Sample records for aberrant systemic artery-pulmonary

  1. Endovascular Treatment of an Aneurysmal Aberrant Systemic Artery Supplying a Pulmonary Sequestrum

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

    Kristensen, Katrine Lawaetz, E-mail: klk@dadlnet.dk; Duus, Louise Aarup, E-mail: louise.brodersen@gmail.com; Elle, Bo, E-mail: Bo.Elle@rsyd.dk

    An aberrant systemic artery originating from the abdominal aorta supplying a pulmonary sequestration is a rare congenital malformation. This causes a left-to-left shunt. Symptoms include recurrent pneumonias, hemoptysis, and, in the long term, heart failure. Aneurysm of the aberrant vessel is rarely seen. Traditionally, treatment of pulmonary sequestrations includes ligation of the feeding vessel and lobectomy. A new promising treatment is an endovascular approach. Only a few cases describe endovascular treatment of pulmonary sequestration. This is the first published case of a giant aneurysmal branch from the abdominal aorta to the normal basal segments of the lung, successfully occluded withmore » an Amplatzer Vascular Plug II (AVP II, St.Jude Medical, MN, USA) alone.« less

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

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

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

    2006-10-15

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

  3. 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

  4. Mycotic pulmonary artery aneurysm following pulmonary artery banding.

    PubMed

    Kumar, R V; Roughneen, P T; de Leval, M R

    1994-01-01

    A neonate with situs inversus, transposition of the great arteries, ventricular septal defect, criss-cross ventricles and hypoplastic right ventricle underwent pulmonary artery banding at the age of 7 days. The course was complicated by septicaemia and subsequently the development of an aneurysm of the pulmonary artery. Serratia marcessans was grown from the band site. The pulmonary artery aneurysm was resected and the pulmonary artery was repaired. The literature is reviewed with the emphasis on diagnosis, natural history and surgical management.

  5. 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

  6. 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.

  7. 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

  8. A Case of Pulmonary Hypertension Due to Fistulas Between Multiple Systemic Arteries and the Right Pulmonary Artery in an Adult Discovered for Occulted Dyspnoea.

    PubMed

    Li, Ji-Feng; Zhai, Zhen-Guo; Kuang, Tu-Guang; Liu, Min; Ma, Zhan-Hong; Li, Yi-Dan; Yang, Yuan-Hua

    2017-08-01

    Pulmonary hypertension (PH) can be caused by a fistula between the systemic and pulmonary arteries. Here, we report a case of PH due to multiple fistulas between systemic arteries and the right pulmonary artery where the ventilation/perfusion scan showed no perfusion in the right lung. A 32-year-old male patient was hospitalised for community-acquired pneumonia. After treatment with antibiotics, the pneumonia was alleviated but dyspnoea persisted. Pulmonary hypertension was diagnosed using right heart catheterisation, which detected the mean pulmonary artery pressure as 37mmHg. The anomalies were confirmed by contrast-enhanced CT scan (CT pulmonary angiography), systemic arterial angiography and pulmonary angiography. Following embolisation of the largest fistula, the haemodynamics and oxygen dynamics did not improve, and even worsened to some extent. After supportive therapy including diuretics and oxygen, the patient's dyspnoea, WHO function class and right heart function by transthoracic echocardiography all improved during follow-up. Pulmonary hypertension can be present even when the right lung perfusion is lost. Closure of fistulas by embolisation, when those fistulas act as the proliferating vessels, may be harmful. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  9. Anomalous origin of circumflex coronary artery from right pulmonary artery in a hypoplastic left heart syndrome child

    PubMed Central

    Kansy, Andrzej; Łaniewski-Wołłk, Przemysław

    2014-01-01

    We describe the case of a newborn with hypoplastic left heart syndrome (HLHS) and aberrant origin of the circumflex coronary artery from the right pulmonary artery. The patient underwent a modified Norwood procedure with direct reimplantation of the circumflex coronary artery to the neo-aorta, but died on the 5th postoperative day because of myocardial failure. Detailed assessment of coronary arteries as part of the routine echocardiographic evaluation of HLHS and intraoperative inspection of them is crucial. PMID:26336423

  10. CXCL12-CXCR4 signalling plays an essential role in proper patterning of aortic arch and pulmonary arteries.

    PubMed

    Kim, Bo-Gyeong; Kim, Yong Hwan; Stanley, Edward L; Garrido-Martin, Eva M; Lee, Young Jae; Oh, S Paul

    2017-11-01

    Chemokine CXCL12 (stromal derived factor 1: SDF1) has been shown to play important roles in various processes of cardiovascular development. In recent avian studies, CXCL12 signalling has been implicated in guidance of cardiac neural crest cells for their participation in the development of outflow tract and cardiac septum. The goal of this study is to investigate the extent to which CXCL12 signalling contribute to the development of aortic arch and pulmonary arteries in mammals. Novel Cxcl12-LacZ reporter and conditional alleles were generated. Using whole mount X-gal staining with the reporter allele and vascular casting techniques, we show that the domain branching pattern of pulmonary arteries in Cxcl12-null mice is completely disrupted and discordant with that of pulmonary veins and airways. Cxcl12-null mice also displayed abnormal and superfluous arterial branches from the aortic arch. The early steps of pharyngeal arch remodelling in Cxcl12-null mice appeared to be unaffected, but vertebral arteries were often missing and prominent aberrant arteries were present parallel to carotid arteries or trachea, similar to aberrant vertebral artery or thyroid ima artery, respectively. Analysis with computed tomography not only confirmed the results from vascular casting studies but also identified abnormal systemic arterial supply to lungs in the Cxcl12-null mice. Tie2-Cre mediated Cxcr4 deletion phenocopied the Cxcl12-null phenotypes, indicating that CXCR4 is the primary receptor for arterial patterning, whereas Cxcl12 or Cxcr4 deletion by Wnt1-Cre did not affect aortic arch patterning. CXCL12-CXCR4 signalling is essential for the correct patterning of aortic arches and pulmonary arteries during development. Superfluous arteries in Cxcl12-null lungs and the aortic arch infer a role of CXCL12 in protecting arteries from uncontrolled sprouting during development of the arterial system. Published on behalf of the European Society of Cardiology. All rights reserved.

  11. Aberrant systemic arterial supply to normal lung arising from the proper hepatic artery discovered during transarterial chemoembolization.

    PubMed

    Walsworth, Matthew K; Yap, Felix Y; McWilliams, Justin P

    2015-11-01

    We report a rare case of dual arterial supply to an otherwise normal lung discovered incidentally during initial angiography performed with the intent of chemoembolization of hepatocellular carcinoma. In addition to normal hepatic arterial supply, the proper hepatic artery provided systemic arterial supply to the lower lobe of the left lung. Subsequent chest computed tomography angiography demonstrated a normal tracheobronchial tree and normal pulmonary arterial supply to the lung. Although other anatomic variants have been reported, there are no other reported cases of systemic arterial supply from the proper hepatic artery to the lung. Identifying systemic arterial supply to the lung during angiography is important while performing transcatheter chemoembolization or radioembolization in the liver in order to minimize non-target embolization of the lung.

  12. Beneficial Effects of Renal Denervation on Pulmonary Vascular Remodeling in Experimental Pulmonary Artery Hypertension.

    PubMed

    Qingyan, Zhao; Xuejun, Jiang; Yanhong, Tang; Zixuan, Dai; Xiaozhan, Wang; Xule, Wang; Zongwen, Guo; Wei, Hu; Shengbo, Yu; Congxin, Huang

    2015-07-01

    Activation of both the sympathetic nervous system and the renin-angiotensin-aldosterone system is closely associated with pulmonary arterial hypertension. We hypothesized that renal denervation decreases renin-angiotensin-aldosterone activity and inhibits the progression of pulmonary arterial hypertension. Twenty-two beagles were randomized into 3 groups. The dogs' pulmonary dynamics were measured before and 8 weeks after injection of 0.1mL/kg dimethylformamide (control dogs) or 2mg/kg dehydromonocrotaline (pulmonary arterial hypertension and pulmonary arterial hypertension + renal denervation dogs). Eight weeks after injection, neurohormone levels and pulmonary tissue morphology were measured. Levels of plasma angiotensin II and endothelin-1 were significantly increased after 8 weeks in the pulmonary arterial hypertension dogs and were higher in the lung tissues of these dogs than in those of the control and renal denervation dogs (mean [standard deviation] angiotensin II: 65 [9.8] vs 38 [6.7], 46 [8.1]; endothelin-1: 96 [10.3] vs 54 [6.2], 67 [9.4]; P < .01). Dehydromonocrotaline increased the mean pulmonary arterial pressure (16 [3.4] mmHg vs 33 [7.3] mmHg; P < .01), and renal denervation prevented this increase. Pulmonary smooth muscle cell proliferation was higher in the pulmonary arterial hypertension dogs than in the control and pulmonary arterial hypertension + renal denervation dogs. Renal denervation attenuates pulmonary vascular remodeling and decreases pulmonary arterial pressure in experimental pulmonary arterial hypertension. The effect of renal denervation may contribute to decreased neurohormone levels. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  13. 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.

  14. Hydronephrosis by an Aberrant Renal Artery: A Case Report

    PubMed Central

    Park, Byoung Seok; Jeong, Taek Kyun; Ma, Seong Kwon; Kim, Soo Wan; Kim, Nam Ho; Choi, Ki Chul; Jeong, Yong Yeon

    2003-01-01

    Ureteropelvic junction obstruction is usually intrinsic and is most common in children. Aberrant renal arteries are present in about 30% of individuals. Aberrant renal arteries to the inferior pole cross anteriorly to the ureter and may cause hydronephrosis. To the best of our knowledge, although there are some papers about aberrant renal arteries producing ureteropelvic junction obstruction, there is no report of a case which is diagnosed by the new modalities, such as computed tomography angiogram (CTA) or magnetic resonance angiogram (MRA). We describe a 36-year-old woman with right hydronephrosis. Kidney ultrasonogram and excretory urogram revealed right hydronephrosis. CTA and MRA clearly displayed an aberrant renal artery and hydronephrosis. The patient underwent surgical exploration. For the evaluation of hydronephrosis by an aberrant renal artery, use of CTA and MRA is advocated. PMID:12760271

  15. 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.

  16. [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.

  17. 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 ...

  18. 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

  19. Update in pulmonary arterial hypertension.

    PubMed

    Mejía Chew, C R; Alcolea Batres, S; Ríos Blanco, J J

    2016-11-01

    Pulmonary arterial hypertension is a rare and progressive disease that mainly affects the pulmonary arterioles (precapillary), regardless of the triggering aetiology. The prevalence of pulmonary hypertension and pulmonary arterial hypertension in Spain is estimated at 19.2 and 16 cases per million inhabitants, respectively. The diagnosis of pulmonary arterial hypertension is based on haemodynamic criteria (mean pulmonary artery pressure ≥25mmHg, pulmonary capillary wedge pressure ≤15mmHg and pulmonary vascular resistance >3 Wood units) and therefore requires the implementation of right cardiac catheterisation. Sequential therapy with a single drug has been used in clinical practice. However, recent European guidelines recommend combined initial therapy in some situations. This review conducts a critical update of our knowledge of this disease according to the latest guidelines and recommendations. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  20. 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 ...

  1. 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.

  2. Clopidogrel in infants with systemic-to-pulmonary-artery shunts.

    PubMed

    Wessel, David L; Berger, Felix; Li, Jennifer S; Dähnert, Ingo; Rakhit, Amit; Fontecave, Sylvie; Newburger, Jane W

    2013-06-20

    Infants with cyanotic congenital heart disease palliated with placement of a systemic-to-pulmonary-artery shunt are at risk for shunt thrombosis and death. We investigated whether the addition of clopidogrel to conventional therapy reduces mortality from any cause and morbidity related to the shunt. In a multicenter, double-blind, event-driven trial, we randomly assigned infants 92 days of age or younger with cyanotic congenital heart disease and a systemic-to-pulmonary-artery shunt to receive clopidogrel at a dose of 0.2 mg per kilogram of body weight per day (467 infants) or placebo (439 infants), in addition to conventional therapy (including aspirin in 87.9% of infants). The primary efficacy end point was a composite of death or heart transplantation, shunt thrombosis, or performance of a cardiac procedure due to an event considered to be thrombotic in nature before 120 days of age. The rate of the composite primary end point did not differ significantly between the clopidogrel group (19.1%) and the placebo group (20.5%) (absolute risk difference, 1.4 percentage points; relative risk reduction with clopidogrel, 11.1%; 95% confidence interval, -19.2 to 33.6; P=0.43), nor did the rates of the three components of the composite primary end point. There was no significant benefit of clopidogrel treatment in any subgroup, including subgroups defined by shunt type. Clopidogrel recipients and placebo recipients had similar rates of overall bleeding (18.8% and 20.2%, respectively) and severe bleeding (4.1% and 3.4%, respectively). Clopidogrel therapy in infants with cyanotic congenital heart disease palliated with a systemic-to-pulmonary-artery shunt, most of whom received concomitant aspirin therapy, did not reduce either mortality from any cause or shunt-related morbidity. (Funded by Sanofi-Aventis and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00396877.).

  3. Emergent total arch replacement for acute type A aortic dissection with aberrant right subclavian artery in a systemic lupus erythematosus patient.

    PubMed

    Kitamura, Hideki; Kimura, Arishige; Fukaya, Shunsuke; Okawa, Yasuhide; Komeda, Masashi

    2016-01-01

    A 50-year-old man with a history of systemic lupus erythematosus and hemodialysis developed acute type A aortic dissection. Computed tomography demonstrated acute type A aortic dissection with chronic distal arch aneurysm and aberrant right subclavian artery that arose from the proximal descending aorta and ran in a retro-esophageal track. Emergent total arch replacement was performed using antegrade cerebral perfusion with circulatory arrest. Both common carotid arteries and the left subclavian artery were chosen as selective cerebral perfusion sites. The right subclavian artery was snared during cerebral perfusion. The right subclavian artery was reconstructed with the right common carotid artery in an end-to-side fashion in the anterior mediastinum. The patient's postoperative course was uneventful, and computed tomography showed excellent blood flow to all four branches. The case description is followed by a discussion of cerebral protection, reconstruction route of the right aberrant subclavian artery and steroids for systemic lupus erythematosus.

  4. Coronary artery to pulmonary artery fistula.

    PubMed

    Dadkhah-Tirani, Heidar; Salari, Arsalan; Shafighnia, Shora; Hosseini, Seyed Fazel; Naghdipoor, Misa

    2013-01-01

    Male, 69 FINAL DIAGNOSIS: Coronary artery to pulmonary artery fistula Symptoms: Chest pain Medication: - Clinical Procedure: Echocardiography • angiography • surgical intervention Specialty: Cardiology • Cardiac Surgery. Rare disease. A coronary artery fistula is an abnormal communication between a coronary artery and one of the cardiac chambers or a great vessel, so bypassing the myocardial capillary network. They are usually discovered incidentally upon coronary angiography. Clinical manifestations are variable depending on the type of fistula, the severity of shunt, site of shunt, and presence of other cardiac condition. We report a 69-year-old man without any previous medical history, who was admitted to our hospital with chest pain. The electrocardiogram (ECG) showed a sinus rhythm with ST depression in V2 to V6 precordial leads. Coronary angiography revealed a coronary artery fistula from left anterior descending coronary artery (LAD) to the main pulmonary artery, right coronary artery blockage and significant stenoses on the LAD and left circumflex artery (LCX). Surgical treatment was chosen because of the total occlusion of the right coronary artery and to relieve of pain to improve quality of life.

  5. Ethyl pyruvate inhibits hypoxic pulmonary vasoconstriction and attenuates pulmonary artery cytokine expression

    PubMed Central

    Tsai, Ben M.; Lahm, Tim; Morrell, Eric D.; Crisostomo, Paul R.; Markel, Troy; Wang, Meijing; Meldrum, Daniel R.

    2009-01-01

    Hypoxic pulmonary vasoconstriction is a common consequence of acute lung injury and may be mediated by increased local production of proinflammatory cytokines. Ethyl pyruvate is a novel anti-inflammatory agent that has been shown to downregulate proinflammatory genes following hemorrhagic shock; however, its effects on hypoxic pulmonary vasoconstriction are unknown. We hypothesized that ethyl pyruvate would inhibit hypoxic pulmonary vasoconstriction and downregulate pulmonary artery cytokine expression during hypoxia. To study this, isometric force displacement was measured in isolated rat pulmonary artery rings (n=8/group) during hypoxia (95% N2/5% CO2) with or without prior ethyl pyruvate (10 mM) treatment. Following 60 minutes of hypoxia, pulmonary artery rings were analyzed for TNF-α and IL-1 mRNA via RT-PCR. Ethyl pyruvate inhibited hypoxic pulmonary artery contraction (4.49±2.32% vs. 88.80±5.68% hypoxia alone) and attenuated the hypoxic upregulation of pulmonary artery TNF and IL-1 mRNA (p<0.05). These data indicate that: 1) hypoxia increases pulmonary artery vasoconstriction and proinflammatory cytokine gene expression; 2) ethyl pyruvate decreases hypoxic pulmonary vasoconstriction and downregulates hypoxia-induced pulmonary artery proinflammatory cytokine gene expression; and 3) ethyl pyruvate may represent a novel therapeutic adjunct in the treatment of acute lung injury. PMID:17574585

  6. Resection-Reconstruction of Aberrant Right Hepatic Artery During Whipple Procedure (Pancreaticoduodenectomy).

    PubMed

    Sayyed, Raza; Rehman, Iffat; Niazi, Imran Khalid; Yusuf, Muhammed Aasim; Syed, Aamir Ali; V, Faisal

    2016-06-01

    Aberrant hepatic arterial anatomy poses a challenge for the surgeon during Whipple procedure. Intraoperative injury to the aberrant vasculature results in hemorrhagic or ischemic complications involving the liver and biliary tree. We report a case of replaced right hepatic artery arising from the superior mesenteric artery in a patient with periampullary carcinoma of the pancreas, undergoing pancreaticoduodenectomy. The aberrant artery was found to be coursing through the pancreatic parenchyma. This is a rare vascular anomaly. Resection of the arterial segment and end-to-end anastomosis was fashioned. Intrapancreatic course of the replaced right hepatic artery is a rare anomaly and is best managed by preoperative identification on radiology and meticulous intra-operative dissection and preservation. However, for an intrapancreatic course, resection and reconstruction may occasionally be required.

  7. [Pulmonary arterial hypertension in intensive care unit and operating room].

    PubMed

    Kerbaul, F; Rondelet, B; Collart, F; Naeije, R; Gouin, F

    2005-05-01

    To review the perioperative anaesthetic management of pulmonary arterial hypertension. Extraction from Pubmed database of French and English articles on the perioperative anaesthetic management of pulmonary hypertension for 9 years. The collected articles were reviewed and selected according their quality and originality. The more recent data were selected. Pulmonary arterial hypertension is classically divided in primary and secondary. Primary pulmonary hypertension (familial and sporadic) is relatively severe and rare. Muscularization of the terminal portion of the pulmonary vascular arterial tree, caused by smooth muscle cell hyperplasia is the first change. Pulmonary arterial hypertension linked with disorders of the respiratory system and hypoxemia or pulmonary venous hypertension including mitral valve disease and chronic left ventricular dysfunction are often associated with high morbidity and mortality. The main consequence of pulmonary hypertension development is the occurrence of right-sided circulatory failure. A better understanding of disease pathophysiology will contribute to the development of new therapies increasing then the prognosis of these patients. The management of primary pulmonary hypertension or secondary pulmonary arterial hypertension is a challenge for the anaesthesiologist because the risk of right ventricular failure is markedly increased.

  8. Management of pulmonary arterial hypertension with a focus on combination therapies.

    PubMed

    Benza, Raymond L; Park, Myung H; Keogh, Anne; Girgis, Reda E

    2007-05-01

    Pulmonary arterial hypertension (PAH) is a rare but frequently fatal condition marked by vasoconstriction and vascular remodeling within small pulmonary arteries. The pathobiology of PAH involves imbalances in a multitude of endogenous mediators, which promote aberrant cellular growth, vasoconstriction and hemostasis within the pulmonary vascular tree. The mechanisms promoting these pathologic effects are complex. This complexity is highlighted by the many overlapping secondary messenger systems through which these mediators work. In light of this natural redundancy, it is not surprising that many of the drugs used to treat PAH, which have shown short-term efficacy, fall "short of the mark" in reversing or halting the progression of this disease in the long run. This very redundancy in pathways makes the case for the use of combination of drugs with differing mechanisms of action to treat PAH. Similar to what is now accepted as the standard of care for the treatment of cancer and left ventricular dysfunction, combination therapy has the greatest promise for inducing the most complete vascular remodeling of the pulmonary vasculature by "shutting down" as many of these pathologic pathways as possible. Combination therapies involving existing therapies or new agents with improved pharmacokinetic and/or pharmacodynamic properties represent an emerging clinical paradigm for patients with sub-optimally managed disease. As emerging data in this field of therapy comes to fruition, further reductions in the morbidity and mortality associated with PAH will manifest. The goal of this report is to review the philosophy of combination therapy and present the available data in this area of study.

