Increased blood carboxyhaemoglobin concentrations in inflammatory pulmonary diseases

PubMed Central

Yasuda, H; Yamaya, M; Yanai, M; Ohrui, T; Sasaki, H

2002-01-01

Background: Exhaled carbon monoxide has been reported to increase in inflammatory pulmonary diseases and to be correlated with blood carboxyhaemoglobin (Hb-CO) concentration. A study was undertaken to determine whether arterial blood Hb-CO increases in patients with inflammatory pulmonary diseases. Methods: The Hb-CO concentration in arterial blood was measured with a spectrophotometer in 34 normal control subjects, 24 patients with bronchial asthma, 52 patients with pneumonia, and 21 patients with idiopathic pulmonary fibrosis (IPF). Results: The mean (SE) Hb-CO concentrations in patients with bronchial asthma during exacerbations (n=24, 1.05 (0.05)%), with pneumonia at the onset of illness (n=52, 1.08 (0.06)%), and with IPF (n=21, 1.03 (0.09)%) were significantly higher than those in control subjects (n=34, 0.60 (0.07)%) (mean difference 0.45% (95% confidence interval (CI) 0.23 to 0.67), p<0.01 in patients with bronchial asthma, mean difference 0.48% (95% CI 0.35 to 0.60), p<0.0001 in patients with pneumonia, and mean difference 0.43% (95% CI 0.26 to 0.61) p<0.001 in patients with IPF). In 20 patients with bronchial asthma the Hb-CO concentration decreased after 3 weeks of treatment with oral glucocorticoids (p<0.001). In 20 patients with pneumonia the Hb-CO concentration had decreased after 3 weeks when patients showed evidence of clinical improvement (p<0.001). The values of C-reactive protein (CRP), an acute phase protein, correlated with Hb-CO concentrations in patients with pneumonia (r=0.74, p<0.0001) and in those with IPF (r=0.46, p<0.01). In patients with bronchial asthma changes in Hb-CO concentrations were significantly correlated with those in forced expiratory volume in 1 second (FEV1) after 3 weeks (r=0.67, p<0.01). Exhaled carbon monoxide (CO) concentrations were correlated with Hb-CO concentrations (n=33, r=0.80, p<0.0001). Conclusions: Hb-CO concentrations are increased in inflammatory pulmonary diseases including bronchial asthma, pneumonia, and

Hypopnea consequent to reduced pulmonary blood flow in the dog.

PubMed

Stremel, R W; Whipp, B J; Casaburi, R; Huntsman, D J; Wasserman, K

1979-06-01

The ventilatory responses to diminished pulmonary blood flow (Qc), as a result of partial cardiopulmonary bypass (PCB), were studied in chloralose-urethan-anesthetized dogs. Qc was reduced by diverting vena caval blood through a membrane gas exchanger and returning it to the ascending aorta. PCB flows of 400--1,600 ml/min were utilized for durations of 2--3 min. Decreasing Qc, while maintaining systemic arterial blood gases and perfusion, results in a significant (P less than 0.05) decrease in expiratory ventilation (VE) (15.9%) and alveolar ventilation (VA) (31.0%). The ventilatory decreases demonstrated for this intact group persist after bilateral cervical vagotomy (Vx), carotid body and carotid sinus denervation (Cx), and combined Vx and Cx. The changes in VE and VA were significantly (P less than 0.001) correlated with VCO2 changes, r = 0.80 and r = 0.93, respectively. These ventilatory changes were associated with an overall average decrease in left ventricular PCO2 of 2.1 Torr; this decrease was significant (P less than 0.05) only in the intact and Cx groups. Decreasing pulmonary blood flow results in a decrease in ventilation that may be CO2 related; however, the exact mechanism remains obscure but must have a component that is independent of vagally mediated cardiac and pulmonary afferents and peripheral baroreceptor and chemoreceptor afferents.

Pulmonary blood flow and pulmonary hypertension: Is the pulmonary circulation flowophobic or flowophilic?

PubMed Central

Kulik, Thomas J.

2012-01-01

Increased pulmonary blood flow (PBF) is widely thought to provoke pulmonary vascular obstructive disease (PVO), but the impact of wall shear stress in the lung is actually poorly defined. We examined information from patients having cardiac lesions which impact the pulmonary circulation in distinct ways, as well as experimental studies, asking how altered hemodynamics impact the risk of developing PVO. Our results are as follows: (1) with atrial septal defect (ASD; increased PBF but low PAP), shear stress may be increased but there is little tendency to develop PVO; (2) with normal PBF but increased pulmonary vascular resistance (PVR; mitral valve disease) shear stress may also be increased but risk of PVO still low; (3) with high PVR and PBF (e.g., large ventricular septal defect), wall shear stress is markedly increased and the likelihood of developing PVO is much higher than with high PBF or PAP only; and (4) with ASD, experimental and clinical observations suggest that increased PBF plus another stimulus (e.g., endothelial inflammation) may be required for PVO. We conclude that modestly increased wall shear stress (e.g., ASD) infrequently provokes PVO, and likely requires other factors to be harmful. Likewise, increased PAP seldom causes PVO. Markedly increased wall shear stress may greatly increase the likelihood of PVO, but we cannot discriminate its effect from the combined effects of increased PAP and PBF. Finally, the age of onset of increased PAP may critically impact the risk of PVO. Some implications of these observations for future investigations are discussed. PMID:23130101

Steep head-down tilt has persisting effects on the distribution of pulmonary blood flow.

PubMed

Henderson, A Cortney; Levin, David L; Hopkins, Susan R; Olfert, I Mark; Buxton, Richard B; Prisk, G Kim

2006-08-01

Head-down tilt has been shown to increase lung water content in animals and alter the distribution of ventilation in humans; however, its effects on the distribution of pulmonary blood flow in humans are unknown. We hypothesized that head-down tilt would increase the heterogeneity of pulmonary blood flow in humans, an effect analogous to the changes seen in the distribution of ventilation, by increasing capillary hydrostatic pressure and fluid efflux in the lung. To test this, we evaluated changes in the distribution of pulmonary blood flow in seven normal subjects before and after 1 h of 30 degrees head-down tilt using the magnetic resonance imaging technique of arterial spin labeling. Data were acquired in triplicate before tilt and at 10-min intervals for 1 h after tilt. Pulmonary blood flow heterogeneity was quantified by the relative dispersion (standard deviation/mean) of signal intensity for all voxels within the right lung. Relative dispersion was significantly increased by 29% after tilt and remained elevated during the 1 h of measurements after tilt (0.84 +/- 0.06 pretilt, 1.09 +/- 0.09 calculated for all time points posttilt, P < 0.05). We speculate that the mechanism most likely responsible for our findings is that increased pulmonary capillary pressures and fluid efflux in the lung resulting from head-down tilt alters regional blood flow distribution.

Rarefaction and blood pressure in systemic and pulmonary arteries

PubMed Central

OLUFSEN, METTE S.; HILL, N. A.; VAUGHAN, GARETH D. A.; SAINSBURY, CHRISTOPHER; JOHNSON, MARTIN

2012-01-01

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

Blood Biomarkers in Idiopathic Pulmonary Fibrosis.

PubMed

Guiot, Julien; Moermans, Catherine; Henket, Monique; Corhay, Jean-Louis; Louis, Renaud

2017-06-01

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease of unknown origin whose incidence has been increasing over the latest decade partly as a consequence of population ageing. New anti-fibrotic therapy including pirfenidone and nintedanib have now proven efficacy in slowing down the disease. Nevertheless, diagnosis and follow-up of IPF remain challenging. This review examines the recent literature on potentially useful blood molecular and cellular biomarkers in IPF. Most of the proposed biomarkers belong to chemokines (IL-8, CCL18), proteases (MMP-1 and MMP-7), and growth factors (IGBPs) families. Circulating T cells and fibrocytes have also gained recent interest in that respect. Up to now, though several interesting candidates are profiling there has not been a single biomarker, which proved to be specific of the disease and predictive of the evolution (decline of pulmonary function test values, risk of acute exacerbation or mortality). Large scale multicentric studies are eagerly needed to confirm the utility of these biomarkers.

Pulmonary diffusing capacity, capillary blood volume, and cardiac output during sustained microgravity

NASA Technical Reports Server (NTRS)

Prisk, G. K.; Guy, Harold J. B.; Elliott, Ann R.; Deutschman, Robert A., III; West, John B.

1993-01-01

We measured pulmonary diffusing capacity (DL), diffusing capacity per unit lung volume, pulmonary capillary blood volume (Vc), membrane diffusing capacity (Dm), pulmonary capillary blood flow or cardiac output (Qc), and cardiac stroke volume (SV) in four subjects exposed to nine days of microgravity. DL in microgravity was elevated compared with preflight standing values and was higher than preflight supine because of the elevation of both Vc and Dm. The elevation in Vc was comparable to that measured supine in 1 G, but the increase in Dm was in sharp contrast to the supine value. We postulate that, in 0 G, pulmonary capillary blood is evenly distributed throughout the lung, providing for uniform capillary filling, leading to an increase in the surface area available for diffusion. By contrast, in the supine 1-G state, the capillaries are less evenly filled, and although a similar increase in blood volume is observed, the corresponding increase in surface area does not occur. DL and its subdivisions showed no adaptive changes from the first measurement 24 h after the start of 0 G to eight days later. Similarly, there were no trends in the postflight data, suggesting that the principal mechanism of these changes was gravitational. The increase in Dm suggests that subclinical pulmonary edema did not result from exposure to 0 G. Qc was modestly increased inflight and decreased postflight compared with preflight standing. Compared with preflight standing, SV was increased 46 percent inflight and decreased 14 percent in the 1st week postflight. There were temporal changes in Qc and SV during 0 G, with the highest values recorded at the first measurement, 24 h into the flight. The lowest values of Qc and SV occurred on the day of return.

Effect of furosemide on pulmonary blood flow distribution in resting and exercising horses

NASA Technical Reports Server (NTRS)

Erickson, H. H.; Bernard, S. L.; Glenny, R. W.; Fedde, M. R.; Polissar, N. L.; Basaraba, R. J.; Walther, S. M.; Gaughan, E. M.; McMurphy, R.; Hlastala, M. P.

1999-01-01

We determined the spatial distribution of pulmonary blood flow (PBF) with 15-micron fluorescent-labeled microspheres during rest and exercise in five Thoroughbred horses before and 4 h after furosemide administration (0.5 mg/kg iv). The primary finding of this study was that PBF redistribution occurred from rest to exercise, both with and without furosemide. However, there was less blood flow to the dorsal portion of the lung during exercise postfurosemide compared with prefurosemide. Furosemide did alter the resting perfusion distribution by increasing the flow to the ventral regions of the lung; however, that increase in flow was abated with exercise. Other findings included 1) unchanged gas exchange and cardiac output during rest and exercise after vs. before furosemide, 2) a decrease in pulmonary arterial pressure after furosemide, 3) an increase in the slope of the relationship of PBF vs. vertical height up the lung during exercise, both with and without furosemide, and 4) a decrease in blood flow to the dorsal region of the lung at rest after furosemide. Pulmonary perfusion variability within the lung may be a function of the anatomy of the pulmonary vessels that results in a predominantly fixed spatial pattern of flow distribution.

Roles of preoperative arterial blood gas tests in the surgical treatment of scoliosis with moderate or severe pulmonary dysfunction.

PubMed

Liu, Jia-Ming; Shen, Jian-Xiong; Zhang, Jian-Guo; Zhao, Hong; Li, Shu-Gang; Zhao, Yu; Qiu, Giu-Xing

2012-01-01

It has been stated that preoperative pulmonary function tests are essential to assess the surgical risk in patients with scoliosis. Arterial blood gas tests have also been used to evaluate pulmonary function before scoliotic surgery. However, few studies have been reported. The aim of this study was to investigate the roles of preoperative arterial blood gas tests in the surgical treatment of scoliosis with moderate or severe pulmonary dysfunction. This study involved scoliotic patients with moderate or severe pulmonary dysfunction (forced vital capacity < 60%) who underwent surgical treatment between January 2002 and April 2010. A total of 73 scoliotic patients (23 males and 50 females) with moderate or severe pulmonary dysfunction were included. The average age of the patients was 16.53 years (ranged 10 - 44). The demographic distribution, medical records, and radiographs of all patients were collected. All patients received arterial blood gas tests and pulmonary function tests before surgery. The arterial blood gas tests included five parameters: partial pressure of arterial oxygen, partial pressure of arterial carbon dioxide, alveolar-arterial oxygen tension gradient, pH, and standard bases excess. The pulmonary function tests included three parameters: forced expiratory volume in 1 second ratio, forced vital capacity ratio, and peak expiratory flow ratio. All five parameters of the arterial blood gas tests were compared between the two groups with or without postoperative pulmonary complications by variance analysis. Similarly, all three parameters of the pulmonary function tests were compared. The average coronal Cobb angle before surgery was 97.42° (range, 50° - 180°). A total of 15 (20.5%) patients had postoperative pulmonary complications, including hypoxemia in 5 cases (33.3%), increased requirement for postoperative ventilatory support in 4 (26.7%), pneumonia in 2 (13.3%), atelectasis in 2 (13.3%), pneumothorax in 1 (6.7%), and hydrothorax in 1 (6

Pulmonary physiology during pulmonary embolism.

PubMed

Elliott, C G

1992-04-01

Acute pulmonary thromboembolism produces a number of pathophysiologic derangements of pulmonary function. Foremost among these alterations is increased pulmonary vascular resistance. For patients without preexistent cardiopulmonary disease, increased pulmonary vascular resistance is directly related to the degree of vascular obstruction demonstrated on the pulmonary arteriogram. Vasoconstriction, either reflexly or biochemically mediated, may contribute to increased pulmonary vascular resistance. Acute pulmonary thromboembolism also disturbs matching of ventilation and blood flow. Consequently, some lung units are overventilated relative to perfusion (increased dead space), while other lung units are underventilated relative to perfusion (venous admixture). True right-to-left shunting of mixed venous blood can occur through the lungs (intrapulmonary shunt) or across the atrial septum (intracardiac shunt). In addition, abnormalities of pulmonary gas exchange (carbon monoxide transfer), pulmonary compliance and airway resistance, and ventilatory control may accompany pulmonary embolism. Thrombolytic therapy can reverse the hemodynamic derangements of acute pulmonary thromboembolism more rapidly than anticoagulant therapy. Limited data suggest a sustained benefit of thrombolytic treatment on the pathophysiologic alterations of pulmonary vascular resistance and pulmonary gas exchange produced by acute pulmonary emboli.

The effect of blood transfusion on pulmonary permeability in cardiac surgery patients: a prospective multicenter cohort study.

PubMed

Vlaar, Alexander P J; Cornet, Alexander D; Hofstra, Jorrit J; Porcelijn, Leendert; Beishuizen, Albertus; Kulik, Willem; Vroom, Margreeth B; Schultz, Marcus J; Groeneveld, A B Johan; Juffermans, Nicole P

2012-01-01

There is an association between blood transfusion and pulmonary complications in cardiac surgery. Mediators of increased pulmonary vascular leakage after transfusion are unknown. We hypothesized that factors may include antibodies or bioactive lipids, which have been implicated in transfusion-related acute lung injury. We performed a prospective cohort study in two university hospital intensive care units in the Netherlands. Pulmonary vascular permeability was measured in cardiac surgery patients after receiving no, restrictive (one or two transfusions), or multiple (five or more transfusions) transfusions (n=20 per group). The pulmonary leak index (PLI), using (67) Ga-labeled transferrin, was determined within 3 hours postoperatively. Blood products were screened for bioactive lipid accumulation and the presence of antibodies. The PLI was elevated in all groups after cardiac surgery. Transfused patients had a higher PLI compared to nontransfused patients (33×10(-3) ± 20×10(-3) vs. 23×10(-3) ± 11×10(-3)/min, p<0.01). The amount of red blood cell (RBC) products, but not of fresh-frozen plasma or platelets, was associated with an increase in PLI (β, 1.6 [0.2-3.0]). Concerning causative factors in the blood product, neither the level of bioactive lipids nor the presence of antibodies was associated with an increase in PLI. Patient factors such as surgery risk and time on cardiopulmonary bypass did not influence the risk of pulmonary leakage after blood transfusion. Transfusion in cardiothoracic surgery patients is associated with an increase in pulmonary capillary permeability, an effect that was dose dependent for RBC products. The level of bioactive lipids or the presence of HLA or HNA antibodies in the transfused products were not associated with increased pulmonary capillary permeability. © 2011 American Association of Blood Banks.

Immunological characterization of pulmonary intravascular macrophages

NASA Technical Reports Server (NTRS)

Chitko-McKown, C. G.; Reddy, D. N.; Chapes, S. K.; McKown, R. D.; Blecha, F.; Spooner, B. S. (Principal Investigator)

1992-01-01

Pulmonary intravascular macrophages (PIMs) are lung macrophages found apposed to the endothelium of pulmonary capillaries. In many species, they are responsible for the clearance of blood-borne particulates and pathogens; however, little else is known about their roles as immunologic effector cells. We compared PIMs with pulmonary alveolar macrophages (PAMs) to determine the relative immunological activities of these two cell populations. Our results suggested that both populations possess similar phagocytic and bactericidal activities. In assays measuring cytotoxicity, PIMs were more cytotoxic than PAMs against virally infected target cells; however, differences between these macrophage populations were not as marked when noninfected targets were used. LPS-stimulated PIMs produced more T-cell proliferative cytokines than PAMs, and both populations of nonstimulated macrophages produced similar amounts of the cytokines. In contrast, PAMs produced more TNF alpha and NO2- than PIMs when both populations were stimulated with LPS; however, nonstimulated PAMs and PIMs produced similar amounts of TNF alpha and NO2. These data suggest that bovine PIMs are immunologically active. Differences between the degrees of activity of PIMs and PAMs indicate that these macrophage populations may have different roles in lung surveillance.

Inhaled NO therapy increases blood nitrite, nitrate and S-nitrosohemoglobin concentrations in infants with pulmonary hypertension

PubMed Central

Ibrahim, Yomna I.; Ninnis, Janet R.; Hopper, Andrew O.; Deming, Douglas D.; Zhang, Amy X.; Herring, Jason L.; Sowers, Lawrence C.; McMahon, Timothy J.; Power, Gordon G.; Blood, Arlin B.

2011-01-01

Objective To measure the circulating concentrations of nitric oxide (NO) adducts with NO bioactivity following inhaled NO therapy in infants with pulmonary hypertension. Study design In this single center study five sequential blood samples were collected from infants with pulmonary hypertension before, during and after therapy with iNO (n=17). Samples were collected from a control group of hospitalized infants without pulmonary hypertension (n=16) and from healthy adults for comparison (n=12). Results After beginning iNO (20 ppm) whole blood nitrite increased about two-fold within two hours (P<0.01). Whole blood nitrate increased to four-fold higher than baseline during treatment with 20ppm iNO (P<0.01). S-nitrosohemoglobin (SNO-Hb) increased measurably after beginning iNO (P<0.01) whereas iron nitrosyl hemoglobin and total Hb-bound NO-species compounds did not change. Conclusion Treatment of pulmonary hypertensive infants with iNO results in increases in nitrite, nitrate, and SNO-Hb in circulating blood. We speculate that these compounds may be carriers of NO bioactivity throughout the body and account for peripheral effects of iNO in the brain, heart and other organs. PMID:21907348

Morphometry-based impedance boundary conditions for patient-specific modeling of blood flow in pulmonary arteries.

PubMed

Spilker, Ryan L; Feinstein, Jeffrey A; Parker, David W; Reddy, V Mohan; Taylor, Charles A

2007-04-01

Patient-specific computational models could aid in planning interventions to relieve pulmonary arterial stenoses common in many forms of congenital heart disease. We describe a new approach to simulate blood flow in subject-specific models of the pulmonary arteries that consists of a numerical model of the proximal pulmonary arteries created from three-dimensional medical imaging data with terminal impedance boundary conditions derived from linear wave propagation theory applied to morphometric models of distal vessels. A tuning method, employing numerical solution methods for nonlinear systems of equations, was developed to modify the distal vasculature to match measured pressure and flow distribution data. One-dimensional blood flow equations were solved with a finite element method in image-based pulmonary arterial models using prescribed inlet flow and morphometry-based impedance at the outlets. Application of these methods in a pilot study of the effect of removal of unilateral pulmonary arterial stenosis induced in a pig showed good agreement with experimental measurements for flow redistribution and main pulmonary arterial pressure. Next, these methods were applied to a patient with repaired tetralogy of Fallot and predicted insignificant hemodynamic improvement with relief of the stenosis. This method of coupling image-based and morphometry-based models could enable increased fidelity in pulmonary hemodynamic simulation.

The value of dual-source multidetector-row computed tomography in determining pulmonary blood supply in patients with pulmonary atresia with ventricular septal defect.

PubMed

Chaosuwannakit, N; Makarawate, P

2018-01-01

Primary evaluation of patients with pulmonary atresia with ventricular septal defect (PA-VSD) traditionally relies upon echocardiography and conventional cardiac angiography (CCA). Cardiac angiography is considered the gold standard for delineation of anatomy in children with PA-VSD. Data comparing CCA and dual-source multidetector-row computed tomography angiography (MDCT) in PA-VSD patients is limited. The objective of this study was to test the hypothesis that MDCT is equivalent to CCA for anatomic delineation in these patients. Twenty-eight patients with PA-VSD underwent CCA and MDCT in close proximity to each other without interval therapy. A retrospective review of these 28 patients was performed. All MDCT data of pulmonary artery morphology, major aortopulmonary collateral arteries (MAPCAs) and type of blood supply (dual vs. single supply) were evaluated by blinded experts and results were compared with CCA. Twenty-eight patients had adequate size right and left pulmonary arteries (21 confluent and 7 non-confluent). Seven patients had complete absence of native pulmonary artery and 3 patients had stenosis of distal branches of pulmonary arteries; all had MAPCAs from descending thoracic aorta and/or subclavian arteries. Sensitivity, specificity, positive and negative predictive value of MDCT for detecting confluent of pulmonary arteries, absence of native pulmonary artery and stenosis of pulmonary arteries were all 100%. Moreover, accuracy of detecting MAPCAs was excellent. These results suggest that MDCT and CCA are equivalent in their ability to delineate pulmonary artery anatomy and MAPCAs. Dual source MDCT provides high diagnostic accuracy in evaluation of pulmonary blood supply in patients with PA-VSD and allows precise characterisation of the condition of pulmonary arteries and MAPCAs which is of paramount importance in managing patients with PA-VSD. (Folia Morphol 2018; 77, 1: 116-122).

Effect of gravitational and inertial forces on vertical distribution of pulmonary blood flow

NASA Technical Reports Server (NTRS)

Chevalier, P. A.; Reed, J. H., Jr.; Vandenberg, R. A.; Wood, E. H.

1978-01-01

Vertical distribution of pulmonary blood flow (VDPBF) was studied, using radioactive microsphere emboli, in dogs without thoracotomy in the right decubitus position during exposure to lateral accelerations of 1, 2, 4, and 6 G. At all levels of force environment studied, an inverse linear relationship was observed between vertical height in the thorax and pulmonary blood flow (ml/min/ml lung tissue) with a decrease in flow to the most dependent region of the lung despite large increases in intravascular pressures at this site. Changes in blood flow were smallest at the mid-lung level, the hydrostatic 'balance point' for vascular and pleural pressures. These force environment-dependent changes in VDPBF are not readily explainable by the Starling resistor analog. Gravity-dependent regional differences in pleural and associated interstitial pressures, plus possible changes in vascular tone resulting from inadequate aeration of blood in the most dependent regions of the lung, probably also affect VDPBF.

[PULMONARY COMPLICATIONS IN CHILDREN, OPERATED ON FOR INBORN HEART FAILURES IN THE ARTIFICIAL BLOOD CIRCULATION ENVIRONMENT].

PubMed

Moshkivska, L V; Nastenko, E A; Golovenko, O S; Lazoryshynets, V V

2015-11-01

The risk factors of pulmonary complications occurrence were analyzed in children, operated on for inborn heart failures in atrificial blood circulation environment. Pulmonary complications rate and the risk factors of their occurrence were analyzed.

Echocardiographic Assessment of the Alterations in Pulmonary Blood Flow Associated with Ketamine and Etomidate Administration in Children with Tetralogy of Fallot.

PubMed

Jha, Ajay K; Gharde, Parag; Chauhan, Sandeep; Kiran, Usha; Malhotra Kapoor, Poonam

2016-02-01

Despite widespread uses of ketamine, the clinical studies determining its effect on pulmonary blood flow in children with tetralogy of Fallot (TOF) are lacking. Furthermore, the quantification of pulmonary blood flow is not possible in these patients, because pulmonary artery catheter is contraindicated. Therefore, the purpose of this study was to evaluate the changes in pulmonary blood flow by intra-operative transesophageal echocardiography after ketamine or etomidate administration in children with TOF. Eleven children each in the two clinical variants of TOF (group A-moderate to severe cyanosis; group B-mild to minimal cyanosis) undergoing intracardiac repair were prospectively studied after endotracheal intubation. A single bolus dose of ketamine (2 mg/kg) and etomidate (0.3 mg/kg) was administered in a random order after 15 minute interval. Hemodynamic, arterial blood gas, and echocardiographic measurements were obtained at 7 consecutive times (T) points (baseline, 1, 2, 4, 6, 8, and 15 minutes after drug administration). Ketamine produced a significant reduction in VTI-T (velocity time integrals total of left upper pulmonary vein), RVOT-PG (right ventricular outflow tract peak gradient), and MG (mean gradient) in group A while those in group B had a significant increase in VTI-T, RVOT-PG, and RVOT-MG at time (T1, T2, T4, and T6; P = 0.00). This divergent behavior, however, was not observed with etomidate. Etomidate does not change pulmonary blood flow. However, ketamine produces divergent effects; it increases pulmonary blood flow in children with minimal cyanosis and decreases pulmonary blood flow in children with moderate to severe cyanosis. © 2015, Wiley Periodicals, Inc.

Airway and alveolar nitric oxide production, lung function, and pulmonary blood flow in sickle cell disease.

PubMed

Lunt, Alan; Ahmed, Na'eem; Rafferty, Gerrard F; Dick, Moira; Rees, David; Height, Sue; Thein, Swee Lay; Greenough, Anne

2016-02-01

Children with sickle cell disease (SCD) often have obstructive lung function abnormalities which could be due to asthma or increased pulmonary blood volume; it is important to determine the underlying mechanism to direct appropriate treatment. In asthmatics, exhaled nitric oxide (FeNO) is elevated. FeNO, however, can also be raised due to increased alveolar production. Our aim, therefore, was to determine if airway or alveolar NO production differed between SCD children and ethnic and age-matched controls. Lung function, airway NO flux and alveolar NO production, and effective pulmonary blood flow were assessed in 18 SCD children and 18 ethnic and age-matched controls. The SCD children compared to the controls had a higher respiratory system resistance (P = 0.0008), alveolar NO production (P = 0.0224), and pulmonary blood flow (P < 0.0001), but not airway NO flux. There was no significant correlation between FeNO and respiratory system resistance in either group, but in the SCD children, there were correlations between alveolar NO production (P = 0.0006) and concentration (P < 0.0001) and pulmonary blood flow. Airway NO flux was not elevated in the SCD children nor correlated with airways obstruction, suggesting that airways obstruction, at least in some SCD children, is not due to asthma.

Exogenous ghrelin improves blood flow distribution in pulmonary hypertension-assessed using synchrotron radiation microangiography.

PubMed

Schwenke, Daryl O; Gray, Emily A; Pearson, James T; Sonobe, Takashi; Ishibashi-Ueda, Hatsue; Campillo, Isabel; Kangawa, Kenji; Umetani, Keiji; Shirai, Mikiyasu

2011-09-01

Ghrelin has cardioprotective properties and, recently, has been shown to improve endothelial function and reduce endothelin-1 (ET-1)-mediated vasoconstriction in peripheral vascular disease. Recently, we reported that ghrelin attenuates pulmonary hypertension (PH) caused by chronic hypoxia (CH), which we hypothesized in this study may be via suppression of the ET-1 pathway. We also aimed to determine whether ghrelin's ability to prevent alterations of the ET-1 pathway also prevented adverse changes in pulmonary blood flow distribution associated with PH. Sprague-Dawley rats were exposed to CH (10% O(2) for 2 weeks) with daily subcutaneous injections of ghrelin (150 μg/kg) or saline. Utilizing synchrotron radiation microangiography, we assessed pulmonary vessel branching structure, which is indicative of blood flow distribution, and dynamic changes in vascular responsiveness to (1) ET-1 (1 nmol/kg), (2) the ET-1(A) receptor antagonist, BQ-123 (1 mg/kg), and (3) ACh (3.0 μg kg⁻¹ min⁻¹). CH impaired blood flow distribution throughout the lung. However, this vessel "rarefaction" was attenuated in ghrelin-treated CH-rats. Moreover, ghrelin (1) reduced the magnitude of endothelial dysfunction, (2) prevented an increase in ET-1-mediated vasoconstriction, and (3) reduced pulmonary vascular remodeling and right ventricular hypertrophy-all adverse consequences associated with CH. These results highlight the beneficial effects of ghrelin for maintaining optimal lung perfusion in the face of a hypoxic insult. Further research is now required to establish whether ghrelin is also an effective therapy for restoring normal pulmonary hemodynamics in patients that already have established PH.

Pulmonary blood flow distribution in sheep: effects of anesthesia, mechanical ventilation, and change in posture

NASA Technical Reports Server (NTRS)

Walther, S. M.; Domino, K. B.; Glenny, R. W.; Hlastala, M. P.

1997-01-01

BACKGROUND: Recent studies providing high-resolution images of pulmonary perfusion have questioned the classical zone model of pulmonary perfusion. Hence the present work was undertaken to provide detailed maps of regional pulmonary perfusion to examine the influence of anesthesia, mechanical ventilation, and posture. METHODS: Pulmonary perfusion was analyzed with intravenous fluorescent microspheres (15 microm) in six sheep studied in four conditions: prone and awake, prone with pentobarbital-anesthesia and breathing spontaneously, prone with anesthesia and mechanical ventilation, and supine with anesthesia and mechanical ventilation. Lungs were air dried at total lung capacity and sectioned into approximately 1,100 pieces (about 2 cm3) per animal. The pieces were weighed and assigned spatial coordinates. Fluorescence was read on a spectrophotometer, and signals were corrected for piece weight and normalized to mean flow. Pulmonary blood flow heterogeneity was assessed using the coefficient of variation of flow data. RESULTS: Pentobarbital anesthesia and mechanical ventilation did not influence perfusion heterogeneity, but heterogeneity increased when the animals were in the supine posture (P < 0.01). Gravitational flow gradients were absent in the prone position but present in the supine (P < 0.001 compared with zero). Pulmonary perfusion was distributed with a hilar-to-peripheral gradient in animals breathing spontaneously (P < 0.05). CONCLUSIONS: The influence of pentobarbital anesthesia and mechanical ventilation on pulmonary perfusion heterogeneity is small compared with the effect of changes in posture. Analysis of flow gradients indicate that gravity plays a small role in determining pulmonary blood flow distribution.

Inhaled nitric oxide therapy increases blood nitrite, nitrate, and s-nitrosohemoglobin concentrations in infants with pulmonary hypertension.

PubMed

Ibrahim, Yomna I; Ninnis, Janet R; Hopper, Andrew O; Deming, Douglas D; Zhang, Amy X; Herring, Jason L; Sowers, Lawrence C; McMahon, Timothy J; Power, Gordon G; Blood, Arlin B

2012-02-01

To measure the circulating concentrations of nitric oxide (NO) adducts with NO bioactivity after inhaled NO (iNO) therapy in infants with pulmonary hypertension. In this single center study, 5 sequential blood samples were collected from infants with pulmonary hypertension before, during, and after therapy with iNO (n = 17). Samples were collected from a control group of hospitalized infants without pulmonary hypertension (n = 16) and from healthy adults for comparison (n = 12). After beginning iNO (20 ppm) whole blood nitrite levels increased approximately two-fold within 2 hours (P<.01). Whole blood nitrate levels increased to 4-fold higher than baseline during treatment with 20 ppm iNO (P<.01). S-nitrosohemoglobin increased measurably after beginning iNO (P<.01), whereas iron nitrosyl hemoglobin and total hemoglobin-bound NO-species compounds did not change. Treatment of pulmonary hypertensive infants with iNO results in increases in levels of nitrite, nitrate, and S-nitrosohemoglobin in circulating blood. We speculate that these compounds may be carriers of NO bioactivity throughout the body and account for peripheral effects of iNO in the brain, heart, and other organs. Copyright © 2012 Mosby, Inc. All rights reserved.

Does corticosteroid therapy impact fetal pulmonary artery blood flow in women at risk for preterm birth?

PubMed

Lindsley, William; Hale, Richard; Spear, Ashley; Adusumalli, Jasvant; Singh, Jasbir; DeStefano, Kimberly; Haeri, Sina

2015-09-01

Maternal corticosteroid administration in pregnancy is known to enhance fetal lung maturity in at risk fetuses. The aim of this study was to test the hypothesis that corticosteroid therapy alters fetal pulmonary blood flow in pregnancies at risk for preterm birth (PTB). We prospectively evaluated main fetal pulmonary artery (MPA) blood flow in pregnant women at risk for PTB and treated with corticosteroids (betamethasone), compared to an uncomplicated cohort without steroid therapy. The Doppler indices of interest included Peak Systolic Velocity (PSV), Resistive Index (RI), Pulsatility Index (PI), Systolic/Diastolic ratio (S/D ratio), Acceleration Time (AT), and Acceleration Time/Ejection Time Ratio (AT/ET ratio), with the latter serving as the primary outcomes due to its stability irrespective of gestational age. When compared with controls, fetuses treated with corticosteroids demonstrated significantly decreased pulmonary artery acceleration time (median: 28.89 (22.22-51.11) vs. 33.33 (22.20-57.00), p=0.006), while all other indices remained similar. We found no difference in pulmonary blood flow between fetuses who developed respiratory distress syndrome (RDS) and those that did not (31.56 +/- 6.842 vs. 32.36 +/- 7.265, p= 0.76). Our data demonstrate altered fetal pulmonary blood flow with corticosteroid therapy, possibly due to increased arterial elastance brought on by medication effect, which leads to the decreased acceleration time or possible gestational age affect. Contrary to a recent report, we did not observe any Doppler differences in fetuses with RDS, which underscores the need for further examination of this proposed association.

Spatial distribution of pulmonary blood flow in dogs in increased force environments

NASA Technical Reports Server (NTRS)

Greenleaf, J. F.; Ritman, E. L.; Chevalier, P. A.; Sass, D. J.; Wood, E. H.

1978-01-01

Spatial distribution of pulmonary blood flow during 2- to 3-min exposures to 6-8 Gy acceleration was studied, using radioactive microspheres in dogs, and compared to previously reported 1 Gy control distributions. Isotope distributions were measured by scintiscanning individual 1-cm-thick cross sections of excised, fixed lungs. Results indicate: (1) the fraction of cardiac output traversing left and right lungs did not change systematically with the duration and magnitude of acceleration; but (2) the fraction is strongly affected by the occurrence or absence of fast deep breaths, which cause an increase or decrease, respectively, in blood flow through the dependent lung; and (3) Gy acceleration caused a significant increase in relative pulmonary vascular resistance (PVR) in nondependent and dependent regions of the lung concurrent with a decrease in PVR in the midsagittal region of the thorax.

[Persistent pulmonary hypertension in a neonate caused by blood aspiration following vaginal blood loss].

PubMed

Krüse-Ruijter, M F; Zimmermann, L J I

2007-07-14

A preterm neonate, with a gestational age of 30 1/7 weeks, was born after a period of prolonged rupture of the membranes and a retroplacental haematoma causing vaginal bleeding. During admission to the neonatal intensive-care unit, mechanical ventilation was indicated because of acute respiratory failure following blood aspiration, which was causing oxygenation and ventilation problems. Endotracheal surfactant was administered and, because of persistent pulmonary hypertension of the newborn (PPHN), NO-inhalation therapy was started. A quick recovery was seen and two days post partum the patient could be extubated. Blood aspiration may cause acute respiratory problems and PPHN, with quick recovery after effective mechanical ventilation, surfactant and NO-inhalation therapy.

Evaluation of optimized bronchoalveolar lavage sampling designs for characterization of pulmonary drug distribution.

PubMed

Clewe, Oskar; Karlsson, Mats O; Simonsson, Ulrika S H

2015-12-01

Bronchoalveolar lavage (BAL) is a pulmonary sampling technique for characterization of drug concentrations in epithelial lining fluid and alveolar cells. Two hypothetical drugs with different pulmonary distribution rates (fast and slow) were considered. An optimized BAL sampling design was generated assuming no previous information regarding the pulmonary distribution (rate and extent) and with a maximum of two samples per subject. Simulations were performed to evaluate the impact of the number of samples per subject (1 or 2) and the sample size on the relative bias and relative root mean square error of the parameter estimates (rate and extent of pulmonary distribution). The optimized BAL sampling design depends on a characterized plasma concentration time profile, a population plasma pharmacokinetic model, the limit of quantification (LOQ) of the BAL method and involves only two BAL sample time points, one early and one late. The early sample should be taken as early as possible, where concentrations in the BAL fluid ≥ LOQ. The second sample should be taken at a time point in the declining part of the plasma curve, where the plasma concentration is equivalent to the plasma concentration in the early sample. Using a previously described general pulmonary distribution model linked to a plasma population pharmacokinetic model, simulated data using the final BAL sampling design enabled characterization of both the rate and extent of pulmonary distribution. The optimized BAL sampling design enables characterization of both the rate and extent of the pulmonary distribution for both fast and slowly equilibrating drugs.

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

Pulmonary edema

MedlinePlus

... congestion; Lung water; Pulmonary congestion; Heart failure - pulmonary edema ... Pulmonary edema is often caused by congestive heart failure . When the heart is not able to pump efficiently, blood ...

Pulmonary blood flow redistribution by increased gravitational force

NASA Technical Reports Server (NTRS)

Hlastala, M. P.; Chornuk, M. A.; Self, D. A.; Kallas, H. J.; Burns, J. W.; Bernard, S.; Polissar, N. L.; Glenny, R. W.

1998-01-01

This study was undertaken to assess the influence of gravity on the distribution of pulmonary blood flow (PBF) using increased inertial force as a perturbation. PBF was studied in unanesthetized swine exposed to -Gx (dorsal-to-ventral direction, prone position), where G is the magnitude of the force of gravity at the surface of the Earth, on the Armstrong Laboratory Centrifuge at Brooks Air Force Base. PBF was measured using 15-micron fluorescent microspheres, a method with markedly enhanced spatial resolution. Each animal was exposed randomly to -1, -2, and -3 Gx. Pulmonary vascular pressures, cardiac output, heart rate, arterial blood gases, and PBF distribution were measured at each G level. Heterogeneity of PBF distribution as measured by the coefficient of variation of PBF distribution increased from 0.38 +/- 0.05 to 0.55 +/- 0.11 to 0.72 +/- 0.16 at -1, -2, and -3 Gx, respectively. At -1 Gx, PBF was greatest in the ventral and cranial and lowest in the dorsal and caudal regions of the lung. With increased -Gx, this gradient was augmented in both directions. Extrapolation of these values to 0 G predicts a slight dorsal (nondependent) region dominance of PBF and a coefficient of variation of 0.22 in microgravity. Analysis of variance revealed that a fixed component (vascular structure) accounted for 81% and nonstructure components (including gravity) accounted for the remaining 19% of the PBF variance across the entire experiment (all 3 gravitational levels). The results are inconsistent with the predictions of the zone model.

Maintenance of pulmonary vasculature tone by blood derived from the inferior vena cava in a rabbit model of cavopulmonary shunt.

PubMed

Ikai, Akio; Shirai, Mikiyasu; Nishimura, Kazunobu; Ikeda, Tadashi; Kameyama, Takayuki; Ueyama, Koji; Komeda, Masashi

2005-01-01

After cavopulmonary shunt in which the superior vena cava is anastomosed to the right pulmonary artery, the right lung is in a unique condition without flow pulsatility and hepatic venous effluent. In a previous study, we reported that hypoxic pulmonary vasoconstriction disappeared in the pulmonary circulation after cavopulmonary shunt. In this study, however, to investigate the influence of pulsatility and hepatic venous effluent on hypoxic pulmonary vasoconstriction in the pulmonary circulation, we developed an alternative cavopulmonary shunt rabbit model that included hepatic venous effluent in the pulmonary circulation and reduced the pulsatility of the pulmonary arterial blood flow. We then observed the physiologic characteristics of the peripheral pulmonary artery after cavopulmonary shunt, specifically the disappearance of hypoxic pulmonary vasoconstriction. Sixteen Japanese white rabbits (12-16 weeks old) were used in this study. With general anesthesia, a cavopulmonary shunt was established by anastomosing the right superior vena cava to the right pulmonary artery in an end-to-side fashion. Of the 16 rabbits for the study, the proximal right pulmonary artery was completely ligated in 5 (atresia group) and partially ligated in 6 (stenosis group). Sham operation was performed in the remaining 5 rabbits. Two weeks later, we analyzed the response of the pulmonary artery (which was divided into three categories: segmental, lobular, and acinar level artery) to hypoxia (8% oxygen inhalation) with a specially designed video radiographic system. Morphometric analysis of the resistance pulmonary artery was done in each group after angiography. Mean pressure and pulse pressure in the right pulmonary artery were not significantly different between the atresia and stenosis groups. The mean pulmonary artery pressures in the atresia and stenosis groups were 8 and 11 mm Hg, respectively. However, the pulse pressure was less than 2 mm Hg in both groups. The baseline

Pulmonary Hypertension in Lambs Transfused with Stored Blood is Prevented by Breathing Nitric Oxide

PubMed Central

Baron, David M.; Yu, Binglan; Lei, Chong; Bagchi, Aranya; Beloiartsev, Arkadi; Stowell, Christopher P.; Steinbicker, Andrea U.; Malhotra, Rajeev; Bloch, Kenneth D.; Zapol, Warren M.

2012-01-01

Background During extended storage, erythrocytes undergo functional changes. These changes reduce the viability of erythrocytes leading to release of oxyhemoglobin, a potent scavenger of nitric oxide. We hypothesized that transfusion of ovine packed erythrocytes (PRBC) stored for prolonged periods would induce pulmonary vasoconstriction in lambs, and that reduced vascular nitric oxide concentrations would increase this vasoconstrictor effect. Methods We developed a model of autologous stored blood transfusion in lambs (n=36). Leukoreduced blood was stored for either 2 days (fresh PRBC) or 40 days (stored PRBC). Fresh or stored PRBC were transfused into donors instrumented for awake hemodynamic measurements. Hemodynamic effects of PRBC transfusion were also studied after infusion of NG-nitro-L-arginine methyl-ester (25 mg/kg) or during inhalation of nitric oxide (80 ppm). Results Cell-free hemoglobin levels were higher in the supernatant of stored PRBC than in supernatant of fresh PRBC (Mean±SD, 148±20 versus 41±13 mg/dl, respectively, P<0.001). Pulmonary artery pressure during transfusion of stored PRBC transiently increased from 13±1 to 18±1 mmHg (P<0.001) and was associated with increased plasma hemoglobin concentrations. NG-nitro-L-arginine methyl-ester potentiated the increase in pulmonary arterial pressure induced by transfusing stored PRBC, whereas inhalation of nitric oxide prevented the vasoconstrictor response. Conclusions Our results suggest that patients with reduced vascular nitric oxide levels due to endothelial dysfunction may be more susceptible to adverse effects of transfusing blood stored for prolonged periods. These patients might benefit from transfusion of fresh PRBC, when available, or inhaled nitric oxide supplementation to prevent the pulmonary hypertension associated with transfusion of stored PRBC. PMID:22293717

Lung remodeling in a porcine model of cyanotic congenital heart defect with decreased pulmonary blood flow.

PubMed

Xu, Yaoqiang; Liu, Yinglong; Li, Zhiqiang; Su, Junwu; Li, Gang; Sun, Lizhong

2012-09-01

Hypoperfusion of the pulmonary vascular bed under the condition of congenital cardiac malformations may lead to progressive pulmonary vascular disease. To improve the mechanistic understanding of this disease, we examined the biochemical and morphological changes of the lung in a relevant animal model and provided valuable insights into the underlying mechanisms of the pathogenesis of pulmonary hypotension. A model of congenital heart defect with decreased pulmonary blood flow was implemented into 8 piglets (the cyanosis group). Another 8 piglets underwent a sham operation (the control group). Two months postoperatively, lung biopsy specimens were harvested for the measurement of the expression levels of MMP-2, MMP-9, TIMP-1, VEGF, and type I and type III collagens. Moreover, the light-microscopic morphology, morphometry, and ultrastructure of lobes were examined. Compared to the controls, the histopathological changes of the pulmonary vasculature in the cyanosis group showed evident hypoplasia and degeneration. The expression levels of MMP-2, MMP-9, TIMP-1, VEGF, and type I collagen, as well as the microvessel density, in the cyanosis group were significantly lower than those in the control group, whereas the level of type III collagen in the cyanosis group was significantly higher than that in the control group. The observed morphological changes may represent an adaptive reaction to the prolonged decrease of pulmonary blood flow. The underlying mechanism of lung remodeling may be attributed to the changes in the expression of structural proteins and cytokines in the pulmonary extracellular matrix induced by modulating factors.

Isolated Major Aortopulmonary Collateral as the Sole Pulmonary Blood Supply to an Entire Lung Segment.

PubMed

Kim, Hannah S; Grady, R Mark; Shahanavaz, Shabana

2017-01-01

Congenital systemic-to-pulmonary collateral arteries or major aortopulmonary collaterals are associated with cyanotic congenital heart disease with decreased pulmonary blood flow. Though it is usually associated with congenital heart diseases, there is an increased incidence of isolated acquired aortopulmonary collaterals in premature infants with chronic lung disease. Interestingly, isolated congenital aortopulmonary collaterals can occur without any lung disease, which may cause congestive heart failure and require closure. We present a neonate with an echocardiogram that showed only left-sided heart dilation. Further workup with a CT angiogram demonstrated an anomalous systemic artery from the descending thoracic aorta supplying the left lower lobe. He eventually developed heart failure symptoms and was taken to the catheterization laboratory for closure of the collateral. However, with the collateral being the only source of blood flow to the entire left lower lobe, he required surgical unifocalization. Isolated aortopulmonary collaterals without any other congenital heart disease or lung disease are rare. Our patient is the first reported case to have an isolated aortopulmonary collateral being the sole pulmonary blood supply to an entire lung segment. Due to its rarity, there is still much to learn about the origin and development of these collaterals that possibly developed prenatally.

[Role of MRI for detection and characterization of pulmonary nodules].

PubMed

Sommer, G; Koenigkam-Santos, M; Biederer, J; Puderbach, M

2014-05-01

Due to physical and technical limitations, magnetic resonance imaging (MRI) has hitherto played only a minor role in image-based diagnostics of the lungs. However, as a consequence of important methodological developments during recent years, MRI has developed into a technically mature and clinically well-proven method for specific pulmonary questions. The purpose of this article is to provide an overview on the currently available sequences and techniques for assessment of pulmonary nodules and analyzes the clinical significance according to the current literature. The main focus is on the detection of lung metastases, the detection of primary pulmonary malignancies in high-risk individuals and the differentiation between pulmonary nodules of benign and malignant character. The MRI technique has a sensitivity of approximately 80 % for detection of malignant pulmonary nodules compared to the reference standard low-dose computed tomography (CT) and is thus somewhat inferior to CT. Advantages of MRI on the other hand are a higher specificity in differentiating malignant and benign pulmonary nodules and the absence of ionizing radiation exposure. A systematic use of MRI as a primary tool for detection and characterization of pulmonary nodules is currently not recommended due to insufficient data. The diagnostic potential of MRI for early detection and staging of malignant pulmonary diseases, however, seems promising. Therefore, further evaluation of MRI as a secondary imaging modality in clinical trials is highly warranted.

Effects of posture on blood flow diversion by hypoxic pulmonary vasoconstriction in dogs

NASA Technical Reports Server (NTRS)

Walther, S. M.; Domino, K. B.; Hlastala, M. P.

1998-01-01

We used differential excretion of sulphur hexafluoride from the left and right lung to measure blood flow diversion by hypoxic pulmonary vasoconstriction (HPV) in the prone and supine positions in dogs (n = 9). Gas exchange was assessed using the multiple inert gas elimination technique. Blood flow diversion from the hypoxic (3% oxygen) left lung was mean 70.7 (SD 11.2)% in the supine compared with 57.0 (12.1)% in the prone position (P < 0.02). The supine position was associated with increased perfusion to low VA/Q regions (P < 0.05). The increased flow diversion with hypoxia in the supine position was associated with more ventilation to high VA/Q regions (P < 0.05). We conclude that flow diversion by hypoxic pulmonary vasoconstriction is greater in the supine position. This effect could contribute to the variable response in gas exchange with positioning in patients with ARDS.

Choice of marker for assessment of RV dysfunction in acute pulmonary embolism : NT-proBNP, pulmonary artery systolic pressure, mean arterial pressure, or blood pressure index.

PubMed

Ates, H; Ates, I; Kundi, H; Yilmaz, F M

2017-12-01

We aimed to examine the value of NT-proBNP, pulmonary artery systolic pressure (PASP), blood pressure index (BPI), and mean arterial pressure (MAP) in the determination of right ventricular dysfunction (RVD) in patients with acute pulmonary embolism (APE). A total of 547 patients diagnosed with APE were included in the study. Demographic characteristics and comorbid conditions of patients were recorded in patient files. For blood pressure measurement, a calibrated digital blood pressure monitor was used at regular intervals. Blood samples were taken from patients at the time of admission for hemogram, biochemical, and hemostasis blood tests. Echocardiography was performed on all patients to detect RVD and evaluate pulmonary artery pressure. PASP (p < 0.001), MAP (p < 0.001), diastolic blood pressure (p < 0.001), D‑dimer (p = 0.001), NT-proBNP (p = 0.001), white blood cell (p < 0.001), and platelet (p = 0.001) counts were higher in APE patients with RVD compared with those without RVD, whereas the mean BPI level (p < 0.001) was lower. BPI had a negative correlation with PASP, NT-proBNP, platelet count, and triglyceride levels in patients with RVD. In regression analysis, BPI and PASP were found to be independent predictors of RVD. In receiver operating characteristic curve analysis, BPI (AUC ± SE = 0.975 ± 0.006; p < 0.001) was found to be the best predictor of RVD with a higher sensitivity (92.8%) and specificity (100%). We found that BPI had a better diagnostic discrimination for RVD compared with PASP and NT-proBNP.

Assessment of bronchial and pulmonary blood supply in non-small cell lung cancer subtypes using computed tomography perfusion.

PubMed

Nguyen-Kim, Thi Dan Linh; Frauenfelder, Thomas; Strobel, Klaus; Veit-Haibach, Patrick; Huellner, Martin W

2015-03-01

The aim of this study was to investigate the dual blood supply of non-small cell lung cancer (NSCLC) and its association with tumor subtype, size, and stage, using computed tomography perfusion (CTP). A total of 54 patients (median age, 65 years; range, 42-79 years; 15 women, 39 men) with suspected lung cancer underwent a CTP scan of the lung tumor. Pulmonary and bronchial vasculature regions of interest were used to calculate independently CTP parameters (blood flow [BF], blood volume [BV], and mean transit time [MTT]) of the tumor tissue. The mean and maximum pulmonary and bronchial perfusion indexes (PImean and PImax) were calculated. The tumoral volume and the largest tumoral diameter were assessed. Differences in CTP parameters and indexes among NSCLC subtypes, tumor stages and tumor dimensions were analyzed using non-parametric tests. According to biopsy, 37 patients had NSCLC (22 adenocarcinomas [ACs], 8 squamous cell carcinomas [SCCs], 7 large-cell carcinomas [LCC]). The mean bronchial BF/pulmonary BF, bronchial BV/pulmonary BV, and bronchial MTT/pulmonary MTT was 41.2 ± 30.0/36.9 ± 24.2 mL/100 mL/min, 11.4 ± 9.7/10.4 ± 9.4 mL/100 mL, and 11.4 ± 4.3/14.9 ± 4.4 seconds, respectively. In general, higher bronchial BF than pulmonary BF was observed in NSCLC (P = 0.014). Using a tumoral volume cutoff of 3.5 cm, a significant difference in pulmonary PImax was found (P = 0.028). There was a significantly higher mean pulmonary BF in LCCs and SCCs compared with ACs (P = 0.018 and P = 0.044, respectively), whereas the mean bronchial BF was only significantly higher in LCCs compared with ACs (P = 0.024). Correspondingly, the PImax was significantly higher in LCCs and SCCs than in ACs (P = 0.001 for both). Differences between bronchial and pulmonary PImean and PImax among T stages and Union Internationale Contre le Cancer stages were not statistically significant (P values ranging from 0.691 to 0.753). The known dual blood supply of NSCLC, which depends on tumor

Expression Profile of Cytokines and Enzymes mRNA in Blood Leukocytes of Dogs with Leptospirosis and Its Associated Pulmonary Hemorrhage Syndrome.

PubMed

Maissen-Villiger, Carla A; Schweighauser, Ariane; van Dorland, H Anette; Morel, Claudine; Bruckmaier, Rupert M; Zurbriggen, Andreas; Francey, Thierry

2016-01-01

Dogs with leptospirosis show similar organ manifestations and disease course as human patients, including acute kidney injury and pulmonary hemorrhage, making this naturally-occurring infection a good animal model for human leptospirosis. Expression patterns of cytokines and enzymes have been correlated with disease manifestations and clinical outcome in humans and animals. The aim of this study was to describe mRNA expression of pro- and anti-inflammatory mediators in canine leptospirosis and to compare it with other renal diseases to identify patterns characterizing the disease and especially its pulmonary form. The mRNA abundance of cytokines (IL-1α, IL-1β, IL-8, IL-10, TNF-α, TGF-β) and enzymes (5-LO, iNOS) was measured prospectively in blood leukocytes from 34 dogs with severe leptospirosis and acute kidney injury, including 22 dogs with leptospirosis-associated pulmonary hemorrhages. Dogs with leptospirosis were compared to 14 dogs with acute kidney injury of other origin than leptospirosis, 8 dogs with chronic kidney disease, and 10 healthy control dogs. Canine leptospirosis was characterized by high 5-LO and low TNF-α expression compared to other causes of acute kidney injury, although the decreased TNF-α expression was also seen in chronic kidney disease. Leptospirosis-associated pulmonary hemorrhage was not characterized by a specific pattern, with only mild changes noted, including increased IL-10 and decreased 5-LO expression on some days in affected dogs. Fatal outcome from pulmonary hemorrhages was associated with low TNF-α, high IL-1β, and high iNOS expression, a pattern possibly expressed also in dogs with other forms of acute kidney injury. The patterns of cytokine and enzyme expression observed in the present study indicate a complex pro- and anti-inflammatory response to the infection with leptospires. The recognition of these signatures may be of diagnostic and prognostic relevance for affected individuals and they may indicate options

129 Xe chemical shift in human blood and pulmonary blood oxygenation measurement in humans using hyperpolarized 129 Xe NMR.

PubMed

Norquay, Graham; Leung, General; Stewart, Neil J; Wolber, Jan; Wild, Jim M

2017-04-01

To evaluate the dependency of the 129 Xe-red blood cell (RBC) chemical shift on blood oxygenation, and to use this relation for noninvasive measurement of pulmonary blood oxygenation in vivo with hyperpolarized 129 Xe NMR. Hyperpolarized 129 Xe was equilibrated with blood samples of varying oxygenation in vitro, and NMR was performed at 1.5 T and 3 T. Dynamic in vivo NMR during breath hold apnea was performed at 3 T on two healthy volunteers following inhalation of hyperpolarized 129 Xe. The 129 Xe chemical shift in RBCs was found to increase nonlinearly with blood oxygenation at 1.5 T and 3 T. During breath hold apnea, the 129 Xe chemical shift in RBCs exhibited a periodic time modulation and showed a net decrease in chemical shift of ∼1 ppm over a 35 s breath hold, corresponding to a decrease of 7-10 % in RBC oxygenation. The 129 Xe-RBC signal amplitude showed a modulation with the same frequency as the 129 Xe-RBC chemical shift. The feasibility of using the 129 Xe-RBC chemical shift to measure pulmonary blood oxygenation in vivo has been demonstrated. Correlation between 129 Xe-RBC signal and 129 Xe-RBC chemical shift modulations in the lung warrants further investigation, with the aim to better quantify temporal blood oxygenation changes in the cardiopulmonary vascular circuit. Magn Reson Med 77:1399-1408, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

Effect of Increased Blood Flow on Pulmonary Circulation Before and During High Altitude Acclimatization.

PubMed

Hilty, Matthias Peter; Müller, Andrea; Flück, Daniela; Siebenmann, Christoph; Rasmussen, Peter; Keiser, Stefanie; Auinger, Katja; Lundby, Carsten; Maggiorini, Marco

2016-12-01

Matthias Peter Hilty, Andrea Mueller, Daniela Flück, Christoph Siebenmann, Peter Rasmussen, Stefanie Keiser, Katja Auinger, Carsten Lundby, and Marco Maggiorini. Effect of increased blood flow on the pulmonary circulation before and during high altitude acclimatization. High Alt Med Biol. 17:305-314, 2016.-Introduction and Methods: Acute exposure to high altitude increases pulmonary artery pressure (Ppa) and pulmonary vascular resistance (PVR). The evolution of Ppa and PVR with continuous hypoxic exposure remains, however, elusive. To test the hypothesis that altitude exposure leads to a persistent elevation in Ppa and PVR throughout acclimatization in seven healthy male subjects, echocardiography was performed at sea level (SL; 488 m) weekly during a 4-week sojourn at 3454 m (HA1-HA4) and upon return (SL2). Pulmonary artery catheterization and bilateral thigh cuff release maneuver were performed at SL and HA3 to study the properties of pulmonary circulation after 3 weeks of acclimatization. Pulmonary artery catheter determined that systolic Ppa (mean ± SEM) was increased from 20 ± 1 at SL to 27 ± 2 mmHg at HA3 (p < 0.01). Echocardiography assessed that systolic Ppa remained equally increased throughout acclimatization (26 ± 2, 25 ± 2, 25 ± 2, and 24 ± 2 mmHg at HA1-HA4; p = 0.93) and returned to baseline upon return (17 ± 2, 18 ± 1 mmHg at SL, SL2; p = 0.3). The same was shown for PVR. Right heart function remained unaffected. Thigh cuff release maneuvers at SL and HA3 resulted in similar increase in cardiac output (2.5 ± 0.5 and 2.2 ± 0.4 L/min; p = 0.61) without affecting mean Ppa. Prolonged altitude exposure leads to a persistent increase in Ppa and PVR without affecting right heart function and is fully reversible within 1 week after return to SL. The thigh cuff release maneuver-induced increase in cardiac output suggests a preserved ability of pulmonary circulation to cope with

Pulmonary Arterial Hypertension

MedlinePlus

Pulmonary Arterial Hypertension What Is Pulmonary Hypertension? To understand pulmonary hypertension (PH) it helps to understand how blood ows throughout your body. While the heart is one organ, it ...

Inhaled nitrite reverses hemolysis-induced pulmonary vasoconstriction in newborn lambs without blood participation

PubMed Central

Blood, Arlin B.; Schroeder, Hobe J.; Terry, Michael H.; Merrill-Henry, Jeanette; Bragg, Shannon L.; Vrancken, Kurt; Liu, Taiming; Herring, Jason L.; Sowers, Lawrence C.; Wilson, Sean M.; Power, Gordon G.

2011-01-01

Background Nitrite can be converted to nitric oxide (NO) by a number of different biochemical pathways. In newborn lambs an aerosol of inhaled nitrite has been found to reduce pulmonary blood pressure, possibly acting via conversion to NO by reaction with intraerythrocytic deoxyhemoglobin. If so, the vasodilating effects of nitrite would be attenuated by free hemoglobin in plasma that would rapidly scavenge NO. Methods and Results Pulmonary vascular pressures and resistances to flow were measured in anesthetized newborn lambs. Plasma hemoglobin concentrations were then elevated, resulting in marked pulmonary hypertension. This effect was attenuated if infused hemoglobin was first oxidized to methemoglobin which does not scavenge NO. These results further implicate NO as a tonic pulmonary vasodilator. Next, while free hemoglobin continued to be infused, the lambs were given inhaled NO gas (20 ppm), inhaled sodium nitrite aerosol (0.87 M), or an intravascular nitrite infusion (3 mg·hr−1 bolus, 5 mg·kg−1·hr−1 infusion). Inhaled NO and inhaled nitrite aerosol both resulted in pulmonary vasodilation. Intravascular infusion of nitrite, however, did not. Increases in exhaled NO gas were observed while breathing the nitrite aerosol (~20 ppb NO) but not during intravascular infusion of nitrite. Conclusions We conclude that the pulmonary vasodilating effect of inhaled nitrite results from its conversion to NO in airway and parenchymal lung tissue and is not dependent on reactions with deoxyhemoglobin in the pulmonary circulation. Inhaled nitrite aerosol remains a promising candidate to reduce pulmonary hypertension in clinical application. PMID:21282501

Blood Perfusion in Microfluidic Models of Pulmonary Capillary Networks: Role of Geometry and Hematocrit

NASA Astrophysics Data System (ADS)

Stauber, Hagit; Waisman, Dan; Sznitman, Josue; Technion-IIT Team; Department of Neonatology Carmel Medical Center; Faculty of Medicine-Technion IIT Collaboration

2015-11-01

Microfluidic platforms are increasingly used to study blood microflows at true physiological scale due to their ability to overcome manufacturing obstacle of complex anatomical morphologies, such as the organ-specific architectures of the microcirculation. In the present work, we utilize microfluidic platforms to devise in vitro models of the underlying pulmonary capillary networks (PCN), where capillary lengths and diameters are similar to the size of RBCs (~ 5-10 μm). To better understand flow characteristics and dispersion of red blood cells (RBCs) in PCNs, we have designed microfluidic models of alveolar capillary beds inspired by the seminal ``sheet flow'' model of Fung and Sobin (1969). Our microfluidic PCNs feature confined arrays of staggered pillars with diameters of ~ 5,7 and 10 μm, mimicking the dense structure of pulmonary capillary meshes. The devices are perfused with suspensions of RBCs at varying hematocrit levels under different flow rates. Whole-field velocity patterns using micro-PIV and single-cell tracking using PTV are obtained with fluorescently-labelled RBCs and discussed. Our experiments deliver a real-scale quantitative description of RBC perfusion characteristics across the pulmonary capillary microcirculation.

Pulmonary endothelial pavement patterns.

PubMed Central

Kibria, G; Heath, D; Smith, P; Biggar, R

1980-01-01

The appearance of the endothelial pavement pattern was studied in the pulmonary trunk, pulmonary veins, aorta, and inferior vena cava of the rat by means of silver staining of the cell borders. The endothelial cell in each of the four blood vessels was found to have its own distinctive shape, fusiform and pointed in the direction of blood flow in the case of the aorta and larger and more rectangular in the pulmonary trunk and pulmonary veins. Detailed quantitation of the dimensions and surface area of the endothelial cells in each blood vessel was carried out by a photographic technique. Pulmonary hypertension was induced in one group of rats by feeding them on Crotalaria spectabilis seeds. The endothelial pavement pattern in their pulmonary trunks became disrupted with many of the cells assuming a fusiform shape reminiscent of aortic endothelium. Many small, new endothelial cells formed in the pulmonary trunk suggesting division of cells to line the enlarging blood vessels. In contrast the endothelial cells of the inferior vena cava merely increased in size to cope with the dilatation of this vein. Images PMID:7385090

Pulmonary Hypertension Overview

MedlinePlus

... well as sleep apnea, are common causes of secondary pulmonary hypertension. Other causes include the following: Congestive heart failure Birth defects in the heart Chronic pulmonary thromboembolism (blood clots in the pulmonary arteries) Acquired immunodeficiency syndrome ( ...

Neutrophil Depletion Suppresses Pulmonary Vascular Hyperpermeability and Occurrence of Pulmonary Edema Caused by Hantavirus Infection in C.B-17 SCID Mice

PubMed Central

Koma, Takaaki; Yoshimatsu, Kumiko; Nagata, Noriyo; Sato, Yuko; Shimizu, Kenta; Yasuda, Shumpei P.; Amada, Takako; Nishio, Sanae; Hasegawa, Hideki

2014-01-01

ABSTRACT Hantavirus infections are characterized by vascular hyperpermeability and neutrophilia. However, the pathogenesis of this disease is poorly understood. Here, we demonstrate for the first time that pulmonary vascular permeability is increased by Hantaan virus infection and results in the development of pulmonary edema in C.B-17 severe combined immunodeficiency (SCID) mice lacking functional T cells and B cells. Increases in neutrophils in the lung and blood were observed when pulmonary edema began to be observed in the infected SCID mice. The occurrence of pulmonary edema was inhibited by neutrophil depletion. Moreover, the pulmonary vascular permeability was also significantly suppressed by neutrophil depletion in the infected mice. Taken together, the results suggest that neutrophils play an important role in pulmonary vascular hyperpermeability and the occurrence of pulmonary edema after hantavirus infection in SCID mice. IMPORTANCE Although hantavirus infections are characterized by the occurrence of pulmonary edema, the pathogenic mechanism remains largely unknown. In this study, we demonstrated for the first time in vivo that hantavirus infection increases pulmonary vascular permeability and results in the development of pulmonary edema in SCID mice. This novel mouse model for human hantavirus infection will be a valuable tool and will contribute to elucidation of the pathogenetic mechanisms. Although the involvement of neutrophils in the pathogenesis of hantavirus infection has largely been ignored, the results of this study using the mouse model suggest that neutrophils are involved in the vascular hyperpermeability and development of pulmonary edema in hantavirus infection. Further study of the mechanisms could lead to the development of specific treatment for hantavirus infection. PMID:24719427

Redistribution of pulmonary blood flow impacts thermodilution-based extravascular lung water measurements in a model of acute lung injury

PubMed Central

Easley, R. Blaine; Mulreany, Daniel G.; Lancaster, Christopher T.; Custer, Jason W.; Fernandez-Bustamante, Ana; Colantuoni, Elizabeth; Simon, Brett A.

2009-01-01

Background Studies using transthoracic thermodilution have demonstrated increased extravascular lung water (EVLW) measurements attributed to progression of edema and flooding during sepsis and acute lung injury. We hypothesize that redistribution of pulmonary blood flow can cause increased apparent EVLW secondary to increased perfusion of thermally silent tissue, not increased lung edema. Methods Anesthetized, mechanically ventilated canines were instrumented with PiCCO® (Pulsion Medical, Munich, Germany) catheters and underwent lung injury by repetitive saline lavage. Hemodynamic and respiratory physiologic data were recorded. After stabilized lung injury, endotoxin was administered to inactivate hypoxic pulmonary vasoconstriction. Computerized tomographic imaging was performed to quantify in vivo lung volume, total tissue (fluid) and air content, and regional distribution of blood flow. Results Lavage injury caused an increase in airway pressures and decreased arterial oxygen content with minimal hemodynamic effects. EVLW and shunt fraction increased after injury and then markedly following endotoxin administration. Computerized tomographic measurements quantified an endotoxin-induced increase in pulmonary blood flow to poorly aerated regions with no change in total lung tissue volume. Conclusions The abrupt increase in EVLW and shunt fraction after endotoxin administration is consistent with inactivation of hypoxic pulmonary vasoconstriction and increased perfusion to already flooded lung regions that were previously thermally silent. Computerized tomographic studies further demonstrate in vivo alterations in regional blood flow (but not lung water) and account for these alterations in shunt fraction and EVLW. PMID:19809280

Establishment of a canine model of acute pulmonary embolism with definite right ventricular dysfunction through introduced autologous blood clots.

PubMed

Zhao, Lin-Bo; Jia, Zhen-Yu; Lu, Guang-Dong; Zhu, Yin-Su; Jing, Lei; Shi, Hai-Bin

2015-04-01

To establish a canine model of acute pulmonary embolism (PE) with right ventricular (RV) dysfunction using autologous blood clots and evaluate by echocardiography and contrast-enhanced Computed Tomography (CT). Autologous blood clots formed in vitro were introduced sequentially into the pulmonary arteries of eight healthy mixed-breed dogs while monitoring pulmonary and systemic hemodynamic function. Blood clots were injected until the mean pulmonary artery pressure (MPAP) reached two-three times the baseline pressure, which was maintained up to 1 hour. The RV function was assessed by echocardiography and ECG-gated dual-source contrast CT. All animals survived the imaging procedure. The post-injection pulmonary angiograms showed extensive PE, and MPAP increased from 16.50±2.45 mmHg to 43.13±4.91 mmHg (P<0.001). On echocardiography, the RV fractional area change decreased from 42.06±3.36 to 27.96±3.54 (P<0.001), and the RV myocardial performance increased from 0.20±0.05 to 0.63±0.16 (P<0.001). On CT, the RV end-systolic volume increased from 11.11±1.81 ml to 24.71±4.60 ml (P<0.001), RV end-diastolic volume from 20.73±2.83 ml to 34.63±5.76 ml (P<0.001), and the four-chamber RV/left ventricular diameter ratio from 0.38±0.07 to 0.81±0.14 (P<0.001). Acute PE with RV dysfunction was established in a large animal model through controlled injection of autologous blood clots, which may be useful for developing and evaluating new therapeutic approaches for acute PE with RV dysfunction. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

The relationship between pulmonary artery wedge pressure and pulmonary blood volume derived from contrast echocardiography: A proof-of-concept study.

