under beating heart. Thus, the pulmonary artery was divided above the orifice level and just above the pulmonary valve, and the commissure between nonfacing and left side sinuses was dissected away from the pulmonary artery wall to obtain lateral flaps. The pulmonary artery defect was reconstructed with a roll using an autologous pericardial patch, while the detached commissure was suspended on the pericardial patch. The long tube constructed using pulmonary artery tissue was anastomosed to the anterior aspect of the ascending aorta. These procedures were performed under beating heart simply by clamping the LMCA, since the preoperative myocardial contrast echocardiography confirmed the adequate coronary collateral flow from the right circulation. The postoperative course was uneventful, and a coronary artery angiogram demonstrated a widely patent LMCA. Our experience suggests that, in adult cases, this procedure could be performed without myocardial ischemia simply by clamping the LMCA because of well-developed coronary collateral arteries. The safety of this technique could be confirmed by myocardial contrast echocardiography. PMID:9591183

  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 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.

  11. Effects of lung recruitment maneuvers on splanchnic organ perfusion during endotoxin-induced pulmonary arterial hypertension.

    PubMed

    Daudel, Fritz; Gorrasi, José; Bracht, Hendrik; Brandt, Sebastian; Krejci, Vladimir; Jakob, Stephan M; Takala, Jukka; Rothen, Hans Ulrich

    2010-11-01

    Lung recruitment maneuvers (RMs), used to reopen atelectatic lung units and to improve oxygenation during mechanical ventilation, may result in hemodynamic impairment. We hypothesize that pulmonary arterial hypertension aggravates the consequences of RMs in the splanchnic circulation. Twelve anesthetized pigs underwent laparotomy and prolonged postoperative ventilation. Systemic, regional, and organ blood flows were monitored. After 6 h (= baseline), a recruitment maneuver was performed with sustained inflation of the lungs. Thereafter, the pigs were randomly assigned to group C (control, n = 6) or group E with endotoxin-induced pulmonary arterial hypertension (n = 6). Endotoxemia resulted in a normotensive and hyperdynamic state and a deterioration of the oxygenation index by 33%. The RM was then repeated in both groups. Pulmonary artery pressure increased during lipopolysaccharide infusion from 17 ± 2 mmHg (mean ± SD) to 31 ± 10 mmHg and remained unchanged in controls (P < 0.05). During endotoxemia, RM decreased aortic pulse pressure from 37 ± 14 mmHg to 27 ± 13 mmHg (mean ± SD, P = 0.024). The blood flows of the renal artery, hepatic artery, celiac trunk, superior mesenteric artery, and portal vein decreased to 71% ± 21%, 69% ± 20%, 76% ± 16%, 79% ± 18%, and 81% ± 12%, respectively, of baseline flows before RM (P < 0.05 all). Organ perfusion of kidney cortex, kidney medulla, liver, and jejunal mucosa in group E decreased to 65% ± 19%, 77% ± 13%, 66% ± 26%, and 71% ± 12%, respectively, of baseline flows (P < 0.05 all). The corresponding recovery to at least 90% of baseline regional blood flow and organ perfusion lasted 1 to 5 min. Importantly, the decreases in regional blood flows and organ perfusion and the time to recovery of these flows did not differ from the controls. In conclusion, lipopolysaccharide-induced pulmonary arterial hypertension does not aggravate the RM-induced significant but short-lasting decreases in systemic, regional, and

  12. CT Findings of Ruptured Intramural Hematoma of the Aorta Extending Along the Pulmonary Artery

    SciTech Connect

    Sueyoshi, Eijun Sakamoto, Ichiro; Uetani, Masataka; Matsuoka, Yojiro; Suenaga, Etsuro

    2007-04-15

    Mediastinal hematoma extending along the pulmonary artery is a rare complication of Stanford type A classic (double-barreled) aortic dissection. Rupture from the posterior aspect of the aortic root penetrates the shared adventitia of the aorta and pulmonary artery. From this location, hematoma can spread along the adventitial planes of the pulmonary arteries out into the lungs. We report a case of ruptured intramural hematoma of the aorta (IMH) extending along the pulmonary artery. To our knowledge, this finding in patients with IMH has not been reported in the literature.

  13. 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.

  14. Patchy deletion of Bmpr1a potentiates proximal pulmonary artery remodeling in mice exposed to chronic hypoxia

    PubMed Central

    Vanderpool, Rebecca R.; El-Bizri, Nesrine; Rabinovitch, Marlene; Chesler, Naomi C

    2012-01-01

    Reduced vascular expression of bone morphogenetic type IA receptor (Bmpr1a) has been found in patients with pulmonary arterial hypertension (PAH). Our previous studies in mice with patchy deletion of Bmpr1a in vascular smooth muscle cells and cardiac myocytes showed decreased distal vascular remodeling despite a similar severity of hypoxic pulmonary hypertension (HPH). We speculate increased stiffness from ectopic deposition of collagen in proximal pulmonary arteries (PAs) might account for HPH. Pulsatile pressure-flow relationships were measured in isolated, ventilated, perfused lungs of SM22α;TRE-Cre;R26R;Bmpr1aflox/flox (KO) mice and wild-type (WT) littermates following 21 days (hypoxia) and 0 days (control) of chronic hypoxia. Pulmonary vascular impedance, which yields insight into proximal and distal arterial remodeling, was calculated. Reduced Bmpr1a expression had no effect on input impedance Z0 (P=0.52) or characteristic impedance ZC (P=0.18) under control conditions; it also had no effect on the decrease in Z0 via acute rho kinase inhibition. However, following chronic hypoxia, reduced Bmpr1a expression increased ZC (P<0.001) without affecting Z0 (P=0.72). These results demonstrate that Bmpr1a deficiency does not significantly alter the hemodynamic function of the distal vasculature or its response to chronic hypoxia but larger, more proximal arteries are affected. In particular, reduced Bmpr1a expression likely decreased dilatation and increased stiffening in response to hypoxia, probably by collagen accumulation. Increased PA stiffness can have a significant impact on right ventricular function. This study illustrates for the first time how proximal pulmonary artery changes in the absence of distal pulmonary artery changes contribute to pulmonary hypertension. PMID:22314711

  15. Calorie Restriction Attenuates Monocrotaline-induced Pulmonary Arterial Hypertension in Rats

    PubMed Central

    Ding, Mingge; Lei, Jingyi; Qu, Yinxian; Zhang, Huan; Xin, Weichuan; Ma, Feng; Liu, Shuwen; Li, Zhichao; Jin, Faguang

    2015-01-01

    Abstract: 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

  16. 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

  17. 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.

  18. 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. PMID:26522587

  19. Update on the clinical utility of sildenafil in the treatment of pulmonary arterial hypertension

    PubMed Central

    Ramani, Gautam V; Park, Myung H

    2010-01-01

    Sildenafil is an orally administered phosphodiesterase type 5 inhibitor that is approved for the treatment of pulmonary arterial hypertension (PAH). The hemodynamic effects of sildenafil are mitigated primarily via potentiating the effects of endogenous nitric oxide, leading to smooth muscle cell relaxation and reductions in pulmonary arterial pressures and pulmonary vascular resistance. When added to standard background therapy in patients with idiopathic or associated PAH from congenital heart disease, anorexigen use, or connective tissue disease, sildenafil treatment results in improved exercise capacity as measured by 6 minute walk distance, improved hemodynamics, and favorable changes in quality of life. Sildenafil use is contraindicated with concomitant nitrate administration, and caution should be exercised when used in combination with antihypertensive agents due to risks of precipitating hypotension. Side effects are generally mild, and include flushing, headaches, and epistaxis. The combination of sildenafil with intravenous epoprostenol is safe and well tolerated, and further improves exercise capacity. Sildenafil is approved only for treatment of PAH, and although emerging data suggest a potential role in treating other types of pulmonary hypertension, larger trials are required to confirm these findings. PMID:20531962

  20. Central retinal artery pressure and carotid artery stenosis

    PubMed Central

    SUN, RAN; PENG, XIAO-YAN; YOU, QI-SHENG; JIAO, LI-QUN; JONAS, JOST B.

    2016-01-01

    The central retinal artery (CRA), which can be non-invasively examined with ophthalmoscopy, may be regarded as an extracranial part of the cerebrovascular system. Assessment of CRA pressure may be of help in assessing the impediment of the intracranial blood circulation in patients with a carotid artery stenosis (CAS). The aim of this study was to explore the potential associations between diastolic central retinal artery pressure (diastCRAP) and CAS. The prospective longitudinal clinical observational study included patients with CAS and a control group without CAS. diastCRAP was assessed using ophthalmodynamometry. The study group consisted of 95 patients with CAS (50 of whom had >75%CAS and underwent surgery; the surgical study group) and a control group of 64 individuals without CAS. In all study participants, a lower diastCRAP was significantly associated with a higher degree of CAS (P<0.001). Multivariate analysis indicated that a higher CAS degree was significantly (correlation coefficient: r=0.75) associated with a higher brachial diastolic blood pressure (P<0.001) and lower diastCRAP (P<0.001). Within the surgical study group at the baseline of the study, diastCRAP was significantly lower at the surgical side than at the contralateral side (P=0.02). The diastCRAP on the surgical side increased significantly (P<0.001) after surgery. In the surgical study group at baseline, diastCRAP on the surgical side was not significantly associated with brachial diastolic blood pressure (P=0.22), whereas after surgery, diastCRAP was significantly associated with brachial diastolic blood pressure (P=0.001). DiastCRAP was found to be significantly and linearly correlated with the degree of CAS in intra-individual inter-eye, inter-individual and intra-individual follow-up comparisons. The strong and linear association between diastCRAP and the degree of CAS suggest that diastCRAP should be explored further for use as an indicator of cerebrovascular status. PMID:26998005

  1. Involvement of calcium-sensing receptors in hypoxia-induced vascular remodeling and pulmonary hypertension by promoting phenotypic modulation of small pulmonary arteries.