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

    PubMed

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

    2007-01-01

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

  10. Pulmonary arterial hypertension in children: diagnosis using ratio of main pulmonary artery to ascending aorta diameter as determined by multi-detector computed tomography.

    PubMed

    Caro-Domínguez, Pablo; Compton, Gregory; Humpl, Tilman; Manson, David E

    2016-09-01

    The ratio of the transverse diameter of the main pulmonary artery (MPA) to ascending aorta as determined at multi-detector CT is a tool that can be used to assess the pulmonary arterial size in cases of pulmonary arterial hypertension in children. To establish a ratio of MPA to ascending aorta diameter using multi-detector CT imaging suggestive of pulmonary arterial hypertension in children. We hypothesize that a defined ratio of MPA to ascending aorta is identifiable on multi-detector CT and that higher ratios can be used to reliably diagnose the presence of pulmonary arterial hypertension in children. We calculated the multi-detector CT ratio of MPA to ascending aorta diameter in 44 children with documented pulmonary arterial hypertension by right heart catheterization and in 44 age- and gender-matched control children with no predisposing factors for pulmonary arterial hypertension. We compared this multi-detector-CT-determined ratio with the MPA pressure in the study group, as well as with the ratio of MPA to ascending aorta in the control group. A threshold ratio value was calculated to accurately identify children with pulmonary arterial hypertension. Children with documented primary pulmonary arterial hypertension have a significantly higher ratio of MPA to ascending aorta (1.46) than children without pulmonary arterial hypertension (1.11). A ratio of 1.3 carries a positive likelihood of 34 and a positive predictive value of 97% for the diagnosis of pulmonary arterial hypertension. The pulmonary arteries were larger in children with pulmonary arterial hypertension than in a control group of normal children. A CT-measured ratio of MPA to ascending aorta of 1.3 should raise the suspicion of pulmonary arterial hypertension in children.

  11. Pulmonary Arterial Hypertension and Neonatal Arterial Switch Surgery for Correction of Transposition of the Great Arteries.

    PubMed

    Domínguez Manzano, Paula; Mendoza Soto, Alberto; Román Barba, Violeta; Moreno Galdó, Antonio; Galindo Izquierdo, Alberto

    2016-09-01

    There are few reports of the appearance of pulmonary arterial hypertension following arterial switch surgery in the neonatal period to correct transposition of the great arteries. We assessed the frequency and clinical pattern of this complication in our series of patients. Our database was reviewed to select patients with transposition of the great arteries corrected by neonatal arterial switch at our hospital and who developed pulmonary hypertension over time. We identified 2 (1.3%) patients with transposition of the great arteries successfully repaired in the first week of life who later experienced pulmonary arterial hypertension. The first patient was a 7-year-old girl diagnosed with severe pulmonary hypertension at age 8 months who did not respond to medical treatment and required lung transplantation. The anatomic pathology findings were consistent with severe pulmonary arterial hypertension. The second patient was a 24-month-old boy diagnosed with severe pulmonary hypertension at age 13 months who did not respond to medical therapy. Pulmonary hypertension is a rare but very severe complication that should be investigated in all patients with transposition of the great arteries who have undergone neonatal arterial switch, in order to start early aggressive therapy for affected patients, given the poor therapeutic response and poor prognosis involved. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  12. Systemic Artery to Pulmonary Vein Fistula After Right Upper Lobectomy Demonstrated by 4-Dimensional Flow Magnetic Resonance Imaging.

    PubMed

    Legras, Antoine; Azarine, Arshid; Poitier, Bastien; Messas, Emmanuel; Le Pimpec-Barthes, Françoise

    2017-08-01

    Postoperative systemic artery to pulmonary vein fistula is very rare. In this report, we describe an exceptional condition of both intrapulmonary arteriovenous fistula and systemic artery to pulmonary vein fistula, involving all right hemithoracic systemic arteries, inducing left-to-left shunt. This condition was responsible for heart failure, 24 years after a right upper lobectomy for inflammatory tumor. Investigations included computed tomographic angiography, arteriography, and four-dimensional flow magnetic resonance imaging. Differential diagnosis and management are discussed. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  13. Systemic Sclerosis-Associated Pulmonary Arterial Hypertension

    PubMed Central

    Chaisson, Neal F.

    2013-01-01

    Pulmonary arterial hypertension (PAH) is the leading cause of death in systemic sclerosis (SSc) and affects up to 12% of all patients with SSc, with a 50% mortality rate within 3 years of PAH diagnosis. Compared with the idiopathic form of PAH (IPAH), patients with SSc-associated PAH (SSc-PAH) have a threefold increased risk of death and may receive a diagnosis late in the course of disease because of insidious onset and the high prevalence of cardiac, musculoskeletal, and pulmonary parenchymal comorbidities. Treatment with conventional forms of PAH therapy often yield poor results compared with IPAH cohorts; unfortunately, the exact reasons behind this remain poorly understood but likely include variations in the pathologic mechanisms, differences in cardiovascular response to increasing afterload, and inadequate strategies to detect and treat SSc-PAH early in its course. Current methods for screening and longitudinal evaluation of SSc-PAH, such as the 6-min walk test, transthoracic echocardiography, and MRI, each have notable advantages and disadvantages. We provide an up-to-date, focused review of SSc-PAH and how it differs from IPAH, including pathogenesis, appropriate screening for disease onset, and new approaches to treatment and longitudinal assessment of this disease. PMID:24081346

  14. Role of secretory phospholipase A(2) in rhythmic contraction of pulmonary arteries of rats with monocrotaline-induced pulmonary arterial hypertension.

    PubMed

    Tanabe, Yoshiyuki; Saito-Tanji, Maki; Morikawa, Yuki; Kamataki, Akihisa; Sawai, Takashi; Nakayama, Koichi

    2012-01-01

    Excessive stretching of the vascular wall in accordance with pulmonary arterial hypertension (PAH) induces a variety of pathogenic cellular events in the pulmonary arteries. We previously reported that indoxam, a selective inhibitor for secretory phospholipase A(2) (sPLA(2)), blocked the stretch-induced contraction of rabbit pulmonary arteries by inhibition of untransformed prostaglandin H(2) (PGH(2)) production. The present study was undertaken to investigate involvement of sPLA(2) and untransformed PGH(2) in the enhanced contractility of pulmonary arteries of experimental PAH in rats. Among all the known isoforms of sPLA(2), sPLA(2)-X transcript was most significantly augmented in the pulmonary arteries of rats with monocrotaline-induced pulmonary hypertension (MCT-PHR). The pulmonary arteries of MCT-PHR frequently showed two types of spontaneous contraction in response to stretch; 27% showed rhythmic contraction, which was sensitive to indoxam and SC-560 (selective COX-1 inhibitor), but less sensitive to NS-398 (selective COX-2 inhibitor); and 47% showed sustained incremental tension (tonic contraction), which was insensitive to indoxam and SC-560, but sensitive to NS-398 and was attenuated to 45% of the control. Only the rhythmically contracting pulmonary arteries of MCT-PHR produced a substantial amount of untransformed PGH(2), which was abolished by indoxam. These results suggest that sPLA(2)-mediated PGH(2) synthesis plays an important role in the rhythmic contraction of pulmonary arteries of MCT-PHR.

  15. 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.

  16. Pedunculated Pulmonary Artery Sarcoma Suggested by Transthoracic Echocardiography.

    PubMed

    Wang, Xiaobing; Ren, Weidong; Yang, Jun

    2016-04-01

    Pulmonary artery sarcoma (PAS) is an extremely rare malignancy. It is usually found after it grows large enough to occupy almost the entire lumen of the pulmonary artery and causes serious clinical symptoms. Thus, it is usually difficult to distinguish PAS from pulmonary thromboembolism based on imaging examinations. Few case reports had shown the attachment of PAS to pulmonary artery, a key characteristic for diagnosis, and differential diagnosis of PAS. In this case, we found a PAS, which did not cause local obstruction and some tumor emboli, which obstructed the branches of the pulmonary arteries and caused pulmonary hypertension and clinical symptoms. Transthoracic echocardiography (TTE) revealed a part of the tumor attached to the intima of the main pulmonary artery with a peduncle and had obvious mobility, which was suggestive of PAS and differentiated it from the pulmonary thromboembolism. To our knowledge, this is the first case report of a pedunculated PAS suggested by TTE. Combined with pulmonary artery computed tomography angiography, the diagnosis of PAS is strongly suggested before the operation. This case indicates that TTE could reveal the attachment and mobility of PAS in the main pulmonary and may provide useful information for the diagnosis and differential diagnosis of PAS, especially a pedunculated PAS. © 2015, Wiley Periodicals, Inc.

  17. Single origin of right and left pulmonary arteries from ascending aorta with atretic main pulmonary artery from right ventricle and left pulmonary sling.

    PubMed

    Hsieh, Min-Ling; Huang, Li-Ting; Wang, Jieh-Neng; Tsai, Yi-Shan

    2015-01-01

    Either left pulmonary sling or single origin of right and left pulmonary arteries (only three cases reported previously) are rare congenital heart anomalies and concomitantly occurred had not been reported. The image presentation is similar to type A1 truncus arteriosus but preserved pulmonary valve and main pulmonary artery development. Copyright © 2015 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

  18. Evaluation of the Microcirculation in Chronic Thromboembolic Pulmonary Hypertension Patients: The Impact of Pulmonary Arterial Remodeling on Postoperative and Follow-Up Pulmonary Arterial Pressure and Vascular Resistance.

    PubMed

    Jujo, Takayuki; Sakao, Seiichiro; Ishibashi-Ueda, Hatsue; Ishida, Keiichi; Naito, Akira; Sugiura, Toshihiko; Shigeta, Ayako; Tanabe, Nobuhiro; Masuda, Masahisa; Tatsumi, Koichiro

    2015-01-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is generally recognized to be caused by persistent organized thrombi that occlude the pulmonary arteries. The aim of this study was to investigate the characteristics of small vessel remodeling and its impact on the hemodynamics in CTEPH patients. Hemodynamic data were obtained from right heart catheterization in 17 CTEPH patients before pulmonary endarterectomy (PEA). Lung tissue specimens were obtained at the time of PEA. Pathological observations and evaluation of quantitative changes in pulmonary muscular arteries and veins were performed using light microscopy on 423 slides in 17 patients. The relationship between the results and the hemodynamics of CTEPH was investigated. Pulmonary arteriopathy and venopathy were recognized in most cases, although no plexiform lesions and no capillary-hemangiomatosis-like lesions were detected in any of the specimens. The severity of pulmonary arteriopathy was correlated with pulmonary vascular resistance (PVR) in the postoperative and follow-up periods. The PVR and mean pulmonary arterial pressure were significantly higher in the high-obstruction group than in the low-obstruction group. The findings in pulmonary venopathy were similar to the findings seen in pulmonary veno-occlusive disease in some cases, although severe venopathy was only observed in a portion of the pulmonary veins. There was a significant correlation between the extent of pulmonary arteriopathy and venopathy, although an effect of pulmonary venopathy to hemodynamics, including pulmonary arterial wedged pressure (PAWP), could not be identified. The vascular remodeling of the pulmonary muscular arteries was closely associated with the hemodynamics of CTEPH. Severe pulmonary arteriopathy might be related to residual pulmonary hypertension after PEA. Those altered pulmonary arteries might be a new target for the persistent PH after the operation.

  19. Wave Intensity Analysis Provides Novel Insights Into Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension.

    PubMed

    Su, Junjing; Manisty, Charlotte; Parker, Kim H; Simonsen, Ulf; Nielsen-Kudsk, Jens Erik; Mellemkjaer, Soren; Connolly, Susan; Lim, P Boon; Whinnett, Zachary I; Malik, Iqbal S; Watson, Geoffrey; Davies, Justin E; Gibbs, Simon; Hughes, Alun D; Howard, Luke

    2017-10-31

    In contrast to systemic hypertension, the significance of arterial waves in pulmonary hypertension (PH) is not well understood. We hypothesized that arterial wave energy and wave reflection are augmented in PH and that wave behavior differs between patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Right heart catheterization was performed using a pressure and Doppler flow sensor-tipped catheter to obtain simultaneous pressure and flow velocity measurements in the pulmonary artery. Wave intensity analysis was subsequently applied to the acquired data. Ten control participants, 11 patients with PAH, and 10 patients with CTEPH were studied. Wave speed and wave power were significantly greater in PH patients compared with controls, indicating increased arterial stiffness and right ventricular work, respectively. The ratio of wave power to mean right ventricular power was lower in PAH patients than CTEPH patients and controls. Wave reflection index in PH patients (PAH: ≈25%; CTEPH: ≈30%) was significantly greater compared with controls (≈4%), indicating downstream vascular impedance mismatch. Although wave speed was significantly correlated to disease severity, wave reflection indexes of patients with mildly and severely elevated pulmonary pressures were similar. Wave reflection in the pulmonary artery increased in PH and was unrelated to severity, suggesting that vascular impedance mismatch occurs early in the development of pulmonary vascular disease. The lower wave power fraction in PAH compared with CTEPH indicates differences in the intrinsic and/or extrinsic ventricular load between the 2 diseases. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  20. Contemporary management of aberrant right subclavian arteries.

    PubMed

    Stone, William M; Ricotta, Joseph J; Fowl, Richard J; Garg, Nitin; Bower, Thomas C; Money, Samuel R

    2011-05-01

    Aberrant origin of right subclavian arteries represents the most common of the aortic arch anomalies. This variant has few published series to guide management. Our goal was to review treatment options and results for these potentially complex reconstructions. A retrospective review was performed on all patients with a diagnosis of aberrant right subclavian artery at our institution between January 2003 and July 2009. A total of 24 patients, which comprises one of the largest series reported, including 10 males and 14 females (mean age: 46.6 years, range: 7-77), were diagnosed with an aberrant right subclavian artery. Sixteen (66%) were diagnosed incidentally, but eight (33%) had symptoms of either dysphagia, upper extremity ischemia, or both. Computed tomography was most commonly used to establish the diagnosis (19 patients, 79%). Magnetic resonance imaging established the diagnosis in three patients (12%), upper gastrointestinal barium study in one (4%), and standard angiography in one (4%). A Kommerell's diverticulum (KD) was the most common associated anomaly (seven patients, 29%). All seven patients (100%) with a KD required intervention for either symptoms or aneurysmal degeneration. Intervention was performed in 10 patients (42%), including carotid subclavian bypass in five (50%), carotid subclavian transposition in three (30%), and ascending aorta to subclavian bypass in two (20%). Four patients (40%) had additional intervention for management of aneurysmal disease of the aorta or KD, with open aortic replacement in two (20%) and aortic endografting in two (20%). There was one perioperative death (10%) in a patient undergoing aortic arch debranching with placement of an aortic endograft. In all, 18 patients survived without symptoms after a mean follow-up of 38 months. Aberrant right subclavian arteries are most commonly found incidentally with computed tomography. The presence of a KD seemed to correlate with the need for intervention. Patients with no

  1. 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

  2. Evaluation of the Microcirculation in Chronic Thromboembolic Pulmonary Hypertension Patients: The Impact of Pulmonary Arterial Remodeling on Postoperative and Follow-Up Pulmonary Arterial Pressure and Vascular Resistance

    PubMed Central

    Ishida, Keiichi; Naito, Akira; Sugiura, Toshihiko; Shigeta, Ayako; Tanabe, Nobuhiro; Masuda, Masahisa; Tatsumi, Koichiro

    2015-01-01

    Background Chronic thromboembolic pulmonary hypertension (CTEPH) is generally recognized to be caused by persistent organized thrombi that occlude the pulmonary arteries. The aim of this study was to investigate the characteristics of small vessel remodeling and its impact on the hemodynamics in CTEPH patients. Methods and Results Hemodynamic data were obtained from right heart catheterization in 17 CTEPH patients before pulmonary endarterectomy (PEA). Lung tissue specimens were obtained at the time of PEA. Pathological observations and evaluation of quantitative changes in pulmonary muscular arteries and veins were performed using light microscopy on 423 slides in 17 patients. The relationship between the results and the hemodynamics of CTEPH was investigated. Pulmonary arteriopathy and venopathy were recognized in most cases, although no plexiform lesions and no capillary-hemangiomatosis-like lesions were detected in any of the specimens. The severity of pulmonary arteriopathy was correlated with pulmonary vascular resistance (PVR) in the postoperative and follow-up periods. The PVR and mean pulmonary arterial pressure were significantly higher in the high-obstruction group than in the low-obstruction group. The findings in pulmonary venopathy were similar to the findings seen in pulmonary veno-occlusive disease in some cases, although severe venopathy was only observed in a portion of the pulmonary veins. There was a significant correlation between the extent of pulmonary arteriopathy and venopathy, although an effect of pulmonary venopathy to hemodynamics, including pulmonary arterial wedged pressure (PAWP), could not be identified. Conclusion The vascular remodeling of the pulmonary muscular arteries was closely associated with the hemodynamics of CTEPH. Severe pulmonary arteriopathy might be related to residual pulmonary hypertension after PEA. Those altered pulmonary arteries might be a new target for the persistent PH after the operation. PMID:26252755

  3. Pulmonary arterial capacitance in children with idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with congenital heart disease: relation to pulmonary vascular resistance, exercise capacity, and survival.

    PubMed

    Sajan, Imran; Manlhiot, Cedric; Reyes, Janette; McCrindle, Brian W; Humpl, Tilman; Friedberg, Mark K

    2011-09-01

    Pediatric pulmonary arterial hypertension (PAH), whether idiopathic PAH (iPAH) or PAH associated with congenital heart disease (aPAH), carries high morbidity and mortality. Low pulmonary arterial capacitance (PAC), defined as right ventricular stroke volume/pulmonary artery pulse pressure, is a risk factor for mortality in adults with PAH. However, the relation of PAC to pulmonary vascular resistance (PVR), exercise endurance, and survival is poorly defined in children. Catheterization and clinical data of children with PAH (mean pulmonary artery pressure >25 mm Hg) were reviewed. Children with pulmonary shunts, stents, collaterals, or pulmonary venous hypertension were excluded. Primary outcomes were 6-minute walk distance and freedom from death/lung transplant. Forty-seven patients were studied. Nineteen (43%) had iPAH, and 28 (57%) had aPAH (7.1 ± 6.2 vs 8.4 ± 5.5 years, P = .45). Patients with iPAH had higher PVR indexed for body surface area (PVRi), lower indexed PAC (PACi), lower exercise tolerance, and lower freedom from death/lung transplant than patients with aPAH. Both higher PVRi (P < .0001) and lower PACi (P = .02) were associated with shorter 6-minute walk distance. A PACi <0.70 mL/mm Hg per square meter or >1.25 mL/mm Hg per square meter and a PVRi >13 Wood units × m(2) were associated with decreased freedom from death or lung transplant. The relationships between PVRi and PACi and survival were independent of each other and not confounded by etiologic group. Low PACi and high PVRi are independently associated with low 6-minute walk distance and survival in children with PAH. Therefore, both should be assessed for better prognostication and management in this high-risk population. Copyright © 2011 Mosby, Inc. All rights reserved.

  4. [The effect of calcitonin gene-related peptide on collagen accumulation in pulmonary arteries of rats with hypoxic pulmonary arterial hypertension].