PubMed

Monahan, Ken; Lenihan, Daniel; Brittain, Evan L; Saliba, Linda; Piana, Robert N; Robison, Leslie L; Hudson, Melissa M; Armstrong, Gregory T

2018-05-14

Pulmonary transit time (PTT) obtained from contrast echocardiography is a marker of global cardiopulmonary function. Pulmonary blood volume (PBV), derived from PTT, may be a noninvasive surrogate for left-sided filling pressures, such as pulmonary artery wedge pressure (PAWP). We sought to assess the relationship between PBV obtained from contrast echocardiography and PAWP. Participants were adult survivors of childhood cancer that had contrast echocardiography performed nearly simultaneously with right-heart catheterization. PTT was derived from time-intensity curves of contrast passage through the right ventricle (RV) and left atrium (LA). PBV relative to overall stroke volume (rPBV) was estimated from the product of PTT and heart rate during RV-LA transit. PAWP was obtained during standard right-heart catheterization. The Spearman correlation coefficient was used to assess the relationship between rPBV and PAWP. The study population consisted of 7 individuals who had contrast echocardiography and right-heart catheterization within 3 hours of each other. There was a wide range of right atrial (1-17 mm Hg), mean pulmonary artery (18-42 mm Hg), and PAW pressures (4-26 mm Hg) as well as pulmonary vascular resistance (<1-6 Wood Units). We observed a statistically significant correlation between rPBV and PAWP (r = .85; P = .02). Relative PBV derived from contrast echocardiography correlates with PAWP. If validated in larger studies, rPBV could potentially be used as an alternative to invasively determine left-sided filling pressure. © 2018 Wiley Periodicals, Inc.

Treatment for unstable pulmonary sequestration injury in patient with severe blunt trauma: A case report.

PubMed

Hiraki, Sakiko; Okada, Yohei; Arai, Yusuke; Ishii, Wataru; Iiduka, Ryoji

2017-08-01

Pulmonary sequestration is a congenital malformation characterized by nonfunctioning tissue not communicating with the tracheobronchial tree. As the blood pressure in the artery feeding the sequestrated lung tissue is higher than that in the normal pulmonary artery, the risk of massive hemorrhage in pulmonary sequestration is high. We herein present the first case of a severe blunt trauma patient with unstable pulmonary sequestration injury. The mechanism of pulmonary sequestration injury is vastly different than that of injury to normal lung. We suggest that proximal feeding artery embolization should be performed before surgical intervention in patients with massive hemorrhage of pulmonary sequestration due to severe chest trauma.

Magnetic Resonance Characterization of Cardiac Adaptation and Myocardial Fibrosis in Pulmonary Hypertension Secondary to Systemic-To-Pulmonary Shunt.

PubMed

Pereda, Daniel; García-Lunar, Inés; Sierra, Federico; Sánchez-Quintana, Damián; Santiago, Evelyn; Ballesteros, Constanza; Encalada, Juan F; Sánchez-González, Javier; Fuster, Valentín; Ibáñez, Borja; García-Álvarez, Ana

2016-09-01

Pulmonary hypertension (PH) and right ventricular (RV) dysfunction are strong predictors of morbidity and mortality among patients with congenital heart disease. Early detection of RV involvement may be useful in the management of these patients. We aimed to assess progressive cardiac adaptation and quantify myocardial extracellular volume in an experimental porcine model of PH because of aorto-pulmonary shunt using cardiac magnetic resonance (CMR). To characterize serial cardiac adaptation, 12 pigs (aorto-pulmonary shunt [n=6] or sham operation [n=6]) were evaluated monthly with right heart catheterization, CMR, and computed tomography during 4 months, followed by pathology analysis. Extracellular volume by CMR in different myocardial regions was studied in 20 animals (aorto-pulmonary shunt [n=10] or sham operation [n=10]) 3 months after the intervention. All shunted animals developed PH. CMR evidenced progressive RV hypertrophy and dysfunction secondary to increased afterload and left ventricular dilatation secondary to volume overload. Shunt flow by CMR strongly correlated with PH severity, left ventricular end-diastolic pressure, and left ventricular dilatation. T1-mapping sequences demonstrated increased extracellular volume at the RV insertion points, the interventricular septum, and the left ventricular lateral wall, reproducing the pattern of fibrosis found on pathology. Extracellular volume at the RV insertion points strongly correlated with pulmonary hemodynamics and RV dysfunction. Prolonged systemic-to-pulmonary shunting in growing piglets induces PH with biventricular remodeling and myocardial fibrosis that can be detected and monitored using CMR. These results may be useful for the diagnosis and management of congenital heart disease patients with pulmonary overcirculation. © 2016 American Heart Association, Inc.

Teaching the effects of gravity and intravascular and alveolar pressures on the distribution of pulmonary blood flow using a classic paper by West et al.

PubMed

Levitzky, Michael G

2006-03-01

"Distribution of blood flow in isolated lung; relation to vascular and alveolar pressures" by J. B. West, C. T. Dollery, and A. Naimark (J Appl Physiol 19: 713-724, 1964) is a classic paper, although it has not yet been included in the Essays on the American Physiological Society Classic Papers Project (http://www.the-aps.org/publications/classics/). This is the paper that originally described the "zones of the lung." The final figure in the paper, which synthesizes the results and discussion, is now seen in most textbooks of physiology or respiratory physiology. The paper is also a model of clear, concise writing. The paper and its final figure can be used to teach or review a number of physiological concepts. These include the effects of gravity on pulmonary blood flow and pulmonary vascular resistance; recruitment and distention of pulmonary vessels; the importance of the transmural pressure on the diameter of collapsible distensible vessels; the Starling resistor; the interplay of the pulmonary artery, pulmonary vein, and alveolar pressures; and the vascular waterfall. In addition, the figure can be used to generate discovery learning and discussion of several physiological or pathophysiological effects on pulmonary vascular resistance and the distribution of pulmonary blood flow.

Right Ventricular Hemodynamics in Patients with Pulmonary Hypertension

NASA Astrophysics Data System (ADS)

Browning, James; Fenster, Brett; Hertzberg, Jean; Schroeder, Joyce

2012-11-01

Recent advances in cardiac magnetic resonance imaging (CMR) have allowed for characterization of blood flow in the right ventricle (RV), including calculation of vorticity and circulation, and qualitative visual assessment of coherent flow patterns. In this study, we investigate qualitative and quantitative differences in right ventricular hemodynamics between subjects with pulmonary hypertension (PH) and normal controls. Fifteen (15) PH subjects and 10 age-matched controls underwent same day 3D time resolved CMR and echocardiography. Echocardiography was used to determine right ventricular diastolic function as well as pulmonary artery systolic pressure (PASP). Velocity vectors, vorticity vectors, and streamlines in the RV were visualized in Paraview and total RV Early (E) and Atrial (A) wave diastolic vorticity was quantified. Visualizations of blood flow in the RV are presented for PH and normal subjects. The hypothesis that PH subjects exhibit different RV vorticity levels than normals during diastole is tested and the relationship between RV vorticity and PASP is explored. The mechanics of RV vortex formation are discussed within the context of pulmonary arterial pressure and right ventricular diastolic function coincident with PH.

Lung function and pulmonary artery blood flow following prenatal maternal retinoic acid and imatinib in the nitrofen model of congenital diaphragmatic hernia.

PubMed

Burgos, Carmen Mesas; Davey, Marcus G; Riley, John S; Jia, Huimin; Flake, Alan W; Peranteau, William H

2017-12-19

Lung and pulmonary vascular maldevelopment in congenital diaphragmatic hernia (CDH) results in significant morbidity and mortality. Retinoic acid (RA) and imatinib have been shown to improve pulmonary morphology following prenatal administration in the rat nitrofen-induced CDH model. It remains unclear if these changes translate into improved function. We evaluated the effect of prenatal RA and imatinib on postnatal lung function, structure, and pulmonary artery (PA) blood flow in the rat CDH model. Olive oil or nitrofen was administered alone or in combination with RA or imatinib to pregnant rats. Pups were assessed for PA blood flow by ultrasound and pulmonary function/morphology following delivery, intubation, and short-term ventilation. Neither RA nor imatinib had a negative effect on lung and body growth. RA accelerated lung maturation indicated by increased alveoli number and thinner interalveolar septa and was associated with decreased PA resistance and improved oxygenation. With the exception of a decreased PA pulsatility index, no significant changes in morphology and pulmonary function were noted following imatinib. Prenatal treatment with RA but not imatinib was associated with improved pulmonary morphology and function, and decreased pulmonary vascular resistance. This study highlights the potential of prenatal pharmacologic therapies, such as RA, for management of CDH. Copyright © 2017 Elsevier Inc. All rights reserved.

Home-based pulmonary rehabilitation improves clinical features and systemic inflammation in chronic obstructive pulmonary disease patients.

PubMed

do Nascimento, Eloisa Sanches Pereira; Sampaio, Luciana Maria Malosá; Peixoto-Souza, Fabiana Sobral; Dias, Fernanda Dultra; Gomes, Evelim Leal Freitas Dantas; Greiffo, Flavia Regina; Ligeiro de Oliveira, Ana Paula; Stirbulov, Roberto; Vieira, Rodolfo Paula; Costa, Dirceu

2015-01-01

Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by chronic airflow limitation that leads beyond the pulmonary changes to important systemic effects. COPD is characterized by pulmonary and systemic inflammation. However, increases in the levels of inflammatory cytokines in plasma are found even when the disease is stable. Pulmonary rehabilitation improves physical exercise capacity and quality of life and decreases dyspnea. The aim of this study was to evaluate whether a home-based pulmonary rehabilitation (HBPR) program improves exercise tolerance in COPD patients, as well as health-related quality of life and systemic inflammation. This prospective study was conducted at the Laboratory of Functional Respiratory Evaluation, Nove de Julho University, São Paulo, Brazil. After anamnesis, patients were subjected to evaluations of health-related quality of life and dyspnea, spirometry, respiratory muscle strength, upper limbs incremental test, incremental shuttle walk test, and blood test for quantification of systemic inflammatory markers (interleukin [IL]-6 and IL-8). At the end of the evaluations, patients received a booklet containing the physical exercises to be performed at home, three times per week for 8 consecutive weeks. Around 25 patients were enrolled, and 14 completed the pre- and post-HBPR ratings. There was a significant increase in the walked distance and the maximal inspiratory pressure, improvements on two components from the health-related quality-of-life questionnaire, and a decrease in plasma IL-8 levels after the intervention. The HBPR is an important and viable alternative to pulmonary rehabilitation for the treatment of patients with COPD; it improves exercise tolerance, inspiratory muscle strength, quality of life, and systemic inflammation in COPD patients.

Blood Level of Polymorphonuclear Neutrophil Leukocytes and Bronchial Hyperreactivity in Chronic Obstructive Pulmonary Disease

PubMed Central

Cukic, Vesna

2015-01-01

Introduction: Polymorphonuclear neutrophil leukocytes (PMNL) have an important defensive role against various microorganisms and other agents, but by liberating various substances, first of all the superoxide anion (O 2¯), they can damage the bronchial mucosa and influence the development of bronchial inflammation which is the fundamental of bronchial hyperreactivity (BHR). Objective: to show the role of the PMNL for development and level of BHR in patients with chronic obstructive pulmonary disease (COPD). Material and methods: We observed 160 patients with COPD treated in Clinic for Pulmonary Diseases and TB “Podhrastovi” Sarajevo during three years :from 2012 to 2014. They were divided into groups and subgroups according to the first registration of BHR in the course of illness and to the number of exacerbations of the disease in one year. The number of blood PMNL was measured in a stable state of disease at the begging and at the end of investigation. Results: The number of blood PMNL was significantly greater in patients with 3 or more exacerbations per one year (p <0.01). Patients with BHR had significantly greater number blood PMNL than patients without BHR (p< 0.05). Patients with 3 exacerbations per year had a statistically significant increase of number of PMNL between first and last examination (p<0.01). Conclusion: There is statistically significant correlation between the number of blood PMNL and the level of BHR in COPD, but future examination need to be done to determine real role and mode of action of PMNL for these processes. PMID:26543311

Surfactant and pulmonary blood flow distributions following treatment of premature lambs with natural surfactant.

PubMed Central

Jobe, A; Ikegami, M; Jacobs, H; Jones, S

1984-01-01

Prematurely delivered lambs were treated with radiolabeled natural surfactant by either tracheal instillation at birth and before the onset of mechanical ventilation, or after 23 +/- 1 (+/- SE) min of mechanical ventilation. Right ventricular blood flow distributions, left ventricular outputs, and left-to-right ductal shunts were measured with radiolabeled microspheres. After sacrifice, the lungs of lambs receiving surfactant at birth inflated uniformly with constant distending pressure while the lungs of lambs treated after a period of ventilation had aerated, partially aerated, and atelectatic areas. All lungs were divided into pieces which were weighed and catalogued as to location. The amount of radiolabeled surfactant and microsphere-associated radioactivity in each piece of lung was quantified. Surfactant was relatively homogenously distributed to pieces of lung from lambs that were treated with surfactant at birth; 48% of lung pieces received amounts of surfactant within +/- 25% of the mean value. Surfactant was preferentially recovered from the aerated pieces of lungs of lambs treated after a period of mechanical ventilation, and the distribution of surfactant to these lungs was very nonhomogeneous. Right ventricular blood flow distributions to the lungs were quite homogeneous in both groups of lambs. However, in 8 of 12 lambs, pulmonary blood flow was preferentially directed away from those pieces of lung that received relatively large amounts of surfactant and toward pieces of lung that received less surfactant. This acute redirection of pulmonary blood flow distribution may result from the local changes in compliances within the lung following surfactant instillation. PMID:6546766

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. © 2015 Wiley Periodicals, Inc.

Pulmonary Microvascular Blood Flow in Mild Chronic Obstructive Pulmonary Disease and Emphysema. The MESA COPD Study.

PubMed

Hueper, Katja; Vogel-Claussen, Jens; Parikh, Megha A; Austin, John H M; Bluemke, David A; Carr, James; Choi, Jiwoong; Goldstein, Thomas A; Gomes, Antoinette S; Hoffman, Eric A; Kawut, Steven M; Lima, Joao; Michos, Erin D; Post, Wendy S; Po, Ming Jack; Prince, Martin R; Liu, Kiang; Rabinowitz, Dan; Skrok, Jan; Smith, Ben M; Watson, Karol; Yin, Youbing; Zambeli-Ljepovic, Alan M; Barr, R Graham

2015-09-01

Smoking-related microvascular loss causes end-organ damage in the kidneys, heart, and brain. Basic research suggests a similar process in the lungs, but no large studies have assessed pulmonary microvascular blood flow (PMBF) in early chronic lung disease. To investigate whether PMBF is reduced in mild as well as more severe chronic obstructive pulmonary disease (COPD) and emphysema. PMBF was measured using gadolinium-enhanced magnetic resonance imaging (MRI) among smokers with COPD and control subjects age 50 to 79 years without clinical cardiovascular disease. COPD severity was defined by standard criteria. Emphysema on computed tomography (CT) was defined by the percentage of lung regions below -950 Hounsfield units (-950 HU) and by radiologists using a standard protocol. We adjusted for potential confounders, including smoking, oxygenation, and left ventricular cardiac output. Among 144 participants, PMBF was reduced by 30% in mild COPD, by 29% in moderate COPD, and by 52% in severe COPD (all P < 0.01 vs. control subjects). PMBF was reduced with greater percentage emphysema-950HU and radiologist-defined emphysema, particularly panlobular and centrilobular emphysema (all P ≤ 0.01). Registration of MRI and CT images revealed that PMBF was reduced in mild COPD in both nonemphysematous and emphysematous lung regions. Associations for PMBF were independent of measures of small airways disease on CT and gas trapping largely because emphysema and small airways disease occurred in different smokers. PMBF was reduced in mild COPD, including in regions of lung without frank emphysema, and may represent a distinct pathological process from small airways disease. PMBF may provide an imaging biomarker for therapeutic strategies targeting the pulmonary microvasculature.

Oxygen saturation and lactate concentration gradient from the right atrium to the pulmonary artery in the immediate postoperative following cardiac surgery with extracorporeal circulation.

PubMed

Pendino, Juan Carlos; Hess, Leonardo; Beltrame, Sergio; Castillo, Gonzalo Aldamiz-Echevarría; Trujillo, John

2017-01-01

This prospective study aimed to characterize the changes in blood lactate concentration and blood oxygen saturation in patients during the immediate postoperative period of cardiac surgery with extracorporeal circulation. Blood samples were collected from 35 patients in a rapid and random order from the arterial line and from the proximal and distal port of a pulmonary artery catheter. The results showed no statistically significant differences between the blood oxygen saturation in the right atrium (72% ± 0.11%) and the blood oxygen saturation in the pulmonary artery (71% ± 0.08%). The blood lactate concentration in the right atrium was 1.7mmol/L ± 0.5mmol/L, and the blood lactate concentration in the pulmonary artery was 1.6mmol/L ± 0.5mmol/L (p < 0.0005). The difference between the blood lactate concentration in the right atrium and the blood lactate concentration in the pulmonary artery might be a consequence of the low blood lactate concentration in the blood from the coronary sinus, as it constitutes an important substrate for the myocardium during this period. The lack of differences between the blood oxygen saturation in the right atrium and the percentage of blood oxygen saturation in the pulmonary artery suggests a lower oxygen extraction by the myocardium given a lower oxygen consumption.

Effect of cage vs. floor litter environments on the pulmonary hypertensive response to intravenous endotoxin and on blood-gas values in broilers.

PubMed

Wang, W; Erf, G F; Wideman, R F

2002-11-01

Intravenous endotoxin has been shown to trigger a delayed pulmonary hypertensive response that varies widely in magnitude and duration among individual broilers. It was proposed that this individual variability may reflect immunological differences acquired during previous respiratory challenges that might have subsequently altered the endotoxin-initiated biochemical cascade. In Experiment 1, we tested the hypothesis that, when compared with broilers reared in clean stainless steel cages (Cage group), broilers reared on floor litter (Floor group) should experience a greater respiratory challenge and therefore may consistently exhibit a more enhanced pulmonary hypertensive response to intravenous endotoxin. Birds in the Cage group were grown in stainless steel cages at a low density (72 birds/8 m2 chamber), and fecal and dander materials were removed daily. Birds in the Floor group were reared on wood-shavings litter at a higher density (110 birds/8 m2 chamber). Pulmonary and systemic mean arterial pressures and blood-gas values were evaluated prior to and following the intravenous administration of 1 mg Salmonella typhimurium endotoxin. Broilers in the Floor and Cage groups exhibited pulmonary hypertensive responses to endotoxin that were very similar in terms of time of onset, duration, and magnitude, as well as variability in the response among individuals. Systemic hypotension also developed similarly in both groups following endotoxin injection. Blood-gas values indicated that the partial pressure of CO2 and the HCO3- concentration in arterial blood were higher (P < 0.05) in the Floor group than in the Cage group prior to and subsequent to the endotoxin injection. In Experiment 2, we reevaluated the effect of a dirty vs. a clean environment on blood-gas values using a different strain of broilers, and confirmed the negative impact of floor rearing on blood-gas values. We conclude that broilers reared on the floor inhaled litter dust and noxious fumes, which

Hereditary Hemorrhagic Telangiectasia (HHT) and Pulmonary Hypertension

MedlinePlus

... has said these might be symptoms of pulmonary hypertension. How does this relate to my HHT? About ... differences are significant. In HHT-associated pulmonary arterial hypertension, abnormal blood flow through the blood vessels in ...

Further characterization of computed tomographic and clinical features for staging and prognosis of idiopathic pulmonary fibrosis in West Highland white terriers.

PubMed

Thierry, Florence; Handel, Ian; Hammond, Gawain; King, Lesley G; Corcoran, Brendan M; Schwarz, Tobias

2017-07-01

Idiopathic pulmonary fibrosis is an interstitial lung disease of unknown etiology resulting in progressive interstitial fibrosis, with a known predilection in West Highland white terriers. In humans, computed tomography (CT) is a standard method for providing diagnostic and prognostic information, and plays a major role in the idiopathic pulmonary fibrosis staging process. Objectives of this retrospective, analytical, cross-sectional study were to establish descriptive criteria for reporting CT findings and test correlations among CT, clinical findings and survival time in West Highland white terriers with idiopathic pulmonary fibrosis. Inclusion criteria for affected West Highland white terriers were a diagnosis of idiopathic pulmonary fibrosis and available CT, bronchoscopy, bronchoalveolar lavage, echocardiography, and routine blood analysis findings. Clinically normal West Highland white terriers were recruited for the control group. Survival times were recorded for affected dogs. The main CT lung pattern and clinical data were blindly and separately graded as mild, moderate, or severe. Twenty-one West Highland white terriers with idiopathic pulmonary fibrosis and 11 control West Highland white terriers were included. The severity of pulmonary CT findings was positively correlated with severity of clinical signs (ρ = 0.48, P = 0.029) and negatively associated with survival time after diagnosis (ρ = -0.56, P = 0.025). Affected dogs had higher lung attenuation (median: -563 Hounsfield Units (HU)) than control dogs (median: -761 HU), (P < 0.001). The most common CT characteristics were ground-glass pattern (16/21) considered as a mild degree of severity, and focal reticular and mosaic ground-glass patterns (10/21) considered as a moderate degree of severity. Findings supported the use of thoracic CT as a method for characterizing idiopathic pulmonary fibrosis in West Highland white terriers and providing prognostic information for owners. © 2017 The Authors

Automated assessment of aortic and main pulmonary arterial diameters using model-based blood vessel segmentation for predicting chronic thromboembolic pulmonary hypertension in low-dose CT lung screening

NASA Astrophysics Data System (ADS)

Suzuki, Hidenobu; Kawata, Yoshiki; Niki, Noboru; Sugiura, Toshihiko; Tanabe, Nobuhiro; Kusumoto, Masahiko; Eguchi, Kenji; Kaneko, Masahiro

2018-02-01

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by obstruction of the pulmonary vasculature by residual organized thrombi. A morphological abnormality inside mediastinum of CTEPH patient is enlargement of pulmonary artery. This paper presents an automated assessment of aortic and main pulmonary arterial diameters for predicting CTEPH in low-dose CT lung screening. The distinctive feature of our method is to segment aorta and main pulmonary artery using both of prior probability and vascular direction which were estimated from mediastinal vascular region using principal curvatures of four-dimensional hyper surface. The method was applied to two datasets, 64 lowdose CT scans of lung cancer screening and 19 normal-dose CT scans of CTEPH patients through the training phase with 121 low-dose CT scans. This paper demonstrates effectiveness of our method for predicting CTEPH in low-dose CT screening.

Pulmonary Microvascular Blood Flow in Mild Chronic Obstructive Pulmonary Disease and Emphysema. The MESA COPD Study

PubMed Central

Hueper, Katja; Vogel-Claussen, Jens; Parikh, Megha A.; Austin, John H. M.; Bluemke, David A.; Carr, James; Choi, Jiwoong; Goldstein, Thomas A.; Gomes, Antoinette S.; Hoffman, Eric A.; Kawut, Steven M.; Lima, Joao; Michos, Erin D.; Post, Wendy S.; Po, Ming Jack; Prince, Martin R.; Liu, Kiang; Rabinowitz, Dan; Skrok, Jan; Smith, Ben M.; Watson, Karol; Yin, Youbing; Zambeli-Ljepovic, Alan M.

2015-01-01

Rationale: Smoking-related microvascular loss causes end-organ damage in the kidneys, heart, and brain. Basic research suggests a similar process in the lungs, but no large studies have assessed pulmonary microvascular blood flow (PMBF) in early chronic lung disease. Objectives: To investigate whether PMBF is reduced in mild as well as more severe chronic obstructive pulmonary disease (COPD) and emphysema. Methods: PMBF was measured using gadolinium-enhanced magnetic resonance imaging (MRI) among smokers with COPD and control subjects age 50 to 79 years without clinical cardiovascular disease. COPD severity was defined by standard criteria. Emphysema on computed tomography (CT) was defined by the percentage of lung regions below −950 Hounsfield units (−950 HU) and by radiologists using a standard protocol. We adjusted for potential confounders, including smoking, oxygenation, and left ventricular cardiac output. Measurements and Main Results: Among 144 participants, PMBF was reduced by 30% in mild COPD, by 29% in moderate COPD, and by 52% in severe COPD (all P < 0.01 vs. control subjects). PMBF was reduced with greater percentage emphysema−950HU and radiologist-defined emphysema, particularly panlobular and centrilobular emphysema (all P ≤ 0.01). Registration of MRI and CT images revealed that PMBF was reduced in mild COPD in both nonemphysematous and emphysematous lung regions. Associations for PMBF were independent of measures of small airways disease on CT and gas trapping largely because emphysema and small airways disease occurred in different smokers. Conclusions: PMBF was reduced in mild COPD, including in regions of lung without frank emphysema, and may represent a distinct pathological process from small airways disease. PMBF may provide an imaging biomarker for therapeutic strategies targeting the pulmonary microvasculature. PMID:26067761

Diabetes Mellitus Associates with Increased Right Ventricular Afterload and Remodeling in Pulmonary Arterial Hypertension.

PubMed

Whitaker, Morgan E; Nair, Vineet; Sinari, Shripad; Dherange, Parinita A; Natarajan, Balaji; Trutter, Lindsey; Brittain, Evan L; Hemnes, Anna R; Austin, Eric D; Patel, Kumar; Black, Stephen M; Garcia, Joe G N; Yuan Md PhD, Jason X; Vanderpool, Rebecca R; Rischard, Franz; Makino, Ayako; Bedrick, Edward J; Desai, Ankit A

2018-06-01

Diabetes mellitus is associated with left ventricular hypertrophy and dysfunction. Parallel studies have also reported associations between diabetes mellitus and right ventricular dysfunction and reduced survival in patients with pulmonary arterial hypertension. However, the impact of diabetes mellitus on the pulmonary vasculature has not been well characterized. We hypothesized that diabetes mellitus and hyperglycemia could specifically influence right ventricular afterload and remodeling in patients with Group I pulmonary arterial hypertension, providing a link to their known susceptibility to right ventricular dysfunction. Using an adjusted model for age, sex, pulmonary vascular resistance, and medication use, associations of fasting blood glucose, glycated hemoglobin, and the presence of diabetes mellitus were evaluated with markers of disease severity in 162 patients with pulmonary arterial hypertension. A surrogate measure of increased pulmonary artery stiffness, elevated pulmonary arterial elastance (P = .012), along with reduced log(pulmonary artery capacitance) (P = .006) were significantly associated with the presence of diabetes mellitus in patients with pulmonary arterial hypertension in a fully adjusted model. Similar associations between pulmonary arterial elastance and capacitance were noted with both fasting blood glucose and glycated hemoglobin. Furthermore, right ventricular wall thickness on echocardiography was greater in pulmonary arterial hypertension patients with diabetes, supporting the link between right ventricular remodeling and diabetes. Cumulatively, these data demonstrate that an increase in right ventricular afterload, beyond pulmonary vascular resistance alone, may influence right ventricular remodeling and provide a mechanistic link between the susceptibility to right ventricular dysfunction in patients with both diabetes mellitus and pulmonary arterial hypertension. Copyright © 2018 Elsevier Inc. All rights reserved.

Regulation of the pulmonary circulation

PubMed Central

Lee, G. de J.

1971-01-01

Factors regulating pressure and flow in the lungs are reviewed with particular emphasis on their role in regulating blood flow velocity and distribution within the lung capillaries. The behaviour of the pulmonary arterial, system, alveolar capillaries, and pulmonary venous system are considered individually. The effect of heart disease on lung capillary blood flow is examined. PMID:4929437

Pulmonary arterial hypertension in pregnancy.

PubMed

Običan, Sarah G; Cleary, Kirsten L

2014-08-01

Pulmonary hypertension is a medical condition characterized by elevated pulmonary arterial pressure and secondary right heart failure. Pulmonary arterial hypertension is a subset of pulmonary hypertension, which is characterized by an underlying disorder of the pulmonary arterial vasculature. Pulmonary hypertension can also occur secondarily to structural cardiac disease, autoimmune disorders, and toxic exposures. Although pregnancies affected by pulmonary hypertension and pulmonary arterial hypertension are rare, the pathophysiology exacerbated by pregnancy confers both high maternal and fetal mortality and morbidity. In light of new treatment modalities and the use of a multidisciplinary approach to care, maternal outcomes may be improving. Copyright © 2014 Elsevier Inc. All rights reserved.

Pulmonary rehabilitation in patients with bronchiectasis: pulmonary function, arterial blood gases, and the 6-minute walk test.

PubMed

van Zeller, Mafalda; Mota, Patrícia Caetano; Amorim, Adelina; Viana, Paulo; Martins, Paula; Gaspar, Luís; Hespanhol, Venceslau; Gomes, Isabel

2012-01-01

Information regarding the effects of pulmonary rehabilitation (PR) on pulmonary function (PF), arterial blood gases (ABG), and 6-minute walk distance (6MWD) in patients with bronchiectasis is scant in the literature. To evaluate the effects of PR on these indices in this population, a retrospective evaluation of those who attended PR from 2007 to 2010, was made. Pulmonary rehabilitation lasted a mean of 12 weeks and included cycle ergometer exercise for 30 minutes, 3 times per week, with additional upper limbs and quadriceps training. PF, ABG, and 6MWD were evaluated before and after PR to determine the potential influence of gender, exacerbations, underlying cause of bronchiectasis, severity of obstruction, and colonization with bacteria. Forty-one patients (48.8% males; median age, 54 years) were included; 25 had severe obstruction and 19 were colonized with bacteria. Following PR, no significant changes were detected in PF or ABG. Median 6MWD before PR was 425 m and post-PR was 450 m (P = .431). Outcomes did not show any interaction with gender, colonization, or exacerbations. However, patients with idiopathic bronchiectasis did show a significant improvement in forced vital capacity in percent of predicted and residual volume after PR (P = .016 and .048, respectively). Patients with severe obstruction showed a statistically significant decrease in percent of predicted residual volume (P = .025). There appears to be a beneficial impact of PR on PF in certain groups of patients with bronchiectasis. In addition, PR indications and protocols for patients with bronchiectasis may need to be adapted to accommodate specific patients, so that expressive exercise capacity improvement can be achieved.

Decrease of pulmonary blood flow detected by phase contrast MRI is correlated with a decrease in lung volume and increase of lung fibrosis area determined by computed tomography in interstitial lung disease.

PubMed

Tsuchiya, Nanae; Yamashiro, Tsuneo; Murayama, Sadayuki

2016-09-01

Lung volume and pulmonary blood flow decrease in patients with interstitial lung disease (ILD). The purpose of this study was to assess the relationship between pulmonary blood flow and lung volume in ILD patients. This research was approved by the institutional review board. Twenty-seven patients (9 men, 18 women; mean age, 59 years; range, 24-79 years) with ILD were included. Blood flow was assessed in the pulmonary trunk and the left and right pulmonary arteries by phase contrast magnetic resonance imaging (MRI). Lung volume and the computed tomography (CT) visual score that indicates the severity of ILD were assessed on the left and right sides by thin-section CT scanning. Lung volume was automatically measured by lung analysis software (VINCENT Ver. 4). The CT visual score was measured by averaging the proportion of abnormal lung area at five anatomic levels. Pearson's correlation coefficient was used to determine the relationship between pulmonary blood flow and lung volume. Pulmonary blood flow showed a significant correlation with lung volume (both: r=0.52, p=0.006; left: r=0.61, p=0.001; right: r=0.54, p=0.004) and CT visual score (both: r=-0.39, p=0.04; left: r=-0.48, p=0.01; right: r=-0.38, p=0.04). Partial correlation analysis, controlled for age, height and weight, showed a significant correlation between pulmonary blood flow and lung volume (both: r=0.43, p=0.03; left: r=0.55, p=0.005; right: r=0.48, p=0.01) and CT visual score (both: r=-0.58, p=0.003; left: r=-0.51, p=0.01; right: r=-0.64, p=0.001). In ILD, reduced pulmonary blood flow is associated with reduced lung volume and increased abnormal lung area. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Automated measurement and classification of pulmonary blood-flow velocity patterns using phase-contrast MRI and correlation analysis.

PubMed

van Amerom, Joshua F P; Kellenberger, Christian J; Yoo, Shi-Joon; Macgowan, Christopher K

2009-01-01

An automated method was evaluated to detect blood flow in small pulmonary arteries and classify each as artery or vein, based on a temporal correlation analysis of their blood-flow velocity patterns. The method was evaluated using velocity-sensitive phase-contrast magnetic resonance data collected in vitro with a pulsatile flow phantom and in vivo in 11 human volunteers. The accuracy of the method was validated in vitro, which showed relative velocity errors of 12% at low spatial resolution (four voxels per diameter), but was reduced to 5% at increased spatial resolution (16 voxels per diameter). The performance of the method was evaluated in vivo according to its reproducibility and agreement with manual velocity measurements by an experienced radiologist. In all volunteers, the correlation analysis was able to detect and segment peripheral pulmonary vessels and distinguish arterial from venous velocity patterns. The intrasubject variability of repeated measurements was approximately 10% of peak velocity, or 2.8 cm/s root-mean-variance, demonstrating the high reproducibility of the method. Excellent agreement was obtained between the correlation analysis and radiologist measurements of pulmonary velocities, with a correlation of R2=0.98 (P<.001) and a slope of 0.99+/-0.01.

Flow Cytometric Quantification of Peripheral Blood Cell β-Adrenergic Receptor Density and Urinary Endothelial Cell-Derived Microparticles in Pulmonary Arterial Hypertension.

PubMed

Rose, Jonathan A; Wanner, Nicholas; Cheong, Hoi I; Queisser, Kimberly; Barrett, Patrick; Park, Margaret; Hite, Corrine; Naga Prasad, Sathyamangla V; Erzurum, Serpil; Asosingh, Kewal

2016-01-01

Pulmonary arterial hypertension (PAH) is a heterogeneous disease characterized by severe angiogenic remodeling of the pulmonary artery wall and right ventricular hypertrophy. Thus, there is an increasing need for novel biomarkers to dissect disease heterogeneity, and predict treatment response. Although β-adrenergic receptor (βAR) dysfunction is well documented in left heart disease while endothelial cell-derived microparticles (Ec-MPs) are established biomarkers of angiogenic remodeling, methods for easy large clinical cohort analysis of these biomarkers are currently absent. Here we describe flow cytometric methods for quantification of βAR density on circulating white blood cells (WBC) and Ec-MPs in urine samples that can be used as potential biomarkers of right heart failure in PAH. Biotinylated β-blocker alprenolol was synthesized and validated as a βAR specific probe that was combined with immunophenotyping to quantify βAR density in circulating WBC subsets. Ec-MPs obtained from urine samples were stained for annexin-V and CD144, and analyzed by a micro flow cytometer. Flow cytometric detection of alprenolol showed that βAR density was decreased in most WBC subsets in PAH samples compared to healthy controls. Ec-MPs in urine was increased in PAH compared to controls. Furthermore, there was a direct correlation between Ec-MPs and Tricuspid annular plane systolic excursion (TAPSE) in PAH patients. Therefore, flow cytometric quantification of peripheral blood cell βAR density and urinary Ec-MPs may be useful as potential biomarkers of right ventricular function in PAH.

Flow Cytometric Quantification of Peripheral Blood Cell β-Adrenergic Receptor Density and Urinary Endothelial Cell-Derived Microparticles in Pulmonary Arterial Hypertension

PubMed Central

Rose, Jonathan A.; Wanner, Nicholas; Cheong, Hoi I.; Queisser, Kimberly; Barrett, Patrick; Park, Margaret; Hite, Corrine; Naga Prasad, Sathyamangla V.; Erzurum, Serpil; Asosingh, Kewal

2016-01-01

Pulmonary arterial hypertension (PAH) is a heterogeneous disease characterized by severe angiogenic remodeling of the pulmonary artery wall and right ventricular hypertrophy. Thus, there is an increasing need for novel biomarkers to dissect disease heterogeneity, and predict treatment response. Although β-adrenergic receptor (βAR) dysfunction is well documented in left heart disease while endothelial cell-derived microparticles (Ec-MPs) are established biomarkers of angiogenic remodeling, methods for easy large clinical cohort analysis of these biomarkers are currently absent. Here we describe flow cytometric methods for quantification of βAR density on circulating white blood cells (WBC) and Ec-MPs in urine samples that can be used as potential biomarkers of right heart failure in PAH. Biotinylated β-blocker alprenolol was synthesized and validated as a βAR specific probe that was combined with immunophenotyping to quantify βAR density in circulating WBC subsets. Ec-MPs obtained from urine samples were stained for annexin-V and CD144, and analyzed by a micro flow cytometer. Flow cytometric detection of alprenolol showed that βAR density was decreased in most WBC subsets in PAH samples compared to healthy controls. Ec-MPs in urine was increased in PAH compared to controls. Furthermore, there was a direct correlation between Ec-MPs and Tricuspid annular plane systolic excursion (TAPSE) in PAH patients. Therefore, flow cytometric quantification of peripheral blood cell βAR density and urinary Ec-MPs may be useful as potential biomarkers of right ventricular function in PAH. PMID:27270458

CARDIOVASCULAR AND BLOOD COAGULATION EFFECTS OF PULMONARY ZINC EXPOSURE

EPA Science Inventory

Cardiovascular damage induced by pulmonary exposure to environmental chemicals can result from direct action or, secondarily, from pulmonary injury. We have developed a rat model of pulmonary exposure to zinc to demonstrate cardiac, coagulative, and fibrinolytic alterations. Mal...

A comparison in vivo dacron wool (Swank) and polyester mesh (Pall) micropore blood transfusion filters in the prevention of pulmonary microembolism associated with massive transfusion.

PubMed Central

Barrett, J; Dhurandhar, H N; Miller, E; Litwin, M S

1975-01-01

Experiments were performed to compare the effectiveness in vivo of the two most widely used micropore blood transfusion filters in preventing detrimental physiologic changes associated with transfusion of microaggregate-containing blood. Exchange transfusion with stored blood having an elevated screen filtration pressure (SFP) through polyester mesh (Pall) filters (Group PM) was followed by decreases in arterial blood pH and O2 consumption, increases in arterial blood pyruvate and lactate concentrations, and a decrease in pulmonary DO2. The lungs of 5 of 6 animals revealed emboli far out in the pulmonary microcirculation. These changes did not occur in animals transfused through dacron wool (Swank) filters (Group DW). Even though an increase after transfusion in pulmonary Qs/Qt in Group PM did not achieve statistical significance when compared to pretransfusion Qs/Qt, it was significantly higher than that in animals in Group DW. Both filters removed considerable quantities of microaggregates; however, the polyester mesh (Pall) filters permitted passage of small microaggregates and development of ditrimental physiologic changes. Dacron wool (Swank) filters completely removed measurable microaggregates and detrimental changes did not occur. Images Fig. 1. Fig. 2. Fig. 3. PMID:242282

Enhanced ventricular pump function and decreased reservoir backflow sustain rise in pulmonary blood flow after reduction of lung liquid volume in fetal lambs.

PubMed

Smolich, Joseph J

2014-02-15

Although a reduction in lung liquid volume increases fetal pulmonary blood flow, the changes in central flow patterns that sustain this increased pulmonary perfusion are unknown. To address this issue, eight anesthetized late-gestation fetal sheep were instrumented with pulmonary trunk (PT), ductus arteriosus (DA), and left pulmonary artery (PA) micromanometer catheters and transit-time flow probes, with blood flow profile and wave intensity analyses performed at baseline and after withdrawal of lung liquid via an endotracheal tube. Reducing lung liquid volume by 19 ± 6 ml/kg (mean ± SD) augmented right ventricular power by 34% (P < 0.001), with distribution of an accompanying increase in mean PT blood flow (245 ± 63 ml/min, P < 0.001) to the lungs (169 ± 91 ml/min, P = 0.001) and across the DA (77 ± 92 ml/min, P = 0.04). However, although PT and DA flow increments were confined to systole and were related to an increased magnitude of flow-increasing, forward-running compression waves, the rise in PA flow spanned both systole (108 ± 66 ml/min) and diastole (61 ± 32 ml/min). Flow profile analysis showed that the step-up in PA diastolic flow was associated with diminished PA diastolic backflow and accompanied by a lesser degree of diastolic right-to-left DA shunting. These data suggest that an increased pulmonary blood flow after reduction of lung liquid volume is associated with substantial changes in PT-DA-PA interactions and underpinned by two main factors: 1) enhanced right ventricular pump function that increases PA systolic inflow and 2) decreased PA diastolic backflow that arises from a fundamental change in PA reservoir function, thereby resulting in greater passage of systolic inflow through the lungs.

Abolished ventilation and perfusion of lung caused by blood clot in the left main bronchus: auto-downregulation of pulmonary arterial blood supply.

PubMed

Afzelius, P; Bergmann, A; Henriksen, J H

2015-09-15

It is generally assumed that the lungs possess arterial autoregulation associated with bronchial obstruction. A patient with pneumonia and congestive heart failure unexpectedly developed frequent haemoptysis. High-resolution CT and diagnostic CT were performed as well as ventilation/perfusion (V/Q) scintigraphy with single-photon emission CT (SPECT)/CT. V/Q SPECT/CT demonstrated abolished ventilation due to obstruction of the left main bronchus and markedly reduced perfusion of the entire left lung, a condition that was completely reversed after removal of a blood clot. We present the first pictorially documented case of hypoxia-induced pulmonary vasoconstriction and flow shift in a main pulmonary artery due to a complete intrinsic obstruction of the ipsilateral main bronchus. The condition is reversible, contingent on being relieved within a few days. 2015 BMJ Publishing Group Ltd.

Fundamentals of management of acute postoperative pulmonary hypertension.

PubMed

Taylor, Mary B; Laussen, Peter C

2010-03-01

In the last several years, there have been numerous advancements in the field of pulmonary hypertension as a whole, but there have been few changes in the management of children with pulmonary hypertension after cardiac surgery. Patients at particular risk for postoperative pulmonary hypertension can be identified preoperatively based on their cardiac disease and can be grouped into four broad categories based on the mechanisms responsible for pulmonary hypertension: 1) increased pulmonary vascular resistance; 2) increased pulmonary blood flow with normal pulmonary vascular resistance; 3) a combination of increased pulmonary vascular resistance and increased blood flow; and 4) increased pulmonary venous pressure. In this review of the immediate postoperative management of pulmonary hypertension, various strategies are discussed including medical therapies, monitoring, ventilatory strategies, and weaning from these supports. With early recognition of patients at particular risk for severe pulmonary hypertension, management strategies can be directed at preventing or minimizing hemodynamic instability and thereby prevent the development of ventricular dysfunction and a low output state.

Regional Distribution of Pulmonary Blood Volume with Dual-Energy Computed Tomography: Results in 42 Subjects.

PubMed

Felloni, Paul; Duhamel, Alain; Faivre, Jean-Baptiste; Giordano, Jessica; Khung, Suonita; Deken, Valérie; Remy, Jacques; Remy-Jardin, Martine

2017-11-01

The noninvasive approach of lung perfusion generated from dual-energy computed tomography acquisitions has entered clinical practice. The purpose of this study was to analyze the regional distribution of iodine within distal portions of the pulmonary arterial bed on dual-source, dual-energy computed tomography examinations in a cohort of subjects without cardiopulmonary pathologies. The study population included 42 patients without cardiorespiratory disease, enabling quantitative and qualitative analysis of pulmonary blood volume after administration of a 40% contrast agent. Qualitative analysis was based on visual assessment. Quantitative analysis was obtained after semiautomatic division of each lung into 18 areas. The iodine concentration did not significantly differ between the right (R) and left (L) lungs (P = .49), with a mean attenuation of 41.35 Hounsfield units (HU) and 41.14 HU, respectively. Three regional gradients of attenuation were observed between: (a) lung bases and apices (P < .001), linked to the conditions of examination (mean Δ: 6.23 in the R lung; 5.96 in the L lung); (b) posterior and anterior parts of the lung (P < .001) due to gravity (mean Δ: 11.92 in the R lung ; 15.93 in the L lung); and (c) medullary and cortical lung zones (P < .001) (mean Δ: 9.35 in the R lung ; 8.37 in the L lung). The intensity of dependent-nondependent (r = 0.42; P < .001) and corticomedullary (r = 0.58; P < .0001) gradients was correlated to the overall iodine concentration. Distribution of pulmonary blood volume is influenced by physiological gradients and scanning conditions. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Blood Count of Eosinophil Polymorphonuclear Leucocytes and Bronchial Hyperreactivity in Chronic Obstructive Pulmonary Disease

PubMed Central

Cukic, Vesna

2017-01-01

Introduction: Polymorphonuclear eosinophil leucocytes (eosinophils) are found in increased numbers in the circulation and sputum in asthma patients, usually in relation to the severity of asthma but it is the question whether they have a significant role in the development and level of bronchial hyperreactivity in patients with chronic obstructive pulmonary disease (COPD). Objective: to show the role of the eosinophils in the development and level of BHR in patients with COPD and so in the severity of illness. Material and methods: We observed 240 patients with COPD treated in Clinic for Pulmonary Diseases and TB «Podhrastovi» Sarajevo during five years: from 2012 to 2016. They were divided into groups and subgroups according to the first registration of BHR in the course of illness and to the number of exacerbations of the disease in one year. The number of blood eosinophils was measured at the onset of exacerbation of the disease before switching on any therapy, at the beginning and at the end of the research. Results: we did not find any significant difference in the eosinophil blood count between the COPD patients with and without BHR, nor according to the time of the first registration of BHR in the course of illness nor according to the number of exacerbations of illness per one year. There was not statistically significant difference in eosinophil count (increase-drop) within any of the groups or subgroups, or between the groups and subgroups between the first and last test. Conclusion: There is not significant correlation between the eosinophil blood count and the level of BHR, number of exacerbations and the severity of COPD. PMID:29284904

An analysis of estimation of pulmonary blood flow by the single-breath method

NASA Technical Reports Server (NTRS)

Srinivasan, R.

1986-01-01

The single-breath method represents a simple noninvasive technique for the assessment of capillary blood flow across the lung. However, this method has not gained widespread acceptance, because its accuracy is still being questioned. A rigorous procedure is described for estimating pulmonary blood flow (PBF) using data obtained with the aid of the single-breath method. Attention is given to the minimization of data-processing errors in the presence of measurement errors and to questions regarding a correction for possible loss of CO2 in the lung tissue. It is pointed out that the estimations are based on the exact solution of the underlying differential equations which describe the dynamics of gas exchange in the lung. The reported study demonstrates the feasibility of obtaining highly reliable estimates of PBF from expiratory data in the presence of random measurement errors.

Computed Tomographic Measures of Pulmonary Vascular Morphology in Smokers and Their Clinical Implications

PubMed Central

Estépar, Raúl San José; Kinney, Gregory L.; Black-Shinn, Jennifer L.; Bowler, Russell P.; Kindlmann, Gordon L.; Ross, James C.; Kikinis, Ron; Han, MeiLan K.; Come, Carolyn E.; Diaz, Alejandro A.; Cho, Michael H.; Hersh, Craig P.; Schroeder, Joyce D.; Reilly, John J.; Lynch, David A.; Crapo, James D.; Wells, J. Michael; Dransfield, Mark T.; Hokanson, John E.

2013-01-01

Rationale: Angiographic investigation suggests that pulmonary vascular remodeling in smokers is characterized by distal pruning of the blood vessels. Objectives: Using volumetric computed tomography scans of the chest we sought to quantitatively evaluate this process and assess its clinical associations. Methods: Pulmonary vessels were automatically identified, segmented, and measured. Total blood vessel volume (TBV) and the aggregate vessel volume for vessels less than 5 mm2 (BV5) were calculated for all lobes. The lobe-specific BV5 measures were normalized to the TBV of that lobe and the nonvascular tissue volume (BV5/TissueV) to calculate lobe-specific BV5/TBV and BV5/TissueV ratios. Densitometric measures of emphysema were obtained using a Hounsfield unit threshold of −950 (%LAA-950). Measures of chronic obstructive pulmonary disease severity included single breath measures of diffusing capacity of carbon monoxide, oxygen saturation, the 6-minute-walk distance, St George’s Respiratory Questionnaire total score (SGRQ), and the body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index. Measurements and Main Results: The %LAA-950 was inversely related to all calculated vascular ratios. In multivariate models including age, sex, and %LAA-950, lobe-specific measurements of BV5/TBV were directly related to resting oxygen saturation and inversely associated with both the SGRQ and BODE scores. In similar multivariate adjustment lobe-specific BV5/TissueV ratios were inversely related to resting oxygen saturation, diffusing capacity of carbon monoxide, 6-minute-walk distance, and directly related to the SGRQ and BODE. Conclusions: Smoking-related chronic obstructive pulmonary disease is characterized by distal pruning of the small blood vessels (<5 mm2) and loss of tissue in excess of the vasculature. The magnitude of these changes predicts the clinical severity of disease. PMID:23656466

Pulmonary nuclear medicine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loken, M.K.

1987-01-01

This book contains 19 chapters. Some of the titles are: Pulmonary Nuclear Medicine; Radionuclide Venography as an Adjunct to V-P Imaging in the Assessment of Thromboembolic Disease; Assessment of Mucous Transport in the Respiratory Tract by Radioisotopic Techniques; Radiolabeled Blood Cells and Tracers in the Study of Acute Pulmonary Injury and ARDS; and Magnetic Resonance Imaging of the Lungs.

[Application of continuous intra-arterial blood gas monitoring system "Paratrend 7" for pulmonary lavage of a patient with alveolar proteinosis].

PubMed

Harigae, M; Hirose, Y; Gamo, M; Hirose, M; Fujiwara, C; Matsuo, K

1999-03-01

We applied a continuous intra-arterial blood gas monitoring system (Paratrend 7) to a patient with pulmonary alveolar proteinosis during pulmonary lavage. Lavage was performed under general anesthesia with one lung ventilation. We inserted the sensor of Patatrend 7 through a 20 G catheter into the radial artery, and monitored pH, PaCO2 and PaO2 continuously throughout the procedure. SpO2 and EtCO2 were also monitored. Saline 1000-1500 ml was instilled and drained repeatedly by volume limited methods. PaO2 values by Paratrend 7 increased during instillation and decreased during drainage of the irrigating fluid. In contrast, PaCO2 value by Paratrend 7 decreased slightly during instillation and increased during drainage. The change of SpO2 was almost the same as that by Paratrend 7, but the response time of pulse oxymetry was a little quicker than Paratrend 7. During the lavage procedure, respiratory and circulatory condition changed very rapidly, and it is necessary to monitor blood gas change intensively. Paratrend 7 is useful as a perioperative monitoring system, but pulse oxymetry might be sufficient during pulmonary lavage considering its cost.

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

PubMed Central

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

2014-01-01

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 and coworkers (Ottesen et al., 2003; Olufsen et al., 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 ≥ 50µm. 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 of circulatory diseases within the lung. PMID:24610385

Characterization of pulmonary function impairments in patients with mucopolysaccharidoses--changes with age and treatment.

PubMed

Lin, Shuan-Pei; Shih, Shou-Chuan; Chuang, Chih-Kuang; Lee, Kuo-Sheng; Chen, Ming-Ren; Niu, Dau-Ming; Chiu, Pao Chin; Lin, Shio Jean; Lin, Hsiang-Yu

2014-03-01

The mucopolysaccharidoses (MPS) comprise a group of inherited lysosomal storage disorders characterized by deficiencies in enzymes catalyzing the degradation of glycosaminoglycans. Impairment of pulmonary function is an important health problem for patients with MPS. However, there are few published reports on the prevalence and severity of pulmonary dysfunction in relation to age and treatment in this disorder. To evaluate pulmonary function in patients with MPS, we performed spirometry in 35 patients (22 males and 13 females; 1 with MPS I, 12 with MPS II, 16 with MPS IVA, and 6 with MPS VI; mean age, 14.6 ± 5.9 years; age range, 6.4 years to 33 years). Forced vital capacity (FVC), forced expired volume in 1 sec (FEV1), FEV1 to FVC ratio (FEV1/FVC), peak expiratory flow (PEF), and mean forced expiratory flow during the middle half of FVC (FEF25-75% ) were measured. Mean FVC, FEV1 , PEF, and FEF25-75% were 74.2%, 73.9%, 64.7%, and 37.1% of the predicted values, respectively. By spirometric classification, 32 patients (91%) had small airway disease (FEF25-75%  < 65%), 17 (48%) had restrictive lung disease, and 3 (9%) had obstructive lung disease. Percent predicted FVC, FEV1 , and PEF, as well as FEV1 /FVC, were all negatively correlated with age (P < 0.01), such that pubertal and post-pubertal patients had significantly lower values than younger patients. Of eight attenuated MPS II and VI patients who underwent follow-up pulmonary function testing after receiving enzyme replacement therapy (ERT) for 1.5-7.4 years, six showed improvements in % predicted FVC and five improved in % predicted FEV1 . Our additional characterization of the types and prevalence of pulmonary function abnormalities seen in MPS patients should be useful for clinical care. © 2013 Wiley Periodicals, Inc.

A Peripheral Blood Signature of Vasodilator-Responsive Pulmonary Arterial Hypertension

PubMed Central

Hemnes, Anna R.; Trammell, Aaron W.; Archer, Stephen L.; Rich, Stuart; Yu, Chang; Nian, Hui; Penner, Niki; Funke, Mitchell; Wheeler, Lisa; Robbins, Ivan M.; Austin, Eric D.; Newman, John H.; West, James

2014-01-01

Background Heterogeneity in response to treatment of pulmonary arterial hypertension (PAH) is a major challenge to improving outcome in this disease. Although vasodilator responsive PAH (VR-PAH) accounts for a minority of cases, VR-PAH has a pronounced response to calcium channel blockers and better survival than non-responsive PAH (VN-PAH). We hypothesized that VR-PAH has a different molecular etiology from VN-PAH that can be detected in the peripheral blood. Methods and Results Microarrays of cultured lymphocytes from VR-PAH and VN-PAH patients followed at Vanderbilt University were performed with quantitative PCR performed on peripheral blood for the 25 most different genes. We developed a decision tree to identify VR-PAH patients based on the results with validation in a second VR-PAH cohort from the University of Chicago. We found broad differences in gene expression patterns on microarray analysis including cell-cell adhesion factors, cytoskeletal and rho/GTPase genes. 13/25 genes tested in whole blood were significantly different: EPDR1, DSG2, SCD5, P2RY5, MGAT5, RHOQ, UCHL1, ZNF652, RALGPS2, TPD52, MKNL1, RAPGEF2 and PIAS1. Seven decision trees were built using expression levels of two genes as the primary genes: DSG2, a desmosomal cadherin involved in Wnt/β-catenin signaling, and RHOQ, which encodes a cytoskeletal protein involved in insulin-mediated signaling. These trees correctly identified 5/5 VR-PAH in the validation cohort. Conclusions VR-PAH and VN-PAH can be differentiated using RNA expression patterns in peripheral blood. These differences may reflect different molecular etiologies of the two PAH phenotypes. This biomarker methodology may identify PAH patients that have a favorable treatment response. PMID:25361553

Assessing potential errors of MRI-based measurements of pulmonary blood flow using a detailed network flow model

PubMed Central

Buxton, R. B.; Prisk, G. K.

2012-01-01

MRI images of pulmonary blood flow using arterial spin labeling (ASL) measure the delivery of magnetically tagged blood to an image plane during one systolic ejection period. However, the method potentially suffers from two problems, each of which may depend on the imaging plane location: 1) the inversion plane is thicker than the imaging plane, resulting in a gap that blood must cross to be detected in the image; and 2) ASL includes signal contributions from tagged blood in conduit vessels (arterial and venous). By using an in silico model of the pulmonary circulation we found the gap reduced the ASL signal to 64–74% of that in the absence of a gap in the sagittal plane and 53–84% in the coronal. The contribution of the conduit vessels varied markedly as a function of image plane ranging from ∼90% of the overall signal in image planes that encompass the central hilar vessels to <20% in peripheral image planes. A threshold cutoff removing voxels with intensities >35% of maximum reduced the conduit vessel contribution to the total ASL signal to ∼20% on average; however, planes with large contributions from conduit vessels underestimate acinar flow due to a high proportion of in-plane flow, making ASL measurements of perfusion impractical. In other image planes, perfusion dominated the resulting ASL images with good agreement between ASL and acinar flow. Similarly, heterogeneity of the ASL signal as measured by relative dispersion is a reliable measure of heterogeneity of the acinar flow distribution in the same image planes. PMID:22539167

Assessing potential errors of MRI-based measurements of pulmonary blood flow using a detailed network flow model.

PubMed

Burrowes, K S; Buxton, R B; Prisk, G K

2012-07-01

MRI images of pulmonary blood flow using arterial spin labeling (ASL) measure the delivery of magnetically tagged blood to an image plane during one systolic ejection period. However, the method potentially suffers from two problems, each of which may depend on the imaging plane location: 1) the inversion plane is thicker than the imaging plane, resulting in a gap that blood must cross to be detected in the image; and 2) ASL includes signal contributions from tagged blood in conduit vessels (arterial and venous). By using an in silico model of the pulmonary circulation we found the gap reduced the ASL signal to 64-74% of that in the absence of a gap in the sagittal plane and 53-84% in the coronal. The contribution of the conduit vessels varied markedly as a function of image plane ranging from ∼90% of the overall signal in image planes that encompass the central hilar vessels to <20% in peripheral image planes. A threshold cutoff removing voxels with intensities >35% of maximum reduced the conduit vessel contribution to the total ASL signal to ∼20% on average; however, planes with large contributions from conduit vessels underestimate acinar flow due to a high proportion of in-plane flow, making ASL measurements of perfusion impractical. In other image planes, perfusion dominated the resulting ASL images with good agreement between ASL and acinar flow. Similarly, heterogeneity of the ASL signal as measured by relative dispersion is a reliable measure of heterogeneity of the acinar flow distribution in the same image planes.

The peripheral blood proteome signature of idiopathic pulmonary fibrosis is distinct from normal and is associated with novel immunological processes.

PubMed

O'Dwyer, David N; Norman, Katy C; Xia, Meng; Huang, Yong; Gurczynski, Stephen J; Ashley, Shanna L; White, Eric S; Flaherty, Kevin R; Martinez, Fernando J; Murray, Susan; Noth, Imre; Arnold, Kelly B; Moore, Bethany B

2017-04-25

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial pneumonia. The disease pathophysiology is poorly understood and the etiology remains unclear. Recent advances have generated new therapies and improved knowledge of the natural history of IPF. These gains have been brokered by advances in technology and improved insight into the role of various genes in mediating disease, but gene expression and protein levels do not always correlate. Thus, in this paper we apply a novel large scale high throughput aptamer approach to identify more than 1100 proteins in the peripheral blood of well-characterized IPF patients and normal volunteers. We use systems biology approaches to identify a unique IPF proteome signature and give insight into biological processes driving IPF. We found IPF plasma to be altered and enriched for proteins involved in defense response, wound healing and protein phosphorylation when compared to normal human plasma. Analysis also revealed a minimal protein signature that differentiated IPF patients from normal controls, which may allow for accurate diagnosis of IPF based on easily-accessible peripheral blood. This report introduces large scale unbiased protein discovery analysis to IPF and describes distinct biological processes that further inform disease biology.

What Is Pulmonary Hypertension?

MedlinePlus

... Disease Venous Thromboembolism Aortic Aneurysm More Pulmonary Hypertension - High Blood Pressure in the Heart-to-Lung System Updated:Jan ... Pressure" This content was last reviewed October 2016. High Blood Pressure • Home • Get the Facts About HBP Introduction What ...

Quantification of lung perfusion blood volume (lung PBV) by dual-energy CT in patients with chronic thromboembolic pulmonary hypertension (CTEPH) before and after balloon pulmonary angioplasty (BPA): Preliminary results.

PubMed

Koike, Hirofumi; Sueyoshi, Eijun; Sakamoto, Ichiro; Uetani, Masataka; Nakata, Tomoo; Maemura, Kouji

2016-09-01

Balloon pulmonary angioplasty (BPA) is a treatment option for patients with chronic thromboembolic pulmonary hypertension (CTEPH). Its effect on pulmonary perfusion has not been quantified; we examined the clinical significance of pulmonary blood volume (PBV) using dual-energy computed tomography (DECT) in patients with CTEPH undergoing BPA. In this retrospective study of 16 BPAs in eight female patients with CTEPH, we evaluated both-lung (n=16), right- or left-lung (n=32), and three right- or left-segment (upper, middle, and lower) (n=96) PBVs before and after BPA, using DECT. We evaluated the relationships between improvement in lung PBV and pulmonary artery (PA) pressure (PAP), cardiac index (CI), pulmonary vascular resistance (PVR), and 6-min walking distance. We measured PA enhancement (PAenh) on DECT images and calculated lung PBV/PAenh to adjust timing. Pre- and post-BPA 6-segment lung PBV/PAenh were 0.067±0.021 and 0.077±0.019, respectively, in the treated segment (p<0.0001). There were significant positive correlations between pre- to post-BPA improvements in both-lung PBV/PAenh and PAP (R=0.69, p=0.005), PVR (R=0.56, p=0.03), and 6-min walking distance (R=0.67, p=0.01). Improved PBV after BPA, reflecting increased lung perfusion, was positively correlated with PAP, PVR, and 6-min walking distance. Lung PBV may be an indicator of BPA treatment effect. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

PubMed Central

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

2014-01-01

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

Pulmonary blood volume (PRV) in rats with chronic mountain sickness

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ou, L.C.; Sardella, G.L.; Hill, N.S.

1986-03-05

Upon chronic exposure to severe hypoxia, Hilltop (H) strain of Sprague-Dawley rats develops excessive polycythemia, severe hypervolemia and marked elevation in pulmonary arterial pressure (PAP), whereas Madison (M) strain develops only moderate responses. Hypervolemia is expected to increase the PBV which might contribute to the development of severe pulmonary hypertension. Two groups of 6 animals each of the H and M strains were exposed to sea level (SL) and a simulated altitude of 18,000 ft for 14 days. At the end of exposure each animal was measured for RBC volume (RBCV), total blood volume (TBV), PBV and PAP under normoxiamore » for control and under hypoxia (10% O/sub 2/) for the hypoxic groups. RBCV was determined by /sup 51/Cr-RBC dilution and PBV was trapped by tightening an implanted loose ligature around the ascending aorta and PA. There were not strain differences in all parameters studied at SL. RBCV, TBV and PAP increased with hypoxia in both strains but significantly more so in H than M. PBV per g lung WT decreased in both strains despite elevated TBV and PAP, but more so in M than H. There were good correlations between the PBV and TBV, and between PAP and PBV in the hypoxic H and M rats. The data suggest that chronic hypoxia reduced the distensibility and perhaps the vascular capacity of the lungs such that small relative increase in PBV could significantly contribute to the rise in PAP.« less

Pulmonary MRI at 3T: Non-enhanced pulmonary magnetic resonance Imaging Characterization Quotients for differentiation of infectious and malignant lesions.

PubMed

Nagel, Sebastian Niko; Kim, Damon; Penzkofer, Tobias; Steffen, Ingo G; Wyschkon, Sebastian; Hamm, Bernd; Schwartz, Stefan; Elgeti, Thomas

2017-04-01

To investigate 3T pulmonary magnetic resonance imaging (MRI) for characterization of solid pulmonary lesions in immunocompromised patients and to differentiate infectious from malignant lesions. Thirty-eight pulmonary lesions in 29 patients were evaluated. Seventeen patients were immunocompromised (11 infections and 6 lymphomas) and 12 served as controls (4 bacterial pneumonias, 8 solid tumors). Ten of the 15 infections were acute. Signal intensities (SI) were measured in the lesion, chest wall muscle, and subcutaneous fat. Scaled SIs as Non-enhanced Imaging Characterization Quotients ((SI Lesion -SI Muscle )/(SI Fat -SI Muscle )*100) were calculated from the T2-weighted images using the mean SI (T2-NICQ mean ) or the 90th percentile of SI (T2-NICQ 90th ) of the lesion. Simple quotients were calculated by dividing the SI of the lesion by the SI of chest wall muscle (e.g. T1-Q mean : SI Lesion /SI Muscle ). Infectious pulmonary lesions showed a higher T2-NICQ mean (40.1 [14.6-56.0] vs. 20.9 [2.4-30.1], p<0.05) and T2-NICQ 90th (74.3 [43.8-91.6] vs. 38.5 [15.8-48.1], p<0.01) than malignant lesions. T1-Q mean was higher in malignant lesions (0.85 [0.68-0.94] vs. 0.93 [0.87-1.09], p<0.05). Considering infections only, T2-NICQ 90th was lower when anti-infectious treatment was administered >24h prior to MRI (81.8 [71.8-97.6] vs. 41.4 [26.6-51.1], p<0.01). Using Youden's index (YI), the optimal cutoff to differentiate infectious from malignant lesions was 43.1 for T2-NICQ mean (YI=0.42, 0.47 sensitivity, 0.95 specificity) and 55.5 for T2-NICQ 90th (YI=0.61, 0.71 sensitivity, 0.91 specificity). Combining T2-NICQ 90th and T1-Q mean increased diagnostic performance (YI=0.72, 0.77 sensitivity, 0.95 specificity). Considering each quotient alone, T2-NICQ 90th showed the best diagnostic performance and could allow differentiation of acute infectious from malignant pulmonary lesions with high specificity. Combining T2-NICQ 90th with T1-Q mean increased overall performance

Abnormal pulmonary function in adults with sickle cell anemia.

PubMed

Klings, Elizabeth S; Wyszynski, Diego F; Nolan, Vikki G; Steinberg, Martin H

2006-06-01

Pulmonary complications of sickle cell anemia (Hb-SS) commonly cause morbidity, yet few large studies of pulmonary function tests (PFTs) in this population have been reported. PFTs (spirometry, lung volumes, and diffusion capacity for carbon monoxide [DLCO]) from 310 adults with Hb-SS were analyzed to determine the pattern of pulmonary dysfunction and their association with other systemic complications of sickle cell disease. Raw PFT data were compared with predicted values. Each subject was subclassified into one of five groups: obstructive physiology, restrictive physiology, mixed obstructive/restrictive physiology, isolated low DLCO, or normal. The association between laboratory data of patients with decreased DLCO or restrictive physiology and those of normal subjects was assessed by multivariate linear regression. Normal PFTs were present in only 31 of 310 (10%) patients. Overall, adults with Hb-SS were characterized by decreased total lung capacities (70.2 +/- 14.7% predicted) and DLCO (64.5 +/- 19.9%). The most common PFT patterns were restrictive physiology (74%) and isolated low DLCO (13%). Decreased DLCO was associated with thrombocytosis (p = 0.05), with hepatic dysfunction (elevated alanine aminotransferase; p = 0.07), and a trend toward renal dysfunction (elevated blood urea nitrogen and creatinine; p = 0.05 and 0.07, respectively). Pulmonary function is abnormal in 90% of adult patients with Hb-SS. Common abnormalities include restrictive physiology and decreased DLCO. Decreased DLCO may indicate more severe sickle vasculopathy characterized by impaired hepatic and renal function.

A novel clinical index for the assessment of RVD in acute pulmonary embolism: Blood pressure index.

PubMed

Ates, Hale; Ates, Ihsan; Kundi, Harun; Arikan, Mehmet Fettah; Yilmaz, Fatma Meric

2017-10-01

This study aims to investigate the role of the blood pressure index (BPI), which is a new index that we developed, in detection of right ventricular dysfunction (RVD) in acute pulmonary embolism (APE). A total of 539 patients, (253 males and 286 females), diagnosed with APE using computer tomography pulmonary angiography were included in the study. The BPI was obtained by dividing systolic blood pressure (SBP) by diastolic blood pressure (DBP). Mean DBP (75±11mmHg vs 63±15mmHg; p<0.001, respectively) was found to be higher in RVD patients compared to those without RVD, whereas BPI (1.5±0.1 vs 1.9±0.2; p<0.001, respectively) was lower. Examining the performance of BPI in prediction of RVD using receiver operating characteristic curve analysis (area under curve±SE=0.975±0.006; p<0.001), it was found that BPI could predict RVD with very high sensitivity (92.8%) and specificity (100%) and had a positive predictive value of 100% and a negative predictive value of 42.1%. According to the analysis, the highest youden index for the optimal prediction value was found to be 0.478 and the BPI≤1.4 was found to predict mortality 68.6% sensitivity and 80.8% specificity (Area under curve±SE=0.777±0.051; p<0.001). We found that BPI was an index with high positive predictive value and low negative predictive value in detection of RVD. Copyright © 2017 Elsevier Inc. All rights reserved.

Intra- and inter-reader reproducibility of blood flow measurements on the ascending aorta and pulmonary artery using cardiac magnetic resonance.