    PubMed

    Peng, Xue; Li, Hong-Xia; Shao, Hong-Jiang; Li, Guang-Wei; Sun, Jian; Xi, Yu-Hui; Li, Hong-Zhu; Wang, Xin-Yan; Wang, Li-Na; Bai, Shu-Zhi; Zhang, Wei-Hua; Zhang, Li; Yang, Guang-Dong; Wu, Ling-Yun; Wang, Rui; Xu, Chang-Qing

    2014-11-01

    Phenotype modulation of pulmonary artery smooth muscle cells (PASMCs) plays an important role during hypoxia-induced vascular remodeling and pulmonary hypertension (PAH). We had previously shown that calcium-sensing receptor (CaSR) is expressed in rat PASMCs. However, little is known about the role of CaSR in phenotypic modulation of PASMCs in hypoxia-induced PAH as well as the underlying mechanisms. In this study, we investigated whether CaSR induces the proliferation of PASMCs in small pulmonary arteries from both rats and human with PAH. PAH was induced by exposing rats to hypoxia for 7-21 days. The mean pulmonary arterial pressure (mPAP), right ventricular hypertrophy index (RVI), the percentage of medial wall thickness to the external diameter (WT %), and cross-sectional total vessel wall area to the total area (WA %) of small pulmonary arteries were determined by hematoxylin and eosin (HE), masson trichrome and Weigert's staining. The protein expressions of matrix metalloproteinase (MMP)-2 and MMP-9, the tissue inhibitors of metalloproteinase (TIMP)-3, CaSR, proliferating cell nuclear antigen (PCNA), phosphorylated extracellular signal-regulated kinase (p-ERK), and smooth muscle cell (SMC) phenotype marker proteins in rat small pulmonary arteries, including calponin, SMα-actin (SMAα), and osteopontin (OPN), were analyzed by immunohistochemistry and Western blotting, respectively. In addition, immunohistochemistry was applied to paraffin-embedded human tissues from lungs of normal human and PAH patients with chronic heart failure (PAH/CHF). Compared with the control group, mPAP, RVI, WT % and WA % in PAH rats were gradually increased with the prolonged hypoxia. At the same time, the expressions of CaSR, MMP-2, MMP-9, TIMP-3, PCNA, OPN, and p-ERK were markedly increased, while the expressions of SMAα and calponin were significantly reduced in lung tissues or small pulmonary arteries of PAH rats. Neomycin (an agonist of CaSR) enhanced but NPS2390 (an

  2. Ambrisentan for the treatment of pulmonary arterial hypertension: improving outcomes

    PubMed Central

    Elshaboury, Soha M; Anderson, Joe R

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vasculature that is associated with severe functional impairment and a poor prognosis. Ambrisentan is a selective endothelin type A receptor antagonist approved for the treatment of patients with PAH World Health Organization group 1. The efficacy and safety of ambrisentan has been evaluated in the ARIES series (Ambrisentan for the Treatment of Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Studies), which has established its use as both monotherapy or in conjunction with other PAH therapies. Specifically, ambrisentan is effective at increasing exercise tolerance, decreasing the risk of functional class deterioration, and prolonging time to clinical worsening. Further, ambrisentan has a favorable effect on mortality, with an 88% patient survival rate after two years of therapy compared with a 61% survival rate as estimated by the National Institute of Health Registry. Ambrisentan is generally well tolerated in all patient groups, with the main side effects of peripheral edema, sinusitis, flushing, and nasal congestion considered to be mild to moderate in nature. Ambrisentan has several favorable qualities that potentially make it more acceptable to patients, including once-daily administration, limited adverse drug reactions and drug-drug interactions, and minimal risk of liver enzyme elevation. Because of the potential risk of teratogenicity associated with ambrisentan, it is only available through a limited distribution program, ie, LEAP (the Letairis Education and Access Program). Ongoing clinical trials will help to clarify the role of ambrisentan in the treatment of PAH. PMID:23674888

  3. 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

  4. Signal transduction in the development of pulmonary arterial hypertension

    PubMed Central

    Malenfant, Simon; Neyron, Anne-Sophie; Paulin, Roxane; Potus, François; Meloche, Jolyane; Provencher, Steeve; Bonnet, Sébastien

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a unique disease. Properly speaking, it is not a disease of the lung. It can be seen more as a microvascular disease occurring mainly in the lungs and affecting the heart. At the cellular level, the PAH paradigm is characterized by inflammation, vascular tone imbalance, pulmonary arterial smooth muscle cell proliferation and resistance to apoptosis and the presence of in situ thrombosis. At a clinical level, the aforementioned abnormal vascular properties alter physically the pulmonary circulation and ventilation, which greatly influence the right ventricle function as it highly correlates with disease severity. Consequently, right heart failure remains the principal cause of death within this cohort of patients. While current treatment modestly improve patients’ conditions, none of them are curative and, as of today, new therapies are lacking. However, the future holds potential new therapies that might have positive influence on the quality of life of the patient. This article will first review the clinical presentation of the disease and the different molecular pathways implicated in the pathobiology of PAH. The second part will review tomorrow's future putative therapies for PAH. PMID:24015329

  5. Pulmonary Pressures and Death in Heart Failure: A Community Study

    PubMed Central

    Bursi, Francesca; McNallan, Sheila M.; Redfield, Margaret M.; Nkomo, Vuyisile T.; Lam, Carolyn S.P.; Weston, Susan A.; Jiang, Ruoxiang; Roger, Véronique L.

    2012-01-01

    Objective To determine among community patients with heart failure (HF), whether pulmonary artery systolic pressure (PASP) assessed by Doppler echocardiography was associated with death and improved risk prediction over established factors, using the integrated discrimination improvement (IDI) and net reclassification improvement (NRI). Background While several studies have focused on idiopathic pulmonary arterial hypertension, less is known about pulmonary hypertension among patients with HF, particularly on its prognostic value in the community. Methods Olmsted County residents with HF between 2003 and 2010 prospectively underwent assessment of ejection fraction (EF), diastolic function, and PASP by Doppler echocardiography. Results PASP was recorded in 1049 of 1153 patients (mean age 76±13, 51% women). Median PASP was 48 mmHg (25th-75th percentile, 37.0-58.0). There were 489 deaths after a follow-up of 2.7±1.9 years. There was a strong positive graded association between PASP and mortality. Increasing PASP was associated with an increased risk of death (HR 1.45, 95%CI 1.13-1.85 for tertile 2; HR 2.07, 95%CI 1.62-2.64 for tertile 3, versus tertile 1), independently of age, sex, comorbidities, EF and diastolic function. Adding PASP to models including these clinical characteristics resulted in an increase in the c-statistic from 0.704 to 0.742 (p=0.007), an IDI gain of 4.2% (p<0.001), and an NRI of 14.1% (p=0.002), indicating that PASP improved prediction of death over traditional prognostic factors. All results were similar for CV death. Conclusion Among community patients with HF, PASP strongly predicts death and provides incremental and clinically relevant prognostic information independently of known predictors of outcomes. PMID:22240126

  6. Arterial stiffness, pulse pressure, and the kidney.

    PubMed

    Safar, Michel E; Plante, Gérard E; Mimran, Albert

    2015-05-01

    Classical studies indicate that the contribution of kidneys to hypertension is almost exclusively related to the association between mean arterial pressure (MAP) and vascular resistance. Recent reports including estimates of glomerular filtration rate (GFR) have shown that pulse pressure (PP) and pulse wave velocity, 2 major indices of arterial stiffness, now emerge as significant predictors of cardiovascular risk and age-associated decline in GFR. Such findings are mainly observed in patients with hypertension and renal failure and in atherosclerotic subjects undergoing coronary angiography. In such patients, amplification of PP between ascending and terminal aorta at the renal site is constantly increased over 10mm Hg (P < 0.001), whereas MAP level remains continuously unmodified. This PP amplification is significantly associated with presence of proteinuria. Furthermore, increases in plasma creatinine and aortic stiffness are independently and positively correlated (P < 0.001) both in cross-sectional and longitudinal studies. All these relationships associating PP, arterial stiffness, and renal function are mainly observed in patients 60 years of age or older. Furthermore, in renal transplant patients and their donors, subjects have been recruited for evaluations of arterial stiffness and posttransplant decline in GFR. Determinants of GFR decline were evaluated 1 and 9 years after transplantation. The first year GFR decline was related to smoking and acute rejection, whereas the later was significantly and exclusively associated with donor age and aortic stiffness. Thus, in hypertensive humans, the observed association between PP and GFR suggests that the 2 parameters are substantially mediated by arterial stiffness, not exclusively by vascular resistance. PMID:25480804

  7. Unilateral Absence of the Left Pulmonary Artery With an Associated Vascular Anomaly in Adulthood

    PubMed Central

    Letter, Haley; Derrick, Edward; Koury, Ibrahim

    2016-01-01

    Left-sided pulmonary artery agenesis is a rare malformation that commonly requires childhood intervention secondary to associated congenital cardiovascular anomalies. We present an uncommon case of left-sided agenesis with an associated right-sided aortic arch and significant hypoplasia of the ipsilateral lung. Additionally, there is radiographic evidence of emphysema and pulmonary artery hypertension. Pulmonary artery agenesis is not a common entity, but should be considered in adult patients presenting with recurrent pneumonias and radiographic evidence suggestive of pulmonary hypoplasia. A prompt diagnosis is beneficial for affected individuals who may be candidates for a revascularization procedure or embolization of collaterals. Earlier diagnosis also allows for proper management and follow-up care, considering pulmonary artery hypertension is a severe complication of pulmonary artery agenesis. PMID:27081588

  8. 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

  9. Pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries: primary repair.

    PubMed

    Carotti, Adriano; Trezzi, Matteo

    2016-01-01

    Primary repair of pulmonary atresia (PA) with ventricular septal defect (VSD) and major aortopulmonary collaterals based on single-stage unifocalization was first reported in 1995. From a midline approach, all collaterals are extensively dissected, translocated in front of the oesophagus and/or the trachea, when required, and directly anastomosed to each other or to the native pulmonary arteries, whenever present, without interposition of prosthetic material. The need for concomitant VSD closure is assessed intraoperatively with a pulmonary flow study according to a standardized protocol. Pulmonary blood supply is established by valved conduit interposition in all patients, regardless of the suitability for VSD closure. Palliation with systemic-pulmonary shunt is reserved for selected cases. Between 1994 and 2015, 94 patients with a median age of 1.09 years (range 0.03-19) underwent single-stage unifocalization at our institution. In 78 (82.1%) of them, an intraoperative pulmonary flow study was utilized to assess acceptability for concomitant VSD closure, which was accomplished in 69 cases (73%). Intraoperatively, following VSD closure, the mean right ventricle-to-aortic pressure ratio was 0.49 ± 0.14. The overall mortality rate was 11.2% (n = 10), with an 82% survival at 12.5 years. At a median follow-up interval of 5.8 years, the right ventricle-to-aortic pressure ratio did not differ significantly from the early postoperative phase. The surgical results of primary repair of PA with VSD and major aortopulmonary collaterals based on single-stage unifocalization and an intraoperative pulmonary flow study are satisfactory and durable, despite the need for repeated percutaneous or surgical reinterventions. PMID:26811506

  10. Off-pump versus on-pump coronary artery revascularization: effects on pulmonary function.

    PubMed

    e Silva, Ana M R P; Saad, Roberto; Stirbulov, Roberto; Rivetti, Luiz A

    2010-07-01

    Many studies have shown important changes in lung function tests after coronary artery surgeries. It is controversial if off-pump surgery can give a better and shorter recovery than the on-pump. A prospective study was conducted on 42 patients submitted to coronary artery surgery and divided into two groups: 21 off-pump using intraluminal shunt (G (I)) and 21 on-pump (G (II)), matched by the anatomical location of the coronary arteries lesions. All patients had spirometric evaluation, blood gas measurements and alveolo-arterial oxygen gradient (A-aDO(2)), at the fourth and 10th postoperative days (PO(4) and PO(10)). Preoperatively, G(I) and G(II) had similar results (P>0.372). Spirometry showed decreases at PO(4) and remained decreased until PO(10) for both groups, with significant differences between the groups. The blood gas measurements showed reduction in arterial oxygen pressure (PaO(2)) and carbon dioxide pressure (PaCO(2)), while there was an increase in A-aDO(2) at PO(4) and PO(10) in both groups. The results suggest that different changes occur in pulmonary function when the surgery is performed with or without cardiopulmonary bypass. The off-pump patients showed significantly greater improvement than the on-pump group. PMID:20403972