    PubMed

    Li, Xian-Wei; Du, Jie; Li, Yuan-Jian

    2013-03-01

    To observe the effect of calcitonin gene-related peptide (CGRP) on pulmonary vascular collagen accumulation in hypoxia rats in order to study the effect of CGRP on hypoxic pulmonary vascular structural remodeling and its possible mechanism. Rats were acclimated for 1 week, and then were randomly divided into three groups: normoxia group, hypoxia group, and hypoxia plus capsaicin group. Pulmonary arterial hypertension was induced by hypoxia in rats. Hypoxia plus capsaicin group, rats were given capsaicin (50 mg/(kg x d), s.c) 4 days before hypoxia to deplete endogenous CGRP. Hypoxia (3% O2) stimulated proliferation of pulmonary arterial smooth muscle cells (PASMCs) and proliferation was measured by BrdU marking. The expression levels of CGRP, phosphorylated ERK1/2 (p-ERK1/ 2), collagen I and collagen III were detected by real-time PCR or Western blot. Right ventricle systolic pressure (RVSP) and mean pulmonary arterial pressure (mPAP) of pulmonary arterial hypertension (PAH) rats induced by hypoxia were higher than those of normoxia rats. By HE and Masson staining, it was demonstrated that hypoxia also significantly induced hypertrophy of pulmonary arteries and increased level of collagen accumulation. Hypoxia dramatically decreased the CGRP level and increased the expression of p-ERK1/2, collagen I, collagen III in pulmonary arteries. All these effects of hypoxia were further aggravated by pre-treatment of rats with capsaicin. CGRP concentration-dependently inhibited hypoxia-induced proliferation of PASMCs, markedly decreased the expression of p-ERK1/2, collagen I and collagen III. All these effects of CGRP were abolished in the presence of CGRP8-37. These results suggest that CGRP might inhibit hypoxia-induced PAH and pulmonary vascular remodeling, through inhibiting phosphorylation of ERK1/2 and alleviating the collagen accumulation of pulmonary arteries.

  5. Aggressive Surgical Resection of Pulmonary Artery Intimal Sarcoma.

    PubMed

    Yamamoto, Yoko; Shintani, Yasushi; Funaki, Soichiro; Taira, Masaki; Ueno, Takayoshi; Kawamura, Tomohiro; Kanzaki, Ryu; Minami, Masato; Sawa, Yoshiki; Okumura, Meinoshin

    2018-05-03

    Intimal sarcoma of the pulmonary artery is a rare and highly malignant neoplasm. We herein report a case of a 30-year-old woman with an extensive right pulmonary artery tumor who underwent an emergent operation. The tumor was aggressively resected with right pneumonectomy and reconstruction of the right ventricle outflow tract and left pulmonary artery. Although the resected margin at the left pulmonary artery was positive, as confirmed by Mouse double minute type 2 homolog staining, she is doing well and remains free of relapse at 16 months after the operation. Copyright © 2018. Published by Elsevier Inc.

  6. The pulmonary artery catheter: a critical reappraisal.

    PubMed

    Gidwani, Umesh K; Mohanty, Bibhu; Chatterjee, Kanu

    2013-11-01

    Balloon floatation pulmonary artery catheters (PACs) have been used for hemodynamic monitoring in cardiac, medical, and surgical intensive care units since the 1970s. With the availability of newer noninvasive diagnostic modalities, particularly echocardiography, the frequency of diagnostic pulmonary artery catheterization has declined. In this review, the evolution of PACs, the results of nonrandomized and randomized studies in various clinical conditions, the uses and abuses of bedside hemodynamic monitoring, and current indications for pulmonary artery catheterization are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Absent right common carotid artery associated with aberrant right subclavian artery.

    PubMed

    Uchino, Akira; Uwabe, Kazuhiko; Osawa, Iichiro

    2018-06-01

    Rarely, the external and internal carotid arteries arise separately from the brachiocephalic trunk and right subclavian artery (SA) or the aortic arch and reflect the absence of a common carotid artery (CCA). We report a 45-year-old man with absent right CCA associated with aberrant right SA, an extremely rare combination, diagnosed by computed tomography (CT) angiography during follow-up for postoperative aortic dissection. Retrospective careful observation of preoperative postcontrast CT revealed the absent right CCA. Previously reported arch variations associated with absent CCA include cervical aortic arch, double aortic arch, and right aortic arch.

  8. 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

  9. Pulmonary artery aneurysm and thrombosis in active tuberculous consolidation.

    PubMed

    Jemshad, A; Ahammed, Shameem; Abdulla, Mansoor C; Musambil, Mohthash

    2015-07-01

    Tuberculosis continues to remain challenging with a variety of complications. We report the case of a 58-year-old female who developed pulmonary artery aneurysm with intra-arterial thrombus as a complication of active tuberculosis. Even though there are reports of pulmonary artery aneurysm in tuberculous cavity, pulmonary artery aneurysm and intra-arterial thrombus in active tuberculosis are very rare. Copyright © 2015 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

  10. 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.

  11. Tamoxifen Therapy to Treat Pulmonary Arterial Hypertension

    ClinicalTrials.gov

    2018-05-16

    Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Primary Pulmonary Hypertension; Lung Diseases; Tamoxifen; Estrogen Receptor Antagonist; Hormone Antagonists; Estrogens

  12. Continuous recording of pulmonary artery pressure in unrestricted subjects.

    PubMed Central

    Ikram, H; Richards, A M; Hamilton, E J; Nicholls, M G

    1984-01-01

    Continuous ambulatory pulmonary artery pressures were recorded using a conventional No 5 French Goodale-Lubin filled catheter linked to the Oxford Medilog system of a portable transducer-perfusion unit and miniaturised recorder. Data retrieval and analysis were performed using a PB2 Medilog playback unit linked to a PDP 11 computer system. The total system has a frequency response linear to 8 Hz allowing accurate pressure recording over the full range of heart rates. Ten recordings in 10 patients yielded artefact free data for 80% or more of the recorded period. This inexpensive reliable method allows pulmonary artery pressures to be recorded in unrestricted subjects. Images PMID:6704262

  13. 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.

  14. 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

  15. Combination of rare right arterial variation with anomalous origins of the vertebral artery, aberrant subclavian artery and persistent trigeminal artery. A case report.

    PubMed

    Ishihara, H; San Millán Ruíz, D; Abdo, G; Asakura, F; Yilmaz, H; Lovblad, K O; Rüfenacht, D A

    2011-09-01

    A 32-year-old woman hospitalized for subarachnoid hemorrhage showed rare arterial variation on the right side with anomalous origins of the vertebral artery, aberrant subclavian artery and persistent trigeminal artery. Angiography showed the right vertebral artery to originate from the right common carotid artery, the right subclavian artery to arise separately from the descending aorta, and persistent trigeminal artery on the right side. The possible embryonic mechanism of this previously unreported variant combination is discussed.

  16. Pulmonary arterial hypertension in schistosomiasis.

    PubMed

    Gavilanes, Francisca; Fernandes, Caio J C; Souza, Rogerio

    2016-09-01

    Schistosomiasis is one of the most prevalent parasitic diseases in the world, being present in more than 70 countries. Pulmonary hypertension is one of the several chronic complications of schistosomiasis; particularly in developing countries, schistosomiasis-associated pulmonary arterial hypertension might represent one of the most prevalent causes of pulmonary arterial hypertension. New epidemiological data reinforce the importance of schistosomiasis in the context of pulmonary hypertension; furthermore, the inflammatory components of the pathophysiology of pulmonary hypertension associated with schistosomiasis have been recently explored, opening the perspective of new targets to be explored. Clinical and hemodynamic features of this particular complication of schistosomiasis, and the role of targeted therapies in this setting, have been better described in recent years. The importance of schistosomiasis-associated pulmonary hypertension is now recognized with better knowledge about its pathophysiology and management. Nevertheless, there is a need for better understanding the predisposal factors (genetic, environmental and so on) for the development of pulmonary hypertension in schistosomiasis as a way to prevent it from occurring. Furthermore, better control programs to decrease disease transmission are still missing, ensuring that we will have to face this devastating complication of schistosomiasis for a long future.

  17. [Pulmonary involvement in systemic sclerosis. Alveolitis, fibrosis and pulmonar arterial hypertension].

    PubMed

    Navarro, Carmen

    2006-11-01

    Pulmonary involvement in systemic sclerosis. Alveolitis, fibrosis and pulmonar arterial hypertension Lung disease is present in most of the patients with systemic sclerosis and is now the most important cause of mortality. Interstitial lung disease and pulmonary hypertension are, so far, the main disorders found and both are difficult to detect at the earliest stages. However, diagnostic tools such as immunological test, lung function test, high resolution CT, bronchoalveolar lavage, echocardiography, right-side cardiac catheterization, or lung biopsy are necessary to accurately evaluate the clinical status and allow to improve the management organ-specific ad hoc. Progress in immunological and vascular therapies as well as other emergence drugs offer new expectations to scleroderma patients. Copyright © 2006 Elsevier España S.L. Barcelona. Published by Elsevier Espana. All rights reserved.

  18. A review of wave mechanics in the pulmonary artery with an emphasis on wave intensity analysis

    PubMed Central

    Su, Junjing; Hilberg, Ole; Howard, Luke; Simonsen, Ulf; Hughes, Alun D

    2016-01-01

    Mean pulmonary arterial pressure and pulmonary vascular resistance remain the most common hemodynamic measures to evaluate the severity and prognosis of pulmonary hypertension. However, pulmonary vascular resistance only captures the non-oscillatory component of the right ventricular hydraulic load and neglects the dynamic compliance of the pulmonary arteries and the contribution of wave transmission. Wave intensity analysis offers an alternative way to assess the pulmonary vasculature in health and disease. Wave speed is a measure of arterial stiffness and the magnitude and timing of wave reflection provide information on the degree of impedance mismatch between the proximal and distal circulation. Studies in the pulmonary artery have demonstrated distinct differences in arterial wave propagation between individuals with and without pulmonary vascular disease. Notably, greater wave speed and greater wave reflection are observed in patients with pulmonary hypertension and in animal models exposed to hypoxia. Studying wave propagation makes a valuable contribution to the assessment of the arterial system in pulmonary hypertension and here, we briefly review the current state of knowledge of the methods used to evaluate arterial waves in the pulmonary artery. PMID:27636734

  19. Determinants of exercise-induced pulmonary arterial hypertension in systemic sclerosis.

    PubMed

    Voilliot, Damien; Magne, Julien; Dulgheru, Raluca; Kou, Seisyou; Henri, Christine; Laaraibi, Saloua; Sprynger, Muriel; Andre, Béatrice; Pierard, Luc A; Lancellotti, Patrizio

    2014-05-15

    Exercise-induced pulmonary arterial hypertension (EIPH) in systemic sclerosis (SSc) has already been observed but its determinants remain unclear. The aim of this study was to determine the incidence and the determinants of EIPH in SSc. We prospectively enrolled 63 patients with SSc (age 54±3years, 76% female) followed in CHU Sart-Tilman in Liège. All patients underwent graded semi-supine exercise echocardiography. Systolic pulmonary arterial pressure (sPAP) was derived from the peak velocity of the tricuspid regurgitation jet and adding the estimation of right atrial pressure, both at rest and during exercise. Resting pulmonary arterial hypertension (PH) was defined as sPAP > 35 mmHg and EIPH as sPAP > 50 mmHg during exercise. The following formulas were used: mean PAP (mPAP) = 0.61 × sPAP + 2, left atrial pressure (LAP)=1.9+1.24 × left ventricular (LV) E/e' and pulmonary vascular resistance (PVR)=(mPAP-LAP)/LV cardiac output (CO) and slope of mPAP-LVCO relationship=changes in mPAP/changes in LVCO. Resting PH was present in 3 patients (7%) and 21 patients developed EIPH (47%). Patients with EIPH had higher resting LAP (10.3 ± 2.2 versus 8.8 ± 2.3 mmHg; p = 0.03), resting PVR (2.6 ± 0.8 vs. 1.4 ± 1.1 Woods units; p=0.004), exercise LAP (13.3 ± 2.3 vs. 9 ± 1.7 mmHg; p < 0.0001), exercise PVR (3.6 ± 0.7 vs. 2.1 ± 0.9 Woods units; p = 0.02) and slope of mPAP-LVCO (5.8 ± 2.4 vs. 2.9 ± 2.1 mmHg/L/min; p < 0.0001). After adjustment for age and gender, exercise LAP (β=3.1 ± 0.8; p=0.001) and exercise PVR (β=7.9 ± 1.7; p=0.0001) were independent determinants of exercise sPAP. EIPH is frequent in SSc patients and is mainly related to both increased exercise LV filling pressure and exercise PVR. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. A review of wave mechanics in the pulmonary artery with an emphasis on wave intensity analysis.

    PubMed

    Su, J; Hilberg, O; Howard, L; Simonsen, U; Hughes, A D

    2016-12-01

    Mean pulmonary arterial pressure and pulmonary vascular resistance (PVR) remain the most common haemodynamic measures to evaluate the severity and prognosis of pulmonary hypertension. However, PVR only captures the non-oscillatory component of the right ventricular hydraulic load and neglects the dynamic compliance of the pulmonary arteries and the contribution of wave transmission. Wave intensity analysis offers an alternative way to assess the pulmonary vasculature in health and disease. Wave speed is a measure of arterial stiffness, and the magnitude and timing of wave reflection provide information on the degree of impedance mismatch between the proximal and distal circulation. Studies in the pulmonary artery have demonstrated distinct differences in arterial wave propagation between individuals with and without pulmonary vascular disease. Notably, greater wave speed and greater wave reflection are observed in patients with pulmonary hypertension and in animal models exposed to hypoxia. Studying wave propagation makes a valuable contribution to the assessment of the arterial system in pulmonary hypertension, and here, we briefly review the current state of knowledge of the methods used to evaluate arterial waves in the pulmonary artery. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  1. Pulmonary Artery Pseudoaneurysm Secondary to Lung Inf lammation.

    PubMed

    Ishimoto, Shinichirou; Sakurai, Hiroyuki; Higure, Ryouta; Kawachi, Riken; Shimamura, Mie

    2018-01-15

    Pulmonary artery aneurysms (PAA) and pseudoaneurysms (PAP) are caused by infections, vasculitis, trauma, pulmonary hypertension, congenital heart disease, and connective tissue disease. Most cases of such aneurysm occur in the trunk or major branches of the pulmonary artery, while the peripheral type is less common. The treatment modalities are medical therapy, surgery, and percutaneous catheter embolization. The mortality rate associated with rupture is approximately 50%. We encountered a case of a 53-year-old man with a pulmonary artery pseudoaneurysm secondary to pneumonia and cavity formation during chemotherapy for acute myeloid leukemia (AML). In diagnosis, contrast-enhanced chest computed tomography (CT) scan and pulmonary angiography were very useful. He was treated with right middle and lower lobectomy. After 1-month follow-up, he could restart additional chemotherapy.

  2. Imaging of acute traumatic aortic tear in patients with an aberrant right subclavian artery.

    PubMed

    Haesemeyer, S W; Gavant, M L

    1999-01-01

    This report describes the radiologic findings and discusses the clinical consequences of acute traumatic aortic tear occurring with an aberrant right subclavian artery. Identification of an aberrant right subclavian artery with acute traumatic aortic tear must be emphasized to reduce iatrogenic morbidity and mortality.

  3. 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

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

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

    Iwazawa, Jin, E-mail: iwazawa.jin@nissay-hp.or.j; Nakamura, Kenji; Hamuro, Masao

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

  5. Anomalous right coronary artery arising from the pulmonary artery and constrictive pericarditis: an unusual association

    PubMed Central

    Silvestre, Odilson Marcos; Adam, Eduardo Leal; de Melo, Dirceu Thiago Pessoa; Dias, Ricardo Ribeiro; Ramires, Felix J. A.; Mady, Charles

    2013-01-01

    ABSTRACT The association of anomalous right coronary artery originating from the pulmonary artery and constrictive pericarditis has never been showed in the literature. We present the first case of this unusual association in a patient with right heart failure. After diagnosis, the patient was referred to surgery and underwent phrenic-to-phrenic pericardiectomy; graft implant of right internal thoracic artery to right coronary artery; and ligation of the anomalous origin of the right coronary artery from the pulmonary artery. Such procedures solved the potential risk of sudden death related to anomalous right coronary artery originating from the pulmonary artery and alleviated the symptoms of heart failure caused by constrictive pericarditis. PMID:24136766

  6. Dasatinib-induced pulmonary arterial hypertension - A rare late complication.

    PubMed

    Ibrahim, Uroosa; Saqib, Amina; Dhar, Vidhya; Odaimi, Marcel

    2018-01-01

    Dasatinib is a dual Src/Abl tyrosine kinase inhibitor approved for frontline and second line treatment of chronic phase chronic myelogenous leukemia. Pulmonary arterial hypertension is defined by an increase in mean pulmonary arterial pressure >25 mmHg at rest. Dasatinib-induced pulmonary hypertension has been reported in less than 1% of patients on chronic dasatinib treatment for chronic myelogenous leukemia. The pulmonary arterial hypertension from dasatinib may be categorized as either group 1 (drug-induced) or group 5 based on various mechanisms that may be involved including the pathogenesis of the disease process of chronic myelogenous leukemia. There have been reports of dasatinib-induced pulmonary arterial hypertension being reversible. We report a case of pulmonary arterial hypertension in a 46-year-old female patient with chronic phase chronic myelogenous leukemia on dasatinib treatment for over 10 years. She had significant improvement in symptoms after discontinuation of dasatinib and initiation of vasodilators. Several clinical questions arise once patients experience significant adverse effects as discussed in our case.

  7. A case of systemic arterial supply to the right lower lobe of the lung: imaging findings and review of the literature.

    PubMed

    Mautone, Marcela; Naidoo, Parm

    2014-03-01

    Systemic arterialization of the lung without pulmonary sequestration is the rarest form of anomalous systemic arterial supply to the lung. This condition is characterised by an aberrant arterial branch arising from the aorta which supplies an area of lung parenchyma with normal bronchopulmonary anatomy. It is often diagnosed following investigation of an incidental cardiac murmur or based on abnormal imaging, as most patients are asymptomatic or minimally symptomatic. Thoracic computed tomography and computed tomography angiography are generally the most useful diagnostic tests. We present a case of a 22-year old female who was diagnosed with systemic arterial supply to a portion of otherwise normal right lower lobe following investigation of low volume haemoptysis.

  8. Fetal Diagnosis of Abnormal Origin of the Left Pulmonary Artery.

    PubMed

    Tretter, Justin T; Tretter, Eric M; Rafii, Daniela Y; Anderson, Robert H; Bhatla, Puneet

    2016-08-01

    Isolated anomalies of the branch pulmonary arteries are rare, more often occurring in the setting of complex congenital heart disease. These isolated anomalies are often not identified in the prenatal period. We describe two cases of isolated anomalies of the left pulmonary artery which were identified on fetal echocardiography and confirmed postnatally, an anomalous left pulmonary artery arising from the base of the left-sided brachiocephalic artery in the setting of a right-sided aortic arch, and a left pulmonary artery sling. These two cases support our current understanding of normal and abnormal development of the extrapericardial arterial vessels and highlight the importance of meticulous attention when sweeping from the three-vessel tracheal view. © 2016, Wiley Periodicals, Inc.

  9. Translocation of an Aberrant Right Subclavian Artery With Resolution of Dysphagia Lusoria.

    PubMed

    Thompson, Jess L; Burkhart, Harold M

    2016-07-01

    The presence of a left aortic arch with an aberrant right subclavian artery is a well-described anatomic variant that rarely causes symptoms. When symptoms of dysphagia lusoria do occur, however, operative intervention may be necessary. The purpose of this report is to describe our preferred surgical approach to treat dysphagia lusoria secondary to an aberrant right subclavian artery. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  10. Effect of hypothermic pulmonary artery flushing on capillary filtration coefficient.

    PubMed

    Andrade, R S; Wangensteen, O D; Jo, J K; Tsai, M Y; Bolman, R M

    2000-07-27

    We previously demonstrated that surfactant dilution and inhibition occur immediately after pulmonary artery flushing with hypothermic modified Euro-Collins solution. Consequently, we speculated that increased capillary permeability contributed to these surfactant changes. To test this hypothesis, we evaluated the effects of hypothermic pulmonary artery flushing on the pulmonary capillary filtration coefficient (Kfc), and additionally performed a biochemical analysis of surfactant. We used a murine isolated, perfused lung model to measure the pulmonary capillary filtration coefficient and hemodynamic parameters, to determine the wet to dry weight ratio, and to evaluate surfactant by biochemical analysis of lung lavage fluid. We defined three study groups. In group I (controls), we harvested lungs without hypothermic pulmonary artery flushing, and measured Kfc immediately. In group II (in situ flush), we harvested lungs after hypothermic pulmonary artery flushing with modified Euro-Collins solution, and then measured Kfc. Experiments in groups I and II were designed to evaluate persistent changes in Kfc after pulmonary artery flushing. In group III (ex vivo flush), we flushed lungs ex vivo to evaluate transient changes in Kfc during hypothermic pulmonary artery flushing. Groups I and II did not differ significantly in capillary filtration coefficient and hemodynamics. Group II showed significant alterations on biochemical surfactant analysis and a significant increase in wet-to-dry weight ratio, when compared with group I. In group III, we observed a significant transient increase in capillary filtration coefficient during pulmonary artery flushing. Hypothermic pulmonary artery flushing transiently increases the capillary filtration coefficient, leads to an increase in the wet to dry weight ratio, and induces biochemical surfactant changes. These findings could be explained by the effects of hypothermic modified Euro-Collins solution on pulmonary capillary

  11. 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.