PubMed

Di Leo, Giovanni; D'Angelo, Ida Daniela; Alì, Marco; Cannaò, Paola Maria; Mauri, Giovanni; Secchi, Francesco; Sardanelli, Francesco

2017-03-01

The aim of our study was to estimate the intra- and inter-reader reproducibility of blood flow measurements in the ascending aorta and main pulmonary artery using cardiac magnetic resonance (CMR) and a semi-automated segmentation method. The ethics committee approved this retrospective study. A total of 50 consecutive patients (35 males and 15 females; mean age±standard deviation 27±13 years) affected by congenital heart disease were reviewed. They underwent CMR for flow analysis of the ascending aorta and main pulmonary artery (1.5 T, through-plane phase-contrast sequences). Two independent readers (R1, trained radiology resident; R2, lower-trained technician student) obtained segmented images twice (>10-day interval), using a semi-automated method of segmentation. Peak velocity, forward and backward flows were obtained. Bland-Altman analysis was used and reproducibility was reported as complement to 100% of the ratio between the coefficient of repeatability and the mean. R1 intra-reader reproducibility for the aorta was 99% (peak velocity), 95% (forward flow) and 49% (backward flow); for the pulmonary artery, 99%, 91% and 90%, respectively. R2 intra-reader reproducibility was 92%, 91% and 38%; 98%, 86% and 87%, respectively. Inter-reader reproducibility for the aorta was 91%, 85% and 20%; for the pulmonary artery 96%, 75%, and 82%, respectively. Our results showed a good to excellent reproducibility of blood flow measurements of CMR together with a semiautomated method of segmentation, for all variables except the backward flow of the ascending aorta, with a limited impact of operator's training.

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 ...

Hypoxic pulmonary vasoconstriction in isolated mouse pulmonary arterial vessels.

PubMed

Strielkov, Ievgen; Krause, Nicole Catherine; Sommer, Natasha; Schermuly, Ralph Theo; Ghofrani, Hossein Ardeschir; Grimminger, Friedrich; Gudermann, Thomas; Dietrich, Alexander; Weissmann, Norbert

2018-06-19

What is the central question of this study? Hypoxic pulmonary vasoconstriction has never been characterized in isolated mouse pulmonary arteries of different generations in detail. What is the main finding and its importance? We found that only small intrapulmonary arteries (80 - 200 μm in diameter) exhibit hypoxic pulmonary vasoconstriction. The observed response was sustained, significantly potentiated by depolarization-induced preconstriction, and not dependent on endothelium and TRPC6 channels. Hypoxic pulmonary vasoconstriction (HPV) is a physiological response of pulmonary arteries, which adapts lung perfusion to regional ventilation. Properties of hypoxic pulmonary vasoconstriction (HPV) vary significantly between animal species. Despite extensive use of mouse models in studies of HPV, this physiological response has never been characterized in isolated mouse pulmonary arteries in detail. We investigated the effect of 80-min exposure to hypoxia on tone in mouse pulmonary arteries of different generations in the presence and absence of preconstriction using wire myography. Hypoxia induced a sustained relaxation in non-preconstricted extrapulmonary arteries (500 - 700 μm in diameter), but not in the presence of KCl-induced preconstriction. Large intrapulmonary arteries (450 - 650 μm) did not exhibit a significant response to the hypoxic challenge. By contrast, in small intrapulmonary arteries (80 - 200 μm), hypoxia elicited a slowly developing sustained constriction, which was independent of endothelium. The response was significantly potentiated in arteries preconstricted with KCl, but not with U46619. HPV was not altered in pulmonary arteries of TRPC6-deficient mice, which suggests that this response corresponds to the sustained phase of biphasic HPV observed earlier in isolated, buffer-perfused, and ventilated mouse lungs. In conclusion, we have established the protocol allowing to study sustained HPV in isolated mouse pulmonary arteries. The

The development of a pseudo-chamber after balloon pulmonary angioplasty: long-term complications of balloon pulmonary angioplasty.

PubMed

Sugiyama, Hisashi; Kise, Hiroaki; Toda, Takako; Hoshiai, Minako

2016-11-01

We experienced a rare complication where extravasation developed a pseudo-chamber long after the balloon pulmonary angioplasty for supravalvular pulmonary stenosis. A 3-month-old girl was diagnosed with an anomalous origin of the left coronary artery from the pulmonary artery. She underwent the Takeuchi procedure at 10 months of age. During the follow-up, the supravalvular pulmonary stenosis deteriorated, and was treated by balloon pulmonary angioplasty with the double balloon technique catheter at 6 years of age. Angiography at the main pulmonary artery showed a small amount of extravasation contrast medium after the procedure. Follow-up echocardiography showed a diminished extravasation hemorrhage. Twelve years later, right ventricular enlargement due to pulmonary regurgitation had been observed on echocardiography. In addition, abnormal echo free space was detected at the left posterior of the left atrium. Enhanced computed tomography clearly demonstrated there was an orifice and extent of the pseudo-chamber. Surgical findings revealed a large tear just distal to the coronary tunnel. We speculated that extravasation blood was limited in the perivascular area early after the procedure but eventually reached the non-adhesive oblique pericardial sinus with age. Consequently, pulmonary to oblique pericardial sinus communication was established and looked like a pseudo-chamber long after the procedure. In conclusion, even if extravasation seems to be limited immediately after the balloon pulmonary angioplasty, it could expand for non-adhesive space and could develop a huge blood space like chamber. Long-term careful observation should be necessary for extravasation of pulmonary artery even with surgical adhesion.

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.

Genetics Home Reference: pulmonary arterial hypertension

MedlinePlus

... Home Health Conditions Pulmonary arterial hypertension Pulmonary arterial hypertension Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Pulmonary arterial hypertension is a progressive disorder characterized by abnormally high ...

[Immersion pulmonary edema].

PubMed

Desgraz, Benoît; Sartori, Claudio; Saubade, Mathieu; Héritier, Francis; Gabus, Vincent

2017-07-12

Immersion pulmonary edema may occur during scuba diving, snorke-ling or swimming. It is a rare and often recurrent disease, mainly affecting individuals aged over 50 with high blood pressure. However it also occurs in young individuals with a healthy heart. The main symptoms are dyspnea, cough and hemoptysis. The outcome is often favorable under oxygen treatment but deaths are reported. A cardiac and pulmonary assessment is necessary to evaluate the risk of recurrence and possible contraindications to immersion.

Blood global DNA methylation is decreased in non-severe chronic obstructive pulmonary disease (COPD) patients.

PubMed

Zinellu, Angelo; Sotgiu, Elisabetta; Fois, Alessandro G; Zinellu, Elisabetta; Sotgia, Salvatore; Ena, Sara; Mangoni, Arduino A; Carru, Ciriaco; Pirina, Pietro

2017-10-01

Alterations in global DNA methylation have been associated with oxidative stress (OS). Since chronic obstructive pulmonary disease (COPD) is characterized by increased oxidative stress we aimed to evaluate the levels of global DNA methylation in this patient group. We assessed methylcytosine (mCyt) levels in DNA from blood collected in 43 COPD patients (29 with mild and 14 with moderate disease) and 43 age- and sex-matched healthy controls. DNA methylation was significantly lower in COPD patients vs. controls (4.20 ± 0.18% mCyt vs. 4.29 ± 0.18% mCyt, p = 0.02). Furthermore, DNA methylation in COPD patients with moderate disease was significantly lower than that in patients with mild disease (4.14 ± 0.15% mCyt vs. 4.23 ± 0.19% mCyt, p < 0.05). Univariate logistic regression analysis showed that lower DNA methylation levels were associated with presence of COPD (crude OR = 0.06, 95% CI 0.00 to 0.67, p = 0.023). This relationship remained significant after adjusting for several confounders (OR 0.03, 95% CI 0.00 to 0.67; p = 0.028). Receiver operating characteristics (ROC) curve analysis demonstrated the area under the curve of mCyt was 0.646, with 46.6% sensitivity and 79.1% specificity for presence of COPD. There were no significant correlations between methylation and OS indices. The presence and severity of COPD is associated with progressively lower DNA methylation in blood. However, this epigenetic alteration seems independent of oxidative stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

Automated method for relating regional pulmonary structure and function: integration of dynamic multislice CT and thin-slice high-resolution CT

NASA Astrophysics Data System (ADS)

Tajik, Jehangir K.; Kugelmass, Steven D.; Hoffman, Eric A.

1993-07-01

We have developed a method utilizing x-ray CT for relating pulmonary perfusion to global and regional anatomy, allowing for detailed study of structure to function relationships. A thick slice, high temporal resolution mode is used to follow a bolus contrast agent for blood flow evaluation and is fused with a high spatial resolution, thin slice mode to obtain structure- function detail. To aid analysis of blood flow, we have developed a software module, for our image analysis package (VIDA), to produce the combined structure-function image. Color coded images representing blood flow, mean transit time, regional tissue content, regional blood volume, regional air content, etc. are generated and imbedded in the high resolution volume image. A text file containing these values along with a voxel's 3-D coordinates is also generated. User input can be minimized to identifying the location of the pulmonary artery from which the input function to a blood flow model is derived. Any flow model utilizing one input and one output function can be easily added to a user selectable list. We present examples from our physiologic based research findings to demonstrate the strengths of combining dynamic CT and HRCT relative to other scanning modalities to uniquely characterize pulmonary normal and pathophysiology.

Pulmonary Fibrosis

MedlinePlus

... and your blood may not get enough oxygen. Causes of pulmonary fibrosis include environmental pollutants, some medicines, some connective tissue ... or scar the lungs. In most cases, the cause cannot be found. This is called ... fibrosis. Symptoms include Shortness of breath A dry, hacking ...

Evidence for local dendritic cell activation in pulmonary sarcoidosis

PubMed Central

2012-01-01

Background Sarcoidosis is a granulomatous disease characterized by a seemingly exaggerated immune response against a difficult to discern antigen. Dendritic cells (DCs) are pivotal antigen presenting cells thought to play an important role in the pathogenesis. Paradoxically, decreased DC immune reactivity was reported in blood samples from pulmonary sarcoidosis patients. However, functional data on lung DCs in sarcoidosis are lacking. We hypothesized that at the site of disease DCs are mature, immunocompetent and involved in granuloma formation. Methods We analyzed myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in broncho-alveolar lavage (BAL) and blood from newly diagnosed, untreated pulmonary sarcoidosis patients and healthy controls using 9-color flowcytometry. DCs, isolated from BAL using flowcytometric sorting (mDCs) or cultured from monocytes (mo-DCs), were functionally assessed in a mixed leukocyte reaction with naïve allogeneic CD4+ T cells. Using Immunohistochemistry, location and activation status of CD11c+DCs was assessed in mucosal airway biopsies. Results mDCs in BAL, but not in blood, from sarcoidosis patients were increased in number when compared with mDCs from healthy controls. mDCs purified from BAL of sarcoidosis patients induced T cell proliferation and differentiation and did not show diminished immune reactivity. Mo-DCs from patients induced increased TNFα release in co-cultures with naïve allogeneic CD4+ T cells. Finally, immunohistochemical analyses revealed increased numbers of mature CD86+ DCs in granuloma-containing airway mucosal biopsies from sarcoidosis patients. Conclusion Taken together, these finding implicate increased local DC activation in granuloma formation or maintenance in pulmonary sarcoidosis. PMID:22513006

Abnormal Pulmonary Function in Adults with Sickle Cell Anemia

PubMed Central

Klings, Elizabeth S.; Wyszynski, Diego F.; Nolan, Vikki G.; Steinberg, Martin H.

2006-01-01

Rationale: Pulmonary complications of sickle cell anemia (Hb-SS) commonly cause morbidity, yet few large studies of pulmonary function tests (PFTs) in this population have been reported. Objectives: PFTs (spirometry, lung volumes, and diffusion capacity for carbon monoxide [DLCO]) from 310 adults with Hb-SS were analyzed to determine the pattern of pulmonary dysfunction and their association with other systemic complications of sickle cell disease. Methods: Raw PFT data were compared with predicted values. Each subject was subclassified into one of five groups: obstructive physiology, restrictive physiology, mixed obstructive/restrictive physiology, isolated low DLCO, or normal. The association between laboratory data of patients with decreased DLCO or restrictive physiology and those of normal subjects was assessed by multivariate linear regression. Measurements and Main Results: Normal PFTs were present in only 31 of 310 (10%) patients. Overall, adults with Hb-SS were characterized by decreased total lung capacities (70.2 ± 14.7% predicted) and DlCO (64.5 ± 19.9%). The most common PFT patterns were restrictive physiology (74%) and isolated low DlCO (13%). Decreased DLCO was associated with thrombocytosis (p = 0.05), with hepatic dysfunction (elevated alanine aminotransferase; p = 0.07), and a trend toward renal dysfunction (elevated blood urea nitrogen and creatinine; p = 0.05 and 0.07, respectively). Conclusions: Pulmonary function is abnormal in 90% of adult patients with Hb-SS. Common abnormalities include restrictive physiology and decreased DLCO. Decreased DLCO may indicate more severe sickle vasculopathy characterized by impaired hepatic and renal function. PMID:16556694

Ultrastructural characterization of pulmonary neoplasms. II. The role of electron microscopy in characterization of uncommon epithelial pulmonary neoplasms, metastatic neoplasms to and from lung, and other tumors, including mesenchymal neoplasms.

PubMed

Herrera, G A; Alexander, C B; Jones, J M

1985-01-01

Ultrastructural analysis through better resolution adds significant information to the evaluation and classification of primary pulmonary neoplasms. Light microscopy is limited in the evaluation of lung neoplasms. In some cases the light microscopic appearance may be entirely misleading, whereas in others it is inconclusive. Immunocytochemistry provides information on cytoplasmic differentiation of various tumors and hence more data on their corresponding phenotypes. The data from immunocytochemistry without corresponding objective electron microscopic evaluation may be very difficult to interpret. Correlation of historical, gross, light, electron microscopic, and immunocytochemical data is essential for a final accurate diagnosis (fig. 20). Fine needle aspiration of pulmonary neoplasms is becoming very fashionable and a diagnosis, including type of neoplasm, is expected on the basis of examination of a limited number of cells which further emphasizes the importance of ultrastructural characterization in helping to establish an accurate diagnosis [63-69]. The current classification of pulmonary neoplasms may need to be modified in the near future to incorporate the newly created data [70-72]. At the present time, there appears to be, at least, a need for a 'double standard', as Sobin [73] has suggested, which would permit the evaluation of the biologic significance of the ultrastructural and immunocytochemical findings (as applied to classification of neoplasms) in an effort to derive meaningful clinicopathologic correlations. Figure 20 emphasizes the additive role which should be played by the various diagnostic modalities to enable a morphologic assessment which would be an accurate predictor of biologic behavior. With an accurate assessment of biologic behavior, a more appropriate and rational approach for therapy is possible. There is also an important role for ultrastructural analysis in metastatic pleural and pulmonary neoplasms, primarily adenocarcinomas, as

Risk Factors for Blood Transfusion With Primary Posterior Lumbar Fusion.

PubMed

Basques, Bryce A; Anandasivam, Nidharshan S; Webb, Matthew L; Samuel, Andre M; Lukasiewicz, Adam M; Bohl, Daniel D; Grauer, Jonathan N

2015-11-01

Retrospective cohort study. To identify factors associated with blood transfusion for primary posterior lumbar fusion surgery, and to identify associations between blood transfusion and other postoperative complications. Blood transfusion is a relatively common occurrence for patients undergoing primary posterior lumbar fusion. There is limited information available describing which patients are at increased risk for blood transfusion, and the relationship between blood transfusion and short-term postoperative outcomes is poorly characterized. The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was used to identify patients undergoing primary posterior lumbar fusion from 2011 to 2013. Multivariate analysis was used to find associations between patient characteristics and blood transfusion, along with associations between blood transfusion and postoperative outcomes. Out of 4223 patients, 704 (16.7%) had a blood transfusion. Age 60 to 69 (relative risk [RR] 1.6), age greater than equal to 70 (RR 1.7), American Society of Anesthesiologists class greater than equal to 3 (RR 1.1), female sex (RR 1.1), pulmonary disease (RR 1.2), preoperative hematocrit less than 36.0 (RR 2.0), operative time greater than equal to 310 minutes (RR 2.9), 2 levels (RR 1.6), and 3 or more levels (RR 2.1) were independently associated with blood transfusion. Interbody fusion (RR 0.9) was associated with decreased rates of blood transfusion. Receiving a blood transfusion was significantly associated with any complication (RR 1.7), sepsis (RR 2.6), return to the operating room (RR 1.7), deep surgical site infection (RR 2.6), and pulmonary embolism (RR 5.1). Blood transfusion was also associated with an increase in postoperative length of stay of 1.4 days (P < 0.001). 1 in 6 patients received a blood transfusion while undergoing primary posterior lumbar fusion, and risk factors for these occurrences were characterized. Strategies to minimize

Quantitative proteomic characterization of the lung extracellular matrix in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis.

PubMed

Åhrman, Emma; Hallgren, Oskar; Malmström, Lars; Hedström, Ulf; Malmström, Anders; Bjermer, Leif; Zhou, Xiao-Hong; Westergren-Thorsson, Gunilla; Malmström, Johan

2018-03-01

Remodeling of the extracellular matrix (ECM) is a common feature in lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Here, we applied a sequential tissue extraction strategy to describe disease-specific remodeling of human lung tissue in disease, using end-stages of COPD and IPF. Our strategy was based on quantitative comparison of the disease proteomes, with specific focus on the matrisome, using data-independent acquisition and targeted data analysis (SWATH-MS). Our work provides an in-depth proteomic characterization of human lung tissue during impaired tissue remodeling. In addition, we show important quantitative and qualitative effects of the solubility of matrisome proteins. COPD was characterized by a disease-specific increase in ECM regulators, metalloproteinase inhibitor 3 (TIMP3) and matrix metalloproteinase 28 (MMP-28), whereas for IPF, impairment in cell adhesion proteins, such as collagen VI and laminins, was most prominent. For both diseases, we identified increased levels of proteins involved in the regulation of endopeptidase activity, with several proteins belonging to the serpin family. The established human lung quantitative proteome inventory and the construction of a tissue-specific protein assay library provides a resource for future quantitative proteomic analyses of human lung tissues. We present a sequential tissue extraction strategy to determine changes in extractability of matrisome proteins in end-stage COPD and IPF compared to healthy control tissue. Extensive quantitative analysis of the proteome changes of the disease states revealed altered solubility of matrisome proteins involved in ECM regulators and cell-ECM communication. The results highlight disease-specific remodeling mechanisms associated with COPD and IPF. Copyright © 2018 Elsevier B.V. All rights reserved.

Fundamentals of pulmonary drug delivery.

PubMed

Groneberg, D A; Witt, C; Wagner, U; Chung, K F; Fischer, A

2003-04-01

Aerosol administration of peptide-based drugs plays an important role in the treatment of pulmonary and systemic diseases and the unique cellular properties of airway epithelium offers a great potential to deliver new compounds. As the relative contributions from the large airways to the alveolar space are important to the local and systemic availability, the sites and mechanism of uptake and transport of different target compounds have to be characterized. Among the different respiratory cells, the ciliated epithelial cells of the larger and smaller airways and the type I and type II pneumocytes are the key players in pulmonary drug transport. With their diverse cellular characteristics, each of these cell types displays a unique uptake possibility. Next to the knowledge of these cellular aspects, the nature of aerosolized drugs, characteristics of delivery systems and the depositional and pulmonary clearance mechanisms display major targets to optimize pulmonary drug delivery. Based on the growing knowledge on pulmonary cell biology and pathophysiology due to modern methods of molecular biology, the future characterization of pulmonary drug transport pathways can lead to new strategies in aerosol drug therapy.

Comparative analysis of Micrococcus luteus isolates from blood cultures of patients with pulmonary hypertension receiving epoprostenol continuous infusion.

PubMed

Hirata, Yoshinori; Sata, Makoto; Makiuchi, Yuko; Morikane, Keita; Wada, Akihito; Okabe, Nobuhiko; Tomoike, Hitonobu

2009-12-01

During the period 2002-2008, at the National Cardiovascular Center, Osaka, 28 Micrococcus luteus isolates and one Kocuria spp. isolate were obtained from blood cultures of pulmonary hypertension (PH) patients who were receiving continuous infusion therapy with epoprostenol. Pulsed-field gel electrophoresis patterns of the isolates were unrelated, suggesting that the infections had multiple origins. The preparation of epoprostenol solution by patients themselves was thought to be a risk factor.

Blood characterization using UV/vis spectroscopy

NASA Astrophysics Data System (ADS)

Mattley, Yvette D.; Mitrani-Gold, F.; Orton, S.; Bacon, Christina P.; Leparc, German F.; Bayona, M.; Potter, Robert L.; Garcia-Rubio, Luis H.

1995-05-01

The current methods used for typing blood involve an agglutination reaction which results from the association of specific antibodies with antigens present on the erythrocyte cell surface. While this method is effective, it requires involved laboratory procedures to detect the cell surface antigens. As an alternative technique, uv/vis spectroscopy has been investigated as a novel way to characterize and differentiate the blood types. Typing with this technique is based on spectral differences which appear throughout portions of both the ultraviolet and visible range. The origin of these spectral differences is unknown and presently under investigation. They may be due to intrinsic absorption differences at the molecular level, and/or they may be due to scattering differences brought about by either subtle variation in cell surface characteristics, cell shape or state of aggregation. As the background optical density in these samples is identified and accounted for, the spectral differences become more defined. This work and the continuation of this project will be included in a general database encompassing a wide range of blood samples. In addition, long term goals involve the investigation of diseased blood with the potential of providing a more rapid diagnosis for blood borne pathogens.

Contralateral decubitus positioning enhances computed tomographic angiographic evaluation of pulmonary vasculature in a patient with a pulmonary arteriovenous malformation.

PubMed

Tafti, Bashir Akhavan; Berenji, Gholam R; Santiago, Silverio; Barack, Bruce M

2012-11-01

Computed tomographic pulmonary angiography has become the diagnostic procedure of choice in patients suspected of having a pulmonary embolus. However, intrapulmonary shunting of blood in a variety of pathologic conditions can cause suboptimal opacification of the pulmonary arterial circulation and result in a suboptimal or even nondiagnostic study. Radiologists should be aware of these conditions and be familiar with positioning techniques to minimize such shunting. We report a patient suspected of having pulmonary embolism, in whom a preexisting unilateral arteriovenous malformation prevented adequate evaluation of the pulmonary circulation. Positioning the patient in the contralateral decubitus position significantly enhanced image quality.

Increase in pulmonary blood flow at birth: role of oxygen and lung aeration.

PubMed

Lang, Justin A R; Pearson, James T; Binder-Heschl, Corinna; Wallace, Megan J; Siew, Melissa L; Kitchen, Marcus J; te Pas, Arjan B; Fouras, Andreas; Lewis, Robert A; Polglase, Graeme R; Shirai, Mikiyasu; Hooper, Stuart B

2016-03-01

Lung aeration stimulates the increase in pulmonary blood flow (PBF) at birth, but the spatial relationships between PBF and lung aeration and the role of increased oxygenation remain unclear. Using simultaneous phase-contrast X-ray imaging and angiography, we have investigated the separate roles of lung aeration and increased oxygenation in PBF changes at birth using near-term (30 days of gestation) rabbit kits (n = 18). Rabbits were imaged before ventilation, then the right lung was ventilated with 100% nitrogen (N2), air or 100% O2 (oxygen), before all kits were switched to ventilation in air, followed by ventilation of both lungs using air. Unilateral ventilation of the right lung with 100% N2 significantly increased heart rate (from 69.4 ± 4.9 to 93.0 ± 15.0 bpm), the diameters of both left and right pulmonary axial arteries, number of visible vessels in both left and right lungs, relative PBF index in both pulmonary arteries, and reduced bolus transit time for both left and right axial arteries (from 1.34 ± 0.39 and 1.81 ± 0.43 s to 0.52 ± 0.17 and 0.89 ± 0.21 s in the left and right axial arteries, respectively). Similar changes were observed with 100% oxygen, but increases in visible vessel number and vessel diameter of the axial arteries were greater in the ventilated right lung during unilateral ventilation. These findings confirm that PBF increase at birth is not spatially related to lung aeration and that the increase in PBF to unventilated regions is unrelated to oxygenation, although oxygen can potentiate this increase. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Effects of altitude and exercise on pulmonary capillary integrity: evidence for subclinical high-altitude pulmonary edema.

PubMed

Eldridge, Marlowe W; Braun, Ruedi K; Yoneda, Ken Y; Walby, William F

2006-03-01

Strenuous exercise may be a significant contributing factor for development of high-altitude pulmonary edema, particularly at low or moderate altitudes. Thus we investigated the effects of heavy cycle ergometer exercise (90% maximal effort) under hypoxic conditions in which the combined effects of a marked increase in pulmonary blood flow and nonuniform hypoxic pulmonary vasoconstriction could add significantly to augment the mechanical stress on the pulmonary microcirculation. We postulated that intense exercise at altitude would result in an augmented permeability edema. We recruited eight endurance athletes and examined their bronchoalveolar lavage fluid (BALF) for red blood cells (RBCs), protein, inflammatory cells, and soluble mediators at 2 and 26 h after intense exercise under normoxic and hypoxic conditions. After heavy exercise, under all conditions, the athletes developed a permeability edema with high BALF RBC and protein concentrations in the absence of inflammation. We found that exercise at altitude (3,810 m) caused significantly greater leakage of RBCs [9.2 (SD 3.1)x10(4) cells/ml] into the alveolar space than that seen with normoxic exercise [5.4 (SD 1.2)x10(4) cells/ml]. At altitude, the 26-h postexercise BALF revealed significantly higher RBC and protein concentrations, suggesting an ongoing capillary leak. Interestingly, the BALF profiles following exercise at altitude are similar to that of early high-altitude pulmonary edema. These findings suggest that pulmonary capillary disruption occurs with intense exercise in healthy humans and that hypoxia augments the mechanical stresses on the pulmonary microcirculation.

Pulmonary tissue volume, cardiac output, and diffusing capacity in sustained microgravity

NASA Technical Reports Server (NTRS)

Verbanck, S.; Larsson, H.; Linnarsson, D.; Prisk, G. K.; West, J. B.; Paiva, M.

1997-01-01

In microgravity (microG) humans have marked changes in body fluids, with a combination of an overall fluid loss and a redistribution of fluids in the cranial direction. We investigated whether interstitial pulmonary edema develops as a result of a headward fluid shift or whether pulmonary tissue fluid volume is reduced as a result of the overall loss of body fluid. We measured pulmonary tissue volume (Vti), capillary blood flow, and diffusing capacity in four subjects before, during, and after 10 days of exposure to microG during spaceflight. Measurements were made by rebreathing a gas mixture containing small amounts of acetylene, carbon monoxide, and argon. Measurements made early in flight in two subjects showed no change in Vti despite large increases in stroke volume (40%) and diffusing capacity (13%) consistent with increased pulmonary capillary blood volume. Late in-flight measurements in four subjects showed a 25% reduction in Vti compared with preflight controls (P < 0.001). There was a concomittant reduction in stroke volume, to the extent that it was no longer significantly different from preflight control. Diffusing capacity remained elevated (11%; P < 0.05) late in flight. These findings suggest that, despite increased pulmonary perfusion and pulmonary capillary blood volume, interstitial pulmonary edema does not result from exposure to microG.

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. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Analysis of decrease in lung perfusion blood volume with occlusive and non-occlusive pulmonary embolisms.

PubMed

Ikeda, Yohei; Yoshimura, Norihiko; Hori, Yoshiro; Horii, Yosuke; Ishikawa, Hiroyuki; Yamazaki, Motohiko; Noto, Yoshiyuki; Aoyama, Hidefumi

2014-12-01

The aim of this study was to determine if lung perfusion blood volume (lung PBV) with non-occlusive pulmonary embolism (PE) differs quantitatively and visually from that with occlusive PE and to investigate if lung PBV with non-occlusive PE remains the same as that without PE. Totally, 108 patients suspected of having acute PE underwent pulmonary dual-energy computed tomography angiography (DECTA) between April 2011 and January 2012. Presence of PE on DECTA was evaluated by one radiologist. Two radiologists visually evaluated the PE distribution (segmental or subsegmental) and its nature (occlusive or non-occlusive) on DECTA and classified perfusion in lung PBV as "decreased," "slightly decreased," and "preserved". Two radiologists used a lung PBV application to set a region of interest (ROI) in the center of the lesion and measured HU values of an iodine map. In the same slice as the ROI of the lesion and close to the lesion, another ROI was set in the normal perfusion area without PE, and HUs were measured. The proportion of lesions was compared between the occlusive and non-occlusive groups. HUs were compared among the occlusive, non-occlusive, and corresponding normal groups. Twenty-five patients had 80 segmental or subsegmental lesions. There were 37 and 43 lesions in the occlusive and non-occlusive groups, respectively. The proportion of decreased lesions was 73.0% (27/37) in the occlusive group, while that of preserved lesions in the non-occlusive group was 76.7% (33/43). There was a significant difference in the proportion of lesions (P<0.001) between the two groups. HUs of the iodine map were significantly higher in the non-occlusive group than in the occlusive group (33.8 ± 8.2 HU vs. 11.9 ± 6.1 HU, P<0.001). There was no significant difference in HUs for the entire lesion between the non-occlusive (33.8 ± 8.2 HU) and corresponding normal group (34.5 ± 6.8 HU; P=0.294). Iodine perfusion tended to be visually and quantitatively preserved in lungs with

Intralober pulmonary sequestration with arterial supply from two different origins: a case report.

PubMed

Erden, Ersin Sukru; Yetim, Tulin Durgun; Balci, Ali; Akcay, Adnan Burak; Hakverdi, Sibel; Demirkose, Mesut

2012-01-01

Pulmonary sequestration is a rare anomaly, which does not have a connection with the bronchial system and gets its blood supply, generally, from the aorta or its branches. Anatomically, two different forms were described: intralobar and extralobar. Although 74% of intralobar pulmonary sequestrations get their blood supply from the descending thoracic aorta, they may get their blood supply from different arteries. Furthermore, there is more than one arterial anomaly in 14.8% of cases. We report an intralobar pulmonary sequestration, in which arterial blood supply is from two different origins (Arcus aorta and celiac trunk). To the best of our knowledge, this is the first case in the literature.

[Impact of multi-layer spiral CT angiography of bronchial artery and pulmonary artery in assessment of the main blood supply to the primary lung cancer].

PubMed

Xiao, Xiang-sheng; Yu, Hong; Li, Hui-min; Liu, Shi-yuan; Li, Cheng-zhou; Liu, Jing

2006-04-01

To investigate the blood supply of primary lung cancer (PLC) using CT angiography for bronchial artery (BA) and pulmonary artery (PA). Thin-section enhanced multi-layer spiral CT (MSCT) were carried out in 147 primary lung cancer patients and 46 healthy subjects as control. Three-dimensional images of bronchial artery and pulmonary artery were obtained using volume render (VR) and multi-planar reconstruction (MPR) or maximum intensity projection (MIP) at the workstation, and their morphological findings and relationship with the mass were assessed. 136 primary lung cancer patients and 32 healthy controls were evaluated for at least one bronchial artery displayed clearly in VR. The detective rate of the bronchial artery was 92.5% and 69.6%, respectively. The bronchial artery caliber and the total section area of lesion side in lung cancer patients were significantly larger than that on the contralateral side and that of the control (P < 0.05). Bronchial artery on the lesion side in lung cancer was dilated and tortuous, directly penetrating into the mass with reticularly anastomosed branches. In the PLC patients, all PA were shown clearly with normal morphological image though crossing over the masses in 54 patients; In 25 PLC patients, the PA being essentially intact, was pushed around and surrounded the mass, giving the "hold ball" sign; In 40 other PLC patients, PA being also intact, the mass surrounded and buried the PA from the outside, crushing the PA flat resulting in an eccentric or centrifugal shrinkage, forming the "dead branch" sign; In the rest 28 patients, the PA was surrounded and even compressed, forming the "residual root" sign. Primary lung cancer patient shows dilated bronchial arteries and increased bronchial artery blood flow, whereas pulmonary arteries just pass through the mass or are compressed by the mass. It is further demonstrated that the bronchial artery, instead of the pulmonary artery, is the main vessel of blood supply to the primary

[Aerosolized iloprost therapy for pulmonary hypertensive crisis in 4 patients with idiopathic pulmonary arterial hypertension].

PubMed

Deng, Ke-wu; Zhou, Yu-jie; Xu, Xi-qi; Wu, Ming-ying; Wang, Guo-hong; Bian, Hong; Chen, Bo; Wang, Chun-bo

2012-10-01

To summary the efficacy and safety of aerosolized iloprost in patients with pulmonary hypertensive crisis. On the basis of conventional therapy, aerosolized iloprost (10 µg per time for 10 - 15 min in 2 hours interval, 8 times per day) was administered to four patients with idiopathic pulmonary arterial hypertension and pulmonary hypertensive crisis. Blood pressure, heart rate, systemic artery oxygen saturation, systolic pulmonary arterial pressure (sPAP) measured by echocardiography and the adverse events were analyzed. After aerosolized iloprost therapy, sPAP was significantly decreased and systemic artery oxygen saturation was improved. Adverse events (nausea, vomiting, diarrhea, dry cough) were observed in two patients, and the iloprost use was stopped in one patient due to severe vomiting and diarrhea. Aerosolized iloprost could significantly reduce the sPAP and improve the systemic artery oxygen saturation in patients with pulmonary hypertension crisis.

Bilateral multiple pulmonary artery aneurysms associated with cavitary pulmonary tuberculosis: a case report.

PubMed

Pallangyo, Pedro; Lyimo, Frederick; Bhalia, Smita; Makungu, Hilda; Nyangasa, Bashir; Lwakatare, Flora; Suranyi, Pal; Janabi, Mohamed

2017-07-19

Pulmonary artery aneurysms constitute <1% of aneurysms occurring in the thoracic cavity. Congenital cardiac defects are responsible for the majority (>50%) of cases, however, pulmonary artery aneurysm is a rare sequelae of pulmonary tuberculosis reported in about 5% of patients with chronic cavitary tuberculosis on autopsy. The natural history of this potentially fatal condition remains poorly understood and guidelines for optimal management are controversial. A 24-year-old man, a nursing student of African descent, was referred to us from an up-country regional hospital with a 4-week history of recurrent episodes of breathlessness, awareness of heartbeats and coughing blood 3 weeks after completing a 6-month course of anti-tuberculosis drugs. A physical examination revealed conjuctival and palmar pallor but there were no stigmata of connective tissue disorders, systemic vasculitides or congenital heart disease. An examination of the cardiovascular system revealed accentuated second heart sound (S 2 ) with early diastolic (grade 1/6) and holosystolic (grade 2/6) murmurs at the pulmonic and tricuspid areas respectively. Blood tests showed iron deficiency anemia, prolonged bleeding time, and mild hyponatremia. A chest radiograph revealed bilateral ovoid-shaped perihilar opacities while a computed tomography scan showed bilateral multiple pulmonary artery pseudoaneurysms with surrounding hematoma together with adjacent cystic changes, consolidations, and tree-in-bud appearance. Our patient refused to undergo surgery and died of aneurismal rupture after 9 days of hospitalization. The presence of intractable hemoptysis among patients with tuberculosis even after completion of anti-tuberculosis course should raise an index of suspicion for pulmonary artery aneurysm. Furthermore, despite of its rarity, early recognition and timely surgical intervention of pulmonary artery aneurysm is crucial to reducing morbidity and preventing the attributed mortality.

Selected contribution: redistribution of pulmonary perfusion during weightlessness and increased gravity

NASA Technical Reports Server (NTRS)

Glenny, R. W.; Lamm, W. J.; Bernard, S. L.; An, D.; Chornuk, M.; Pool, S. L.; Wagner, W. W. Jr; Hlastala, M. P.; Robertson, H. T.

2000-01-01

To compare the relative contributions of gravity and vascular structure to the distribution of pulmonary blood flow, we flew with pigs on the National Aeronautics and Space Administration KC-135 aircraft. A series of parabolas created alternating weightlessness and 1.8-G conditions. Fluorescent microspheres of varying colors were injected into the pulmonary circulation to mark regional blood flow during different postural and gravitational conditions. The lungs were subsequently removed, air dried, and sectioned into approximately 2 cm(3) pieces. Flow to each piece was determined for the different conditions. Perfusion heterogeneity did not change significantly during weightlessness compared with normal and increased gravitational forces. Regional blood flow to each lung piece changed little despite alterations in posture and gravitational forces. With the use of multiple stepwise linear regression, the contributions of gravity and vascular structure to regional perfusion were separated. We conclude that both gravity and the geometry of the pulmonary vascular tree influence regional pulmonary blood flow. However, the structure of the vascular tree is the primary determinant of regional perfusion in these animals.

Gross pulmonary thrombosis in a greyhound.

PubMed

Baines, E A; Watson, P J; Stidworthy, M F; Herrtage, M E

2001-09-01

A two-year-old greyhound was presented with progressive dyspnoea. Radiography showed a hypovascular lung pattern with hyperlucent lung fields and echocardiography revealed a large thrombus in the main pulmonary artery. Blood results showed azotaemia and marked hypoalbuminaemia. The dog's clinical condition continued to deteriorate and it was euthanased. Postmortem examination confirmed the presence of the pulmonary thrombus and revealed idiopathic membranous glomerulonephritis.

Association of air pollution sources and aldehydes with biomarkers of blood coagulation, pulmonary inflammation, and systemic oxidative stress.

PubMed

Altemose, Brent; Robson, Mark G; Kipen, Howard M; Ohman Strickland, Pamela; Meng, Qingyu; Gong, Jicheng; Huang, Wei; Wang, Guangfa; Rich, David Q; Zhu, Tong; Zhang, Junfeng

2017-05-01

Using data collected before, during, and after the 2008 Summer Olympic Games in Beijing, this study examines associations between biomarkers of blood coagulation (vWF, sCD62P and sCD40L), pulmonary inflammation (EBC pH, EBC nitrite, and eNO), and systemic oxidative stress (urinary 8-OHdG) with sources of air pollution identified utilizing principal component analysis and with concentrations of three aldehydes of health concern. Associations between the biomarkers and the air pollution source types and aldehydes were examined using a linear mixed effects model, regressing through seven lag days and controlling for ambient temperature, relative humidity, gender, and day of week for the biomarker measurements. The biomarkers for pulmonary inflammation, particularly EBC pH and eNO, were most consistently associated with vehicle and industrial combustion, oil combustion, and vegetative burning. The biomarkers for blood coagulation, particularly vWF and sCD62p, were most consistently associated with oil combustion. Systemic oxidative stress biomarker (8-OHdG) was most consistently associated with vehicle and industrial combustion. The associations of the biomarkers were generally not significant or consistent with secondary formation of pollutants and with the aldehydes. The findings support policies to control anthropogenic pollution sources rather than natural soil or road dust from a cardio-respiratory health standpoint.

Comparison of computed tomography pulmonary angiography and point-of-care tests for pulmonary thromboembolism diagnosis in dogs.

PubMed

Goggs, R; Chan, D L; Benigni, L; Hirst, C; Kellett-Gregory, L; Fuentes, V L

2014-04-01

To evaluate the feasibility of CT pulmonary angiography for identification of naturally occurring pulmonary thromboembolism in dogs using predefined diagnostic criteria and to assess the ability of echocardiography, cardiac troponins, D-dimers and kaolin-activated thromboelastography to predict the presence of pulmonary thromboembolism in dogs. Twelve dogs with immune-mediated haemolytic anaemia and evidence of respiratory distress were prospectively evaluated. Dogs were sedated immediately before CT pulmonary angiography using intravenous butorphanol. Spiral CT pulmonary angiography was performed with a 16 detector-row CT scanner using a pressure injector to infuse contrast media through peripheral intravenous catheters. Pulmonary thromboembolism was diagnosed using predefined criteria. Contemporaneous tests included echocardiography, arterial blood gas analysis, kaolin-activated thromboelastography, D-dimers and cardiac troponins. Based on predefined criteria, four dogs were classified as pulmonary thromboembolism positive, three dogs were suspected to have pulmonary thromboembolism and the remaining five dogs had negative scans. The four dogs identified with pulmonary thromboembolism all had discrete filling defects in main or lobar pulmonary arteries. None of the contemporaneous tests was discriminant for pulmonary thromboembolism diagnosis, although the small sample size was limiting. CT pulmonary angiography can be successfully performed in dogs under sedation, even in at-risk patients with respiratory distress and can both confirm and rule out pulmonary thromboembolism in dogs. © 2014 British Small Animal Veterinary Association.

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

PubMed Central

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

2010-01-01

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

Smooth Muscle-Mediated Connective Tissue Remodeling in Pulmonary Hypertension

NASA Astrophysics Data System (ADS)

Mecham, Robert P.; Whitehouse, Loren A.; Wrenn, David S.; Parks, William C.; Griffin, Gail L.; Senior, Robert M.; Crouch, Edmond C.; Stenmark, Kurt R.; Voelkel, Norbert F.

1987-07-01

Abnormal accumulation of connective tissue in blood vessels contributes to alterations in vascular physiology associated with disease states such as hypertension and atherosclerosis. Elastin synthesis was studied in blood vessels from newborn calves with severe pulmonary hypertension induced by alveolar hypoxia in order to investigate the cellular stimuli that elicit changes in pulmonary arterial connective tissue production. A two- to fourfold increase in elastin production was observed in pulmonary artery tissue and medial smooth muscle cells from hypertensive calves. This stimulation of elastin production was accompanied by a corresponding increase in elastin messenger RNA consistent with regulation at the transcriptional level. Conditioned serum harvested from cultures of pulmonary artery smooth muscle cells isolated from hypertensive animals contained one or more low molecular weight elastogenic factors that stimulated the production of elastin in both fibroblasts and smooth muscle cells and altered the chemotactic responsiveness of fibroblasts to elastin peptides. These results suggest that connective tissue changes in the pulmonary vasculature in response to pulmonary hypertension are orchestrated by the medial smooth muscle cell through the generation of specific differentiation factors that alter both the secretory phenotype and responsive properties of surrounding cells.

Characterization of the seven-day course of pulmonary response following unilateral lung acid injury in rats.

PubMed

Setzer, Florian; Schmidt, Barbara; Hueter, Lars; Schwarzkopf, Konrad; Sänger, Jörg; Schreiber, Torsten

2018-01-01

Aspiration of gastric acid is an important cause of acute lung injury. The time course of the pulmonary response to such an insult beyond the initial 48 hours is incompletely characterized. The purpose of this study was to comprehensively describe the pulmonary effects of focal lung acid injury over a seven day period in both directly injured and not directly injured lung tissue. Male Wistar rats underwent left-endobronchial instillation with hydrochloric acid and were sacrificed at 4, 24, 48, 96 or 168 h after the insult. Healthy non-injured animals served as controls. We assessed inflammatory cell counts and cytokine levels in right and left lung lavage fluid and blood, arterial oxygen tension, alterations in lung histology, lung wet-to-dry weight ratio and differential lung perfusion. Lung acid instillation induced an early strong inflammatory response in the directly affected lung, peaking at 4-24 hours, with only partial resolution after 7 days. A less severe response with complete resolution after 4 days was seen in the opposite lung. Alveolar cytokine levels, with exception of IL-6, only partially reflected the localization of lung injury and the time course of the functional and histologic alterations. Alveolar leucocyte subpopulations exhibited different time courses in the acid injured lung with persistent elevation of alveolar lymphocytes and macrophages. After acid instillation there was an early transient decrease in arterial oxygen tension and lung perfusion was preferentially distributed to the non-injured lung. These findings provide a basis for further research in the field of lung acid injury and for studies exploring effects of mechanical ventilation on injured lungs. Incomplete recovery in the directly injured lung 7 days after acid instillation suggests that increased vulnerability and susceptibility to further noxious stimuli are still present at that time.

Pulmonary Vascular Congestion: A Mechanism for Distal Lung Unit Dysfunction in Obesity.

PubMed

Oppenheimer, Beno W; Berger, Kenneth I; Ali, Saleem; Segal, Leopoldo N; Donnino, Robert; Katz, Stuart; Parikh, Manish; Goldring, Roberta M

2016-01-01

Obesity is characterized by increased systemic and pulmonary blood volumes (pulmonary vascular congestion). Concomitant abnormal alveolar membrane diffusion suggests subclinical interstitial edema. In this setting, functional abnormalities should encompass the entire distal lung including the airways. We hypothesize that in obesity: 1) pulmonary vascular congestion will affect the distal lung unit with concordant alveolar membrane and distal airway abnormalities; and 2) the degree of pulmonary congestion and membrane dysfunction will relate to the cardiac response. 54 non-smoking obese subjects underwent spirometry, impulse oscillometry (IOS), diffusion capacity (DLCO) with partition into membrane diffusion (DM) and capillary blood volume (VC), and cardiac MRI (n = 24). Alveolar-capillary membrane efficiency was assessed by calculation of DM/VC. Mean age was 45±12 years; mean BMI was 44.8±7 kg/m2. Vital capacity was 88±13% predicted with reduction in functional residual capacity (58±12% predicted). Despite normal DLCO (98±18% predicted), VC was elevated (135±31% predicted) while DM averaged 94±22% predicted. DM/VC varied from 0.4 to 1.4 with high values reflecting recruitment of alveolar membrane and low values indicating alveolar membrane dysfunction. The most abnormal IOS (R5 and X5) occurred in subjects with lowest DM/VC (r2 = 0.31, p<0.001; r2 = 0.34, p<0.001). Cardiac output and index (cardiac output / body surface area) were directly related to DM/VC (r2 = 0.41, p<0.001; r2 = 0.19, p = 0.03). Subjects with lower DM/VC demonstrated a cardiac output that remained in the normal range despite presence of obesity. Global dysfunction of the distal lung (alveolar membrane and distal airway) is associated with pulmonary vascular congestion and failure to achieve the high output state of obesity. Pulmonary vascular congestion and consequent fluid transudation and/or alterations in the structure of the alveolar capillary membrane may be considered often

Thermographic venous blood flow characterization with external cooling stimulation

NASA Astrophysics Data System (ADS)

Saxena, Ashish; Ng, E. Y. K.; Raman, Vignesh

2018-05-01

Experimental characterization of blood flow in a human forearm is done with the application of continuous external cooling based active thermography method. Qualitative and quantitative detection of the blood vessel in a thermal image is done, along with the evaluation of blood vessel diameter, blood flow direction, and velocity in the target blood vessel. Subtraction based image manipulation is performed to enhance the feature contrast of the thermal image acquired after the removal of external cooling. To demonstrate the effect of occlusion diseases (obstruction), an external cuff based occlusion is applied after the removal of cooling and its effect on the skin rewarming is studied. Using external cooling, a transit time method based blood flow velocity estimation is done. From the results obtained, it is evident that an external cooling based active thermography method can be used to develop a diagnosis tool for superficial blood vessel diseases.

Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease.

PubMed

Yun, Jeong H; Lamb, Andrew; Chase, Robert; Singh, Dave; Parker, Margaret M; Saferali, Aabida; Vestbo, Jørgen; Tal-Singer, Ruth; Castaldi, Peter J; Silverman, Edwin K; Hersh, Craig P

2018-06-01

Eosinophilic airway inflammation in patients with chronic obstructive pulmonary disease (COPD) is associated with exacerbations and responsivity to steroids, suggesting potential shared mechanisms with eosinophilic asthma. However, there is no consistent blood eosinophil count that has been used to define the increased exacerbation risk. We sought to investigate blood eosinophil counts associated with exacerbation risk in patients with COPD. Blood eosinophil counts and exacerbation risk were analyzed in patients with moderate-to-severe COPD by using 2 independent studies of former and current smokers with longitudinal data. The Genetic Epidemiology of COPD (COPDGene) study was analyzed for discovery (n = 1,553), and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study was analyzed for validation (n = 1,895). A subset of the ECLIPSE study subjects were used to assess the stability of blood eosinophil counts over time. COPD exacerbation risk increased with higher eosinophil counts. An eosinophil count threshold of 300 cells/μL or greater showed adjusted incidence rate ratios for exacerbations of 1.32 in the COPDGene study (95% CI, 1.10-1.63). The cutoff of 300 cells/μL or greater was validated for prospective risk of exacerbation in the ECLIPSE study, with adjusted incidence rate ratios of 1.22 (95% CI, 1.06-1.41) using 3-year follow-up data. Stratified analysis confirmed that the increased exacerbation risk associated with an eosinophil count of 300 cells/μL or greater was driven by subjects with a history of frequent exacerbations in both the COPDGene and ECLIPSE studies. Patients with moderate-to-severe COPD and blood eosinophil counts of 300 cells/μL or greater had an increased risk exacerbations in the COPDGene study, which was prospectively validated in the ECLIPSE study. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Pharmacodynamic and pharmacokinetic assessment of pulmonary rehabilitation mixture for the treatment of pulmonary fibrosis.

PubMed

Zhao, Juanjuan; Ren, Yan; Qu, Yubei; Jiang, Wanglin; Lv, Changjun

2017-06-14

Pulmonary rehabilitation mixture (PRM), a Chinese herbal medicine formula, has been used to treat pulmonary fibrosis for decades. In this study, we systematically evaluated the pharmacodynamic and pharmacokinetic performance of PRM. The pharmacodynamic results showed that PRM could improve the condition of CoCl 2 -stimulated human type II alveolar epithelial cells, human pulmonary microvascular endothelial cells, human lung fibroblasts and pulmonary fibrosis rats induced by bleomycin, PRM treatment reduced the expression of platelet-derived growth factor, fibroblast growth factor, toll-like receptor 4, high-mobility group box protein 1 and hypoxia-inducible factor 1α. In the pharmacokinetic study, an accurate and sensitive ultra-high performance liquid chromatography tandem mass spectrometry method was developed and validated for the simultaneous determination of calycosin, calycosin-7-O-glucoside, formononetin, ononin and mangiferin of PRM in the rat plasma for the first time. The method was then successfully applied to the comparative pharmacokinetic study of PRM in normal and pulmonary fibrosis rats. The five constituents could be absorbed in the blood after the oral administration of PRM and exhibited different pharmacokinetic behaviors in normal and pulmonary fibrosis rats. In summary, PRM exhibited a satisfactory pharmacodynamic and pharmacokinetic performance, which highlights PRM as a potential multi-target oral drug for the treatment of pulmonary fibrosis.

[Significance of extravascular lung water index, pulmonary vascular permeability index, and in- trathoracic blood volume index in the differential diagnosis of burn-induced pulmonary edema].

PubMed

Lei, Li; Jiajun, Sheng; Guangyi, Wang; Kaiyang, Lyu; Jing, Qin; Gongcheng, Liu; Bing, Ma; Shichu, Xiao; Shihui, Zhu

2015-06-01

To appraise the significance of extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI), and intrathoracic blood volume index (ITBVI) in the differential diagnosis of the type of burn-induced pulmonary edema. The clinical data of 38 patients, with severe burn hospitalized in our burn ICU from December 2011 to September 2014 suffering from the complication of pulmonary edema within one week post burn and treated with mechanical ventilation accompanied by pulse contour cardiac output monitoring, were retrospectively analyzed. The patients were divided into lung injury group ( L, n = 17) and hydrostatic group (H, n = 21) according to the diagnosis of pulmonary edema. EVLWI, PVPI, ITBVI, oxygenation index, and lung injury score ( LIS) were compared between two groups, and the correlations among the former four indexes and the correlations between each of the former three indexes and types of pulmonary edema were analyzed. Data were processed with t test, chi-square test, Mann-Whitney U test, Pearson correlation test, and accuracy test [receiver operating characteristic (ROC) curve]. There was no statistically significant difference in EVLWI between group L and group H, respectively (12.9 ± 3.1) and (12.1 ± 2.1) mL/kg, U = 159.5, P > 0.05. The PVPI and LIS of patients in group L were respectively 2.6 ± 0.5 and (2.1 ± 0.6) points, and they were significantly higher than those in group H [1.4 ± 0.3 and (1.0 ± 0.6) points, with U values respectively 4.5 and 36.5, P values below 0.01]. The ITBVI and oxygenation index of patients in group L were respectively (911 197) mL/m2 and (136 ± 69) mmHg (1 mmHg = 0.133 kPa), which were significantly lower than those in group H [(1,305 ± 168) mL/m2 and (212 ± 60) mmHg, with U values respectively 21.5 and 70.5, P values below 0.01]. In group L, there was obviously positive correlation between EVLWI and PVPI, or EVLWI and ITBVI (with r values respectively 0.553 and 0.807, P < 0.05 or P < 0.01), and

BMP type II receptor as a therapeutic target in pulmonary arterial hypertension.

PubMed

Orriols, Mar; Gomez-Puerto, Maria Catalina; Ten Dijke, Peter

2017-08-01

Pulmonary arterial hypertension (PAH) is a chronic disease characterized by a progressive elevation in mean pulmonary arterial pressure. This occurs due to abnormal remodeling of small peripheral lung vasculature resulting in progressive occlusion of the artery lumen that eventually causes right heart failure and death. The most common cause of PAH is inactivating mutations in the gene encoding a bone morphogenetic protein type II receptor (BMPRII). Current therapeutic options for PAH are limited and focused mainly on reversal of pulmonary vasoconstriction and proliferation of vascular cells. Although these treatments can relieve disease symptoms, PAH remains a progressive lethal disease. Emerging data suggest that restoration of BMPRII signaling in PAH is a promising alternative that could prevent and reverse pulmonary vascular remodeling. Here we will focus on recent advances in rescuing BMPRII expression, function or signaling to prevent and reverse pulmonary vascular remodeling in PAH and its feasibility for clinical translation. Furthermore, we summarize the role of described miRNAs that directly target the BMPR2 gene in blood vessels. We discuss the therapeutic potential and the limitations of promising new approaches to restore BMPRII signaling in PAH patients. Different mutations in BMPR2 and environmental/genetic factors make PAH a heterogeneous disease and it is thus likely that the best approach will be patient-tailored therapies.

Pulmonary function in space

NASA Technical Reports Server (NTRS)

West, J. B.; Elliott, A. R.; Guy, H. J.; Prisk, G. K.

1997-01-01

The lung is exquisitely sensitive to gravity, and so it is of interest to know how its function is altered in the weightlessness of space. Studies on National Aeronautics and Space Administration (NASA) Spacelabs during the last 4 years have provided the first comprehensive data on the extensive changes in pulmonary function that occur in sustained microgravity. Measurements of pulmonary function were made on astronauts during space shuttle flights lasting 9 and 14 days and were compared with extensive ground-based measurements before and after the flights. Compared with preflight measurements, cardiac output increased by 18% during space flight, and stroke volume increased by 46%. Paradoxically, the increase in stroke volume occurred in the face of reductions in central venous pressure and circulating blood volume. Diffusing capacity increased by 28%, and the increase in the diffusing capacity of the alveolar membrane was unexpectedly large based on findings in normal gravity. The change in the alveolar membrane may reflect the effects of uniform filling of the pulmonary capillary bed. Distributions of blood flow and ventilation throughout the lung were more uniform in space, but some unevenness remained, indicating the importance of nongravitational factors. A surprising finding was that airway closing volume was approximately the same in microgravity and in normal gravity, emphasizing the importance of mechanical properties of the airways in determining whether they close. Residual volume was unexpectedly reduced by 18% in microgravity, possibly because of uniform alveolar expansion. The findings indicate that pulmonary function is greatly altered in microgravity, but none of the changes observed so far will apparently limit long-term space flight. In addition, the data help to clarify how gravity affects pulmonary function in the normal gravity environment on Earth.

[Acute heart failure: acute cardiogenic pulmonary edema and cardiogenic shock].

PubMed

Sánchez Marteles, Marta; Urrutia, Agustín

2014-03-01

Acute cardiogenic pulmonary edema and cardiogenic shock are two of the main forms of presentation of acute heart failure. Both entities are serious, with high mortality, and require early diagnosis and prompt and aggressive management. Acute pulmonary edema is due to the passage of fluid through the alveolarcapillary membrane and is usually the result of an acute cardiac episode. Correct evaluation and clinical identification of the process is essential in the management of acute pulmonary edema. The initial aim of treatment is to ensure hemodynamic stability and to correct hypoxemia. Other measures that can be used are vasodilators such as nitroglycerin, loop diuretics and, in specific instances, opioids. Cardiogenic shock is characterized by sustained hypoperfusion, pulmonary wedge pressure > 18 mmHg and a cardiac index < 2.2l/min/m(2). The process typically presents with hypotension (systolic blood pressure < 90 mmHg or a decrease in mean arterial pressure > 30 mmHg) and absent or reduced diuresis (< 0.5 ml/kg/h). The most common cause is left ventricular failure due to acute myocardial infarction. Treatment consists of general measures to reverse acidosis and hypoxemia, as well as the use of vasopressors and inotropic drugs. Early coronary revascularization has been demonstrated to improve survival in shock associated with ischaemic heart disease. Copyright © 2014 Elsevier España, S.L. All rights reserved.

PPAR-γ Regulates Carnitine Homeostasis and Mitochondrial Function in a Lamb Model of Increased Pulmonary Blood Flow

PubMed Central

Rafikov, Ruslan; Kumar, Sanjiv; Hou, Yali; Oishi, Peter E.; Datar, Sanjeev A.; Raff, Gary; Fineman, Jeffrey R.; Black, Stephen M.

2012-01-01

Objective Carnitine homeostasis is disrupted in lambs with endothelial dysfunction secondary to increased pulmonary blood flow (Shunt). Our recent studies have also indicated that the disruption in carnitine homeostasis correlates with a decrease in PPAR-γ expression in Shunt lambs. Thus, this study was carried out to determine if there is a causal link between loss of PPAR-γ signaling and carnitine dysfunction, and whether the PPAR-γ agonist, rosiglitazone preserves carnitine homeostasis in Shunt lambs. Methods and Results siRNA-mediated PPAR-γ knockdown significantly reduced carnitine palmitoyltransferases 1 and 2 (CPT1 and 2) and carnitine acetyltransferase (CrAT) protein levels. This decrease in carnitine regulatory proteins resulted in a disruption in carnitine homeostasis and induced mitochondrial dysfunction, as determined by a reduction in cellular ATP levels. In turn, the decrease in cellular ATP attenuated NO signaling through a reduction in eNOS/Hsp90 interactions and enhanced eNOS uncoupling. In vivo, rosiglitazone treatment preserved carnitine homeostasis and attenuated the development of mitochondrial dysfunction in Shunt lambs maintaining ATP levels. This in turn preserved eNOS/Hsp90 interactions and NO signaling. Conclusion Our study indicates that PPAR-γ signaling plays an important role in maintaining mitochondrial function through the regulation of carnitine homeostasis both in vitro and in vivo. Further, it identifies a new mechanism by which PPAR-γ regulates NO signaling through Hsp90. Thus, PPAR-γ agonists may have therapeutic potential in preventing the endothelial dysfunction in children with increased pulmonary blood flow. PMID:22962578

Pulmonary nodule characterization, including computer analysis and quantitative features.

PubMed

Bartholmai, Brian J; Koo, Chi Wan; Johnson, Geoffrey B; White, Darin B; Raghunath, Sushravya M; Rajagopalan, Srinivasan; Moynagh, Michael R; Lindell, Rebecca M; Hartman, Thomas E

2015-03-01

Pulmonary nodules are commonly detected in computed tomography (CT) chest screening of a high-risk population. The specific visual or quantitative features on CT or other modalities can be used to characterize the likelihood that a nodule is benign or malignant. Visual features on CT such as size, attenuation, location, morphology, edge characteristics, and other distinctive "signs" can be highly suggestive of a specific diagnosis and, in general, be used to determine the probability that a specific nodule is benign or malignant. Change in size, attenuation, and morphology on serial follow-up CT, or features on other modalities such as nuclear medicine studies or MRI, can also contribute to the characterization of lung nodules. Imaging analytics can objectively and reproducibly quantify nodule features on CT, nuclear medicine, and magnetic resonance imaging. Some quantitative techniques show great promise in helping to differentiate benign from malignant lesions or to stratify the risk of aggressive versus indolent neoplasm. In this article, we (1) summarize the visual characteristics, descriptors, and signs that may be helpful in management of nodules identified on screening CT, (2) discuss current quantitative and multimodality techniques that aid in the differentiation of nodules, and (3) highlight the power, pitfalls, and limitations of these various techniques.

Total anomalous pulmonary venous return

MedlinePlus

... the heart do not attach normally to the left atrium (left upper chamber of the heart). Instead, they attach ... returns through the pulmonary (lung) veins to the left side of the heart, which sends blood out ...

AltitudeOmics: effect of reduced barometric pressure on detection of intrapulmonary shunt, pulmonary gas exchange efficiency, and total pulmonary resistance.

PubMed

Petrassi, Frank A; Davis, James T; Beasley, Kara M; Evero, Oghenero; Elliott, Jonathan E; Goodman, Randall D; Futral, Joel E; Subudhi, Andrew; Solano-Altamirano, J Manuel; Goldman, Saul; Roach, Robert C; Lovering, Andrew T

2018-05-01

Blood flow through intrapulmonary arteriovenous anastomoses (Q IPAVA ) occurs in healthy humans at rest and during exercise when breathing hypoxic gas mixtures at sea level and may be a source of right-to-left shunt. However, at high altitudes, Q IPAVA is reduced compared with sea level, as detected using transthoracic saline contrast echocardiography (TTSCE). It remains unknown whether the reduction in Q IPAVA (i.e., lower bubble scores) at high altitude is due to a reduction in bubble stability resulting from the lower barometric pressure (P B ) or represents an actual reduction in Q IPAVA . To this end, Q IPAVA , pulmonary artery systolic pressure (PASP), cardiac output (Q T ), and the alveolar-to-arterial oxygen difference (AaDO 2 ) were assessed at rest and during exercise (70-190 W) in the field (5,260 m) and in the laboratory (1,668 m) during four conditions: normobaric normoxia (NN; [Formula: see text] = 121 mmHg, P B  = 625 mmHg; n = 8), normobaric hypoxia (NH; [Formula: see text] = 76 mmHg, P B  = 625 mmHg; n = 7), hypobaric normoxia (HN; [Formula: see text] = 121 mmHg, P B  = 410 mmHg; n = 8), and hypobaric hypoxia (HH; [Formula: see text] = 75 mmHg, P B  = 410 mmHg; n = 7). We hypothesized Q IPAVA would be reduced during exercise in isooxic hypobaria compared with normobaria and that the AaDO 2 would be reduced in isooxic hypobaria compared with normobaria. Bubble scores were greater in normobaric conditions, but the AaDO 2 was similar in both isooxic hypobaria and normobaria. Total pulmonary resistance (PASP/Q T ) was elevated in HN and HH. Using mathematical modeling, we found no effect of hypobaria on bubble dissolution time within the pulmonary transit times under consideration (<5 s). Consequently, our data suggest an effect of hypobaria alone on pulmonary blood flow. NEW & NOTEWORTHY Blood flow through intrapulmonary arteriovenous anastomoses, detected by transthoracic saline contrast echocardiography, was reduced during exercise

Measurement of pulmonary capillary blood flow in infants by plethysmography.

PubMed Central

Stocks, J; Costeloe, K; Winlove, C P; Godfrey, S

1977-01-01

An accurate method for measuring effective pulmonary capillary blood flow (Qc eff) in infants has been developed with an adaptation of the plethysmographic technique. Measurements were made on 19 preterm. 14 small-for-dates, and 7 fullterm normal infants with a constant volume whole body plethysmograph in which the infant rebreathed nitrous oxide. There was a highly significant correlation between Qc eff and body weight, and this relationship was unaffected by premature delivery or intrauterine growth retardation. Mean Qc eff in preterm, small-for dates, and fullterm infants was 203, 208 and 197 ml min-1 kg-1, respectively, with no significant differences between the groups. A significant negative correlation existed between Qc eff and haematocrit in the preterm infants. There was no relationship between weight standardized Qc eff and postnatal age in any of the groups. With this technique, it was possible to readily recognise the presence of rapid recirculation (indicative of shunting) in several of the infants, suggesting that rebreathing methods for the assessment of Qc eff should not be applied indiscriminately during the neonatal period. By taking care to overcome the potential sources of technical error, it was possible to obtain highly reproducible results of Qc eff in infants over a wider age range than has been previously reported. PMID:838861

Pulmonary vascular remodelling in a high-altitude Aymara Indian

NASA Astrophysics Data System (ADS)

Heath, Donald; Williams, David

1991-12-01

A histological study of the pulmonary vasculature in a young male high-altitude Aymara Indian revealed four aspects of interest. There was muscularization of the terminal portion of the pulmonary arterial tree to involve pulmonary arterioles as small as 15 μm in diameter, thus forming a basis for the slightly increased pulmonary vascular resistance of native highlanders. Intimal longitudinal muscle was found in pulmonary arteries and arterioles and thought to be due to chronic alveolar hypoxia. Inner muscular tubes similar to those found in chronic obstructive lung disease were present. Pulmonary veins and venules also showed intimal muscularization suggesting that alveolar hypoxia affects vascular smooth muscle cells per se irrespective of their situation. The nature of the remodelling in a pulmonary blood vessel depends on a combination of hypoxia and haemodynamics.

Relationship of cerebral blood flow to aortic-to-pulmonary collateral/shunt flow in single ventricles

PubMed Central

Fogel, Mark A; Li, Christine; Wilson, Felice; Pawlowski, Tom; Nicolson, Susan C; Montenegro, Lisa M; Berenstein, Laura Diaz; Spray, Thomas L; Gaynor, J William; Fuller, Stephanie; Keller, Marc S; Harris, Matthew A; Whitehead, Kevin K; Clancy, Robert; Elci, Okan; Bethel, Jim; Vossough, Arastoo; Licht, Daniel J

2016-01-01

Objective Patients with single ventricle can develop aortic-to-pulmonary collaterals (APCs). Along with systemic-to-pulmonary artery shunts, these structures represent a direct pathway from systemic to pulmonary circulations, and may limit cerebral blood flow (CBF). This study investigated the relationship between CBF and APC flow on room air and in hypercarbia, which increases CBF in patients with single ventricle. Methods 106 consecutive patients with single ventricle underwent 118 cardiac magnetic resonance (CMR) scans in this cross-sectional study; 34 prior to bidirectional Glenn (BDG) (0.50±0.30 years old), 50 prior to Fontan (3.19±1.03 years old) and 34 3–9 months after Fontan (3.98±1.39 years old). Velocity mapping measured flows in the aorta, cavae and jugular veins. Analysis of variance (ANOVA) and multiple linear regression were used. Significance was p<0.05. Results A strong inverse correlation was noted between CBF and APC/shunt both on room air and with hypercarbia whether CBF was indexed to aortic flow or body surface area, independent of age, cardiopulmonary bypass time, Po2 and Pco2 (R=−0.67–−0.70 for all patients on room air, p<0.01 and R=−0.49–−0.90 in hypercarbia, p<0.01). Correlations were not different between surgical stages. CBF was lower, and APCs/shunt flow was higher prior to BDG than in other stages. Conclusions There is a strong inverse relationship between CBF and APC/shunt flow in patients with single ventricle throughout surgical reconstruction on room air and in hypercarbia independent of other factors. We speculate that APC/shunt flow may have a negative impact on cerebral development and neurodevelopmental outcome. Interventions on APC may modify CBF, holding out the prospect for improving neurodevelopmental trajectory. Trial Registration Number NCT02135081. PMID:26048877

Pulse oximetry in the pulmonary tissue for the non-invasive measurement of mixed venous oxygen saturation.

PubMed

Nitzan, Meir; Nitzan, Itamar

2013-08-01

The oxygen saturation of the systemic arterial blood is associated with the adequacy of respiration, and can be measured non-invasively by pulse oximetry in the systemic tissue. The oxygen saturation of the blood in the pulmonary artery, the mixed venous blood, reflects the balance between oxygen supply to the systemic tissues and their oxygen demand. The mixed venous oxygen saturation has also clinical significance because it is used in Fick equation for the quantitative measurement of cardiac output. At present the measurement of the mixed venous oxygen saturation is invasive and requires insertion of a Swan-Ganz catheter into the pulmonary artery. We suggest a noninvasive method for the measurement of the mixed venous oxygen saturation in infants, pulmonary pulse oximetry. The method is similar to the systemic pulse oximetry, which is based on the different light absorption curves of oxygenated and deoxygenated hemoglobin and on the analysis of photoplethysmographic curves in two wavelengths. The proposed pulmonary pulse oximeter includes light-sources of two wavelengths in the infrared, which illuminate the pulmonary tissue through the thoracic wall. Part of the light which is scattered back from the pulmonary tissue and passes through the thoracic wall is detected, and for each wavelength a pulmonary photoplethysmographic curve is obtained. The pulmonary photoplethysmographic curves reflect blood volume increase during systole in the pulmonary arteries in the lung tissue, which contain mixed venous blood. The ratio R of the amplitude-to-baseline ratio for the two wavelengths is related to the mixed venous oxygen saturation through equations derived for the systemic pulse oximetry. The method requires the use of extinction coefficients values for oxygenated and deoxygenated hemoglobin, which can be found in the literature. Copyright © 2013 Elsevier Ltd. All rights reserved.

Stretch-induced contraction in pulmonary arteries.