  11. Abnormal branch of right pulmonary artery (A7): a case report and literature review.

    PubMed

    Atari, Maiko; Nakajima, Yuki; Fukuhara, Mitsuro; Iijima, Yoshihito; Kinoshita, Hiroyasu; Akiyama, Hirohiko; Minamiya, Yoshihiro; Uramoto, Hidetaka

    2016-12-01

    In thoracic surgery, anatomic variations of pulmonary artery increase the risks for vessel injury and critical mistakes during pulmonary artery resection. We report a case of lung cancer with an extremely rare branch, a mediastinal A7 pulmonary artery. Some case reports of the mediastinal pulmonary artery exist until now. However, to the best of our knowledge, this is the first case of a medial basal segmental artery (from the following, it is referred to as A7) branching directly from main pulmonary artery in the literature. Therefore, there is no report that showed three-dimensional computed tomography (3D-CT) and operative findings. So, these information is very useful for thoracic surgeon. A 67-year-old man was admitted to our hospital in order to undergo operation for the treatment of lung cancer. We detected the anomalies preoperatively by 3D-CT. The 3D-CT shows the A7 pulmonary artery branches from the right main pulmonary artery directly. According to previous literature, the cases of a single branch from main pulmonary artery to lower lobe are only five cases. And, the only two of them are right side including our case. In spite of an extremely rare case, we were able to successfully perform a right middle lobectomy because the information obtained from the 3D-CT findings was sufficiently understood preoperatively. PMID:26943692

  12. 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

  13. 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

  14. Finger arterial pressure measurement with Finapres.

    PubMed

    Wesseling, K H

    1996-01-01

    Finger arterial pressure measurement with Finapres has been available since a decade. Its availability has promoted at least 300 methodological and research papers over these years, outlining the usefulness and the limitations of the method and the device. Finapres is based on the volume clamp method of Peñáz and the Physiocal criteria of Wesseling. Tracking of intraarterial pressure is usually satisfactory even under conditions of strongly changing hemodynamics and high and very low blood pressures. Finapres accuracy is similar to that of other non-invasive methods. Systolic pressure levels scatter more than mean and diastolic levels. One source of error is physiologic and determined by the peripheral measurement site of the finger, causing pulse waveform distortion and a pressure gradient. The Finapres waveform can be filtered, however, to obtain a brachial pressure wave. This decreases systolic scatter under vaso-constrictive drug infusion and dynamic exercise to exhaustion, conditions where precision of systolic tracking has been criticized in the literature. Recently, level correction techniques were found which shift finger pressure up or down based on a regression equation with finger systolic and diastolic pressures. This procedure requires no additional measurements yet improves systolic, diastolic and mean level accuracy and precision remarkably. Finally, we show how to judge the quality of a Finapres recording from the behavior of Physiocal. PMID:8896298

  15. Selexipag for the treatment of pulmonary arterial hypertension.

    PubMed

    Sharma, Kamal

    2016-01-01

    The endothelin (ET), nitric oxide (NO) and prostacyclin (PGI2) pathways are involved in pulmonary arterial hypertension (PAH) pathogenesis. While ET and NO are targeted early in the disease process, limitations of current pharmacotherapies that target the PGI2 pathway (PGI2 or PGI2 analogues) result in them not being used or delayed. Selexipag is a novel oral, selective agonist of the PGI2 (IP) receptor. Activation of the IP receptor induces vasodilation in the pulmonary circulation and inhibits the proliferation of vascular smooth muscle cells, key factors in PAH pathogenesis. By combining oral dosing with improved receptor selectivity, selexipag may enable earlier combination therapy targeting the three-molecular pathways of PAH with anticipated improvements in daily- and long-term clinical function and outcome in PAH. PMID:26567613

  16. Upregulation of canonical transient receptor potential channel in the pulmonary arterial smooth muscle of a chronic thromboembolic pulmonary hypertension rat model.

    PubMed

    Yun, Xin; Chen, Yuqin; Yang, Kai; Wang, Sabrina; Lu, Wenju; Wang, Jian

    2015-12-01

    Chronic ligation of the left main pulmonary artery (PA) results in pulmonary vascular remodeling and sustained vasoconstriction. This method has been used to generate a postobstructive pulmonary vasculopathy model to mimic severe chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study was to examine the cellular and molecular mechanisms underlying CTEPH and to provide evidence for potential treatments. The CTEPH rat model was induced by surgical left PA ligation (LPAL). Right ventricular systolic pressure (RVSP), lung histochemistry and plasma D-dimer measurements were carried out to evaluate the model. A fluorescence microscope was used to measure the basal intracellular Ca(2+) concentration ([Ca(2+)]i) and store-operated Ca(2+) entry (SOCE) in rat distal pulmonary arterial smooth muscle cells through a Fura-2 fluorescence-based method. The expression of the canonical transient receptor potential channel 1 (TRPC1) and TRPC6 was determined by western blotting and real-time quantitative PCR in isolated distal pulmonary arteries (PA). At the time points of 2 and 5 weeks postsurgery, the RVSP showed significant increases in the LPAL groups in comparison with the respective control groups. LPAL also led to right ventricular hypertrophy (RVH), distal pulmonary arterial remodeling in unobstructed territories and persistently higher plasma D-dimer levels. Increases of the basal [Ca(2+)]i and SOCE in LPAL were associated with a clear upregulation of TRPC1 and TRPC6 expression in the distal PA. Our study demonstrated that LPAL successfully reproduced the vascular tone changes that mimic CTEPH pathogenesis. In this model, the increased RVSP and RVH are likely related to enhanced SOCE and upregulated TRPC1 and TRPC6 expression levels in the distal PA. PMID:26155749

  17. [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

  18. Pulmonary artery involvement in Takayasu's arteritis with lung infarction and pulmonary aspergillosis.

    PubMed

    Narita, Jun-Ichi; Ito, Satoshi; Terada, Masaki; Saitoh, Yasuharu; Igarashi, Ken-Ichi; Nakano, Masaaki; Suzuki, Eiichi; Arakawa, Masaaki; Gejyo, Fumitake

    2002-10-01

    We describe a patient with a chronic case of pulmonary involvement of Takayasu's arteritis in the resected lung. A 49-year-old woman was first diagnosed with Takayasu's arteritis at age 30 years. On her first admission, she presented with Takayasu's arteritis and pneumonia with cavitation in the left lung. After recovering from pneumonia, she was treated initially with prednisolone, 30 mg/day, and remained well until she developed hemoptysis at age 34 years. Findings suggesting aspergilloma were found in the same lobe on chest x-ray film when she was 46 years of age. By age 49 years, the hemoptysis became massive, and she was admitted for surgery. Left upper lobectomy and partial resection of S6 and S8 pulmonary segments were performed. Histologic analysis of the resected lung revealed typical pathologic findings of pulmonary artery involvement in Takayasu's arteritis, such as stenosis recanalization and a vessel-in-vessel feature, but not active vasculitis. Infection probably occurred in the cavity of the infarcted tissue. Pulmonary artery involvement is common in Takayasu's arteritis, but the aspergilloma in this corticosteroid-treated patient is an uncommon complication. PMID:17041382

  19. Development of advanced pulmonary vascular disease in D-transposition of the great arteries after the neonatal arterial switch operation.

    PubMed Central

    Rivenes, S M; Grifka, R G; Feltes, T F

    1998-01-01

    We report the case of a neonate with D-transposition of the great arteries who, after undergoing an uneventful arterial switch operation at the age of 4 days, was found at the age of 42 months to have developed advanced pulmonary vascular disease. Because the arterial switch operation was performed when our patient was only 4 days old, this case challenges the hypothesis that postnatal hemodynamics alone dictate the development of advanced pulmonary vascular disease in infants and children with transposition of the great arteries. Images PMID:9782561

  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. Sympathetic neuroeffector transmission to pulmonary vascular smooth muscle in porcine superior mesenteric arterial occlusion (SMAO) shock.

    PubMed

    Greenberg, S; Glenn, T M; Eddy, L J; Rebert, R R

    1980-01-01

    Splanchnic arterial occlusion shock results in pulmonary endothelial damage and depression of porcine intralobar pulmonary artery and vein contractility. This study evaluates the functional integrity of the adrenergic nerves innervating intralobar pulmonary arteries and veins and the changes in neurotransmission following 1) superior mesenteric artery occlusion (SMAO) shock in swine; 2) sequential inhibition of prostacyclin, thromboxane, and prostaglandin synthesis; and 3) mechanical stripping of the endothelium. Rings of porcine intralobar pulmonary arteries and veins were obtained from sham and SMAO shocked swine. They were suspended in muscle baths and stimulated transmurally at 1-32 Hz, 2 msec duration, 2 msec delay at 7.5-10V. Some experiments were performed on rings of intralobular pulmonary arteries and veins in which the endothelium was stripped with a razor blade. Appropriate inverted-reverted controls were used to account for any deleterious effects of the preparatory techniques involved in stripping. Intralobar pulmonary arteries and veins from sham swine contracted in response to 1 Hz, with maximum responses at 32 Hz. The responses to nerve stimulation were enhanced by cocaine and inhibited by phentolamine, an alpha-receptor antagonist. Inhibition of endothelial prostacyclin synthesis, as well as endothelial stripping, diminished by 30-40% the responses to nerve stimulation. The responses to nerve stimulation were depressed in both intralobar pulmonary arteries and veins in SMAO shocked swine. The data demonstrate physiologic regulation of neural control in porcine pulmonary blood vessels. Furthermore, the data suggest that prostaglandin, the vascular endothelium, and shock, may modify this process. PMID:7315616

  2. Coronary Artery Bypass Grafting for an Anomalous Left Coronary Artery from the Pulmonary Artery in a 73-Year-Old Female.

    PubMed

    Ishida, Narihiro; Shimabukuro, Katsuya; Ogura, Hiroki; Takemura, Hirofumi; Doi, Kiyoshi

    2016-06-01

    Anomalous left coronary artery from the pulmonary artery (ALCAPA) in adults is a rare congenital coronary abnormality. We report a case of ALCAPA in a 73-year-old female managed by total arterial revascularization. doi: 10.1111/jocs.12755 (J Card Surg 2016;31:380-382). PMID:27102973

  3. mTORC2 coordinates pulmonary artery smooth muscle cell metabolism, proliferation and survival in pulmonary arterial hypertension

    PubMed Central

    Goncharov, Dmitry A.; Kudryashova, Tatiana V.; Ziai, Houman; Ihida-Stansbury, Kaori; DeLisser, Horace; Krymskaya, Vera P.; Tuder, Rubin M.; Kawut, Steven M.; Goncharova, Elena A.