  12. Pulmonary arterial hypertension

    PubMed Central

    2013-01-01

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

  13. Histopathology of the great vessels in patients with pulmonary arterial hypertension in association with congenital heart disease: large pulmonary arteries matter too.

    PubMed

    Prapa, Matina; McCarthy, Karen P; Dimopoulos, Konstantinos; Sheppard, Mary N; Krexi, Dimitra; Swan, Lorna; Wort, S John; Gatzoulis, Michael A; Ho, Siew Yen

    2013-10-03

    Pulmonary arterial hypertension (PAH) is considered primarily a disease of the distal pulmonary arteries whereas little is known on the effect of long-standing pulmonary hypertension on the larger proximal pulmonary arteries. This study aims to investigate the structural changes in the great arteries of adults who developed PAH in association with congenital heart disease (CHD), with severe cases termed Eisenmenger syndrome. We performed macroscopic and light microscopy analyses on the great arteries of 10 formalin-fixed human hearts from patients with PAH/CHD and compared them to age-matched healthy controls. A detailed histology grading score was used to assess the severity of medial wall abnormalities. Severe atherosclerotic lesions were found macroscopically in the elastic pulmonary arteries of 4 PAH/CHD specimens and organised thrombi in 3; none were present in the controls. Significant medial wall abnormalities were present in the pulmonary trunk (PT), including fibrosis (80%), and atypical elastic pattern (80%). Cyst-like formations were present in less than one third of patients and were severe in a single case leading to wall rupture. The cumulative PT histology grading score was significantly higher in PAH/CHD cases compared to controls (p<0.0001) and correlated positively with larger PT diameters (ρ=0.812, p<0.0001) and the degree of medial wall hypertrophy (ρ=0.749, p<0.0001). Chronic PAH in association with CHD results in marked macroscopic and histological abnormalities in the large pulmonary arteries. These abnormalities are likely to affect haemodynamics and contribute to morbidity and mortality in this cohort. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Role of Hypoxia-Induced Brain Derived Neurotrophic Factor in Human Pulmonary Artery Smooth Muscle

    PubMed Central

    Hartman, William; Helan, Martin; Smelter, Dan; Sathish, Venkatachalem; Thompson, Michael; Pabelick, Christina M.; Johnson, Bruce; Prakash, Y. S.

    2015-01-01

    Background Hypoxia effects on pulmonary artery structure and function are key to diseases such as pulmonary hypertension. Recent studies suggest that growth factors called neurotrophins, particularly brain-derived neurotrophic factor (BDNF), can influence lung structure and function, and their role in the pulmonary artery warrants further investigation. In this study, we examined the effect of hypoxia on BDNF in humans, and the influence of hypoxia-enhanced BDNF expression and signaling in human pulmonary artery smooth muscle cells (PASMCs). Methods and Results 48h of 1% hypoxia enhanced BDNF and TrkB expression, as well as release of BDNF. In arteries of patients with pulmonary hypertension, BDNF expression and release was higher at baseline. In isolated PASMCs, hypoxia-induced BDNF increased intracellular Ca2+ responses to serotonin: an effect altered by HIF1α inhibition or by neutralization of extracellular BDNF via chimeric TrkB-Fc. Enhanced BDNF/TrkB signaling increased PASMC survival and proliferation, and decreased apoptosis following hypoxia. Conclusions Enhanced expression and signaling of the BDNF-TrkB system in PASMCs is a potential mechanism by which hypoxia can promote changes in pulmonary artery structure and function. Accordingly, the BDNF-TrkB system could be a key player in the pathogenesis of hypoxia-induced pulmonary vascular diseases, and thus a potential target for therapy. PMID:26192455

  15. Pulmonary artery relative area change detects mild elevations in pulmonary vascular resistance and predicts adverse outcome in pulmonary hypertension.

    PubMed

    Swift, Andrew J; Rajaram, Smitha; Condliffe, Robin; Capener, Dave; Hurdman, Judith; Elliot, Charlie; Kiely, David G; Wild, Jim M

    2012-10-01

    The aim of this study was to evaluate the clinical use of magnetic resonance imaging measurements related to pulmonary artery stiffness in the evaluation of pulmonary hypertension (PH). A total of 134 patients with suspected PH underwent right heart catheterization (RHC) and magnetic resonance imaging on a 1.5-T scanner within 2 days. Phase contrast imaging at the pulmonary artery trunk and cine cardiac views were acquired. Pulmonary artery area change (AC), relative AC (RAC), compliance (AC/pulse pressure from RHC), distensibility (RAC/pulse pressure from RHC), right ventricular functional indices, and right ventricular mass were all derived. Regression curve fitting identified the statistical model of best fit between RHC measurements and pulmonary artery stiffness indices. The diagnostic accuracy and prognostic value of noninvasive AC and RAC were also assessed. The relationship between pulmonary vascular resistance and pulmonary artery RAC was best reflected by an inverse linear model. Patients with mild elevation in pulmonary vascular resistance (<4 Woods units) demonstrated reduced RAC (P = 0.02) and increased right ventricular mass index (P < 0.0001) without significant loss of right ventricular function (P = 0.17). At follow-up of 0 to 40 months, 18 patients with PH had died (16%). Analysis of Kaplan-Meier plots showed that both AC and RAC predicted mortality (log-rank test, P = 0.046 and P = 0.012, respectively). Area change and RAC were also predictors of mortality using univariate Cox proportional hazards regression analysis (P = 0.046 and P = 0.03, respectively). Noninvasive assessment of pulmonary artery RAC is a marker sensitive to early increased vascular resistance in PH and is a predictor of adverse outcome.

  16. Variations of pulmonary arteries and other associated defects in Tetralogy of Fallot.

    PubMed

    Sheikh, Abdul Malik; Kazmi, Uzma; Syed, Najam Hyder

    2014-01-01

    The objective of study was to determine pulmonary artery variations and other associated cardiac defects in patients with Tetralogy of Fallot. This cross-sectional, descriptive study was carried out at The Children's Hospital and the Institute of Child Health, Lahore, from January 2006 to December 2012. All patients with Tetralogy of Fallot, who underwent cardiac catheterization during this period, were included. Standard cine-angiograms were done to record the pulmonary artery sizes and associated cardiac defects. A total of 576 patients with Tetralogy of Fallot were catheterized. Pulmonary Artery abnormalities were present in 109 (18.92%) patients. The commonest abnormality was isolated Left Pulmonary Artery stenosis (n = 60, 10.4%) followed by supra-valvular stenosis (n = 9, 1.6%). Left Pulmonary Artery was absent in seven patients(1.2%), while 1 patient (0.2%) had both absent right and left Pulmonary Arteries with segmental branch pulmonary arteries originating directly from Main Pulmonary Artery. Associated cardiac lesions included right aortic arch in 72 (12.5%), additional muscular Ventricular Septal Defect in 31 (5.4%), Patent Ductus Arteriosus in 31 (5.4%), bilateral Superior Vena Cava 36(6.2%), Atrial Septal Defect 4(0.7%) and Major Aortopulmonary Collateral Arteries in 75(13%) patients. Significant coronary artery abnormalities were present in 28(4.9%) children. Pulmonary artery abnormalities were present in 18.92% of patients with Tetralogy of Fallot. Isolated Left Pulmonary Artery origin stenosis was the most common abnormality. Significant associated cardiac lesions including Patent Ductus Arteriosus , additional muscular Ventricular Septal Defect, coronary artery abnormalities, bilateral Superior Vena Cava, Atrial Septal Defect and Major Aortopulmonary Collateral Arteries were present in one-third of the patients.

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

    PubMed

    Kawut, Steven M

    2014-06-01

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

  18. Trial occlusion to assess the risk of persistent pulmonary arterial hypertension after closure of a large patent ductus arteriosus in adolescents and adults with elevated pulmonary artery pressure.

    PubMed

    Zhang, Duan-Zhen; Zhu, Xian-Yang; Lv, Bei; Cui, Chun-Sheng; Han, Xiu-Min; Sheng, Xiao-Tang; Wang, Qi-Guang; Zhang, Po

    2014-08-01

    No method is available to predict whether patients with patent ductus arteriosus (PDA) and severe pulmonary arterial hypertension (PAH) will show persistent postprocedural PAH (PP-PAH) after PDA closure. This study evaluated the usefulness of trial occlusion for predicting PP-PAH after transcatheter PDA closure in patients with severe PAH. Trial occlusion was performed in 137 patients (age ≥12 years) with PDA and severe PAH. All patients undergoing trial occlusion had a mean pulmonary artery pressure ≥45 mm Hg, pulmonary:systemic flow (Qp/Qs) ratio >1.5, and pulmonary:systemic resistance (Rp/Rs) ratio <0.7. A total of 135 patients (98%) showing stable hemodynamics during occlusion trial underwent successful device closure. Linear correlation analysis revealed weak or moderate relationships between the baseline and post-trial pulmonary artery pressures and pulmonary:systemic pressure (Pp/Ps) ratios. Patients were followed up for 1 to 10 years (median: 5 years). PP-PAH (systolic pulmonary artery pressure >50 mm Hg by Doppler echocardiography) was detected in 17 patients (13%), who displayed no significant differences in sex and age compared with patients without PP-PAH. According to discriminant analysis, the strongest discriminators between patients with and without PP-PAH were the baseline left ventricular end-diastolic volume and the baseline and post-trial systolic Pp/Ps ratios. In particular, a post-trial systolic Pp/Ps ratio >0.5 correctly classified 100% of the PP-PAH and non-PAH patients. Trial occlusion is a feasible method to predict PP-PAH in patients with PDA and severe PAH. A post-trial systolic Pp/Ps ratio >0.5 indicates a high risk of PP-PAH occurrence after device closure. © 2014 American Heart Association, Inc.

  19. Congenital anomalies of the pulmonary arteries: spectrum of findings on computed tomography.

    PubMed

    Bueno, J; Flors, L; Mejía, M

    Congenital anomalies of the pulmonary arteries are uncommon. They can occur in isolation or in association with congenital heart defects. Isolated congenital anomalies remain undiscovered until they are reported as incidental findings on imaging tests, usually not until adolescence. We review the embryological development and normal anatomy of the pulmonary arteries as well as the spectrum of computed tomography findings for various congenital anomalies: unilateral interruption of the pulmonary artery, anomalous origin of the left pulmonary artery (pulmonary artery sling), idiopathic aneurysm of the pulmonary artery, and other anomalies associated with congenital heart defects. Congenital anomalies of the pulmonary arteries represent a diagnostic challenge for clinicians and radiologists. Computed tomography is useful for their diagnosis, and general radiologists need to be familiar with their imaging appearance because they are often discovered incidentally. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Right cervical aortic arch with aberrant left subclavian artery.

    PubMed

    Tjang, Yanto S; Aramendi, José I; Crespo, Alejandro; Hamzeh, Gadah; Voces, Roberto; Rodríguez, Miguel A

    2008-08-01

    The combination of right cervical aortic arch, aberrant retroesophageal left subclavian artery originating from a Kommerell's diverticulum, and a ligamentum arteriosum, constitutes a rare form of vascular ring. Two patients aged 21 days and 54 years, who were diagnosed by multislice 3-dimensional computed tomography and magnetic resonance imaging, underwent surgical division of a vascular ring. The adult required resection of a Kommerell's aneurysm and subclavian artery reimplantation.

  1. Magnetic guide-wire navigation in pulmonary and systemic arterial catheterization: initial experience in pigs.

    PubMed

    Grosse-Wortmann, Lars; Grabitz, Ralf; Seghaye, Marie-Christine

    2007-04-01

    Cardiovascular catheterization can be challenging whenever a stenosis or an abnormal vascular course interferes with probing the target vessel. This study addresses the feasibility of navigating a guide wire with a magnetic tip by an external magnetic field through pulmonary and systemic arteries in an experimental porcine model. We investigated six piglets using magnetic guide-wire navigation. Two pulmonary arteriograms were taken from different angles in order to reconstruct the three-dimensional vessel anatomy. A computer interface then calculated three-dimensional coordinates for the vessel in space. Using these coordinates, two external magnets were positioned to create magnetic vectors along the expected vessel course. Magnetically enabled guide wires were then navigated into the vessels using the magnetic field to orient the guide-wire tips. Aortic and renal branches were addressed in a similar fashion. Difficulty in reaching the target vessel was reflected by the number of attempts that were necessary. After 10 failed attempts, the maneuver was recorded to have failed. Thirty-five of 37 (94.6%) arteries with branches at acute angles were reached successfully using magnetic navigation. In two pigs, the left upper lobe artery could not be probed. Peripheral arteries of small diameter were easier to reach than large central arteries, requiring less attempts. Magnetic guide-wire navigation is feasible in the arteries of the lungs, the head and neck, and the kidneys. It is particularly useful in entering small arterial branches at acute angles and may facilitate interventional therapy in a variety of vascular diseases in children and adults.

  2. Effects of atorvastatin and losartan on monocrotaline-induced pulmonary artery remodeling in rats.

    PubMed

    Xie, Liangdi; Lin, Peisen; Xie, Hong; Xu, Changsheng

    2010-01-01

    Structural remodeling of pulmonary artery plays an important role in maintaining sustained pulmonary arterial hypertension (PAH). The anti-remodeling effects of statins have been reported in systemic hypertension. In this study, we studied the effects of atovastatin (Ato) or losartan (Los) in monocrotaline (MCL)-induced pulmonary artery remodeling using a rat model. Forty Sprague-Dawley (SD) rats were randomly assigned into four groups (n = 10): normal control (Ctr), PAH, PAH treated with Los, and PAH treated with Ato. We found that in the Los- or Ato-treated group, the mean pulmonary arterial pressure, right heart hypertrophy index, ratio of wall/lumen thickness (WT%), as well as the wall/lumen area (WA%) were significantly reduced compared to the PAH group. Also in pulmonary arteries dissected from rats in the Ato- or Los-treated group, in both mRNA and protein levels, the expression of α1C subunit of voltage-gated calcium channel (Ca(v)α1c) was downregulated, while sarcoplasmic/endoplasmic reticulum calcium-ATPase (SERCA-2a) and inositol 1,4,5 triphosphate receptor 1 (IP3R-1) upregulated. However, the mRNA level of RyR-3 subunit of calcium regulating channel was increased, whereas its protein level was reduced in the treated groups. Our results suggest that atorvastatin or losartan may regress the remodeling of the pulmonary artery in pulmonary hypertensive rats, with differential expression of calcium regulating channels.

  3. 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

  4. Transcatheter recanalization of ligated main pulmonary artery.

    PubMed

    Bhole, Vinay; Wright, John G C; Stumper, Oliver

    2007-04-01

    A 12.5-year-old boy with tricuspid atresia and quadriplegic cerebral palsy presented with increasing cyanosis after previous palliation with a cavopulmonary shunt and ligation of the main pulmonary artery (MPA). Because of severe physical disabilities he was not considered suitable for Fontan completion. He underwent successful transcatheter stent recanalization of the ligated MPA. This re-established anterograde flow to the pulmonary arteries resulting in marked improvement in saturations.

  5. Angioscopy Is Useful In The Evaluation Of Chronic Pulmonary Arterial Obstruction

    NASA Astrophysics Data System (ADS)

    Shure, Deborah; Gregoratos, Gabriel; Moser, Kenneth M.

    1984-10-01

    We have previously described a fiberoptic angioscope for diagnostic use in the right heart and pulmonary arteries. The instrument has a 4 mm 0.D., a proximal flexion control lever, and a 0.8 mm inner channel used to inflate a polyurethane balloon attached to the distal end of the instrument. A conventional xenon light source provides illumination. The instrument is inserted through a right jugular venotomy and passed into the right heart and pulmonary arteries using direct vision and fluoroscopic guidance. The procedure has been performed in 4 patients with pulmonary hypertension suspected to be caused by chronic pulmonary emboli. Chronic emboli were found in two patients and central (resectable) emboli could be distinguished from peripheral ones. The third patient had normal pulmonary arterial intima and a final diagnosis of primary pulmonary hypertension was made. The fourth patient had extrinsic compression of pulmonary arteries by enlarged mediastinal nodes secondary to fibrosing mediastinitis. No complications occurred. We conclude that angioscopy appears to be useful in the diagnostic evaluation of patients with suspected chronic obstruction of the pulmonary arteries.

  6. 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.

  7. New insights in the treatment strategy for pulmonary arterial hypertension.

    PubMed

    Sahara, Makoto; Takahashi, Toshiyuki; Imai, Yasushi; Nakajima, Toshiaki; Yao, Atsushi; Morita, Toshihiro; Hirata, Yasunobu; Nagai, Ryozo

    2006-10-01

    Recent advances in our understanding of the pathophysiological and molecular mechanisms involved in pulmonary arterial hypertension have led to the development of novel and rational pharmacological therapies. In addition to conventional therapy (i.e., supplemental oxygen and calcium channel blockers), prostacyclin or endothelin receptor antagonists have been recommended as a first-line therapy for pulmonary arterial hypertension. However, these treatments have potential limitations with regard to their long-term efficacy and improvement in survival. Furthermore, intravenous prostacyclin (epoprostenol) therapy, which is recommended by most experts for patients with New York Heart Association (NYHA) functional class IV, is complicated, uncomfortable for patients, and expensive because of the cumbersome administration system. Considering these circumstances, it is necessary to develop additional novel therapeutic approaches that target the various components of this multifactorial disease. In this short review, we present an overview of the current treatment options for pulmonary arterial hypertension and describe a case report with primary pulmonary hypertension. A male patient with NYHA functional class IV and showing no response to calcium channel blockers and prostacyclin exhibited significantly improved exercise tolerance and hemodynamics and long-term survival for more than 2.5 years after receiving an oral combination therapy of a phosphodiesterase type 5 inhibitor (sildenafil), phosphodiesterase type 3 inhibitor (pimobendan), and nicorandil. We also discuss the background and plausible potential mechanisms involved in this case, as well as future perspectives in the treatment of pulmonary arterial hypertension.

  8. Interventional Management of Massive Hemothorax Due to Inadvertent Puncture of an Aberrant Right Subclavian Artery

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

    Jahnke, Thomas, E-mail: thomas.jahnke@gmx.net; Schaefer, Phillip Jost; Heller, Martin

    2008-07-15

    We report a case of massive hemothorax due to inadvertent puncture of an aberrant right subclavian artery during central venous access. Iatrogenic laceration at the origin of the right internal thoracic artery was successfully treated with coil embolization of the internal thoracic artery followed by stent-graft placement into the subclavian artery. Due to its elongated and abnormal course, an aberrant right subclavian artery may predispose to inadvertent puncture during vein catheterization and should be recognized as a potential threat for such procedures. Our case emphasizes that ultrasound guidance should be used routinely for central venous lines wherever possible.

  9. [Pregnancy in pulmonary arterial hypertension patients].

    PubMed

    Rosengarten, Dror; Kramer, Mordechai R

    2013-09-01

    Pulmonary arterial hypertension (PAH) is a disorder defined by elevated mean pulmonary arterial pressure. PAH can be idiopathic or associated with a variety of medical conditions such as scleroderma, congenital heart disease, left heart failure, lung disease or chronic pulmonary thromboembolism. This progressive disease can cause severe right heart failure and death. Normal physiologic changes that occur during pregnancy may produce fatal consequences in PAH patients. Current guidelines recommend that pregnancy be avoided or terminated early in women with PAH. During the past decade, new advanced therapies for PAH have emerged gathering reports of successful pregnancies in patients with pulmonary hypertension. Substantial risk still exists and current recommendations have not changed. Nevertheless, in selected cases, if a patient insists on continuing the pregnancy, being fully aware of the risks involved, an intensive treatment approach should be implemented in experienced centers. This is necessary in order to control pulmonary hypertension during pregnancy and reduce the risk so as to improve outcomes. This review will focus on the pathophysiology of PAH in pregnancy and appropriate management during pregnancy, delivery and the post-partum period.

  10. Nonmassive acute pulmonary embolism: evaluation of the impact of pulmonary arterial wall distensibility on the assessment of the CT obstruction score.