PubMed

Kulik, T J; Evans, J N; Gamble, W J

1988-12-01

Stretch stimulates contraction of systemic blood vessels, but the response has not been described in pulmonary vessels. To determine whether pulmonary arteries contract when stretched, isolated cylindrical segments of pulmonary arteries were suspended between two parallel wires, stretched, and the active force was generated in response to stretch measured. Eighty-nine percent of segments from small (in situ diameter less than 1,000 microns) feline pulmonary arteries contracted when stretched, and in 65% of these the magnitude of stretch was related to the magnitude of contraction. Large (in situ diameter greater than or equal to 1,000 microns) feline pulmonary arteries did not contract with stretch. Multiple, rapidly repeated stretches resulted in a diminution of active force development. Stretch-induced contraction required external Ca2+ and was abolished by diltiazem (10 microns), but it was not affected by phenoxybenzamine, phentolamine, diethylcarbamazine, or mechanical removal of endothelium. Indomethacin blunted but did not abolish stretch-induced contraction, an effect that may have been nonspecific. This study suggests that stretch can act, probably directly, on smooth muscle in small feline pulmonary arteries to elicit contraction and that it may be a determinant of pulmonary vascular tone. In addition, feline pulmonary arteries are suitable for the in vitro study of stretch-induced contraction.

Pulmonary Hyperinflation and Left Ventricular Mass

PubMed Central

Smith, Benjamin M; Kawut, Steven M.; Bluemke, David A; Basner, Robert C; Gomes, Antoinette S; Hoffman, Eric; Kalhan, Ravi; Lima, João AC; Liu, Chia-Ying; Michos, Erin D; Prince, Martin R; Rabbani, LeRoy; Rabinowitz, Daniel; Shimbo, Daichi; Shea, Steven; Barr, R Graham

2013-01-01

Background Left ventricular (LV) mass is an important predictor of heart failure and cardiovascular mortality, yet determinants of LV mass are incompletely understood. Pulmonary hyperinflation in chronic obstructive pulmonary disease (COPD) may contribute to changes in intrathoracic pressure that increase LV wall stress. We therefore hypothesized that residual lung volume in COPD would be associated with greater LV mass. Methods and results The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited smokers aged 50–79 years who were free of clinical cardiovascular disease. LV mass was measured by cardiac magnetic resonance. Pulmonary function testing was performed according to guidelines. Regression models were used to adjust for age, sex, body size, blood pressure and other cardiac risk factors. Among 119 MESA COPD Study participants, mean age was 69±6 years, 55% were male and 65% had COPD, mostly of mild or moderate severity. Mean LV mass was 128±34 grams. Residual lung volume was independently associated with greater LV mass (7.2 grams per standard deviation increase in residual volume; 95% CI 2.2 to 12; P=0.004), and was similar in magnitude to that of systolic blood pressure (7.6 grams per standard deviation increase in systolic blood pressure, 95% CI 4.3 to 11 grams; p<0.001). Similar results were observed for LV mass to end-diastolic volume ratio (p=0.02) and with hyperinflation measured as residual volume to total lung capacity ratio (P=0.009). Conclusions Pulmonary hyperinflation, as measured by residual lung volume or residual lung volume to total lung capacity ratio, is associated with greater LV mass. PMID:23493320

Redistribution of pulmonary blood flow during unilateral hypoxia in prone and supine dogs

NASA Technical Reports Server (NTRS)

Mann, C. M.; Domino, K. B.; Walther, S. M.; Glenny, R. W.; Polissar, N. L.; Hlastala, M. P.

1998-01-01

We used fluorescent-labeled microspheres in pentobarbital-anesthetized dogs to study the effects of unilateral alveolar hypoxia on the pulmonary blood flow distribution. The left lung was ventilated with inspired O2 fraction of 1.0, 0.09, or 0.03 in random order; the right lung was ventilated with inspired O2 fraction of 1.0. The lungs were removed, cleared of blood, dried at total lung capacity, then cubed to obtain approximately 1,500 small pieces of lung ( approximately 1.7 cm3). The coefficient of variation of flow increased (P < 0.001) in the hypoxic lung but was unchanged in the hyperoxic lung. Most (70-80%) variance in flow in the hyperoxic lung was attributable to structure, in contrast to only 30-40% of the variance in flow in the hypoxic lung (P < 0.001). When adjusted for the change in total flow to each lung, 90-95% of the variance in the hyperoxic lung was attributable to structure compared with 70-80% in the hypoxic lung (P < 0.001). The hilar-to-peripheral gradient, adjusted for change in total flow, decreased in the hypoxic lung (P = 0.005) but did not change in the hyperoxic lung. We conclude that hypoxic vasoconstriction alters the regional distribution of flow in the hypoxic, but not in the hyperoxic, lung.

Nano-liposomal dry powder inhaler of tacrolimus: preparation, characterization, and pulmonary pharmacokinetics.

PubMed

Chougule, Mahavir; Padhi, Bijay; Misra, Ambikanandan

2007-01-01

The studies were undertaken to evaluate feasibility of pulmonary delivery of liposomaly encapsulated tacrolimus dry powder inhaler for prolonged drug retention in lungs as rescue therapy to prevent refractory rejection of lungs after transplantation. Tacrolimus encapsulated liposomes were prepared by thin film evaporation technique and liposomal dispersion was passed through high pressure homogenizer. Tacrolimus nano-liposomes (NLs) were separated by centrifugation and characterized. NLs were dispersed in phosphate buffer saline (PBS) pH 7.4 containing different additives like lactose, sucrose, and trehalose, and L-leucine as antiadherent. The dispersion was spray dried and spray dried powders were characterized. In vitro and in vivo pulmonary deposition was performed using Andersen Cascade Impactor and intratracheal instillation in rats respectively. NLs were found to have average size of 140 nm, 96% +/- 1.5% drug entrapment, and zeta potential of 1.107 mV. Trehalose based formulation was found to have low density, good flowability, particle size of 9.46 +/- 0.8 microm, maximum fine particle fraction (FPF) of 71.1 +/- 2.5%, mean mass aerodynamic diameter (MMAD) 2.2 +/- 0.1 microm, and geometric standard deviation (GSD) 1.7 +/- 0.2. Developed formulations were found to have in vitro prolonged drug release up to 18 hours, following Higuchi's Controlled Release model. In vivo studies revealed maximal residence of tacrolimus within lungs of 24 hours, suggesting slow clearance from the lungs. The investigation provides a practical approach for direct delivery of tacrolimus encapsulated in NLs for controlled and prolonged retention at the site of action. It may play a promising role as rescue therapy in reducing the risk of acute rejection and chronic rejection.

Inflow-weighted pulmonary perfusion: comparison between dynamic contrast-enhanced MRI versus perfusion scintigraphy in complex pulmonary circulation

PubMed Central

2013-01-01

Background Due to the different properties of the contrast agents, the lung perfusion maps as measured by 99mTc-labeled macroaggregated albumin perfusion scintigraphy (PS) are not uncommonly discrepant from those measured by dynamic contrast-enhanced MRI (DCE-MRI) using indicator-dilution analysis in complex pulmonary circulation. Since PS offers the pre-capillary perfusion of the first-pass transit, we hypothesized that an inflow-weighted perfusion model of DCE-MRI could simulate the result by PS. Methods 22 patients underwent DCE-MRI at 1.5T and also PS. Relative perfusion contributed by the left lung was calculated by PS (PSL%), by DCE-MRI using conventional indicator dilution theory for pulmonary blood volume (PBVL%) and pulmonary blood flow (PBFL%) and using our proposed inflow-weighted pulmonary blood volume (PBViwL%). For PBViwL%, the optimal upper bound of the inflow-weighted integration range was determined by correlation coefficient analysis. Results The time-to-peak of the normal lung parenchyma was the optimal upper bound in the inflow-weighted perfusion model. Using PSL% as a reference, PBVL% showed error of 49.24% to −40.37% (intraclass correlation coefficient RI = 0.55) and PBFL% had error of 34.87% to −27.76% (RI = 0.80). With the inflow-weighted model, PBViwL% had much less error of 12.28% to −11.20% (RI = 0.98) from PSL%. Conclusions The inflow-weighted DCE-MRI provides relative perfusion maps similar to that by PS. The discrepancy between conventional indicator-dilution and inflow-weighted analysis represents a mixed-flow component in which pathological flow such as shunting or collaterals might have participated. PMID:23448679

Computer-assisted diagnostic tool to quantify the pulmonary veins in sickle cell associated pulmonary hypertension

NASA Astrophysics Data System (ADS)

Jajamovich, Guido H.; Pamulapati, Vivek; Alam, Shoaib; Mehari, Alem; Kato, Gregory J.; Wood, Bradford J.; Linguraru, Marius George

2012-03-01

Pulmonary hypertension is a common cause of death among patients with sickle cell disease. This study investigates the use of pulmonary vein analysis to assist the diagnosis of pulmonary hypertension non-invasively with CT-Angiography images. The characterization of the pulmonary veins from CT presents two main challenges. Firstly, the number of pulmonary veins is unknown a priori and secondly, the contrast material is degraded when reaching the pulmonary veins, making the edges of these vessels to appear faint. Each image is first denoised and a fast marching approach is used to segment the left atrium and pulmonary veins. Afterward, a geodesic active contour is employed to isolate the left atrium. A thinning technique is then used to extract the skeleton of the atrium and the veins. The locations of the pulmonary veins ostia are determined by the intersection of the skeleton and the contour of the atrium. The diameters of the pulmonary veins are measured in each vein at fixed distances from the corresponding ostium, and for each distance, the sum of the diameters of all the veins is computed. These indicators are shown to be significantly larger in sickle-cell patients with pulmonary hypertension as compared to controls (p-values < 0.01).

Cytokine–Ion Channel Interactions in Pulmonary Inflammation

PubMed Central

Hamacher, Jürg; Hadizamani, Yalda; Borgmann, Michèle; Mohaupt, Markus; Männel, Daniela Narcissa; Moehrlen, Ueli; Lucas, Rudolf; Stammberger, Uz

2018-01-01

The lungs conceptually represent a sponge that is interposed in series in the bodies’ systemic circulation to take up oxygen and eliminate carbon dioxide. As such, it matches the huge surface areas of the alveolar epithelium to the pulmonary blood capillaries. The lung’s constant exposure to the exterior necessitates a competent immune system, as evidenced by the association of clinical immunodeficiencies with pulmonary infections. From the in utero to the postnatal and adult situation, there is an inherent vital need to manage alveolar fluid reabsorption, be it postnatally, or in case of hydrostatic or permeability edema. Whereas a wealth of literature exists on the physiological basis of fluid and solute reabsorption by ion channels and water pores, only sparse knowledge is available so far on pathological situations, such as in microbial infection, acute lung injury or acute respiratory distress syndrome, and in the pulmonary reimplantation response in transplanted lungs. The aim of this review is to discuss alveolar liquid clearance in a selection of lung injury models, thereby especially focusing on cytokines and mediators that modulate ion channels. Inflammation is characterized by complex and probably time-dependent co-signaling, interactions between the involved cell types, as well as by cell demise and barrier dysfunction, which may not uniquely determine a clinical picture. This review, therefore, aims to give integrative thoughts and wants to foster the unraveling of unmet needs in future research. PMID:29354115

Compositional changes in lipid microdomains of air-blood barrier plasma membranes in pulmonary interstitial edema.

PubMed

Palestini, Paola; Calvi, Chiara; Conforti, Elena; Daffara, Rossella; Botto, Laura; Miserocchi, Giuseppe

2003-10-01

We evaluated in anesthetized rabbits the compositional changes of plasmalemmal lipid microdomains from lung tissue samples after inducing pulmonary interstitial edema (0.5 ml/kg for 3 h, leading to approximately 5% increase in extravascular water). Lipid microdomains (lipid rafts and caveolae) were present in the detergent-resistant fraction (DRF) obtained after discontinuous sucrose density gradient. DRF was enriched in caveolin-1, flotillin, aquaporin-1, GM1, cholesterol, sphingomyelin, and phosphatidylserine, and their contents significantly increased in interstitial edema. The higher DRF content in caveolin, flotillin, and aquaporin-1 and of the ganglioside GM1 suggests an increase both in caveolar domains and in lipid rafts, respectively. Compositional changes could be ascribed to endothelial and epithelial cells that provide most of plasma membrane surface area in the air-blood barrier. Alterations in lipid components in the plasma membrane may reflect rearrangement of floating lipid platforms within the membrane and/or lipid translocation from intracellular stores. Lipid traffic could be stimulated by the marked increase in hydraulic interstitial pressure after initial water accumulation, from approximately -10 to 5 cmH2O, due to the low compliance of the pulmonary tissue, in particular in the basement membranes and in the interfibrillar substance. Compositional changes in lipid microdomains represent a sign of cellular activation and suggest the potential role of mechanotransduction in response to developing interstitial edema.

A study of the role of IL-12 in pulmonary tuberculosis using the whole blood flowcytometry technique.

PubMed

Zahran, Wafaa A; Ghonaim, Mabrouk M; Koura, Bothina A; El-Banna, Hassan; Ali, Sahar M; El-Sheikh, Nabila

2006-01-01

Pulmonary tuberculosis remains a major health problem. It is caused by Mycobacterium tuberculosis, which elicits a T-cell dependent immune response, initiated by monocytes through a large number of cytokines of which interleukin-12 is thought to play a critical role in initiation and regulation of T-helper (Th-1) like responses. To better understand the role of IL-12 in pulmonary tuberculosis patients, intracellular IL-12 in peripheral blood-derived monocytes was examined by flowcytometery. The percentage of monocytes producing IL-12 was measured after invitro stimulation of heparinized whole blood with mycobacterial protein antigens (culture filtrate). Of the 22 active tuberculosis patients, 17 were recent cases and 5 recurrent cases. Healthy controls were 14 individuals with detectable reaction to purified protein derivative (PPD+) and 14 without detectable reaction to PPD. The role of different factors affecting disease outcome such as treatment, age, gender, smoking, severity of disease and presence of other complications on the percentage of monocytes producing IL-12 was studied. Recurrent TB patients had a higher number of monocytes producing IL-12 in unstimulated cultures compared to other groups (P < 0.001). However, after in vitro stimulation there was a significant decrease in the number of monocytes producing IL-12 in recurrent TB patients as compared to recently diagnosed TB patients and healthy PPD+ individuals (P < 0.001). Antituberculosis chemotherapy was the only factor that had significant effect on the percentage of monocytes producing IL-12 (p < 0.05) while other studied factors did not show significant effect (p > 0.05). It is concluded that IL-12 plays a prominent regulatory role in tuberculosis.

[Recurrent pulmonary infection and oral mucosal ulcer].

PubMed

Kuang, Fei-Mei; Tang, Lan-Lan; Zhang, Hui; Xie, Min; Yang, Ming-Hua; Yang, Liang-Chun; Yu, Yan; Cao, Li-Zhi

2017-04-01

An 8-year-old girl who had experienced intermittent cough and fever over a 3 year period, was admitted after experiencing a recurrence for one month. One year ago the patient experienced a recurrent oral mucosal ulcer. Physical examination showed vitiligo in the skin of the upper right back. Routine blood tests and immune function tests performed in other hospitals had shown normal results. Multiple lung CT scans showed pulmonary infection. The patient had recurrent fever and cough and persistent presence of some lesions after anti-infective therapy. The antitubercular therapy was ineffective. Routine blood tests after admission showed agranulocytosis. Gene detection was performed and she was diagnosed with dyskeratosis congenita caused by homozygous mutation in RTEL1. Patients with dyskeratosis congenita with RTEL1 gene mutation tend to develop pulmonary complications. Since RTEL1 gene sequence is highly variable with many mutation sites and patterns and can be inherited via autosomal dominant or recessive inheritance, this disease often has various clinical manifestations, which may lead to missed diagnosis or misdiagnosis. For children with unexplained recurrent pulmonary infection, examinations of the oral cavity, skin, and nails and toes should be taken and routine blood tests should be performed to exclude dyskeratosis congenita. There are no specific therapies for dyskeratosis congenita at present, and when bone marrow failure and pulmonary failure occur, hematopoietic stem cell transplantation and lung transplantation are the only therapies. Androgen and its derivatives are effective in some patients. Drugs targeting the telomere may be promising for patients with dyskeratosis congenita.

Usefulness of interferon-γ release assay for the diagnosis of sputum smear-negative pulmonary and extra-pulmonary TB in Zhejiang Province, China.

PubMed

Ji, Lei; Lou, Yong-Liang; Wu, Zhong-Xiu; Jiang, Jin-Qin; Fan, Xing-Li; Wang, Li-Fang; Liu, Xiao-Xiang; Du, Peng; Yan, Jie; Sun, Ai-Hua

2017-09-01

Quick diagnosis of smear-negative pulmonary tuberculosis (TB) and extra-pulmonary TB are urgently needed in clinical diagnosis. Our research aims to investigate the usefulness of the interferon-γ release assay (IGRA) for the diagnosis of smear-negative pulmonary and extra-pulmonary TB. We performed TB antibody and TB-IGRA tests on 389 pulmonary TB patients (including 120 smear-positive pulmonary TB patients and 269 smear-negative pulmonary TB patients), 113 extra-pulmonary TB patients, 81 patients with other pulmonary diseases and 100 healthy controls. Blood samples for the TB-Ab test and the TB-IGRA were collected, processed, and interpreted according to the manufacturer's protocol. The detection ratio of smear-positive pulmonary TB patients and smear-negative pulmonary TB patients were 90.8% (109 of 120) and 89.6% (241 of 269), respectively. There was no statistically significant difference of its performance between these two sample sets (P > 0.05). The detection ratio of positive TB patients and extra-pulmonary TB patients were 90.0% (350 of 389) and 87.6% (99 of 113), respectively, which was not significantly different (P > 0.05). In this work, the total detection ratio using TB-IGRA was 89.4%, therefore TB-IGRA has diagnostic values in smear-negative pulmonary TB and extra-pulmonary TB diagnosis.

Pulmonary Morbidity in Infancy after Exposure to Chorioamnionitis in Late Preterm Infants.

PubMed

McDowell, Karen M; Jobe, Alan H; Fenchel, Matthew; Hardie, William D; Gisslen, Tate; Young, Lisa R; Chougnet, Claire A; Davis, Stephanie D; Kallapur, Suhas G

2016-06-01

Chorioamnionitis is an important cause of preterm birth, but its impact on postnatal outcomes is understudied. To evaluate whether fetal exposure to inflammation is associated with adverse pulmonary outcomes at 6 to 12 months' chronological age in infants born moderate to late preterm. Infants born between 32 and 36 weeks' gestational age were prospectively recruited (N = 184). Chorioamnionitis was diagnosed by placenta and umbilical cord histology. Select cytokines were measured in samples of cord blood. Validated pulmonary questionnaires were administered (n = 184), and infant pulmonary function testing was performed (n = 69) between 6 and 12 months' chronological age by the raised volume rapid thoracoabdominal compression technique. A total of 25% of participants had chorioamnionitis. Although infant pulmonary function testing variables were lower in infants born preterm compared with historical normative data for term infants, there were no differences between infants with chorioamnionitis (n = 20) and those without (n = 49). Boys and black infants had lower infant pulmonary function testing measurements than girls and white infants, respectively. Chorioamnionitis exposure was associated independently with wheeze (odds ratio [OR], 2.08) and respiratory-related physician visits (OR, 3.18) in the first year of life. Infants exposed to severe chorioamnionitis had increased levels of cord blood IL-6 and greater pulmonary morbidity at age 6 to 12 months than those exposed to mild chorioamnionitis. Elevated IL-6 was associated with significantly more respiratory problems (OR, 3.23). In infants born moderate or late preterm, elevated cord blood IL-6 and exposure to histologically identified chorioamnionitis was associated with respiratory morbidity during infancy without significant changes in infant pulmonary function testing measurements. Black compared with white and boy compared with girl infants had lower infant pulmonary function testing

Pulmonary Morbidity in Infancy after Exposure to Chorioamnionitis in Late Preterm Infants

PubMed Central

McDowell, Karen M.; Jobe, Alan H.; Fenchel, Matthew; Hardie, William D.; Gisslen, Tate; Young, Lisa R.; Chougnet, Claire A.; Davis, Stephanie D.

2016-01-01

Rationale: Chorioamnionitis is an important cause of preterm birth, but its impact on postnatal outcomes is understudied. Objectives: To evaluate whether fetal exposure to inflammation is associated with adverse pulmonary outcomes at 6 to 12 months’ chronological age in infants born moderate to late preterm. Methods: Infants born between 32 and 36 weeks’ gestational age were prospectively recruited (N = 184). Chorioamnionitis was diagnosed by placenta and umbilical cord histology. Select cytokines were measured in samples of cord blood. Validated pulmonary questionnaires were administered (n = 184), and infant pulmonary function testing was performed (n = 69) between 6 and 12 months’ chronological age by the raised volume rapid thoracoabdominal compression technique. Measurements and Main Results: A total of 25% of participants had chorioamnionitis. Although infant pulmonary function testing variables were lower in infants born preterm compared with historical normative data for term infants, there were no differences between infants with chorioamnionitis (n = 20) and those without (n = 49). Boys and black infants had lower infant pulmonary function testing measurements than girls and white infants, respectively. Chorioamnionitis exposure was associated independently with wheeze (odds ratio [OR], 2.08) and respiratory-related physician visits (OR, 3.18) in the first year of life. Infants exposed to severe chorioamnionitis had increased levels of cord blood IL-6 and greater pulmonary morbidity at age 6 to 12 months than those exposed to mild chorioamnionitis. Elevated IL-6 was associated with significantly more respiratory problems (OR, 3.23). Conclusions: In infants born moderate or late preterm, elevated cord blood IL-6 and exposure to histologically identified chorioamnionitis was associated with respiratory morbidity during infancy without significant changes in infant pulmonary function testing measurements. Black compared with white

The clinical usefulness of extravascular lung water and pulmonary vascular permeability index to diagnose and characterize pulmonary edema: a prospective multicenter study on the quantitative differential diagnostic definition for acute lung injury/acute respiratory distress syndrome

PubMed Central

2012-01-01

Introduction Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by features other than increased pulmonary vascular permeability. Pulmonary vascular permeability combined with increased extravascular lung water content has been considered a quantitative diagnostic criterion of ALI/ARDS. This prospective, multi-institutional, observational study aimed to clarify the clinical pathophysiological features of ALI/ARDS and establish its quantitative diagnostic criteria. Methods The extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI) were measured using the transpulmonary thermodilution method in 266 patients with PaO2/FiO2 ratio ≤ 300 mmHg and bilateral infiltration on chest radiography, in 23 ICUs of academic tertiary referral hospitals. Pulmonary edema was defined as EVLWI ≥ 10 ml/kg. Three experts retrospectively determined the pathophysiological features of respiratory insufficiency by considering the patients' history, clinical presentation, chest computed tomography and radiography, echocardiography, EVLWI and brain natriuretic peptide level, and the time course of all preceding findings under systemic and respiratory therapy. Results Patients were divided into the following three categories on the basis of the pathophysiological diagnostic differentiation of respiratory insufficiency: ALI/ARDS, cardiogenic edema, and pleural effusion with atelectasis, which were noted in 207 patients, 26 patients, and 33 patients, respectively. EVLWI was greater in ALI/ARDS and cardiogenic edema patients than in patients with pleural effusion with atelectasis (18.5 ± 6.8, 14.4 ± 4.0, and 8.3 ± 2.1, respectively; P < 0.01). PVPI was higher in ALI/ARDS patients than in cardiogenic edema or pleural effusion with atelectasis patients (3.2 ± 1.4, 2.0 ± 0.8, and 1.6 ± 0.5; P < 0.01). In ALI/ARDS patients, EVLWI increased with increasing pulmonary vascular permeability (r = 0.729, P < 0.01) and was weakly

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

First case of fatal pulmonary peliosis without any other organ involvement in a young testosterone abusing male.

PubMed

Vougiouklakis, Theodore; Mitselou, Antigoni; Batistatou, Anna; Boumba, Vassiliki; Charalabopoulos, Konstantinos

2009-04-15

Peliosis is a rare lesion characterized by the presence of blood-filled cysts, with unknown true incidence and etiology. It has been most frequently reported to the liver (peliosis hepatis) and to other organs of the mononuclear phagocytic system, such as spleen, bone marrow and lymph nodes. However, other organs may also be affected. Its occurrence has been linked to wasting conditions such as tuberculosis, cancer, immunosuppression and the use of androgenic-anabolic steroids. Herein, we report a case of pulmonary peliosis, in a 29-year-old man who was abusing testosterone as it was proved by toxicological analysis. To our knowledge this is the third reported case of pulmonary peliosis and the first one that is not associated with peliosis of any other organ.

Combined Pulmonary Fibrosis and Emphysema Syndrome

PubMed Central

Rounds, Sharon I. S.

2012-01-01

There is increasing clinical, radiologic, and pathologic recognition of the coexistence of emphysema and pulmonary fibrosis in the same patient, resulting in a clinical syndrome known as combined pulmonary fibrosis and emphysema (CPFE) that is characterized by dyspnea, upper-lobe emphysema, lower-lobe fibrosis, and abnormalities of gas exchange. This syndrome frequently is complicated by pulmonary hypertension, acute lung injury, and lung cancer. The CPFE syndrome typically occurs in male smokers, and the mortality associated with this condition, especially if pulmonary hypertension is present, is significant. In this review, we explore the current state of the literature and discuss etiologic factors and clinical characteristics of the CPFE syndrome. PMID:22215830

Ageing and endurance training effects on quantity and quality of pulmonary vascular bed in healthy men

PubMed Central

2014-01-01

It has recently been demonstrated that in healthy individuals, peak oxygen consumption is associated with a greater pulmonary capillary blood volume and a more distensible pulmonary circulation. Our cross-sectional study suggests that, in healthy men aged 20 to 60 years (n = 63), endurance sport practice (vigorous-intensity domain of the International Physical Activity Questionnaire) is associated with better quantity (pulmonary capillary blood volume) and quality (slope of increase in lung diffusion for carbon monoxide on exercise) of the pulmonary vascular bed, partly counterbalancing the deleterious effects of ageing, which remains to be demonstrated in a prospective longitudinal design. PMID:24460636

Nano-liposomal dry powder inhaler of tacrolimus: Preparation, characterization, and pulmonary pharmacokinetics

PubMed Central

Chougule, Mahavir; Padhi, Bijay; Misra, Ambikanandan

2007-01-01

The studies were undertaken to evaluate feasibility of pulmonary delivery of liposomaly encapsulated tacrolimus dry powder inhaler for prolonged drug retention in lungs as rescue therapy to prevent refractory rejection of lungs after transplantation. Tacrolimus encapsulated liposomes were prepared by thin film evaporation technique and liposomal dispersion was passed through high pressure homogenizer. Tacrolimus nano-liposomes (NLs) were separated by centrifugation and characterized. NLs were dispersed in phosphate buffer saline (PBS) pH 7.4 containing different additives like lactose, sucrose, and trehalose, and L-leucine as antiadherent. The dispersion was spray dried and spray dried powders were characterized. In vitro and in vivo pulmonary deposition was performed using Andersen Cascade Impactor and intratracheal instillation in rats respectively. NLs were found to have average size of 140 nm, 96% ± 1.5% drug entrapment, and zeta potential of 1.107 mV. Trehalose based formulation was found to have low density, good flowability, particle size of 9.46 ± 0.8 μm, maximum fine particle fraction (FPF) of 71.1 ± 2.5%, mean mass aerodynamic diameter (MMAD) 2.2 ± 0.1 μm, and geometric standard deviation (GSD) 1.7 ± 0.2. Developed formulations were found to have in vitro prolonged drug release up to 18 hours, following Higuchi’s Controlled Release model. In vivo studies revealed maximal residence of tacrolimus within lungs of 24 hours, suggesting slow clearance from the lungs. The investigation provides a practical approach for direct delivery of tacrolimus encapsulated in NLs for controlled and prolonged retention at the site of action. It may play a promising role as rescue therapy in reducing the risk of acute rejection and chronic rejection. PMID:18203434

Inflow-weighted pulmonary perfusion: comparison between dynamic contrast-enhanced MRI versus perfusion scintigraphy in complex pulmonary circulation.

PubMed

Lin, Yi-Ru; Tsai, Shang-Yueh; Huang, Teng-Yi; Chung, Hsiao-Wen; Huang, Yi-Luan; Wu, Fu-Zong; Lin, Chu-Chuan; Peng, Nan-Jing; Wu, Ming-Ting

2013-02-28

Due to the different properties of the contrast agents, the lung perfusion maps as measured by 99mTc-labeled macroaggregated albumin perfusion scintigraphy (PS) are not uncommonly discrepant from those measured by dynamic contrast-enhanced MRI (DCE-MRI) using indicator-dilution analysis in complex pulmonary circulation. Since PS offers the pre-capillary perfusion of the first-pass transit, we hypothesized that an inflow-weighted perfusion model of DCE-MRI could simulate the result by PS. 22 patients underwent DCE-MRI at 1.5T and also PS. Relative perfusion contributed by the left lung was calculated by PS (PS(L%)), by DCE-MRI using conventional indicator dilution theory for pulmonary blood volume (PBV(L%)) and pulmonary blood flow (PBFL%) and using our proposed inflow-weighted pulmonary blood volume (PBV(iw)(L%)). For PBViw(L%), the optimal upper bound of the inflow-weighted integration range was determined by correlation coefficient analysis. The time-to-peak of the normal lung parenchyma was the optimal upper bound in the inflow-weighted perfusion model. Using PSL% as a reference, PBV(L%) showed error of 49.24% to -40.37% (intraclass correlation coefficient R(I) = 0.55) and PBF(L%) had error of 34.87% to -27.76% (R(I) = 0.80). With the inflow-weighted model, PBV(iw)(L%) had much less error of 12.28% to -11.20% (R(I) = 0.98) from PS(L%). The inflow-weighted DCE-MRI provides relative perfusion maps similar to that by PS. The discrepancy between conventional indicator-dilution and inflow-weighted analysis represents a mixed-flow component in which pathological flow such as shunting or collaterals might have participated.

A Low Peripheral Blood CD4/CD8 Ratio Is Associated with Pulmonary Emphysema in HIV.

PubMed

Triplette, Matthew; Attia, Engi F; Akgün, Kathleen M; Soo Hoo, Guy W; Freiberg, Matthew S; Butt, Adeel A; Wongtrakool, Cherry; Goetz, Matthew Bidwell; Brown, Sheldon T; Graber, Christopher J; Huang, Laurence; Crothers, Kristina

2017-01-01

The prevalence of emphysema is higher among HIV-infected (HIV+) individuals compared to HIV-uninfected persons. While greater tobacco use contributes, HIV-related effects on immunity likely confer additional risk. Low peripheral blood CD4+ to CD8+ T-lymphocyte (CD4/CD8) ratio may reflect chronic inflammation in HIV and may be a marker of chronic lung disease in this population. Therefore, we sought to determine whether the CD4/CD8 ratio was associated with chronic obstructive pulmonary disease (COPD), particularly the emphysema subtype, in a cohort of HIV+ subjects. We performed a cross-sectional analysis of 190 HIV+ subjects enrolled in the Examinations of HIV Associated Lung Emphysema (EXHALE) study. Subjects underwent baseline laboratory assessments, pulmonary function testing and chest computed tomography (CT) analyzed for emphysema severity and distribution. We determined the association between CD4/CD8 ratio and emphysema, and the association between CD4/CD8 ratio and pulmonary function markers of COPD. Mild or greater emphysema (>10% lung involvement) was present in 31% of subjects. Low CD4/CD8 ratio was associated with >10% emphysema in multivariable models, adjusting for risk factors including smoking, current and nadir CD4 count and HIV RNA level. Those with CD4/CD8 ratio <0.4 had 6.3 (1.1-39) times the odds of >10% emphysema compared to those with a ratio >1.0 in fully adjusted models. A low CD4/CD8 ratio was also associated with reduced diffusion capacity (DLCO). A low CD4/CD8 ratio was associated with emphysema and low DLCO in HIV+ subjects, independent of other risk factors and clinical markers of HIV. The CD4/CD8 ratio may be a useful, clinically available, marker for risk of emphysema in HIV+ subjects in the antiretroviral therapy (ART) era.

A Low Peripheral Blood CD4/CD8 Ratio Is Associated with Pulmonary Emphysema in HIV

PubMed Central

Attia, Engi F.; Akgün, Kathleen M.; Soo Hoo, Guy W.; Freiberg, Matthew S.; Butt, Adeel A.; Wongtrakool, Cherry; Goetz, Matthew Bidwell; Brown, Sheldon T.; Graber, Christopher J.; Huang, Laurence; Crothers, Kristina

2017-01-01

Objectives The prevalence of emphysema is higher among HIV-infected (HIV+) individuals compared to HIV-uninfected persons. While greater tobacco use contributes, HIV-related effects on immunity likely confer additional risk. Low peripheral blood CD4+ to CD8+ T-lymphocyte (CD4/CD8) ratio may reflect chronic inflammation in HIV and may be a marker of chronic lung disease in this population. Therefore, we sought to determine whether the CD4/CD8 ratio was associated with chronic obstructive pulmonary disease (COPD), particularly the emphysema subtype, in a cohort of HIV+ subjects. Methods We performed a cross-sectional analysis of 190 HIV+ subjects enrolled in the Examinations of HIV Associated Lung Emphysema (EXHALE) study. Subjects underwent baseline laboratory assessments, pulmonary function testing and chest computed tomography (CT) analyzed for emphysema severity and distribution. We determined the association between CD4/CD8 ratio and emphysema, and the association between CD4/CD8 ratio and pulmonary function markers of COPD. Results Mild or greater emphysema (>10% lung involvement) was present in 31% of subjects. Low CD4/CD8 ratio was associated with >10% emphysema in multivariable models, adjusting for risk factors including smoking, current and nadir CD4 count and HIV RNA level. Those with CD4/CD8 ratio <0.4 had 6.3 (1.1–39) times the odds of >10% emphysema compared to those with a ratio >1.0 in fully adjusted models. A low CD4/CD8 ratio was also associated with reduced diffusion capacity (DLCO). Conclusions A low CD4/CD8 ratio was associated with emphysema and low DLCO in HIV+ subjects, independent of other risk factors and clinical markers of HIV. The CD4/CD8 ratio may be a useful, clinically available, marker for risk of emphysema in HIV+ subjects in the antiretroviral therapy (ART) era. PMID:28122034

Management of pulmonary arterial hypertension.

PubMed

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

2015-05-12

Pulmonary hypertension (PH) is common and may result from a number of disorders, including left heart disease, lung disease, and chronic thromboembolic disease. Pulmonary arterial hypertension (PAH) is an uncommon disease characterized by progressive remodeling of the distal pulmonary arteries, resulting in elevated pulmonary vascular resistance and, eventually, in right ventricular failure. Over the past decades, knowledge of the basic pathobiology of PAH and its natural history, prognostic indicators, and therapeutic options has exploded. A thorough evaluation of a patient is critical to correctly characterize the PH. Cardiac studies, including echocardiography and right heart catheterization, are key elements in the assessment. Given the multitude of treatment options currently available for PAH, assessment of risk and response to therapy is critical in long-term management. This review also underscores unique situations, including perioperative management, intensive care unit management, and pregnancy, and highlights the importance of collaborative care of the PAH patient through a multidisciplinary approach. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Assessment of pulmonary vascular reactivity to oxygen using fractional moving blood volume in fetuses with normal lung development and pulmonary hypoplasia in congenital diaphragmatic hernia.

PubMed

DeKoninck, Philip; Jimenez, Julio; Russo, Francesca M; Hodges, Ryan; Gratacós, Eduard; Deprest, Jan

2014-10-01

The objective of this study is to evaluate whether assessment pulmonary vascular reactivity in response to maternal hyperoxygenation using fractional moving blood volume (FMBV) is associated with lesser variability between individual measurements than what is observed with direct Doppler measurements. Forty-five measurements were performed in 15 singleton fetuses with normal lung development at three time points in the latter half of pregnancy (range: 25.9-36.7 weeks). We further evaluated five fetuses with severe congenital diaphragmatic hernia. Lung perfusion was assessed using power Doppler ultrasound, and images were stored for offline FMBV calculation, both at base line and during oxygen administration (9 L/min for 10 min). The proportionate difference between both measurements is further referred to as deltaFMBV. Overall, 91% of images were of sufficient quality for further analysis. There was no correlation between pulmonary reactivity to oxygen (deltaFMBV) and gestational age in controls (12.9 ± 32.1%). Moreover, deltaFMBV showed large variability between subjects, as well as within the same fetus throughout gestation. We observed good intraobserver (0.88; 0.84) and interobserver (0.88; 0.77) reproducibility for both controls and congenital diaphragmatic hernia, respectively (intraclass correlation coefficients). Despite being a reproducible method to study the lung vasculature, the large variability of FMBV following hyperoxygenation limits its clinical translation. © 2014 John Wiley & Sons, Ltd.

Massive plasmablast response elicited in the acute phase of hantavirus pulmonary syndrome.

PubMed

García, Marina; Iglesias, Ayelén; Landoni, Verónica I; Bellomo, Carla; Bruno, Agostina; Córdoba, María Teresa; Balboa, Luciana; Fernández, Gabriela C; Sasiain, María Del Carmen; Martínez, Valeria P; Schierloh, Pablo

2017-05-01

Beside its key diagnostic value, the humoral immune response is thought to play a protective role in hantavirus pulmonary syndrome. However, little is known about the cell source of these antibodies during ongoing human infection. Herein we characterized B-cell subsets circulating in Andes-virus-infected patients. A notable potent plasmablast (PB) response that increased 100-fold over the baseline levels was observed around 1 week after the onset of symptoms. These PB present a CD3 neg CD19 low CD20 neg CD38 hi CD27 hi CD138 +/- IgA +/- surface phenotype together with the presence of cytoplasmic functional immunoglobulins. They are large lymphocytes (lymphoblasts) morphologically coincident with the 'immunoblast-like' cells that have been previously described during blood cytology examinations of hantavirus-infected patients. Immunoreactivity analysis of white blood cell lysates suggests that some circulating PB are virus-specific but we also observed a significant increase of reactivity against virus-unrelated antigens, which suggests a possible bystander effect by polyclonal B-cell activation. The presence of this large and transient PB response raises the question as to whether these cells might have a protective or pathological role during the ongoing hantavirus pulmonary syndrome and suggest their practical application as a diagnostic/prognostic biomarker. © 2017 John Wiley & Sons Ltd.

[Pulmonary hypertensive crisis in children with idiopathic pulmonary arterial hypertension undergoing cardiac catheterization: the risk factors and clinical aspects].

PubMed

Zhang, C; Zhu, Y; Li, Q Q; Gu, H

2018-06-02

Objective: To investigate the risk factors, clinical features, treatments, and prevention of pulmonary hypertensive crisis (PHC) in children with idiopathic pulmonary arterial hypertension (IPAH) undergoing cardiac catheterization. Methods: This retrospective study included 67 children who were diagnosed with IPAH and underwent cardiac catheterization between April 2009 and June 2017 in Beijing Anzhen Hospital. The medical histories, clinical manifestations, treatments, and outcomes were characterized. Statistical analyses were performed using t test, χ(2) test and a multiple Logistic regression analysis. Results: During cardiac catheterization, five children developed PHC who presented with markedly elevated pulmonary artery pressure and central venous pressure, decline in systemic arterial pressure and oxygen saturation. Heart rate decreased in 4 cases and increased in the remaining one. After the treatments including cardiopulmonary resuscitation, pulmonary vasodilator therapy, improving cardiac output and blood pressure, and correction of acidosis, 4 of the 5 cases recovered, while 1 died of severe right heart failure with irreversible PHC 3 days after operation. Potential PHC was considered in 7 other patients, whose pulmonary artery pressure increased and exceeded systemic arterial pressure, oxygen saturation decreased, and central venous pressure and vital signs were relatively stable. Univariate analysis showed that the risk factors of PHC in children with IPAH undergoing cardiac catheterization were younger age ( t= 3.160, P= 0.004), low weight ( t= 4.004, P< 0.001), general anesthesia (χ(2)=4.970, P= 0.026), history of syncope (χ(2)=4.948, P= 0.026), and WHO cardiac functional class Ⅲ or Ⅳ (χ(2)=19.013, P< 0.001). Multivariate Logistic regression analysis revealed that worse WHO cardiac functional class ( Wald =13.128, P< 0.001, OR= 15.076, 95% CI : 3.475-65.418) was the independent risk factor of PHC. Conclusions: PHC is a severe and extremely

[General anesthesia for a patient with pulmonary hypertension, bronchial asthma and obesity].

PubMed

Nakamura, Shinji; Nishiyama, Tomoki; Hanaoka, Kazuo

2005-10-01

The management of the patient with pulmonary hypertension is a challenge for the anesthesiologists because the risk of right-sided heart failure is markedly increased. We experienced a case of general anesthesia for a patient with pulmonary hypertension (mean pulmonary arterial pressure 39 mmHg), bronchial asthma and obesity. A 31-year-old woman was scheduled for arytenoid rotation for left recurrent nerve palsy. We applied routine monitors (noninvasive blood-pressure, five-lead electrocardiogram, pulse oximeter), and direct blood pressure monitoring through the radial artery. Anesthesia was induced with midazolam 4 mg, fentanyl 100 microg and sevoflurane 5%, and maintained with sevoflurane (1-2%) and nitrous oxide in oxygen. Surgery was completed in 100 minutes without any complications. We could successfully perform general anesthesia in a patient complicated by pulmonary hypertension, bronchial asthma and obesity, without invasive right-sided heart catheterization.

Primary extraskeletal myxoid chondrosarcoma of pulmonary arteries: a rare mimic of acute pulmonary thromboembolism.

PubMed

Gadabanahalli, Karthik; Belaval, Vinay V; Bhat, Venkatraman; Gorur, Imran M

2015-04-01

Primary extraskeletal myxoid chondrosarcoma of the pulmonary arteries is a very rare entity. Multimodality imaging reports on this entity are few. Myxoid chondrosarcoma is characterized by chondroid and neurogenic differentiation in extraskeletal locations. These tumours represent fewer than 2.5% of all soft-tissue sarcomas, and are most commonly found in the lower extremities, limb girdles, distal extremities and trunk. We report an unusual case of a 31-year old man with histopathologically proven extraskeletal myxoid chondrosarcoma of the pulmonary arteries mimicking acute pulmonary thromboembolism. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Novel Approaches to Pulmonary Arterial Hypertension Drug Discovery

PubMed Central

Sung, Yon K.; Yuan, Ke; de Jesus Perez, Vinicio A.

2016-01-01

Introduction Pulmonary arterial hypertension (PAH) is a rare disorder associated with abnormally elevated pulmonary pressures that, if untreated, leads to right heart failure and premature death. The goal of drug development for PAH is to develop effective therapies that halt, or ideally, reverse the obliterative vasculopathy that results in vessel loss and obstruction of blood flow to the lungs. Areas Covered This review summarizes the current approach to candidate discovery in PAH and discusses the currently available drug discovery methods that should be implemented to prioritize targets and obtain a comprehensive pharmacological profile of promising compounds with well-defined mechanisms. Expert opinion To improve the successful identification of leading drug candidates, it is necessary that traditional pre-clinical studies are combined with drug screening strategies that maximize the characterization of biological activity and identify relevant off-target effects that could hinder the clinical efficacy of the compound when tested in human subjects. A successful drug discovery strategy in PAH will require collaboration of clinician scientists with medicinal chemists and pharmacologists who can identify compounds with an adequate safety profile and biological activity against relevant disease mechanisms. PMID:26901465

Pulmonary toxocariasis: a case report and literature review.

PubMed

Ranasuriya, G; Mian, A; Boujaoude, Z; Tsigrelis, C

2014-06-01

Toxocariasis is a parasitic disease caused by Toxocara canis or T. cati. We report a patient with toxocariasis who presented with dyspnea, high-grade eosinophilia, and bilateral pulmonary nodules. To further characterize the pulmonary manifestations of toxocariasis, we have reviewed 11 previously published pulmonary toxocariasis cases. The most common pulmonary symptoms in our review were cough and dyspnea, and the most common finding on chest imaging was bilateral pulmonary nodules. Risk factors for Toxocara infection primarily included exposure to dogs. Most patients received albendazole and responded well. A high index of suspicion is needed to diagnose this otherwise preventable parasitic disease.

Influence of protein ingestion on human splanchnic and whole-body oxygen consumption, blood flow, and blood temperature.

PubMed

Brundin, T; Wahren, J

1994-05-01

Splanchnic and whole-body oxygen uptake, blood flow, and blood temperature were studied in 10 healthy subjects before and during 2 hours after oral ingestion of 900 kJ of fish protein. Indirect calorimetry and catheter techniques were used, including blood thermometry in arterial, pulmonary arterial, and hepatic venous blood. After the meal, pulmonary oxygen uptake increased from a basal value of 272 +/- 11 to 332 +/- 23 mL/min. During the first postprandial hour, splanchnic oxygen uptake increased from 62 +/- 5 to 93 +/- 9 mL/min (+50%, P < .05), thereby accounting for 62% +/- 17% of the simultaneous increase in whole-body oxygen consumption. During the second postprandial hour, splanchnic oxygen uptake increased no further, whereas in the extrasplanchnic tissues the oxygen consumption increased, now accounting for the entire simultaneous increase in pulmonary oxygen uptake. Cardiac output increased from basal 6.4 +/- 0.4 to 7.5 +/- 0.5 L/min. Splanchnic blood flow changed little while the arteriohepatic venous oxygen difference increased from 46 +/- 3 to 54 +/- 4 mL/L. Arterial and hepatic venous blood temperatures increased by almost 0.3 degrees C, reflecting a considerable accumulation of heat, indicating a conversion into a positive thermal balance. It is concluded that after protein ingestion, (1) oxygen uptake increases mainly in the splanchnic organs during the first hour, and thereafter exclusively in the extrasplanchnic tissues; (2) the blood flow increases mainly in extrasplanchnic tissues; and (3) the blood temperature increases almost linearly, indicating an upward adjustment of the temperature setpoint in the central thermosensors.

Protective effects of drag-reducing polymers in a rat model of monocrotaline-induced pulmonary hypertension.

PubMed

Wang, Yali; Hu, Feng; Mu, Xiaoyan; Wu, Feng; Yang, Dechun; Zheng, Guixiang; Sun, Xiaoning; Gong, Kaizheng; Zhang, Zhengang

2016-01-27

Drag-reducing polymers (DRPs) are blood-soluble macromolecules which may increase blood flow and reduce vascular resistance. The purpose of the present study was to observe the effect of DRPs on monocrotaline-induced pulmonary hypertension (PH) in the rat model. A total of 64 male Wistar rats were randomly divided into four groups: Group I (pulmonary hypertension model + DRP treatment); Group II (pulmonary hypertension model + saline treatment); Group III (control + DRP treatment); Group IV (control + saline treatment). After five weeks, comparisons were made of the following indices: survival rate, body weight, blood pressure, right ventricular systolic pressure, right ventricular hypertrophy, wall thickness of pulmonary arteries, the internal diameter of small pulmonary arteries, plasma IL-1β and IL-6. The survival rate after 5 weeks varied significantly across all groups (P=0.013), but the survival rates of Groups I and II were not statistically significantly different. Administration of DRP (intravenous injection twice weekly) attenuated the PH-induced increase in right ventricular systolic pressure and suppressed the increases in right ventricular (RV) weight and the ratio of right ventricular weight to left ventricle plus septum weight (RV/LV + S). DRP treatment also significantly decreased the wall thickness of pulmonary arteries, augmented the internal diameter of small pulmonary arteries, and suppressed increases in the plasma levels of IL-1β and IL-6. DRP treatment with intravenous injection effectively inhibited the development of monocrotaline-induced pulmonary hypertension in the rat model. DRPs may have potential application for the treatment of pulmonary hypertension.

Evaluation of a whole-blood chemiluminescent immunoassay of IFN-γ, IP-10, and MCP-1 for diagnosis of active pulmonary tuberculosis and tuberculous pleurisy patients.

PubMed

Liang, Yan; Wang, Ying; Li, Hang; Yang, Yourong; Liu, Jianyang; Yu, Ting; Wu, Xueqiong

2016-10-01

The study explored the use of IP-10, MCP-1, and IFN-γ as biomarkers to improve the diagnoses of active pulmonary tuberculosis and tuberculous pleurisy. We enrolled 267 individuals, including 134 TB patients, 93 patients with non-tuberculous pulmonary diseases, and 40 healthy controls. Whole bloods were stimulated in vitro with rCFP-10/ESAT-6 protein antigen of Mycobacterium tuberculosis. The levels of IFN-γ, IP-10, and MCP-1 in cultured supernatants of whole bloods were detected by a chemiluminescence immunoassay. A receiver operating characteristic (ROC) curve was drawn to determine the cutoff value for diagnosing TB and to evaluate the diagnostic efficacies of the IFN-γ, IP-10, and MCP-1 for TB. The antigen-specific release of each cytokine, IFN-γ, IP-10, and MCP-1, was significantly higher in the TB groups than in either the non-tuberculous pulmonary disease group (p < 0.001) or the healthy control group (p < 0.001). The ROC curves indicated cutoff values for IFN-γ, IP-10, and MCP-1 at 147.8, 160.4, and 496.4 pg/mL, respectively. The sensitivity, specificity, PPV, NPV, and diagnostic efficiency for IFN-γ were 85.8%, 70.7%, 74.7%, 83.2%, and 78.3%, respectively; for IP-10 were 72.4%, 75.9%, 75.2%, 73.2%, and 74.2%, respectively; and for MCP-1 were 90.3%, 97.0%, 96.8%, 90.8%, and 93.6%, respectively. IFN-γ combined MCP-1 improved the sensitivity to 97.8% compared with IFN-γ (p < 0.001). Our findings indicate high sensitivity and specificity of MCP-1 as novel biomarkers for the diagnosis of active pulmonary tuberculosis and tuberculous pleurisy. © 2016 APMIS. Published by John Wiley & Sons Ltd.

Pulmonary embolism from gunshot missiles.

PubMed

Bernini, C O; Junqueira, A R; Horita, L T; Birolini, D; Branco, P D; de Oliveira, M R

1983-05-01

In patients having missile wounds, the most bizarre trajectories and lodgment sites have been reported. Entry of the missile into the blood stream and subsequent embolization is quite an uncommon event. Isolated reports published in the literature date back to the beginning of the century. This article was undertaken to present two instances of pulmonary embolism due to gunshot missiles. Most investigators agree that the missile should be removed when located in the pulmonary artery and its branches because of the high risk of severe complications, such as pulmonary infarction, secondary thrombosis, infection, erosion of the arterial wall and local hemorrhage. In such instances, a thoracotomy is recommended. The alternative treatment in the instances reported herein, conceived and successfully performed by us, was embolectomy through percutaneous cardiovascular catheterization. As a novel procedure, the method has proved effective and liable to minimal risk.

Melatonin Decreases Pulmonary Vascular Remodeling and Oxygen Sensitivity in Pulmonary Hypertensive Newborn Lambs

PubMed Central

Astorga, Cristian R.; González-Candia, Alejandro; Candia, Alejandro A.; Figueroa, Esteban G.; Cañas, Daniel; Ebensperger, Germán; Reyes, Roberto V.; Llanos, Aníbal J.; Herrera, Emilio A.

2018-01-01

Background: Chronic hypoxia and oxidative stress during gestation lead to pulmonary hypertension of the neonate (PHN), a condition characterized by abnormal pulmonary arterial reactivity and remodeling. Melatonin has strong antioxidant properties and improves pulmonary vascular function. Here, we aimed to study the effects of melatonin on the function and structure of pulmonary arteries from PHN lambs. Methods: Twelve lambs (Ovis aries) gestated and born at highlands (3,600 m) were instrumented with systemic and pulmonary catheters. Six of them were assigned to the control group (CN, oral vehicle) and 6 were treated with melatonin (MN, 1 mg.kg−1.d−1) during 10 days. At the end of treatment, we performed a graded oxygenation protocol to assess cardiopulmonary responses to inspired oxygen variations. Further, we obtained lung and pulmonary trunk samples for histology, molecular biology, and immunohistochemistry determinations. Results: Melatonin reduced the in vivo pulmonary pressor response to oxygenation changes. In addition, melatonin decreased cellular density of the media and diminished the proliferation marker KI67 in resistance vessels and pulmonary trunk (p < 0.05). This was associated with a decreased in the remodeling markers α-actin (CN 1.28 ± 0.18 vs. MN 0.77 ± 0.04, p < 0.05) and smoothelin-B (CN 2.13 ± 0.31 vs. MN 0.88 ± 0.27, p < 0.05). Further, melatonin increased vascular density by 134% and vascular luminal surface by 173% (p < 0.05). Finally, melatonin decreased nitrotyrosine, an oxidative stress marker, in small pulmonary vessels (CN 5.12 ± 0.84 vs. MN 1.14 ± 0.34, p < 0.05). Conclusion: Postnatal administration of melatonin blunts the cardiopulmonary response to hypoxia, reduces the pathological vascular remodeling, and increases angiogenesis in pulmonary hypertensive neonatal lambs.These effects improve the pulmonary vascular structure and function in the neonatal period under chronic hypoxia. PMID:29559926

Relationship of cerebral blood flow to aortic-to-pulmonary collateral/shunt flow in single ventricles.

PubMed

Fogel, Mark A; Li, Christine; Wilson, Felice; Pawlowski, Tom; Nicolson, Susan C; Montenegro, Lisa M; Diaz Berenstein, Laura; Spray, Thomas L; Gaynor, J William; Fuller, Stephanie; Keller, Marc S; Harris, Matthew A; Whitehead, Kevin K; Clancy, Robert; Elci, Okan; Bethel, Jim; Vossough, Arastoo; Licht, Daniel J

2015-08-01

Patients with single ventricle can develop aortic-to-pulmonary collaterals (APCs). Along with systemic-to-pulmonary artery shunts, these structures represent a direct pathway from systemic to pulmonary circulations, and may limit cerebral blood flow (CBF). This study investigated the relationship between CBF and APC flow on room air and in hypercarbia, which increases CBF in patients with single ventricle. 106 consecutive patients with single ventricle underwent 118 cardiac magnetic resonance (CMR) scans in this cross-sectional study; 34 prior to bidirectional Glenn (BDG) (0.50±0.30 years old), 50 prior to Fontan (3.19±1.03 years old) and 34 3-9 months after Fontan (3.98±1.39 years old). Velocity mapping measured flows in the aorta, cavae and jugular veins. Analysis of variance (ANOVA) and multiple linear regression were used. Significance was p<0.05. A strong inverse correlation was noted between CBF and APC/shunt both on room air and with hypercarbia whether CBF was indexed to aortic flow or body surface area, independent of age, cardiopulmonary bypass time, Po2 and Pco2 (R=-0.67--0.70 for all patients on room air, p<0.01 and R=-0.49--0.90 in hypercarbia, p<0.01). Correlations were not different between surgical stages. CBF was lower, and APCs/shunt flow was higher prior to BDG than in other stages. There is a strong inverse relationship between CBF and APC/shunt flow in patients with single ventricle throughout surgical reconstruction on room air and in hypercarbia independent of other factors. We speculate that APC/shunt flow may have a negative impact on cerebral development and neurodevelopmental outcome. Interventions on APC may modify CBF, holding out the prospect for improving neurodevelopmental trajectory. NCT02135081. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Intravital imaging of a pulmonary endothelial surface layer in a murine sepsis model.

PubMed

Park, Inwon; Choe, Kibaek; Seo, Howon; Hwang, Yoonha; Song, Eunjoo; Ahn, Jinhyo; Hwan Jo, You; Kim, Pilhan

2018-05-01

Direct intravital imaging of an endothelial surface layer (ESL) in pulmonary microcirculation could be a valuable approach to investigate the role of a vascular endothelial barrier in various pathological conditions. Despite its importance as a marker of endothelial cell damage and impairment of the vascular system, in vivo visualization of ESL has remained a challenging technical issue. In this work, we implemented a pulmonary microcirculation imaging system integrated to a custom-design video-rate laser scanning confocal microscopy platform. Using the system, a real-time cellular-level microscopic imaging of the lung was successfully performed, which facilitated a clear identification of individual flowing erythrocytes in pulmonary capillaries. Subcellular level pulmonary ESL was identified in vivo by fluorescence angiography using a dextran conjugated fluorophore to label blood plasma and the red blood cell (RBC) exclusion imaging analysis. Degradation of ESL width was directly evaluated in a murine sepsis model in vivo , suggesting an impairment of pulmonary vascular endothelium and endothelial barrier dysfunction.

Intravital imaging of a pulmonary endothelial surface layer in a murine sepsis model

PubMed Central

Park, Inwon; Choe, Kibaek; Seo, Howon; Hwang, Yoonha; Song, Eunjoo; Ahn, Jinhyo; Hwan Jo, You; Kim, Pilhan

2018-01-01

Direct intravital imaging of an endothelial surface layer (ESL) in pulmonary microcirculation could be a valuable approach to investigate the role of a vascular endothelial barrier in various pathological conditions. Despite its importance as a marker of endothelial cell damage and impairment of the vascular system, in vivo visualization of ESL has remained a challenging technical issue. In this work, we implemented a pulmonary microcirculation imaging system integrated to a custom-design video-rate laser scanning confocal microscopy platform. Using the system, a real-time cellular-level microscopic imaging of the lung was successfully performed, which facilitated a clear identification of individual flowing erythrocytes in pulmonary capillaries. Subcellular level pulmonary ESL was identified in vivo by fluorescence angiography using a dextran conjugated fluorophore to label blood plasma and the red blood cell (RBC) exclusion imaging analysis. Degradation of ESL width was directly evaluated in a murine sepsis model in vivo, suggesting an impairment of pulmonary vascular endothelium and endothelial barrier dysfunction. PMID:29760995

Pulmonary changes in liver transplant candidates with hepatitis C cirrhosis.

PubMed

Al-Moamary, M S; Gorka, T; Al-Traif, I H; Al-Jahdali, H H; Al-Shimemeri, A A; Al-Kanway, B; Abdulkareeem, A A; Abdulkareeem, A A

2001-12-01

Several studies have shown that pulmonary abnormalities are common in patients with end-stage liver disease. However, most of these studies were conducted on patients with heterogeneous etiologies. Therefore, we studied these changes in a homogenous group of hepatitis C cirrhotic patients who were potential candidates for liver transplantation. The charts of 81 patients from King Fahad National Guard Hospital, Riyadh, Kingdom of Saudi Arabia with hepatitis C cirrhosis who were evaluated for liver transplantation were reviewed. The following data was retrieved: echocardiography with micro-bubble study, arterial blood gases, and pulmonary function tests of 81 candidates and reviewed over 3 years from 1994 to 1997. The mean age was 53 (+/-9) years with male to female ratio of 1.4:1. Echocardiographic micro-bubble study, revealed 4 of 62 (7%) had an intrapulmonary shunt. Arterial blood gases results were pH of 7.44 (+/-0.4), partial arterial tension of carbon dioxide of 33 mm Hg (+/-4), partial arterial tension of oxygen of 84 mm Hg (+/-12), and alveolar-arterial gradient of 30 mm Hg (+/-10). Eleven percent had obstructive airway disease, 17% had restrictive lung impairment, and 43% had reduced diffusion capacity. Seventy five percent of patients with reduced diffusion capacity had normal lung volumes. Various pulmonary function test abnormalities did not lead to significant differences in arterial blood gases. Pulmonary changes were frequent in liver transplant candidates with hepatitis C virus cirrhosis with reduced diffusion capacity being the most. Apart from the effect of hepatopulmonary syndrome on arterial oxygenation, other pulmonary abnormalities were not significantly different.

Serum-borne bioactivity caused by pulmonary multiwalled carbon nanotubes induces neuroinflammation via blood-brain barrier impairment.

PubMed

Aragon, Mario J; Topper, Lauren; Tyler, Christina R; Sanchez, Bethany; Zychowski, Katherine; Young, Tamara; Herbert, Guy; Hall, Pamela; Erdely, Aaron; Eye, Tracy; Bishop, Lindsey; Saunders, Samantha A; Muldoon, Pretal P; Ottens, Andrew K; Campen, Matthew J

2017-03-07

Pulmonary exposure to multiwalled carbon nanotubes (MWCNTs) causes indirect systemic inflammation through unknown pathways. MWCNTs translocate only minimally from the lungs into the systemic circulation, suggesting that extrapulmonary toxicity may be caused indirectly by lung-derived factors entering the circulation. To assess a role for MWCNT-induced circulating factors in driving neuroinflammatory outcomes, mice were acutely exposed to MWCNTs (10 or 40 µg/mouse) via oropharyngeal aspiration. At 4 h after MWCNT exposure, broad disruption of the blood-brain barrier (BBB) was observed across the capillary bed with the small molecule fluorescein, concomitant with reactive astrocytosis. However, pronounced BBB permeation was noted, with frank albumin leakage around larger vessels (>10 µm), overlain by a dose-dependent astroglial scar-like formation and recruitment of phagocytic microglia. As affirmed by elevated inflammatory marker transcription, MWCNT-induced BBB disruption and neuroinflammation were abrogated by pretreatment with the rho kinase inhibitor fasudil. Serum from MWCNT-exposed mice induced expression of adhesion molecules in primary murine cerebrovascular endothelial cells and, in a wound-healing in vitro assay, impaired cell motility and cytokinesis. Serum thrombospondin-1 level was significantly increased after MWCNT exposure, and mice lacking the endogenous receptor CD36 were protected from the neuroinflammatory and BBB permeability effects of MWCNTs. In conclusion, acute pulmonary exposure to MWCNTs causes neuroinflammatory responses that are dependent on the disruption of BBB integrity.

Effects of exercise training on pulmonary hemodynamics, functional capacity and inflammation in pulmonary hypertension

PubMed Central

Richter, Manuel J.; Grimminger, Jan; Krüger, Britta; Ghofrani, Hossein A.; Mooren, Frank C.; Gall, Henning; Pilat, Christian; Krüger, Karsten

2017-01-01

Pulmonary hypertension (PH) is characterized by severe exercise limitation mainly attributed to the impairment of right ventricular function resulting from a concomitant elevation of pulmonary vascular resistance and pressure. The unquestioned cornerstone in the management of patients with pulmonary arterial hypertension (PAH) is specific vasoactive medical therapy to improve pulmonary hemodynamics and strengthen right ventricular function. Nevertheless, evidence for a beneficial effect of exercise training (ET) on pulmonary hemodynamics and functional capacity in patients with PH has been growing during the past decade. Beneficial effects of ET on regulating factors, inflammation, and metabolism have also been described. Small case-control studies and randomized clinical trials in larger populations of patients with PH demonstrated substantial improvements in functional capacity after ET. These findings were accompanied by several studies that suggested an effect of ET on inflammation, although a direct link between this effect and the therapeutic benefit of ET in PH has not yet been demonstrated. On this background, the aim of the present review is to describe current concepts regarding the effects of exercise on the pulmonary circulation and pathophysiological limitations, as well as the clinical and mechanistic effects of exercise in patients with PH. PMID:28680563

Facts about Total Anomalous Pulmonary Venous Return or TAPVR

MedlinePlus

... and the right atrium. The goal of the surgical repair of TAPVR is to restore normal blood flow through the heart. To repair this defect, doctors usually connect the pulmonary veins to the left atrium, close off any abnormal connections between blood vessels, and close the atrial septal ...

Characterization of Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome: A Qualitative Analysis.

PubMed

Rodrigue, Claudie; Beauchesne, Marie-France; Mallette, Valérie; Lemière, Catherine; Larivée, Pierre; Blais, Lucie

2017-06-01

Approximately 15-20% of patients with chronic obstructive pulmonary disease (COPD) also display characteristics of asthma. In May 2014, the asthma-COPD overlap syndrome (ACOS) was briefly addressed in the Global Initiative for Asthma (GINA) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy documents. We evaluated how pulmonologists diagnose and treat ACOS and how they assess its control. Pulmonologists from two university healthcare centers, having ≥ 1 year experience, treating patients with asthma, COPD, or ACOS, were invited to participate in focus groups. Two focus groups (1 hour duration) were convened with seven and five participants, respectively. According to pulmonologists from both institutions, ACOS is a new name for an existing syndrome rather than a new disease. It is characterized by incomplete reversible airflow limitations and changes in forced expiratory volume in one second over time. The pulmonologists noted that its diagnosis must be based on clinical characteristics, pulmonary function test results, and clinical intuition. To diagnose ACOS, pulmonologists must rely on their clinical judgment. They also agreed that the treatment of patients with ACOS should target the features of both asthma and COPD. Pulmonologists from both institutions used asthma control criteria to assess ACOS control. A deeper understanding would enable clinicians to establish specific criteria for the diagnosis, treatment, and follow-up of subjects with ACOS.

Tobacco-smoking induced GPR15-expressing T cells in blood do not indicate pulmonary damage.

PubMed

Bauer, Mario; Fink, Beate; Seyfarth, Hans-Jürgen; Wirtz, Hubert; Frille, Armin

2017-11-28

Recently, it was shown that chronic tobacco smoking evokes specific cellular and molecular changes in white blood cells by an excess of G protein-coupled receptor 15 (GPR15)-expressing T cells as well as a hypomethylation at DNA CpG site cg05575921 in granulocytes. In the present study, we aimed to clarify the general usefulness of these two biomarkers as putative signs of non-cancerous change in homeostasis of the lungs. In a clinical cohort consisting of 42 patients with chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD) and pneumonia and a control cohort of 123 volunteers, the content of GPR15-expressing blood cells as well as the degree of methylation at cg05575921 were analysed by flow-cytometry and pyrosequencing, respectively. Smoking behaviour was estimated by questionnaire and cotinine level in plasma. Never-smoking patients could be distinguished from former and current smokers by both the proportion of GPR15-expressing T cells as well as cg05575921 methylation in granulocytes, with 100% and 97% specificity and 100% sensitivity, respectively. However, both parameters were not affected by lung diseases. The degrees of both parameters were not changed neither in non-smoking nor smoking patients, compared to appropriate control cohorts of volunteers. The degree of GPR15-expressing cells among T cells as well as the methylation at cg05575921 in granulocytes in blood are both rather signs of tobacco-smoking induced systemic inflammation because they don't indicate specifically non-cancerous pathological changes in the lungs.

Pulmonary Hypertension and Other Potentially Fatal Pulmonary Complications in Systemic Juvenile Idiopathic Arthritis

PubMed Central

Kimura, Yukiko; Weiss, Jennifer E.; Haroldson, Kathryn L.; Lee, Tzielan; Punaro, Marilynn; Oliveira, Sheila; Rabinovich, Egla; Riebschleger, Meredith; Antón, Jordi; Blier, Peter R.; Gerloni, Valeria; Hazen, Melissa M; Kessler, Elizabeth; Onel, Karen; Passo, Murray H; Rennebohm, Robert M; Wallace, Carol A; Woo, Patricia; Wulffraat, Nico

2015-01-01

Objectives Systemic Juvenile Idiopathic Arthritis (sJIA) is characterized by fevers, rash and arthritis, for which IL1 and IL6 inhibitors appear effective. Pulmonary artery hypertension (PAH), interstitial lung disease (ILD) and alveolar proteinosis (AP) have been recently reported in sJIA patients with increased frequency. Our aim was to characterize and compare these cases to a larger cohort of sJIA patients. Methods sJIA patients who developed PAH, ILD and/or AP were identified through an electronic listserv, and their demographic, sJIA and pulmonary disease characteristics, and medication exposure information were collected. These features were compared to a cohort of sJIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Results Patients (N=25) were significantly (p<0.05) more likely than the CARRA registry cohort (N=389) to be female, have more systemic features, and to have been exposed to an IL-1 inhibitor, tocilizumab, infliximab, corticosteroids, intravenous immunoglobulin, cyclosporine and cyclophosphamide. Eighty% were diagnosed after 2004. Twenty (80%) patients had MAS during their disease course and 15 (60%) had MAS at pulmonary diagnosis. Sixteen patients had PAH, 5 AP and 7 ILD. Seventeen (68%) patients were taking or recently (≤1 month) discontinued a biologic agent at pulmonary symptom onset; 12 (48%) were taking anti-IL1 therapy (primarily anakinra). Seventeen (68%) patients died at a mean of 8.8 months from pulmonary diagnosis. Conclusions PAH, AP and ILD are under-recognized complications of sJIA which are frequently fatal. These may be the result of severe uncontrolled systemic disease activity, and may be influenced by medication exposure. PMID:23139240

Pruning of the Pulmonary Vasculature in Asthma: The SARP Cohort.