    2014-01-01

    Background Enhanced proliferation, resistance to apoptosis and metabolic shift to glycolysis of pulmonary arterial vascular smooth muscle cells (PAVSMC) are key pathophysiological components of pulmonary vascular remodeling in idiopathic pulmonary arterial hypertension (IPAH). The role of distinct mTOR complexes mTORC1 (mTOR-raptor) and mTORC2 (mTOR-rictor) in PAVSMC proliferation and survival in PAH and their therapeutic relevance is unknown. Methods and Results Immunohistochemical and immunoblot analyses revealed that mTORC1 and mTORC2 pathways are markedly up-regulated in small remodeled PAs and isolated distal PAVSMC from IPAH subjects that have increased ATP levels, proliferation and survival that depend on glycolytic metabolism. siRNA- and pharmacological-based analysis showed that while both mTORC1 and mTORC2 contributing to proliferation, only mTORC2 is required for ATP generation and survival of IPAH PAVSMC. mTORC2 down-regulated energy sensor AMPK allowing activation of mTORC1-S6 and increased proliferation, and deficiency of pro-apoptotic protein Bim and IPAH PAVSMC survival. Nox4 protein levels were increased in IPAH PAVSMC that was necessary for mTORC2 activation, proliferation and survival. Nox4 levels and mTORC2 signaling were significantly up-regulated in small PAs from hypoxia-exposed rats at days 2-28 of hypoxia. Treatment with the mTOR kinase inhibitor PP242 at days 15-28 suppressed mTORC2, but not Nox4, induced SM-specific apoptosis in small PAs and reversed hypoxia-induced pulmonary vascular remodeling in rats. Conclusions These data provide a novel mechanistic link of Nox4-dependent activation of mTORC2 via energy sensor AMPK to increased proliferation and survival of PAVSMC in PAH suggesting a new potential pathway for the therapeutic interventions. PMID:24270265

  4. Primary Pulmonary Artery Sarcoma on Dual-Time Point FDG PET/CT Imaging.

    PubMed

    Li, Juan; Zhao, Qian; He, Lirong; Zhuang, Xiaoqing; Li, Fang

    2016-08-01

    A 59-year-old man presented cough, chest pain, and shortness of breath for 2 weeks and fever for 4 days. A contrast chest CT revealed a large right pulmonary artery filling defect, suggestive of pulmonary embolism that failed to respond to anticoagulation therapy. FDG PET/CT was performed to evaluate possible malignancy, which revealed intense activity in the right main pulmonary artery without any extrathoracic abnormality. The ratio of the SUVmax of this lesion to the liver was significantly increased in the delayed PET images. The pathological examination demonstrated primary pulmonary artery sarcoma. PMID:27163460

  5. 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

  6. Alteration of Pulse Pressure Stimulates Arterial Wall Matrix Remodeling

    PubMed Central

    Yao, Qingping; Hayman, Danika M.; Dai, Qiuxia; Lindsey, Merry L.; Han, Hai-Chao

    2010-01-01

    The effect of pulse pressure on arterial wall remodeling remains unclear, although remodeling of the arterial wall under hypertensive pressure and elevated flow has been well documented. The objective of this study was to evaluate matrix remodeling in arteries under nonpulsatile and hyperpulsatile pressure as compared to arteries under normal pulsatile pressure. Using a novel ex vivo organ culture model that allowed us to change pressure pulsatility without changing mean pressure or flow, arteries were cultured for 7 days under normal, nonpulsatile, and hyperpulsatile pressures with the same mean pressure and flow rate. Fenestrae in internal elastic lamina (IEL), collagen content, connexin 43, and fibronectin proteins were examined in these arteries using confocal microscopy, immunoblotting, and immunohistochemistry. Our results showed that the mean fenestrae size and area fraction of fenestrae to total area of IEL decreased 51 % and 45 % in arteries cultured under nonpulsatile pressure and decreased 45 % and 54 % under hyperpulsatile pressure, respectively, compared to arteries under normal pulsatile pressure. There was no difference in fibronectin (FN) and collagen III levels among the three pulse groups, while collagen I and connexin 43 expression increased 80.8% and 35.3% in the hyperpulsatile arteries, respectively, but not in nonpulsatile arteries. In conclusion, our results demonstrated, for the first time, that an increase or elimination in pulse pressure from its normal physiologic level stimulates arterial wall matrix structural changes. Hyperpulsatile pressure has a more pronounced effect than the diminished pulse pressure, which may provide a mechanism for increased wall stiffness in arteries under hyperpulsatile pressure. PMID:19831481

  7. MiRNA-199a-5p influences pulmonary artery hypertension via downregulating Smad3.

    PubMed

    Liu, Yuanhua; Liu, Guanghui; Zhang, Hui; Wang, Jing

    2016-05-13

    MicroRNAs (miRNAs) play important roles in pulmonary artery hypertension (PAH). Recently, it has been reported that miR-199a-5p participates in the progression of chronic obstructive pulmonary disease, ventricular hypertrophy and heart failure. However, the roles of miR-199a-5p in PAH are still unclear. In the present study, miR-199a-5p was investigated in PAH rat models and in human pulmonary artery smooth muscle cells (HPASMCs) and endothelial cells (HPAECs). The expression of miR-199a-5p was significantly increased following PAH induction, and anti-miR-199a-5p could increase the nitric oxide (NO) level and decrease the PAH-induced upregulation of pulmonary artery pressure and right ventricular hypertrophy. Moreover, in HPASMCs and HPAECs, miR-199a-5p overexpression could inhibit the level of NO and promote the concentration of Ca(2+), but anti-miR-199a-5p showed opposite results. Further analysis demonstrated that miR-199a-5p attenuated the expression of Smad3. Importantly, Smad3 was confirmed to be the target gene of miR-199a-5p using dual-luciferase reporter assay. Mechanism analyses revealed that the downregulation of NO and the upregulation of Ca(2+) caused by miR-199a-5p were all reversed by Smad3 overexpression in HPASMCs and HPAECs. Moreover, in PAH model, Smad3, p-Smad3 and Smad4 were all downregulated in lung tissues, and SIS3 (Smad3 inhibitor) could reverse the effects of anti-miR-199a-5p in PAH rats. Our date suggest that miR-199a-5p may function as a regulator of PAH by targeting Smad3, indicating a novel therapeutic strategy for patients with PAH. PMID:27038547

  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. Management of a child with pulmonary arterial hypertension presenting with systemic hypertension.

    PubMed

    Flores, Saul; Daily, Joshua; Pratap, Jayant Nick; Cash, Michelle C; Hirsch, Russel

    2016-02-01

    We describe the course and management of a 12-year-old girl with severe pulmonary arterial hypertension who initially presented with severe systemic hypertension. Successful therapy included pulmonary vasodilators and an atrial septostomy, while ensuring adequate maintenance of her systemic vascular resistance to maintain cardiac output. Clear understanding of the physiology and judicious medical management in patients with severe pulmonary arterial hypertension using extreme compensatory mechanisms is vitally important. PMID:26082002

  10. 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

  11. Phosphodiesterase type 5 inhibitors in pulmonary arterial hypertension.

    PubMed

    Montani, David; Chaumais, Marie-Camille; Savale, Laurent; Natali, Delphine; Price, Laura C; Jaïs, Xavier; Humbert, Marc; Simonneau, Gérald; Sitbon, Olivier

    2009-09-01

    Pulmonary arterial hypertension (PAH) is a rare disease characterized by vascular proliferation and remodeling, resulting in a progressive increase in pulmonary arterial resistance, right heart failure, and death. The pathogenesis of PAH is multifactorial, with endothelial cell dysfunction playing an integral role. This endothelial dysfunction is characterized by an overproduction of vasoconstrictors and proliferative factors, such as endothelin-1, and a reduction of vasodilators and antiproliferative factors, such prostacyclin and nitric oxide. Phosphodiesterase type 5 (PDE-5) is implicated in this process by inactivating cyclic guanosine monophosphate, the nitric oxide pathway second messenger. PDE-5 is abundantly expressed in lung tissue, and appears to be upregulated in PAH. Three oral PDE-5 inhibitors are available (sildenafil, tadalafil, and vardenafil) and are the recommended first-line treatment for erectile dysfunction. Experimental studies have shown the beneficial effects of PDE-5 inhibitors on pulmonary vascular remodeling and vasodilatation, justifying their investigation in PAH. Randomized clinical trials in monotherapy or combination therapy have been conducted in PAH with sildenafil and tadalafil, which are therefore currently the approved PDE-5 inhibitors in PAH treatment. Sildenafil and tadalafil significantly improve clinical status, exercise capacity, and hemodynamics of PAH patients. Combination therapy of PDE-5 inhibitors with prostacyclin analogs and endothelin receptor antagonists may be helpful in the management of PAH although further studies are needed in this area. The third PDE-5 inhibitor, vardenafil, is currently being investigated in PAH. Side effects are usually mild and transient and include headache, flushing, nasal congestion, digestive disorders, and myalgia. Mild and moderate renal or hepatic failure does not significantly affect the metabolism of PDE-5 inhibitors, whereas coadministration of bosentan decreases sildenafil and

  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. Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection

    PubMed Central

    Scherzer, Rebecca; Heringer, Amanda S.; Macgregor, John S.; Martin, Jeffrey N.; Deeks, Steven G.; Ganz, Peter

    2016-01-01

    Background HIV infection is an independent risk factor for PAH, but the underlying pathogenesis remains unclear. ET-1 is a robust vasoconstrictor and key mediator of pulmonary vascular homeostasis. Higher levels of ET-1 predict disease severity and mortality in other forms of PAH, and endothelin receptor antagonists are central to treatment, including in HIV-associated PAH. The direct relationship between ET-1 and PAH in HIV-infected individuals is not well described. Methods We measured ET-1 and estimated pulmonary artery systolic pressure (PASP) with transthoracic echocardiography (TTE) in 106 HIV-infected individuals. Participants with a PASP ≥ 30 mmHg (n = 65) underwent right heart catheterization (RHC) to definitively diagnose PAH. We conducted multivariable analysis to identify factors associated with PAH. Results Among 106 HIV-infected participants, 80% were male, the median age was 52 years and 77% were on antiretroviral therapy. ET-1 was significantly associated with higher values of PASP [14% per 0.1 pg/mL increase in ET-1, p = 0.05] and PASP ≥ 30 mmHg [PR (prevalence ratio) = 1.24, p = 0.012] on TTE after multivariable adjustment for PAH risk factors. Similarly, among the 65 individuals who underwent RHC, ET-1 was significantly associated with higher values of mean pulmonary artery pressure and PAH (34%, p = 0.003 and PR = 2.43, p = 0.032, respectively) in the multivariable analyses. Conclusions Higher levels of ET-1 are independently associated with HIV-associated PAH as hemodynamically assessed by RHC. Our findings suggest that excessive ET-1 production in the setting of HIV infection impairs pulmonary endothelial function and contributes to the development of PAH. PMID:26752193

  14. Blood flow redistribution and ventilation-perfusion mismatch during embolic pulmonary arterial occlusion

    PubMed Central

    Burrowes, K. S.; Clark, A. R.; Tawhai, M. H.