    PubMed

    Bigot, Julien; Rémy-Jardin, Martine; Duhamel, Alain; Gorgos, Andréi-Bogdan; Faivre, Jean-Baptiste; Rémy, Jacques

    2010-02-01

    To evaluate the impact of pulmonary arterial wall distensibility on the assessment of a computed tomography (CT) score in patients with nonmassive pulmonary embolism (PE) (ie, Mastora score). The arterial wall distensibility of five central pulmonary arteries (pulmonary artery trunk, right and left main pulmonary arteries, right and left interlobar pulmonary arteries) was studied on ECG-gated CT angiographic studies of the chest in 15 patients with no pulmonary arterial hypertension (group 1; mean pulmonary artery pressure: 17.2 mm Hg) and 9 patients with nonmassive PE (group 2), using 2D reconstructions at every 10% of the R-R interval. The systolic and diastolic reconstruction time windows of the examined arteries were identical in the 2 groups, obtained at 20% and 80% of the R-R interval, respectively. No statistically significant difference was observed between the mean values of the pulmonary arterial wall distensibility between the 2 groups, varying between 20.5% and 24% in group 1 and between 23.3% and 25.9% in group 2. The coefficients of variation of the average arterial surfaces were found to vary between 4.30% and 6.50% in group 1 and 4.2% and 8.4% in group 2. Except the pulmonary artery trunk in group 2, all the intraclass correlation coefficients were around 0.8 or greater than 0.8, that is the cutoff for good homogeneity of measurements. The pulmonary arterial wall systolic-diastolic distensibility does not interfere with the assessment of a CT obstruction score in the setting of nonmassive PE.

  11. Non-valvular main pulmonary artery vegetation associated with aortopulmonary window.

    PubMed

    Unal, M; Tuncer, C; Serçe, K; Bostan, M; Gökçe, M; Erem, C

    1995-01-01

    We present a 32-year-old female with aortopulmonary window and vegetation of non-valvular main pulmonary artery. The aortopulmonary window is a rare congenital disease in which the aorta and pulmonary arteries are communicated by a defect of variable diameter. The pulmonic valve is the least commonly involved valve in bacterial endocarditis, but there is no vegetation of non-valvular main pulmonary artery in the literature. Colour duplex sonography showed an aortopulmonary window with aortic regurgitation. Magnetic resonance (MR) imaging demonstrating the vegetation on the wall of main pulmonary artery, is an useful and complementary method, and can be used for demonstration of congenital and acquired cardiovascular pathologies including aortopulmonary window and subpulmonic or suprapulmonic vegetations.

  12. Connective tissue disease-associated pulmonary arterial hypertension

    PubMed Central

    Howard, Luke S.

    2015-01-01

    Although rare in its idiopathic form, pulmonary arterial hypertension (PAH) is not uncommon in association with various associated medical conditions, most notably connective tissue disease (CTD). In particular, it develops in approximately 10% of patients with systemic sclerosis and so these patients are increasingly screened to enable early detection. The response of patients with systemic sclerosis to PAH-specific therapy appears to be worse than in other forms of PAH. Survival in systemic sclerosis-associated PAH is inferior to that observed in idiopathic PAH. Potential reasons for this include differences in age, the nature of the underlying pulmonary vasculopathy and the ability of the right ventricle to cope with increased afterload between patients with systemic sclerosis-associated PAH and idiopathic PAH, while coexisting cardiac and pulmonary disease is common in systemic sclerosis-associated PAH. Other forms of connective tissue-associated PAH have been less well studied, however PAH associated with systemic lupus erythematosus (SLE) has a better prognosis than systemic sclerosis-associated PAH and likely responds to immunosuppression. PMID:25705389

  13. Diagnosis, Evaluation and Treatment of Pulmonary Arterial Hypertension in Children

    PubMed Central

    Frank, Benjamin S.

    2018-01-01

    Pulmonary Hypertension (PH), the syndrome of elevated pressure in the pulmonary arteries, is associated with significant morbidity and mortality for affected children. PH is associated with a wide variety of potential underlying causes, including cardiac, pulmonary, hematologic and rheumatologic abnormalities. Regardless of the cause, for many patients the natural history of PH involves progressive elevation in pulmonary arterial resistance and pressure, right ventricular dysfunction, and eventually heart failure. In recent years, a number of pulmonary arterial hypertension (PAH)-targeted therapies have become available to reduce pulmonary artery pressure and improve outcome. A growing body of evidence in both the adult and pediatric literature demonstrates enhanced quality of life, functional status, and survival among treated patients. This review provides a description of select etiologies of PH seen in pediatrics and an update on the most recent data pertaining to evaluation and management of children with PH/PAH. The available evidence for specific classes of PAH-targeted therapies in pediatrics is additionally discussed. PMID:29570688

  14. 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 ...

  15. 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.

  16. GPCRs in pulmonary arterial hypertension: tipping the balance.

    PubMed

    Iyinikkel, Jean; Murray, Fiona

    2018-02-21

    Pulmonary arterial hypertension (PAH) is a progressive, fatal disease characterised by increased pulmonary vascular resistance and excessive proliferation of pulmonary artery smooth muscle cells (PASMC). GPCRs, which are attractive pharmacological targets, are important regulators of pulmonary vascular tone and PASMC phenotype. PAH is associated with the altered expression and function of a number of GPCRs in the pulmonary circulation, which leads to the vasoconstriction and proliferation of PASMC and thereby contributes to the imbalance of pulmonary vascular tone associated with PAH; drugs targeting GPCRs are currently used clinically to treat PAH and extensive preclinical work supports the utility of a number of additional GPCRs. Here we review how GPCR expression and function changes with PAH and discuss why GPCRs continue to be relevant drug targets for the disease. © 2018 The British Pharmacological Society.

  17. 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.

  18. The role of platelets in the development and progression of pulmonary arterial hypertension.

    PubMed

    Kazimierczyk, Remigiusz; Kamiński, Karol

    2018-06-06

    Pulmonary arterial hypertension is a multifactorial disease characterized by vasoconstriction, vascular remodeling, inflammation and thrombosis. Although an increasing number of research confirmed that pulmonary artery endothelial cells, pulmonary artery smooth muscle cells as well as platelets have a role in the pulmonary arterial hypertension pathogenesis, it is still unclear what integrates these factors. In this paper, we review the evidence that platelets through releasing a large variety of chemokines could actively impact the pulmonary arterial hypertension pathogenesis and development. A recent publication revealed that not only an excess of platelet derived cytokines, but also a deficiency may be associated with pulmonary arterial hypertension development and progression. Hence, a simple platelet blockade may not be a correct action to treat pulmonary arterial hypertension. Our review aims to analyse the interactions between the platelets and different types of cells involved in pulmonary arterial hypertension pathogenesis. This knowledge could help to find novel therapeutic options and improve prognosis in this devastating disease. Copyright © 2018 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.

  19. 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

  20. 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

  1. NMDA-Type Glutamate Receptor Activation Promotes Vascular Remodeling and Pulmonary Arterial Hypertension.

    PubMed

    Dumas, Sébastien J; Bru-Mercier, Gilles; Courboulin, Audrey; Quatredeniers, Marceau; Rücker-Martin, Catherine; Antigny, Fabrice; Nakhleh, Morad K; Ranchoux, Benoit; Gouadon, Elodie; Vinhas, Maria-Candida; Vocelle, Matthieu; Raymond, Nicolas; Dorfmüller, Peter; Fadel, Elie; Perros, Frédéric; Humbert, Marc; Cohen-Kaminsky, Sylvia

    2018-05-29

    Excessive proliferation and apoptosis resistance in pulmonary vascular cells underlie vascular remodeling in pulmonary arterial hypertension (PAH). Specific treatments for PAH exist, mostly targeting endothelial dysfunction, but high pulmonary arterial pressure still causes heart failure and death. Pulmonary vascular remodeling may be driven by metabolic reprogramming of vascular cells to increase glutaminolysis and glutamate production. The N -methyl-d-aspartate receptor (NMDAR), a major neuronal glutamate receptor, is also expressed on vascular cells, but its role in PAH is unknown. We assessed the status of the glutamate-NMDAR axis in the pulmonary arteries of patients with PAH and controls through mass spectrometry imaging, Western blotting, and immunohistochemistry. We measured the glutamate release from cultured pulmonary vascular cells using enzymatic assays and analyzed NMDAR regulation/phosphorylation through Western blot experiments. The effect of NMDAR blockade on human pulmonary arterial smooth muscle cell proliferation was determined using a BrdU incorporation assay. We assessed the role of NMDARs in vascular remodeling associated to pulmonary hypertension, in both smooth muscle-specific NMDAR knockout mice exposed to chronic hypoxia and the monocrotaline rat model of pulmonary hypertension using NMDAR blockers. We report glutamate accumulation, upregulation of the NMDAR, and NMDAR engagement reflected by increases in GluN1-subunit phosphorylation in the pulmonary arteries of human patients with PAH. K v channel inhibition and type A-selective endothelin receptor activation amplified calcium-dependent glutamate release from human pulmonary arterial smooth muscle cell, and type A-selective endothelin receptor and platelet-derived growth factor receptor activation led to NMDAR engagement, highlighting crosstalk between the glutamate-NMDAR axis and major PAH-associated pathways. The platelet-derived growth factor-BB-induced proliferation of human

  2. Resolution of Behçet's syndrome associated pulmonary arterial aneurysms with infliximab.

    PubMed

    Schreiber, Benjamin E; Noor, Nadim; Juli, Christoph F; Haskard, Dorian O

    2011-12-01

    We describe the successful treatment of pulmonary arterial aneurysms in Behçet's syndrome using a tumor necrosis factor (TNF) inhibitor. A case is reported of Behçet's syndrome complicated by pulmonary arterial aneurysms that responded to anti-TNF therapy. This is accompanied by a literature review of previously published cases. We searched the English language medical literature using the PubMed and Medline search terms: "Behçet's," "Pulmonary aneurysms," and "infliximab," "etanercept," or "adalimumab." A 43-year-old man with a 6-month history of oral and genital ulcers, weight loss, and fatigue developed arterial aneurysms in the common carotid and common iliac arteries and thromboses in a femoral vein and pulmonary arteries. Treatment with high-dose oral corticosteroids and pulsed intravenous cyclophosphamide was initiated but while on treatment he developed pulmonary arterial aneurysms with hemoptysis. His treatment was changed to intravenous infliximab with methotrexate to which he showed a good response with marked clinical improvement, reduction in his inflammatory markers, and regression of the pulmonary arterial aneurysms. The review of the literature identified 3 reported cases of treatment of pulmonary arterial aneurysms in Behçet's syndrome with anti-TNF therapy, with good outcomes in each case. Pulmonary artery aneurysms are important complications of Behçet's syndrome. Anti-TNF inhibitors should be considered in patients who do not respond to treatment with corticosteroids and cyclophosphamide. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Prenatal diagnosis of left pulmonary artery-to-pulmonary vein fistula and its successful surgical repair in a neonate.

    PubMed

    Ostras, Oleksii; Kurkevych, Andrii; Bohuta, Lyubomyr; Yalynska, Tetyana; Raad, Tammo; Lewin, Mark; Yemets, Illya

    2015-04-01

    Pulmonary arteriovenous fistula is a rare disease. To the best of our knowledge, prenatal diagnosis of a fistula between the left pulmonary artery and the left pulmonary vein has not been described in the medical literature. We report a case of the prenatal diagnosis of a left pulmonary artery-to-pulmonary vein fistula, followed by successful neonatal surgical repair.

  4. 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

  5. Preliminary Experience of Endovascular Embolization Using N-Butyl Cyanoacrylate for Hemoptysis due to Infectious Pulmonary Artery Pseudoaneurysms via Systemic Arterial Approach.

    PubMed

    Torikai, Hideyuki; Hasegawa, Ichiro; Jinzaki, Masahiro; Narimatsu, Yoshiaki

    2017-10-01

    We report 5 patients with hemoptysis due to infectious pulmonary artery pseudoaneurysm (PAP) treated with endovascular embolization using N-butyl cyanoacrylate (NBCA) injected via bronchial and nonbronchial systemic arterial approaches. Infectious diseases included inactive tuberculosis (n = 3), nontuberculous mycobacteriosis (n = 1), and chronic infection of unknown origin (n = 1). Seven PAPs were detected on selective systemic angiography, and injection of NBCA was performed. Disappearance of all PAPs was confirmed on systemic arteriography after the intervention. In all patients, hemoptysis was stopped without major complications, and it did not recur during the follow-up period (mean, 351 d; range, 285-427 d). Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

  6. Transcatheter closure of patent ductus arteriosus with severe pulmonary arterial hypertension in adults.

    PubMed

    Yan, C; Zhao, S; Jiang, S; Xu, Z; Huang, L; Zheng, H; Ling, J; Wang, C; Wu, W; Hu, H; Zhang, G; Ye, Z; Wang, H

    2007-04-01

    Surgical closure of patent ductus arteriosus (PDA) with severe pulmonary arterial hypertension in adults carries higher risk than in children. To investigate the application of self-expandable occluders for transcatheter closure of PDA associated with severe pulmonary arterial hypertension in adults, and the assessment of immediate and short-term results. 29 adult patients (6 men, 23 women) underwent attempted transcatheter closure of PDA at a mean (standard deviation (SD)) age of 31.1 (11.4) years (range 18-58 years) and a mean (SD) weight of 54.1 (7.1) kg (range 42-71 kg). On the basis of haemodynamic and clinical data obtained before and after trial occlusion, the final duct occlusion was determined and carried out. Radiographs of the chest, electrocardiograms and echocardiograms were used for follow-up evaluation of the treatment within 1 day, 1 month and 3-6 months after successful closure. 20 of the 29 patients had successful occlusion (group 1), and 9 patients failed (named group 2). In group 1, in which occlusion was successful, mean (SD) pulmonary arterial pressures decreased markedly after trial occlusion: 78 (19.3) mm Hg (range 50-125 mm Hg) before occlusion and 41 (13.8) mm Hg (range 23-77 mm Hg) after occlusion. Systemic arterial oxygen saturation was found to be >90% in 19 patients and <90% in the remaining patient before inhalation of oxygen, and >95% during inhalation of oxygen or after occlusion in all 20 patients. In group 2, the occlusion was not successful, because in two patients the device was not available; another two patients showed worsening of symptoms. The other five patients showed increased pulmonary arterial pressures after trial closure; their mean (SD) pulmonary arterial pressures increased by 10.3 (6) mm Hg (4-16 mm Hg) after trial occlusion, and systemic arterial oxygen saturation was 85.5% (2.6%) (range 82.6-88%) before inhalation of oxygen and 94.7% (1.7%) (range 90.7-99.1%) during inhalation of oxygen. In group 1, the

  7. Surgical repair of an aberrant splenic artery aneurysm: report of a case.

    PubMed

    Illuminati, Giulio; LaMuraglia, Glenn; Nigri, Giuseppe; Vietri, Francesco

    2007-03-01

    Aneurysms of the splenic artery are the most common splanchnic aneurysms. Aneurysms of a splenic artery with an anomalous origin from the superior mesenteric artery are however rare, with eight previously reported cases. Their indications for treatment are superposable to those of aneurysms affecting an orthotopic artery. Methods of treatment of this condition include endovascular, minimally invasive techniques and surgical resection. We report one more case of aneurysm of an aberrant splenic artery, treated with surgical resection, and preservation of the spleen.

  8. Prenatal Diagnosis of Left Pulmonary Artery-to-Pulmonary Vein Fistula and Its Successful Surgical Repair in a Neonate

    PubMed Central

    Kurkevych, Andrii; Bohuta, Lyubomyr; Yalynska, Tetyana; Raad, Tammo; Lewin, Mark; Yemets, Illya

    2015-01-01

    Pulmonary arteriovenous fistula is a rare disease. To the best of our knowledge, prenatal diagnosis of a fistula between the left pulmonary artery and the left pulmonary vein has not been described in the medical literature. We report a case of the prenatal diagnosis of a left pulmonary artery-to-pulmonary vein fistula, followed by successful neonatal surgical repair. PMID:25873833

  9. Partial anomalous left pulmonary artery: report of two cases and review of literature.

    PubMed

    Sen, Supratim; Winlaw, David S; Sholler, Gary F

    2015-06-01

    We describe two cases of anomalous origin of the left lower-lobe pulmonary artery from the right pulmonary artery. The primary diagnosis was mitral atresia, hypoplastic left ventricle, aortic arch hypoplasia in the first child, and tetralogy of Fallot in the second. In both cases, the pulmonary trunk gave rise to a left pulmonary artery in the normal position. In addition, a second branch of the left pulmonary artery arose from the right pulmonary artery, and passed posterior and inferior to the left main or upper-lobe bronchus to supply the left lower lobe. In this review, we compare our findings with previously reported examples of this extremely rare cardiac malformation, and discuss possible embryological explanations for the lesion.

  10. 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.

  11. Management of patients with pulmonary arterial hypertension due to congenital heart disease: recent advances and future directions.

    PubMed

    Blok, Ilja M; van Riel, Annelieke C M J; Mulder, Barbara J M; Bouma, Berto J

    2015-12-01

    Pulmonary arterial hypertension is a serious complication of adult congenital heart disease associated with systemic-to-pulmonary shunts. Although early shunt closure restricts development of pulmonary arterial hypertension, patients remain at risk even after repair. The development of pulmonary arterial hypertension is associated with a markedly increased morbidity and mortality. It is important to identify patients with a poor prognosis using disease specific markers. Echocardiography and biomarkers arise as practical tools to determine the risk of mortality. Although pulmonary arterial hypertension cannot be cured, four classes of disease-targeting therapies are currently available and several promising therapies are being studied. There is a shift in drug studies towards more clinically relevant endpoints such as time to clinical worsening and morbidity and mortality events.

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

    PubMed

    Grech, Victor; Grixti, Cynthia

    2010-06-02

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

  13. MicroRNA-Dependent Control of Serotonin-Induced Pulmonary Arterial Contraction.

    PubMed

    Dahan, Diana; Hien, Tran Thi; Tannenberg, Philip; Ekman, Mari; Rippe, Catarina; Boettger, Thomas; Braun, Thomas; Tran-Lundmark, Karin; Tran, Phan-Kiet; Swärd, Karl; Albinsson, Sebastian

    2017-01-01

    Serotonin (5-HT) is considered to play a role in pulmonary arterial hypertension by regulating vascular remodeling and smooth muscle contractility. Here, arteries from mice with inducible and smooth muscle-specific deletion of Dicer were used to address mechanisms by which microRNAs control 5-HT-induced contraction. Mice were used 5 weeks after Dicer deletion, and pulmonary artery contractility was analyzed by wire myography. No change was seen in right ventricular systolic pressure following dicer deletion, but systemic blood pressure was reduced. Enhanced 5-HT-induced contraction in Dicer KO pulmonary arteries was associated with increased 5-HT2A receptor mRNA expression whereas 5-HT1B and 5-HT2B receptor mRNAs were unchanged. Contraction by the 5-HT2A agonist TCB-2 was increased in Dicer KO as was the response to the 5-HT2B agonist BW723C86. Effects of Src and protein kinase C inhibition were similar in control and KO arteries, but the effect of inhibition of Rho kinase was reduced. We identified miR-30c as a potential candidate for 5-HT2A receptor regulation as it repressed 5-HT2A mRNA and protein. Our findings show that 5-HT receptor signaling in the arterial wall is subject to regulation by microRNAs and that this entails altered 5-HT2A receptor expression and signaling. © 2017 S. Karger AG, Basel.

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

    PubMed

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

    2016-03-01

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

  15. 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.

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

    PubMed Central

    2010-01-01

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

  17. Three-dimensional segmentation of pulmonary artery volume from thoracic computed tomography imaging

    NASA Astrophysics Data System (ADS)

    Lindenmaier, Tamas J.; Sheikh, Khadija; Bluemke, Emma; Gyacskov, Igor; Mura, Marco; Licskai, Christopher; Mielniczuk, Lisa; Fenster, Aaron; Cunningham, Ian A.; Parraga, Grace

    2015-03-01

    Chronic obstructive pulmonary disease (COPD), is a major contributor to hospitalization and healthcare costs in North America. While the hallmark of COPD is airflow limitation, it is also associated with abnormalities of the cardiovascular system. Enlargement of the pulmonary artery (PA) is a morphological marker of pulmonary hypertension, and was previously shown to predict acute exacerbations using a one-dimensional diameter measurement of the main PA. We hypothesized that a three-dimensional (3D) quantification of PA size would be more sensitive than 1D methods and encompass morphological changes along the entire central pulmonary artery. Hence, we developed a 3D measurement of the main (MPA), left (LPA) and right (RPA) pulmonary arteries as well as total PA volume (TPAV) from thoracic CT images. This approach incorporates segmentation of pulmonary vessels in cross-section for the MPA, LPA and RPA to provide an estimate of their volumes. Three observers performed five repeated measurements for 15 ex-smokers with ≥10 pack-years, and randomly identified from a larger dataset of 199 patients. There was a strong agreement (r2=0.76) for PA volume and PA diameter measurements, which was used as a gold standard. Observer measurements were strongly correlated and coefficients of variation for observer 1 (MPA:2%, LPA:3%, RPA:2%, TPA:2%) were not significantly different from observer 2 and 3 results. In conclusion, we generated manual 3D pulmonary artery volume measurements from thoracic CT images that can be performed with high reproducibility. Future work will involve automation for implementation in clinical workflows.