PubMed

Ash, Samuel Y; Rahaghi, Farbod N; Come, Carolyn E; Ross, James C; Colon, Alysha G; Cardet-Guisasola, Juan Carlos; Dunican, Eleanor M; Bleecker, Eugene R; Castro, Mario; Fahy, John V; Fain, Sean B; Gaston, Benjamin M; Hoffman, Eric A; Jarjour, Nizar N; Mauger, David T; Wenzel, Sally E; Levy, Bruce D; San Jose Estepar, Raul; Israel, Elliot; Washko, George R

2018-04-19

Loss of the peripheral pulmonary vasculature, termed vascular pruning, is associated with disease severity in patients with chronic obstructive pulmonary disease. To determine if pulmonary vascular pruning is associated with asthma severity and exacerbations. We measured the total pulmonary blood vessel volume (TBV) and the blood vessel volume of vessels less than 5mm2 in cross sectional area (BV5) and of vessels less than 10mm2 (BV10) in cross sectional area on non-contrast computed tomographic scans of participants from the Severe Asthma Research Program. Lower values of the BV5 to TBV ratio (BV5/TBV) and the BV10 to TBV ratio (BV10/TBV) represented vascular pruning (loss of the peripheral pulmonary vasculature). Compared to healthy controls, severe asthmatics had more pulmonary vascular pruning. Among asthmatics, those with poor asthma control had more pruning than those well-controlled disease. Pruning of the pulmonary vasculature was also associated with lower percent predicted forced expiratory volume in one second and forced vital capacity, greater peripheral and sputum eosinophilia and higher bronchoalveolar lavage SAA/LXA4, but not with low attenuation area or with sputum neutrophilia. Compared with individuals with less pruning, individuals with the most vascular pruning had a 150% greater odds of reporting an asthma exacerbation (OR 2.50; CI: 1.05, 5.98; p=0.039 for BV10/TBV), and reported 45% more asthma exacerbations during follow-up (IRR 1.45; CI: 1.02, 2.06; p=0.036 for BV10/TBV). Pruning of the peripheral pulmonary vasculature is associated with asthma severity, control and exacerbations, as well as with lung function and eosinophilia.

Development and Characterization of an Inducible Rat Model of Chronic Thromboembolic Pulmonary Hypertension.

PubMed

Arias-Loza, Paula-Anahi; Jung, Pius; Abeßer, Marco; Umbenhauer, Sandra; Williams, Tatjana; Frantz, Stefan; Schuh, Kai; Pelzer, Theo

2016-05-01

Chronic thromboembolic pulmonary hypertension (CTEPH) is an entity of PH that not only limits patients quality of life but also causes significant morbidity and mortality. The treatment of choice is pulmonary endarterectomy. However numerous patients do not qualify for pulmonary endarterectomy or present with residual vasculopathy post pulmonary endarterectomy and require specific vasodilator treatment. Currently, there is no available specific small animal model of CTEPH that could serve as tool to identify targetable molecular pathways and to test new treatment options. Thus, we generated and standardized a rat model that not only resembles functional and histological features of CTEPH but also emulates thrombi fibrosis. The pulmonary embolism protocol consisted of 3 sequential tail vein injections of fibrinogen/collagen-covered polystyrene microspheres combined with thrombin and administered to 10-week-old male Wistar rats. After the third embolism, rats developed characteristic features of CTEPH including elevated right ventricular systolic pressure, right ventricular cardiomyocyte hypertrophy, pulmonary artery remodeling, increased serum brain natriuretic peptide levels, thrombi fibrosis, and formation of pulmonary cellular-fibrotic lesions. The current animal model seems suitable for detailed study of CTEPH pathophysiology and permits preclinical testing of new pharmacological therapies against CTEPH. © 2016 American Heart Association, Inc.

[Special beds. Pulmonary therapy system].

PubMed

Calixto Rodríguez, Joaquín; Rodríguez Martínez, Xavier; Marín i Vivó, Gemma; Paunellas Albert, Josep

2008-10-01

To be bedridden reduces one's capacity to move and produces muscular debility that affects the respiratory system leading to a decreased effectiveness in expectoration, the ability to spit up sputum. The pulmonary therapy system integrated in a bed is the result of applying motorized elements to the articulation points of the bad in order to achieve safe positions at therapeutic angles, which improve the breathing-perfusion (blood flow) relationship. This system also makes it possible to apply vibration waves to the patient which favor the elimination of bronchial-pulmonary secretions, the rehabilitation of the bedridden patient and decrease the work load for nursing personnel.

Venous Fragment Embolism to the Pulmonary Artery: A Rare Occurrence - Case Report and Literature Review of Venous Fragment Embolization to the Pulmonary Artery

DTIC Science & Technology

2009-09-01

identified the high density (3000 Hounsfield Units ) intravascular pulmonary fragment in the same location, right lower lobe pulmonary artery, measuring...debridement and a four- compartment fasciotomy due to increasing compartment pressures. Anticoagulation was continued, 4 units of blood Report...NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Uniformed

Effects of Slow Deep Breathing at High Altitude on Oxygen Saturation, Pulmonary and Systemic Hemodynamics

PubMed Central

Bilo, Grzegorz; Revera, Miriam; Bussotti, Maurizio; Bonacina, Daniele; Styczkiewicz, Katarzyna; Caldara, Gianluca; Giglio, Alessia; Faini, Andrea; Giuliano, Andrea; Lombardi, Carolina; Kawecka-Jaszcz, Kalina; Mancia, Giuseppe; Agostoni, Piergiuseppe; Parati, Gianfranco

2012-01-01

Slow deep breathing improves blood oxygenation (SpO2) and affects hemodynamics in hypoxic patients. We investigated the ventilatory and hemodynamic effects of slow deep breathing in normal subjects at high altitude. We collected data in healthy lowlanders staying either at 4559 m for 2–3 days (Study A; N = 39) or at 5400 m for 12–16 days (Study B; N = 28). Study variables, including SpO2 and systemic and pulmonary arterial pressure, were assessed before, during and after 15 minutes of breathing at 6 breaths/min. At the end of slow breathing, an increase in SpO2 (Study A: from 80.2±7.7% to 89.5±8.2%; Study B: from 81.0±4.2% to 88.6±4.5; both p<0.001) and significant reductions in systemic and pulmonary arterial pressure occurred. This was associated with increased tidal volume and no changes in minute ventilation or pulmonary CO diffusion. Slow deep breathing improves ventilation efficiency for oxygen as shown by blood oxygenation increase, and it reduces systemic and pulmonary blood pressure at high altitude but does not change pulmonary gas diffusion. PMID:23152851

Effects of slow deep breathing at high altitude on oxygen saturation, pulmonary and systemic hemodynamics.

PubMed

Bilo, Grzegorz; Revera, Miriam; Bussotti, Maurizio; Bonacina, Daniele; Styczkiewicz, Katarzyna; Caldara, Gianluca; Giglio, Alessia; Faini, Andrea; Giuliano, Andrea; Lombardi, Carolina; Kawecka-Jaszcz, Kalina; Mancia, Giuseppe; Agostoni, Piergiuseppe; Parati, Gianfranco

2012-01-01

Slow deep breathing improves blood oxygenation (Sp(O2)) and affects hemodynamics in hypoxic patients. We investigated the ventilatory and hemodynamic effects of slow deep breathing in normal subjects at high altitude. We collected data in healthy lowlanders staying either at 4559 m for 2-3 days (Study A; N = 39) or at 5400 m for 12-16 days (Study B; N = 28). Study variables, including Sp(O2) and systemic and pulmonary arterial pressure, were assessed before, during and after 15 minutes of breathing at 6 breaths/min. At the end of slow breathing, an increase in Sp(O2) (Study A: from 80.2±7.7% to 89.5±8.2%; Study B: from 81.0±4.2% to 88.6±4.5; both p<0.001) and significant reductions in systemic and pulmonary arterial pressure occurred. This was associated with increased tidal volume and no changes in minute ventilation or pulmonary CO diffusion. Slow deep breathing improves ventilation efficiency for oxygen as shown by blood oxygenation increase, and it reduces systemic and pulmonary blood pressure at high altitude but does not change pulmonary gas diffusion.

Transcriptomics analysis of lungs and peripheral blood of crystalline silica-exposed rats

PubMed Central

Sellamuthu, Rajendran; Umbright, Christina; Roberts, Jenny R.; Chapman, Rebecca; Young, Shih-Houng; Richardson, Diana; Cumpston, Jared; McKinney, Walter; Chen, Bean T.; Frazer, David; Li, Shengqiao; Kashon, Michael; Joseph, Pius

2015-01-01

Minimally invasive approaches to detect/predict target organ toxicity have significant practical applications in occupational toxicology. The potential application of peripheral blood transcriptomics as a practical approach to study the mechanisms of silica-induced pulmonary toxicity was investigated. Rats were exposed by inhalation to crystalline silica (15 mg/m3, 6 h/day, 5 days) and pulmonary toxicity and global gene expression profiles of lungs and peripheral blood were determined at 32 weeks following termination of exposure. A significant elevation in bronchoalveolar lavage fluid lactate dehydrogenase activity and moderate histological changes in the lungs, including type II pneumocyte hyperplasia and fibrosis, indicated pulmonary toxicity in the rats. Similarly, significant infiltration of neutrophils and elevated monocyte chemotactic protein-1 levels in the lungs showed pulmonary inflammation in the rats. Microarray analysis of global gene expression profiles identified significant differential expression [>1.5-fold change and false discovery rate (FDR) p < 0.01] of 520 and 537 genes, respectively, in the lungs and blood of the exposed rats. Bioinformatics analysis of the differentially expressed genes demonstrated significant similarity in the biological processes, molecular networks, and canonical pathways enriched by silica exposure in the lungs and blood of the rats. Several genes involved in functions relevant to silica-induced pulmonary toxicity such as inflammation, respiratory diseases, cancer, cellular movement, fibrosis, etc, were found significantly differentially expressed in the lungs and blood of the silica-exposed rats. The results of this study suggested the potential application of peripheral blood gene expression profiling as a toxicologically relevant and minimally invasive surrogate approach to study the mechanisms underlying silica-induced pulmonary toxicity. PMID:22861000

Too much TV causes lung blood clot deaths.

PubMed

2016-08-10

Lung blood clots - also known as pulmonary embolisms - usually stem from clots in the leg or pelvis after inactivity has slowed blood flow. It is particularly dangerous if the clot travels to the lung and lodges in a small blood vessel.

Semi-quantitative assessment of pulmonary perfusion in children using dynamic contrast-enhanced MRI

NASA Astrophysics Data System (ADS)

Fetita, Catalin; Thong, William E.; Ou, Phalla

2013-03-01

This paper addresses the study of semi-quantitative assessment of pulmonary perfusion acquired from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in a study population mainly composed of children with pulmonary malformations. The automatic analysis approach proposed is based on the indicator-dilution theory introduced in 1954. First, a robust method is developed to segment the pulmonary artery and the lungs from anatomical MRI data, exploiting 2D and 3D mathematical morphology operators. Second, the time-dependent contrast signal of the lung regions is deconvolved by the arterial input function for the assessment of the local hemodynamic system parameters, ie. mean transit time, pulmonary blood volume and pulmonary blood flow. The discrete deconvolution method implements here a truncated singular value decomposition (tSVD) method. Parametric images for the entire lungs are generated as additional elements for diagnosis and quantitative follow-up. The preliminary results attest the feasibility of perfusion quantification in pulmonary DCE-MRI and open an interesting alternative to scintigraphy for this type of evaluation, to be considered at least as a preliminary decision in the diagnostic due to the large availability of the technique and to the non-invasive aspects.

Impairments of Antigen-Presenting Cells in Pulmonary Tuberculosis

PubMed Central

Sakhno, Ludmila V.; Shevela, Ekaterina Ya.; Tikhonova, Marina A.; Nikonov, Sergey D.; Ostanin, Alexandr A.; Chernykh, Elena R.

2015-01-01

The phenotype and functional properties of antigen-presenting cells (APC), that is, circulating monocytes and generated in vitro macrophages and dendritic cells, were investigated in the patients with pulmonary tuberculosis (TB) differing in lymphocyte reactivity to M. tuberculosis antigens (PPD-reactive versus PPD-anergic patients). We revealed the distinct impairments in patient APC functions. For example, the monocyte dysfunctions were displayed by low CD86 and HLA-DR expression, 2-fold increase in CD14+CD16+ expression, the high numbers of IL-10-producing cells, and enhanced IL-10 and IL-6 production upon LPS-stimulation. The macrophages which were in vitro generated from peripheral blood monocytes under GM-CSF were characterized by Th1/Th2-balance shifting (downproduction of IFN-γ coupled with upproduction of IL-10) and by reducing of allostimulatory activity in mixed lymphocyte culture. The dendritic cells (generated in vitro from peripheral blood monocytes upon GM-CSF + IFN-α) were characterized by impaired maturation/activation, a lower level of IFN-γ production in conjunction with an enhanced capacity to produce IL-10 and IL-6, and a profound reduction of allostimulatory activity. The APC dysfunctions were found to be most prominent in PPD-anergic patients. The possible role of APC impairments in reducing the antigen-specific T-cell response to M. tuberculosis was discussed. PMID:26339660

Metabolic Profiling of Right Ventricular-Pulmonary Vascular Function Reveals Circulating Biomarkers of Pulmonary Hypertension.

PubMed

Lewis, Gregory D; Ngo, Debby; Hemnes, Anna R; Farrell, Laurie; Domos, Carly; Pappagianopoulos, Paul P; Dhakal, Bishnu P; Souza, Amanda; Shi, Xu; Pugh, Meredith E; Beloiartsev, Arkadi; Sinha, Sumita; Clish, Clary B; Gerszten, Robert E

2016-01-19

Pulmonary hypertension and associated right ventricular (RV) dysfunction are important determinants of morbidity and mortality, which are optimally characterized by invasive hemodynamic measurements. This study sought to determine whether metabolite profiling could identify plasma signatures of right ventricular-pulmonary vascular (RV-PV) dysfunction. We measured plasma concentrations of 105 metabolites using targeted mass spectrometry in 71 individuals (discovery cohort) who underwent comprehensive physiological assessment with right-sided heart catheterization and radionuclide ventriculography at rest and during exercise. Our findings were validated in a second cohort undergoing invasive hemodynamic evaluations (n = 71), as well as in an independent cohort with or without known pulmonary arterial (PA) hypertension (n = 30). In the discovery cohort, 21 metabolites were associated with 2 or more hemodynamic indicators of RV-PV function (i.e., resting right atrial pressure, mean PA pressure, pulmonary vascular resistance [PVR], and PVR and PA pressure-flow response [ΔPQ] during exercise). We identified novel associations of RV-PV dysfunction with circulating indoleamine 2,3-dioxygenase (IDO)-dependent tryptophan metabolites (TMs), tricarboxylic acid intermediates, and purine metabolites and confirmed previously described associations with arginine-nitric oxide metabolic pathway constituents. IDO-TM levels were inversely related to RV ejection fraction and were particularly well correlated with exercise PVR and ΔPQ. Multisite sampling demonstrated transpulmonary release of IDO-TMs. IDO-TMs also identified RV-PV dysfunction in a validation cohort with known risk factors for pulmonary hypertension and in patients with established PA hypertension. Metabolic profiling identified reproducible signatures of RV-PV dysfunction, highlighting both new biomarkers and pathways for further functional characterization. Copyright © 2016 American College of Cardiology

Role of Circulating miRNAs as Biomarkers in Idiopathic Pulmonary Arterial Hypertension: Possible Relevance of miR-23a

PubMed Central

Sarrion, Irene; Milian, Lara; Juan, G.; Ramon, Mercedes; Furest, Idelfonso; Carda, Carmen; Cortijo Gimeno, Julio; Mata Roig, Manuel

2015-01-01

Idiopathic pulmonary hypertension (IPAH) is a rare disease characterized by a progressive increase in pulmonary vascular resistance leading to heart failure. MicroRNAs (miRNAs) are small noncoding RNAs that control the expression of genes, including some involved in the progression of IPAH, as studied in animals and lung tissue. These molecules circulate freely in the blood and their expression is associated with the progression of different vascular pathologies. Here, we studied the expression profile of circulating miRNAs in 12 well-characterized IPAH patients using microarrays. We found significant changes in 61 miRNAs, of which the expression of miR23a was correlated with the patients' pulmonary function. We also studied the expression profile of circulating messenger RNA (mRNAs) and found that miR23a controlled 17% of the significantly changed mRNA, including PGC1α, which was recently associated with the progression of IPAH. Finally we found that silencing of miR23a resulted in an increase of the expression of PGC1α, as well as in its well-known regulated genes CYC, SOD, NRF2, and HO1. The results point to the utility of circulating miRNA expression as a biomarker of disease progression. PMID:25815108

Prevalence and treatment of persistent pulmonary hypertension in the newborn in a Mexican pediatric hospital.

PubMed

Ortiz, Mario I; Estévez-Castillo, Ramón; Bautista-Rivas, Martha M; Romo-Hernández, Georgina; López-Cadena, Juan M; Copca-García, José A

2010-01-01

Persistent pulmonary hypertension of the newborn is defined as the failure of the normal circulatory transition that occurs after birth. It is a syndrome characterized by marked pulmonary hypertension that causes hypoxemia and right-to-left extra-pulmonary shunting of blood. In the treatment of persistent pulmonary hypertension of the newborn, the goal is to increase oxygen flow to the baby's organs to prevent serious health problems. Treatment may include medication, mechanical ventilation and respiratory therapy. We performed a retrospective, descriptive and transversal study to investigate the prevalence and treatment of neonatal patients with persistent pulmonary hypertension who were admitted at the Hospital del Niño DIF from 2004 to 2008. Data, collected from hospital charts, included demographic, clinical course and use of medication. A total of 38 patients were included (prevalence of 5.7%). The average age of patients was 8.4 +/- 1.4 days. The mortality rate was 42.1%. Data were collected and 45 different drugs were given to the pediatric patients. The median number of drugs/inpatient was 8.3 (1-18). The therapeutic class most prescribed was anti-infective (29.9% of all the prescriptions), followed by cardiovascular and renal drugs (26.4% of all the prescriptions) and gastrointestinal agents (14.6% of all the prescriptions). Ranitidine was the drug most commonly used, followed by ampicillin and midazolam. We found a high mortality rate and as in many studies, the therapeutic class most used were anti-infectives.

Phenotypic, ultra-structural and functional characterization of bovine peripheral blood dendritic cell subsets

USDA-ARS?s Scientific Manuscript database

Dendritic cells (DC) are multifunctional cells that bridge the gap between innate and adaptive immune systems. In bovine, significant information is lacking on the precise identity and role of peripheral blood DC subsets. In this study, we identify and characterize bovine peripheral blood DC subsets...

Anomalous left coronary artery from the pulmonary artery

MedlinePlus

... begins from the pulmonary artery instead of the aorta. ALCAPA is present at birth (congenital) . Causes ALCAPA ... the normal heart, the LCA originates from the aorta. It supplies oxygen-rich blood to the heart ...

Blood Clots

MedlinePlus

... lungs where it becomes wedged, preventing adequate blood flow. This is called a pulmonary (lung) embolism (PE) and can be extremely dangerous. It is estimated that each year DVT affects as many as 900,000 1 people in the United States and kills up to 100,000. 2 Despite ...

Pulmonary Veno-Occlusive Disease: A Newly Recognized Cause of Severe Pulmonary Hypertension in Dogs.

PubMed

Williams, K; Andrie, K; Cartoceti, A; French, S; Goldsmith, D; Jennings, S; Priestnall, S L; Wilson, D; Jutkowitz, A

2016-07-01

Pulmonary hypertension is a well-known though poorly characterized disease in veterinary medicine. In humans, pulmonary veno-occlusive disease (PVOD) is a rare cause of severe pulmonary hypertension with a mean survival time of 2 years without lung transplantation. Eleven adult dogs (5 males, 6 females; median age 10.5 years, representing various breeds) were examined following the development of severe respiratory signs. Lungs of affected animals were evaluated morphologically and with immunohistochemistry for alpha smooth muscle actin, desmin, CD31, CD3, CD20, and CD204. All dogs had pulmonary lesions consistent with PVOD, consisting of occlusive remodeling of small- to medium-sized pulmonary veins, foci of pulmonary capillary hemangiomatosis (PCH), and accumulation of hemosiderophages; 6 of 11 dogs had substantial pulmonary arterial medial and intimal thickening. Ultrastructural examination and immunohistochemistry showed that smooth muscle cells contributed to the venous occlusion. Increased expression of CD31 was evident in regions of PCH indicating increased numbers of endothelial cells in these foci. Spindle cells strongly expressing alpha smooth muscle actin and desmin co-localized with foci of PCH; similar cells were present but less intensely labeled elsewhere in non-PCH alveoli. B cells and macrophages, detected by immunohistochemistry, were not co-localized with the venous lesions of canine PVOD; small numbers of CD3-positive T cells were occasionally in and around the wall of remodeled veins. These findings indicate a condition in dogs with clinically severe respiratory disease and pathologic features resembling human PVOD, including foci of pulmonary venous remodeling and PCH. © The Author(s) 2016.

Emerging Metabolic Therapies in Pulmonary Arterial Hypertension

PubMed Central

Harvey, Lloyd D.; Chan, Stephen Y.

2017-01-01

Pulmonary hypertension (PH) is an enigmatic vascular disorder characterized by pulmonary vascular remodeling and increased pulmonary vascular resistance, ultimately resulting in pressure overload, dysfunction, and failure of the right ventricle. Current medications for PH do not reverse or prevent disease progression, and current diagnostic strategies are suboptimal for detecting early-stage disease. Thus, there is a substantial need to develop new diagnostics and therapies that target the molecular origins of PH. Emerging investigations have defined metabolic aberrations as fundamental and early components of disease manifestation in both pulmonary vasculature and the right ventricle. As such, the elucidation of metabolic dysregulation in pulmonary hypertension allows for greater therapeutic insight into preventing, halting, or even reversing disease progression. This review will aim to discuss (1) the reprogramming and dysregulation of metabolic pathways in pulmonary hypertension; (2) the emerging therapeutic interventions targeting these metabolic pathways; and (3) further innovation needed to overcome barriers in the treatment of this devastating disease. PMID:28375184

Oxidant-antioxidant balance in the blood of patients with chronic obstructive pulmonary disease after smoking cessation.

PubMed

Woźniak, Alina; Górecki, Dariusz; Szpinda, Michał; Mila-Kierzenkowska, Celestyna; Woźniak, Bartosz

2013-01-01

The effect of smoking cessation on the oxidative stress in patients with chronic obstructive pulmonary disease (COPD) was assessed. We recruited 73 smokers with COPD (study group), whose blood was analysed before smoking cessation, after the 1st, 2nd, and 3rd months of abstinence, 35 healthy nonsmokers (Control I), and 35 smokers with COPD (Control II). Blood was taken once in Control I and 4 times (every month) in Control II. In the study group conjugated dienes (CDs) level in plasma and erythrocytes before smoking cessation was 3 and 6.5 times higher than in Control I, respectively (P < 0.001), while thiobarbituric acid-reactive substances (TBARS) level was 89% (P < 0.001) and 51% higher (P < 0.01), respectively. Superoxide dismutase (SOD) activity was 40% higher (P < 0.05) while glutathione peroxidase (GPx) was 41% lower (P < 0.001) than in Control I. In Control II, the similar differences as compared to Control I were observed throughout the study. Smoking cessation resulted in decrease of CDs, TBARS, and SOD and GPx increase, with no changes in catalase and vitamins A and E. COPD is accompanied by oxidative stress. A three-month tobacco abstinence facilitated restoring the oxidant-antioxidant balance systemically, but it did not affect spirometric parameters.

Ibn nafis - a forgotten genius in the discovery of pulmonary blood circulation.

PubMed

Akmal, M; Zulkifle, M; Ansari, Ah

2010-03-01

Scientific theories take centuries to come into existence and they keep on evolving. Uncountable intellectual minds work on these theories; some fail to do anything about it; some add a little after tremendous efforts, and some people give remarkable and unforgettable contribution.As far as credit is concerned, the person who is able to prove the theory by his facts and who clears the maximum doubts by his observations, experimentations, facts and reasoning, gets the credit for that theory, and this should be done with honesty.The theory of pulmonary circulation took more than 2000 years to come into existence as we know it today. With the passage of time different people were given credit. Some say that it was given to Galen; some say it was Michael Servetus; others say that Realdus Columbus was the real discoverer; some gave the credit to Ibn Nafis, and finally people gave the credit to William Harvey. But after the rediscovery of Ibn Nafis' manuscript no.62243 titled Sharah al Tashreeh al Qanoon, or "Commentary on the anatomy of Canon of Avicenna" in 1924 AD in Europe, it became clear that Ibn Nafis had described the pulmonary circulation almost 300 years before Harvey, and the historians like Aldo Mieli, Max Mayrhoff, Edward Coppola etc. clearly state that Ibn Nafis is the real discoverer of the pulmonary circulation and that he should be given the credit for the discovery of the pulmonary circulation.

Improved pulmonary vascular reactivity and decreased hypertrophic remodeling during nonhypercapnic acidosis in experimental pulmonary hypertension

PubMed Central

Christou, Helen; Reslan, Ossama M.; Mam, Virak; Tanbe, Alain F.; Vitali, Sally H.; Touma, Marlin; Arons, Elena; Mitsialis, S. Alex; Kourembanas, Stella

2012-01-01

Pulmonary hypertension (PH) is characterized by pulmonary arteriolar remodeling with excessive pulmonary vascular smooth muscle cell (VSMC) proliferation. This results in decreased responsiveness of pulmonary circulation to vasodilator therapies. We have shown that extracellular acidosis inhibits VSMC proliferation and migration in vitro. Here we tested whether induction of nonhypercapnic acidosis in vivo ameliorates PH and the underlying pulmonary vascular remodeling and dysfunction. Adult male Sprague-Dawley rats were exposed to hypoxia (8.5% O2) for 2 wk, or injected subcutaneously with monocrotaline (MCT, 60 mg/kg) to develop PH. Acidosis was induced with NH4Cl (1.5%) in the drinking water 5 days prior to and during the 2 wk of hypoxic exposure (prevention protocol), or after MCT injection from day 21 to 28 (reversal protocol). Right ventricular systolic pressure (RVSP) and Fulton's index were measured, and pulmonary arteriolar remodeling was analyzed. Pulmonary and mesenteric artery contraction to phenylephrine (Phe) and high KCl, and relaxation to acetylcholine (ACh) and sodium nitroprusside (SNP) were examined ex vivo. Hypoxic and MCT-treated rats demonstrated increased RVSP, Fulton's index, and pulmonary arteriolar thickening. In pulmonary arteries of hypoxic and MCT rats there was reduced contraction to Phe and KCl and reduced vasodilation to ACh and SNP. Acidosis prevented hypoxia-induced PH, reversed MCT-induced PH, and resulted in reduction in all indexes of PH including RVSP, Fulton's index, and pulmonary arteriolar remodeling. Pulmonary artery contraction to Phe and KCl was preserved or improved, and relaxation to ACh and SNP was enhanced in NH4Cl-treated PH animals. Acidosis alone did not affect the hemodynamics or pulmonary vascular function. Phe and KCl contraction and ACh and SNP relaxation were not different in mesenteric arteries of all groups. Thus nonhypercapnic acidosis ameliorates experimental PH, attenuates pulmonary arteriolar thickening

Evolving Concepts of Pulmonary Hypertension Secondary to Left Heart Disease.

PubMed

Ramu, Bhavadharini; Thenappan, Thenappan

2016-04-01

Pulmonary hypertension associated with left heart disease is the most common form of pulmonary hypertension. Although its pathophysiology remains incompletely understood, it is now well recognized that the presence of pulmonary hypertension is associated with a worse prognosis. Right ventricular failure has independent and additive prognostic value over pulmonary hypertension for adverse outcomes in left heart disease. Recently, several new terminologies have been introduced to better define and characterize the nature and severity of pulmonary hypertension. Several new treatment options including the use of pulmonary arterial hypertension specific therapies are being considered, but there is lack of evidence. Here, we review the recent advances in this field and summarize the diagnostic and therapeutic modalities of use in the management of pulmonary hypertension associated with left heart disease.

Pulmonary artery sarcoma with angiosarcoma phenotype mimicking pleomorphic malignant fibrous histiocytoma: a case report

PubMed Central

2012-01-01

Abstract Primary sarcomas of the major blood vessels can be classified based on location in relationship to the wall or by histologic type. Angiosarcomas are malignant neoplasms that arise from the endothelial lining of the blood vessels; those arising in the intimal compartment of pulmonary artery are rare. We report a case of pulmonary artery angiosarcoma in a 36-year old female with pulmonary masses. The patient had no other primary malignant neoplasm, thus excluding a metastatic lesion. Gross examination revealed a thickened right pulmonary artery and a necrotic and hemorrhagic tumor, filling and occluding the vascular lumen. The mass extended distally, within the pulmonary vasculature of the right lung. Microscopically, an intravascular undifferentiated tumor was identified. The tumor cells showed expression for vascular markers VEGFR, VEGFR3, PDGFRa, FGF, Ulex europaeus, FVIII, FLI-1, CD31 and CD34; p53 was overexpressed and Ki67 proliferative rate was increased. Intravascular angiosarcomas are aggressive neoplasms, often associated with poor outcome. Virtual slide The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2315906377648045. PMID:23134683

The pathophysiology of chronic thromboembolic pulmonary hypertension.

PubMed

Simonneau, Gérald; Torbicki, Adam; Dorfmüller, Peter; Kim, Nick

2017-03-31

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, progressive pulmonary vascular disease that is usually a consequence of prior acute pulmonary embolism. CTEPH usually begins with persistent obstruction of large and/or middle-sized pulmonary arteries by organised thrombi. Failure of thrombi to resolve may be related to abnormal fibrinolysis or underlying haematological or autoimmune disorders. It is now known that small-vessel abnormalities also contribute to haemodynamic compromise, functional impairment and disease progression in CTEPH. Small-vessel disease can occur in obstructed areas, possibly triggered by unresolved thrombotic material, and downstream from occlusions, possibly because of excessive collateral blood supply from high-pressure bronchial and systemic arteries. The molecular processes underlying small-vessel disease are not completely understood and further research is needed in this area. The degree of small-vessel disease has a substantial impact on the severity of CTEPH and postsurgical outcomes. Interventional and medical treatment of CTEPH should aim to restore normal flow distribution within the pulmonary vasculature, unload the right ventricle and prevent or treat small-vessel disease. It requires early, reliable identification of patients with CTEPH and use of optimal treatment modalities in expert centres. Copyright ©ERS 2017.

Encapsulation of Alpha-1 antitrypsin in PLGA nanoparticles: In Vitro characterization as an effective aerosol formulation in pulmonary diseases

PubMed Central

2012-01-01

Background Alpha 1- antitrypsin (α1AT) belongs to the superfamily of serpins and inhibits different proteases. α1AT protects the lung from cellular inflammatory enzymes. In the absence of α1AT, the degradation of lung tissue results to pulmonary complications. The pulmonary route is a potent noninvasive route for systemic and local delivery. The aerosolized α1AT not only affects locally its main site of action but also avoids remaining in circulation for a long period of time in peripheral blood. Poly (D, L lactide-co glycolide) (PLGA) is a biodegradable and biocompatible polymer approved for sustained controlled release of peptides and proteins. The aim of this work was to prepare a wide range of particle size as a carrier of protein-loaded nanoparticles to deposit in different parts of the respiratory system especially in the deep lung. Various lactide to glycolide ratio of the copolymer was used to obtain different release profile of the drug which covers extended and rapid drug release in one formulation. Results Nonaqueous and double emulsion techniques were applied for the synthesis of nanoparticles. Nanoparticles were characterized in terms of surface morphology, size distribution, powder X-ray diffraction (XRD), encapsulation efficiency, in vitro drug release, FTIR spectroscopy and differential scanning calorimetry (DSC). To evaluate the nanoparticles cytotoxicity, cell cytotoxicity test was carried out on the Cor L105 human epithelial lung cancer cell line. Nanoparticles were spherical with an average size in the range of 100 nm to 1μ. The encapsulation efficiency was found to be higher when the double emulsion technique was applied. XRD and DSC results indicated that α1AT encapsulated in the nanoparticles existed in an amorphous or disordered-crystalline status in the polymer matrix. The lactic acid to glycolic acid ratio affects the release profile of α1AT. Hence, PLGA with a 50:50 ratios exhibited the ability to release %60 of the drug within 8

[From acute pulmonary embolism to chronic thromboembolic pulmonary hypertension: Pathobiology and pathophysiology].

PubMed

Beltrán-Gámez, Miguel E; Sandoval-Zárate, Julio; Pulido, Tomás

Chronic thromboembolic pulmonary hypertension (CTEPH) represents a unique subtype of pulmonary hypertension characterized by the presence of mechanical obstruction of the major pulmonary vessels caused by venous thromboembolism. CTEPH is a progressive and devastating disease if not treated, and is the only subset of PH potentially curable by a surgical procedure known as pulmonary endarterectomy. The clot burden and pulmonary embolism recurrence may contribute to the development of CTEPH however only few thrombophilic factors have been found to be associated. A current hypothesis is that CTEPH results from the incomplete resolution and organization of thrombus modified by inflammatory, immunologic and genetic mechanisms, leading to the development of fibrotic stenosis and adaptive vascular remodeling of resistance vessels. The causes of thrombus non-resolution have yet to be fully clarified. CTEPH patients often display severe PH that cannot be fully explained by the degree of pulmonary vascular obstruction apparent on imaging studies. In such cases, the small vessel disease and distal obstructive thrombotic lesions beyond the sub-segmental level may contribute for out of proportion elevated PVR. The processes implicated in the development of arteriopathy and micro-vascular changes might explain the progressive nature of PH and gradual clinical deterioration with poor prognosis, as well as lack of correlation between measurable hemodynamic parameters and vascular obstruction even in the absence of recurrent venous thromboembolism. This review summarizes the most relevant up-to-date aspects on pathobiology and pathophysiology of CTEPH. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

Partial anomalous pulmonary venous connection to the superior vena cava.

PubMed

Aramendi, José I; Rey, Estibaliz; Hamzeh, Gadah; Crespo, Alejandro; Luis, Maite; Voces, Roberto

2011-04-01

We describe the surgical technique of reimplantation of the right superior pulmonary vein into the left atrium in 2 patients with partial anomalous pulmonary venous connection to the superior vena cava without atrial septal defect. A right axillary minithoracotomy is done through the fourth intercostal space. The pulmonary vein is detached from its origin in the superior vena cava. This is sutured with 6-0 reabsorbable polydioxanone suture (Ethicon, Somerville, NJ). A lateral clamp is applied to the left atrium, and the pulmonary vein is reimplanted. The patient is extubated in the operating room. Neither cardiopulmonary bypass nor blood transfusion was required. It is simple, safe, and reproducible. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Steady-state MRA techniques with a blood pool contrast agent improve visualization of pulmonary venous anatomy and left atrial patency compared with time-resolved MRA pre- and postcatheter ablation in atrial fibrillation.

PubMed

Rustogi, Rahul; Galizia, Mauricio; Thakrar, Darshit; Merritt, Bryce; Bi, Xiaoming; Collins, Jeremy; Carr, James C

2015-11-01

To compare steady-state magnetic resonance angiography (SS-MRA), using a blood pool contrast agent, with the established technique of time-resolved MRA (TR-MRA), in pulmonary vein mapping and left atrial patency. Twenty-one patients (12 males, age 58.3 ± 8.4 years; 9 females; 57 ± 10 years) undergoing pulmonary vein mapping were evaluated with TR-MRA (TWIST) and SS-MRA. Orthogonal measurements and areas for four veins per patient per technique were assessed by Friedman's test. Overall intertechnique mean difference for any pulmonary vein orthogonal measurement and area was 0.02 ± 0.34 cm (P = 0.705), and 0.2 ± 0.08 cm(2) (P < 0.001). Interobserver correlation was strong for diameter and area measurements using the three methods with a range of 0.72-0.94, and 0.87-0.97, respectively. Left atrial appendage image quality score for TR-MRA was significantly lower than the other two methods (P < 0.001). Both observers detected more stenosis on inversion recovery (IR)-True FISP compared to TR-MRA and IR-FLASH. SS-MRA with a blood pool agent compared favorably to the established technique of TR-MRA for quantitative assessment of pulmonary venous anatomy. SS-MRA offers greater spatial resolution than TR-MRA with increased confidence for ruling out left atrial appendage filling defect. © 2015 Wiley Periodicals, Inc.

Pulmonary artery stiffness in chronic obstructive pulmonary disease (COPD) and emphysema: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study.

PubMed

Liu, Chia-Ying; Parikh, Megha; Bluemke, David A; Balte, Pallavi; Carr, James; Dashnaw, Stephen; Poor, Hooman D; Gomes, Antoinette S; Hoffman, Eric A; Kawut, Steven M; Lima, Joao A C; McAllister, David A; Prince, Martin A; Vogel-Claussen, Jens; Barr, R Graham

2018-01-01

Chronic obstructive pulmonary disease (COPD) and particularly emphysema are characterized by stiffness of the aorta, due in part to accelerated elastin degradation in the lungs and aorta. Stiffness of the pulmonary arteries (PAs) may also be increased in COPD and emphysema, but data are lacking. We assessed PA stiffness using MRI in patients with COPD and related these measurements to COPD severity and percent emphysema. The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited 290 participants, age 50-79 years with 10 or more packyears and free of clinical cardiovascular disease. COPD severity were defined on postbronchodilator spirometry by ATS/ERS criteria. Percent emphysema was defined as the percentage of regions of the lung < -950 Hounsfield units on full-lung computed tomography (CT). PA stain was defined by the percent change in cross-sectional PA area between systole and diastole on MRI. Blood flow across the tricuspid and mitral valves was assessed by phase-contrast MRI for determination of the ventricular diastolic dysfunction (E/A ratio). PA strain was reduced in COPD compared with controls (P = 0.002) and was inversely correlated with COPD severity (P = 0.004). PA strain was inversely associated to percent emphysema (P = 0.01). PA strain was also markedly correlated with right ventricular diastolic dysfunction measured by E/A ratios in the fully adjusted mix models (P = 0.02). PA strain is reduced in COPD, related in part to percent emphysema on CT scan, which may have implications for pulmonary small vessel flow and right ventricular function. 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:262-271. © 2017 International Society for Magnetic Resonance in Medicine.

Cerebral perfusion and oxygenation after the Norwood procedure: comparison of right ventricle-pulmonary artery conduit with modified Blalock-Taussig shunt.

PubMed

Kussman, Barry D; Gauvreau, Kimberlee; DiNardo, James A; Newburger, Jane W; Mackie, Andrew S; Booth, Karen L; del Nido, Pedro J; Roth, Stephen J; Laussen, Peter C

2007-03-01

The proposed physiologic advantage of the modified Norwood procedure using a right ventricle-pulmonary artery conduit to supply pulmonary blood flow, compared with a modified Blalock-Taussig shunt, is reduced runoff from the systemic-to-pulmonary circulation during diastole, resulting in a higher diastolic blood pressure and improved systemic perfusion. We hypothesized that the modified Norwood procedure is associated with improved cerebral perfusion and oxygenation. Transcranial Doppler sonography and near-infrared spectroscopy were performed in neonates undergoing the Norwood procedure with either a modified Blalock-Taussig shunt (n = 14) or right ventricle-pulmonary artery conduit (n = 13). Diastolic blood pressure was significantly higher in the right ventricle-pulmonary artery group at 6 hours after bypass (46 +/- 7 vs 40 +/- 4 mm Hg; P = .03), on postoperative day 1 (45 +/- 6 vs 37 +/- 5 mm Hg; P = .002), and on postoperative day 2 (46 +/- 7 vs 37 +/- 4 mm Hg; P = .001). Cerebral diastolic blood flow velocity did not differ significantly between groups at any time point or over time, but cerebral systolic blood flow velocity was higher over time in the Blalock-Taussig group (P = .01). No significant differences in regional cerebral oxygen saturation were found between groups at baseline or after bypass. Blood flow velocities and cerebral oxygen saturation did not differ significantly according to use of regional low-flow perfusion. The higher diastolic blood pressure after the modified Norwood procedure is not associated with higher cerebral blood flow velocities or regional cerebral oxygen saturation. This may imply an equal vulnerability to the cerebral injury associated with hemodynamic instability in the early postoperative period.

Non-invasive Characterization of the Histopathologic Features of Pulmonary Nodules of the Lung Adenocarcinoma Spectrum using Computer Aided Nodule Assessment and Risk Yield (CANARY) – a Pilot Study

PubMed Central

Maldonado, Fabien; Boland, Jennifer M.; Raghunath, Sushravya; Aubry, Marie Christine; Bartholmai, Brian J.; deAndrade, Mariza; Hartman, Thomas E.; Karwoski, Ronald A.; Rajagopalan, Srinivasan; Sykes, Anne-Marie; Yang, Ping; Yi, Eunhee S.; Robb, Richard A.; Peikert, Tobias

2013-01-01

Introduction Pulmonary nodules of the adenocarcinoma spectrum are characterized by distinctive morphological and radiological features and variable prognosis. Non-invasive high-resolution computed-tomography (HRCT)-based risk stratification tools are needed to individualize their management. Methods Radiological measurements of histopathologic tissue invasion were developed in a training set of 54 pulmonary nodules of the adenocarcinoma spectrum and validated in 86 consecutively resected nodules. Nodules were isolated and characterized by computer-aided analysis and data were analyzed by Spearman correlation, sensitivity, specificity as well as the positive and negative predictive values. Results Computer Aided Nodule Assessment and Risk Yield (CANARY) can non-invasively characterize pulmonary nodules of the adenocarcinoma spectrum. Unsupervised clustering analysis of HRCT data identified 9 unique exemplars representing the basic radiologic building blocks of these lesions. The exemplar distribution within each nodule correlated well with the proportion of histologic tissue invasion, Spearman R=0.87,p < 0.0001 and 0.89,p < 0.0001 for the training and the validation set, respectively. Clustering of the exemplars in three-dimensional space corresponding to tissue invasion and lepidic growth was used to develop a CANARY decision algorithm, which successfully categorized these pulmonary nodules as “aggressive” (invasive adenocarcinoma) or “indolent” (adenocarcinoma in situ and minimally invasive adenocarcinoma). Sensitivity, specificity, positive predictive value and negative predictive value of this approach for the detection of “aggressive” lesions were 95.4%, 96.8%, 95.4% and 96.8%, respectively in the training set and 98.7%, 63.6%, 94.9% and 87.5%, respectively in the validation set. Conclusion CANARY represents a promising tool to non-invasively risk stratify pulmonary nodules of the adenocarcinoma spectrum. PMID:23486265

Distinctive metabolomic fingerprint in scleroderma patients with pulmonary arterial hypertension.

PubMed

Deidda, Martino; Piras, Cristina; Cadeddu Dessalvi, Christian; Locci, Emanuela; Barberini, Luigi; Orofino, Susanne; Musu, Mario; Mura, Mario Nicola; Manconi, Paolo Emilio; Finco, Gabriele; Atzori, Luigi; Mercuro, Giuseppe

2017-08-15

Pulmonary arterial hypertension (PAH) in systemic sclerosis (SS) identifies a poor prognosis subset of patients. Recent studies suggested a "metabolic theory" on the development of pulmonary arterial hypertension. On this basis we performed a metabolomic study in order to evaluate whether differences in pulmonary arterial blood metabolites were identifiable in SS patients with increased pulmonary vascular resistance (PVR). We studied 18 SS patients (age 58.7±15.6years) free of pulmonary fibrosis who underwent a right heart catheterization (RHC). A blood sample was collected during the RHC in the distal peripheral circulation of the pulmonary arteries to perform the metabolomic analysis. Based on PVR we divided the population into Group A (n=8; PVR=1.16±0.23WU) and Group B (n=10; PVR=2.67±0.67WU; p<0.001 vs Group A). No significant differences were identified in terms of anthropometric, clinical, echo and therapeutic characteristics. At RHC the 2 groups showed a difference in mean pulmonary pressure values (Group A: 20±4mmHg; Group B: 27±3.4mmHg; p=0.03), with mild PAH in Group B. We applied an OSC-PLS-DA with a clear clusterization; SSc patients with PAH showed an increase in acetate, alanine, lactate, and lipoprotein levels and a decrease in γ-aminobutyrate, arginine, betaine, choline, creatine, creatinine, glucose, glutamate, glutamine, glycine, histidine, phenylalanine, and tyrosine levels CONCLUSIONS: Our results suggest that, despite similar clinical and disease-related parameters, SSc patients who develop PAH have an unfavorable metabolic profile able to cause an impaired production of metabolites with protective effects on endothelial cells. Copyright © 2017 Elsevier B.V. All rights reserved.

A porous media theory for characterization of membrane blood oxygenation devices

NASA Astrophysics Data System (ADS)

Sano, Yoshihiko; Adachi, Jun; Nakayama, Akira

2013-07-01

A porous media theory has been proposed to characterize oxygen transport processes associated with membrane blood oxygenation devices. For the first time, a rigorous mathematical procedure based a volume averaging procedure has been presented to derive a complete set of the governing equations for the blood flow field and oxygen concentration field. As a first step towards a complete three-dimensional numerical analysis, one-dimensional steady case is considered to model typical membrane blood oxygenator scenarios, and to validate the derived equations. The relative magnitudes of oxygen transport terms are made clear, introducing a dimensionless parameter which measures the distance the oxygen gas travels to dissolve in the blood as compared with the blood dispersion length. This dimensionless number is found so large that the oxygen diffusion term can be neglected in most cases. A simple linear relationship between the blood flow rate and total oxygen transfer rate is found for oxygenators with sufficiently large membrane surface areas. Comparison of the one-dimensional analytic results and available experimental data reveals the soundness of the present analysis.

[Analysis of clinical features in patients with pneumoconiosis complicated with pulmonary emphysema].

PubMed

Li, X; Dai, W R; Li, L; Liu, W F; Yang, Z X; Xie, L

2017-11-20

Objective: To investigate the clinical features of pneumoconiosis complicated with pulmo-nary emphysema. Methods: selected 868 patients with pneumoconiosis were selected from December 2015 to December 2016 in Hunan occupational disease prevention and treatment hospital. Collected the results of high-resolution spiral CT, arterial blood gas, ECG, pulmonary function and MRC score. The subjects were divided into pneumoconiosis complicated with pulmonary emphysema group and simple pneumoconiosis group accord-ing to the results of HRCT. The smoking, MRC score, pulmonary function, blood gas and complications were compared. Results: A total of 868 patients were enrolled in the study. Emphysema 232 people, accounting for 26.73%. The incidence of emphysema in the first phase of pneumoconiosis was 12.69%, and the incidence rate of emphysema in pneumoconiosis was 17.03%, The incidence of three Stage pneumoconiosis was highest, up to 60.76%, the incidence of emphysema increased with the increase of stages of pneumoconiosis ( P =0.000) .The smoking index of pneumoconiosis combined with emphysema group was significantly higher than that of simple pneumoconiosis group ( P <0.01) . The MRC score of pneumoconiosis complicated with pulmonary em-physema group was higher than that of simple pneumoconiosis group ( P =0.000) . In pneumoconiosis complicat-ed with pulmonary emphysema group the FEV(1.0)%, FVC%, FEV(1.0)/FVC, DLCO%, oxygen partial pressure were significantly lower than that of simple pneumoconiosis group ( P ≤0.05) . The combined rate of Bullae of lung in pneumoconiosis complicated with pulmonary emphysema group was higher than that of simple pneumo-coniosis group ( P <0.01) . Conclusion: pneumoconiosis stage and smoking. Patients with pneumoconiosis com-plicated with pulmonary emphysema had heavier breathing difficulties, more serious pulmonary function and active endurance, the degree of hypoxia is more serious, and had a higher incidence of complications. The pul-monary

Oral antioxidants improve leg blood flow during exercise in patients with chronic obstructive pulmonary disease

PubMed Central

Rossman, Matthew J.; Trinity, Joel D.; Garten, Ryan S.; Ives, Stephen J.; Conklin, Jamie D.; Barrett-O'Keefe, Zachary; Witman, Melissa A. H.; Bledsoe, Amber D.; Morgan, David E.; Runnels, Sean; Reese, Van R.; Zhao, Jia; Amann, Markus; Wray, D. Walter

2015-01-01

The consequence of elevated oxidative stress on exercising skeletal muscle blood flow as well as the transport and utilization of O2 in patients with chronic obstructive pulmonary disease (COPD) is not well understood. The present study examined the impact of an oral antioxidant cocktail (AOC) on leg blood flow (LBF) and O2 consumption during dynamic exercise in 16 patients with COPD and 16 healthy subjects. Subjects performed submaximal (3, 6, and 9 W) single-leg knee extensor exercise while LBF (Doppler ultrasound), mean arterial blood pressure, leg vascular conductance, arterial O2 saturation, leg arterial-venous O2 difference, and leg O2 consumption (direct Fick) were evaluated under control conditions and after AOC administration. AOC administration increased LBF (3 W: 1,604 ± 100 vs. 1,798 ± 128 ml/min, 6 W: 1,832 ± 109 vs. 1,992 ± 120 ml/min, and 9W: 2,035 ± 114 vs. 2,187 ± 136 ml/min, P < 0.05, control vs. AOC, respectively), leg vascular conductance, and leg O2 consumption (3 W: 173 ± 12 vs. 210 ± 15 ml O2/min, 6 W: 217 ± 14 vs. 237 ± 15 ml O2/min, and 9 W: 244 ± 16 vs 260 ± 18 ml O2/min, P < 0.05, control vs. AOC, respectively) during exercise in COPD, whereas no effect was observed in healthy subjects. In addition, the AOC afforded a small, but significant, improvement in arterial O2 saturation only in patients with COPD. Thus, these data demonstrate a novel beneficial role of AOC administration on exercising LBF, O2 consumption, and arterial O2 saturation in patients with COPD, implicating oxidative stress as a potential therapeutic target for impaired exercise capacity in this population. PMID:26188020

[Value of preoperative pulmonary artery diastolic pressure on predicting primary graft dysfunction after bilateral lung transplantation for patients with idiopathic pulmonary fibrosis].

PubMed

Zhang, Feng; Xu, Hongyang; Jiang, Shuyun; Li, Jiaqiong; Lu, Shunmei; Wang, Dapeng; Zang, Zhidong; Pan, Hong; Chen, Jingyu

2017-05-01

To analyze the value of the potential risk factors on predicting primary graft dysfunction (PGD) after bilateral lung transplantation for the patients with idiopathic pulmonary fibrosis (IPF). A retrospective study was conducted. Fifty-eight patients with IPF who underwent the bilateral lung transplantation admitted to Wuxi People's Hospital Affiliated to Nanjing Medical University from June 2014 to March 2017 were enrolled. The grade 3 PGD happened within 72 hours after transplantation was taken as the outcome event, and these patients were divided into PGD and non-PGD groups. The age, gender, body mass index (BMI), underlying disease, and N-terminal-probrain natriuretic peptide (NT-proBNP) before operation, pulmonary artery systolic pressure (PASP), pulmonary artery diastolic pressure (PADP), and mean pulmonary artery pressure (mPAP) before and after operation, duration of operation, the volume of blood transfusion during operation and postoperation, the use of extracorporeal membrane oxygenation (ECMO) during the operation, blood purification treatment after operation, and shock within 3 days after operation were recorded. The differences of parameters mentioned above between the two groups were compared. The predictive factors of PGD were searched by binary logistic regression analysis, and the receiver operating characteristic curve (ROC) was plotted to analyze the predictive value of preoperative PADP for grade 3 PGD after transplantation. Among 58 patients who underwent the bilateral lung transplantation, 52 patients were enrolled. The rest patients were excluded because of incomplete clinical data. There were 17 patients in the PGD group, with a mortality rate of 47.06%. The non-PGD group included 35 patients with a mortality rate of 8.57%. PADP and mPAP ahead of operation, the dosage of red cells suspension after the operation, and the total amount of blood transfusion during and after the operation in PGD group were significantly higher than those in non

Influence of Gravity on Blood Volume and Flow Distribution

NASA Technical Reports Server (NTRS)

Pendergast, D.; Olszowka, A.; Bednarczyk, E.; Shykoff, B.; Farhi, L.

1999-01-01

In our previous experiments during NASA Shuttle flights SLS 1 and 2 (9-15 days) and EUROMIR flights (30-90 days) we observed that pulmonary blood flow (cardiac output) was elevated initially, and surprisingly remained elevated for the duration of the flights. Stroke volume increased initially and then decreased, but was still above 1 Gz values. As venous return was constant, the changes in SV were secondary to modulation of heart rate. Mean blood pressure was at or slightly below 1 Gz levels in space, indicating a decrease in total peripheral resistance. It has been suggested that plasma volume is reduced in space, however cardiac output/venous return do not return to 1 Gz levels over the duration of flight. In spite of the increased cardiac output, central venous pressure was not elevated in space. These data suggest that there is a change in the basic relationship between cardiac output and central venous pressure, a persistent "hyperperfusion" and a re-distribution of blood flow and volume during space flight. Increased pulmonary blood flow has been reported to increase diffusing capacity in space, presumably due to the improved homogeneity of ventilation and perfusion. Other studies have suggested that ventilation may be independent of gravity, and perfusion may not be gravity- dependent. No data for the distribution of pulmonary blood volume were available for flight or simulated microgravity. Recent studies have suggested that the pulmonary vascular tree is influenced by sympathetic tone in a manner similar to that of the systemic system. This implies that the pulmonary circulation is dilated during microgravity and that the distribution of blood flow and volume may be influenced more by vascular control than by gravity. The cerebral circulation is influenced by sympathetic tone similarly to that of the systemic and pulmonary circulations; however its effects are modulated by cerebral autoregulation. Thus it is difficult to predict if cerebral perfusion is

21 CFR 864.7140 - Activated whole blood clotting time tests.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Activated whole blood clotting time tests. 864....7140 Activated whole blood clotting time tests. (a) Identification. An activated whole blood clotting... pulmonary embolism by measuring the coagulation time of whole blood. (b) Classification. Class II...

21 CFR 864.7140 - Activated whole blood clotting time tests.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Activated whole blood clotting time tests. 864....7140 Activated whole blood clotting time tests. (a) Identification. An activated whole blood clotting... pulmonary embolism by measuring the coagulation time of whole blood. (b) Classification. Class II...

21 CFR 864.7140 - Activated whole blood clotting time tests.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Activated whole blood clotting time tests. 864....7140 Activated whole blood clotting time tests. (a) Identification. An activated whole blood clotting... pulmonary embolism by measuring the coagulation time of whole blood. (b) Classification. Class II...

21 CFR 864.7140 - Activated whole blood clotting time tests.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Activated whole blood clotting time tests. 864....7140 Activated whole blood clotting time tests. (a) Identification. An activated whole blood clotting... pulmonary embolism by measuring the coagulation time of whole blood. (b) Classification. Class II...

21 CFR 864.7140 - Activated whole blood clotting time tests.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Activated whole blood clotting time tests. 864....7140 Activated whole blood clotting time tests. (a) Identification. An activated whole blood clotting... pulmonary embolism by measuring the coagulation time of whole blood. (b) Classification. Class II...

Trace elements in blood samples of smoker and nonsmoker active pulmonary tuberculosis patients from Jamshoro, Pakistan.

PubMed

Memon, Zainab Manzoor; Yilmaz, Erkan; Shah, Afsheen Mushtaque; Sahin, Ugur; Kazi, Tasneem Gul; Devrajani, Bikha Ram; Soylak, Mustafa

2017-12-01

Pulmonary tuberculosis (PTB) is a serious public threat throughout the world. PTB and smoking have a strong correlation. Malnutrition, poverty, addiction, overcrowding, illiteracy, unemployment, and poor hygienic conditions are the collective aspects for the disease progress. Pakistan is the fifth among 22 high tuberculosis (TB) burden countries and the fourth regarding multidrug-resistant tuberculosis (MDR-TB). The aim of study was to determine the concentration of essential and toxic elements from blood samples of smoker and nonsmoker PTB patients by inductively coupled plasma mass spectrometry (ICP-MS) followed by microwave acid digestion and compared with control subjects (n = 30). Eighty PTB patients were selected from different hospitals with age ranging 20-70 years. It was interpreted that the mean age among males and females was found to be 35.6 ± 1.4 and 33.5 ± 1.2, respectively, and the male patients were highly affected in contrast to females. Essential elements such as Mn, Fe, Zn, and Se were statistically found to be lower while Ca, Co, and Cu were found to be higher compared to the control group (p = 0.00). However, toxic elements like Al, Cr, Ni, As, Cd, and Pb were statistically elevated in smokers than nonsmokers. Further research is needed to understand the degree of the impact of essential trace elements on treatment outcome (follow-up) followed by balanced healthy nutritional supplementation along with medical therapy, consequently improving the pulmonary tuberculosis outcome and survival as well.

Pulmonary artery dissection causing haemothorax in a cat: potential role of Dirofilaria immitis infection and literature review.

PubMed

Biasato, I; Tursi, M; Zanet, S; Longato, E; Capucchio, M T

2017-02-01

A 7-year-old male castrated domestic short-haired cat suddenly died. Gross examination revealed severe right-sided haemothorax with blood clots, four adult filarial nematodes in the blood clots and the caudal vena cava and haemorrhage dissecting into the tunica media of the right pulmonary artery. Histopathological investigation showed fibrosis of the tunica intima and disorganization/fragmentation of the elastic fibres accompanied by fibrous tissue deposition in the tunica media of both branches of pulmonary artery. Degenerative vasculopathy (intimal fibromuscular hyperplasia and medial hypertrophy/hyperplasia) involving pulmonary arteries was also observed. The polymerase chain reaction amplification and sequencing confirmed the identification of the parasite as Dirofilaria immitis. A diagnosis of pulmonary artery dissection with haemothorax and concomitant heartworm disease was formulated. Degenerative processes of the tunica media have been reported to cause pulmonary artery dissection in both humans and animals. Pulmonary artery remodelling induced by heartworms may be considered the underlying cause in the first case of feline pulmonary artery dissection, herein described. Copyright © 2016 Elsevier B.V. All rights reserved.

Early pulmonary response is critical for extra-pulmonary carbon nanoparticle mediated effects: comparison of inhalation versus intra-arterial infusion exposures in mice.

PubMed

Ganguly, Koustav; Ettehadieh, Dariusch; Upadhyay, Swapna; Takenaka, Shinji; Adler, Thure; Karg, Erwin; Krombach, Fritz; Kreyling, Wolfgang G; Schulz, Holger; Schmid, Otmar; Stoeger, Tobias

2017-06-20

The death toll associated with inhaled ambient particulate matter (PM) is attributed mainly to cardio-vascular rather than pulmonary effects. However, it is unclear whether the key event for cardiovascular impairment is particle translocation from lung to circulation (direct effect) or indirect effects due to pulmonary particle-cell interactions. In this work, we addressed this issue by exposing healthy mice via inhalation and intra-arterial infusion (IAI) to carbon nanoparticles (CNP) as surrogate for soot, a major constituent of (ultrafine) urban PM. Equivalent surface area CNP doses in the blood (30mm 2 per animal) were applied by IAI or inhalation (lung-deposited dose 10,000mm 2 ; accounting for 0.3% of lung-to-blood CNP translocation). Mice were analyzed for changes in hematology and molecular markers of endothelial/epithelial dysfunction, pro-inflammatory reactions, oxidative stress, and coagulation in lungs and extra-pulmonary organs after CNP inhalation (4 h and 24 h) and CNP infusion (4 h). For methodological reasons, we used two different CNP types (spark-discharge and Printex90), with very similar physicochemical properties [≥98 and ≥95% elemental carbon; 10 and 14 nm primary particle diameter; and 800 and 300 m 2 /g specific surface area] for inhalation and IAI respectively. Mild pulmonary inflammatory responses and significant systemic effects were observed following 4 h and 24 h CNP inhalation. Increased retention of activated leukocytes, secondary thrombocytosis, and pro-inflammatory responses in secondary organs were detected following 4 h and 24 h of CNP inhalation only. Interestingly, among the investigated extra-pulmonary tissues (i.e. aorta, heart, and liver); aorta revealed as the most susceptible extra-pulmonary target following inhalation exposure. Bypassing the lungs by IAI however did not induce any extra-pulmonary effects at 4 h as compared to inhalation. Our findings indicate that extra-pulmonary effects due to CNP

Segmentation of blood clot from CT pulmonary angiographic images using a modified seeded region growing algorithm method

NASA Astrophysics Data System (ADS)

Park, Bumwoo; Furlan, Alessandro; Patil, Amol; Bae, Kyongtae T.

2010-03-01

Pulmonary embolism (PE) is a medical condition defined as the obstruction of pulmonary arteries by a blood clot, usually originating in the deep veins of the lower limbs. PE is a common but elusive illness that can cause significant disability and death if not promptly diagnosed and effectively treated. CT Pulmonary Angiography (CTPA) is the first line imaging study for the diagnosis of PE. While clinical prediction rules have been recently developed to associate short-term risks and stratify patients with acute PE, there is a dearth of objective biomarkers associated with the long-term prognosis of the disease. Clot (embolus) burden is a promising biomarker for the prognosis and recurrence of PE and can be quantified from CTPA images. However, to our knowledge, no study has reported a method for segmentation and measurement of clot from CTPA images. Thus, the purpose of this study was to develop a semi-automated method for segmentation and measurement of clot from CTPA images. Our method was based on Modified Seeded Region Growing (MSRG) algorithm which consisted of two steps: (1) the observer identifies a clot of interest on CTPA images and places a spherical seed over the clot; and (2) a region grows around the seed on the basis of a rolling-ball process that clusters the neighboring voxels whose CT attenuation values are within the range of the mean +/- two standard deviations of the initial seed voxels. The rollingball propagates iteratively until the clot is completely clustered and segmented. Our experimental results revealed that the performance of the MSRG was superior to that of the conventional SRG for segmenting clots, as evidenced by reduced degrees of over- or under-segmentation from adjacent anatomical structures. To assess the clinical value of clot burden for the prognosis of PE, we are currently applying the MSRG for the segmentation and volume measurement of clots from CTPA images that are acquired in a large cohort of patients with PE in an on

Regional myocardial extraction of a radioiodinated branched chain fatty acid during right ventricular pressure overload due to acute pulmonary hypertension

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hurford, W.; Lowenstein, E.; Zapol, W.

1985-05-01

To determine whether branched chain fatty acid extraction is reduced during right ventricular (RV) dysfunction due to acute pulmonary artery hypertension, studies were done in 6 anesthetized dogs. Regional branched chain fatty acid extraction was measured by comparing the myocardial uptake of I-125 labeled 15-(p-(iodophenyl))-3-methylpentadecanoic acid (I-PDA) to myocardial blood flow. Acute pulmonary hypertension was induced by incremental intravenous injection of 100 micron diameter glass beads into six pentobarbital anesthetized, mechanically ventilated dogs. Myocardial blood flow was measured by radiolabeled microspheres both under baseline conditions and during pulmonary hypertension. Mean RV pressure rose from 12 +- 2 (mean +- SEM)more » to 30 +-3mmHg resulting in a 225 +- 16% increase in RV stroke work. RV ejection fraction, as assessed by gated blood pool scans fell from 39 +- 2 to 18 +- 2%. Left ventricular (LV) pressures, stroke work and ejection fraction were unchanged. Myocardial blood flow increased 132 + 59% in the RV free wall and 67 +- 22% in the RV septum. LV blood flow was unchanged. Despite increased RV work and myocardial blood flow, no differences were noted in the branched chain fatty acid extraction ratios among LV or RV free walls or septum. The authors conclude that early RV dysfunction associated with pulmonary artery hypertension is not due to inadequate myocardial blood flow or branched chain fatty acid extraction.« less

Functional morphology and patterns of blood flow in the heart of Python regius.

PubMed

Starck, J Matthias

2009-06-01

Brightness-modulated ultrasonography, continuous-wave Doppler, and pulsed-wave Doppler-echocardiography were used to analyze the functional morphology of the undisturbed heart of ball pythons. In particular, the action of the muscular ridge and the atrio-ventricular valves are key features to understand how patterns of blood flow emerge from structures directing blood into the various chambers of the heart. A step-by-step image analysis of echocardiographs shows that during ventricular diastole, the atrio-ventricular valves block the interventricular canals so that blood from the right atrium first fills the cavum venosum, and blood from the left atrium fills the cavum arteriosum. During diastole, blood from the cavum venosum crosses the muscular ridge into the cavum pulmonale. During middle to late systole the muscular ridge closes, thus prohibiting further blood flow into the cavum pulmonale. At the same time, the atrio-ventricular valves open the interventricular canal and allow blood from the cavum arteriosum to flow into the cavum venosum. In the late phase of ventricular systole, all blood from the cavum pulmonale is pressed into the pulmonary trunk; all blood from the cavum venosum is pressed into both aortas. Quantitative measures of blood flow volume showed that resting snakes bypass the pulmonary circulation and shunt about twice the blood volume into the systemic circulation as into the pulmonary circulation. When digesting, the oxygen demand of snakes increased tremendously. This is associated with shunting more blood into the pulmonary circulation. The results of this study allow the presentation of a detailed functional model of the python heart. They are also the basis for a functional hypothesis of how shunting is achieved. Further, it was shown that shunting is an active regulation process in response to changing demands of the organism (here, oxygen demand). Finally, the results of this study support earlier reports about a dual pressure

Characterization of fibroblasts from hypertrophied right ventricle of pulmonary hypertensive rats.

PubMed

Imoto, Keisuke; Okada, Muneyoshi; Yamawaki, Hideyuki

2018-06-02

Pulmonary arterial hypertension (PAH), which is characterized by an elevation of pulmonary arterial resistance, leads to a lethal right heart failure. It is an urgent issue to clarify the pathogenesis of PAH-induced right heart failure. The present study aimed to elucidate the characteristics of cardiac fibroblasts (CFs) isolated from hypertrophied right ventricles of monocrotaline (MCT)-induced PAH model rats. CFs were isolated from the right ventricles of MCT-injected rats (MCT-CFs) and saline-injected control rats (CONT-CFs). Expression of α-smooth muscle actin and collagen type I in MCT-CFs was lower than that in CONT-CFs. On the other hand, proliferation, migration, and matrix metalloproteinase (MMP)-9 production were significantly enhanced in MCT-CFs. In MCT-CFs, phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and Ca 2+ /calmodulin-dependent protein kinase (CaMK) II was significantly enhanced. In addition to mRNA expression of Orai1, a Ca 2+ release-activated Ca 2+ channel, and stromal interaction molecules (STIM) 1, an endoplasmic reticulum Ca 2+ sensor, the associated store-operated Ca 2+ entry (SOCE) was significantly higher in MCT-CFs than CONT-CFs. Pharmacological inhibition of ERK1/2 pathway prevented the enhanced proliferation of MCT-CFs. The enhanced migration of MCT-CFs was prevented by a pharmacological inhibition of ERK1/2, JNK, CaMKII, or SOCE pathway. The enhanced MMP-9 production in MCT-CFs was prevented by a pharmacological inhibition of ERK1/2, CaMKII, or SOCE pathway but not JNK. The present results suggested that MCT-CFs exhibit proliferative and migratory phenotypes perhaps through multiple signaling pathways. This study for the first time determined the characteristics of CFs isolated from hypertrophied right ventricles of MCT-induced PAH model rats.

Persistent pulmonary hypertension of the newborn.

PubMed

Nair, P M C; Bataclan, Maria Flordeliz A

2004-06-01

This article attempts to define a complicated, yet not rare disease of the neonate, which presents with extreme hypoxemia due to increased pulmonary vascular resistance, resulting in diversion of the pulmonary venous blood through persistent fetal channels, namely ductus arteriosus and foramen ovale. Pathophysiology, diagnostic approach and the various modalities of management are analyzed. Persistent pulmonary hypertension of the newborn is multi-factorial, which is reflected in the management as well. These babies are extremely labile to hypoxia and should be stabilized with minimum handling. One hundred percent oxygen and ventilation are the mainstay of treatment. The role of hyperventilation, alkalinization, various non-specific vasodilators such as tolazoline, magnesium sulphate, selective vasodilators such as inhaled nitric oxide, adenosine and the role of high frequency oscillatory ventilation and extra corporeal membrane oxygenation are discussed. With the newer modalities of management, the outlook has improved with mortality of less than 20% and fewer long-term deficits.

Detection and Characterization of Circulating Tumour Cells from Frozen Peripheral Blood Mononuclear Cells

PubMed Central

Lu, David; Graf, Ryon P.; Harvey, Melissa; Madan, Ravi A.; Heery, Christopher; Marte, Jennifer; Beasley, Sharon; Tsang, Kwong Y.; Krupa, Rachel; Louw, Jessica; Wahl, Justin; Bales, Natalee; Landers, Mark; Marrinucci, Dena; Schlom, Jeffrey; Gulley, James L.; Dittamore, Ryan

2015-01-01

Retrospective analysis of patient tumour samples is a cornerstone of clinical research. CTC biomarker characterization offers a non-invasive method to analyse patient samples. However, current CTC technologies require prospective blood collection, thereby reducing the ability to utilize archived clinical cohorts with long-term outcome data. We sought to investigate CTC recovery from frozen, archived patient PBMC pellets. Matched samples from both mCRPC patients and mock samples, which were prepared by spiking healthy donor blood with cultured prostate cancer cell line cells, were processed “fresh” via Epic CTC Platform or from “frozen” PBMC pellets. Samples were analysed for CTC enumeration and biomarker characterization via immunofluorescent (IF) biomarkers, fluorescence in-situ hybridization (FISH) and CTC morphology. In the frozen patient PMBC samples, the median CTC recovery was 18%, compared to the freshly processed blood. However, abundance and localization of cytokeratin (CK) and androgen receptor (AR) protein, as measured by IF, were largely concordant between the fresh and frozen CTCs. Furthermore, a FISH analysis of PTEN loss showed high concordance in fresh vs. frozen. The observed data indicate that CTC biomarker characterization from frozen archival samples is feasible and representative of prospectively collected samples. PMID:28936240

Pulmonary vascular input impedance is a combined measure of pulmonary vascular resistance and stiffness and predicts clinical outcomes better than pulmonary vascular resistance alone in pediatric patients with pulmonary hypertension.