    2011-01-01

    Acute pulmonary embolism causes redistribution of blood in the lung, which impairs ventilation/perfusion matching and gas exchange and can elevate pulmonary arterial pressure (PAP) by increasing pulmonary vascular resistance (PVR). An anatomically-based multi-scale model of the human pulmonary circulation was used to simulate pre- and post-occlusion flow, to study blood flow redistribution in the presence of an embolus, and to evaluate whether reduction in perfused vascular bed is sufficient to increase PAP to hypertensive levels, or whether other vasoconstrictive mechanisms are necessary. A model of oxygen transfer from air to blood was included to assess the impact of vascular occlusion on oxygen exchange. Emboli of 5, 7, and 10 mm radius were introduced to occlude increasing proportions of the vasculature. Blood flow redistribution was calculated after arterial occlusion, giving predictions of PAP, PVR, flow redistribution, and micro-circulatory flow dynamics. Because of the large flow reserve capacity (via both capillary recruitment and distension), approximately 55% of the vasculature was occluded before PAP reached clinically significant levels indicative of hypertension. In contrast, model predictions showed that even relatively low levels of occlusion could cause localized oxygen deficit. Flow preferentially redistributed to gravitationally non-dependent regions regardless of occlusion location, due to the greater potential for capillary recruitment in this region. Red blood cell transit times decreased below the minimum time for oxygen saturation (<0.25 s) and capillary pressures became high enough to initiate cell damage (which may result in edema) only after ~80% of the lung was occluded. PMID:22140626

  15. 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

  16. Veno-arterial ECMO for rescue of severe airway hemorrhage with rigid bronchoscopy after pulmonary artery thromboendarterectomy.

    PubMed

    Chacón-Alves, Silvia; Pérez-Vela, Jose Luis; Grau-Carmona, Teodoro; Domínguez-Aguado, Helena; Marín-Mateos, Helena; Renes-Carreño, Emilio

    2016-07-01

    Pulmonary endarterectomy (PEA) is the treatment of choice to relieve pulmonary artery obstruction in patients with chronic thromboembolic pulmonary hypertension (CTEPH). We present a patient with airway obstruction and acute respiratory failure due to large blood clots obstructing the trachea and main left bronchus. This condition was accompanied by right ventricle failure and cardiogenic shock. A venoarterial ECMO system was used for cardiopulmonary support before extracting the clots and clearing the airway by rigid bronchoscopy. PMID:27229321

  17. 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

  18. Hybrid intraoperative pulmonary artery stenting in redo congenital cardiac surgeries

    PubMed Central

    Sridhar, Anuradha; Subramanyan, Raghavan; Premsekar, Rajasekaran; Chidambaram, Shanthi; Agarwal, Ravi; Manohar, Soman Rema Krishna; Cherian, K.M.

    2014-01-01

    Objective Reconstruction of branch pulmonary arteries (PAs) can be challenging in redo congenital heart surgeries. Treatment options like percutaneous stent implantation and surgical patch angioplasty may yield suboptimal results. We present our experience with hybrid intraoperative stenting which may be an effective alternative option. Methods We retrospectively analyzed data of all patients with PA stenosis who underwent intraoperative PA branch stenting in our institution between January 2011 and December 2012. Results Ten patients [6 females, median age 10 (1.4 to 37) years], underwent hybrid stenting of the PA. Primary cardiac diagnoses were pulmonary atresia with ventricular septal defect (VSD) in three patients, pulmonary atresia with intact ventricular septum in two, Tetralogy of Fallot (TOF) in one, Double outlet right ventricle (DORV) with pulmonary stenosis (PS) in one, complex single ventricle in two and VSD with bilateral branch PA stenosis in one patient. Concomitant surgeries were revision/reconstruction of RV-PA conduit in 4, Fontan completion in 4, repair of TOF with conduit placement in 1 and VSD closure in 1 patient. The left PA was stented in 7, the right in 2 and both in 1, with a total of 11 stents. There were no complications related to stent implantation. Two early postoperative deaths were unrelated to stent implantation. At mean follow-up period of 14.8 (12–26) months, stent position and patency were satisfactory in all survivors. None of them needed repeat dilatation or surgical reintervention. Conclusion Hybrid stenting of branch PA is a safe and effective option for PA reconstruction in redo cardiac surgeries. With meticulous planning, it can be safely performed without fluoroscopy. PMID:24581095

  19. Regulation of Cell Cycle Regulators by SIRT1 Contributes to Resveratrol-Mediated Prevention of Pulmonary Arterial Hypertension

    PubMed Central

    Zhou, Shuang; Li, Meng-Tao; Jia, Yu-Yan; Liu, Jin-Jing; Wang, Qian; Tian, Zhuang; Liu, Yong-Tai; Chen, Hou-Zao; Liu, De-Pei; Zeng, Xiao-Feng

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a major cause of morbidity and mortality in rheumatic diseases. Vascular remodeling due to the proliferation of pulmonary arterial smooth muscle cells (PASMCs) is central to the development of PAH. To date, it is still unclear if Silence Information Regulator 1 (SIRT1) regulates cell cycle regulators in the proliferation of PASMCs and contributes to prevention of PAH by resveratrol. In this study, we found that a significant decrease of SIRT1 expression levels in platelet-derived growth factor BB (PDGF-BB) treated human PASMCs (HPASMCs) and in monocrotaline (MCT) induced PAH rat. Overexpression of SIRT1 induced G1 phase arrest and increased p21 expression but decreased cyclin D1 expression in PDGF-BB treated HPASMCs. Moreover, resveratrol attenuated pulmonary arterial remodeling, decreased pulmonary arterial pressure, and upregulated SIRT1 and p21 expression but downregulated cyclin D1 expression in MCT induced PAH rat. Notably, knockdown of SIRT1 eliminated the regulation of resveratrol on p21 and cyclin D1 expression in PDGF-BB treated HPASMCs. These results demonstrated that SIRT1 mediated the regulation of resveratrol on the expression of cell cycle regulatory molecules. It suggests that SIRT1 exerts a protective role in PAH associated with rheumatic diseases and can be a potential treatment target. PMID:26273643

  20. 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.

  1. 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 ...

  2. 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

  3. Partial lung resection of supernumerary tracheal bronchus combined with pulmonary artery sling in an adult: report of a case.

    PubMed

    Miyazaki, Takuro; Yamasaki, Naoya; Tsuchiya, Tomoshi; Matsumoto, Keitaro; Hayashi, Hideyuki; Izumikawa, Koichi; Izumikawa, Kinichi; Nagayasu, Takeshi

    2015-03-01

    An adult case of pulmonary resection for repeated infections in a supernumerary tracheal bronchus combined with a pulmonary artery sling is reported. A 33-year-old woman with a pulmonary artery sling was referred for recurrent lung infections. Chest computed tomography showed the left pulmonary artery arising from the right pulmonary artery and coursing posterior to the trachea. The lung parenchyma connected to the tracheal bronchus showed dense opacity and traction bronchiectasis. Partial pulmonary resection was performed with an ultrasonically activated scalpel after the tracheal bronchus was auto-sutured. The patient's postoperative course was uneventful, and she is now in good condition. PMID:23852428

  4. Pulmonary Arterial Capacitance Is an Important Predictor of Mortality in Heart Failure With a Preserved Ejection Fraction

    PubMed Central

    Al-Naamani, Nadine; Preston, Ioana R.; Paulus, Jessica K.; Hill, Nicholas S.; Roberts, Kari E.

    2015-01-01

    OBJECTIVES The purpose of this study was to determine the predictors of mortality in patients with pulmonary hypertension (PH) associated with heart failure with preserved ejection fraction (HFpEF). BACKGROUND PH is commonly associated with HFpEF. The predictors of mortality for patients with these conditions are not well characterized. METHODS In a prospective cohort of patients with right heart catheterization, we identified 73 adult patients who had pulmonary hypertension due to left heart disease (PH-LHD) associated with HFpEF (left ventricular ejection fraction ≥50% by echocardiography); hemodynamically defined as a mean pulmonary artery pressure ≥25 mm Hg and pulmonary artery wedge pressure >15 mm Hg. PH severity was classified according to the diastolic pressure gradient (DPG). Cox proportional hazards ratios were used to estimate the associations between clinical variables and mortality. Receiver-operating characteristic curves were used to evaluate the ability of hemodynamic measurements to predict mortality. RESULTS The mean age for study subjects was 69 ± 12 years and 74% were female. Patients classified as having combined post-capillary PH and pre-capillary PH (DPG ≥7) were not at increased risk of death as compared to patients with isolated post-capillary PH (DPG <7). A baseline pulmonary arterial capacitance (PAC) of <1.1 ml/mm Hg was 91% sensitive in predicting mortality, with better discriminatory ability than DPG, transpulmonary gradient, or pulmonary vascular resistance (area under the curve of 0.73, 0.50, 0.45, and 0.37, respectively). Fifty-seven subjects underwent acute vasoreactivity testing with inhaled nitric oxide. Acute vasodilator response by the Rich or Sitbon criteria was not associated with improved survival. CONCLUSIONS PAC is the best predictor of mortality in our cohort and may be useful in describing phenotypic subgroups among those with PH-LHD associated with HFpEF. Acute vasodilator testing did not predict outcome in our

  5. Are Transcutaneous O2 and CO2 determinations of value in Pulmonary Arterial Hypertension?

    PubMed Central

    Tonelli, Adriano R.; Alkukhun, Laith; Cikach, Frank; Ahmed, Mostafa; Dweik, Raed A.

    2015-01-01

    Background We hypothesized that transcutaneous gas determinations of O2 and CO2 (TcPO2 and TcPCO2) are associated with the severity of pulmonary arterial hypertension (PAH). Methods In this cross-sectional study we included consecutive patients with PAH (group 1 pulmonary hypertension (PH)) (n=34). Transcutaneous gas determinations were compared to those of age- and gender-matched healthy controls (n=14), non-group 1 PH (n=19) or patients with high estimated right ventricular systolic pressure on echocardiography but without hemodynamic evidence of PH (n=12). Results In patients with PAH, TcPO2 and TcPCO2 were significantly associated with PaO2 (R= 0.44, p=0.03) and PaCO2 (R=0.77, p<0.001), respectively. TcPO2/FiO2 (mean difference: −65.0 [95% CI: −121.3–8.7]) and TcPCO2 (mean difference: −7.4 [95% CI: −11.6–3.1]) were significantly lower in patients with PAH than healthy controls. TcPCO2 was useful in discriminating PAH patients from other individuals (AUC: 0.74 (95% CI of 0.62–0.83)). TcPO2/FiO2 ratio was significantly associated with mean PAP, TPG, PVR, CI, SVI, DLCO, 6-min walk distance and components of the CAMPHOR questionnaire. Conclusions Transcutaneous pressure of CO2 was lower in patients with PAH. Transcutaneous pressure of O2 over inspired fraction of O2 ratio was inversely associated with severity of disease in patients with pulmonary arterial hypertension. PMID:25641509

  6. Bidirectional Glenn with interruption of antegrade pulmonary blood flow: Which is the preferred option: Ligation or division of the pulmonary artery?

    PubMed Central

    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

  7. 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.

  8. Endothelial Krüppel-Like Factor 4 Modulates Pulmonary Arterial Hypertension

    PubMed Central

    Shatat, Mohammad A.; Tian, Hongmei; Zhang, Rongli; Tandon, Gaurav; Hale, Andrew; Fritz, Jason S.; Zhou, Guangjin; Martínez-González, José; Rodríguez, Cristina; Champion, Hunter C.