  18. Mid-term outcomes of patients undergoing adjustable pulmonary artery banding

    PubMed Central

    Talwar, Sachin; Kamat, Neeraj Aravind; Choudhary, Shiv Kumar; Ramakrishnan, Sivasubramanian; Saxena, Anita; Juneja, Rajnish; Kothari, Shyam Sunder; Airan, Balram

    2016-01-01

    Objective The adjustable pulmonary artery band (APAB) has been demonstrated by us earlier to be superior to the conventional pulmonary artery banding (CPAB), in terms of reduced early morbidity and mortality. In this study, we assessed the adequacy of the band and its complications over the mid-term. Methods Between 2002 and 2012, 73 patients underwent adjustable PAB, and their operative and follow-up data were collected and analyzed. Results There was one early death following the APAB. Follow-up data were available for 57 patients of which 44 patients (61.7%) underwent definitive repair, 10 were awaiting definitive repair, and 3 patients were kept on medical follow-up because of inadequate fall in pulmonary artery (PA) pressures. 14 patients (19%) were lost to follow-up. Major PA distortion or stenosis was absent in the majority. 1 patient had pseudoaneurysm of the main pulmonary artery (MPA) with sternal sinus infection and required surgical reconstruction. 1 patient had infective endocarditis of the pulmonary valve managed medically. Band migration was not encountered. There were two deaths after definitive repair and one after APAB. Conclusions Patients undergoing APAB fulfilled the desired objectives of the pulmonary artery banding (PAB) with minimum PA complications in the mid-term. This added to the early postoperative benefits, makes the APAB an attractive alternative to the CPAB. PMID:26896271

  19. 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

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

    PubMed

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

    2015-12-01

    Pythons are unique amongst snakes in having different pressures in the aortas and pulmonary arteries because of intraventricular pressure separation. In this study, we investigate whether this correlates with different blood vessel strength in the ball python Python regius. We excised segments from the left, right, and dorsal aortas, and from the two pulmonary arteries. These were subjected to tensile testing. We show that the aortic vessel wall is significantly stronger than the pulmonary artery wall in P. regius. Gross morphological characteristics (vessel wall thickness and correlated absolute amount of collagen content) are likely the most influential factors. Collagen fiber thickness and orientation are likely to have an effect, though the effect of collagen fiber type and cross-links between fibers will need further study. © 2015 Wiley Periodicals, Inc.

  1. Pulmonary artery wave propagation and reservoir function in conscious man: impact of pulmonary vascular disease, respiration and dynamic stress tests.

    PubMed

    Su, Junjing; Manisty, Charlotte; Simonsen, Ulf; Howard, Luke S; Parker, Kim H; Hughes, Alun D

    2017-10-15

    Wave travel plays an important role in cardiovascular physiology. However, many aspects of pulmonary arterial wave behaviour remain unclear. Wave intensity and reservoir-excess pressure analyses were applied in the pulmonary artery in subjects with and without pulmonary hypertension during spontaneous respiration and dynamic stress tests. Arterial wave energy decreased during expiration and Valsalva manoeuvre due to decreased ventricular preload. Wave energy also decreased during handgrip exercise due to increased heart rate. In pulmonary hypertension patients, the asymptotic pressure at which the microvascular flow ceases, the reservoir pressure related to arterial compliance and the excess pressure caused by waves increased. The reservoir and excess pressures decreased during Valsalva manoeuvre but remained unchanged during handgrip exercise. This study provides insights into the influence of pulmonary vascular disease, spontaneous respiration and dynamic stress tests on pulmonary artery wave propagation and reservoir function. Detailed haemodynamic analysis may provide novel insights into the pulmonary circulation. Therefore, wave intensity and reservoir-excess pressure analyses were applied in the pulmonary artery to characterize changes in wave propagation and reservoir function during spontaneous respiration and dynamic stress tests. Right heart catheterization was performed using a pressure and Doppler flow sensor tipped guidewire to obtain simultaneous pressure and flow velocity measurements in the pulmonary artery in control subjects and patients with pulmonary arterial hypertension (PAH) at rest. In controls, recordings were also obtained during Valsalva manoeuvre and handgrip exercise. The asymptotic pressure at which the flow through the microcirculation ceases, the reservoir pressure related to arterial compliance and the excess pressure caused by arterial waves increased in PAH patients compared to controls. The systolic and diastolic rate constants

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

    PubMed

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

    2014-11-01

    This study investigates the respirability and efficacy of peptide-micelle hybrid nanoparticles as carriers for inhalational therapy of pulmonary arterial hypertension (PAH). CARSKNKDC (CAR), a cell-penetrating and lung-homing peptide, conjugated polyethylene glycol-distearoyl-phosphoethanolamine micelles containing fasudil, an investigational anti-PAH drug, were prepared by solvent evaporation method and characterized for various physicochemical properties. The pharmacokinetics and pharmacological efficacy of hybrid particles containing fasudil were evaluated in healthy rats and monocrotaline-induced PAH rats. CAR micelles containing fasudil had an entrapment efficiency of approximately 58%, showed controlled release of the drug, and were monodispersed with an average size of approximately 14 nm. Nuclear magnetic resonance scan confirmed the drug's presence in the core of peptide-micelle hybrid particles. Compared with plain micelles, CAR peptide increased the cellular uptake by approximately 1.7-fold and extended the drug half-life by approximately fivefold. The formulations were more prone to accumulate in the pulmonary vasculature than in the peripheral blood, which is evident from the ratio of the extent of reduction of pulmonary and systemic arterial pressures. On the whole, this study demonstrates that peptide-polymer hybrid micelles can serve as inhalational carriers for PAH therapy. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  3. Pulmonary artery dissection in eight dogs with patent ductus arteriosus.

    PubMed

    Scansen, Brian A; Simpson, Elaine M; López-Alvarez, Jordi; Thomas, William P; Bright, Janice M; Eason, Bryan D; Rush, John E; Dukes-McEwan, Joanna; Green, Henry W; Cunningham, Suzanne M; Visser, Lance C; Kent, Agnieszka M; Schober, Karsten E

    2015-06-01

    To describe a series of dogs with pulmonary artery dissection and patent ductus arteriosus (PDA). Eight dogs. Retrospective case series. Pulmonary artery dissection was diagnosed in 8 dogs, 3 were Weimaraners. Four dogs presented in left-sided congestive heart failure, 4 presented for murmur evaluation and without clinical signs, and 1 presented in right-sided congestive heart failure. In 7 dogs the dissection was first documented concurrent with a diagnosis of uncorrected PDA. In the other dog, with pulmonary valve stenosis and PDA, the dissection was observed on autopsy examination 17 months after balloon pulmonary valvuloplasty and ductal closure. Median age at presentation for the 7 dogs with antemortem diagnosis of pulmonary artery dissection was 3.5 years (range, 1.5-4 years). Three dogs had the PDA surgically ligated, 2 dogs did not undergo PDA closure, 1 dog failed transcatheter occlusion of the PDA with subsequent surgical ligation, 1 dog underwent successful transcatheter device occlusion of the PDA, and 1 dog had the PDA closed by transcatheter coil delivery 17 months prior to the diagnosis of pulmonary artery dissection. The 2 dogs that did not have the PDA closed died 1 and 3 years after diagnosis due to heart failure. Pulmonary artery dissection is a potential complication of PDA in dogs, the Weimaraner breed may be at increased risk, presentation is often in mature dogs, and closure of the PDA can be performed and appears to improve outcome. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Changes in pulmonary arterial wall mechanical properties and lumenal architecture with induced vascular remodeling

    NASA Astrophysics Data System (ADS)

    Molthen, Robert C.; Heinrich, Amy E.; Haworth, Steven T.; Dawson, Christopher A.

    2004-04-01

    To explore and quantify pulmonary arterial remodeling we used various methods including micro-CT, high-resolution 3-dimensional x-ray imaging, to examine the structure and function of intact pulmonary vessels in isolated rat lungs. The rat is commonly used as an animal model for studies of pulmonary hypertension (PH) and the accompanying vascular remodeling, where vascular remodeling has been defined primarily by changes in the vessel wall composition in response to hypertension inducing stimuli such as chronic hypoxic exposure (CHE) or monocrotaline (MCT) injection. Little information has been provided as to how such changes affect the vessel wall mechanical properties or the lumenal architecture of the pulmonary arterial system that actually account for the hemodynamic consequences of the remodeling. In addition, although the link between primary forms of pulmonary hypertension and inherited genetics is well established, the role that genetic coding plays in hemodynamics and vascular remodeling is not. Therefore, we are utilizing Fawn-Hooded (FH), Sprague-Dawley (SD) and Brown Norway (BN)rat strains along with unique imaging methods to parameterize both vessel distensibility and lumenal morphometry using a principal pulmonary arterial pathway analysis based on self-consistency. We have found for the hypoxia model, in addition to decreased body weight, increased hematocrit, increased right ventricular hypertrophy, the distensibility of the pulmonary arteries is shown to decrease significantly in the presence of remodeling.

  5. Pulmonary hemodynamics and gas exchange in off pump coronary artery bypass grafting.

    PubMed

    Vedin, Jenny; Jensen, Ulf; Ericsson, Anders; Samuelsson, Sten; Vaage, Jarle

    2005-10-01

    To investigate the influence of cardiopulmonary bypass on pulmonary hemodynamics and gas exchange. Low risk patients admitted for elective coronary artery bypass grafting were randomized to either on (n=25) or off pump (n=25) surgery. Central hemodynamics, gas exchange, and venous admixture were studied during and up to 20 h after surgery. There was no difference in pulmonary vascular resistance index (P=0.16), right ventricular stroke work index (P>0.2), mean pulmonary artery pressure (P>0.2) or pulmonary capillary wedge pressure (P>0.2) between groups. Soon after surgery there was a tendency towards higher cardiac index (P=0.07) in the off pump group. Arterial oxygen tension (P>0.2), hematocrit (P>0.2), venous admixture (P>0.2), and arterial-venous oxygen content difference (P=0.12) did not differ between groups. This prospective, randomized study showed no difference in pulmonary hemodynamics, pulmonary gas exchange, and venous admixture, in low risk patients undergoing off pump compared to on pump coronary artery bypass surgery.

  6. [The role of N-acetylcysteine against the injury of pulmonary artery induced by LPS].

    PubMed

    Huang, Xin-li; Ling, Yi-ling; Zhu, Tie-nian

    2002-11-01

    To investigate the alleviating effect of N-acetylcysteine (NAC) on lung injury induced by lipopolysaccharides (LPS) and its mechanism. The effects of NAC on changes of the pulmonary arterial reactivity and the ultrastructure of pulmonary arterial endothelium induced by LPS were observed with the isolated artery ring technique and scanning electron microscope (SEM). Malondialdehyde (MDA), nitric oxide (NO) contents and superoxide dismutase (SOD) activity of pulmonary artery tissues were detected. The exposure of pulmonary artery to LPS (4 microg/ml, 7 h) led to reduction of endothelium-dependent relaxation response to acetylcholine (ACh), which was reversed by the concomitant exposure to NAC (0.5 mmol/L, 7 h), whereas NAC itself had no effect on the response. Significant structural injury were observed under SEM in LPS group and alleviated the changes in LPS + NAC group. The MDA, NO contents increased but SOD activity decreased in LPS group, which were reversed by the concomitant exposure to NAC. NAC protects pulmonary artery endothelium and enhances endothelium-dependent relaxation response of pulmonary artery by antioxidation effect, which may be one of the mechanisms of its reversing pulmonary artery hypertension and following lung injury induced by LPS.

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

    PubMed

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

    2014-06-20

    This review summarizes an expanding body of knowledge indicating that failure to resolve inflammation and altered immune processes underlie the development of pulmonary arterial hypertension. The chemokines and cytokines implicated in pulmonary arterial hypertension that could form a biomarker platform are discussed. Pre-clinical studies that provide the basis for dysregulated immunity in animal models of the disease are reviewed. In addition, we present therapies that target inflammatory/immune mechanisms that are currently enrolling patients, and discuss others in development. We show how genetic and metabolic abnormalities are inextricably linked to dysregulated immunity and adverse remodeling in the pulmonary arteries. © 2014 American Heart Association, Inc.

  8. Histone deacetylation contributes to low extracellular superoxide dismutase expression in human idiopathic pulmonary arterial hypertension

    PubMed Central

    Woods, Crystal; Stearman, Robert S.; Venkataraman, Sujatha; Ferguson, Bradley S.; Swain, Kalin; Bowler, Russell P.; Geraci, Mark W.; Ihida-Stansbury, Kaori; Stenmark, Kurt R.; McKinsey, Timothy A.; Domann, Frederick E.

    2016-01-01

    Epigenetic mechanisms, including DNA methylation and histone acetylation, regulate gene expression in idiopathic pulmonary arterial hypertension (IPAH). These mechanisms can modulate expression of extracellular superoxide dismutase (SOD3 or EC-SOD), a key vascular antioxidant enzyme, and loss of vascular SOD3 worsens outcomes in animal models of pulmonary arterial hypertension. We hypothesized that SOD3 gene expression is decreased in patients with IPAH due to aberrant DNA methylation and/or histone deacetylation. We used lung tissue and pulmonary artery smooth muscle cells (PASMC) from subjects with IPAH at transplantation and from failed donors (FD). Lung SOD3 mRNA expression and activity was decreased in IPAH vs. FD. In contrast, mitochondrial SOD (Mn-SOD or SOD2) protein expression was unchanged and intracellular SOD activity was unchanged. Using bisulfite sequencing in genomic lung or PASMC DNA, we found the methylation status of the SOD3 promoter was similar between FD and IPAH. Furthermore, treatment with 5-aza-2′-deoxycytidine did not increase PASMC SOD3 mRNA, suggesting DNA methylation was not responsible for PASMC SOD3 expression. Though total histone deacetylase (HDAC) activity, histone acetyltransferase (HAT) activity, acetylated histones, and acetylated SP1 were similar between IPAH and FD, treatment with two selective class I HDAC inhibitors increased SOD3 only in IPAH PASMC. Class I HDAC3 siRNA also increased SOD3 expression. Trichostatin A, a pan-HDAC inhibitor, decreased proliferation in IPAH, but not in FD PASMC. These data indicate that histone deacetylation, specifically via class I HDAC3, decreases SOD3 expression in PASMC and HDAC inhibitors may protect IPAH in part by increasing PASMC SOD3 expression. PMID:27233998

  9. Detection of patent ductus arteriosus with intraoperative transesophageal echocardiography in a patient undergoing closure of coronary artery to pulmonary artery fistula.

    PubMed

    Miyata, Yuka; Hayashi, Yukio

    2017-01-01

    Coronary artery to pulmonary artery fistula is an unusual vascular anomaly, and the shunt ratio of this fistula is usually small. We report anesthetic management of a 55-year-old female with annuloaortic ectasia, aortic valve regurgitation, and coronary artery to pulmonary artery fistula undergoing radical repair. We calculated the left-to-right shunt ratio after placement of a pulmonary artery catheter and found that the ratio was unexpectedly high. Thus, we explored the presence of another shunt by intraoperative transesophageal echocardiography and found patent ductus arteriosus undiagnosed before operation. A combination of a pulmonary artery catheter and transesophageal echocardiography is useful to explore the presence of another shunt, such as patent ductus arteriosus during anesthesia.

  10. [The heart catheter table is not the operating table : Intraindividual comparison of pulmonary artery pressures].

    PubMed

    Ziegler, M U; Reinelt, H

    2018-05-01

    Patients undergoing cardiac surgery need extensive and invasive monitoring, which needs to be individually adapted for each patient and requires a diligent risk-benefit analysis. The use of a pulmonary artery catheter (PAC) seems to be justifiable in certain cases; therefore, the preoperative diagnosis of pulmonary hypertension represents an indication for perioperative monitoring with PAC in the S3 guidelines of the German Society for Anesthesiology and Intensive Care Medicine (DGAI). In many cases, however, this preoperative diagnosis cannot be confirmed intraoperatively. We wanted to find out whether this is just an impression or whether there actually are significant differences between preoperative, intraoperative and postoperative pulmonary artery pressures. After obtaining ethical approval, we retrospectively compared the pulmonary pressures of cardiac surgery patients with an elevated pulmonary pressure during preoperative right heart catheterization with those obtained intraoperatively and postoperatively by means of a PAC. All patients with a preoperatively documented pulmonary artery pressure of 40 mmHg or above and an intraoperative use of a PAC during a 4-year period were included. Exclusion criteria were intracardiac shunts, cardiogenic shock, emergency procedures, pulmonary hypertension of non-cardiac origin and a time span of more than 1 year between right heart catheterization and surgery. We included 90 patients. In the whole group and in the subgroups (according to diagnosis, time elapsed between heart catheterization and operation and pulmonary pressure), there were significant differences between preoperative and intraoperative pulmonary and systemic pressures. Systemic and pulmonary artery pressures were significantly higher during preoperative catheterization than intraoperatively. The systemic systolic pressure/systolic pulmonary pressure ratio, however, remained constant. The intraoperative and postoperative systemic and pulmonary

  11. Lineage Analysis in Pulmonary Arterial Hypertension

    DTIC Science & Technology

    2013-06-01

    monocrotaline pyrrole . The fate of lacZ-expressing cells will be correlated with immunofluorescent staining of endothelial marker CD31, mesenchymal marker...A) Pilot study: Time course of development of pulmonary hypertension in pneumonectomized mice injected with monocrotaline pyrrole (P/MCTP, n = 4... pyrrole . A, B) Normal muscular pulmonary artery (PA) adjacent to bronchiole (Br) A) hematoxylin and eosin stain (H&E), B) elastin-van Gieson stain (EVG

  12. [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

  13. Inhibition of Notch3 prevents monocrotaline-induced pulmonary arterial hypertension.

    PubMed

    Zhang, Yonghong; Xie, Xinming; Zhu, Yanting; Liu, Lu; Feng, Wei; Pan, Yilin; Zhai, Cui; Ke, Rui; Li, Shaojun; Song, Yang; Fan, Yuncun; Fan, Fenling; Wang, Xiaochuang; Li, Fengjuan; Li, Manxiang

    2015-01-01

    It has been shown that activation of Notch3 signaling is involved in the development of pulmonary arterial hypertension (PAH) by stimulating pulmonary arteries remodeling, while the molecular mechanisms underlying this are still largely unknown. The aims of this study are to address these issues. Monocrotaline dramatically increased right ventricle systolic pressure to 39.0 ± 2.6 mmHg and right ventricle hypertrophy index to 53.4 ± 5.3% (P < 0.05 versus control) in rats, these were accompanied with significantly increased proliferation and reduced apoptosis of pulmonary vascular cells as well as pulmonary arteries remodeling. Treatment of PAH model with specific Notch inhibitor DAPT significantly reduced right ventricle systolic pressure to 26.6 ± 1.3 mmHg and right ventricle hypertrophy index to 33.5 ± 2.6% (P < 0.05 versus PAH), suppressed proliferation and enhanced apoptosis of pulmonary vascular cells as well as inhibited pulmonary arteries remodeling. Our results further indicated that level of Notch3 protein and NICD3 were increased in MCT-induced model of PAH, this was accompanied with elevation of Skp2 and Hes1 protein level and reduction of P27Kip1. Administration of rats with DAPT-prevented MCT induced these changes. Our results suggest that Notch3 signaling activation stimulated pulmonary vascular cells proliferation by Skp2-and Hes1-mediated P27Kip1 reduction, and Notch3 might be a new target to treat PAH.

  14. Pulmonary Arterial Hypertension Associated With Systemic Lupus Erythematosus: Results From the French Pulmonary Hypertension Registry.