PubMed

Hunter, Kendall S; Lee, Po-Feng; Lanning, Craig J; Ivy, D Dunbar; Kirby, K Scott; Claussen, Lori R; Chan, K Chen; Shandas, Robin

2008-01-01

Pulmonary vascular resistance (PVR) is the current standard for evaluating reactivity in children with pulmonary arterial hypertension (PAH). However, PVR measures only the mean component of right ventricular afterload and neglects pulsatile effects. We recently developed and validated a method to measure pulmonary vascular input impedance, which revealed excellent correlation between the zero harmonic impedance value and PVR and suggested a correlation between higher-harmonic impedance values and pulmonary vascular stiffness. Here we show that input impedance can be measured routinely and easily in the catheterization laboratory, that impedance provides PVR and pulmonary vascular stiffness from a single measurement, and that impedance is a better predictor of disease outcomes compared with PVR. Pressure and velocity waveforms within the main pulmonary artery were measured during right heart catheterization of patients with normal pulmonary artery hemodynamics (n = 14) and those with PAH undergoing reactivity evaluation (49 subjects, 95 conditions). A correction factor needed to transform velocity into flow was obtained by calibrating against cardiac output. Input impedance was obtained off-line by dividing Fourier-transformed pressure and flow waveforms. Exceptional correlation was found between the indexed zero harmonic of impedance and indexed PVR (y = 1.095x + 1.381, R2 = 0.9620). In addition, the modulus sum of the first 2 harmonics of impedance was found to best correlate with indexed pulse pressure over stroke volume (y = 13.39x - 0.8058, R2 = 0.7962). Among a subset of patients with PAH (n = 25), cumulative logistic regression between outcomes to total indexed impedance was better (R(L)2 = 0.4012) than between outcomes and indexed PVR (R(L)2 = 0.3131). Input impedance can be consistently and easily obtained from pulse-wave Doppler and a single catheter pressure measurement, provides comprehensive characterization of the main components of RV afterload, and

Pathophysiological effect of fat embolism in a canine model of pulmonary contusion.

PubMed

Elmaraghy, A W; Aksenov, S; Byrick, R J; Richards, R R; Schemitsch, E H

1999-08-01

The objective of this study was to determine the individual and combined effects of pulmonary contusion and fat embolism on the hemodynamics and pulmonary pathophysiology in a canine model of acute traumatic pulmonary injury. After a thoracotomy, twenty-one skeletally mature dogs were randomly assigned to one of three groups. Unilateral pulmonary contusion alone was produced in Group 1 (seven dogs); pulmonary contusion and fat embolism, in Group 2 (seven dogs); and fat embolism alone, in Group 3 (seven dogs). Pulmonary contusion was produced by standardized compression of the left lung with a piezoelectric force transducer. Fat embolism was produced by femoral and tibial reaming followed by pressurization of the intramedullary canals. Cardiac output, systolic blood pressure, peak airway pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, partial pressure of arterial oxygen, and partial pressure of carbon dioxide were monitored for all groups. From these data, several outcome parameters were calculated: total thoracic compliance, alveolar-arterial oxygen gradient, and ratio of partial pressure of arterial oxygen to fractional inspired oxygen concentration. All of the dogs were killed after eight hours, and tissue samples were obtained from the brain, kidneys, and lungs for histological analysis. Lung samples were assigned scores for pulmonary edema (the presence of fluid in the alveoli) and inflammation (the presence of neutrophils or hyaline membranes, or both). The percentage of the total area occupied by fat was determined. Pulmonary contusion alone caused a significant increase in the alveolar-arterial oxygen gradient but only after seven hours (p = 0.034). Fat embolism alone caused a significant transient decrease in systolic blood pressure (p = 0.001) and a significant transient increase in pulmonary arterial pressure (p = 0.01) and pulmonary capillary wedge pressure (p = 0.015). Fat embolism alone also caused a significant sustained

Return of the pulmonary nodule: the radiologist's key role in implementing the 2015 BTS guidelines on the investigation and management of pulmonary nodules.

PubMed

Graham, Richard N J; Baldwin, David R; Callister, Matthew E J; Gleeson, Fergus V

2016-01-01

The British Thoracic Society has published new comprehensive guidelines for the management of pulmonary nodules. These guidelines are significantly different from those previously published, as they use two malignancy prediction calculators to better characterize the risk of malignancy. There are recommendations for a higher nodule size threshold for follow-up (≥5 mm or ≥80 mm(3)) and a reduction of the follow-up period to 1 year for solid pulmonary nodules; both of these will reduce the number of follow-up CT scans. PET-CT plays a crucial role in characterization also, with an ordinal scale being recommended for reporting. Radiologists will be the key in implementing these guidelines, and routine use of volumetric image-analysis software will be required to manage patients with pulmonary nodules correctly.

Heterogeneous mechanics of the mouse pulmonary arterial network.

PubMed

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

2016-10-01

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

Hemodynamic, pulmonary vascular, and myocardial abnormalities secondary to pharmacologic constriction of the fetal ductus arteriosus. A possible mechanism for persistent pulmonary hypertension and transient tricuspid insufficiency in the newborn infant.

PubMed

Levin, D L; Mills, L J; Weinberg, A G

1979-08-01

The prostaglandin synthetase inhibitor indomethacin was given orally or intravenously to pregnant ewes. This resulted in a significant rise in the fetal pulmonary-to-systemic arterial mean blood pressure difference across the ductus arteriosus, presumably secondary to constriction of the ductus arteriosus. In five experiments the pressure difference could be promptly but temporarily reversed by the administration of prostaglandin E1 (PGE1) into the fetal inferior vena cava. Fetal lungs from study and control animals were fixed by perfusion at measured pulmonary arterial mean blood pressure, and fifth-generation resistance vessels were studied. The medial width/external diameter ratio was significantly increased in the study vs the control lungs due to increased smooth muscle and decreased external diameter. In addition, study fetuses had acute degenerative myocardial changes in the tricuspid valve papillary muscles, the right ventricular free wall and the interventricular septum. Similar changes were not seen in control fetuses. Indomethacin administration during pregnancy causes constriction of the fetal ductus arteriosus, fetal pulmonary arterial hypertension, and right ventricular damage. If severe, this may cause rapid fetal death. If less severe, in the newborn infant, this mechanism may be one cause of persistent pulmonary hypertension due to vasoconstriction and increased pulmonary arterial smooth muscle and/or tricuspid insufficiency due to papillary muscle infarction.

The effect of lung deformation on the spatial distribution of pulmonary blood flow

PubMed Central

Arai, Tatsuya J.; Theilmann, Rebecca J.; Sá, Rui Carlos; Villongco, Michael T.

2016-01-01

Key points Pulmonary perfusion measurement using magnetic resonance imaging combined with deformable image registration enabled us to quantify the change in the spatial distribution of pulmonary perfusion at different lung volumes.The current study elucidated the effects of tidal volume lung inflation [functional residual capacity (FRC) + 500 ml and FRC + 1 litre] on the change in pulmonary perfusion distribution.Changes in hydrostatic pressure distribution as well as transmural pressure distribution due to the change in lung height with tidal volume inflation are probably bigger contributors to the redistribution of pulmonary perfusion than the changes in pulmonary vasculature resistance caused by lung tissue stretch. Abstract Tidal volume lung inflation results in structural changes in the pulmonary circulation, potentially affecting pulmonary perfusion. We hypothesized that perfusion is recruited to regions receiving the greatest deformation from a tidal breath, thus ensuring ventilation–perfusion matching. Density‐normalized perfusion (DNP) magnetic resonance imaging data were obtained in healthy subjects (n = 7) in the right lung at functional residual capacity (FRC), FRC+500 ml, and FRC+1.0 l. Using deformable image registration, the displacement of a sagittal lung slice acquired at FRC to the larger volumes was calculated. Registered DNP images were normalized by the mean to estimate perfusion redistribution (nDNP). Data were evaluated across gravitational regions (dependent, middle, non‐dependent) and by lobes (upper, RUL; middle, RML; lower, RLL). Lung inflation did not alter mean DNP within the slice (P = 0.10). The greatest expansion was seen in the dependent region (P < 0.0001: dependent vs non‐dependent, P < 0.0001: dependent vs middle) and RLL (P = 0.0015: RLL vs RUL, P < 0.0001: RLL vs RML). Neither nDNP recruitment to RLL [+500 ml = −0.047(0.145), +1 litre = 0.018(0.096)] nor to dependent lung [+500 ml = −0

World Health Organization Group I Pulmonary Hypertension: Epidemiology and Pathophysiology.

PubMed

Prins, Kurt W; Thenappan, Thenappan

2016-08-01

Pulmonary arterial hypertension (PAH) is a debilitating disease characterized by pathologic remodeling of the resistance pulmonary arteries, ultimately leading to right ventricular (RV) failure and death. In this article we discuss the definition of PAH, the initial epidemiology based on the National Institutes of Health Registry, and the updated epidemiology gleaned from contemporary registries, pathogenesis of pulmonary vascular dysfunction and proliferation, and RV failure in PAH. Copyright © 2016 Elsevier Inc. All rights reserved.

Arterial hypertension and hypertrophic pulmonary osteopathy associated with aortic valvular endocarditis in a dog.

PubMed

Vulgamott, J C; Clark, R G

1980-08-01

A 5-year-old spayed female Doberman Pinscher was referred for clinical evaluation following two acute episodes of lameness, lethargy, and respiratory dyspnea. The femoral pulse had a bounding "water-hammer" quality. Arterial blood pressures were 280 mm of Hg to greater than 300 mm of Hg during systole and approximately 40 mm of Hg during diastole. Systolic blood pressure was lowered to 210 mm of Hg, using prazosin. Radiography revealed extensive pulmonary interstitial markings and smooth subperiosteal expansions of the long bones indicative of hypertrophic pulmonary osteopathy. Despite symptomatic treatment, the dog's health gradually deteriorated, and it died 9 days after referral. Necropsy revealed vegetative endocarditis of the aortic valve. Insufficiency of the aortic valve was believed to be responsible for the systolic hypertension and the hypertrophic pulmonary osteopathy.

[Interpretation and use of routine pulmonary function tests: Spirometry, static lung volumes, lung diffusion, arterial blood gas, methacholine challenge test and 6-minute walk test].

PubMed

Bokov, P; Delclaux, C

2016-02-01

Resting pulmonary function tests (PFT) include the assessment of ventilatory capacity: spirometry (forced expiratory flows and mobilisable volumes) and static volume assessment, notably using body plethysmography. Spirometry allows the potential definition of obstructive defect, while static volume assessment allows the potential definition of restrictive defect (decrease in total lung capacity) and thoracic hyperinflation (increase in static volumes). It must be kept in mind that this evaluation is incomplete and that an assessment of ventilatory demand is often warranted, especially when facing dyspnoea: evaluation of arterial blood gas (searching for respiratory insufficiency) and measurement of the transfer coefficient of the lung, allowing with the measurement of alveolar volume to calculate the diffusing capacity of the lung for CO (DLCO: assessment of alveolar-capillary wall and capillary blood volume). All these pulmonary function tests have been the subject of an Americano-European Task force (standardisation of lung function testing) published in 2005, and translated in French in 2007. Interpretative strategies for lung function tests have been recommended, which define abnormal lung function tests using the 5th and 95th percentiles of predicted values (lower and upper limits of normal values). Thus, these recommendations need to be implemented in all pulmonary function test units. A methacholine challenge test will only be performed in the presence of an intermediate pre-test probability for asthma (diagnostic uncertainty), which is an infrequent setting. The most convenient exertional test is the 6-minute walk test that allows the assessment of walking performance, the search for arterial desaturation and the quantification of dyspnoea complaint. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Detection and Characterization of Carcinoma Cells in the Blood

NASA Astrophysics Data System (ADS)

Racila, Emilian; Euhus, David; Weiss, Arthur J.; Rao, Chandra; McConnell, John; Terstappen, Leon W. M. M.; Uhr, Jonathan W.

1998-04-01

A highly sensitive assay combining immunomagnetic enrichment with multiparameter flow cytometric and immunocytochemical analysis has been developed to detect, enumerate, and characterize carcinoma cells in the blood. The assay can detect one epithelial cell or less in 1 ml of blood. Peripheral blood (10-20 ml) from 30 patients with carcinoma of the breast, from 3 patients with prostate cancer, and from 13 controls was examined by flow cytometry for the presence of circulating epithelial cells defined as nucleic acid+, CD45-, and cytokeratin+. Highly significant differences in the number of circulating epithelial cells were found between normal controls and patients with cancer including 17 with organ-confined disease. To determine whether the circulating epithelial cells in the cancer patients were neoplastic cells, cytospin preparations were made after immunomagnetic enrichment and were analyzed. Epithelial cells from patients with breast cancer generally stained with mAbs against cytokeratin and 3 of 5 for mucin-1. In contrast, no cells that stained for these antigens were observed in the blood from normal controls. The morphology of the stained cells was consistent with that of neoplastic cells. Of 8 patients with breast cancer followed for 1-10 months, there was a good correlation between changes in the level of tumor cells in the blood with both treatment with chemotherapy and clinical status. The present assay may be helpful in early detection, in monitoring disease, and in prognostication.

From blood to bubbles: Time resolved micro-particle detection and characterization by scattered ultrasound

NASA Astrophysics Data System (ADS)

Roy, Ronald A.

2004-05-01

Robert Apfel believed in the creative application of acoustics technology to difficult problems in biomedical sensing. Much of his work in this area focused on material characterization, with the intention of effecting diagnosis. His early work in blood cell characterization employed acoustic levitation to measure the bulk mechanical properties of human red blood cells. This subsequently paved the way to the use of high-frequency acoustic scattering to yield the compressibility and density of individual blood cells. Technology developed in this later effort was then adapted to the very difficult problem of transient micro-cavitation detection, and the active cavitation detector (ACD) was born. This paper traces this line of work from its origins and, in the process, serves to celebrate Bob Apfel's peerless ingenuity and irrepressible creativity.

Pulmonary hypertension

MedlinePlus

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

IDENTIFICATION AND CHARACTERIZATION OF DISEASE USING PULMONARY FUNCTION TESTS

EPA Science Inventory

Abstract
Pulmonary function testing is used routinely in human medicine to objectively define functional deficits in individuals with respiratory disease. Despite the fact that respiratory disease is a common problem in veterinary medicine, evaluation of the small animal pa...

[Estimation of pulmonary hypertension in lung and valvular heart diseases by perfusion lung scintigraphy].

PubMed

Fujii, T; Tanaka, M; Yazaki, Y; Kitabayashi, H; Koizumi, T; Kubo, K; Sekiguchi, M; Yano, K

1999-06-01

To estimate pulmonary hypertension, we measured postural differences in pulmonary blood flow for the lateral decubitus positions on perfusion lung scintigrams with Tc-99 m macro-aggregated albumin, applying the method devised by Tanaka et al (Eur J Nucl Med 17: 320-326, 1990). Utilizing a scintillation camera coupled to a minicomputer system, changes in the distribution of pulmonary blood flow caused by gravitational effects, namely, changes in the total count ratios for the right lung versus the left lung in the right and left lateral decubitus positions (R/L), were obtained for 44 patients with lung disease, 95 patients with valvular heart disease, and 23 normal subjects. Mean standard deviation in the R/L ratios was 3.09 +/- 1.28 for the normal subjects, 1.97 +/- 0.89 for the patients with lung disease, and 1.59 +/- 0.59 for the patients with valvular heart disease. The R/L ratios correlated with mean pulmonary arterial pressure and cardio-thoracic ratios in the lung disease and valvular heart disease groups, with pulmonary arteriolar resistance in the former, and with pulmonary capillary wedge pressure in the latter. Defining pulmonary hypertension (> 20 mmHg) as an R/L ratio of less than 1.81, which is the mean-1 standard deviation for normal subjects, the sensitivity and the specificity of the R/L ratio for the diagnosis of pulmonary hypertension were 62.9% and 76.2%, respectively, for the lung disease patients, and 80.3% and 61.8%, respectively, for the valvular heart disease patients. This method seems to be useful for the pathophysiologic evaluation of pulmonary perfusion in cases of lung disease and valvular heart disease.

Imaging of pulmonary emphysema: A pictorial review

PubMed Central

Takahashi, Masashi; Fukuoka, Junya; Nitta, Norihisa; Takazakura, Ryutaro; Nagatani, Yukihiro; Murakami, Yoko; Otani, Hideji; Murata, Kiyoshi

2008-01-01

The term ‘emphysema’ is generally used in a morphological sense, and therefore imaging modalities have an important role in diagnosing this disease. In particular, high resolution computed tomography (HRCT) is a reliable tool for demonstrating the pathology of emphysema, even in subtle changes within secondary pulmonary lobules. Generally, pulmonary emphysema is classified into three types related to the lobular anatomy: centrilobular emphysema, panlobular emphysema, and paraseptal emphysema. In this pictorial review, we discuss the radiological – pathological correlation in each type of pulmonary emphysema. HRCT of early centrilobular emphysema shows an evenly distributed centrilobular tiny areas of low attenuation with ill-defined borders. With enlargement of the dilated airspace, the surrounding lung parenchyma is compressed, which enables observation of a clear border between the emphysematous area and the normal lung. Because the disease progresses from the centrilobular portion, normal lung parenchyma in the perilobular portion tends to be preserved, even in a case of far-advanced pulmonary emphysema. In panlobular emphysema, HRCT shows either panlobular low attenuation or ill-defined diffuse low attenuation of the lung. Paraseptal emphysema is characterized by subpleural well-defined cystic spaces. Recent topics related to imaging of pulmonary emphysema will also be discussed, including morphometry of the airway in cases of chronic obstructive pulmonary disease, combined pulmonary fibrosis and pulmonary emphysema, and bronchogenic carcinoma associated with bullous lung disease. PMID:18686729

Noninvasive mechanical ventilation in chronic obstructive pulmonary disease and in acute cardiogenic pulmonary edema.

PubMed

Rialp Cervera, G; del Castillo Blanco, A; Pérez Aizcorreta, O; Parra Morais, L

2014-03-01

Noninvasive ventilation (NIV) with conventional therapy improves the outcome of patients with acute respiratory failure due to hypercapnic decompensation of chronic obstructive pulmonary disease (COPD) or acute cardiogenic pulmonary edema (ACPE). This review summarizes the main effects of NIV in these pathologies. In COPD, NIV improves gas exchange and symptoms, reducing the need for endotracheal intubation, hospital mortality and hospital stay compared with conventional oxygen therapy. NIV may also avoid reintubation and may decrease the length of invasive mechanical ventilation. In ACPE, NIV accelerates the remission of symptoms and the normalization of blood gas parameters, reduces the need for endotracheal intubation, and is associated with a trend towards lesser mortality, without increasing the incidence of myocardial infarction. The ventilation modality used in ACPE does not affect the patient prognosis. Copyright © 2012 Elsevier España, S.L. y SEMICYUC. All rights reserved.

Lung cancer perfusion: can we measure pulmonary and bronchial circulation simultaneously?

PubMed

Yuan, Xiaodong; Zhang, Jing; Ao, Guokun; Quan, Changbin; Tian, Yuan; Li, Hong

2012-08-01

To describe a new CT perfusion technique for assessing the dual blood supply in lung cancer and present the initial results. This study was approved by the institutional review board. A CT protocol was developed, and a dual-input CT perfusion (DI-CTP) analysis model was applied and evaluated regarding the blood flow fractions in lung tumours. The pulmonary trunk and the descending aorta were selected as the input arteries for the pulmonary circulation and the bronchial circulation respectively. Pulmonary flow (PF), bronchial flow (BF), and a perfusion index (PI, = PF/ (PF + BF)) were calculated using the maximum slope method. After written informed consent was obtained, 13 consecutive subjects with primary lung cancer underwent DI-CTP. Perfusion results are as follows: PF, 13.45 ± 10.97 ml/min/100 ml; BF, 48.67 ± 28.87 ml/min/100 ml; PI, 21 % ± 11 %. BF is significantly larger than PF, P < 0.001. There is a negative correlation between the tumour volume and perfusion index (r = 0.671, P = 0.012). The dual-input CT perfusion analysis method can be applied successfully to lung tumours. Initial results demonstrate a dual blood supply in primary lung cancer, in which the systemic circulation is dominant, and that the proportion of the two circulation systems is moderately dependent on tumour size. A new CT perfusion technique can assess lung cancer's dual blood supply. A dual blood supply was confirmed with dominant bronchial circulation in lung cancer. The proportion of the two circulations is moderately dependent on tumour size. This new technique may benefit the management of lung cancer.

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

PubMed Central

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

2013-01-01

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

Reduced pulmonary blood flow in regions of injury 2 hours after acid aspiration in rats.

PubMed

Richter, Torsten; Bergmann, Ralf; Musch, Guido; Pietzsch, Jens; Koch, Thea

2015-01-01

Aspiration-induced lung injury can decrease gas exchange and increase mortality. Acute lung injury following acid aspiration is characterized by elevated pulmonary blood flow (PBF) in damaged lung areas in the early inflammation stage. Knowledge of PBF patterns after acid aspiration is important for targeting intravenous treatments. We examined PBF in an experimental model at a later stage (2 hours after injury). Anesthetized Wistar-Unilever rats (n = 5) underwent unilateral endobronchial instillation of hydrochloric acid. The PBF distribution was compared between injured and uninjured sides and with that of untreated control animals (n = 6). Changes in lung density after injury were measured using computed tomography (CT). Regional PBF distribution was determined quantitatively in vivo 2 hours after acid instillation by measuring the concentration of [(68)Ga]-radiolabeled microspheres using positron emission tomography. CT scans revealed increased lung density in areas of acid aspiration. Lung injury was accompanied by impaired gas exchange. Acid aspiration decreased the arterial pressure of oxygen from 157 mmHg [139;165] to 74 mmHg [67;86] at 20 minutes and tended toward restoration to 109 mmHg [69;114] at 110 minutes (P < 0.001). The PBF ratio of the middle region of the injured versus uninjured lungs of the aspiration group (0.86 [0.7;0.9], median [25%;75%]) was significantly lower than the PBF ratio in the left versus right lung of the control group (1.02 [1.0;1.05]; P = 0.016). The PBF pattern 2 hours after aspiration-induced lung injury showed a redistribution of PBF away from injured regions that was likely responsible for the partial recovery from hypoxemia over time. Treatments given intravenously 2 hours after acid-induced lung injury may not preferentially reach the injured lung regions, contrary to what occurs during the first hour of inflammation. Please see related article: http://dx.doi.org/10.1186/s12871-015-0014-z.

[Correlation between arterial and venous blood gas analysis parameters in patients with acute exacerbation of chronic obstructive pulmonary disease].

PubMed

Novović, Miloš; Topić, Vesna

2012-01-01

Arterial blood gas (ABG) analyses have an important role in the assessment and monitoring of the metabolic and oxygen status of patients with acute exacerbation of chronic obstructive pulmonary disease (COPD). Arterial puncture could have a lot of adverse effects, while sampling of venous blood is simpler and is not so invasive. The aim of this study was to evaluate whether venous blood gas (VBG) values of pH, partial pressure of carbon dioxide (PCO2), partial oxygen pressure (PO2), bicarbonate (HCO3), and venous and arterial blood oxygen saturation (SO2) can reliably predict ABG levels in patients with acute exacerbation of COPD. Forty-seven patients with a prior diagnosis of COPD were included in this prospective study. The patients with acute exacerbation of this disease were examined at the General Hospital EMS Department in Prijepolje. ABG samples were taken immediately after venous sampling, and both were analyzed. The Pearson correlation coefficients between arterial and venous parameters were 0.828, 0.877, 0.599, 0.896 and 0.312 for pH, PCO2, PO2, HCO3 and SO2, respectively. The statistically significant correlation between arterial and venous pH, PCO2 and HCO3, values was found in patients with acute exacerbation of COPD (p<0.001). When we cannot provide arterial blood for analysis, venous values of the pH, Pv,CO2 and HCO3 parameters can be an alternative to their arterial equivalents in the interpretation of the metabolic status in patients with acute exacerbation of COPD, while the values of venous Pv,O, and Sv,O2 cannot be used as predictors in the assessment of oxygen status of such patients.

Alveolar recruitment manoeuvre is safe in children prone to pulmonary hypertensive crises following open heart surgery: a pilot study.

PubMed

Amorim, Erica de Freitas; Guimaraes, Viviane Assuncao; Carmona, Fabio; Carlotti, Ana Paula de Carvalho Panzeri; Manso, Paulo Henrique; Ferreira, Cesar Augusto; Klamt, Jyrson Guilherme; Vicente, Walter Villela de Andrade

2014-05-01

To test the tolerance and safety of an alveolar recruitment manoeuvre performed in the immediate postoperative period of corrective open heart surgery in children with congenital heart disease associated with excessive pulmonary blood flow and pulmonary arterial hypertension due to left-to-right shunt. Ten infants aged 1-24 months with congenital heart disease associated with excessive pulmonary blood flow and pulmonary artery hypertension (mean pulmonary artery pressure ≥ 25 mmHg) were evaluated. The alveolar recruitment manoeuvre was performed in the operating theatre right after skin closure, and consisted of three successive stages of 30 s each, intercalated by a 1-min interval of baseline ventilation. Positive end-expiratory pressure was set to 10 cmH2O in the first stage and to 15 cmH2O in the two last ones, while the peak inspiratory pressure was kept at to 30 cmH2O in the first stage and at 35 cmH2O in the latter ones. Haemodynamic and respiratory variables were recorded. There was a slight but significant increase in mean pulmonary artery pressure from baseline to Stage 3 (P = 0.0009), as well as between Stages 1 and 2 (P = 0.0001), and 1 and 3 (P = 0.001), with no significant difference between Stages 2 and 3 (P = 0.06). Upon completion of the third stage, there were significant increases in arterial haemoglobin saturation as measured by pulse oximetry (P = 0.0009), arterial blood partial pressure of oxygen (P = 0.04), venous blood oxygen saturation of haemoglobin (P = 0.03) and arterial oxygen partial pressure over inspired oxygen fraction ratio (P = 0.04). A significant reduction in arterial blood partial pressure of carbon dioxide (P = 0.01) and in end tidal carbon dioxide also occurred (P = 0.009). The manoeuvre was well tolerated and besides a slight and transitory elevation in mean pulmonary artery, no other adverse haemodynamic or ventilatory effect was elicited. The alveolar recruitment manoeuvre seemed to be safe and well tolerated immediately

Noninvasive Doppler Tissue Measurement of Pulmonary Artery Compliance in Children with Pulmonary Hypertension

PubMed Central

Dyer, Karrie; Lanning, Craig; Das, Bibhuti; Lee, Po-Feng; Ivy, D. Dunbar; Valdes-Cruz, Lilliam; Shandas, Robin

2007-01-01

Background We have shown previously that input impedance of the pulmonary vasculature provides a comprehensive characterization of right ventricular afterload by including compliance. However, impedance-based compliance assessment requires invasive measurements. Here, we develop and validate a noninvasive method to measure pulmonary artery (PA) compliance using ultrasound color M-mode (CMM) Doppler tissue imaging (DTI). Methods Dynamic compliance (Cdyn) of the PA was obtained from CMM DTI and continuous wave Doppler measurement of the tricuspid regurgitant velocity. Cdyn was calculated as: [(Ds − Dd)/(Dd × Ps)] × 104; where Ds = systolic diameter, Dd = diastolic diameter, and Ps = systolic pressure. The method was validated both in vitro and in 13 patients in the catheterization laboratory, and then tested on 27 pediatric patients with pulmonary hypertension, with comparison with 10 age-matched control subjects. Cdyn was also measured in an additional 13 patients undergoing reactivity studies. Results Instantaneous diameter measured using CMM DTI agreed well with intravascular ultrasound measurements in the in vitro models. Clinically, Cdyn calculated by CMM DTI agreed with Cdyn calculated using invasive techniques (23.4 ± 16.8 vs 29.1 ± 20.6%/100 mm Hg; P = not significant). Patients with pulmonary hypertension had significantly lower peak wall velocity values and lower Cdyn values than control subjects (P < .01). Cdyn values followed an exponentially decaying relationship with PA pressure, indicating the nonlinear stress–strain behavior of these arteries. Reactivity in Cdyn agreed with reactivity measured using impedance techniques. Conclusion The Cdyn method provides a noninvasive means of assessing PA compliance and should be useful as an additional measure of vascular reactivity subsequent to pulmonary vascular resistance in patients with pulmonary hypertension. PMID:16581479

Sample characterization of automobile and forklift diesel exhaust particles and comparative pulmonary toxicity in mice.

PubMed

Singh, Pramila; DeMarini, David M; Dick, Colin A J; Tabor, Dennis G; Ryan, Jeff V; Linak, William P; Kobayashi, Takahiro; Gilmour, M Ian

2004-06-01

Two samples of diesel exhaust particles (DEPs) predominate in health effects research: an automobile-derived DEP (A-DEP) sample and the National Institute of Standards Technology standard reference material (SRM 2975) generated from a forklift engine. A-DEPs have been tested extensively for their effects on pulmonary inflammation and exacerbation of allergic asthmalike responses. In contrast, SRM 2975 has been tested thoroughly for its genotoxicity. In the present study, we combined physical and chemical analyses of both DEP samples with pulmonary toxicity testing in CD-1 mice to compare the two materials and to make associations between their physicochemical properties and their biologic effects. A-DEPs had more than 10 times the amount of extractable organic material and less than one-sixth the amount of elemental carbon compared with SRM 2975. Aspiration of 100 micro g of either DEP sample in saline produced mild acute lung injury; however, A-DEPs induced macrophage influx and activation, whereas SRM 2975 enhanced polymorphonuclear cell inflammation. A-DEPs stimulated an increase in interleukin-6 (IL-6), tumor necrosis factor alpha, macrophage inhibitory protein-2, and the TH2 cytokine IL-5, whereas SRM 2975 only induced significant levels of IL-6. Fractionated organic extracts of the same quantity of DEPs (100 micro g) did not have a discernable effect on lung responses and will require further study. The disparate results obtained highlight the need for chemical, physical, and source characterization of particle samples under investigation. Multidisciplinary toxicity testing of diesel emissions derived from a variety of generation and collection conditions is required to meaningfully assess the health hazards associated with exposures to DEPs. Key words: automobile, diesel exhaust particles, forklift, mice, pulmonary toxicity, SRM 2975.

Sample characterization of automobile and forklift diesel exhaust particles and comparative pulmonary toxicity in mice.

PubMed Central

Singh, Pramila; DeMarini, David M; Dick, Colin A J; Tabor, Dennis G; Ryan, Jeff V; Linak, William P; Kobayashi, Takahiro; Gilmour, M Ian

2004-01-01

Two samples of diesel exhaust particles (DEPs) predominate in health effects research: an automobile-derived DEP (A-DEP) sample and the National Institute of Standards Technology standard reference material (SRM 2975) generated from a forklift engine. A-DEPs have been tested extensively for their effects on pulmonary inflammation and exacerbation of allergic asthmalike responses. In contrast, SRM 2975 has been tested thoroughly for its genotoxicity. In the present study, we combined physical and chemical analyses of both DEP samples with pulmonary toxicity testing in CD-1 mice to compare the two materials and to make associations between their physicochemical properties and their biologic effects. A-DEPs had more than 10 times the amount of extractable organic material and less than one-sixth the amount of elemental carbon compared with SRM 2975. Aspiration of 100 micro g of either DEP sample in saline produced mild acute lung injury; however, A-DEPs induced macrophage influx and activation, whereas SRM 2975 enhanced polymorphonuclear cell inflammation. A-DEPs stimulated an increase in interleukin-6 (IL-6), tumor necrosis factor alpha, macrophage inhibitory protein-2, and the TH2 cytokine IL-5, whereas SRM 2975 only induced significant levels of IL-6. Fractionated organic extracts of the same quantity of DEPs (100 micro g) did not have a discernable effect on lung responses and will require further study. The disparate results obtained highlight the need for chemical, physical, and source characterization of particle samples under investigation. Multidisciplinary toxicity testing of diesel emissions derived from a variety of generation and collection conditions is required to meaningfully assess the health hazards associated with exposures to DEPs. Key words: automobile, diesel exhaust particles, forklift, mice, pulmonary toxicity, SRM 2975. PMID:15175167

The effect of lung deformation on the spatial distribution of pulmonary blood flow.

PubMed

Arai, Tatsuya J; Theilmann, Rebecca J; Sá, Rui Carlos; Villongco, Michael T; Hopkins, Susan R

2016-11-01

Pulmonary perfusion measurement using magnetic resonance imaging combined with deformable image registration enabled us to quantify the change in the spatial distribution of pulmonary perfusion at different lung volumes. The current study elucidated the effects of tidal volume lung inflation [functional residual capacity (FRC) + 500 ml and FRC + 1 litre] on the change in pulmonary perfusion distribution. Changes in hydrostatic pressure distribution as well as transmural pressure distribution due to the change in lung height with tidal volume inflation are probably bigger contributors to the redistribution of pulmonary perfusion than the changes in pulmonary vasculature resistance caused by lung tissue stretch. Tidal volume lung inflation results in structural changes in the pulmonary circulation, potentially affecting pulmonary perfusion. We hypothesized that perfusion is recruited to regions receiving the greatest deformation from a tidal breath, thus ensuring ventilation-perfusion matching. Density-normalized perfusion (DNP) magnetic resonance imaging data were obtained in healthy subjects (n = 7) in the right lung at functional residual capacity (FRC), FRC+500 ml, and FRC+1.0 l. Using deformable image registration, the displacement of a sagittal lung slice acquired at FRC to the larger volumes was calculated. Registered DNP images were normalized by the mean to estimate perfusion redistribution (nDNP). Data were evaluated across gravitational regions (dependent, middle, non-dependent) and by lobes (upper, RUL; middle, RML; lower, RLL). Lung inflation did not alter mean DNP within the slice (P = 0.10). The greatest expansion was seen in the dependent region (P < 0.0001: dependent vs non-dependent, P < 0.0001: dependent vs middle) and RLL (P = 0.0015: RLL vs RUL, P < 0.0001: RLL vs RML). Neither nDNP recruitment to RLL [+500 ml = -0.047(0.145), +1 litre = 0.018(0.096)] nor to dependent lung [+500 ml = -0.058(0.126), +1 litre = -0

Interferon-gamma response to the treatment of active pulmonary and extra-pulmonary tuberculosis.

PubMed

Liang, L; Shi, R; Liu, X; Yuan, X; Zheng, S; Zhang, G; Wang, W; Wang, J; England, K; Via, L E; Cai, Y; Goldfeder, L C; Dodd, L E; Barry, C E; Chen, R Y

2017-10-01

Interferon-gamma (IFN-γ) release assays (IGRAs) are used to diagnose tuberculosis (TB) but not to measure treatment response. To measure IFN-γ response to active anti-tuberculosis treatment. Patients from the Henan Provincial Chest Hospital, Henan, China, with TB symptoms and/or signs were enrolled into this prospective, observational cohort study and followed for 6 months of treatment, with blood and sputum samples collected at 0, 2, 4, 6, 8, 16 and 24 weeks. The QuantiFERON® TB-Gold assay was run on collected blood samples. Participants received a follow-up telephone call at 24 months to determine relapse status. Of the 152 TB patients enrolled, 135 were eligible for this analysis: 118 pulmonary (PTB) and 17 extra-pulmonary TB (EPTB) patients. IFN-γ levels declined significantly over time among all patients (P = 0.002), with this decline driven by PTB patients (P = 0.001), largely during the initial 8 weeks of treatment (P = 0.019). IFN-γ levels did not change among EPTB patients over time or against baseline culture or drug resistance status. After 6 months of effective anti-tuberculosis treatment, IFN-γ levels decreased significantly in PTB patients, largely over the initial 8 weeks of treatment. IFN-γ concentrations may offer some value for monitoring anti-tuberculosis treatment response among PTB patients.

Investigation of the relative effects of vascular branching structure and gravity on pulmonary arterial blood flow heterogeneity via an image-based computational model.

PubMed

Burrowes, Kelly S; Hunter, Peter J; Tawhai, Merryn H

2005-11-01

A computational model of blood flow through the human pulmonary arterial tree has been developed to investigate the relative influence of branching structure and gravity on blood flow distribution in the human lung. Geometric models of the largest arterial vessels and lobar boundaries were first derived using multidetector row x-ray computed tomography (MDCT) scans. Further accompanying arterial vessels were generated from the MDCT vessel endpoints into the lobar volumes using a volume-filling branching algorithm. Equations governing the conservation of mass and momentum were solved within the geometric model to calculate pressure, velocity, and vessel radius. Blood flow results in the anatomically based model, with and without gravity, and in a symmetric geometric model were compared to investigate their relative contributions to blood flow heterogeneity. Results showed a persistent blood flow gradient and flow heterogeneity in the absence of gravitational forces in the anatomically based model. Comparison with flow results in the symmetric model revealed that the asymmetric vascular branching structure was largely responsible for producing this heterogeneity. Analysis of average results in varying slice thicknesses illustrated a clear flow gradient because of gravity in "lower resolution" data (thicker slices), but on examination of higher resolution data, a trend was less obvious. Results suggest that although gravity does influence flow distribution, the influence of the tree branching structure is also a dominant factor. These results are consistent with high-resolution experimental studies that have demonstrated gravity to be only a minor determinant of blood flow distribution.

Pulmonary hypertension due to acute respiratory distress syndrome

PubMed Central

Ñamendys-Silva, S.A.; Santos-Martínez, L.E.; Pulido, T.; Rivero-Sigarroa, E.; Baltazar-Torres, J.A.; Domínguez-Cherit, G.; Sandoval, J.

2014-01-01

Our aims were to describe the prevalence of pulmonary hypertension in patients with acute respiratory distress syndrome (ARDS), to characterize their hemodynamic cardiopulmonary profiles, and to correlate these parameters with outcome. All consecutive patients over 16 years of age who were in the intensive care unit with a diagnosis of ARDS and an in situ pulmonary artery catheter for hemodynamic monitoring were studied. Pulmonary hypertension was diagnosed when the mean pulmonary artery pressure was >25 mmHg at rest with a pulmonary artery occlusion pressure or left atrial pressure <15 mmHg. During the study period, 30 of 402 critically ill patients (7.46%) who were admitted to the ICU fulfilled the criteria for ARDS. Of the 30 patients with ARDS, 14 met the criteria for pulmonary hypertension, a prevalence of 46.6% (95% CI; 28-66%). The most common cause of ARDS was pneumonia (56.3%). The overall mortality was 36.6% and was similar in patients with and without pulmonary hypertension. Differences in patients' hemodynamic profiles were influenced by the presence of pulmonary hypertension. The levels of positive end-expiratory pressure and peak pressure were higher in patients with pulmonary hypertension, and the PaCO2 was higher in those who died. The level of airway pressure seemed to influence the onset of pulmonary hypertension. Survival was determined by the severity of organ failure at admission to the intensive care unit. PMID:25118626

Distribution of pulmonary ventilation and perfusion during short periods of weightlessness

NASA Technical Reports Server (NTRS)

Michels, D. B.; West, J. B.

1978-01-01

Airborne experiments were conducted on four trained normal male subjects (28-40 yr) to study pulmonary function during short periods (22-27 sec) of zero gravity obtained by flying a jet aircraft through appropriate parabolic trajectories. The cabin was always pressurized to a sea-level altitude. The discussion is limited to pulmonary ventilation and perfusion. The results clearly demonstrate that gravity is the major factor causing nonuniformity in the topographical distribution of pulmonary ventilation. More importantly, the results suggest that virtually all the topographical nonuniformity of ventilation, blood flow, and lung volume observed under 1-G conditions are eliminated during short periods of zero gravity.

Ibn al-Nafis, the pulmonary circulation, and the Islamic Golden Age

PubMed Central

West, John B.

2008-01-01

Ibn al-Nafis (1213–1288) was an Arab physician who made several important contributions to the early knowledge of the pulmonary circulation. He was the first person to challenge the long-held contention of the Galen School that blood could pass through the cardiac interventricular septum, and in keeping with this he believed that all the blood that reached the left ventricle passed through the lung. He also stated that there must be small communications or pores (manafidh in Arabic) between the pulmonary artery and vein, a prediction that preceded by 400 years the discovery of the pulmonary capillaries by Marcello Malpighi. Ibn al-Nafis and another eminent physiologist of the period, Avicenna (ca. 980–1037), belong to the long period between the enormously influential school of Galen in the 2nd century, and the European scientific Renaissance in the 16th century. This is an epoch often given little attention by physiologists but is known to some historians as the Islamic Golden Age. Its importance is briefly discussed here. PMID:18845773

Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suzuki, Chihiro; Takahashi, Masafumi; Morimoto, Hajime

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 bymore » 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.« less

Compartmentalized bronchoalveolar IFN-gamma and IL-12 response in human pulmonary tuberculosis.

PubMed

Herrera, Maria Teresa; Torres, Martha; Nevels, Denarra; Perez-Redondo, Carlos Núñez; Ellner, Jerrold J; Sada, Eduardo; Schwander, Stephan K

2009-01-01

Human tuberculosis (TB) principally involves the lungs, where local immunity impacts on the load of Mycobacterium tuberculosis (M.tb). Because concomitants of local Th1 immunity are still under-explored in humans, we characterized immune responses in bronchoalveolar cells (BACs) and systemically in peripheral blood mononuclear cells (PBMCs) in persons with active pulmonary TB and in healthy community controls. PPD- and live M.tb-induced IFN-gamma-production were observed in CD4(+), CD8(+), gammadeltaTCR(+), and CD56(+) alveolar T cell subpopulations and NK cells (CD3(-)CD56(+)). IFN-gamma-producing CD4(+) T cells (mostly CD45RO(+)) were more abundant (p<0.05). M.tb-induced IL-12p70, but interestingly also IL-4, was increased (p<0.05) in BACs from TB patients. Constitutive expression of IL-12Rbeta1 and IL-12Rbeta2 mRNA in BACs and PBMCs and IFN-gammaR1 in BACs was similar in both study groups. Data were normalized to account for differences in proportions of alveolar T cells and macrophages in the study groups. IFN-gamma-production and its induction by IL-12R engagement occur virtually unimpaired in the bronchoalveolar spaces of patients with pulmonary TB. The reasons for the apparent failure to control M. tuberculosis growth during active pulmonary TB disease is unknown but could be the expression of locally acting immunosuppressive mechanisms that subvert the antimycobacterial effects of IFN-gamma.

Cavitary pulmonary metastases

PubMed Central

Chaudhuri, M. Ray

1970-01-01

Cavitation in pulmonary metastases is more common than might be supposed from the small number of cases (75) previously reported. Twenty-five cases of cavitary pulmonary metastases were seen at the London Chest Hospital from 1964 to 1969. The primary sites were the large intestine (8), opposite lung (4), cervix (3), stomach, oesophagus, pancreas, and larynx (2 each) and anal canal and kidney (1 each). The size of the cavities ranged from 1·0 to 6·0 cm., and their wall thickness from 0·3 to 2·5 cm. Only in three cases was there an identifiable communication with the bronchial tree and only in these three cases were neoplastic cells found in the sputum. The main microscopic feature was vascular invasion, which was found in the vicinity of every metastasis; thrombosis was seen in 14 cases. It seems that the principal cause of necrosis and subsequent cavitation in metastatic tumours of the lung is interference with their blood supply by vascular involvement. Images PMID:5452295

Teaching Pulmonary Gas Exchange Physiology Using Computer Modeling

ERIC Educational Resources Information Center

Kapitan, Kent S.

2008-01-01

Students often have difficulty understanding the relationship of O[subscript 2] consumption, CO[subscript 2] production, cardiac output, and distribution of ventilation-perfusion ratios in the lung to the final arterial blood gas composition. To overcome this difficulty, I have developed an interactive computer simulation of pulmonary gas exchange…

DNA Damage and Pulmonary Hypertension

PubMed Central

Ranchoux, Benoît; Meloche, Jolyane; Paulin, Roxane; Boucherat, Olivier; Provencher, Steeve; Bonnet, Sébastien

2016-01-01

Pulmonary hypertension (PH) is defined by a mean pulmonary arterial pressure over 25 mmHg at rest and is diagnosed by right heart catheterization. Among the different groups of PH, pulmonary arterial hypertension (PAH) is characterized by a progressive obstruction of distal pulmonary arteries, related to endothelial cell dysfunction and vascular cell proliferation, which leads to an increased pulmonary vascular resistance, right ventricular hypertrophy, and right heart failure. Although the primary trigger of PAH remains unknown, oxidative stress and inflammation have been shown to play a key role in the development and progression of vascular remodeling. These factors are known to increase DNA damage that might favor the emergence of the proliferative and apoptosis-resistant phenotype observed in PAH vascular cells. High levels of DNA damage were reported to occur in PAH lungs and remodeled arteries as well as in animal models of PH. Moreover, recent studies have demonstrated that impaired DNA-response mechanisms may lead to an increased mutagen sensitivity in PAH patients. Finally, PAH was linked with decreased breast cancer 1 protein (BRCA1) and DNA topoisomerase 2-binding protein 1 (TopBP1) expression, both involved in maintaining genome integrity. This review aims to provide an overview of recent evidence of DNA damage and DNA repair deficiency and their implication in PAH pathogenesis. PMID:27338373

Treatment of pulmonary brucellosis: a systematic review.

PubMed

Solera, Javier; Solís García Del Pozo, Julián

2017-01-01

Pulmonary involvement is a rare, focal complication of human brucellosis. The aim of this review is to describe clinical and radiologic features, treatment administered and clinical course of these patients. Areas covered: We conducted a systematic search of scientific reports of brucellosis with pulmonary involvement published from January 1985 to July 2016. Four main patterns of disease were observed: pneumonia, pleural effusion, nodules and interstitial pattern. Cough and fever were the most common symptoms. Brucella spp. culture was obtained from blood (50%) or pleural fluid. Treatment is based on the same antibiotics and combinations of antibiotics as for patients with acute no complicated brucellosis. The most frequent antimicrobial combination was doxycycline and rifampin for six weeks. The clinical course was favorable in most reports, and mortality was remarkably low (<1%). Expert commentary: Non-specific clinical and radiological manifestations were the main reason for the delay in proper treatment. Difficulty in distinguishing Brucellosis from other pulmonary infections, such as tuberculosis, sometimes posed an added diagnostic challenge.

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.

Blood product transfusion in emergency department patients: a case-control study of practice patterns and impact on outcome.

PubMed

Beyer, Alexander; Rees, Ryan; Palmer, Christopher; Wessman, Brian T; Fuller, Brian M

2017-12-01

Blood product transfusion occurs in a significant percentage of intensive care unit (ICU) patients. Pulmonary complications, such as acute respiratory distress syndrome (ARDS), occurring in the setting of transfusion, are associated with increased morbidity and mortality. Contrary to the ICU setting, there is little evidence describing the epidemiology of transfusion in the emergency department (ED) or its potential impact on outcome. The objectives of this study were to: (1) characterize transfusion practices in the ED with respect to patient characteristics and pre-transfusion laboratory values; and (2) investigate the effect of ED blood product transfusion on the incidence of pulmonary complications after admission. We hypothesized that blood product transfusion would increase the event rate for pulmonary complications, and have a negative impact on other clinically significant outcomes. This was a retrospective case-control study with one-one matching of 204 transfused ED patients to 204 non-transfused controls. The primary outcome was a composite pulmonary outcome that included: acute respiratory failure, new need for ICU admission, and ARDS. Multivariable logistic regression was used to evaluate the primary outcome as a function of transfusion. One-hundred twenty four (60.8%) patients were transfused packed red blood cells (PRBC) in the ED. The mean pre-transfusion hemoglobin level was 8.5 g/dl. There were 73 patients with a hemoglobin value ≥10 g/dl; 19 (26.0%) received a PRBC transfusion. A total of 54 (26.5%) patients were transfused platelets. The main indications were thrombocytopenia (27.8%) and neurologic injury (24.1%). Ten patients had a platelet level <10,000 (guideline recommended threshold for transfusion to prevent spontaneous hemorrhage). The mean platelet count for neurologic injury patients was 197,000 prior to transfusion. The primary outcome occurred in 26 control patients (12.7%), as compared with 28 cases (13.7%). In multivariable

High-altitude pulmonary hypertension is associated with a free radical-mediated reduction in pulmonary nitric oxide bioavailability

PubMed Central

Bailey, Damian M; Dehnert, Christoph; Luks, Andrew M; Menold, Elmar; Castell, Christian; Schendler, Guido; Faoro, Vitalie; Gutowski, Mariusz; Evans, Kevin A; Taudorf, Sarah; James, Philip E; McEneny, J; Young, Ian S; Swenson, Erik R; Mairbäurl, Heimo; Bärtsch, Peter; Berger, Marc M

2010-01-01

High altitude (HA)-induced pulmonary hypertension may be due to a free radical-mediated reduction in pulmonary nitric oxide (NO) bioavailability. We hypothesised that the increase in pulmonary artery systolic pressure (PASP) at HA would be associated with a net transpulmonary output of free radicals and corresponding loss of bioactive NO metabolites. Twenty-six mountaineers provided central venous and radial arterial samples at low altitude (LA) and following active ascent to 4559 m (HA). PASP was determined by Doppler echocardiography, pulmonary blood flow by inert gas re-breathing, and vasoactive exchange via the Fick principle. Acute mountain sickness (AMS) and high-altitude pulmonary oedema (HAPE) were diagnosed using clinical questionnaires and chest radiography. Electron paramagnetic resonance spectroscopy, ozone-based chemiluminescence and ELISA were employed for plasma detection of the ascorbate free radical (A·−), NO metabolites and 3-nitrotyrosine (3-NT). Fourteen subjects were diagnosed with AMS and three of four HAPE-susceptible subjects developed HAPE. Ascent decreased the arterio-central venous concentration difference (a-cvD) resulting in a net transpulmonary loss of ascorbate, α-tocopherol and bioactive NO metabolites (P < 0.05 vs. LA). This was accompanied by an increased a-cvD and net output of A·− and lipid hydroperoxides (P < 0.05 vs. sea level, SL) that correlated against the rise in PASP (r= 0.56–0.62, P < 0.05) and arterial 3-NT (r= 0.48–0.63, P < 0.05) that was more pronounced in HAPE. These findings suggest that increased PASP and vascular resistance observed at HA are associated with a free radical-mediated reduction in pulmonary NO bioavailability. PMID:20876202

Acute and chronic dissection of pulmonary artery: new challenges in pulmonary arterial hypertension?

PubMed

Florczyk, Michał; Wieteska, Maria; Kurzyna, Marcin; Gościniak, Piotr; Pepke-Żaba, Joanna; Biederman, Andrzej; Torbicki, Adam

2018-01-01

Right ventricular failure is a leading cause of mortality in patients with pulmonary arterial hypertension (PAH). However, up to 25% of such patients die unexpectedly, without warning signs of hemodynamical decompensation. We previously documented that pulmonary artery (PA) dilatation significantly increases the risk of those deaths. Some of them may be due to dissection of PA resulting in cardiac tamponade. However, direct confirmation of this mechanism is difficult as most of such deaths occur outside hospitals. We present 4 patients with severe PAH and PA dilatation in whom PA dissection has been confirmed. Three patients had IPAH, one had PAH associated with congenital heart disease. All patients had mean pulmonary artery pressure (PAP) > 50 mmHg at diagnosis and dissection occurred late in the course of apparently well controlled disease (6 to 14 years). Several clinical elements were common to our patients - high systolic PAP, long lasting PH, progressive dilatation of PA to more than 50 mm with chest pain prior to dissection. However, clinical course followed three different patterns: sudden death due to cardiac tamponade, hemopericarditis caused by blood leaking from dissected aneurysm with imminent but not immediate cardiac tamponade, or chronic asymptomatic PA dissection. Indeed, two of our patients are alive and on lung transplantation waiting list for more than 2 years now. Further research is needed to suggest optimal management strategies for patients with stable PAH but significantly dilated proximal pulmonary arteries or confirmed PA dissection depending on the clinical presentation and expected outcome.

Advanced Techniques in Pulmonary Function Test Analysis Interpretation and Diagnosis

PubMed Central

Gildea, T.J.; Bell, C. William

1980-01-01

The Pulmonary Functions Analysis and Diagnostic System is an advanced clinical processing system developed for use at the Pulmonary Division, Department of Medicine at the University of Nebraska Medical Center. The system generates comparative results and diagnostic impressions for a variety of routine and specialized pulmonary functions test data. Routine evaluation deals with static lung volumes, breathing mechanics, diffusing capacity, and blood gases while specialized tests include lung compliance studies, small airways dysfunction studies and dead space to tidal volume ratios. Output includes tabular results of normal vs. observed values, clinical impressions and commentary and, where indicated, a diagnostic impression. A number of pulmonary physiological and state variables are entered or sampled (A to D) with periodic status reports generated for the test supervisor. Among the various physiological variables sampled are respiratory frequency, minute ventilation, oxygen consumption, carbon dioxide production, and arterial oxygen saturation.

Intrapleural instillation of autologous blood for persistent air leak in spontaneous pneumothorax in patients with advanced chronic obstructive pulmonary disease.

PubMed

Cao, Guo qiang; Kang, Jun; Wang, Fangwen; Wang, Hucheng

2012-05-01

We evaluated the safety and efficacy of increasing doses of autologous blood patch pleurodesis in treating persistent air leaks in patients with advanced chronic obstructive pulmonary disease (COPD). Forty-four patients with COPD and spontaneous pneumothorax (SP) on the 7th day after intercostal tube drainage were randomly assigned to 4 groups, with 11 patients in each group. Groups A, B, and C were given increasing doses of autologous blood--ie, 0.5 mL/kg, 1 mL/kg, 2 mL/kg, respectively--whereas group D was given 1 mL/kg normal saline only. The procedure was repeated if the air leak persisted on postoperative days 9 and 11. Patients in group D crossed over and received autologous blood as in group B if the air leak was still present on the 13th postoperative day. No patient died in the study. The air leak was sealed by the 13th postoperative day only in patients with air leaks smaller than size 3. Air leaks were classified as 0 to 3 [12], ie, size 0=no air leak; size 1=air leak on vigorous coughing only; size 2=small continuous air leak on gentle respiration; and size 3=large continuous air leak on gentle respiration. The success rates by the 13th postoperative day in groups A, B, C, and D were 27%, 82%, 82%, and 9%, respectively. The success rate (82%) was significantly higher in groups B and C than in group A (p=0.003) and D (p>0.01). Using autologous blood to treat secondary spontaneous pneumothorax (SSP) in patients with advanced COPD is easy, safe, and effective. The dose of blood required for autologous blood patch pleurodesis should be dependent on the body weight, and 1 mL/kg blood may be efficient. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

The expression of Mirc1/Mir17-92 cluster in sputum samples correlates with pulmonary exacerbations in cystic fibrosis patients.

PubMed

Krause, Kathrin; Kopp, Benjamin T; Tazi, Mia F; Caution, Kyle; Hamilton, Kaitlin; Badr, Asmaa; Shrestha, Chandra; Tumin, Dmitry; Hayes, Don; Robledo-Avila, Frank; Hall-Stoodley, Luanne; Klamer, Brett G; Zhang, Xiaoli; Partida-Sanchez, Santiago; Parinandi, Narasimham L; Kirkby, Stephen E; Dakhlallah, Duaa; McCoy, Karen S; Cormet-Boyaka, Estelle; Amer, Amal O

2018-07-01

Cystic fibrosis (CF) is a multi-organ disorder characterized by chronic sino-pulmonary infections and inflammation. Many patients with CF suffer from repeated pulmonary exacerbations that are predictors of worsened long-term morbidity and mortality. There are no reliable markers that associate with the onset or progression of an exacerbation or pulmonary deterioration. Previously, we found that the Mirc1/Mir17-92a cluster which is comprised of 6 microRNAs (Mirs) is highly expressed in CF mice and negatively regulates autophagy which in turn improves CF transmembrane conductance regulator (CFTR) function. Therefore, here we sought to examine the expression of individual Mirs within the Mirc1/Mir17-92 cluster in human cells and biological fluids and determine their role as biomarkers of pulmonary exacerbations and response to treatment. Mirc1/Mir17-92 cluster expression was measured in human CF and non-CF plasma, blood-derived neutrophils, and sputum samples. Values were correlated with pulmonary function, exacerbations and use of CFTR modulators. Mirc1/Mir17-92 cluster expression was not significantly elevated in CF neutrophils nor plasma when compared to the non-CF cohort. Cluster expression in CF sputum was significantly higher than its expression in plasma. Elevated CF sputum Mirc1/Mir17-92 cluster expression positively correlated with pulmonary exacerbations and negatively correlated with lung function. Patients with CF undergoing treatment with the CFTR modulator Ivacaftor/Lumacaftor did not demonstrate significant change in the expression Mirc1/Mir17-92 cluster after six months of treatment. Mirc1/Mir17-92 cluster expression is a promising biomarker of respiratory status in patients with CF including pulmonary exacerbation. Published by Elsevier B.V.

THE RAPID SHALLOW BREATHING RESULTING FROM PULMONARY CONGESTION AND EDEMA

PubMed Central

Churchill, Edward D.; Cope, Oliver

1929-01-01

These experiments record the effects of the experimental production of pulmonary congestion and edema in a lung completely isolated from the general circulation, but with an intact nerve supply. The resulting changes are: a slowing of the heart rate, a fall in systemic blood pressure and a temporary inhibition of respiration succeeded by rapid shallow breathing. The pulse rate and blood pressure show a rapid and spontaneous return to initial conditions. The respirations show a partial but not a complete return to their former rate and depth. The effects on respiration are similar to those described by Dunn and Binger and Moore which follow multiple embolism of the pulmonary circuit with starch granules. The alterations in the pulse rate and blood pressure are characteristic of the effects of vagal stimulation. A chemical effect on the respiratory center is excluded by the nature of the preparation. These results, therefore, add further evidence to support the hypothesis that the rapid shallow breathing attending congestion and edema of the lungs is due to the stimulation of nerve endings in the lungs. PMID:19869562

An Earth-Based Model of Microgravity Pulmonary Physiology

NASA Technical Reports Server (NTRS)

Hirschl, Ronald B.; Bull, Joseph L.; Grothberg, James B.

2004-01-01

There are currently only two practical methods of achieving micro G for experimentation: parabolic flight in an aircraft or space flight, both of which have limitations. As a result, there are many important aspects of pulmonary physiology that have not been investigated in micro G. We propose to develop an earth-based animal model of micro G by using liquid ventilation, which will allow us to fill the lungs with perfluorocarbon, and submersing the animal in water such that the density of the lungs is the same as the surrounding environment. By so doing, we will eliminate the effects of gravity on respiration. We will first validate the model by comparing measures of pulmonary physiology, including cardiac output, central venous pressures, lung volumes, and pulmonary mechanics, to previous space flight and parabolic flight measurements. After validating the model, we will investigate the impact of micro G on aspects of lung physiology that have not been previously measured. These will include pulmonary blood flow distribution, ventilation distribution, pulmonary capillary wedge pressure, ventilation-perfusion matching, and pleural pressures and flows. We expect that this earth-based model of micro G will enhance our knowledge and understanding of lung physiology in space which will increase in importance as space flights increase in time and distance.

Blood eosinophil count and pneumonia risk in patients with chronic obstructive pulmonary disease: a patient-level meta-analysis.

PubMed

Pavord, Ian D; Lettis, Sally; Anzueto, Antonio; Barnes, Neil

2016-09-01

Inhaled corticosteroids are important in the management of chronic obstructive pulmonary disease (COPD), but can slightly increase the risk of pneumonia in patients with moderate-to-severe COPD. Patients with circulating eosinophil counts of 2% or more of blood leucocytes respond better to inhaled corticosteroids than do those with counts of less than 2% and it was therefore postulated that blood eosinophil count might also have an effect on the risk of pneumonia in patients with COPD. In this post-hoc meta-analysis, we investigate whether a 2% threshold can identify patients who differ in their risk of pneumonia, irrespective of inhaled corticosteroid treatment. From the GlaxoSmithKline trial registry, we selected randomised, double-blind, clinical trials of patients with COPD that had: inhaled corticosteroid arms (fluticasone propionate and salmeterol or fluticasone furoate and vilanterol); a control arm (not given inhaled fluticasone); and pre-randomisation measurements of blood eosinophil counts and were of at least 24 weeks in duration. With use of specified terms from the Medical Dictionary for Regulatory Activities we identified pneumonia adverse events in patient-level data. We calculated number of patients with pneumonia events, stratified by baseline blood eosinophil count (<2% vs ≥2% of blood leucocytes) and whether or not patients had received inhaled corticosteroids. We identified ten trials (conducted between 1998 and 2011), with eosinophil count data available for 10 861 patients with COPD. 4043 patients had baseline blood eosinophil counts of less than 2% and 6818 patients had baseline blood eosinophil counts of 2% or more. 149 (3·7%) patients with counts less than 2% had one or more pneumonia adverse events compared with 215 (3·2%) with counts of 2% or more (hazard ratio [HR] 1·31; 95% CI 1·06-1·62). In patients not treated with inhaled corticosteroids, 40 (3·8%) patients with less than 2% blood eosinophil counts had a pneumonia event

Individual dose adjustment of riociguat in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

PubMed

Hill, Nicholas S; Rahaghi, Franck F; Sood, Namita; Frey, Reiner; Ghofrani, Hossein-Ardeschir

2017-08-01

Riociguat is a soluble guanylate cyclase stimulator that has been approved for the treatment of pulmonary arterial hypertension and inoperable chronic thromboembolic pulmonary hypertension or persistent/recurrent pulmonary hypertension following pulmonary endarterectomy. Riociguat is administered using an 8-week individual dose-adjustment scheme whereby a patient initially receives riociguat 1.0 mg three times daily (tid), and the dose is then increased every 2 weeks in the absence of hypotension, indicated by systolic blood pressure measurements and symptoms, up to a maximum dose of 2.5 mg tid. The established riociguat dose-adjustment scheme allows the dose of riociguat to be individually optimized in terms of tolerability and efficacy. The majority of patients in the phase III clinical trials and their long-term extension phases achieved the maximum riociguat dose, whereas some patients remained on lower doses. There is evidence that these patients may experience benefits at riociguat doses lower than 2.5 mg tid, with improvement in exercise capacity being observed after only 2-4 weeks of treatment in the phase III studies and in the exploratory 1.5 mg-maximum patient group of PATENT-1. This review aims to provide an overview of the rationale behind the riociguat dose-adjustment scheme and examine its application to both clinical trials and real-life clinical practice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pulmonary Hypertension

MedlinePlus

... together all groups are called pulmonary hypertension.) Group 1 Pulmonary Arterial Hypertension Group 1 PAH includes: PAH ... information, go to "Types of Pulmonary Hypertension." ) Group 1 Pulmonary Arterial Hypertension Group 1 pulmonary arterial hypertension ( ...

Coagulopathy in patients with acute pulmonary embolism: a pilot study of whole blood coagulation and markers of endothelial damage.

PubMed

Lehnert, Per; Johansson, Pär I; Ostrowski, Sisse R; Møller, Christian H; Bang, Lia E; Olsen, Peter Skov; Carlsen, Jørn

2017-02-01

Whole blood coagulation and markers of endothelial damage were studied in patients with acute pulmonary embolism (PE), and evaluated in relation to PE severity. Twenty-five patients were enrolled prospectively each having viscoelastical analysis of whole blood done using thrombelastography (TEG) and Multiplate aggregometry. Fourteen of these patients were investigated for endothelial damage by ELISA measurements of Syndecan-1 (endothelial glycocalyx degradation), soluble endothelial Selectin (endothelial cell activation), soluble Thrombomodulin (endothelial cell injury) and Histone Complexed DNA fragments (endothelial cytotoxic histones). The mean values of TEG and Multiplate parameters were all within the reference levels, but a significant difference between patients with high and intermediate risk PE was observed for Ly30 (lytic activity) 1.5% [0-10] vs. 0.2% [0-2.2] p = .04, and ADP (platelet reactivity) 92 U [20-145] vs. 59 U [20-111] p = .03. A similar difference was indicated for functional fibrinogen 21 mm [17-29] vs. 18 mm [3-23] p = .05. Analysis of endothelial markers identified a significant difference in circulating levels between high and intermediate risk PE patients for Syndecan-1 118.6 ng/mL [76-133] vs. 36.3 ng/mL [11.8-102.9] p = .008. In conclusion, patients with acute PE had normal whole blood coagulation, but high risk PE patients had signs of increased activity of the haemostatic system and significantly increased level of endothelial glycocalyx degradation.

Pulmonary arterial remodeling induced by a Th2 immune response

PubMed Central

Daley, Eleen; Emson, Claire; Guignabert, Christophe; de Waal Malefyt, Rene; Louten, Jennifer; Kurup, Viswanath P.; Hogaboam, Cory; Taraseviciene-Stewart, Laimute; Voelkel, Norbert F.; Rabinovitch, Marlene; Grunig, Ekkehard; Grunig, Gabriele

2008-01-01

Pulmonary arterial remodeling characterized by increased vascular smooth muscle density is a common lesion seen in pulmonary arterial hypertension (PAH), a deadly condition. Clinical correlation studies have suggested an immune pathogenesis of pulmonary arterial remodeling, but experimental proof has been lacking. We show that immunization and prolonged intermittent challenge via the airways with either of two different soluble antigens induced severe muscularization in small- to medium-sized pulmonary arteries. Depletion of CD4+ T cells, antigen-specific T helper type 2 (Th2) response, or the pathogenic Th2 cytokine interleukin 13 significantly ameliorated pulmonary arterial muscularization. The severity of pulmonary arterial muscularization was associated with increased numbers of epithelial cells and macrophages that expressed a smooth muscle cell mitogen, resistin-like molecule α, but surprisingly, there was no correlation with pulmonary hypertension. Our data are the first to provide experimental proof that the adaptive immune response to a soluble antigen is sufficient to cause severe pulmonary arterial muscularization, and support the clinical observations in pediatric patients and in companion animals that muscularization represents one of several injurious events to the pulmonary artery that may collectively contribute to PAH. PMID:18227220

The evaluation of pulmonary hypertension using right ventricular myocardial isovolumic relaxation time.

PubMed

Dambrauskaite, Virginija; Delcroix, Marion; Claus, Piet; Herbots, Lieven; Palecek, Tomas; D'hooge, Jan; Bijnens, Bart; Rademakers, Frank; Sutherland, George R

2005-11-01

Right ventricular (RV) blood pool-derived isovolumic relaxation time (IVRT) correlates well with systolic pulmonary arterial pressure (PAP). However, because of complex parameter derivation, the method is rarely used. The aim of this study was to validate the measurement of myocardial velocity imaging-derived RV IVRT (IVRT') against invasively measured PAP. Transthoracic echocardiography with myocardial velocity imaging and right heart catheterization were performed in 33 patients with pulmonary hypertension. Blood pool IVRT and myocardial IVRTs for the tricuspid valve annulus ring, basal and apical RV free wall segments were measured and compared with data from 33 age- and sex-matched control subjects. Measured IVRTs were significantly longer in patients with pulmonary hypertension than in control subjects. The strongest correlation (R = 0.74, P < .0001) was found between systolic PAP and the heart rate-corrected IVRT' derived from the basal RV free wall segment. The basal segment IVRT' corrected for heart rate correlates well with the invasive PAP measurement and, therefore, can be used to predict systolic PAP. It can even be considered as an alternative to tricuspid regurgitation-derived PAP systolic when tricuspid regurgitation is nonrecordable. A proposed method to derive systolic PAP should be used while screening the patients at risk for pulmonary hypertension, monitoring the disease progression and the effect of treatment.

Noninvasive Doppler tissue measurement of pulmonary artery compliance in children with pulmonary hypertension.

PubMed

Dyer, Karrie; Lanning, Craig; Das, Bibhuti; Lee, Po-Feng; Ivy, D Dunbar; Valdes-Cruz, Lilliam; Shandas, Robin

2006-04-01

We have shown previously that input impedance of the pulmonary vasculature provides a comprehensive characterization of right ventricular afterload by including compliance. However, impedance-based compliance assessment requires invasive measurements. Here, we develop and validate a noninvasive method to measure pulmonary artery (PA) compliance using ultrasound color M-mode (CMM) Doppler tissue imaging (DTI). Dynamic compliance (C(dyn)) of the PA was obtained from CMM DTI and continuous wave Doppler measurement of the tricuspid regurgitant velocity. C(dyn) was calculated as: [(D(s) - D(d))/(D(d) x P(s))] x 10(4); where D(s) = systolic diameter, D(d) = diastolic diameter, and P(s) = systolic pressure. The method was validated both in vitro and in 13 patients in the catheterization laboratory, and then tested on 27 pediatric patients with pulmonary hypertension, with comparison with 10 age-matched control subjects. C(dyn) was also measured in an additional 13 patients undergoing reactivity studies. Instantaneous diameter measured using CMM DTI agreed well with intravascular ultrasound measurements in the in vitro models. Clinically, C(dyn) calculated by CMM DTI agreed with C(dyn) calculated using invasive techniques (23.4 +/- 16.8 vs 29.1 +/- 20.6%/100 mm Hg; P = not significant). Patients with pulmonary hypertension had significantly lower peak wall velocity values and lower C(dyn) values than control subjects (P < .01). C(dyn) values followed an exponentially decaying relationship with PA pressure, indicating the nonlinear stress-strain behavior of these arteries. Reactivity in C(dyn) agreed with reactivity measured using impedance techniques. The C(dyn) method provides a noninvasive means of assessing PA compliance and should be useful as an additional measure of vascular reactivity subsequent to pulmonary vascular resistance in patients with pulmonary hypertension.