    2014-01-01

    Krüppel-like factor 4 (KLF4) is a transcription factor expressed in the vascular endothelium, where it promotes anti-inflammatory and anticoagulant states, and increases endothelial nitric oxide synthase expression. We examined the role of endothelial KLF4 in pulmonary arterial (PA) hypertension (PAH). Mice with endothelial KLF4 knockdown were exposed to hypoxia for 3 weeks, followed by measurement of right ventricular and PA pressures, pulmonary vascular muscularization, and right ventricular hypertrophy. The effect of KLF4 on target gene expression was assessed in lungs from these mice, verified in vitro by small interfering RNA (siRNA) knockdown of KLF4, and further studied at the promoter level with cotransfection experiments. KLF4 expression was measured in lung tissue from patients with PAH and normal control subjects. We found that, after hypoxia, right ventricular and PA pressures were significantly higher in KLF4 knockdown animals than controls. Knockdown animals also had more severe pulmonary vascular muscularization and right ventricular hypertrophy. KLF4 knockdown resulted in increased pulmonary expression of endothelin-1 and decreased expression of endothelial nitric oxide synthase, endothelin receptor subtype B, and prostacyclin synthase. Concordant findings were observed in vitro, both with siRNA knockdown of KLF4 and promoter activity assays. Finally, KLF4 expression was reduced in lungs from patients with PAH. In conclusion, endothelial KLF4 regulates the transcription of genes involved in key pathways implicated in PAH, and its loss exacerbates pulmonary hypertension in response to chronic hypoxia in mice. These results introduce a novel transcriptional modulator of PAH, with the potential of becoming a new therapeutic target. PMID:24156273

  9. 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.

  10. 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. PMID:24851934

  11. Pathways in pulmonary arterial hypertension: the future is here.

    PubMed

    Sitbon, Olivier; Morrell, Nicholasw

    2012-12-01

    It is well established that the endothelin, nitric oxide and prostacyclin pathways play an important role in the development of pulmonary arterial hypertension (PAH). Indeed, the therapeutic options currently available for the management of PAH all act on one of these mechanistic pathways. However, this is an exciting time for both clinicians and scientists, as increased understanding of the mechanisms involved in the pathogenesis and progression of PAH has resulted in the development of a number of novel therapeutic options. This article highlights how the introduction of new compounds such as macitentan, riociguat and selexipag, which act on the endothelin, nitric oxide and prostacyclin pathways, respectively, have the potential to further improve the prognosis for patients with PAH. PMID:23204120

  12. An update on medical therapy for pulmonary arterial hypertension.

    PubMed

    Wu, Yan; O'Callaghan, Dermot S; Humbert, Marc

    2013-12-01

    Over the past 20 years, great progress has been made in the treatment of pulmonary arterial hypertension (PAH). Available therapies target one of three principal pathways: the endothelin (ET), nitric oxide (NO) or the prostacyclin (PGI2) pathway. Evidence shows that current drugs, used either as monotherapy or in different combinations, can improve exercise capacity, clinical symptoms, hemodynamics and even survival in PAH. Unfortunately, the disease remains incurable and the prognosis of the disease is still poor. However, existing and novel potent antiproliferative therapies are being explored, and new agents targeting different and/or additional pathways are likely to become available to clinicians in the near future. Promising candidates include tyrosine kinase antagonists (e.g. imatinib); soluble guanylate cyclase stimulators (riociguat); an oral analog of prostacyclin (selexipag); and a tissue targeting endothelin receptor antagonist (macitentan). Phase II or III trials have either been completed or are underway to evaluate the safety and efficacy of these various therapies. PMID:24122306

  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. Pulmonary arterial hypertension: on the way to a manageable disease.

    PubMed

    Mucke, Hermann A M

    2008-09-01

    Pulmonary arterial hypertension (PAH) is an orphan disease for which no specific pharmacological therapy was available until 1996. Pharmacotherapy for PAH is currently dominated by three endothelin receptor antagonists, bosentan, ambrisentan and sitaxentan (which is not yet approved in the US), and the PDE5 inhibitor sildenafil. Drug candidates undergoing phase III clinical trials for PAH include inhalable and oral treprostinil, aviptadil (an inhalable vasoactive intestinal peptide), and the PDE5 inhibitor tadalafil. Riociguat, a soluble guanylate cyclase stimulator, is scheduled to enter phase III clinical trials in 2008. By approximately 2010, the role of infusable or injectable PGs as treatment for PAH will likely diminish significantly, while inhalable nitric oxide will remain as mainstay therapy in neonatal PAH. Benefits in survival and quality-of-life will decide if any of the more experimental approaches that utilize newly discovered molecular pathways in PAH will ultimately result in marketed drugs. PMID:18729002

  15. New Trial Designs and Potential Therapies for Pulmonary Artery Hypertension

    PubMed Central

    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.

    2014-01-01

    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. PMID:24355645

  16. 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

  17. 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

  18. Optimising the management of pulmonary arterial hypertension patients: emergency treatments.

    PubMed

    Delcroix, M; Naeije, R

    2010-09-01

    Pulmonary arterial hypertension (PAH) is a rare and potentially fatal disease whose management is usually restricted to a few specialised centres. As patients do not necessarily live in the neighbourhood of these centres, daily care and emergencies have to be delegated to first and second lines. Treatment guidelines do not usually provide recommendations for acute emergency situations as evidence is scarce. This short review provides a description of our therapeutic protocols based on available data. A model of transmural organisation of care for PAH patients, currently applied in Belgium, is described. Thereafter, based on an analysis of the reasons of death in the PAH population, a review of the main emergencies is provided. Cardiac arrest and resuscitation, decompensated right heart failure, respiratory failure, arrhythmia, pericardial effusion, haemoptysis, surgery and drug-related adverse events will be discussed successively. Case reports showing the precariousness of PAH patients will enforce our thesis of the need for optimal patient management organisation. PMID:20956193

  19. Stretch-activated channels in pulmonary arterial smooth muscle cells from normoxic and chronically hypoxic rats.

    PubMed

    Ducret, Thomas; El Arrouchi, Jalila; Courtois, Arnaud; Quignard, Jean-François; Marthan, Roger; Savineau, Jean-Pierre

    2010-11-01

    Stretch-activated channels (SACs) act as membrane mechanotransducers since they convert physical forces into biological signals and hence into a cell response. Pulmonary arterial smooth muscle cells (PASMCs) are continuously exposed to mechanical stimulations e.g., compression and stretch, that are enhanced under conditions of pulmonary arterial hypertension (PAH). Using the patch-clamp technique (cell-attached configuration) in PASMCs, we showed that applying graded negative pressures (from 0 to -60 mmHg) to the back end of the patch pipette increases occurrence and activity of SACs. The current-voltage relationship (from -80 to +40 mV) was almost linear with a reversal potential of 1 mV and a slope conductance of 34 pS. SACs were inhibited in the presence of GsMTx-4, a specific SACs blocker. Using microspectrofluorimetry (indo-1), we found that hypotonic-induced cell swelling increases intracellular Ca(2+) concentration ([Ca(2+)](i)). This [Ca(2+)](i) increase was markedly inhibited in the absence of external Ca(2+) or in the presence of the following blockers of SACs: gadolinium, streptomycin, and GsMTx-4. Interestingly, in chronically hypoxic rats, an animal model of PAH, SACs were more active and hypotonic-induced calcium response in PASMCs was significantly higher (nearly a two-fold increase). Moreover, unlike in normoxic rats, intrapulmonary artery rings from hypoxic rats mounted in a Mulvany myograph, exhibited a myogenic tone sensitive to SAC blockers. In conclusion, this work demonstrates that SACs in rat PASMCs can be activated by membrane stretch as well as hypotonic stimulation and are responsible for [Ca(2+)](i) increase. The link between SACs activation-induced calcium response and myogenic tone in chronically hypoxic rats suggests that SACs are an important element for the increased pulmonary vascular tone in PAH and that they may represent a molecular target for PAH treatment. PMID:21035852

  20. 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.

  1. Diagnosis and Rescue of a Kinked Pulmonary Artery Catheter

    PubMed Central

    Mouawad, Nicolas J.; Stein, Erica J.; Moran, Kenneth R.; Go, Michael R.; Papadimos, Thomas J.

    2015-01-01

    Invasive hemodynamic monitoring with a pulmonary catheter has been relatively routine in cardiovascular and complex surgical operations as well as in the management of critical illnesses. However, due to multiple potential complications and its invasive nature, its use has decreased over the years and less invasive methods such as transesophageal echocardiography and hemodynamic sensors have gained widespread favor. Unlike these less invasive forms of hemodynamic monitoring, pulmonary artery catheters require an advanced understanding of cardiopulmonary physiology, anatomy, and the potential for complications in order to properly place, manage, and interpret the device. We describe a case wherein significant resistance was encountered during multiple unsuccessful attempts at removing a patient's catheter secondary to kinking and twisting of the catheter tip. These attempts to remove the catheter serve to demonstrate potential rescue options for such a situation. Ultimately, successful removal of the catheter was accomplished by simultaneous catheter retraction and sheath advancement while gently pulling both objects from the cannulation site. In addition to being skilled in catheter placement, it is imperative that providers comprehend the risks and complications of this invasive monitoring tool. PMID:26075106

  2. [Pulmonary arterial hypertension: a voyage around the year 2008].

    PubMed

    Baloira, Adolfo

    2009-01-01

    There have been spectacular developments in pulmonary arterial hypertension (PAH), both in its treatment and knowledge of its pathogenesis. Several studies have been published throughout 2008 that have contributed to improve these two aspects a little. As regards the pathogenesis, mutations in BMPR2 continue gaining points as fundamental factors in the development of the disease. It has been shown that patients who carry any of them have a more rapid and severe clinical course. There is a relationship between the BMPR2 pathway and inflammation of the pulmonary vascular tree. A new anti-endothelin drug, ambrisentan, has also appeared on the scene this year. With an efficacy comparable to other drugs of its group, the secondary effects appear to be a lot less. An important work has been the demonstration of an improvement in several parameters in functional class II in patients with PAH with bosentan. Results using new combinations, such as sildenafil and epoprostenol, have also been presented. A common type of PAH is that which seems to be associated with thromboembolic disease. Treatment with sildenafil and in some selected cases, percutaneous angioplasty, has obtained favourable responses. Finally, in 2008, two new consensus documents have emerged, one Spanish and the other British, which in the light of current knowledge, give a clearer insight into the management of this serious disease. PMID:19303531

  3. [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

  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. PMID:25101718

  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. 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.