    PubMed

    Hachulla, Eric; Jais, Xavier; Cinquetti, Gaël; Clerson, Pierre; Rottat, Laurence; Launay, David; Cottin, Vincent; Habib, Gilbert; Prevot, Grégoire; Chabanne, Céline; Foïs, Eléna; Amoura, Zahir; Mouthon, Luc; Le Guern, Véronique; Montani, David; Simonneau, Gérald; Humbert, Marc; Sobanski, Vincent; Sitbon, Olivier

    2018-01-01

    Pulmonary arterial hypertension (PAH) is a rare complication of systemic lupus erythematosus (SLE). We identified all patients with SLE and PAH (SLE-PAH) who were enrolled in the French Pulmonary Hypertension Registry with a diagnosis confirmed by right heart catheterization (RHC). A control group of 101 patients with SLE without known PAH was selected from SLE expert centers participating in the Pulmonary Hypertension Registry. Survival was estimated by the Kaplan-Meier method. Hazard ratios associated with potential predictors of death were estimated using Cox proportional hazard models. Of the 69 patients with SLE-PAH identified in the French Pulmonary Hypertension Registry, 51 were included in the study. They did not differ from the control group regarding age, sex, or duration of SLE at the time of the analysis but had a higher frequency of anti-SSA and anti-SSB antibodies. The delay between SLE diagnosis and PAH diagnosis was 4.9 years (range, 2.8-12.9) years. The 3- and 5-year overall survival rates were 89.4% (95% CI, 76.2%-96.5%) and 83.9% (95% CI, 68.8%-92.1%), respectively. The survival rate was significantly better in patients with anti-U1-RNP antibodies (P = .04). Patients with SLE-PAH have an overall 5-year survival rate of 83.9% after the PAH diagnosis. Anti-SSA/SSB antibodies may be a risk factor for PAH, and the presence of anti-U1-RNP antibodies appears to be a protective factor regarding survival. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  15. Anomalous Left Coronary Artery from the Pulmonary Artery: Masquerading as Peripartum Cardiomyopathy.

    PubMed

    Frigault, Jonathan; Lafrenière-Bessi, Valérie; Perron, Jean; Bédard, Élisabeth; Philippon, François; Poirier, Paul; Larose, Éric; Jacques, Frédéric

    2018-03-09

    Diagnosed with peripartum cardiomyopathy 8 years earlier, a 45-year-old female suffered sudden cardiac death. Following resuscitation, the patient was diagnosed with an anomalous origin of the left coronary artery from the pulmonary artery and underwent a successful coronary repair. The management of a patient with clinical features of cardiomyopathy is reviewed. Anomalous left coronary artery originating from the pulmonary artery (ALCAPA) is a rare but potentially lethal congenital anomaly affecting 1 in 300,000 live births 1 . Infants may have clinical features of myocardial ischemia and congestive heart failure 2 . Most surgically untreated patients die within the first year of life 3 . Although rare in teenagers and adults, this syndrome can cause sudden cardiac death 3 . ALCAPA that becomes clinically significant in the peripartum period and that is misdiagnosed for a postpartum cardiomyopathy, such as presented herein, is a very rare occurrence. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  16. 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.

  17. Dual origin of the right vertebral artery from the right common carotid and aberrant right subclavian arteries.

    PubMed

    Moshayedi, Pouria; Walker, Gregory B; Tavakoli, Sina; Desai, Shashvat M; Jadhav, Ashutosh P

    2018-07-01

    This report describes a case of duplicated origin of the right vertebral artery incidentally found in a young patient. Computed tomographic angiography and digital subtraction angiography showed a dominant branch derived from the right common carotid artery and an accessory branch that derived from the right subclavian artery, which aberrantly originated from the far left aortic arch, and adjoined the dominant branch at the C5 level. We discuss angiographic findings, clinical implications and embryological basis for this rare anomaly. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. [Analysis of factors related to pulmonary hypertensive crisis in patients with idiopathic pulmonary arterial hypertension].

    PubMed

    Zhang, Chen; Li, Qiangqiang; Zhu, Yan; Gu, Hong

    2014-06-10

    To explore the risk and protective factors for pulmonary hypertensive crisis (PHC) in patients with idiopathic pulmonary arterial hypertension (IPAH). A retrospective study was performed for 65 patients with a diagnosis of IPAH between January 2010 and December 2013. According to clinical manifestations, they were divided into two groups of susceptibility and non-susceptibility to PHC. Clinical and hemodynamic parameters were analyzed in univariate and multivariate manners. Among them, there were 32 males and 33 females with a mean age of (14.4 ± 12.3) (10/12-47.3) years. Twenty-three patients had typical manifestations of PHC and 18 of them were induced by exercises.Univariate analysis revealed that the proportion of patients with World Health Organization (WHO) functional class III-IV in PHC-susceptible group was significantly higher than PHC-nonsusceptible group (60.9% vs 23.8%, P = 0.003) while the percentage of patent foramen ovale in PHC-susceptible group was significantly lower than PHC-nonsusceptible group (8.7% vs 45.2%, P = 0.003).In patients with WHO functional classI-II, hemodynamic variables including the decline of pulmonary arterial pressure and positive rate in vasoreactivity testing in PHC-susceptible group were significantly higher than PHC-nonsusceptible group.In patients with WHO functional class III-IV, baseline pulmonary arterial pressure and mean right atrial pressure in PHC-susceptible group were significantly higher than those in PHC-nonsusceptible group. Multivariate Logistic regression analysis revealed that, for those with WHO functional class III-IV (OR = 23.45, 95%CI: 2.85-193.09) and the decline of systolic pulmonary arterial pressure in vasoreactivity testing (OR = 1.12, 95%CI: 1.04-1.22) were independent risk factors for PHC in IPAH patients while patent foramen ovale (OR = 0.01, 95%CI: 0.00-0.52) was a protective factor. PHC in IPAH patients is correlated with WHO functional class, pulmonary vascular reactivity, baseline pulmonary

  19. Contribution of reactive oxygen species to the pathogenesis of pulmonary arterial hypertension

    PubMed Central

    Naik, Jay S.; Weise-Cross, Laura; Detweiler, Neil D.; Herbert, Lindsay M.; Yellowhair, Tracylyn R.; Resta, Thomas C.

    2017-01-01

    Pulmonary arterial hypertension is associated with a decreased antioxidant capacity. However, neither the contribution of reactive oxygen species to pulmonary vasoconstrictor sensitivity, nor the therapeutic efficacy of antioxidant strategies in this setting are known. We hypothesized that reactive oxygen species play a central role in mediating both vasoconstrictor and arterial remodeling components of severe pulmonary arterial hypertension. We examined the effect of the chemical antioxidant, TEMPOL, on right ventricular systolic pressure, vascular remodeling, and enhanced vasoconstrictor reactivity in both chronic hypoxia and hypoxia/SU5416 rat models of pulmonary hypertension. SU5416 is a vascular endothelial growth factor receptor antagonist and the combination of chronic hypoxia/SU5416 produces a model of severe pulmonary arterial hypertension with vascular plexiform lesions/fibrosis that is not present with chronic hypoxia alone. The major findings from this study are: 1) compared to hypoxia alone, hypoxia/SU5416 exposure caused more severe pulmonary hypertension, right ventricular hypertrophy, adventitial lesion formation, and greater vasoconstrictor sensitivity through a superoxide and Rho kinase-dependent Ca2+ sensitization mechanism. 2) Chronic hypoxia increased medial muscularization and superoxide levels, however there was no effect of SU5416 to augment these responses. 3) Treatment with TEMPOL decreased right ventricular systolic pressure in both hypoxia and hypoxia/SU5416 groups. 4) This effect of TEMPOL was associated with normalization of vasoconstrictor responses, but not arterial remodeling. Rather, medial hypertrophy and adventitial fibrotic lesion formation were more pronounced following chronic TEMPOL treatment in hypoxia/SU5416 rats. Our findings support a major role for reactive oxygen species in mediating enhanced vasoconstrictor reactivity and pulmonary hypertension in both chronic hypoxia and hypoxia/SU5416 rat models, despite a

  20. Preceding bronchial cutting for exposure of the pulmonary artery buried in scar tissue after chemoradiotherapy.

    PubMed

    Nomori, Hiroaki; Cong, Yue; Sugimura, Hiroshi

    2017-01-01

    It is often difficult to expose the pulmonary artery buried in a scar tissue, especially in lung cancer patients that responded well to neoadjuvant chemoradiotherapy. Difficulty to access pulmonary artery branches may lead to potentially unnecessary pneumonectomy. To complete lobectomy in such cases, a technique with preceding bronchial cutting for exposure of the pulmonary artery is presented. After dissecting the pulmonary vein, the lobar bronchus is cut from the opposite side of the pulmonary artery with scissors. The back wall of the lobar bronchus is cut using a surgical knife from the luminal face, which can expose the pulmonary artery behind the bronchial stump and then complete lobectomy. Fourteen patients have been treated using the present technique, enabling complete resection by lobectomy (including sleeve lobectomy in 3 patients) without major bleeding. The present procedure can expose pulmonary artery buried in scar tissue, resulting in making the lobectomy safer.

  1. Wave reflections in the pulmonary arteries analysed with the reservoir–wave model

    PubMed Central

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

    2014-01-01

    Conventional haemodynamic analysis of pressure and flow in the pulmonary circulation yields incident and reflected waves throughout the cardiac cycle, even during diastole. The reservoir–wave model provides an alternative haemodynamic analysis consistent with minimal wave activity during diastole. Pressure and flow in the main pulmonary artery were measured in anaesthetized dogs and the effects of hypoxia and nitric oxide, volume loading and positive end-expiratory pressure were observed. The reservoir–wave model was used to determine the reservoir contribution to pressure and flow and once subtracted, resulted in ‘excess’ quantities, which were treated as wave-related. Wave intensity analysis quantified the contributions of waves originating upstream (forward-going waves) and downstream (backward-going waves). In the pulmonary artery, negative reflections of incident waves created by the right ventricle were observed. Overall, the distance from the pulmonary artery valve to this reflection site was calculated to be 5.7 ± 0.2 cm. During 100% O2 ventilation, the strength of these reflections increased 10% with volume loading and decreased 4% with 10 cmH2O positive end-expiratory pressure. In the pulmonary arterial circulation, negative reflections arise from the junction of lobar arteries from the left and right pulmonary arteries. This mechanism serves to reduce peak systolic pressure, while increasing blood flow. PMID:24756638

  2. Right ventricle performances with echocardiography and 99mTc myocardial perfusion imaging in pulmonary arterial hypertension patients.

    PubMed

    Liu, Jie; Fei, Lei; Huang, Guang-Qing; Shang, Xiao-Ke; Liu, Mei; Pei, Zhi-Jun; Zhang, Yong-Xue

    2018-05-01

    Right heart catheterization is commonly used to measure right ventricle hemodynamic parameters and is the gold standard for pulmonary arterial hypertension diagnosis; however, it is not suitable for patients' long-term follow-up. Non-invasive echocardiography and nuclear medicine have been applied to measure right ventricle anatomy and function, but the guidelines for the usefulness of clinical parameters remain to be established. The goal of this study is to identify reliable clinical parameters of right ventricle function in pulmonary arterial hypertension patients and analyze the relationship of these clinical parameters with the disease severity of pulmonary arterial hypertension. In this study, 23 normal subjects and 23 pulmonary arterial hypertension patients were recruited from January 2015 to March 2016. Pulmonary arterial hypertension patients were classified into moderate and severe pulmonary arterial hypertension groups according to their mean pulmonary arterial pressure levels. All the subjects were subjected to physical examination, chest X-ray, 12-lead electrocardiogram, right heart catheterization, two-dimensional echocardiography, and technetium 99m ( 99m Tc) myocardial perfusion imaging. Compared to normal subjects, the right heart catheterization indexes including right ventricle systolic pressure, right ventricle end diastolic pressure, pulmonary artery systolic pressure, pulmonary artery diastolic pressure, pulmonary vascular resistance, and right ventricle end systolic pressure increased in pulmonary arterial hypertension patients and were correlated with mean pulmonary arterial pressure levels. Echocardiography parameters, including tricuspid regurgitation peak velocity, tricuspid regurgitation pressure gradient, tricuspid annular plane systolic excursion and fractional area, right ventricle-myocardial performance index, were significantly associated with the mean pulmonary arterial pressure levels in pulmonary arterial hypertension patients

  3. Aberrant Left Inferior Bronchial Artery Originating from the Left Gastric Artery in a Patient with Acute Massive Hemoptysis

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

    Jiang, Sen, E-mail: jasfly77@vip.163.com; Sun, Xi-Wen, E-mail: xwsun@citiz.net; Yu, Dong, E-mail: yudong_mail@126.com

    Massive hemoptysis is a life-threatening condition, and the major source of bleeding in this condition is the bronchial circulation. Bronchial artery embolization is a safe and effective treatment for controlling hemoptysis. However, the sites of origin of the bronchial arteries (BAs) have numerous anatomical variations, which can result in a technical challenge to identify a bleeding artery. We present a rare case of a left inferior BA that originated from the left gastric artery in a patient with recurrent massive hemoptysis caused by bronchiectasis. The aberrant BA was embolized, and hemoptysis has been controlled for 8 months.

  4. Surgical correction of an aberrant right subclavian artery in a dog.

    PubMed

    Yoon, Hun-Young; Jeong, Soon-wuk

    2011-10-01

    A diagnosis of an aberrant right subclavian artery was made in a 3-month-old Boston terrier. Surgical correction was performed after confirming adequate collateral circulation. Reports of surgical correction and evaluation of the perioperative thoracic limb blood pressure are rare in dogs.

  5. Platelet-derived growth factor receptor-β and epidermal growth factor receptor in pulmonary vasculature of systemic sclerosis-associated pulmonary arterial hypertension versus idiopathic pulmonary arterial hypertension and pulmonary veno-occlusive disease: a case-control study.

    PubMed

    Overbeek, Maria J; Boonstra, Anco; Voskuyl, Alexandre E; Vonk, Madelon C; Vonk-Noordegraaf, Anton; van Berkel, Maria P A; Mooi, Wolter J; Dijkmans, Ben A C; Hondema, Laurens S; Smit, Egbert F; Grünberg, Katrien

    2011-04-14

    Systemic sclerosis (SSc) complicated by pulmonary arterial hypertension (PAH) carries a poor prognosis, despite pulmonary vascular dilating therapy. Platelet-derived growth factor receptor-β (PDGFR-β) and epidermal growth factor receptor (EGFR) are potential therapeutic targets for PAH because of their proliferative effects on vessel remodelling. To explore their role in SScPAH, we compared PDGFR- and EGFR-mmunoreactivity in lung tissue specimens from SScPAH. We compared staining patterns with idiopathic PAH (IPAH) and pulmonary veno-occlusive disease (PVOD), as SScPAH vasculopathy differs from IPAH and sometimes displays features of PVOD. Immunoreactivity patterns of phosphorylated PDGFR-β (pPDGFR-β) and the ligand PDGF-B were evaluated to provide more insight into the patterns of PDGFR-b activation. Lung tissue specimens from five SScPAH, nine IPAH, six PVOD patients and five controls were examined. Immunoreactivity was scored for presence, distribution and intensity. All SScPAH and three of nine IPAH cases (P = 0.03) showed PDGFR-β-immunoreactivity in small vessels (arterioles/venules); of five SScPAH vs. two of nine IPAH cases (P = 0.02) showed venous immunoreactivity. In small vessels, intensity was stronger in SScPAH vs. IPAH. No differences were found between SScPAH and PVOD. One of five normal controls demonstrated focally mild immunoreactivity. There were no differences in PDGF-ligand and pPDGFR-b-immunoreactivity between patient groups; however, pPDGFR-b-immunoreactivity tended to be more prevalent in SScPAH small vasculature compared to IPAH. Vascular EGFR-immunoreactivity was limited to arterial and arteriolar walls, without differences between groups. No immunoreactivity was observed in vasculature of normals. PDGFR-β-immunoreactivity in SScPAH is more common and intense in small- and post-capillary vessels than in IPAH and does not differ from PVOD, fitting in with histomorphological distribution of vasculopathy. PDGFR-β immunoreactivity

  6. Aortic Implantation of Anomalous Origin of the Left Coronary Artery From the Pulmonary Artery: Long-Term Outcomes.

    PubMed

    Mongé, Michael C; Eltayeb, Osama; Costello, John M; Sarwark, Anne E; Carr, Michael R; Backer, Carl L

    2015-07-01

    Since 1989 all patients with anomalous origin of the left coronary artery from the pulmonary artery at our institution have been treated with aortic implantation. The purpose of this review was to assess the late outcomes of these patients, especially regarding left ventricular (LV) function and mitral valve insufficiency. Between 1989 and 2014, 36 patients had aortic implantation of anomalous origin of the left coronary artery from the pulmonary artery. Mean age at surgery was 2.5 ± 5.1 years (median, 0.5 years). Operative strategy included antegrade cold-blood cardioplegia, main pulmonary artery transection, aortic implantation with a large button of pulmonary artery, pulmonary reconstruction with fresh autologous pericardium, and prolonged postoperative inotropic and ventilator support. Mitral regurgitation and LV dysfunction were graded as 0 to 4 (0 = none, 1 = trivial, 1.5 = trivial-mild, 2 = mild, 2.5 = mild-moderate, 3 = moderate, 3.5 = moderate-severe, and 4 = severe). Mean mitral regurgitation grade preoperatively was 2.95 ± 0.95. Mean LV dysfunction grade was 3.14 ± 1.27. Mean cross-clamp and cardiopulmonary bypass times were 49.1 ± 18 minutes (median, 48.5 minutes) and 147.5 ± 45 minutes (median, 139 minutes), respectively. There was no operative or late mortality. Four patients had delayed sternal closure. Mean duration of ventilator support was 11 ± 6.6 days (median, 9 days). Two patients required 3 and 6 days of postoperative extracorporeal mechanical circulatory support. Mean length of stay was 25 ± 18 days (median, 19 days). No patient has required reoperation for supravalvar pulmonary stenosis, coronary stenosis, or mitral valve repair or replacement. Late echocardiographic follow-up shows a mean mitral regurgitation grade of 1.67 ± 1.05 and a mean LV dysfunction grade of 0.23 ± 0.68. Aortic implantation is our procedure of choice for patients with anomalous origin of the left coronary artery from the pulmonary artery. No patient required

  7. [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.

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

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

    Sueyoshi, Eijun, E-mail: EijunSueyoshi@aol.com; Sakamoto, Ichiro; Uetani, Masataka

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

  9. Role of chymase in cigarette smoke-induced pulmonary artery remodeling and pulmonary hypertension in hamsters.

    PubMed

    Wang, Tao; Han, Su-Xia; Zhang, Shang-Fu; Ning, Yun-Ye; Chen, Lei; Chen, Ya-Juan; He, Guang-Ming; Xu, Dan; An, Jin; Yang, Ting; Zhang, Xiao-Hong; Wen, Fu-Qiang

    2010-03-31

    Cigarette smoking is an important risk factor for pulmonary arterial hypertension (PAH) in chronic obstructive pulmonary disease (COPD). Chymase has been shown to function in the enzymatic production of angiotensin II (AngII) and the activation of transforming growth factor (TGF)-beta1 in the cardiovascular system. The aim of this study was to determine the potential role of chymase in cigarette smoke-induced pulmonary artery remodeling and PAH. Hamsters were exposed to cigarette smoke; after 4 months, lung morphology and tissue biochemical changes were examined using immunohistochemistry, Western blotting, radioimmunoassay and reverse-transcription polymerase chain reaction. Our results show that chronic cigarette smoke exposure significantly induced elevation of right ventricular systolic pressures (RVSP) and medial hypertrophy of pulmonary arterioles in hamsters, concurrent with an increase of chymase activity and synthesis in the lung. Elevated Ang II levels and enhanced TGF-beta1/Smad signaling activation were also observed in smoke-exposed lungs. Chymase inhibition with chymostatin reduced the cigarette smoke-induced increase in chymase activity and Ang II concentration in the lung, and attenuated the RVSP elevation and the remodeling of pulmonary arterioles. Chymostatin did not affect angiotensin converting enzyme (ACE) activity in hamster lungs. These results suggest that chronic cigarette smoke exposure can increase chymase activity and expression in hamster lungs. The capability of activated chymase to induce Ang II formation and TGF-beta1 signaling may be part of the mechanism for smoking-induced pulmonary vascular remodeling. Thus, our study implies that blockade of chymase might provide benefits to PAH smokers.

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

    PubMed Central

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

    2011-01-01

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

  11. Patent ductus arteriosus with persistent pulmonary artery hypertension after transcatheter closure.

    PubMed

    Feng, Jianqi; Kong, Xiangqing; Sheng, Yanhui; Yang, Rong

    2016-01-01

    To observe the change in pulmonary artery systolic pressure (PASP) of patients with persistent pulmonary arterial hypertension (PAH) after patent ductus arteriosus (PDA) occlusion. After occlusion of PDA in patients with PAH, some patients still tend to suffer from persistent PAH. A chest X-ray, an electrocardiogram, and an echocardiogram were performed on nine patients at 24 hours, 1 and 6 months, and 1 year serially. There was a significant fall ( P <0.05) in mean PASP after occlusion (to 59.3±12.7 mmHg). However, the aortic pressure and systemic arterial oxygen saturation changed slightly ( P >0.05). During the follow up, there was a further fall in the PASP in five patients (No 1, 5, 6, 7, and 8). Four patients (No 2, 3, 4, and 8) showed the evidence of worsening PAH and were treated with sildenafil. Patient 2 died from acute right heart failure after a period of 11 months from the time of transcatheter closure, triggered by pulmonary infection. Some patients with borderline hemodynamic data with PDA and PAH can deteriorate or keep sustained PAH after PDA closure. The treatment of permanent closure to these patients must be cautious.