Normal reference values for regional pulmonary peripheral airspace epithelial permeability. Influence of pneumonectomy and the smoking habit.

PubMed

Todisco, T; Dottorini, M; Rossi, F; Baldoncini, A; Palumbo, R

1989-01-01

Peripheral airspace epithelial permeability (PAEP) to diethylentriaminopentacetate (DTPA), an index of pulmonary integrity, was measured in 3 groups of subjects for different purposes: (1) to establish vertical regional reference values; (2) to determine the physiological role of acute doubling of total pulmonary blood flow; (3) to quantify the pulmonary epithelial damage in smokers and the possibility of lung protection by an agent stimulating surfactant production. This study broadens previous knowledge of PAEP. First of all, regional reference values are given for young normal nonsmoking subjects and the existence of a vertical gradient of PAEP is confirmed. Furthermore, this study shows that this gradient is independent of the vertical blood flow gradient, since an acute increase of total blood flow in pneumonectomized patients does not modify the regional distribution of PAEP. Finally, it is confirmed that the cigarette smoker's lung is more permeable than the controls and that probably a drug-stimulating surfactant production gives some protection against damage due to chronic smoking.

Dextromethorphan mediated bitter taste receptor activation in the pulmonary circuit causes vasoconstriction.

PubMed

Upadhyaya, Jasbir D; Singh, Nisha; Sikarwar, Anurag S; Chakraborty, Raja; Pydi, Sai P; Bhullar, Rajinder P; Dakshinamurti, Shyamala; Chelikani, Prashen

2014-01-01

Activation of bitter taste receptors (T2Rs) in human airway smooth muscle cells leads to muscle relaxation and bronchodilation. This finding led to our hypothesis that T2Rs are expressed in human pulmonary artery smooth muscle cells and might be involved in regulating the vascular tone. RT-PCR was performed to reveal the expression of T2Rs in human pulmonary artery smooth muscle cells. Of the 25 T2Rs, 21 were expressed in these cells. Functional characterization was done by calcium imaging after stimulating the cells with different bitter agonists. Increased calcium responses were observed with most of the agonists, the largest increase seen for dextromethorphan. Previously in site-directed mutational studies, we have characterized the response of T2R1 to dextromethorphan, therefore, T2R1 was selected for further analysis in this study. Knockdown with T2R1 specific shRNA decreased mRNA levels, protein levels and dextromethorphan-induced calcium responses in pulmonary artery smooth muscle cells by up to 50%. To analyze if T2Rs are involved in regulating the pulmonary vascular tone, ex vivo studies using pulmonary arterial and airway rings were pursued. Myographic studies using porcine pulmonary arterial and airway rings showed that stimulation with dextromethorphan led to contraction of the pulmonary arterial and relaxation of the airway rings. This study shows that dextromethorphan, acting through T2R1, causes vasoconstrictor responses in the pulmonary circuit and relaxation in the airways.

The Critical Role of Pulmonary Arterial Compliance in Pulmonary Hypertension

PubMed Central

Prins, Kurt W.; Pritzker, Marc R.; Scandurra, John; Volmers, Karl; Weir, E. Kenneth

2016-01-01

The normal pulmonary circulation is a low-pressure, high-compliance system. Pulmonary arterial compliance decreases in the presence of pulmonary hypertension because of increased extracellular matrix/collagen deposition in the pulmonary arteries. Loss of pulmonary arterial compliance has been consistently shown to be a predictor of increased mortality in patients with pulmonary hypertension, even more so than pulmonary vascular resistance in some studies. Decreased pulmonary arterial compliance causes premature reflection of waves from the distal pulmonary vasculature, leading to increased pulsatile right ventricular afterload and eventually right ventricular failure. Evidence suggests that decreased pulmonary arterial compliance is a cause rather than a consequence of distal small vessel proliferative vasculopathy. Pulmonary arterial compliance decreases early in the disease process even when pulmonary artery pressure and pulmonary vascular resistance are normal, potentially enabling early diagnosis of pulmonary vascular disease, especially in high-risk populations. With the recognition of the prognostic importance of pulmonary arterial compliance, its impact on right ventricular function, and its contributory role in the development and progression of distal small-vessel proliferative vasculopathy, pulmonary arterial compliance is an attractive target for the treatment of pulmonary hypertension. PMID:26848601

Pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis.

PubMed

Ortiz-Bautista, Carlos; Hernández-González, Ignacio; Escribano-Subías, Pilar

2017-03-22

Pulmonary veno-occlusive disease is a rare cause of pulmonary hypertension which is part, together with pulmonary capillary hemangiomatosis, of the special designation (subgroup 1') within pulmonary hypertension group 1 in the latest classification of the pulmonary hypertension World Symposium. Recent discovery that gene mutations in eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) are responsible for inherited forms of pulmonary veno-occlusive disease has changed the role of genetic testing, acquiring relevant importance in the diagnosis of these patients. Despite the advances in genetic, cellular and molecular basis knowledge in the last decade, pulmonary veno-occlusive disease remains as a rare aetiology of pulmonary hypertension without any effective medical treatment approved and poor outcomes. This document aims to review the advances occurred in the understanding of pulmonary veno-occlusive disease in the last years. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

TL1A/DR3 axis involvement in the inflammatory cytokine network during pulmonary sarcoidosis.

PubMed

Facco, M; Cabrelle, A; Calabrese, F; Teramo, A; Cinetto, F; Carraro, S; Martini, V; Calzetti, F; Tamassia, N; Cassatella, M A; Semenzato, G; Agostini, C

2015-01-01

TNF-like ligand 1A (TL1A), a recently recognized member of the TNF superfamily, and its death domain receptor 3 (DR3), firstly identified for their relevant role in T lymphocyte homeostasis, are now well-known mediators of several immune-inflammatory diseases, ranging from rheumatoid arthritis to inflammatory bowel diseases to psoriasis, whereas no data are available on their involvement in sarcoidosis, a multisystemic granulomatous disease where a deregulated T helper (Th)1/Th17 response takes place. In this study, by flow cytometry, real-time PCR, confocal microscopy and immunohistochemistry analyses, TL1A and DR3 were investigated in the pulmonary cells and the peripheral blood of 43 patients affected by sarcoidosis in different phases of the disease (29 patients with active sarcoidosis, 14 with the inactive form) and in 8 control subjects. Our results demonstrated a significant higher expression, both at protein and mRNA levels, of TL1A and DR3 in pulmonary T cells and alveolar macrophages of patients with active sarcoidosis as compared to patients with the inactive form of the disease and to controls. In patients with sarcoidosis TL1A was strongly more expressed in the lung than the blood, i.e., at the site of the involved organ. Additionally, zymography assays showed that TL1A is able to increase the production of matrix metalloproteinase 9 by sarcoid alveolar macrophages characterized, in patients with the active form of the disease, by reduced mRNA levels of the tissue inhibitor of metalloproteinase (TIMP)-1. These data suggest that TL1A/DR3 interactions are part of the extended and complex immune-inflammatory network that characterizes sarcoidosis during its active phase and may contribute to the pathogenesis and to the progression of the disease.

Ambulatory blood pressure profiles in familial dysautonomia.

PubMed

Goldberg, Lior; Bar-Aluma, Bat-El; Krauthammer, Alex; Efrati, Ori; Sharabi, Yehonatan

2018-02-12

Familial dysautonomia (FD) is a rare genetic disease that involves extreme blood pressure fluctuations secondary to afferent baroreflex failure. The diurnal blood pressure profile, including the average, variability, and day-night difference, may have implications for long-term end organ damage. The purpose of this study was to describe the circadian pattern of blood pressure in the FD population and relationships with renal and pulmonary function, use of medications, and overall disability. We analyzed 24-h ambulatory blood pressure monitoring recordings in 22 patients with FD. Information about medications, disease severity, renal function (estimated glomerular filtration, eGFR), pulmonary function (forced expiratory volume in 1 s, FEV1) and an index of blood pressure variability (standard deviation of systolic pressure) were analyzed. The mean (± SEM) 24-h blood pressure was 115 ± 5.6/72 ± 2.0 mmHg. The diurnal blood pressure variability was high (daytime systolic pressure standard deviation 22.4 ± 1.5 mmHg, nighttime 17.2 ± 1.6), with a high frequency of a non-dipping pattern (16 patients, 73%). eGFR, use of medications, FEV1, and disability scores were unrelated to the degree of blood pressure variability or to dipping status. This FD cohort had normal average 24-h blood pressure, fluctuating blood pressure, and a high frequency of non-dippers. Although there was evidence of renal dysfunction based on eGFR and proteinuria, the ABPM profile was unrelated to the measures of end organ dysfunction or to reported disability.

Evaluation of blood flow distribution asymmetry and vascular geometry in patients with Fontan circulation using 4-D flow MRI

PubMed Central

Jarvis, Kelly; Schnell, Susanne; Barker, Alex J.; Garcia, Julio; Lorenz, Ramona; Rose, Michael; Chowdhary, Varun; Carr, James; Robinson, Joshua D.; Rigsby, Cynthia K.; Markl, Michael

2016-01-01

Background Asymmetrical caval to pulmonary blood flow is suspected to cause complications in patients with Fontan circulation. The aim of this study was to test the feasibility of 4-D flow MRI for characterizing the relationship between 3-D blood flow distribution and vascular geometry. Objective We hypothesized that both flow distribution and geometry can be calculated with low interobserver variability and will detect a direct relationship between flow distribution and Fontan geometry. Materials and methods Four-dimensional flow MRI was acquired in 10 Fontan patients (age: 16±4 years [mean ± standard deviation; range 9–21 years]). The Fontan connection was isolated by 3-D segmentation to evaluate flow distribution from the inferior vena cava (IVC) and superior vena cava (SVC) to the left and right pulmonary arteries (LPA, RPA) and to characterize geometry (cross-sectional area, caval offset, vessel angle). Results Flow distribution results indicated SVC flow tended toward the RPA while IVC flow was more evenly distributed (SVC to RPA: 78%±28 [9–100], IVC to LPA: 54%±28 [4–98]). There was a significant relationship between pulmonary artery cross-sectional area and flow distribution (IVC to RPA: R2=0.50, P=0.02; SVC to LPA: R2=0.81, P=0.0004). Good agreement was found between observers and for flow distribution when compared to net flow values. Conclusion Four-dimensional (4-D) flow MRI was able to detect relationships between flow distribution and vessel geometry. Future studies are warranted to investigate the potential of patient specific hemodynamic analysis to improve diagnostic capability. PMID:27350377

Chemotherapy-induced pulmonary hypertension: role of alkylating agents.

PubMed

Ranchoux, Benoît; Günther, Sven; Quarck, Rozenn; Chaumais, Marie-Camille; Dorfmüller, Peter; Antigny, Fabrice; Dumas, Sébastien J; Raymond, Nicolas; Lau, Edmund; Savale, Laurent; Jaïs, Xavier; Sitbon, Olivier; Simonneau, Gérald; Stenmark, Kurt; Cohen-Kaminsky, Sylvia; Humbert, Marc; Montani, David; Perros, Frédéric

2015-02-01

Pulmonary veno-occlusive disease (PVOD) is an uncommon form of pulmonary hypertension (PH) characterized by progressive obstruction of small pulmonary veins and a dismal prognosis. Limited case series have reported a possible association between different chemotherapeutic agents and PVOD. We evaluated the relationship between chemotherapeutic agents and PVOD. Cases of chemotherapy-induced PVOD from the French PH network and literature were reviewed. Consequences of chemotherapy exposure on the pulmonary vasculature and hemodynamics were investigated in three different animal models (mouse, rat, and rabbit). Thirty-seven cases of chemotherapy-associated PVOD were identified in the French PH network and systematic literature analysis. Exposure to alkylating agents was observed in 83.8% of cases, mostly represented by cyclophosphamide (43.2%). In three different animal models, cyclophosphamide was able to induce PH on the basis of hemodynamic, morphological, and biological parameters. In these models, histopathological assessment confirmed significant pulmonary venous involvement highly suggestive of PVOD. Together, clinical data and animal models demonstrated a plausible cause-effect relationship between alkylating agents and PVOD. Clinicians should be aware of this uncommon, but severe, pulmonary vascular complication of alkylating agents. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Acute control of pulmonary regurgitation with a balloon "valve". An experimental investigation.

PubMed

Siwek, L G; Applebaum, R E; Jones, M; Clark, R E

1985-09-01

Operations for certain congenital cardiac lesions can produce pulmonary regurgitation. Pulmonary regurgitation contributes to right ventricular dysfunction, which may cause early postoperative morbidity and mortality. To ameliorate the problems of pulmonary regurgitation during the early postoperative period, we evaluated a method for its acute control. Complete pulmonary valvectomy was performed utilizing inflow occlusion in eight sheep. A catheter with a 15 ml spherical balloon was positioned in the pulmonary arterial trunk; its inflation and deflation were regulated by an intra-aortic balloon pump unit. Blood flow from the pulmonary arterial trunk and forward and regurgitant fraction were determined from electromagnetic flow transducer recordings. The regurgitant fraction with uncontrolled pulmonary regurgitation was 38% +/- 3% (forward flow = 42 +/- 5 ml/beat and regurgitant flow = 16 +/- 2 ml/beat). Inflation of the balloon during diastole was timed to completely eliminate pulmonary regurgitation. This balloon control of pulmonary regurgitation increased pulmonary arterial diastolic pressure from 12 +/- 1 to 17 +/- 1 mm Hg (p less than 0.0001) and decreased pulmonary arterial systolic pressure from 31 +/- 3 to 27 +/- 1 mm Hg (p = 0.06). Pulmonary arterial pulse pressure decreased from 19 +/- 3 to 9 +/- 1 mm Hg (p less than 0.003). Elimination of pulmonary regurgitation decreased right ventricular stroke volume (25 +/- 3 versus 42 +/- 5 ml/beat, p less than 0.0002) and resulted in a 46% reduction in right ventricular stroke work (5.0 +/- 0.6 versus 9.4 +/- 1.0 gm-m/beat, p less than 0.001) with no change in net forward pulmonary artery flow. Thus, acute pulmonary regurgitation can be controlled and this control improves overall hemodynamic status and decreases right ventricular work.

[Pulmonary oxalosis with necrotizing pulmonary aspergillosis].

PubMed

Khabir, Abdelmajid; Makni, Salwa; Ayadi, Lobna; Boudawara, Tahia; Frikha, Imed; Sahnoun, Youssef; Jlidi, Rachid

2002-04-01

Pulmonary oxalosis is a very rare pseudotumoral lesion; it is often secondary to an aspergillus infection. Oxalic acid (C(2)H(2)O(4)) is a mycotoxin released by Aspergillus niger and sometimes by several other fungi, including A flavus and A fumigatus. We report a case of a 69 year old man, with previous history of pulmonary tuberculosis, followed for recurrent hemoptysis. On the chest radiography, the right upper lobe lung showed a cavitary lesion with thick and irregular walls and a dense material that suggested a pulmonary aspergilloma. Microscopically, it was a pulmonary oxalosis associated with chronic necrotising pulmonary aspergillosis. Our aim is to discuss the epidemiological characteristics, the diagnosis and the histogenesis of this unusual lesion.

Pulmonary vasculature in COPD: The silent component.

PubMed

Blanco, Isabel; Piccari, Lucilla; Barberà, Joan Albert

2016-08-01

Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction that results from an inflammatory process affecting the airways and lung parenchyma. Despite major abnormalities taking place in bronchial and alveolar structures, changes in pulmonary vessels also represent an important component of the disease. Alterations in vessel structure are highly prevalent and abnormalities in their function impair gas exchange and may result in pulmonary hypertension (PH), an important complication of the disease associated with reduced survival and worse clinical course. The prevalence of PH is high in COPD, particularly in advanced stages, although it remains of mild to moderate severity in the majority of cases. Endothelial dysfunction, with imbalance between vasodilator/vasoconstrictive mediators, is a key determinant of changes taking place in pulmonary vasculature in COPD. Cigarette smoke products may perturb endothelial cells and play a critical role in initiating vascular changes. The concurrence of inflammation, hypoxia and emphysema further contributes to vascular damage and to the development of PH. The use of drugs that target endothelium-dependent signalling pathways, currently employed in pulmonary arterial hypertension, is discouraged in COPD due to the lack of efficacy observed in randomized clinical trials and because there is compelling evidence indicating that these drugs may worsen pulmonary gas exchange. The subgroup of patients with severe PH should be ideally managed in centres with expertise in both PH and chronic lung diseases because alterations of pulmonary vasculature might resemble those observed in pulmonary arterial hypertension. Because this condition entails poor prognosis, it warrants specialist treatment. © 2016 Asian Pacific Society of Respirology.

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.

Pulmonary Predictors of Incident Diabetes in Smokers

PubMed Central

Kinney, Gregory L.; Baker, Emma H.; Klein, Oana L.; Black-Shinn, Jennifer L.; Wan, Emily S.; Make, Barry; Regan, Elizabeth; Bowler, Russell P.; Lutz, Sharon M.; Young, Kendra A.; Duca, Lindsey M.; Washko, George R.; Silverman, Edwin K.; Crapo, James D.; Hokanson, John E.

2016-01-01

Background: Diabetes mellitus and its complications are a large and increasing burden for health care worldwide. Reduced pulmonary function has been observed in diabetes (both type 1 and type 2), and this reduction is thought to occur prior to diagnosis. Other measures of pulmonary health are associated with diabetes, including lower exercise tolerance, greater dyspnea, lower quality of life (as measured by the St. George’s Respiratory Questionaire [SGRQ]) and susceptibility to lung infection and these measures may also predate diabetes diagnosis. Methods: We examined 7080 participants in the COPD Genetic Epidemiology (COPDGene) study who did not report diabetes at their baseline visit and who provided health status updates during 4.2 years of longitudinal follow-up (LFU). We used Cox proportional hazards modeling, censoring participants at final LFU contact, reported mortality or report of incident diabetes to model predictors of diabetes. These models were constructed using known risk factors as well as proposed markers related to pulmonary health, forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, respiratory exacerbations (RE), 6-minute walk distance (6MWD), pulmonary associated quality of life (as measured by the SGRQ), corticosteroid use, chronic bronchitis and dyspnea. Results: Over 21,519 person years of follow-up, 392 of 7080 participants reported incident diabetes which was associated with expected predictors; increased body mass index (BMI), high blood pressure, high cholesterol and current smoking status. Age, gender and accumulated smoking exposure were not associated with incident diabetes. Additionally, preserved ratio with impaired spirometry (PRISm) pattern pulmonary function, reduced 6MWD and any report of serious pulmonary events were associated with incident diabetes. Conclusions: This cluster of pulmonary indicators may aid clinicians in identifying and treating patients with pre- or undiagnosed diabetes. PMID

Characterization of primary pulmonary adenosquamous carcinoma-associated pleural effusion.

PubMed

Stewart, Jennifer; Holloway, Andrew; Rasotto, Roberta; Bowlt, Kelly

2016-03-01

A 10-year-old, female spayed Shih Tzu was presented due to weight loss, increased respiratory effort and lethargy, determined to be secondary to a congenital para-esophageal diaphragmatic defect with partial herniation of the stomach and spleen. Four days following reduction surgery of the displaced abdominal organs thoracic effusion developed. Thoracic fluid evaluation revealed a cell-rich, protein-poor modified transudate with neutrophils, reactive mesothelial cells, and atypical epitheloid cells which occasionally appeared to be keratinizing, consistent with neoplastic exfoliation. Thoracic effusion recurred 2 days later, with similar characteristics as the initial sample. Computed tomography (CT) indicated consolidation and displacement of the right middle and accessory lung lobes. Exploratory thoracic surgery demonstrated a thickened, hyperemic right middle lung lobe, and thickened pericardial diaphragmatic ligament. Histologic evaluation of these tissues identified a primary pulmonary adenosquamous carcinoma with intravascular and pleural invasion. Based on these cytologic, histologic, and clinical findings, we conclude that primary pulmonary carcinomas may involve superficial thoracic structures and exfoliate into a thoracic effusion. © 2016 American Society for Veterinary Clinical Pathology.

Variations in respiratory excretion of carbon dioxide can be used to calculate pulmonary blood flow.

PubMed

Preiss, David A; Azami, Takafumi; Urman, Richard D

2015-02-01

A non-invasive means of measuring pulmonary blood flow (PBF) would have numerous benefits in medicine. Traditionally, respiratory-based methods require breathing maneuvers, partial rebreathing, or foreign gas mixing because exhaled CO2 volume on a per-breath basis does not accurately represent alveolar exchange of CO2. We hypothesized that if the dilutional effect of the functional residual capacity was accounted for, the relationship between the calculated volume of CO2 removed per breath and the alveolar partial pressure of CO2 would be reversely linear. A computer model was developed that uses variable tidal breathing to calculate CO2 removal per breath at the level of the alveoli. We iterated estimates for functional residual capacity to create the best linear fit of alveolar CO2 pressure and CO2 elimination for 10 minutes of breathing and incorporated the volume of CO2 elimination into the Fick equation to calculate PBF. The relationship between alveolar pressure of CO2 and CO2 elimination produced an R(2) = 0.83. The optimal functional residual capacity differed from the "actual" capacity by 0.25 L (8.3%). The repeatability coefficient leveled at 0.09 at 10 breaths and the difference between the PBF calculated by the model and the preset blood flow was 0.62 ± 0.53 L/minute. With variations in tidal breathing, a linear relationship exists between alveolar CO2 pressure and CO2 elimination. Existing technology may be used to calculate CO2 elimination during quiet breathing and might therefore be used to accurately calculate PBF in humans with healthy lungs.

Fulminant antenatal pulmonary oedema in a woman with hypertension and superimposed preeclampsia

PubMed Central

Kubota-Sjogren, Yukiko; Nelson-Piercy, Catherine

2015-01-01

An asymptomatic 40-year-old para 1 black African woman with pre-existing hypertension and a booking blood pressure of 120/80 mm Hg, was admitted with superimposed preeclampsia diagnosed because of worsening hypertension and significant proteinuria at 27+5 weeks gestation. Antenatally, her blood pressure was controlled with labetalol, and blood tests including serum creatinine were within normal limits for pregnancy. Three days later, the patient developed severe hypertension despite treatment, and reported sudden onset severe shortness of breath; oxygen saturations on air dropped to 93%. Auscultation revealed widespread crepitations leading to a working diagnosis of pulmonary oedema. Despite appropriate management, respiratory function continued to deteriorate and she required intubation, ventilation and emergency caesarean section under general anaesthesia. A live male infant was delivered floppy and was intubated and resuscitated. He awaits discharge home on oxygen. The mother's pulmonary oedema resolved postpartum. Echocardiogram showed left ventricular hypertrophy but normal left ventricular function and the patient's hypertension is being controlled on medication. PMID:26607194

Distribution of transvascular pathway sizes through the pulmonary microvascular barrier.

PubMed

McNamee, J E

1987-01-01

Mathematical models of solute and water exchange in the lung have been helpful in understanding factors governing the volume flow rate and composition of pulmonary lymph. As experimental data and models become more encompassing, parameter identification becomes more difficult. Pore sizes in these models should approach and eventually become equivalent to actual physiological pathway sizes as more complex and accurate models are tried. However, pore sizes and numbers vary from model to model as new pathway sizes are added. This apparent inconsistency of pore sizes can be explained if it is assumed that the pulmonary blood-lymph barrier is widely heteroporous, for example, being composed of a continuous distribution of pathway sizes. The sieving characteristics of the pulmonary barrier are reproduced by a log normal distribution of pathway sizes (log mean = -0.20, log s.d. = 1.05). A log normal distribution of pathways in the microvascular barrier is shown to follow from a rather general assumption about the nature of the pulmonary endothelial junction.

Falciparum malaria infection with invasive pulmonary aspergillosis in immunocompetent host – case report

NASA Astrophysics Data System (ADS)

Andriyani, Y.

2018-03-01

Invasive pulmonary aspergillosis is an extraordinary rare in the immunocompetent host. Falciparum malaria contributes to high morbidity and mortality of malaria infection cases in the world. The impairments of both humoral and cellular immunity could be the reason of invasive pulmonary aspergillosis in falciparum malaria infection. Forty-nine years old patient came with fever, jaundice, pain in the right abdomen, after visiting a remote area in Africa about one month before admission. Blood films and rapid test were positive for Plasmodium falciparum. After malaria therapy in five days, consciousness was altered into somnolence and intubated with respiratory deterioration. Invasive pulmonary aspergillosis after falciparum malaria infection is life-threatening. There should be awareness of physicians of invasive pulmonary aspergillosis in falciparum malaria infection.

THE EFFECT OF PULMONARY CONGESTION ON THE ON THE VENTILATION OF THE LUNGS

PubMed Central

Drinker, Cecil K.; Peabody, Francis W.; Blumgart, Herrmann L.

1922-01-01

1. A method is described for producing pulmonary congestion, together with what may be termed a differential spirometer method for studying lung ventilation. 2. The method utilized permits an approximately accurate prediction of degrees of pulmonary edema in the living animal, and suggests avenues of approach for the very difficult problems of pulmonary capillary pressure. 3. It is shown that intravascular blood can encroach markedly upon the pulmonary air space. Although the methods used in these animal experiments do not resemble vital capacity measurements in man, their result is so definite that their applicability to clinical conditions may be considered. 4. The similarity between the experiments described and certain conditions of cardiac decompensation, of which mitral stenosis is the best example, is pointed out. PMID:19868589

Pulmonary venous flow index as a predictor of pulmonary vascular resistance variability in congenital heart disease with increased pulmonary flow: a comparative study before and after oxygen inhalation.

PubMed

Rivera, Ivan Romero; Mendonça, Maria Alayde; Andrade, José Lázaro; Moises, Valdir; Campos, Orlando; Silva, Célia Camelo; Carvalho, Antonio Carlos

2013-09-01

There is no definitive and reliable echocardiographic method for estimating the pulmonary vascular resistance (PVR) to differentiate persistent vascular disease from dynamic pulmonary hypertension. The aim of this study was to analyze the relationship between the pulmonary venous blood flow velocity-time integral (VTIpv) and PVR. Eighteen patients (10 females; 4 months to 22 years of age) with congenital heart disease and left to right shunt were studied. They underwent complete cardiac catheterization, including measurements of the PVR and Qp:Qs ratio, before and after 100% oxygen inhalation. Simultaneous left inferior pulmonary venous flow VTIpv was obtained by Doppler echocardiography. The PVR decreased significantly from 5.0 ± 2.6 W to 2.8 ± 2.2 W (P = 0.0001) with a significant increase in the Qp:Qs ratio, from 3.2 ± 1.4 to 4.9 ± 2.4 (P = 0.0008), and the VTIpv increased significantly from 22.6 ± 4.7 cm to 28.1 ± 6.2 cm (P = 0.0002) after 100% oxygen inhalation. VTIpv correlated well with the PVR and Qp:Qs ratio (r = -0.74 and 0.72, respectively). Diagnostic indexes indicated a sensitivity of 86%, specificity of 75%, accuracy of 83%, a positive predictive value of 92% and a negative predictive value of 60%. The VTIpv correlated well with the PVR. The measurement of this index before and after oxygen inhalation may become a useful noninvasive test for differentiating persistent vascular disease from dynamic and flow-related pulmonary hypertension. © 2013, Wiley Periodicals, Inc.

Iloprost ameliorates post-ischemic lung reperfusion injury and maintains an appropriate pulmonary ET-1 balance.

PubMed

Kawashima, Masahiro; Nakamura, Takayuki; Schneider, Sven; Vollmar, Brigitte; Lausberg, Henning F; Bauer, Michael; Menger, Michael D; Schäfers, Hans-Joachim

2003-07-01

Ischemia-reperfusion (I/R) injury of the lung involves increased pulmonary vascular resistance. Prostaglandins are thought to have a beneficial effect in lung transplantation, but their mechanism in I/R injury is unknown. We investigated whether iloprost, a stable prostacyclin analogue, prevents I/R-associated pulmonary vascular dysfunction and whether it affects endothelin-1 (ET-1) balance. In an isolated blood-perfusion model, we subjected lungs of Lewis rats to 45 minutes of ischemia at 37 degrees C and randomly allocated the lungs to 3 groups (n = 6 each): iloprost (33.3 nmol/liter) added to the perfusate before ischemia and reperfusion (ILO+IR), iloprost (33.3 nmol/liter) given only before reperfusion (ILO+R), and controls without iloprost treatment (ILO-). Reperfusion induced marked pulmonary edema in non-treated controls (ILO-), which was attenuated in ILO+R lungs and completely prevented in ILO+IR lungs. At 60 minutes reperfusion, arterial oxygen tension was significantly greater in both ILO+R and ILO+IR lungs compared with ILO- controls. Mean pulmonary artery pressure and pulmonary vascular resistance were slightly decreased in the ILO+R and significantly decreased in the ILO+IR group compared with the ILO- controls. Plasma levels of big ET-1, measured in both afferent and efferent blood, showed that I/R results in increased pulmonary venous levels of big ET-1. Interestingly, the increased venoarterial ET-1 gradient in ILO- lungs decreased significantly in the ILO+IR group. We demonstrated in an isolated lung perfusion model that iloprost ameliorates post-ischemic lung reperfusion injury and maintains an appropriate pulmonary ET-1 balance.

Impact of Pulmonary Artery Pressure on Exercise Function in Severe COPD

PubMed Central

Sims, Michael W.; Margolis, David J.; Localio, A. Russell; Panettieri, Reynold A.; Kawut, Steven M.; Christie, Jason D.

2009-01-01

Background: Although pulmonary hypertension commonly complicates COPD, the functional consequences of increased pulmonary artery pressures in patients with this condition remain poorly defined. Methods: We conducted a cross-sectional analysis of a cohort of 362 patients with severe COPD who were evaluated for lung transplantation. Patients with pulmonary hemodynamics measured by cardiac catheterization and available 6-min walk test results were included. The association of mean pulmonary artery pressure (mPAP) with pulmonary function, echocardiographic variables, and 6-min walk distance was assessed. Results: The prevalence of pulmonary hypertension (mPAP, > 25 mm Hg; pulmonary artery occlusion pressure [PAOP], < 16 mm Hg) was 23% (95% confidence interval, 19 to 27%). In bivariate analysis, higher mPAP was associated with lower FVC and FEV1, higher Pco2 and lower Po2 in arterial blood, and more right heart dysfunction. Multivariate analysis demonstrated that higher mPAP was associated with shorter distance walked in 6 min, even after adjustment for age, gender, race, height, weight, FEV1, and PAOP (−11 m for every 5 mm Hg rise in mPAP; 95% confidence interval, −21 to −0.7; p = 0.04). Conclusions: Higher pulmonary artery pressures are associated with reduced exercise function in patients with severe COPD, even after controlling for demographics, anthropomorphics, severity of airflow obstruction, and PAOP. Whether treatments aimed at lowering pulmonary artery pressures may improve clinical outcomes in COPD, however, remains unknown. PMID:19318664

Pulmonary artery enlargement and cystic fibrosis pulmonary exacerbations: a cohort study

PubMed Central

Wells, J. Michael; Farris, Roopan F.; Gosdin, Taylor A.; Dransfield, Mark T.; Wood, Michelle E.; Bell, Scott C.; Rowe, Steven M.

2017-01-01

, positive Pseudomonas status, and FEV1/FVC [HR 1.14 (95%CI 0.80–1.62), P=0.82]). Interpretation PA enlargement is prevalent in adult CF patients and is associated with acute pulmonary exacerbation risk in two well-characterized cohorts. PA:A may be a predictive marker in CF. PMID:27298019

Pulmonary capillary haemangiomatosis: a rare cause of pulmonary hypertension.

PubMed

Babu, K Anand; Supraja, K; Singh, Raj B

2014-01-01

Pulmonary capillary haemangiomatosis (PCH) is a rare disorder of unknown aetiology, characterised by proliferating capillaries that invade the pulmonary interstitium, alveolar septae and the pulmonary vasculature. It is often mis-diagnosed as primary pulmonary hypertension and pulmonary veno-occlusive disease. Pulmonary capillary haemangiomatosis is a locally aggressive benign vascular neoplasm of the lung. We report the case of a 19-year-old female who was referred to us in the early post-partum period with severe pulmonary artery hypertension, which was diagnosed as PCH by open lung biopsy.

Framework for 3D histologic reconstruction and fusion with in vivo MRI: Preliminary results of characterizing pulmonary inflammation in a mouse model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rusu, Mirabela, E-mail: mirabela.rusu@gmail.com; Wang, Haibo; Madabhushi, Anant

Purpose: Pulmonary inflammation is associated with a variety of diseases. Assessing pulmonary inflammation on in vivo imaging may facilitate the early detection and treatment of lung diseases. Although routinely used in thoracic imaging, computed tomography has thus far not been compellingly shown to characterize inflammation in vivo. Alternatively, magnetic resonance imaging (MRI) is a nonionizing radiation technique to better visualize and characterize pulmonary tissue. Prior to routine adoption of MRI for early characterization of inflammation in humans, a rigorous and quantitative characterization of the utility of MRI to identify inflammation is required. Such characterization may be achieved by considering exmore » vivo histology as the ground truth, since it enables the definitive spatial assessment of inflammation. In this study, the authors introduce a novel framework to integrate 2D histology, ex vivo and in vivo imaging to enable the mapping of the extent of disease from ex vivo histology onto in vivo imaging, with the goal of facilitating computerized feature analysis and interrogation of disease appearance on in vivo imaging. The authors’ framework was evaluated in a preclinical preliminary study aimed to identify computer extracted features on in vivo MRI associated with chronic pulmonary inflammation. Methods: The authors’ image analytics framework first involves reconstructing the histologic volume in 3D from individual histology slices. Second, the authors map the disease ground truth onto in vivo MRI via coregistration with 3D histology using the ex vivo lung MRI as a conduit. Finally, computerized feature analysis of the disease extent is performed to identify candidate in vivo imaging signatures of disease presence and extent. Results: The authors evaluated the framework by assessing the quality of the 3D histology reconstruction and the histology—MRI fusion, in the context of an initial use case involving characterization of chronic

Framework for 3D histologic reconstruction and fusion with in vivo MRI: Preliminary results of characterizing pulmonary inflammation in a mouse model.

PubMed

Rusu, Mirabela; Golden, Thea; Wang, Haibo; Gow, Andrew; Madabhushi, Anant

2015-08-01

Pulmonary inflammation is associated with a variety of diseases. Assessing pulmonary inflammation on in vivo imaging may facilitate the early detection and treatment of lung diseases. Although routinely used in thoracic imaging, computed tomography has thus far not been compellingly shown to characterize inflammation in vivo. Alternatively, magnetic resonance imaging (MRI) is a nonionizing radiation technique to better visualize and characterize pulmonary tissue. Prior to routine adoption of MRI for early characterization of inflammation in humans, a rigorous and quantitative characterization of the utility of MRI to identify inflammation is required. Such characterization may be achieved by considering ex vivo histology as the ground truth, since it enables the definitive spatial assessment of inflammation. In this study, the authors introduce a novel framework to integrate 2D histology, ex vivo and in vivo imaging to enable the mapping of the extent of disease from ex vivo histology onto in vivo imaging, with the goal of facilitating computerized feature analysis and interrogation of disease appearance on in vivo imaging. The authors' framework was evaluated in a preclinical preliminary study aimed to identify computer extracted features on in vivo MRI associated with chronic pulmonary inflammation. The authors' image analytics framework first involves reconstructing the histologic volume in 3D from individual histology slices. Second, the authors map the disease ground truth onto in vivo MRI via coregistration with 3D histology using the ex vivo lung MRI as a conduit. Finally, computerized feature analysis of the disease extent is performed to identify candidate in vivo imaging signatures of disease presence and extent. The authors evaluated the framework by assessing the quality of the 3D histology reconstruction and the histology-MRI fusion, in the context of an initial use case involving characterization of chronic inflammation in a mouse model. The authors

An Earth-based Model of Microgravity Pulmonary Physiology

NASA Technical Reports Server (NTRS)

Hirschl, Ronald B.; Bull, Joseph L.; Grotberg, James B.

2004-01-01

There are currently only two practical methods of achieving microgravity for experimentation: parabolic flight in an aircraft or space flight, both of which have limitations. As a result, there are many important aspects of pulmonary physiology that have not been investigated in microgravity. We propose to develop an earth-based animal model of microgravity by using liquid ventilation, which will allow us to fill the lungs with perfluorocarbon, and submersing the animal in water such that the density of the lungs is the same as the surrounding environment. By so doing, we will eliminate the effects of gravity on respiration. We will first validate the model by comparing measures of pulmonary mechanics, to previous space flight and parabolic flight measurements. After validating the model, we will investigate the impact of microgravity on aspects of lung physiology that have not been previously measured. These will include pulmonary blood flow distribution, ventillation distribution, pulmonary capillary wedge pressure, ventilation-perfusion matching and pleural pressures and flows. We expect that this earth-based model of microgravity will enhance our knowledge and understanding of lung physiology in space which will increase in importance as space flights increase in time and distance.

Engineered cell and tissue models of pulmonary fibrosis.

PubMed

Sundarakrishnan, Aswin; Chen, Ying; Black, Lauren D; Aldridge, Bree B; Kaplan, David L

2018-04-01

Pulmonary fibrosis includes several lung disorders characterized by scar formation and Idiopathic Pulmonary Fibrosis (IPF) is a particularly severe form of pulmonary fibrosis of unknown etiology with a mean life expectancy of 3years' post-diagnosis. Treatments for IPF are limited to two FDA approved drugs, pirfenidone and nintedanib. Most lead candidate drugs that are identified in pre-clinical animal studies fail in human clinical trials. Thus, there is a need for advanced humanized in vitro models of the lung to improve candidate treatments prior to moving to human clinical trials. The development of 3D tissue models has created systems capable of emulating human lung structure, function, and cell and matrix interactions. The specific models accomplish these features and preliminary studies conducted using some of these systems have shown potential for in vitro anti-fibrotic drug testing. Further characterization and improvements will enable these tissue models to extend their utility for in vitro drug testing, to help identify signaling pathways and mechanisms for new drug targets, and potentially reduce animal models as standard pre-clinical models of study. In the current review, we contrast different in vitro models based on increasing dimensionality (2D, 2.5D and 3D), with added focus on contemporary 3D pulmonary models of fibrosis. Copyright © 2017. Published by Elsevier B.V.

Measurements of pulmonary vascular permeability with PET and gallium-68 transferrin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mintun, M.A.; Dennis, D.R.; Welch, M.J.

1987-11-01

We quantified pulmonary vascular permeability with positron emission tomography (PET) and gallium-68-(/sup 68/Ga) labeled transferrin. Six dogs with oleic acid-induced lung injury confined to the left lower lobe, two normal human volunteers, and two patients with the adult respiratory distress syndrome (ARDS) were evaluated. Lung tissue-activity measurements were obtained from sequential 1-5 min PET scans collected over 60 min, after in vivo labeling of transferrin through intravenous administration of (/sup 68/Ga)citrate. Blood-activity measurements were measured from simultaneously obtained peripheral blood samples. A forward rate constant describing the movement of transferrin from pulmonary vascular to extravascular compartments, the pulmonary transcapillary escapemore » rate (PTCER), was then calculated from these data using a two-compartment model. In dogs, PTCER was 49 +/- 18 in normal lung tissue and 485 +/- 114 10(-4) min-1 in injured lung. A repeat study in these dogs 4 hr later showed no significant change. Values in the human subjects showed similarly marked differences between normal and abnormal lung tissue. We conclude that PET will be a useful method of evaluating vascular permeability changes after acute lung injury.« less

The cancer theory of pulmonary arterial hypertension

PubMed Central

Boucherat, Olivier; Vitry, Geraldine; Trinh, Isabelle; Paulin, Roxane; Provencher, Steeve; Bonnet, Sebastien

2017-01-01

Pulmonary arterial hypertension (PAH) remains a mysterious killer that, like cancer, is characterized by tremendous complexity. PAH development occurs under sustained and persistent environmental stress, such as inflammation, shear stress, pseudo-hypoxia, and more. After inducing an initial death of the endothelial cells, these environmental stresses contribute with time to the development of hyper-proliferative and apoptotic resistant clone of cells including pulmonary artery smooth muscle cells, fibroblasts, and even pulmonary artery endothelial cells allowing vascular remodeling and PAH development. Molecularly, these cells exhibit many features common to cancer cells offering the opportunity to exploit therapeutic strategies used in cancer to treat PAH. In this review, we outline the signaling pathways and mechanisms described in cancer that drive PAH cells’ survival and proliferation and discuss the therapeutic potential of antineoplastic drugs in PAH. PMID:28597757

Pulmonary decompression sickness at altitude: early symptoms and circulating gas emboli

NASA Technical Reports Server (NTRS)

Balldin, Ulf I.; Pilmanis, Andrew A.; Webb, James T.

2002-01-01

INTRODUCTION: Pulmonary altitude decompression sickness (DCS) is a rare condition. 'Chokes' which are characterized by the triad of substernal pain, cough, and dyspnea, are considered to be associated with severe accumulation of gas bubbles in the pulmonary capillaries and may rapidly develop into a life-threatening medical emergency. This study was aimed at characterizing early symptomatology and the appearance of venous gas emboli (VGE). METHODS: Symptoms of simulated-altitude DCS and VGE (with echo-imaging ultrasound) were analyzed in 468 subjects who participated in 22 high altitude hypobaric chamber research protocols from 1983 to 2001 at Brooks Air Force Base, TX. RESULTS: Of 2525 subject-exposures to simulated altitude, 1030 (41%) had symptoms of DCS. Only 29 of those included DCS-related pulmonary symptoms. Of these, only 3 subjects had all three pulmonary symptoms of chokes; 9 subjects had two of the pulmonary symptoms; and 17 subjects had only one. Of the 29 subject-exposures with pulmonary symptoms, 27 had VGE and 21 had severe VGE. The mean onset times of VGE and symptoms in the 29 subject-exposures were 42 +/- 30 min and 109 +/- 61 min, respectively. In 15 subjects, the symptoms disappeared during recompression to ground level followed by 2 h of oxygen breathing. In the remaining 14 cases, the symptoms disappeared with immediate hyperbaric oxygen treatment. CONCLUSIONS: Pulmonary altitude DCS or chokes is confirmed to be a rare condition. Our data showed that when diagnosed early, recompression to ground level pressure and/or hyperbaric oxygen treatment was 100% successful in resolving the symptoms.

Diagnosis and management of solitary pulmonary nodules.

PubMed

Jeong, Yeon Joo; Lee, Kyung Soo; Kwon, O Jung

2008-12-01

The advent of computed tomography (CT) screening with or without the help of computer-aided detection systems has increased the detection rate of solitary pulmonary nodules (SPNs), including that of early peripheral lung cancer. Helical dynamic (HD)CT, providing the information on morphologic and hemodynamic characteristics with high specificity and reasonably high accuracy, can be used for the initial assessment of SPNs. (18)F-fluorodeoxyglucose PET/CT is more sensitive at detecting malignancy than HDCT. Therefore, PET/CT may be selectively performed to characterize SPNs when HDCT gives an inconclusive diagnosis. Serial volume measurements are currently the most reliable methods for the tissue characterization of subcentimeter nodules. When malignant nodule is highly suspected for subcentimeter nodules, video-assisted thoracoscopic surgery nodule removal after nodule localization using the pulmonary nodule-marker system may be performed for diagnosis and treatment.

Effects of perfluorohexane vapor on relative blood flow distribution in an animal model of surfactant-depleted lung injury

NASA Technical Reports Server (NTRS)

Hubler, Matthias; Souders, Jennifer E.; Shade, Erin D.; Polissar, Nayak L.; Bleyl, Jorg U.; Hlastala, Michael P.

2002-01-01

OBJECTIVE: To test the hypothesis that treatment with vaporized perfluorocarbon affects the relative pulmonary blood flow distribution in an animal model of surfactant-depleted acute lung injury. DESIGN: Prospective, randomized, controlled trial. SETTING: A university research laboratory. SUBJECTS: Fourteen New Zealand White rabbits (weighing 3.0-4.5 kg). INTERVENTIONS: The animals were ventilated with an FIO(2) of 1.0 before induction of acute lung injury. Acute lung injury was induced by repeated saline lung lavages. Eight rabbits were randomized to 60 mins of treatment with an inspiratory perfluorohexane vapor concentration of 0.2 in oxygen. To compensate for the reduced FIO(2) during perfluorohexane treatment, FIO(2) was reduced to 0.8 in control animals. Change in relative pulmonary blood flow distribution was assessed by using fluorescent-labeled microspheres. MEASUREMENTS AND MAIN RESULTS: Microsphere data showed a redistribution of relative pulmonary blood flow attributable to depletion of surfactant. Relative pulmonary blood flow shifted from areas that were initially high-flow to areas that were initially low-flow. During the study period, relative pulmonary blood flow of high-flow areas decreased further in the control group, whereas it increased in the treatment group. This difference was statistically significant between the groups (p =.02) as well as in the treatment group compared with the initial injury (p =.03). Shunt increased in both groups over time (control group, 30% +/- 10% to 63% +/- 20%; treatment group, 37% +/- 20% to 49% +/- 23%), but the changes compared with injury were significantly less in the treatment group (p =.03). CONCLUSION: Short treatment with perfluorohexane vapor partially reversed the shift of relative pulmonary blood flow from high-flow to low-flow areas attributable to surfactant depletion.

The dose-response relationship for hypoxic pulmonary vasoconstriction.

PubMed

Marshall, B E; Clarke, W R; Costarino, A T; Chen, L; Miller, F; Marshall, C

1994-05-01

In 12 pentobarbital anesthetized dogs the lungs were independently ventilated with a double piston ventilator. The right lung was ventilated throughout with 100% oxygen. Blood was drawn from the right atrium and pumped through a bubble oxygenator to a cannula in the ligated left main pulmonary artery. The pressures in the left main pulmonary artery and the left atrium were recorded during constant flow while the oxygen tension in the left lung alveolar gas and the perfusate were varied either to match each other (Protocol 1) or differ (Protocol 2) over the range from "zero" to "100%" oxygen. From the combined data a three dimensional response surface for hypoxic pulmonary vasoconstriction was derived. The maximum increase of pulmonary vascular resistance (r%PVRmax) was defined at a stimulus oxygen tension (PSO2) of 10 mmHg amounting to a 3.15 +/- (0.18)-fold increase of the vascular resistance on "100%" oxygen. The stimulus oxygen tension was shown to be PSO2 = PVO2(0.41) x PAO2(0.59) and the dose-response sigmoid for hypoxic pulmonary vasoconstriction in canine lungs was derived as r%PVRmax = 100 (PSO2(-2.616))/(6.683 x 10(-5) + PSO2(-2.616)) These results appear to reconcile observations from a number of laboratories and to be of quite general application.

Systemic rapamycin to prevent in-stent stenosis in peripheral pulmonary arterial disease: early clinical experience.

PubMed

Hallbergson, Anna; Esch, Jesse J; Tran, Trang X; Lock, James E; Marshall, Audrey C

2016-10-01

We have taken a novel approach using oral rapamycin - sirolimus - as a medical adjunct to percutaneous therapy in patients with in-stent stenosis and high risk of right ventricular failure. Peripheral pulmonary artery stenosis can result in right ventricular hypertension, dysfunction, and death. Percutaneous pulmonary artery angioplasty and stent placement acutely relieve obstructions, but patients frequently require re-interventions due to re-stenosis. In patients with tetralogy of Fallot or arteriopathy, the problem of in-stent stenosis contributes to the rapidly recurrent disease. Rapamycin was administered to 10 patients (1.5-18 years) with peripheral pulmonary stenosis and in-stent stenosis and either right ventricular hypertension, pulmonary blood flow maldistribution, or segmental pulmonary hypertension. Treatment was initiated around the time of catheterisation and continued for 1-3 months. Potential side-effects were monitored by clinical review and blood tests. Target serum rapamycin level (6-10 ng/ml) was accomplished in all patients; eight of the nine patients who returned for clinically indicated catheterisations demonstrated reduction in in-stent stenosis, and eight of the 10 patients experienced no significant side-effects. Among all, one patient developed diarrhoea requiring drug discontinuation, and one patient experienced gastrointestinal bleeding while on therapy that was likely due to an indwelling feeding tube and this patient tolerated rapamycin well following tube removal. Our initial clinical experience supports that patients with peripheral pulmonary artery stenosis can be safely treated with rapamycin. Systemic rapamycin may provide a novel medical approach to reduce in-stent stenosis.

Interstitial pneumonia and pulmonary hypertension associated with suspected ehrlichiosis in a dog.

PubMed

Toom, Marjolein Lisette den; Dobak, Tetyda Paulina; Broens, Els Marion; Valtolina, Chiara

2016-07-07

In dogs with canine monocytic ehrlichiosis (CME), respiratory signs are uncommon and clinical and radiographic signs of interstitial pneumonia are poorly described. However, in human monocytic ehrlichiosis, respiratory signs are common and signs of interstitial pneumonia are well known. Pulmonary hypertension (PH) is classified based on the underlying disease and its treatment is aimed at reducing the clinical signs and, if possible, addressing the primary disease process. PH is often irreversible, but can be reversible if it is secondary to a treatable underlying etiology. CME is currently not generally recognized as one of the possible diseases leading to interstitial pneumonia and secondary PH in dogs. Only one case of PH associated with CME has been reported worldwide. A seven-year-old, male intact, mixed breed dog was presented with 2 weeks history of lethargy and dyspnea. The dog previously lived in the Cape Verdean islands. Physical examination showed signs of right-sided congestive heart failure and poor peripheral perfusion. Thoracic radiography showed moderate right-sided cardiomegaly with dilation of the main pulmonary artery and a mild diffuse interstitial lung pattern with peribronchial cuffing. Echocardiography showed severe pulmonary hypertension with an estimated pressure gradient of 136 mm Hg. On arterial blood gas analysis, severe hypoxemia was found and complete blood count revealed moderate regenerative anemia and severe thrombocytopenia. A severe gamma hyperglobulinemia was also documented. Serology for Ehrlichia canis was highly positive. Treatment with oxygen supplementation, a typed packed red blood cell transfusion and medical therapy with doxycycline, pimobendan and sildenafil was initiated and the dog improved clinically. Approximately 2 weeks later, there was complete resolution of all clinical signs and marked improvement of the PH. This report illustrates that CME might be associated with significant pulmonary disease and should be

[Preparation of panax notoginseng saponins-tanshinone H(A) composite method for pulmonary delivery with spray-drying method and its characterization].

PubMed

Wang, Hua-Mei; Fu, Ting-Ming; Guo, Li-Wei

2013-02-01

To prepare panax notoginseng saponins-tanshinone II(A) composite particles for pulmonary delivery, in order to explore a dry powder particle preparation method ensuring synchronized arrival of multiple components of traditional Chinese medicine compounds at absorption sites. Panax notoginseng saponins-tanshinone II(A) composite particles were prepared with spray-drying method, and characterized by scanning electron microscopy (SEM), confocal laser scanning microscope (CLSM), X-ray diffraction (XRD), infrared analysis (IR), dry laser particle size analysis, high performance liquid chromatography (HPLC) and the aerodynamic behavior was evaluated by a Next Generation Impactor (NGI). The dry powder particles produced had narrow particle size distribution range and good aerodynamic behavior, and could realize synchronized administration of multiple components. The spray-drying method is used to combine traditional Chinese medicine components with different physical and chemical properties in the same particle, and product into traditional Chinese medicine compound particles in line with the requirements for pulmonary delivery.

Pulmonary endarterectomy outputs in chronic thromboembolic pulmonary hypertension.

PubMed

López Gude, María Jesús; Pérez de la Sota, Enrique; Pérez Vela, Jose Luís; Centeno Rodríguez, Jorge; Muñoz Guijosa, Christian; Velázquez, María Teresa; Alonso Chaterina, Sergio; Hernández González, Ignacio; Escribano Subías, Pilar; Cortina Romero, José María

2017-07-07

Pulmonary thromboendarterectomy surgery is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension; extremely high pulmonary vascular resistance constitutes a risk factor for hospital mortality. The objective of this study was to analyze the immediate and long-term results of the surgical treatment of chronic thromboembolic pulmonary hypertension in patients with very severe pulmonary hypertension. Since February 1996, we performed 160 pulmonary thromboendarterectomies. We divided the patient population in 2 groups: group 1, which included 40 patients with pulmonary vascular resistance≥1090dyn/sec/cm -5 , and group 2, which included the remaining 120 patients. Hospital mortality (15 vs. 2.5%), reperfusion pulmonary edema (33 vs. 14%) and heart failure (23 vs. 3.3%) were all higher in group 1; however, after one year of follow-up, there were no significant differences in the clinical, hemodynamic and echocardiographic conditions of both groups. Survival rate after 5 years was 77% in group 1 and 92% in group 2 (P=.033). After the learning curve including the 46 first patients, there was no difference in hospital mortality (3.8 vs. 2.3%) or survival rate after 5 years (96.2% in group 1 and 96.2% in group 2). Pulmonary thromboendarterectomy is linked to significantly higher morbidity and mortality rates in patients with severe chronic thromboembolic pulmonary hypertension. Nevertheless, these patients benefit the same from the procedure in the mid-/long-term. In our experience, after the learning curve, this surgery is safe in severe pulmonary hypertension and no level of pulmonary vascular resistance should be an absolute counter-indication for this surgery. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

A microengineered model of RBC transfusion-induced pulmonary vascular injury.

PubMed

Seo, Jeongyun; Conegliano, David; Farrell, Megan; Cho, Minseon; Ding, Xueting; Seykora, Thomas; Qing, Danielle; Mangalmurti, Nilam S; Huh, Dongeun

2017-06-13

Red blood cell (RBC) transfusion poses significant risks to critically ill patients by increasing their susceptibility to acute respiratory distress syndrome. While the underlying mechanisms of this life-threatening syndrome remain elusive, studies suggest that RBC-induced microvascular injury in the distal lung plays a central role in the development of lung injury following blood transfusion. Here we present a novel microengineering strategy to model and investigate this key disease process. Specifically, we created a microdevice for culturing primary human lung endothelial cells under physiological flow conditions to recapitulate the morphology and hemodynamic environment of the pulmonary microvascular endothelium in vivo. Perfusion of the microengineered vessel with human RBCs resulted in abnormal cytoskeletal rearrangement and release of intracellular molecules associated with regulated necrotic cell death, replicating the characteristics of acute endothelial injury in transfused lungs in vivo. Our data also revealed the significant effect of hemodynamic shear stress on RBC-induced microvascular injury. Furthermore, we integrated the microfluidic endothelium with a computer-controlled mechanical stretching system to show that breathing-induced physiological deformation of the pulmonary microvasculature may exacerbate vascular injury during RBC transfusion. Our biomimetic microsystem provides an enabling platform to mechanistically study transfusion-associated pulmonary vascular complications in susceptible patient populations.

The long-term effects of arteriovenous fistula creation on the development of pulmonary hypertension in hemodialysis patients.

PubMed

Unal, Aydin; Tasdemir, Kutay; Oymak, Sema; Duran, Mustafa; Kocyigit, Ismail; Oguz, Fatih; Tokgoz, Bulent; Sipahioglu, Murat Hayri; Utas, Cengiz; Oymak, Oktay

2010-10-01

The aim of this prospective study was to evaluate long-term effects of arteriovenous fistula (AVF) on the development of pulmonary arterial hypertension (PAH) and the relationship between blood flow rate of AVF and pulmonary artery pressure (PAP) in the patients with end-stage renal disease (ESRD). This prospective study was performed in 20 patients with ESRD. Before an AVF was surgically created for hemodialysis, the patients were evaluated by echocardiography. Then, an AVF was surgically created in all patients. After mean 23.50 ± 2.25 months, the second evaluation was performed by echocardiography. Also, the blood flow rate of AVF was measured at the second echocardiographic evaluation. Pulmonary arterial hypertension was defined as a systolic PAP above 35 mmHg at rest. Mean age of 20 patients with ESRD was 55.05 ± 13.64 years; 11 of 20 patients were males. Pulmonary arterial hypertension was detected in 6 (30%) patients before AVF creation and in 4 (20%) patients after AVF creation. Systolic PAP value was meaningfully lower after AVF creation than before AVF creation (29.95 ± 10.26 mmHg vs. 35.35 ± 7.86 mmHg, respectively, P: 0.047). However, there was no significant difference between 2 time periods in terms of presence of PAH (P>0.05). Pulmonary artery pressure did not correlate with blood flow rate of AVF and duration after AVF creation (P>0.05). In hemodialysis patients, a surgically created AVF has no significant effect on the development of PAH within a long-term period. Similarly, blood flow rate of AVF also did not affect remarkably systolic PAP within the long-term period. © 2010 The Authors. Hemodialysis International © 2010 International Society for Hemodialysis.

Oral N-acetylcysteine and exercise tolerance in mild chronic obstructive pulmonary disease.

PubMed

Hirai, Daniel M; Jones, Joshua H; Zelt, Joel T; da Silva, Marianne L; Bentley, Robert F; Edgett, Brittany A; Gurd, Brendon J; Tschakovsky, Michael E; O'Donnell, Denis E; Neder, J Alberto

2017-05-01

Heightened oxidative stress is implicated in the progressive impairment of skeletal muscle vascular and mitochondrial function in chronic obstructive pulmonary disease (COPD). Whether accumulation of reactive oxygen species contributes to exercise intolerance in the early stages of COPD is unknown. The purpose of the present study was to determine the effects of oral antioxidant treatment with N -acetylcysteine (NAC) on respiratory, cardiovascular, and locomotor muscle function and exercise tolerance in patients with mild COPD. Thirteen patients [forced expiratory volume in 1 s (FEV 1 )-to-forced vital capacity ratio < lower limit of normal (LLN) and FEV 1 ≥ LLN) were enrolled in a double-blind, randomized crossover study to receive NAC (1,800 mg/day) or placebo for 4 days. Severe-intensity constant-load exercise tests were performed with noninvasive measurements of central hemodynamics (stroke volume, heart rate, and cardiac output via impedance cardiography), arterial blood pressure, pulmonary ventilation and gas exchange, quadriceps muscle oxygenation (near-infrared spectroscopy), and estimated capillary blood flow. Nine patients completed the study with no major adverse clinical effects. Although NAC elevated plasma glutathione by ~27% compared with placebo ( P < 0.05), there were no differences in exercise tolerance (placebo: 325 ± 47 s, NAC: 336 ± 51 s), central hemodynamics, arterial blood pressure, pulmonary ventilation or gas exchange, locomotor muscle oxygenation, or capillary blood flow from rest to exercise between conditions ( P > 0.05 for all). In conclusion, modulation of plasma redox status with oral NAC treatment was not translated into beneficial effects on central or peripheral components of the oxygen transport pathway, thereby failing to improve exercise tolerance in nonhypoxemic patients with mild COPD. NEW & NOTEWORTHY Acute antioxidant treatment with N -acetylcysteine (NAC) elevated plasma glutathione but did not modulate central or

Neonatal right ventricle to pulmonary connection as a palliative procedure for pulmonary atresia with ventricular septal defect or severe tetralogy of Fallot.

PubMed

Gerelli, Sébastien; van Steenberghe, Mathieu; Murtuza, Bari; Bojan, Mirela; Harding, Ekoué Diana; Bonnet, Damien; Vouhé, Pascal R; Raisky, Olivier

2014-02-01

Right ventricle to pulmonary artery connection (RVPA connection) without prosthetic material has been our ideal strategy to palliate pulmonary atresia with ventricular septal defect (VSD) or severe tetralogy of Fallot for the last decade. We speculate that RVPA connection ensures adequate postoperative haemodynamics for symptomatic neonates and promotes pulmonary artery rehabilitation. The present study was undertaken to assess the outcome of this strategy. Between 2000 and 2010, among 107 patients who benefited from an RVPA connection, 57 were neonates. Forty-eight of these underwent autologous tissue reconstruction, 5 using left atrial appendage. Median weight was 2.9 kg (range 1.8-4.4). Median Nakata index was 100 mm2/m2 (range 17-185 mm2/m2); 12% had major aortopulmonary collaterals. All patients were reviewed retrospectively. End-points were death or complete repair; reintervention for restrictive pulmonary blood flow was considered as failure. At follow-up, we evaluated reintervention after complete repair, and quality of life. There were 2 early deaths (RV hypoplasia and RV failure) and 3 late sudden deaths (range 3-6 months). Pulmonary blood flow required to be increased in 8 patients: 4 underwent shunt after a median delay of 1 month; RVPA connection enlargement was needed in 3; 1 patient had percutaneous angioplasty. Finally, 47 patients (81%) had a complete repair, of which 70% were performed without prosthetic material at a median age of 7 months (range 2-53), with a median Nakata index of 221 mm2/m2 (range 102-891). One patient died early and 1 was a failure with opening of the VSD after intracardiac repair. At last follow-up, 4 patients were still awaiting repair, with 1 late death and 5 who had required reintervention after intracardiac repair; there were 3 conduit replacements and 2 balloon dilatation patch enlargements. The neonatal RVPA connection approach (i) provides an acceptable survival rate with a satisfactory haemodynamic adaptation, (ii

A pig model of acute right ventricular afterload increase by hypoxic pulmonary vasoconstriction.

PubMed

Knai, Kathrine; Skjaervold, Nils Kristian

2017-01-03

The aim of this study was to construct a non-invasive model for acute right ventricular afterload increase by hypoxic pulmonary vasoconstriction. Intact animal models are vital to improving our understanding of the pathophysiology of acute right ventricular failure. Acute right ventricular failure is caused by increased afterload of the right ventricle by chronic or acute pulmonary hypertension combined with regionally or globally reduced right ventricular contractile capacity. Previous models are hampered by their invasiveness; this is unfortunate as the pulmonary circulation is a low-pressure system that needs to be studied in closed chest animals. Hypoxic pulmonary vasoconstriction is a mechanism that causes vasoconstriction in alveolar vessels in response to alveolar hypoxia. In this study we explored the use of hypoxic pulmonary vasoconstriction as a means to increase the pressure load on the right ventricle. Pulmonary hypertension was induced by lowering the FiO 2 to levels below the physiological range in eight anesthetized and mechanically ventilated pigs. The pigs were monitored with blood pressure measurements and blood gases. The mean pulmonary artery pressures (mPAP) of the animals increased from 18.3 (4.2) to 28.4 (4.6) mmHg and the pulmonary vascular resistance (PVR) from 254 (76) dyns/cm 5 to 504 (191) dyns/cm 5 , with a lowering of FiO 2 from 0.30 to 0.15 (0.024). The animals' individual baseline mPAPs varied substantially as did their response to hypoxia. The reduced FiO 2 level yielded an overall lowering in oxygen offer, but the global oxygen consumption was unaltered. We showed in this study that the mPAP and the PVR could be raised by approximately 100% in the study animals by lowering the FiO 2 from 0.30 to 0.15 (0.024). We therefore present a novel method for minimally invasive (closed chest) right ventricular afterload manipulations intended for future studies of acute right ventricular failure. The method should in theory be reversible

CCL21 and IP-10 as blood biomarkers for pulmonary involvement in systemic lupus erythematosus patients.

PubMed

Odler, B; Bikov, A; Streizig, J; Balogh, C; Kiss, E; Vincze, K; Barta, I; Horváth, I; Müller, V

2017-05-01

Biomarkers for pulmonary manifestations in systemic lupus erythematosus (SLE) are missing. Plasma samples of nine SLE patients with known pulmonary involvement (SLE pulm ) and nine SLE patients without pulmonary involvement (SLE) were tested by multiplex microarray analysis for various cyto- and chemokines. Significantly decreased lung function paramters for forced vital capacity (FVC), total lung capacity (TLC), diffusion capacity for carbon monoxide (DL CO ) and diffusion of CO corrected on lung volume (KL CO ) were observed in SLE pulm as compared to SLE patients. CC chemokine ligand 21 (CCL21) and interferon gamma-induced protein 10 (IP-10) levels were significantly higher in SLE pulm , than in patients without pulmonary manifestations. CCL21 correlated negatively with DL CO ( r = -0.73; p < 0.01) and KL CO ( r = -0.62; p < 0.01), while IP-10 with FVC and forced expiratory volume one second. Receiver Operating Characteristics (ROC) analysis confirmed high sensitivity and specificity for the separation of SLE patients with and without pulmonary involvement for the chemokines CCL21 (Area Under Curve (AUC): 0.85; sensitivity%: 88.90; specificity%: 75.00; p < 0.01) and IP-10 (AUC: 0.82; sensitivity%: 66.67, specificity%: 100; p < 0.01). Pleuropulmonary manifestations in SLE patients associated with lung functional and DL CO /KL CO changes and were associated with significant increase in CCL21 and IP-10. These chemokines might serve as potential biomarkers of lung involvement in SLE patients.

Positive correlation between postoperative tumor recurrence and changes in circulating tumor cell counts in pulmonary venous blood (pvCTC) during surgical manipulation in non-small cell lung cancer.

PubMed

Hashimoto, Masaki; Tanaka, Fumihiro; Yoneda, Kazue; Takuwa, Teruhisa; Matsumoto, Seiji; Okumura, Yoshitomo; Kondo, Nobuyuki; Tsujimura, Tohru; Nakano, Takashi; Hasegawa, Seiki

2018-01-01

In non-small cell lung cancer (NSCLC), circulating tumor cells (CTC) are shed and circulate to the peripheral blood through the pulmonary vein. Previously, CTC count in pulmonary venous blood (pvCTC) was shown to significantly increase after surgical manipulation. Therefore, we assessed the correlation between the changes in the pvCTC count (ΔpvCTC) and clinical outcomes. Consecutive patients with peripheral-type, NSCLC, who underwent lobectomy or bi-lobectomy through open thoracotomy, were enrolled prospectively. Before and after lobectomy, 2.5 mL of blood was drawn from the associated lobar pulmonary vein (PV), and was served for the quantitative evaluation of CTC using the CellSearch ® system. The cut-off point of ΔpvCTC was determined according to clinical outcomes and ΔpvCTC using receiver operation characteristic (ROC) curve. Then the correlation between ΔpvCTC and clinical outcomes was evaluated by Kaplan-Meier analyses and log-rank test. In addition, the correlation between ΔpvCTC and perioperative variables was assessed. A total of 30 patients were enrolled, tumor recurrence occurred in 11 patients over a median follow-up of 64.4 months. Of these, 7 patients had distant metastasis and 4 had local recurrence. The median ΔpvCTC was 49 cells/2.5 mL, and pvCTC-count was increased during surgical manipulation in 24 patients (80%). We divided patients into two groups based on ΔpvCTC with the cut-off value as 119 cells/2.5 mL according to ROC curve. Significant shorter time to distant metastasis (TDM) (P=0.0123) was observed in high ΔpvCTC group (ΔpvCTC ≥119 cells/2.5 mL) than low ΔpvCTC group (ΔpvCTC <119 cells/ 2.5mL). Neither disease-free survival (DFS) nor overall survival (OS) was significantly correlated with ΔpvCTC. Increasing pvCTC count during surgical manipulation was significantly correlated with postoperative distant metastasis in completely resected NSCLC patients. Significant shorter TDM was observed in patient with high ΔpvCTC group.

Hantavirus pulmonary syndrome.

PubMed

Macneil, Adam; Nichol, Stuart T; Spiropoulou, Christina F

2011-12-01

Hantavirus pulmonary syndrome (HPS) is a severe disease characterized by a rapid onset of pulmonary edema followed by respiratory failure and cardiogenic shock. The HPS associated viruses are members of the genus Hantavirus, family Bunyaviridae. Hantaviruses have a worldwide distribution and are broadly split into the New World hantaviruses, which includes those causing HPS, and the Old World hantaviruses [including the prototype Hantaan virus (HTNV)], which are associated with a different disease, hemorrhagic fever with renal syndrome (HFRS). Sin Nombre virus (SNV) and Andes virus (ANDV) are the most common causes of HPS in North and South America, respectively. Case fatality of HPS is approximately 40%. Pathogenic New World hantaviruses infect the lung microvascular endothelium without causing any virus induced cytopathic effect. However, virus infection results in microvascular leakage, which is the hallmark of HPS. This article briefly reviews the knowledge on HPS-associated hantaviruses accumulated since their discovery, less than 20 years ago. Published by Elsevier B.V.

Novel therapeutic approach for pulmonary emphysema using gelatin microspheres releasing basic fibroblast growth factor in a canine model.

PubMed

Chang, Sung Soo; Yokomise, Hiroyasu; Matsuura, Natsumi; Gotoh, Masashi; Tabata, Yasuhiko

2014-08-01

The prognosis of patients with emphysema is poor as there is no truly effective treatment. Our previous study showed that the alveolar space was smaller and the microvessel density was higher in a canine emphysema model after the intrapulmonary arterial administration of gelatin microspheres slowly releasing basic fibroblast growth factor (bFGF-GMS). In the present study, we evaluated the functional effect of injecting bFGF-GMS via the pulmonary artery in this canine pulmonary emphysema model. Using the porcine pancreatic elastase (PPE)-induced total emphysema model, we approximated the value of lung compliance with a Power Lab System, and performed blood gas analysis in a control group, a total emphysema group, and a bFGF group in which bFGF-GMS were injected toward the whole pulmonary artery via the femoral vein. Each group comprised five dogs. Lung compliance was higher in the total emphysema group than in the control group (p = 0.031), and the bFGF group showed no significant improvement of lung compliance vs. the total emphysema group (p = 0.112). PaO2 (partial pressure of oxygen in arterial blood) was improved by administering bFGF-GMS in the total emphysema model (p = 0.027). In the canine total emphysema model, blood gas parameters were improved by the whole pulmonary arterial administration of bFGF-GMS. This method has the potential to be an effective novel therapy for pulmonary emphysema.