  7. 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. PMID:25739970

  8. Time Resolved MRA: Evaluation of Intrapulmonary Circulation Parameters in Pulmonary Arterial Hypertension

    PubMed Central

    Jeong, Hyun J.; Vakil, Parmede; Sheehan, John J.; Shah, Sanjiv J.; Cuttica, Michael; Carr, James C.; Carroll, Timothy J.; Davarpanah, Amir

    2010-01-01

    Purpose To determine whether pulmonary arterial and venous transit times measured by time-resolved MRA can be used as a diagnostic tool for pulmonary arterial hypertension (PAH). Materials and Methods 12 patients with confirmed PAH and 10 healthy volunteers were scanned with IRB approval. Time-resolved MRA and 2D phase contrast flow images of the pulmonary vasculature were acquired. Pulmonary arterial and venous transit times (PaTT and PvTT) and pulmonary valve flow (PVF) were obtained. Pulmonary arterial and pulmonary venous blood volumes (PaBV and PvBV) were calculated as the product of flow and transit time. Results Patients with PAH showed statistically significant increases in PaTT and PvTT (p<0.0004, p<0.05 respectively) compared to controls. PaBV (165.2 ± 92.0ml) was significantly higher in PAH subjects than controls (97.0 ± 47.1 ml) (p<0.04), whereas PvBV (127.9 ± 148.9ml) of PAH subjects had no significant increase from those of healthy controls (142.5 ± 104.1 ml) (p<0.38). Conclusion Pulmonary arterial transit times measured using time-resolved MRA can be used as a simple, non-invasive metric for detection of altered hemodynamics in PAH. PMID:21182144

  9. 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

  10. Anomalous origin of the left coronary artery from the pulmonary artery in children: 15 years experience.

    PubMed

    Zheng, Jianyong; Ding, Wenhong; Xiao, Yanyan; Jin, Mei; Zhang, Guizhen; Cheng, Pei; Han, Ling

    2011-01-01

    This study aimed to illustrate the experience of treating children with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). The clinical data for 19 children with ALCAPA admitted to Beijing Anzhen Hospital from August 1993 to June 2009 were reviewed. According to the data, 47.4% (9/19) of the patients had a misdiagnosis of endocardial fibroelastosis, and 15.8% (3/19) had a misdiagnosis of dilated cardiomyopathy. Electrocardiography showed abnormal Q waves with T wave inversion in leads I, avL, and V4-V6 of 18 patients, especially in lead avL. The ratio of proximal right coronary artery diameter to aotic root diameter exceeded 0.20 for 15 of 16 patients. Apical ventricular aneurysm or aneurysmal dilation (52.6%,10/19), enhanced echogenicity of papillary muscles (84.2%, 16/19), and increased coronary collaterals (78.9%, 15/19) were detected frequently during echocardiography. A total of 18 patients underwent cardiac surgery including left coronary artery (LCA) ligation for 1 patient (5.6%), LCA ligation plus coronary artery bypass grafting for 1 patient (5.6%), Takeuchi operation for 7 patients (38.9%), and LCA reimplantation for 9 patients (50.0%). Five patients died in the hospital, and the remainder were asymptomatic during a follow-up period of 6 to 166 months. Their abnormal Q waves gradually regressed, and left ventricular systolic function and size returned to normal with alleviation of mitral insufficiency. The clinical features of ALCAPA are helpful for determining an accurate diagnosis. This anomaly can be treated successfully by several types of operations with good prognosis. PMID:20976445

  11. 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

  12. 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

  13. 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

  14. Epigenetic mechanisms in pulmonary arterial hypertension: the need for global perspectives.

    PubMed

    Chelladurai, Prakash; Seeger, Werner; Pullamsetti, Soni Savai

    2016-06-01

    Pulmonary arterial hypertension (PAH) is a severe and progressive disease, characterised by high pulmonary artery pressure that usually culminates in right heart failure. Recent findings of alterations in the DNA methylation state of superoxide dismutase 2 and granulysin gene loci; histone H1 levels; aberrant expression levels of histone deacetylases and bromodomain-containing protein 4; and dysregulated microRNA networks together suggest the involvement of epigenetics in PAH pathogenesis. Thus, PAH pathogenesis evidently involves the interplay of a predisposed genetic background, epigenetic state and injurious events. Profiling the genome-wide alterations in the epigenetic mechanisms, such as DNA methylation or histone modification pattern in PAH vascular cells, may explain the great variability in susceptibility and disease severity that is frequently associated with pronounced remodelling and worse clinical outcome. Moreover, the influence of genetic predisposition and the acquisition of epigenetic alterations in response to environmental cues in PAH progression and establishment has largely been unexplored on a genome-wide scale. In order to gain insights into the molecular mechanisms leading to the development of PAH and to design novel therapeutic strategies, high-throughput approaches have to be adopted to facilitate systematic identification of the disease-specific networks using next-generation sequencing technologies, the application of these technologies in PAH has been relatively trivial to date. PMID:27246590

  15. Regulation and function of miR-214 in pulmonary arterial hypertension

    PubMed Central

    Deng, Lin; Grant, Jennifer S.; Pinel, Karine; Thomas, Matthew; Morrell, Nicholas W.; MacLean, Margaret R.; Baker, Andrew H.; Denby, Laura

    2016-01-01

    Abstract Dysregulation of microRNAs (miRNAs) can contribute to the etiology of diseases, including pulmonary arterial hypertension (PAH). Here we investigated a potential role for the miR-214 stem loop miRNA and the closely linked miR-199a miRNAs in PAH. All 4 miRNAs were upregulated in the lung and right ventricle (RV) in mice and rats exposed to the Sugen (SU) 5416 hypoxia model of PAH. Further, expression of the miRNAs was increased in pulmonary artery smooth muscle cells exposed to transforming growth factor β1 but not BMP4. We then examined miR-214−/− mice exposed to the SU 5416 hypoxia model of PAH or normoxic conditions and littermate controls. There were no changes in RV systolic pressure or remodeling observed between the miR-214−/− and wild-type hypoxic groups. However, we observed a significant increase in RV hypertrophy (RVH) in hypoxic miR-214−/− male mice compared with controls. Further, we identified that the validated miR-214 target phosphatase and tensin homolog was upregulated in miR-214−/− mice. Thus, miR-214 stem loop loss leads to elevated RVH and may contribute to the heart failure associated with PAH. PMID:27162619

  16. 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. PMID:25547257

  17. 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.

  18. Relating external compressing pressure to mean arterial pressure in non-invasive blood pressure measurements.

    PubMed

    Chin, K Y; Panerai, R B

    2015-01-01

    Arterial volume clamping uses external compression of an artery to provide continuous non-invasive measurement of arterial blood pressure. It has been assumed that mean arterial pressure (MAP) corresponds to the point where unloading leads to the maximum oscillation of the arterial wall as reflected by photoplethysmogram (PPG), an assumption that has been challenged. Five subjects were recruited for the study (three males, mean age (SD) = 32 (15) years). The PPG waveform was analysed to identify the relationship between the external compressing pressure, PPG pulse amplitude and MAP. Two separate tests were carried out at compression step intervals of 10 mmHg and 2 mmHg, respectively. No significant differences were found between the two tests. The bias between the compressing pressure and the MAP was -4.7 ± 5.63 mmHg (p < 0.001) showing a normal distribution. Further research is needed to identify optimal algorithms for estimation of MAP using PPG associated with arterial compression. PMID:25429784

  19. [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

  20. Imaging of extralobar pulmonary sequestration in a patient with tetralogy of Fallot with pulmonary atresia, ventricular septal defect and multiple aorto-pulmonary collateral arteries with multidetector computed tomography.

    PubMed

    Greil, Gerald F; Schoebinger, Max; Kuettner, Axel; Schaefer, Jürgen F; Hofbeck, Michael; Claussen, Claus D; Meinzer, Hans-Peter; Sieverding, Ludger

    2008-01-01

    Complex pulmonary vascular blood supply is common in patients with tetralogy of Fallot with pulmonary atresia, major systemic to pulmonary collateral arteries and hypoplastic or deficient central pulmonary arteries. An extralobar lung sequestration, which has not been described previously in these patients, was imaged in a 6-week-old infant with multidetector computed tomography with sub-millimeter resolution. Arterial and venous vessels were analyzed using three-dimensional vascular exploration tools and results were confirmed with cardiac catheterization. PMID:18715464

  1. Pulmonary Artery Abnormalities in Ex-smokers with and without Airflow Obstruction.

    PubMed

    Lindenmaier, Tamas J; Kirby, Miranda; Paulin, Gregory; Mielniczuk, Lisa; Cunningham, Ian A; Mura, Marco; Licskai, Christopher; Parraga, Grace

    2016-04-01

    Pulmonary vascular disease is a common complication of chronic obstructive pulmonary disease (COPD), and an important risk factor for COPD exacerbations and death. We explored the relationship between pulmonary artery volumes measured using thoracic computed tomography (CT) and lung structure-function measured using spirometry, CT and magnetic resonance imaging (MRI) in 124 ex-smokers with (n = 68) and without (n = 56) airflow obstruction, and a control group of 35 never-smokers. We observed significantly greater main (p = .01), right (p = .001) and total (p = .003) pulmonary artery volumes in ex-smokers with airflow obstruction as compared to ex-smokers without airflow obstruction. There were also significantly greater pulmonary artery volumes in both ex-smoker subgroups, compared to the never-smoker subgroup (p = .008). For all participants, there were significant correlations for pulmonary artery volumes with the ratio of the forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC), the diffusing capacity of the lung for carbon monoxide (DLCO%pred), airway count, MRI ventilation defect percent and MRI apparent diffusion coefficients. In ex-smokers, ventilation defect percent was significantly correlated with right (r = 0.27, p = .02) and total (r = 0.25, p = .03) pulmonary artery volumes. Multivariate zero-inflated Poisson regression analysis showed that FEV1%pred (p = .004), DLCO%pred (p = .03), the six minute walk distance (p = .04) and total pulmonary artery volume (p = .03) were significant predictors of acute exacerbations of COPD, while the number of previous exacerbations was not. In conclusion, pulmonary artery enlargement measured using thoracic CT was observed even in ex-smokers without airflow obstruction and was predictive of COPD exacerbations in ex-smokers with airflow obstruction. PMID:26606693

  2. 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. PMID:26391679

  3. 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

  4. 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

  5. Reversible pulmonary arterial hypertension associated with interferon-beta treatment for multiple sclerosis

    PubMed Central

    Gibbons, E; Promislow, S; Davies, RA; Chandy, G; Stewart, DJ; Contreras-Dominguez, V; Pugliese, C; Dunne, R; Mielniczuk, LM

    2015-01-01

    Interferon (IFN) therapy has an important role in the treatment of multiple sclerosis and chronic hepatitis C infection. A few case reports have described an association between IFN therapy and the development of irreversible pulmonary arterial hypertension (PAH), and it is currently listed as a possible drug-induced cause of PAH in the most recent classification of pulmonary hypertension. A causal link between IFN use and PAH remains to be elucidated; many reports of PAH resulting from IFN occur in individuals with some other risk factor for PAH. The authors present a case involving a patient with multiple sclerosis with no known risk factors for PAH, who developed severe PAH after exposure to IFN therapy. The patient experienced significant clinical and hemodynamic improvement, with normalization of her pulmonary pressures after the initiation of combination therapy for PAH. At 28 months after diagnosis, she remains asymptomatic with no hemodynamic evidence of PAH and has been off all PAH therapy for 10 months. PMID:26083539

  6. 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

  7. Endothelin-1 receptor antagonist BQ123 prevents pulmonary artery hypertension induced by low ambient temperature in broilers.

    PubMed

    Yang, Ying; Qiao, Jian; Wu, Zhenlong; Chen, Yue; Gao, Mingyu; Ou, Deyuan; Wang, Huiyu

    2005-12-01

    Evidence has indicated that endothelin-1 is related to the pathogenesis of hypertension. To characterize the role of endothelin-1 (ET-1) in the development of pulmonary hypertension syndrome in broilers, the blockade effect of ETA receptor (ET(A)) antagonist, BQ123, on blood pressure in experimental models of pulmonary hypertension was examined. Birds were locally anesthetized and instrumented with venous catheters for pulmonary arterial pressure (PAP) and right ventricular pressure (RVP), followed by packed cell volume (PCV) and Ascites heart index (AHI) measured, after exposed to low ambient temperature for 7 or 14 d. In treated groups, BQ123 (0.4 or 2.0 microg each time, 2 times a day), administered in abdominal cavities for 7 or 14 d during birds kept in low ambient temperature, prevented both PAP and RVP increasing, especially the high dose BQ123 lowered PAP and RVP to normotensive levels as that in control under normal temperature, whereas significant increases (p<0.05) were found in the two parameters of broilers in both untreated and saline treated group under low ambient temperature compared with those of birds in control. Furthermore, there was also a reduction in low ambient temperature-induced right ventricular hypertrophy in the groups administered BQ123. The preventive effect of BQ123 suggests that ET-1 is associated with the development of broilers' pulmonary hypertension, which leads to the development of ascites, and BQ123 can prevent the occurrence of pulmonary hypertension. PMID:16327149

  8. 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

  9. Severe pulmonary arterial hypertensive rats are tolerant to mild exercise

    PubMed Central

    Hartman, Lauren J.; Scruggs, April K.; McLendon, Jared M.; Haven, April K.; Bauer, Natalie N.

    2015-01-01

    Abstract A frequently used end point of clinical outcomes in patients with pulmonary arterial hypertension (PAH) is the 6-minute walk distance. Furthermore, some data suggest that mild to moderate exercise as an intervention in stable PAH is beneficial. Some of these questions have been recapitulated in the monocrotaline and hypoxia animal models of pulmonary hypertension. However, mild exercise and walk distance as end points have not been rigorously examined in the severe progressive Sugen 5416/hypoxia/normoxia (Su/Hx/Nx) animal model of PAH at each stage of worsening disease. Our hypothesis was that animals that were preselected as runners would have increased walk times and improved right ventricle/left ventricle plus septum (RV/LV+S) ratios, echocardiography, and histology compared with nonexercised Su/Hx/Nx animals. We examined four groups of rats: Su/Hx/Nx sedentary, Su/Hx/Nx exercised, control sedentary, and control exercised. Echocardiography was performed at 5, 8, and 13 weeks to assess right ventricular inner diameter in diastole and left ventricular eccentricity index. We found no difference between exercised and sedentary Su/Hx/Nx rats, and both were worsened compared with controls. Rats were euthanized at 13 weeks, and we found that neither RV/LV+S nor the occurrence of occlusive lesions were influenced by exercise. Most interesting, however, was that despite progressive PAH development, exercised Su/Hx/Nx rats showed no decrease in time or distance for treadmill exercise. In all, our data suggest that, despite severe PAH development, Su/Hx/Nx rats retain the same treadmill exercise capacity as control animals. PMID:26064461

  10. Drug treatment of pulmonary arterial hypertension: current and future agents.

    PubMed

    Hoeper, Marius M

    2005-01-01

    During the last decade we have witnessed substantial improvements in the therapeutic options for pulmonary arterial hypertension (PAH), including true innovations targeting some of the mechanisms involved in the pathogenesis of this devastating disease. Intravenous epoprostenol was the first drug to improve symptoms and survival of patients with PAH. Novel prostanoids, including subcutaneous treprostinil and inhaled iloprost, also have beneficial effects in many patients, although their long-term efficacy is less well known. Among the newer treatments for PAH, endothelin receptor antagonists and phosphodiesterase type 5 (PDE5) inhibitors have reshaped clinical practice. The endothelin receptor antagonist bosentan has been approved in many parts of the world and most current guidelines recommend this drug as first-line treatment for patients with PAH in functional class III. Novel endothelin receptor antagonists such as sitaxsentan sodium and ambrisentan are currently being investigated. The PDE5 sildenafil is also being intensively studied in patients with pulmonary hypertension, and most of the available data look promising, although approval for PAH is still pending. Other PDE5 inhibitors have not yet undergone extensive study in PAH. The increasing insight into the pathogenesis of PAH opens several new therapeutic opportunities, which include vasoactive intestinal peptide, selective serotonin reuptake inhibitors, adrenomedullin and HMG-CoA reductase inhibitors (statins). However, PAH is a complex disorder and targeting a single pathway can not be expected to be uniformly successful. Thus, combining substances with different modes of action is expected to improve symptoms, haemodynamics and survival in PAH patients, although combination therapy has yet to undergo the scrutiny of large randomised clinical trials. PMID:15977967

  11. 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

  12. ACTIVATION OF GATA-4 BY SEROTONIN IN PULMONARY ARTERY SMOOTH MUSCLE CELLS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Serotonin (5-HT) is a mitogen of pulmonary artery smooth muscle cells (PASMC) and plays an important role in the development of pulmonary hypertension. Signal transduction initiated by 5-HT involves serotonin transporter (SERT)-dependent generation of reactive oxygen species (ROS) and activation of...

  13. Pulmonary Artery Pseudoaneurysm: A Rare Cause of Hemoptysis in a Child.

    PubMed

    Vaideeswar, Pradeep; Karande, Sunil; Yadav, Subhash; Pardeshi, Kirti

    2016-01-01

    Aneurysms and pseudoaneurysms of pulmonary vasculature are uncommon occurrences that contribute to mortality and morbidity, without timely diagnosis and intervention. We report a fatal massive hemoptysis in a child due to a consolidation-related pulmonary arterial pseudoaneurysm, an extremely rare phenomenon. PMID:26366670

  14. 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.

  15. 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.

  16. Sildenafil versus nitric oxide for acute vasodilator testing in pulmonary arterial hypertension

    PubMed Central

    Felix, Janine F.; Voswinckel, Robert; Sommer, Natascha; Franco, Oscar H.; Grimminger, Friedrich; Reichenberger, Frank; Seeger, Werner; Gall, Henning

    2015-01-01

    Abstract Vasoreactivity testing with inhaled NO is recommended for pulmonary arterial hypertension (PAH) because of its therapeutic and prognostic value. Sildenafil has acute pulmonary vasodilating properties, but its diagnostic and prognostic impact in PAH is unknown. Our objective was to compare acute vasodilating responses to sildenafil and those to NO during right heart catheterization and also their prognostic values in patients with PAH. Ninety-nine patients with idiopathic PAH and 99 with associated PAH underwent vasoreactivity testing with NO and sildenafil. Only mild adverse effects of sildenafil, in the form of hypotension, were observed, at a rate of 4.5%. The acute responder rate was 8.1% for NO and 11.6% for sildenafil. The NO-induced response in mean pulmonary arterial pressure and cardiac output correlated with the response to sildenafil. Thirteen patients were long-term responders to calcium channel blockers (CCBs), and 3 of them were correctly identified by acute vasoreactivity test with both drugs. The specificity of the vasoreactivity test for identifying long-term CCB responders was 88.9% for NO and 85.1% for sildenafil testing. A trend toward better survival was found in sildenafil and NO responders, compared with nonresponders. Use of sildenafil for vasoreactivity testing is safe. Sildenafil may be useful as alternative vasoreactivity-testing agent, identifying the same number of long-term CCB responders as NO. However, NO seems to be a more ideal testing drug because of its pharmacologic properties. Moreover, sildenafil vasoreactivity testing might contribute to an improved estimate of prognosis among patients with PAH. PMID:26064455

  17. 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

  18. The unique heart sound signature of children with pulmonary artery hypertension

    PubMed Central

    Elgendi, Mohamed; Bobhate, Prashant; Jain, Shreepal; Guo, Long; Kumar, Shine; Rutledge, Jennifer; Coe, Yashu; Zemp, Roger; Schuurmans, Dale

    2015-01-01

    Abstract 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

  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. Pulmonary artery closure in combination with patch technique for treating congenital heart disease combined with large patent ductus arteriosus: A clinical study of 9 cases

    PubMed Central

    Wen, Bing; Yang, Junya; Liu, Huiruo; Jiao, Zhouyang; Zhao, Wenzeng

    2016-01-01

    Objective: To document clinical experience of treating congenital heart disease combined with large patent ductus arteriosus with pulmonary artery closure in combination with patch technique. Methods: Thirty-six patients (8 males and 28 females) who suffered from congenital heart disease and underwent hybrid surgery in the First Affiliated Hospital of Zhengzhou University from October 2010 to February 2014 were selected for this study. They aged 14 to 39 years and weighed 32.20 to 61.50 kg. Diameter of arterial duct was between 10 mm and 13 mm; 28 cases were tube type, 4 cases were funnel type and four cases were window type. All patients had moderate or severe pulmonary arterial hypertension; besides, there were 28 cases of ventricular septal defect, 16 cases of atrial septal defect, eight cases of aortic insufficiency, four cases of mitral stenosis and insufficiency and four cases of infectious endocarditis. Cardz Pulmonary Bypass (CPB) was established after chest was opened along the middle line. With the help of Transesophageal echocardiography, large patent ductus arteriosus was blocked off through pulmonary artery. Pulmonary artery was cut apart after blocking of heart. Large patent ductus arteriosus on the side of pulmonary artery was strengthened with autologous pericardial patch. Results: Of 36 patients, 32 patients had patent ductus arteriosus closure device and four patients had atrial septal defect closure device. Pulmonary arteries of 36 cases were all successfully closed. Systolic pressure declined after closure ((54.86±19.23) mmHg vs (96.05±23.07) mmHg, p<0.05); average pulmonary arterial pressure also declined after closure ((39.15±14.83) mmHg vs (72.88±15.76) mmHg, p<0.05). The patients were followed up for one to fifty one months (average 11.5 months). Compared to before surgery, left atrial diameter, left ventricular diameter and pulmonary artery diameter all narrowed after surgery. Besides, clinical symptoms were relieved and cardiac

  1. ["Tracking" the magnitude of arterial pressure in the circulatory system].

    PubMed

    Amosov, N M; Beregovskiĭ, B A; Lissova, O I; Palets, B L

    1976-11-01

    Steady--state characteristics of arterial and venous pressure, cardiac output, total peripheral resistance, heart rate, and pumping heart capacity depending on blood volume change were studied in dogs under conditons of rest, exercises, light and deep narcosis. The tracking mean arterial pressure was found to be the main principle of hemodynamic regulation. In unanesthetized animals the tracking is based on heart regulation component mainly, while under light narcosis it is the vascular component. In deep narcosis it is the suppressed tracking principle: arterial pressure change is proportional to blood volume changes. PMID:1022536