Impact of agglomeration state of nano- and submicron sized gold particles on pulmonary inflammation

PubMed Central

2010-01-01

Background Nanoparticle (NP) toxicity testing comes with many challenges. Characterization of the test substance is of crucial importance and in the case of NPs, agglomeration/aggregation state in physiological media needs to be considered. In this study, we have addressed the effect of agglomerated versus single particle suspensions of nano- and submicron sized gold on the inflammatory response in the lung. Rats were exposed to a single dose of 1.6 mg/kg body weight (bw) of spherical gold particles with geometric diameters of 50 nm or 250 nm diluted either by ultrapure water or by adding phosphate buffered saline (PBS). A single dose of 1.6 mg/kg bw DQ12 quartz was used as a positive control for pulmonary inflammation. Extensive characterization of the particle suspensions has been performed by determining the zetapotential, pH, gold concentration and particle size distribution. Primary particle size and particle purity has been verified using transmission electron microscopy (TEM) techniques. Pulmonary inflammation (total cell number, differential cell count and pro-inflammatory cytokines), cell damage (total protein and albumin) and cytotoxicity (alkaline phosphatase and lactate dehydrogenase) were determined in bronchoalveolar lavage fluid (BALF) and acute systemic effects in blood (total cell number, differential cell counts, fibrinogen and C-reactive protein) 3 and 24 hours post exposure. Uptake of gold particles in alveolar macrophages has been determined by TEM. Results Particles diluted in ultrapure water are well dispersed, while agglomerates are formed when diluting in PBS. The particle size of the 50 nm particles was confirmed, while the 250 nm particles appear to be 200 nm using tracking analysis and 210 nm using TEM. No major differences in pulmonary and systemic toxicity markers were observed after instillation of agglomerated versus single gold particles of different sizes. Both agglomerated as well as single nanoparticles were taken up by

Drug Treatment of Pulmonary Hypertension in Children

PubMed Central

Vorhies, Erika E; Ivy, David Dunbar

2013-01-01

Pulmonary arterial hypertension (PAH) is a rare disease in infants and children that is associated with significant morbidity and mortality. The disease is characterized by progressive pulmonary vascular functional and structural changes resulting in increased pulmonary vascular resistance and eventual right heart failure and death. In the majority of pediatric patients, PAH is idiopathic or associated with congenital heart disease and rarely is associated with other conditions such as connective tissue or thromboembolic disease. Although treatment of the underlying disease and reversal of advanced structural changes has not yet been achieved with current therapy, quality of life and survival have been improved significantly. Targeted pulmonary vasodilator therapies, including endothelin receptor antagonists, prostacyclin analogues and phosphodiesterase type 5 inhibitors, have demonstrated hemodynamic and functional improvement in children. The management of pediatric PAH remains challenging as treatment decisions continue to depend largely on results from evidence-based adult studies and the clinical experience of pediatric experts. This article reviews the current drug therapies and their use in the management of PAH in children. PMID:24114695

Preparation and Characterization of Doripenem-Loaded Microparticles for Pulmonary Delivery.

PubMed

Yildiz-Peköz, Ayca; Akbal, Ozlem; Tekarslan, S Hande; Sagirli, A Olcay; Mulazimoglu, Lütfiye; Morina, Deniz; Cevher, Erdal

2018-06-07

microparticles. P. aeruginosa showed the same susceptibility to all doripenem-loaded microparticle formulations. Cell viability of microparticles was between 70% ± 0.08% and 90% ± 0.04% at 0.5 and 10 mg/mL concentration, respectively. Doripenem-loaded microparticles, produced using a combination of ionotropic gelation and spray-drying methods, are suitable for pulmonary drug delivery based on their particles size, zeta potential, cytotoxicity and high production yield. To our knowledge, this is the first study that microparticles containing doripenem were produced and characterized.

Minimally Invasive Surgical Pulmonary Embolectomy: A Potential Alternative to Conventional Sternotomy.

PubMed

Pasrija, Chetan; Shah, Aakash; Sultanik, Elliot; Rouse, Michael; Ghoreishi, Mehrdad; Bittle, Gregory J; Boulos, Francesca; Griffith, Bartley P; Kon, Zachary N

Surgical pulmonary embolectomy has gained increasing popularity over the past decade with multiple series reporting excellent outcomes in the treatment of submassive pulmonary embolism. However, a significant barrier to the broader adoption of surgical pulmonary embolectomy remains the large incision and long recovery after a full sternotomy. We report the safety and efficacy of using a minimally invasive approach to surgical pulmonary embolectomy. All consecutive patients undergoing surgical pulmonary embolectomy for a submassive pulmonary embolism (2015-2017) were reviewed. Patients were stratified as conventional or minimally invasive. The minimally invasive approach included a 5- to 7-cm skin incision with upper hemisternotomy to the third intercostal space. The primary outcomes were in-hospital and 90-day survival. Thirty patients (conventional = 20, minimally invasive = 10) were identified. Operative time was similar between the two groups, but cardiopulmonary bypass time was significantly longer in the minimally invasive group (58 vs 94 minutes, P = 0.04). While ventilator time and intensive care unit length of stay were similar between groups, hospital length of stay was 4.5 days shorter in the minimally invasive group, and there was a trend toward less blood product use. In-hospital and 90-day survival was 100%. Within the minimally invasive cohort, median right ventricular dysfunction at discharge was none-mild and no patient experienced postoperative renal failure, deep sternal wound infection, sepsis, or stroke. Minimally invasive surgical pulmonary embolectomy appears to be a feasible approach in the treatment of patients with a submassive pulmonary embolism. A larger, prospective analysis comparing this modality with conventional surgical pulmonary embolectomy may be warranted.

Acquired pulmonary artery stenosis in four dogs.

PubMed

Scansen, Brian A; Schober, Karsten E; Bonagura, John D; Smeak, Daniel D

2008-04-15

4 dogs with acquired pulmonary artery stenosis (PAS) were examined for various clinical signs. One was a mixed-breed dog with congenital valvular PAS that subsequently developed peripheral PAS, one was a Golden Retriever with pulmonary valve fibrosarcoma, one was a Pembroke Welsh Corgi in which the left pulmonary artery had inadvertently been ligated during surgery for correction of patent ductus arteriosus, and one was a Boston Terrier with a heart-base mass compressing the pulmonary arteries. All 4 dogs were evaluated with 2-dimensional and Doppler echocardiography to characterize the nature and severity of the stenoses; other diagnostic tests were also performed. The mixed-breed dog with valvular and peripheral PAS was euthanized, surgical resection of the pulmonic valve mass was performed in the Golden Retriever, corrective surgery was performed on the Pembroke Welsh Corgi with left pulmonary artery ligation, and the Boston Terrier with the heart-base mass was managed medically. Acquired PAS in dogs may manifest as a clinically silent heart murmur, syncope, or right-sided heart failure. The diagnosis is made on the basis of imaging findings, particularly results of 2-dimensional and Doppler echocardiography. Treatment may include surgical, interventional, or medical modalities and is targeted at resolving the inciting cause.

Over-expression of thymosin β4 in granulomatous lung tissue with active pulmonary tuberculosis.

PubMed

Kang, Yun-Jeong; Jo, Jin-Ok; Ock, Mee Sun; Yoo, Young-Bin; Chun, Bong-Kwon; Oak, Chul-Ho; Cha, Hee-Jae

2014-05-01

Recent studies have shown that thymosin β4 (Tβ4) stimulates angiogenesis by inducing vascular endothelial growth factor (VEGF) expression and stabilizing hypoxia inducible factor-1α (HIF-1α) protein. Pulmonary tuberculosis (TB), a type of granulomatous disease, is accompanied by intense angiogenesis and VEGF levels have been reported to be elevated in serum or tissue inflamed by pulmonary tuberculosis. We investigated the expression of Tβ4 in granulomatous lung tissues at various stages of active pulmonary tuberculosis, and we also examined the expression patterns of VEGF and HIF-1α to compare their Tβ4 expression patterns in patients' tissues and in the tissue microarray of TB patients. Tβ4 was highly expressed in both granulomas and surrounding lymphocytes in nascent granulomatous lung tissue, but was expressed only surrounding tissues of necrotic or caseous necrotic regions. The expression pattern of HIF-1α was similar to that of Tβ4. VEGF was expressed in both granulomas and blood vessels surrounding granulomas. The expression pattern of VEGF co-localized with CD31 (platelet endothelial cell adhesion molecule, PECAM-1), a blood endothelial cell marker, and partially co-localized with Tβ4. However, the expression of Tβ4 did not co-localize with alveolar macrophages. Stained alveolar macrophages were present surrounding regions of granuloma highly expressing Tβ4. We also analyzed mRNA expression in the sputum of 10 normal and 19 pulmonary TB patients. Expression of Tβ4 was significantly higher in patients with pulmonary tuberculosis than in normal controls. These data suggest that Tβ4 is highly expressed in granulomatous lung tissue with active pulmonary TB and is associated with HIF-1α- and VEGF-mediated inflammation and angiogenesis. Furthermore, the expression of Tβ4 in the sputum of pulmonary tuberculosis patients can be used as a potential marker for diagnosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pulmonary hypoplasia in Jarcho-Levin syndrome.

PubMed

Rodríguez, Luis M; García-García, Inés; Correa-Rivas, María S; García-Fragoso, Lourdes

2004-03-01

Jarcho-Levin syndrome, also known as spondylothoracic dysplasia and characterized by short trunk dwarfism, "crab-like" rib cage, with ribs and vertebral defects; it is not uncommon in Puerto Ricans. Many patients die in early infancy due to respiratory compromise associated to lung restriction and the reported cases emphasize mostly the skeletal malformations associated to the syndrome. We report the autopsy findings in a newborn with isolated Jarcho-Levin syndrome emphasizing pulmonary pathology. He was a pre-term male who died of respiratory failure at three hours old and, autopsy findings confirmed the clinical diagnosis. Internal examination showed hypoplastic lungs with normal lobation. The histological structure appeared normal and relatively mature; the diaphragm showed eventration and unilateral absence of musculature. This case shows the worst spectum of the Jarcho-Levin syndrome: pulmonary hypoplasia not compatible with extrauterine life. Since thoracic restriction is present during the fetal period, the degree of pulmonary hypoplasia probably defines survival beyond the neonatal period.

Proteins and antibodies in serum, plasma, and whole blood-size characterization using asymmetrical flow field-flow fractionation (AF4).

PubMed

Leeman, Mats; Choi, Jaeyeong; Hansson, Sebastian; Storm, Matilda Ulmius; Nilsson, Lars

2018-05-29

The analysis of aggregates of therapeutic proteins is crucial in order to ensure efficacy and patient safety. Typically, the analysis is performed in the finished formulation to ensure that aggregates are not present. An important question is, however, what happens to therapeutic proteins, with regard to oligomerization and aggregation, after they have been administrated (i.e., in the blood). In this paper, the separation of whole blood, plasma, and serum is shown using asymmetric flow field-flow fractionation (AF4) with a minimum of sample pre-treatment. Furthermore, the analysis and size characterization of a fluorescent antibody in blood plasma using AF4 are demonstrated. The results show the suitability and strength of AF4 for blood analysis and open new important routes for the analysis and characterization of therapeutic proteins in the blood.

RhoA/Rho-kinase signaling: a therapeutic target in pulmonary hypertension.

PubMed

Barman, Scott A; Zhu, Shu; White, Richard E

2009-01-01

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by progressive elevation of pulmonary arterial pressure and vascular resistance due to pulmonary vasoconstriction and vessel remodeling as well as inflammation. Rho-kinases (ROCKs) are one of the best-described effectors of the small G-protein RhoA, and ROCKs are involved in a variety of cellular functions including muscle cell contraction, proliferation and vascular inflammation through inhibition of myosin light chain phosphatase and activation of downstream mediators. A plethora of evidence in animal models suggests that heightened RhoA/ROCK signaling is important in the pathogenesis of pulmonary hypertension by causing enhanced constriction and remodeling of the pulmonary vasculature. Both animal and clinical studies suggest that ROCK inhibitors are effective for treatment of severe PAH with minimal risk, which supports the premise that ROCKs are important therapeutic targets in pulmonary hypertension and that ROCK inhibitors are a promising new class of drugs for this devastating disease.

Pulmonary vascular response to exercise in symptomatic heart failure with reduced ejection fraction and pulmonary hypertension.

PubMed

Verbrugge, Frederik H; Dupont, Matthias; Bertrand, Philippe B; Nijst, Petra; Grieten, Lars; Dens, Joseph; Verhaert, David; Janssens, Stefan; Tang, W H Wilson; Mullens, Wilfried

2015-03-01

To study pulmonary vascular response patterns to exercise in heart failure with reduced ejection fraction (HFrEF) and pulmonary hypertension (PH). In this prospective single-centre cohort study, consecutive symptomatic HFrEF patients (n = 40) with mean pulmonary arterial pressure (MPAP) ≥25 mmHg, pulmonary artery wedge pressure (PAWP) >15 mmHg, and cardiac index <2.5 L/min.m(2) , received protocol-driven titrated sodium nitroprusside (SNP) and diuretics to reach mean arterial blood pressure 65-75 mmHg and PAWP ≤15 mmHg. Patients performed symptom-limited supine bicycle testing under continued SNP administration. Afterwards, SNP was gradually withdrawn, renin-angiotensin system blockers uptitrated, and hydralazine added to maintain haemodynamic targets. Subsequently, bicycle testing was repeated. Patients presented with pulmonary vascular resistance (PVR) = 3.8 ± 1.4 Wood Units at rest, decreasing to 2.9 ± 0.9 Wood Units after decongestion, with PH was completely reversed (MPAP <25 mmHg) in 22%. From rest to maximal exercise, the cardiac index did not change significantly (P = 0.334 under SNP; P-value = 0.552 under oral therapy). A dynamic exercise-induced PVR increase >3.5 Wood Units was noted in 19 patients (48%) under oral therapy vs. five (13%) under SNP. Such exercise-induced PVR increase was associated with a 33% relative decrease in right ventricular stroke work index (P = 0.037). Even after thorough decongestion and under continuous afterload reduction, PH secondary to HFrEF is completely reversible in only a minority of patients. Others demonstrate an exercise-induced PVR increase, associated with impaired right ventricular stroke work, which might be ameliorated by nitric oxide donor support. © 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.

Plasma proteome analysis in patients with pulmonary arterial hypertension: an observational cohort study.

PubMed

Rhodes, Christopher J; Wharton, John; Ghataorhe, Pavandeep; Watson, Geoffrey; Girerd, Barbara; Howard, Luke S; Gibbs, J Simon R; Condliffe, Robin; Elliot, Charles A; Kiely, David G; Simonneau, Gerald; Montani, David; Sitbon, Olivier; Gall, Henning; Schermuly, Ralph T; Ghofrani, H Ardeschir; Lawrie, Allan; Humbert, Marc; Wilkins, Martin R

2017-09-01

Idiopathic and heritable pulmonary arterial hypertension form a rare but molecularly heterogeneous disease group. We aimed to measure and validate differences in plasma concentrations of proteins that are associated with survival in patients with idiopathic or heritable pulmonary arterial hypertension to improve risk stratification. In this observational cohort study, we enrolled patients with idiopathic or heritable pulmonary arterial hypertension from London (UK; cohorts 1 and 2), Giessen (Germany; cohort 3), and Paris (France; cohort 4). Blood samples were collected at routine clinical appointment visits, clinical data were collected within 30 days of blood sampling, and biochemical data were collected within 7 days of blood sampling. We used an aptamer-based assay of 1129 plasma proteins, and patient clinical details were concealed to the technicians. We identified a panel of prognostic proteins, confirmed with alternative targeted assays, which we evaluated against the established prognostic risk equation for pulmonary arterial hypertension derived from the REVEAL registry. All-cause mortality was the primary endpoint. 20 proteins differentiated survivors and non-survivors in 143 consecutive patients with idiopathic or heritable pulmonary arterial hypertension with 2 years' follow-up (cohort 1) and in a further 75 patients with 2·5 years' follow-up (cohort 2). Nine proteins were both prognostic independent of plasma NT-proBNP concentrations and confirmed by targeted assays. The functions of these proteins relate to myocardial stress, inflammation, pulmonary vascular cellular dysfunction and structural dysregulation, iron status, and coagulation. A cutoff-based score using the panel of nine proteins provided prognostic information independent of the REVEAL equation, improving the C statistic from area under the curve 0·83 (for REVEAL risk score, 95% CI 0·77-0·89; p<0·0001) to 0·91 (for panel and REVEAL 0·87-0·96; p<0·0001) and improving

[Total cavopulmonary connection for grown diminutive pulmonary artery after staged Blalock-Taussig shunt].

PubMed

Uchita, S; Matsuo, K; Ishida, T; Okajima, Y; Aotsuka, H; Fujiwara, T

1998-11-01

We report a two-year-old girl with asplenia, [A, L, L] DORV, pulmonary atresia, common AV valve, PDA, and TAPVC, who successfully underwent total cavo pulmonary connection (TCPC). Deep cyanosis was pointed out since birth. Cardiac catheterization performed on the sixth day after birth revealed a diminutive pulmonary artery tree of which PA index was 41 mm2/m2. Left modified Blalock-Taussig shunt was created at 27 days of age. The PA index increased to 282 mm2/mm2, but disparity in diameter between the left and the right pulmonary artery was yielded by PDA subsidence. Therefore additional contralateral B-T shunt was made at one year of age. Follow-up cardiac catheterization at 28 months of age showed well developed pulmonary artery; PA index of 460 mm2/m2, right pulmonary resistance (Rp) of 3.49 units, left Rp of 2.33 units, and estimated total Rp was 1.39. According to study, bidirectional Glenn procedure or TCPC was indicated. Considering necessity of urgent repair of common pulmonary vein obstruction, regurgitation of the common atrio-ventricular valve and pulmonary artery stenosis, TCPC was performed with concomitant repair of the associated lesions. Severe butterfly-figure stenosis of the central PA was augmented by anastomosing both the left SVC and the left-sided atrium. In conclusion, diminutive pulmonary artery could be adequately grown by phase-in Blalock-Taussig shunts. Pulmonary blood flow scintigraphy was thought to be useful for estimation of pulmonary resistance in such cases with different pulmonary resistance between right and left PA.

Circulating big endothelin-1: an active role in pulmonary thromboendarterectomy?

PubMed

Langer, Frank; Bauer, Michael; Tscholl, Dietmar; Schramm, Rene; Kunihara, Takashi; Lausberg, Henning; Georg, Thomas; Wilkens, Heinrike; Schäfers, Hans-Joachim

2005-11-01

Pulmonary thromboendarterectomy is an effective treatment for patients with chronic thromboembolic pulmonary hypertension. The early postoperative course may be associated with pulmonary vasoconstriction and profound systemic vasodilation. We investigated the potential involvement of endothelins in these hemodynamic alterations. Seventeen patients with chronic thromboembolic pulmonary hypertension (pulmonary vascular resistance, 1015 +/- 402 dyne x s x cm(-5) [mean +/- SD]) underwent pulmonary thromboendarterectomy with cardiopulmonary bypass and deep hypothermic circulatory arrest. Peripheral arterial blood samples were drawn before sternotomy, during cardiopulmonary bypass before and after deep hypothermic circulatory arrest, and 0, 8, 16, and 24 hours after surgery and were analyzed for big endothelin-1. The patients were divided into 2 groups according to whether their preoperative big endothelin-1 plasma level was above or below the cutoff point of 2.1 pg/mL, as determined by receiver operating characteristic curve analysis (group A, big endothelin-1 <2.1 pg/mL, n = 8; group B, big endothelin-1 > or =2.1 pg/mL, n = 9). Patients in group B, with higher preoperative big endothelin-1 levels (3.2 +/- 1.0 pg/mL vs 1.5 +/- 0.4 pg/mL; P < .001), were poorer operative candidates (preoperative mean pulmonary artery pressure, 51.3 +/- 7.1 mm Hg vs 43.6 +/- 6.2 mm Hg; P = .006) and had a poorer outcome (mean pulmonary artery pressure 24 hours after surgery, 32.6 +/- 9.5 mm Hg vs 21.8 +/- 6.2 mm Hg; P < .001). Positive correlations were found between preoperative big endothelin-1 levels and preoperative mean pulmonary artery pressure (r = 0.56; P = .02) as well as postoperative mean pulmonary artery pressure at 0 hours (r = 0.70; P = .002) and 24 hours (r = 0.63; P = .006) after surgery. Preoperative big endothelin-1 levels predicted outcome (postoperative mean pulmonary artery pressure at 24 hours after surgery) after pulmonary thromboendarterectomy (area under the

Role of Transcription Factors in Pulmonary Artery Smooth Muscle Cells: An Important Link to Hypoxic Pulmonary Hypertension.

PubMed

Di Mise, Annarita; Wang, Yong-Xiao; Zheng, Yun-Min

2017-01-01

Hypoxia, namely a lack of oxygen in the blood, induces pulmonary vasoconstriction and vasoremodeling, which serve as essential pathologic factors leading to pulmonary hypertension (PH). The underlying molecular mechanisms are uncertain; however, pulmonary artery smooth muscle cells (PASMCs) play an essential role in hypoxia-induced pulmonary vasoconstriction, vasoremodeling, and PH. Hypoxia causes oxidative damage to DNAs, proteins, and lipids. This damage (oxidative stress) modulates the activity of ion channels and elevates the intracellular calcium concentration ([Ca 2+ ] i , Ca 2+ signaling) of PASMCs. The oxidative stress and increased Ca 2+ signaling mutually interact with each other, and synergistically results in a variety of cellular responses. These responses include functional and structural abnormalities of mitochondria, sarcoplasmic reticulum, and nucleus; cell contraction, proliferation, migration, and apoptosis, as well as generation of vasoactive substances, inflammatory molecules, and growth factors that mediate the development of PH. A number of studies reveal that various transcription factors (TFs) play important roles in hypoxia-induced oxidative stress, disrupted PAMSC Ca 2+ signaling and the development and progress of PH. It is believed that in the pathogenesis of PH, hypoxia facilitates these roles by mediating the expression of multiple genes. Therefore, the identification of specific genes and their transcription factors implicated in PH is necessary for the complete understanding of the underlying molecular mechanisms. Moreover, this identification may aid in the development of novel and effective therapeutic strategies for PH.

Diagnosis and outcome of a dog with iatrogenic hyperadrenocorticism and secondary pulmonary mineralization.

PubMed

Blois, Shauna L; Caron, Isabelle; Mitchell, Colleen

2009-04-01

A 6-year-old, spayed female dog was evaluated for a history of chronic coughing, excessive panting, and lethargy. Iatrogenic hyperadrenocorticism was diagnosed, and pulmonary mineralization was documented with a 99m Technitium-methylene diphosphonate (99mTc-MDP) scan. Blood gas analysis showed hypoxia. Clinical signs resolved and blood gas values returned to normal when corticosteroid therapy was discontinued.

Diagnosis and outcome of a dog with iatrogenic hyperadrenocorticism and secondary pulmonary mineralization

PubMed Central

Blois, Shauna L.; Caron, Isabelle; Mitchell, Colleen

2009-01-01

A 6-year-old, spayed female dog was evaluated for a history of chronic coughing, excessive panting, and lethargy. Iatrogenic hyperadrenocorticism was diagnosed, and pulmonary mineralization was documented with a 99mTechnitium-methylene diphosphonate (99mTc-MDP) scan. Blood gas analysis showed hypoxia. Clinical signs resolved and blood gas values returned to normal when corticosteroid therapy was discontinued. PMID:19436448

Autonomic nervous system involvement in pulmonary arterial hypertension.

PubMed

Vaillancourt, Mylène; Chia, Pamela; Sarji, Shervin; Nguyen, Jason; Hoftman, Nir; Ruffenach, Gregoire; Eghbali, Mansoureh; Mahajan, Aman; Umar, Soban

2017-12-04

Pulmonary arterial hypertension (PAH) is a chronic pulmonary vascular disease characterized by increased pulmonary vascular resistance (PVR) leading to right ventricular (RV) failure. Autonomic nervous system involvement in the pathogenesis of PAH has been demonstrated several years ago, however the extent of this involvement is not fully understood. PAH is associated with increased sympathetic nervous system (SNS) activation, decreased heart rate variability, and presence of cardiac arrhythmias. There is also evidence for increased renin-angiotensin-aldosterone system (RAAS) activation in PAH patients associated with clinical worsening. Reduction of neurohormonal activation could be an effective therapeutic strategy for PAH. Although therapies targeting adrenergic receptors or RAAS signaling pathways have been shown to reverse cardiac remodeling and improve outcomes in experimental pulmonary hypertension (PH)-models, the effectiveness and safety of such treatments in clinical settings have been uncertain. Recently, novel direct methods such as cervical ganglion block, pulmonary artery denervation (PADN), and renal denervation have been employed to attenuate SNS activation in PAH. In this review, we intend to summarize the multiple aspects of autonomic nervous system involvement in PAH and overview the different pharmacological and invasive strategies used to target autonomic nervous system for the treatment of PAH.

Lung excision of non-small-cell lung cancer leaves cancer cells in residual lobe: cytological detection using pulmonary vein blood.

PubMed

Sawabata, Noriyoshi; Funaki, Soichiro; Shintani, Yasushi; Okumura, Meinosin

2016-02-01

Lung excision to treat non-small-cell lung cancer (NSCLC) is associated with a worse prognosis when compared with a lobectomy. Cancer relapse may be caused by tumour cells remaining in the residual lobe, the possibility of dislodged cancer cells in the residual lobe is assessed using pulmonary vein blood (PVB) from the resected lung. Twenty-eight patients with pathological stage I NSCLC who underwent lung excision followed by a lobectomy were evaluated according to the status of isolated tumour cells (ITCs) (origin of circulating tumour cells) in PVB from the resected lobe. Survival was also assessed according to the status of ITCs. The rate of ITC presence was 60.7% and depended on margin distance/tumour size (M/T) with a threshold of 1.0-30.8% (4/13) in M/T greater than or equal to 1.0 and 86.7% (13/15) in M/T smaller than 1.0 (P = 0.001). PVB-ITC status was no ITCs (N) in 11 (39.3%), only singular cells (S) in 13 (50.0%) and clustered cells (C) in 4 (14.3%). In addition, the survival status of patients with clustered cells was exclusively wrong. After pulmonary excision for lung cancer, tumour cells remain in the residual lobe and the morphology of which may indicate recurrence. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

The prognostic blood biomarker proadrenomedullin for outcome prediction in patients with chronic obstructive pulmonary disease (COPD): a qualitative clinical review.

PubMed

Schuetz, Philipp; Marlowe, Robert J; Mueller, Beat

2015-03-01

Plasma proadrenomedullin (ProADM) is a blood biomarker that may aid in multidimensional risk assessment of patients with chronic obstructive pulmonary disease (COPD). Co-secreted 1:1 with adrenomedullin (ADM), ProADM is a less biologically active, more chemically stable surrogate for this pluripotent regulatory peptide, which due to biological and ex vivo physical characteristics is difficult to reliably directly quantify. Upregulated by hypoxia, inflammatory cytokines, bacterial products, and shear stress and expressed widely in pulmonary cells and ubiquitously throughout the body, ADM exerts or mediates vasodilatory, natriuretic, diuretic, antioxidative, anti-inflammatory, antimicrobial, and metabolic effects. Observational data from four separate studies totaling 1366 patients suggest that as a single factor, ProADM is a significant independent, and accurate, long-term all-cause mortality predictor in COPD. This body of work also suggests that combined with different groups of demographic/clinical variables, ProADM provides significant incremental long-term mortality prediction power relative to the groups of variables alone. Additionally, the literature contains indications that ProADM may be a global cardiopulmonary stress marker, potentially supplying prognostic information when cardiopulmonary exercise testing results such as 6-min walk distance are unavailable due to time or other resource constraints or to a patient's advanced disease. Prospective, randomized, controlled interventional studies are needed to demonstrate whether ProADM use in risk-based guidance of site-of-care, monitoring, and treatment decisions improves clinical, quality-of-life, or pharmacoeconomic outcomes in patients with COPD.

Development of occlusive neointimal lesions in distal pulmonary arteries of endothelin B receptor-deficient rats: a new model of severe pulmonary arterial hypertension.

PubMed

Ivy, D Dunbar; McMurtry, Ivan F; Colvin, Kelley; Imamura, Masatoshi; Oka, Masahiko; Lee, Dong-Seok; Gebb, Sarah; Jones, Peter Lloyd

2005-06-07

Human pulmonary arterial hypertension (PAH) is characterized by proliferation of vascular smooth muscle and, in its more severe form, by the development of occlusive neointimal lesions. However, few animal models of pulmonary neointimal proliferation exist, thereby limiting a complete understanding of the pathobiology of PAH. Recent studies of the endothelin (ET) system demonstrate that deficiency of the ET(B) receptor predisposes adult rats to acute and chronic hypoxic PAH, yet these animals fail to develop neointimal lesions. Herein, we determined and thereafter showed that exposure of ET(B) receptor-deficient rats to the endothelial toxin monocrotaline (MCT) leads to the development of neointimal lesions that share hallmarks of human PAH. The pulmonary hemodynamic and morphometric effects of 60 mg/kg MCT in control (MCT(+/+)) and ET(B) receptor-deficient (MCT(sl/sl)) rats at 6 weeks of age were assessed. MCT(sl/sl) rats developed more severe PAH, characterized by elevated pulmonary artery pressure, diminished cardiac output, and right ventricular hypertrophy. In MCT(sl/sl) rats, morphometric evaluation revealed the presence of neointimal lesions within small distal pulmonary arteries, increased medial wall thickness, and decreased arterial-to-alveolar ratio. In keeping with this, barium angiography revealed diminished distal pulmonary vasculature of MCT(sl/sl) rat lungs. Cells within neointimal lesions expressed smooth muscle and endothelial cell markers. Moreover, cells within neointimal lesions exhibited increased levels of proliferation and were located in a tissue microenvironment enriched with vascular endothelial growth factor, tenascin-C, and activated matrix metalloproteinase-9, factors already implicated in human PAH. Finally, assessment of steady state mRNA showed that whereas expression of ET(B) receptors was decreased in MCT(sl/sl) rat lungs, ET(A) receptor expression increased. Deficiency of the ET(B) receptor markedly accelerates the progression of

Development of Occlusive Neointimal Lesions in Distal Pulmonary Arteries of Endothelin B Receptor–Deficient Rats: A New Model of Severe Pulmonary Arterial Hypertension

PubMed Central

Ivy, D. Dunbar; McMurtry, Ivan F.; Colvin, Kelley; Imamura, Masatoshi; Oka, Masahiko; Lee, Dong-Seok; Gebb, Sarah; Jones, Peter Lloyd

2007-01-01

Background Human pulmonary arterial hypertension (PAH) is characterized by proliferation of vascular smooth muscle and, in its more severe form, by the development of occlusive neointimal lesions. However, few animal models of pulmonary neointimal proliferation exist, thereby limiting a complete understanding of the pathobiology of PAH. Recent studies of the endothelin (ET) system demonstrate that deficiency of the ETB receptor predisposes adult rats to acute and chronic hypoxic PAH, yet these animals fail to develop neointimal lesions. Herein, we determined and thereafter showed that exposure of ETB receptor–deficient rats to the endothelial toxin monocrotaline (MCT) leads to the development of neointimal lesions that share hallmarks of human PAH. Methods and Results The pulmonary hemodynamic and morphometric effects of 60 mg/kg MCT in control (MCT+/+) and ETB receptor–deficient (MCTsl/sl) rats at 6 weeks of age were assessed. MCTsl/sl rats developed more severe PAH, characterized by elevated pulmonary artery pressure, diminished cardiac output, and right ventricular hypertrophy. In MCTsl/sl rats, morphometric evaluation revealed the presence of neointimal lesions within small distal pulmonary arteries, increased medial wall thickness, and decreased arterial-to-alveolar ratio. In keeping with this, barium angiography revealed diminished distal pulmonary vasculature of MCTsl/sl rat lungs. Cells within neointimal lesions expressed smooth muscle and endothelial cell markers. Moreover, cells within neointimal lesions exhibited increased levels of proliferation and were located in a tissue microenvironment enriched with vascular endothelial growth factor, tenascin-C, and activated matrix metalloproteinase-9, factors already implicated in human PAH. Finally, assessment of steady state mRNA showed that whereas expression of ETB receptors was decreased in MCTsl/sl rat lungs, ETA receptor expression increased. Conclusions Deficiency of the ETB receptor markedly

Adiponectin Attenuates Lung Fibroblasts Activation and Pulmonary Fibrosis Induced by Paraquat

PubMed Central

He, Ya-rong; Lau, Wayne Bond; Zeng, Zhi; Liang, Zong-an

2015-01-01

Pulmonary fibrosis is one of the most common complications of paraquat (PQ) poisoning, which demands for more effective therapies. Accumulating evidence suggests adiponectin (APN) may be a promising therapy against fibrotic diseases. In the current study, we determine whether the exogenous globular APN isoform protects against pulmonary fibrosis in PQ-treated mice and human lung fibroblasts, and dissect the responsible underlying mechanisms. BALB/C mice were divided into control group, PQ group, PQ + low-dose APN group, and PQ + high-dose APN group. Mice were sacrificed 3, 7, 14, and 21 days after PQ treatment. We compared pulmonary histopathological changes among different groups on the basis of fibrosis scores, TGF-β1, CTGF and α-SMA pulmonary content via Western blot and real-time quantitative fluorescence-PCR (RT-PCR). Blood levels of MMP-9 and TIMP-1 were determined by ELISA. Human lung fibroblasts WI-38 were divided into control group, PQ group, APN group, and APN receptor (AdipoR) 1 small-interfering RNA (siRNA) group. Fibroblasts were collected 24, 48, and 72 hours after PQ exposure for assay. Cell viability and apoptosis were determined via Kit-8 (CCK-8) and fluorescein Annexin V-FITC/PI double labeling. The protein and mRNA expression level of collagen type III, AdipoR1, and AdipoR2 were measured by Western blot and RT-PCR. APN treatment significantly decreased the lung fibrosis scores, protein and mRNA expression of pulmonary TGF-β1, CTGF and α-SMA content, and blood MMP-9 and TIMP-1 in a dose-dependent manner (p<0.05). Pretreatment with APN significantly attenuated the reduced cell viability and up-regulated collagen type III expression induced by PQ in lung fibroblasts, (p<0.05). APN pretreatment up-regulated AdipoR1, but not AdipoR2, expression in WI-38 fibroblasts. AdipoR1 siRNA abrogated APN-mediated protective effects in PQ-exposed fibroblasts. Taken together, our data suggests APN protects against PQ-induced pulmonary fibrosis in a dose

Adiponectin attenuates lung fibroblasts activation and pulmonary fibrosis induced by paraquat.

PubMed

Yao, Rong; Cao, Yu; He, Ya-rong; Lau, Wayne Bond; Zeng, Zhi; Liang, Zong-an

2015-01-01

Pulmonary fibrosis is one of the most common complications of paraquat (PQ) poisoning, which demands for more effective therapies. Accumulating evidence suggests adiponectin (APN) may be a promising therapy against fibrotic diseases. In the current study, we determine whether the exogenous globular APN isoform protects against pulmonary fibrosis in PQ-treated mice and human lung fibroblasts, and dissect the responsible underlying mechanisms. BALB/C mice were divided into control group, PQ group, PQ + low-dose APN group, and PQ + high-dose APN group. Mice were sacrificed 3, 7, 14, and 21 days after PQ treatment. We compared pulmonary histopathological changes among different groups on the basis of fibrosis scores, TGF-β1, CTGF and α-SMA pulmonary content via Western blot and real-time quantitative fluorescence-PCR (RT-PCR). Blood levels of MMP-9 and TIMP-1 were determined by ELISA. Human lung fibroblasts WI-38 were divided into control group, PQ group, APN group, and APN receptor (AdipoR) 1 small-interfering RNA (siRNA) group. Fibroblasts were collected 24, 48, and 72 hours after PQ exposure for assay. Cell viability and apoptosis were determined via Kit-8 (CCK-8) and fluorescein Annexin V-FITC/PI double labeling. The protein and mRNA expression level of collagen type III, AdipoR1, and AdipoR2 were measured by Western blot and RT-PCR. APN treatment significantly decreased the lung fibrosis scores, protein and mRNA expression of pulmonary TGF-β1, CTGF and α-SMA content, and blood MMP-9 and TIMP-1 in a dose-dependent manner (p<0.05). Pretreatment with APN significantly attenuated the reduced cell viability and up-regulated collagen type III expression induced by PQ in lung fibroblasts, (p<0.05). APN pretreatment up-regulated AdipoR1, but not AdipoR2, expression in WI-38 fibroblasts. AdipoR1 siRNA abrogated APN-mediated protective effects in PQ-exposed fibroblasts. Taken together, our data suggests APN protects against PQ-induced pulmonary fibrosis in a dose

Pulmonary function recovery demonstrated by ventilation-perfusion scan after posterior vertebral column resection for severe adolescent idiopathic scoliosis: a case report.

PubMed

Fujii, Takeshi; Watanabe, Kota; Toyama, Yoshiaki; Matsumoto, Morio

2014-09-01

Case report. To describe a case in which a patient regained pulmonary function, assessed by ventilation-perfusion scans, after undergoing posterior vertebral column resection (VCR) to correct severe adolescent idiopathic scoliosis (AIS) with associated pulmonary dysfunction. Pulmonary improvement after corrective surgery for AIS has been reported. Ventilation-perfusion scans are useful for assessing pulmonary function. However, these scans have not been used to examine the recovery of pulmonary function after VCR for severe AIS with pulmonary dysfunction. A patient was described in whom ventilation-perfusion scans were used to examine improvements in impaired air ventilation and blood perfusion after VCR surgery for severe AIS. The relevant literature was reviewed. An 18-year-old male came to Keio University Hospital with exertional dyspnea associated with severe AIS. Radiographs showed severe scoliosis of 91° at T6-T12, and hypokyphosis of 6° at T5-T12. Computed tomographic scans showed narrowing of the thoracic cage on the convex side of the main thoracic curve, with the vertebral bodies at the apex of the curve obstructing the right main bronchus. Pulmonary function tests revealed a percent vital capacity of 44% and percent forced expiratory volume in 1 second of 76%. A ventilation-perfusion scan showed decreased air ventilation and blood perfusion in the right lung. The patient underwent posterior correction surgery, which used segmental pedicle screws with a VCR at T9. The scoliosis was corrected to 28°, and the kyphosis to 14°. Postoperative computed tomographic scans showed expansion of the right main bronchus. A ventilation-perfusion scan conducted 1 year after surgery showed clear improvement in both ventilation and blood perfusion in the right lung. The patient's forced expiratory volume in 1 second had increased to 91%. This is the first report in which ventilation-perfusion scans were used to examine improvements in impaired air ventilation and

Expression of Toll-like Receptor 2 and 4 in Peripheral Blood Neutrophil Cells from Patients with Chronic Obstructive Pulmonary Disease

PubMed Central

Tripathi, Prashant Mani; Kant, Surya; Yadav, Ravi Shanker; Kushwaha, Ram Awadh Singh; Prakash, Ved; Rizvi, Sayed Husian Mustafa; Parveen, Arshiya; Mahdi, Abbas Ali; Ahmad, Iqbal

2017-01-01

Objectives Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality around the world. Preliminary studies have evaluated the association between innate immunity including Toll-like receptors (TLRs) and airway samples of patients with COPD. The role of TLRs in peripheral blood neutrophils is poorly understood. Hence, this study aimed to investigate the role of TLR2 and TLR4 in peripheral blood neutrophils of COPD patients. Methods A total of 101 COPD cases and an equal number of healthy controls participated in this case-control study. Peripheral blood neutrophils were isolated from all participants and cultured for 24 hours through lipopolysaccharide (LPS) stimulation. The gene expressions of TLR2 and TLR4 were assessed by real-time polymerase chain reaction. The protein levels of interleukin (IL)-8 and matrix metalloproteinase (MMP)-9 were measured in neutrophils cell culture supernatants using enzyme-linked immunosorbent assay (ELISA). Results The levels of IL-8 and MMP-9 were significantly higher in patients with COPD compared to healthy controls. Similarly, the gene expression of TLR2 and TLR4 were increased in LPS stimulated peripheral blood neutrophils of patients with COPD. Smoke pack years was positively correlated with IL-8 levels and negatively correlated with forced expiratory volume in the first second % (r = -0.33; p = 0.023) and FEV1/forced vital capacity (FVC) (r = -0.27; p = 0.011). Conclusions The increased expression of TLR2 and TLR4 suggests its role in disease pathogenesis of COPD. Smoke pack years was negatively associated with spirometric parameters in COPD patients. This may help to predict the smokers without COPD who risk developing the condition in the future. PMID:29218124

Dysregulated renin-angiotensin-aldosterone system contributes to pulmonary arterial hypertension

PubMed Central

De Man, Frances; Tu, Ly; Handoko, Louis; Rain, Silvia; Ruiter, Gerrina; François, Charlène; Schalij, Ingrid; Dorfmüller, Peter; Simonneau, Gérald; Fadel, Elie; Perros, Frederic; Boonstra, Anco; Postmus, Piet; Van Der Velden, Jolanda; Vonk-Noordegraaf, Anton; Humbert, Marc; Eddahibi, Saadia; Guignabert, Christophe

2012-01-01

Rationale Patients with idiopathic pulmonary arterial hypertension (iPAH) often have a low cardiac output. To compensate, neurohormonal systems like renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system are upregulated but this may have long-term negative effects on the progression of iPAH. Objectives Assess systemic and pulmonary RAAS-activity in iPAH-patients and determine the efficacy of chronic RAAS-inhibition in experimental PAH. Measurements and Main Results We collected 79 blood samples from 58 iPAH-patients in the VU University Medical Center Amsterdam (between 2004–2010), to determine systemic RAAS-activity. We observed increased levels of renin, angiotensin (Ang) I and AngII, which was associated with disease progression (p<0.05) and mortality (p<0.05). To determine pulmonary RAAS-activity, lung specimens were obtained from iPAH-patients (during lung transplantation, n=13) and controls (during lobectomy or pneumonectomy for cancer, n=14). Local RAAS-activity in pulmonary arteries of iPAH-patients was increased, demonstrated by elevated ACE-activity in pulmonary endothelial cells and increased AngII type 1 (AT1) receptor expression and signaling. In addition, local RAAS- upregulation was associated with increased pulmonary artery smooth muscle cell proliferation via enhanced AT1-receptor signaling in iPAH-patients compared to controls. Finally, to determine the therapeutic potential of RAAS-activity, we assessed the chronic effects of an AT1-receptor antagonist (losartan) in the monocrotaline PAH-rat model (60 mg/kg). Losartan delayed disease progression, decreased RV afterload and pulmonary vascular remodeling and restored right ventricular-arterial coupling in PAH-rats. Conclusions Systemic and pulmonary RAAS-activities are increased in iPAH-patients and associated with increased pulmonary vascular remodeling. Chronic inhibition of RAAS by losartan is beneficial in experimental PAH. PMID:22859525

Pulmonary capillary pressure in pulmonary hypertension.

PubMed

Souza, Rogerio; Amato, Marcelo Britto Passos; Demarzo, Sergio Eduardo; Deheinzelin, Daniel; Barbas, Carmen Silvia Valente; Schettino, Guilherme Paula Pinto; Carvalho, Carlos Roberto Ribeiro

2005-04-01

Pulmonary capillary pressure (PCP), together with the time constants of the various vascular compartments, define the dynamics of the pulmonary vascular system. Our objective in the present study was to estimate PCPs and time constants of the vascular system in patients with idiopathic pulmonary arterial hypertension (IPAH), and compare them with these measures in patients with acute respiratory distress syndrome (ARDS). We conducted the study in two groups of patients with pulmonary hypertension: 12 patients with IPAH and 11 with ARDS. Four methods were used to estimate the PCP based on monoexponential and biexponential fitting of pulmonary artery pressure decay curves. PCPs in the IPAH group were considerably greater than those in the ARDS group. The PCPs measured using the four methods also differed significantly, suggesting that each method measures the pressure at a different site in the pulmonary circulation. The time constant for the slow component of the biexponential fit in the IPAH group was significantly longer than that in the ARDS group. The PCP in IPAH patients is greater than normal but methodological limitations related to the occlusion technique may limit interpretation of these data in isolation. Different disease processes may result in different times for arterial emptying, with resulting implications for the methods available for estimating PCP.

Interleukin-6 overexpression induces pulmonary hypertension.

PubMed

Steiner, M Kathryn; Syrkina, Olga L; Kolliputi, Narasaish; Mark, Eugene J; Hales, Charles A; Waxman, Aaron B

2009-01-30

Inflammatory cytokine interleukin (IL)-6 is elevated in the serum and lungs of patients with pulmonary artery hypertension (PAH). Several animal models of PAH cite the potential role of inflammatory mediators. We investigated role of IL-6 in the pathogenesis of pulmonary vascular disease. Indices of pulmonary vascular remodeling were measured in lung-specific IL-6-overexpressing transgenic mice (Tg(+)) and compared to wild-type (Tg(-)) controls in both normoxic and chronic hypoxic conditions. The Tg(+) mice exhibited elevated right ventricular systolic pressures and right ventricular hypertrophy with corresponding pulmonary vasculopathic changes, all of which were exacerbated by chronic hypoxia. IL-6 overexpression increased muscularization of the proximal arterial tree, and hypoxia enhanced this effect. It also reproduced the muscularization and proliferative arteriopathy seen in the distal arteriolar vessels of PAH patients. The latter was characterized by the formation of occlusive neointimal angioproliferative lesions that worsened with hypoxia and were composed of endothelial cells and T-lymphocytes. IL-6-induced arteriopathic changes were accompanied by activation of proangiogenic factor, vascular endothelial growth factor, the proproliferative kinase extracellular signal-regulated kinase, proproliferative transcription factors c-MYC and MAX, and the antiapoptotic proteins survivin and Bcl-2 and downregulation of the growth inhibitor transforming growth factor-beta and proapoptotic kinases JNK and p38. These findings suggest that IL-6 promotes the development and progression of pulmonary vascular remodeling and PAH through proproliferative antiapoptotic mechanisms.

Cocaine-induced pulmonary changes: HRCT findings *

PubMed Central

de Almeida, Renata Rocha; Zanetti, Gláucia; Souza, Arthur Soares; de Souza, Luciana Soares; Silva, Jorge Luiz Pereira e; Escuissato, Dante Luiz; Irion, Klaus Loureiro; Mançano, Alexandre Dias; Nobre, Luiz Felipe; Hochhegger, Bruno; Marchiori, Edson

2015-01-01

Abstract Objective: To evaluate HRCT scans of the chest in 22 patients with cocaine-induced pulmonary disease. Methods: We included patients between 19 and 52 years of age. The HRCT scans were evaluated by two radiologists independently, discordant results being resolved by consensus. The inclusion criterion was an HRCT scan showing abnormalities that were temporally related to cocaine use, with no other apparent causal factors. Results: In 8 patients (36.4%), the clinical and tomographic findings were consistent with "crack lung", those cases being studied separately. The major HRCT findings in that subgroup of patients included ground-glass opacities, in 100% of the cases; consolidations, in 50%; and the halo sign, in 25%. In 12.5% of the cases, smooth septal thickening, paraseptal emphysema, centrilobular nodules, and the tree-in-bud pattern were identified. Among the remaining 14 patients (63.6%), barotrauma was identified in 3 cases, presenting as pneumomediastinum, pneumothorax, and hemopneumothorax, respectively. Talcosis, characterized as perihilar conglomerate masses, architectural distortion, and emphysema, was diagnosed in 3 patients. Other patterns were found less frequently: organizing pneumonia and bullous emphysema, in 2 patients each; and pulmonary infarction, septic embolism, eosinophilic pneumonia, and cardiogenic pulmonary edema, in 1 patient each. Conclusions: Pulmonary changes induced by cocaine use are varied and nonspecific. The diagnostic suspicion of cocaine-induced pulmonary disease depends, in most of the cases, on a careful drawing of correlations between clinical and radiological findings. PMID:26398752

Genetic characterization of hantaviruses associated with sigmodontine rodents in an endemic area for hantavirus pulmonary syndrome in southern Brazil.

PubMed

de Oliveira, Renata Carvalho; Padula, Paula J; Gomes, Raphael; Martinez, Valeria P; Bellomo, Carla; Bonvicino, Cibele R; Freire e Lima, Danúbia Inês; Bragagnolo, Camila; Caldas, Antônio C S; D'Andrea, Paulo S; de Lemos, Elba R S

2011-03-01

An ecological assessment of reservoir species was conducted in a rural area (Jaborá) in the mid-west of the state of Santa Catarina in southern Brazil, where hantavirus pulmonary syndrome is endemic, to evaluate the prevalence of hantavirus infection in wild rodents. Blood and tissue samples were collected from 507 rodents during seven field trips from March 2004 to April 2006. Some of the animals were karyotyped to confirm morphological identification. Phylogenetic reconstructions of rodent specimens, based on the mitochondrial DNA cytochrome b gene sequences, were also obtained. Hantavirus antibody was found in 22 (4.3%) of the 507 rodents: 5 Akodon montensis, 2 Akodon paranaensis, 14 Oligoryzomys nigripes, and 1 Sooretamys angouya. Viral RNAs detected in O. nigripes and A. montensis were amplified and sequenced. O. nigripes virus genome was 97.5% (nt) and 98.4% (nt) identical to sequences published for Araucaria (Juquitiba-like) virus based on N and G2 fragment sequences. Viral sequences from A. montensis strain showed 89% and 88% nucleotide identities in a 905-nt fragment of the nucleocapsid (N) protein-coding region of the S segment when it was compared with two other Akodontine rodent-associated viruses from Paraguay, A. montensis and Akodon cursor, respectively. Phylogenetic analysis showed the cocirculation of two genetic hantavirus lineages in the state of Santa Catarina, one from O. nigripes and the other from A. montensis, previously characterized in Brazil and Paraguay, respectively. The hantavirus associated with A. montensis, designed Jaborá virus, represents a distinct phylogenetic lineage among the Brazilian hantaviruses.

[Clinical, biochemical and allergological indices characterizing occupational diseases of the bronchial and pulmonary system in employees at aluminium production].

PubMed

Kudaeva, I V; Dyakovich, O A; Beygel, E A; Masnavieva, L B; Naumova, O V; Budarina, L A

There are many harmful factors that possess a damaging impact on the body of employees at aluminum production. It leads to the development of bronchial asthma (BA), chronic nonobstructive bronchitis (CNB) and chronic obstructive pulmonary disease (COPD). The pathogenesis of these disorders, as well as sensitizing effect offluorine in the aluminum production is not fully understood. The purpose of this work was to study the characteristics of laboratory indices in patients with occupational diseases of the respiratory system. In workers of aluminum production with the diagnosis of occupational diseases of respiratory system (15 patients with a diagnosis of asthma, 30 CNB cases, 20 COPD patients) we evaluated the content of total protein, total cholesterol, high density lipoprotein cholesterol (HDLC), total calcium, phosphorus, ceruloplasmin, hematological indices and performed emigration of leukocytes braking test (TTEEL). Clinical and biochemical profile ofpersons with occupational asthma was characterized by a low level of total calcium and ceruloplasmin, a high concentration of phosphorus in the blood serum and inhibition of leukocyte emigration in the test with sodium fluoride. For aluminum production CNB workers characteristic active proatherogenic process was pronounced by a decrease in the HDLC level and an increase in atherogenic index; higher hematocrit value and concentration of erythrocytes, and more than 50% of cases of sensitization to the presence of sodium fluoride. COPD cases had occupational lower average concentration of hemoglobin in the erythrocyte, total protein in serum, as well as polymorphic variant response to sodium fluoride in the form of a depression and activation of leucocytes emigration.

Flexible microwave ablation applicator for the treatment of pulmonary malignancies

NASA Astrophysics Data System (ADS)

Pfannenstiel, Austin; Keast, Tom; Kramer, Steve; Wibowo, Henky; Prakash, Punit

2017-02-01

Microwave ablation (MWA) is an emerging minimally invasive treatment option for malignant lung tumors. Compared to other energy modalities, such as radiofrequency ablation, MWA offers the advantages of deeper penetration within high impedance tissues such as aerated lung, shorter treatment times, and less susceptibility to the cooling heat-sink effects of air and blood flow. Previous studies have demonstrated clinical use of MWA for treating lung tumors; however, these procedures have relied upon the percutaneous application of rigid microwave antennas. The objective of our work was to develop and characterize a novel flexible microwave applicator which could be integrated with a bronchoscopic imaging and software guidance platform to expand the use of MWA as a treatment option for small (< 2cm) pulmonary tumors. This applicator would allow physicians an even less invasive, immediate treatment option for lung tumors identified within the scope of current medical procedures. It may also improve applicator placement accuracy and increase efficacy while minimizing the risk of procedural complications. A 2D-axisymmetric coupled FEM electromagnetic-heat transfer model was implemented to characterize expected antenna radiation patterns, ablation size and shape, and optimize antenna design for lung tissue. A prototype device was fabricated and evaluated in ex vivo tissues to verify simulation results and serve as proof-of-concept. Additional experiments were conducted in an in vivo animal model to further characterize the proposed system.

REACTIVE OXYGEN AND NITROGEN SPECIES IN PULMONARY HYPERTENSION

PubMed Central

Tabima, Diana M.; Frizzell, Sheila; Gladwin, Mark T.

2013-01-01

Pulmonary vascular disease can be defined as either a disease affecting the pulmonary capillaries and pulmonary arterioles, termed pulmonary arterial hypertension, or as a disease affecting the left ventricle, called pulmonary venous hypertension. Pulmonary arterial hypertension (PAH) is a disorder of the pulmonary circulation characterized by endothelial dysfunction, as well as intimal and smooth muscle proliferation. Progressive increases in pulmonary vascular resistance and pressure impair the performance of the right ventricle, resulting in declining cardiac output, reduced exercise capacity, right heart failure, and ultimately death. While the primary and heritable forms of the disease are thought to affect over 5,000 patients in the U.S., the disease can occur secondary to congenital heart disease, most advanced lung diseases, and many systemic diseases. Multiple studies implicate oxidative stress in the development of PAH. Further, this oxidative stress has been shown to be associated with alterations in reactive oxygen species (ROS), reactive nitrogen species (RNS) and nitric oxide (NO) signaling pathways, whereby bioavailable NO is decreased and ROS and RNS production are increased. Many canonical ROS and NO signaling pathways are simultaneously disrupted in PAH, with increased expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and xanthine oxidoreductase, uncoupling of endothelial NO synthase (eNOS), and reduction in mitochondrial number, as well as impaired mitochondrial function. Upstream dysregulation of ROS/NO redox homeostasis impairs vascular tone and contributes to the pathological activation of anti-apoptotic and mitogenic pathways, leading to cell proliferation and obliteration of the vasculature. This manuscript will review the available data regarding the role of oxidative and nitrosative stress and endothelial dysfunction in the pathophysiology of pulmonary hypertension, and provide a description of targeted therapies

Omentin protects against LPS-induced ARDS through suppressing pulmonary inflammation and promoting endothelial barrier via an Akt/eNOS-dependent mechanism.

PubMed

Qi, Di; Tang, Xumao; He, Jing; Wang, Daoxin; Zhao, Yan; Deng, Wang; Deng, Xinyu; Zhou, Guoqi; Xia, Jing; Zhong, Xi; Pu, Shenglan

2016-09-08

Acute respiratory distress syndrome (ARDS) is characterized by increased pulmonary inflammation and endothelial barrier permeability. Omentin has been shown to benefit obesity-related systemic vascular diseases; however, its effects on ARDS are unknown. In the present study, the level of circulating omentin in patients with ARDS was assessed to appraise its clinical significance in ARDS. Mice were subjected to systemic administration of adenoviral vector expressing omentin (Ad-omentin) and one-shot treatment of recombinant human omentin (rh-omentin) to examine omentin's effects on lipopolysaccharide (LPS)-induced ARDS. Pulmonary endothelial cells (ECs) were treated with rh-omentin to further investigate its underlying mechanism. We found that a decreased level of circulating omentin negatively correlated with white blood cells and procalcitonin in patients with ARDS. Ad-omentin protected against LPS-induced ARDS by alleviating the pulmonary inflammatory response and endothelial barrier injury in mice, accompanied by Akt/eNOS pathway activation. Treatment of pulmonary ECs with rh-omentin attenuated inflammatory response and restored adherens junctions (AJs), and cytoskeleton organization promoted endothelial barrier after LPS insult. Moreover, the omentin-mediated enhancement of EC survival and differentiation was blocked by the Akt/eNOS pathway inactivation. Therapeutic rh-omentin treatment also effectively protected against LPS-induced ARDS via the Akt/eNOS pathway. Collectively, these data indicated that omentin protects against LPS-induced ARDS by suppressing inflammation and promoting the pulmonary endothelial barrier, at least partially, through an Akt/eNOS-dependent mechanism. Therapeutic strategies aiming to restore omentin levels may be valuable for the prevention or treatment of ARDS.

Gender, sex hormones and pulmonary hypertension

PubMed Central

Austin, Eric D.; Lahm, Tim; West, James; Tofovic, Stevan P.; Johansen, Anne Katrine; MacLean, Margaret R.; Alzoubi, Abdallah; Oka, Masahiko

2013-01-01

Most subtypes of pulmonary arterial hypertension (PAH) are characterized by a greater susceptibility to disease among females, although females with PAH appear to live longer after diagnosis. While this “estrogen paradoxȍ of enhanced female survival despite increased female susceptibility remains a mystery, recent progress has begun to shed light upon the interplay of sex hormones, the pathogenesis of pulmonary hypertension, and the right ventricular response to stress. For example, emerging data in humans and experimental models suggest that estrogens or differential sex hormone metabolism may modify disease risk among susceptible subjects, and that estrogens may interact with additional local factors such as serotonin to enhance the potentially damaging chronic effects of estrogens on the pulmonary vasculature. Regardless, it remains unclear why not all estrogenic compounds behave equally, nor why estrogens appear to be protective in certain settings but detrimental in others. The contribution of androgens and other compounds, such as dehydroepiandrosterone, to pathogenesis and possibly treatment must be considered as well. In this review, we will discuss the recent understandings on how estrogens, estrogen metabolism, dehydroepiandrosterone, and additional susceptibility factors may all contribute to the pathogenesis or potentially to the treatment of pulmonary hypertension, by evaluating current human, cell-based, and experimental model data. PMID:24015330

Eosinophilic and Neutrophilic Airway Inflammation in the Phenotyping of Mild-to-Moderate Asthma and Chronic Obstructive Pulmonary Disease.

PubMed

Górska, Katarzyna; Paplińska-Goryca, Magdalena; Nejman-Gryz, Patrycja; Goryca, Krzysztof; Krenke, Rafał

2017-04-01

Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases with different inflammatory phenotypes. Various inflammatory mediators play a role in these diseases. The aim of this study was to analyze the neutrophilic and eosinophilic airway and systemic inflammation as the phenotypic characterization of patients with asthma and COPD. Twenty-four patients with asthma and 33 patients with COPD were enrolled in the study. All the patients were in mild-to-moderate stage of disease, and none of them were treated with inhaled corticosteroids. Concentrations of IL-6, neutrophil elastase (NE), matrix metalloproteinase 9 (MMP-9), eosinophil cationic protein (ECP), and IL-33 and IL-17 in serum and induced sputum (IS) were measured by enzyme-linked immunosorbent assay (ELISA). The cellular composition of blood and IS was evaluated. Hierarchical clustering of patients was performed for the combination of selected clinical features and mediators. Asthma and COPD can be differentiated based on eosinophilic/neutrophilic systemic or airway inflammation with unsatisfactory efficiency. Hierarchical clustering of patients based on blood eosinophil percentage and clinical data revealed two asthma clusters differing in the number of positive skin prick tests and one COPD cluster with two subclusters characterized by low and high blood eosinophil concentrations. Clustering of patients according to IS measurements and clinical data showed two main clusters: pure asthma characterized by high eosinophil/atopy status and mixed asthma and COPD cluster with low eosinophil/atopy status. The neutrophilic phenotype of COPD was associated with more severe airway obstruction and hyperinflation.

Reversal of reflex pulmonary vasoconstriction induced by main pulmonary arterial distension.

PubMed

Juratsch, C E; Grover, R F; Rose, C E; Reeves, J T; Walby, W F; Laks, M M

1985-04-01

Distension of the main pulmonary artery (MPA) induces pulmonary hypertension, most probably by neurogenic reflex pulmonary vasoconstriction, although constriction of the pulmonary vessels has not actually been demonstrated. In previous studies in dogs with increased pulmonary vascular resistance produced by airway hypoxia, exogenous arachidonic acid has led to the production of pulmonary vasodilator prostaglandins. Hence, in the present study, we investigated the effect of arachidonic acid in seven intact anesthetized dogs after pulmonary vascular resistance was increased by MPA distention. After steady-state pulmonary hypertension was established, arachidonic acid (1.0 mg/min) was infused into the right ventricle for 16 min; 15-20 min later a 16-mg bolus of arachidonic acid was injected. MPA distension was maintained throughout the study. Although the infusion of arachidonic acid significantly lowered the elevated pulmonary vascular resistance induced by MPA distension, the pulmonary vascular resistance returned to control levels only after the bolus injection of arachidonic acid. Notably, the bolus injection caused a biphasic response which first increased the pulmonary vascular resistance transiently before lowering it to control levels. In dogs with resting levels of pulmonary vascular resistance, administration of arachidonic acid in the same manner did not alter the pulmonary vascular resistance. It is concluded that MPA distension does indeed cause reflex pulmonary vasoconstriction which can be reversed by vasodilator metabolites of arachidonic acid. Even though this reflex may help maintain high pulmonary vascular resistance in the fetus, its function in the adult is obscure.

High expression of high-mobility group box 1 in the blood and lungs is associated with the development of chronic obstructive pulmonary disease in smokers.

PubMed

Ko, Hsin-Kuo; Hsu, Wen-Hu; Hsieh, Chih-Cheng; Lien, Te-Cheng; Lee, Tzong-Shyuan; Kou, Yu Ru

2014-02-01

High-mobility group box 1 (HMGB1) is an important mediator in multiple pathological conditions, but the expression of HMGB1 in chronic obstructive pulmonary disease (COPD) has not yet been completely investigated. We aimed to analyze the relationship between HMGB1 expression in blood and lung tissue and the development of COPD. Twenty-eight patients admitted for single pulmonary surgical intervention were enrolled. The expression of HMGB1 in blood and lung tissue was evaluated by enzyme-linked immunosorbent assay analysis and immunohistochemistry stain, respectively. The study patients were divided into smokers with COPD (n = 11), smokers without COPD (n = 8) and non-smoker healthy controls (n = 9). Smokers with COPD compared with smokers without COPD and healthy controls were older in age, with lower post-bronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV1 /FVC) ratio (63.1 ± 5.5 vs 77.6 ± 3.6 and 84.5 ± 5.8, P < 0.001 and P < 0.001, respectively) and higher levels of plasma HMGB1 (93.2 ± 139.9 vs 7.3 ± 4.8 and 17.0 ± 19.6 ng/mL, P = 0.016 and P = 0.021, respectively). In smokers with COPD, the numbers and portion of HMGB1-expressing cells in epithelium and submucosal areas were significantly increased. Notably, plasma HMGB1 levels negatively correlated with post-bronchodilator FEV1 /FVC ratio (r = -0.585, P = 0.008) in smokers, but not in non-smokers. In smokers, high expression of HMGB1 in the blood and lungs is related to the lung function impairment and appears to be associated with the development of COPD. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

Application of image flow cytometry for the characterization of red blood cell morphology

NASA Astrophysics Data System (ADS)

Pinto, Ruben N.; Sebastian, Joseph A.; Parsons, Michael; Chang, Tim C.; Acker, Jason P.; Kolios, Michael C.

2017-02-01

Red blood cells (RBCs) stored in hypothermic environments for the purpose of transfusion have been documented to undergo structural and functional changes over time. One sign of the so-called RBC storage lesion is irreversible damage to the cell membrane. Consequently, RBCs undergo a morphological transformation from regular, deformable biconcave discocytes to rigid spheroechinocytes. The spherically shaped RBCs lack the deformability to efficiently enter microvasculature, thereby reducing the capacity of RBCs to oxygenate tissue. Blood banks currently rely on microscope techniques that include fixing, staining and cell counting in order to morphologically characterize RBC samples; these methods are labor intensive and highly subjective. This study presents a novel, high-throughput RBC morphology characterization technique using image flow cytometry (IFC). An image segmentation template was developed to process 100,000 images acquired from the IFC system and output the relative spheroechinocyte percentage. The technique was applied on samples extracted from two blood bags to monitor the morphological changes of the RBCs during in vitro hypothermic storage. The study found that, for a given sample of RBCs, the IFC method was twice as fast in data acquisition, and analyzed 250-350 times more RBCs than the conventional method. Over the lifespan of the blood bags, the mean spheroechinocyte population increased by 37%. Future work will focus on expanding the template to segregate RBC images into more subpopulations for the validation of the IFC method against conventional techniques; the expanded template will aid in establishing quantitative links between spheroechinocyte increase and other RBC storage lesion characteristics.

Pulmonary microvascular dysfunction and pathological changes induced by blast injury in a rabbit model.

PubMed

Wu, Si Yu; Han, Geng Fen; Kang, Jian Yi; Zhang, Liang Chao; Wang, Ai Min; Wang, Jian Min

2016-09-01

Vascular leakage has been proven to play a critical role in the incidence and development of explosive pulmonary barotrauma. Quantitatively investigated in the present study was the severity of vascular leakage in a gradient blast injury series, as well as ultrastructural evidence relating to pulmonary vascular leakage. One hundred adult male New Zealand white rabbits were randomly divided into 5 groups according to distance from the detonator (10 cm, 15 cm, 20 cm, 30 cm, and sham control). Value of pulmonary vascular leakage was monitored by a radioactive 125I-albumin labeling method. Pathological changes caused by the blast wave were examined under light and electron microscopes. Transcapillary escape rate of 125I-albumin and residual radioactivity in both lungs increased significantly at the distances of 10 cm, 15 cm, and 20 cm, suggesting increased severity of vascular leakage in these groups. Ultrastructural observation showed swelling of pulmonary capillary endothelial cells and widened gap between endothelial cells in the 10-cm and 15-cm groups. Primary blast wave can result in pulmonary capillary blood leakage. Blast wave can cause swelling of pulmonary capillary endothelial cells and widened gap between endothelial cells, which may be responsible for pulmonary vascular leakage.

Influence of physical preconditioning on the responsiveness of rat pulmonary artery after pulmonary ischemia/reperfusion.

PubMed

Delbin, Maria Andréia; Moraes, Camila; Camargo, Enilton; Mussi, Ricardo K; Antunes, Edson; de Nucci, Gilberto; Zanesco, Angelina

2007-07-01

The aim of this work was to evaluate the effect of physical preconditioning in the responsiveness of rat pulmonary rings submitted to lung ischemia/reperfusion (IR). Wistar rats were divided into three groups: Sedentary sham-operated (SD/SHAM); sedentary submitted to ischemia/reperfusion (SD/IR) and trained submitted to ischemia/reperfusion (TR/IR) animals. Exercise training consisted in sessions of 60 min/day running sessions, 5 days/week for 8 weeks. Left pulmonary IR was performed by occluding for 90 min and reperfusing for 120 min. After that, pulmonary arteries were isolated and concentration-response curves to acetylcholine (ACh), histamine (HIST), sodium nitroprusside (SNP), phenylephrine and U46619 were obtained. Neither potency (-log EC(50)) nor maximal responses (E(max)) were modified for ACh and HIST in all groups. On the other hand, the potency for SNP was significantly increased in TR/IR group (8.23+/-0.06) compared to SD/IR group (7.85+/-0.04). Contractile responses mediated by a-adrenergic receptor were markedly decreased in IR groups (SD/IR: 6.75+/-0.06 and TR/IR: 6.62+/-0.04) compared to SD/SHAM (7.33+/-0.05). No changes were seen for the U46619 in all groups. In conclusion, the present study shows that exercise training has no protective actions in the local blood vessel where the IR process takes place.

Pulmonary tuberculosis

MedlinePlus

TB; Tuberculosis - pulmonary; Mycobacterium - pulmonary ... Pulmonary TB is caused by the bacterium Mycobacterium tuberculosis (M tuberculosis) . TB is contagious. This means the bacteria is easily spread from an infected person ...

Pulmonary Rehabilitation

MedlinePlus

... as pulmonary hypertension and interstitial lung disease can benefit as well. What is Pulmonary Rehabilitation? Pulmonary rehabilitation is a program of education and exercise that helps you manage your breathing ...

Targeting of antibody-conjugated plasminogen activators to the pulmonary vasculature.