  12. An unusual neonatal presentation of anomalous origin of the left coronary artery arising from the pulmonary artery.

    PubMed

    Garty, Y; Guri, A; Shinwell, E S; Matitiau, A

    2008-01-01

    We describe a previously unreported neonatal presentation of an anomalous origin of the left coronary artery arising from the pulmonary artery. This is a full-term female infant after normal pregnancy and delivery. The baby was diagnosed at 2 days of age due to weak femoral pulses noted on the routine nursery discharge examination. The cardiac examination revealed weak pulses everywhere and mild tachypnea and tachycardia. An electrocardiogram showed clear signs of ischemia. Echocardiography demonstrated an anomalous origin of the left coronary artery arising from the pulmonary artery with bidirectional blood flow. There was a severely depressed left ventricular function and mild mitral valve regurgitation. At 4 days of age, the infant underwent complete successful surgical repair with reimplantation of the anomalous coronary artery to the aorta. She recovered slowly but well. Fifteen months later she is doing well with no cardiac residua. A neonatal presentation is very unusual due to protective high pulmonary resistance after birth, with gradual decline in pressure and gradual onset of heart failure. This case may be related to an unusually rapid drop in pulmonary vascular resistance causing very early cardiac ischemia. (c) 2007 S. Karger AG, Basel.

  13. Late Diagnosed Left Coronary to the Pulmonary Artery Large Fistulae: An Interesting and Incidental Cath Lab Finding

    PubMed Central

    de Melo, Pedro H. M. Craveiro; Abreu-Silva, Érlon O.; Coura, Fernando Barbiero; Rios, Gleyson Moraes; Potério, Daniel Izzet

    2016-01-01

    Coronary artery anomalies are congenital changes in their origin, course, and/or structure. Most of them are discovered as incidental findings during coronary angiographic studies or at autopsies. A coronary artery fistulae involve a communication between a coronary artery and a chamber of the heart or any segment of the systemic or pulmonary circulation. We present herein the case of a 67-year-old man with a recent history of exertional angina and dyspnea to usual daily activities whose coronary angiogram revealed an interesting and incidental coronary-pulmonary artery large fistulae. PMID:28053791

  14. Late Diagnosed Left Coronary to the Pulmonary Artery Large Fistulae: An Interesting and Incidental Cath Lab Finding.

    PubMed

    Oliveira, Marcos Danillo P; de Melo, Pedro H M Craveiro; Abreu-Silva, Érlon O; Coura, Fernando Barbiero; Rios, Gleyson Moraes; Potério, Daniel Izzet

    2016-01-01

    Coronary artery anomalies are congenital changes in their origin, course, and/or structure. Most of them are discovered as incidental findings during coronary angiographic studies or at autopsies. A coronary artery fistulae involve a communication between a coronary artery and a chamber of the heart or any segment of the systemic or pulmonary circulation. We present herein the case of a 67-year-old man with a recent history of exertional angina and dyspnea to usual daily activities whose coronary angiogram revealed an interesting and incidental coronary-pulmonary artery large fistulae.

  15. Severe pulmonary arterial hypertension due to Angiostrongylosus vasorum in a dog

    PubMed Central

    Nicolle, Audrey P.; Chetboul, Valérie; Tessier-Vetzel, Dominique; Sampedrano, Carolina Carlos; Aletti, Edouard; Pouchelon, Jean-Louis

    2006-01-01

    A dog was presented with a history of dyspnea, coughing, and ascites. Angiostrongylosis and severe pulmonary arterial hypertension (PAH) were found, as well as a marked discordance between the electrical and mechanical events of the heart. Pulmonary arterial hypertension related to Angiostrongylus vasorum has rarely been reported. PMID:16933559

  16. The β2 agonist terbutaline specifically decreases pulmonary arterial pressure under normoxia and hypoxia via α adrenoceptor antagonism.

    PubMed

    Neumann, Vanessa; Knies, Ralf; Seidinger, Alexander; Simon, Annika; Lorenz, Kristina; Matthey, Michaela; Breuer, Johannes; Wenzel, Daniela

    2018-05-01

    Pulmonary hypertension is a severe, incurable disease with a poor prognosis. Although treatment regimens have improved during the last 2 decades, current pharmacologic strategies are limited and focus on the modulation of only a few pathways related to endothelin, NO, and prostacyclin signaling. Therefore, the identification of novel molecular targets is urgently needed. We found that the β 2 adrenoceptor (AR) agonists terbutaline (TER) and salbutamol induced a dose-dependent vasorelaxation in large pulmonary arteries but not aortas of mouse. This effect was found to be independent of β ARs and the endothelium but was determined by the type of the preconstrictor. Vasodilation by β 2 AR agonists occurred after pretreatment of pulmonary arteries with phenylephrine and serotonin, both agonists of α 1 ARs, but was absent after preconstriction with the thromboxane analog U46619. These data indicated α-adrenolytic activity of β 2 AR agonists, which was confirmed by a right shift of the phenylephrine dose-response curve by TER. This effect was physiologically relevant because TER also relaxed small intrapulmonary arteries in lung slices and diminished pulmonary arterial pressure in an isolated perfused lung model under normoxia and hypoxia. Finally, TER applied as an aerosol also selectively decreased pulmonary arterial pressure without effects on systemic blood pressure and heart rate in mouse in vivo. Thus, β 2 AR agonists display α-adrenolytic activity in pulmonary arteries ex vivo and in vivo, and may provide a novel option to reduce pulmonary arterial pressure in pulmonary hypertension.-Neumann, V., Knies, R., Seidinger, A., Simon, A., Lorenz, K., Matthey, M., Breuer, J., Wenzel, D. The β 2 agonist terbutaline specifically decreases pulmonary arterial pressure under normoxia and hypoxia via α adrenoceptor antagonism.

  17. Pulmonary arterial distension and vagal afferent nerve activity in anaesthetized dogs.

    PubMed

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

    2004-03-16

    Distension of the main pulmonary artery and its bifurcation are known to result in a reflex vasoconstriction and increased respiratory drive; however, these responses are observed at abnormally high distending pressures. In this study we recorded afferent activity from pulmonary arterial baroreceptors to investigate their stimulus-response characteristics and to determine whether they are influenced by physiological changes in intrathoracic pressure. In chloralose-anaesthetized dogs, a cardiopulmonary bypass was established, the pulmonary trunk and its main branches were vascularly isolated and perfused with venous blood at pulsatile pressures designed to simulate the normal pulmonary arterial pressure waveform. Afferent slips of a cervical vagus were dissected and nerve fibres identified that displayed discharge patterns with characteristics expected from pulmonary arterial baroreceptors. Recordings were obtained with (a) chest open (b) chest closed and resealed, and (c) with phasic negative intrathoracic pressures in the resealed chest. Pressure-discharge characteristics obtained in the open-chest animals indicated that the threshold pulmonary pressure (corresponding to 5% of the overall response) was 17.1 +/- 2.9 and the inflexion point of the curve was 29.2 +/- 3.3 mmHg (mean +/-S.E.M). In closed-chest animals the threshold and inflexion pressures were reduced to 12.0 +/- 1.7 and 20.7 +/- 1.8 mmHg. Application of phasic negative intrathoracic pressures further reduced the threshold and inflexion pressures to 9.5 +/- 1.2 mmHg (P < 0.05 vs. open) and 14.7 +/- 0.8 mmHg (P < 0.003 vs. open and P < 0.02 vs. atmospheric). These results indicate that under physiological conditions, with closed-chest and phasic negative intrathoracic pressure changes similar to those associated with normal breathing, activity from pulmonary baroreceptors is obtained at physiological pulmonary arterial pressures in intact animals.

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

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

    Anand, Girija, E-mail: gijanandm@hotmail.com; Lewanski, Conrad R.; Cowman, Steven A.

    2011-02-15

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

  19. 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

  20. High-resolution CT evaluation of bronchial lumen to vertebral body, pulmonary artery to vertebral body and bronchial lumen to pulmonary artery ratios in Dirofilaria immitis-infected cats with and without selamectin administration.

    PubMed

    Lee-Fowler, Tekla M; Cole, Robert C; Dillon, A Ray; Graham, Shannon; Tillson, D Michael; Barney, Sharron

    2017-10-01

    Objectives The bronchial lumen to pulmonary artery (BA) ratio is utilized to evaluate pulmonary pathology on CT images. The BA ratio may be unreliable when changes are present in bronchial and pulmonary arteries concurrently. Bronchial lumen to vertebral body (BV) and pulmonary artery to vertebral body (AV) ratios have been established in normal cats and may serve as an alternative. This study aimed to evaluate the BV, AV and BA ratios in cats before and after infection with Dirofilaria immitis, with and without selamectin administration, and to characterize the distribution of disease. Methods Archived CT images were reviewed from three groups of cats: D immitis-infected untreated (n = 6); infected pretreated with selamectin (n = 6); uninfected untreated (n = 5). The BV, AV and BA ratios were calculated for all lung lobes for baseline (D0) and day 240 (D240) postinfection. Ratios and percentage change from baseline were compared between lobes and between groups. Results BV and AV ratios were more consistent in identifying abnormalities when disease was present in bronchial and arteries concurrently than BA ratios. Infected untreated cats had significant changes in both BV and AV ratios and percentage change from baseline. Abnormal BV and AV ratios were noted in the infected selamectin group, although less widely distributed. Conclusions and relevance The BV and AV ratios more accurately identified bronchial and pulmonary artery abnormalities in D immitis-infected cats. Both bronchial and pulmonary artery changes were present in infected cats, decreasing the diagnostic application of the BA ratio. Pulmonary artery changes were more widely distributed than bronchial changes in the lung. Heartworm-infected cats receiving selamectin had bronchial and pulmonary artery changes but to a lesser extent than untreated heartworm-infected cats. The CT-derived BV and AV ratios are a useful measure to evaluate lung disease of cats.

  1. Computed tomography angiography reveals stenosis and aneurysmal dilation of an aberrant right subclavian artery causing systemic blood pressure misreading in an old Pekinese dog

    PubMed Central

    KIM, Jaehwan; EOM, Kidong; YOON, Hakyoung

    2017-01-01

    A 14-year-old dog weighing 4 kg presented with hypotension only in the right forelimb. Thoracic radiography revealed a round soft tissue opacity near the aortic arch and below the second thoracic vertebra on a lateral view. Three-dimensional computed tomography angiography clearly revealed stenosis and aneurysmal dilation of an aberrant right subclavian artery. Stenosis and aneurysm of an aberrant subclavian artery should be included as a differential diagnosis in dogs showing a round soft tissue opacity near the aortic arch and below the thoracic vertebra on the lateral thoracic radiograph. PMID:28496026

  2. Computed tomography angiography reveals stenosis and aneurysmal dilation of an aberrant right subclavian artery causing systemic blood pressure misreading in an old Pekinese dog.

    PubMed

    Kim, Jaehwan; Eom, Kidong; Yoon, Hakyoung

    2017-06-16

    A 14-year-old dog weighing 4 kg presented with hypotension only in the right forelimb. Thoracic radiography revealed a round soft tissue opacity near the aortic arch and below the second thoracic vertebra on a lateral view. Three-dimensional computed tomography angiography clearly revealed stenosis and aneurysmal dilation of an aberrant right subclavian artery. Stenosis and aneurysm of an aberrant subclavian artery should be included as a differential diagnosis in dogs showing a round soft tissue opacity near the aortic arch and below the thoracic vertebra on the lateral thoracic radiograph.

  3. Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth muscle cell survival patterns to promote pulmonary arterial hypertension

    PubMed Central

    Aghamohammadzadeh, Reza; Zhang, Ying-Yi; Stephens, Thomas E.; Arons, Elena; Zaman, Paula; Polach, Kevin J.; Matar, Majed; Yung, Lai-Ming; Yu, Paul B.; Bowman, Frederick P.; Opotowsky, Alexander R.; Waxman, Aaron B.; Loscalzo, Joseph; Leopold, Jane A.; Maron, Bradley A.

    2016-01-01

    Activation of the mammalian target of rapamycin complex 1 (mTORC1) subunit Raptor induces cell growth and is a downstream target of Akt. Elevated levels of aldosterone activate Akt, and, in pulmonary arterial hypertension (PAH), correlate with pulmonary arteriole thickening, which suggests that mTORC1 regulation by aldosterone may mediate adverse pulmonary vascular remodeling. We hypothesized that aldosterone-Raptor signaling induces abnormal pulmonary artery smooth muscle cell (PASMC) survival patterns to promote PAH. Remodeled pulmonary arterioles from SU-5416/hypoxia-PAH rats and monocrotaline-PAH rats with hyperaldosteronism expressed increased levels of the Raptor target, p70S6K, which provided a basis for investigating aldosterone-Raptor signaling in human PASMCs. Aldosterone (10−9 to 10−7 M) increased Akt/mTOR/Raptor to activate p70S6K and increase proliferation, viability, and apoptosis resistance in PASMCs. In PASMCs transfected with Raptor–small interfering RNA or treated with spironolactone/eplerenone, aldosterone or pulmonary arterial plasma from patients with PAH failed to increase p70S6K activation or to induce cell survival in vitro. Optimal inhibition of pulmonary arteriole Raptor was achieved by treatment with Staramine-monomethoxy polyethylene glycol that was formulated with Raptor-small interfering RNA plus spironolactone in vivo, which decreased arteriole muscularization and pulmonary hypertension in 2 experimental animal models of PAH in vivo. Up-regulation of mTORC1 by aldosterone is a critical pathobiologic mechanism that controls PASMC survival to promote hypertrophic vascular remodeling and PAH.—Aghamohammadzadeh, R., Zhang, Y.-Y., Stephens, T. E., Arons, E., Zaman, P., Polach, K. J., Matar, M., Yung, L.-M., Yu, P. B., Bowman, F. P., Opotowsky, A. R., Waxman, A. B., Loscalzo, J., Leopold, J. A., Maron, B. A. Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery

  4. Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth muscle cell survival patterns to promote pulmonary arterial hypertension.

    PubMed

    Aghamohammadzadeh, Reza; Zhang, Ying-Yi; Stephens, Thomas E; Arons, Elena; Zaman, Paula; Polach, Kevin J; Matar, Majed; Yung, Lai-Ming; Yu, Paul B; Bowman, Frederick P; Opotowsky, Alexander R; Waxman, Aaron B; Loscalzo, Joseph; Leopold, Jane A; Maron, Bradley A

    2016-07-01

    Activation of the mammalian target of rapamycin complex 1 (mTORC1) subunit Raptor induces cell growth and is a downstream target of Akt. Elevated levels of aldosterone activate Akt, and, in pulmonary arterial hypertension (PAH), correlate with pulmonary arteriole thickening, which suggests that mTORC1 regulation by aldosterone may mediate adverse pulmonary vascular remodeling. We hypothesized that aldosterone-Raptor signaling induces abnormal pulmonary artery smooth muscle cell (PASMC) survival patterns to promote PAH. Remodeled pulmonary arterioles from SU-5416/hypoxia-PAH rats and monocrotaline-PAH rats with hyperaldosteronism expressed increased levels of the Raptor target, p70S6K, which provided a basis for investigating aldosterone-Raptor signaling in human PASMCs. Aldosterone (10(-9) to 10(-7) M) increased Akt/mTOR/Raptor to activate p70S6K and increase proliferation, viability, and apoptosis resistance in PASMCs. In PASMCs transfected with Raptor-small interfering RNA or treated with spironolactone/eplerenone, aldosterone or pulmonary arterial plasma from patients with PAH failed to increase p70S6K activation or to induce cell survival in vitro Optimal inhibition of pulmonary arteriole Raptor was achieved by treatment with Staramine-monomethoxy polyethylene glycol that was formulated with Raptor-small interfering RNA plus spironolactone in vivo, which decreased arteriole muscularization and pulmonary hypertension in 2 experimental animal models of PAH in vivo Up-regulation of mTORC1 by aldosterone is a critical pathobiologic mechanism that controls PASMC survival to promote hypertrophic vascular remodeling and PAH.-Aghamohammadzadeh, R., Zhang, Y.-Y., Stephens, T. E., Arons, E., Zaman, P., Polach, K. J., Matar, M., Yung, L.-M., Yu, P. B., Bowman, F. P., Opotowsky, A. R., Waxman, A. B., Loscalzo, J., Leopold, J. A., Maron, B. A. Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth

  5. 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

  6. Prevalence of chronic obstructive pulmonary disease among patients with systemic arterial hypertension without respiratory symptoms.

    PubMed

    Rabahi, Marcelo Fouad; Pereira, Sheila Alves; Silva Júnior, José Laerte Rodrigues; de Rezende, Aline Pacheco; Castro da Costa, Adeliane; de Sousa Corrêa, Krislainy; Conde, Marcus Barreto

    2015-01-01

    The diagnosis of chronic obstructive pulmonary disease (COPD) is often delayed until later stages of the disease. The purpose of the present study was to determine the prevalence of COPD among adults on treatment for systemic arterial hypertension independently of the presence of respiratory symptoms. This cross-sectional study included adults aged ≥40 years with tobacco/occupational exposure and systemic arterial hypertension diagnosed at three Primary Health Care facilities in Goiania, Brazil. Patients were evaluated using a standardized respiratory questionnaire and spirometry. COPD prevalence was measured considering the value of forced vital capacity and/or forced expiratory volume in 1 second <0.70. Of a total of 570 subjects, 316 (55%) met inclusion criteria and were invited to participate. Two hundred and thirty-three (73.7%) patients with arterial hypertension reported at least one respiratory symptom, while 83 (26.3%) reported no respiratory symptoms; 41 (17.6%) patients with arterial hypertension and at least one respiratory symptom, and 10 (12%) patients with arterial hypertension but no respiratory symptoms were diagnosed with COPD (P=0.24). The prevalence of COPD in people with no previous COPD diagnosis was greater among those with no respiratory symptoms (100%) than among those with respiratory symptoms (56.1%) (P=0.01). Our findings suggest that regardless of the presence of respiratory symptoms, individuals aged ≥40 years with tobacco/occupational exposure and arterial hypertension may benefit from spirometric evaluation.

  7. Pulmonary artery pressure increases during commercial air travel in healthy passengers.

    PubMed

    Smith, Thomas G; Talbot, Nick P; Chang, Rae W; Wilkinson, Elizabeth; Nickol, Annabel H; Newman, David G; Robbins, Peter A; Dorrington, Keith L

    2012-07-01

    It is not known whether the mild hypoxia experienced by passengers during commercial air travel triggers hypoxic pulmonary vasoconstriction and increases pulmonary artery pressure in flight. Insidious pulmonary hypertensive responses could endanger susceptible passengers who have cardiopulmonary disease or increased hypoxic pulmonary vascular sensitivity. Understanding these effects may improve pre-flight assessment of fitness-to-fly and reduce in-flight morbidity and mortality. Eight healthy volunteers were studied during a scheduled commercial airline flight from London, UK, to Denver, CO. The aircraft was a Boeing 777 and the duration of the flight was 9 h. Systolic pulmonary artery pressure (sPAP) was assessed by portable Doppler echocardiography during the flight and over the following week in Denver, where the altitude (5280 ft/1610 m) simulates a commercial airliner environment. Cruising cabin altitude ranged between 5840 and 7170 ft (1780 to 2185 m), and mean arterial oxygen saturation was 95 +/- 0.6% during the flight. Mean sPAP increased significantly in flight by 6 +/- 1 mmHg to 33 +/- 1 mmHg, an increase of approximately 20%. After landing in Denver, sPAP was still 3 +/- 1 mmHg higher than baseline and remained elevated at 30 +/- 1 mmHg for a further 12 h. Pulmonary artery pressure increases during commercial air travel in healthy passengers, raising the possibility that hypoxic pulmonary hypertension could develop in susceptible individuals. A hypoxia altitude simulation test with simultaneous echocardiography ('HAST-echo') may be beneficial in assessing fitness to fly in vulnerable patients.

  8. 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.

  9. Superoxide differentially controls pulmonary and systemic vascular tone through multiple signalling pathways

    PubMed Central

    Snetkov, Vladimir A.; Smirnov, Sergey V.; Kua, Justin; Aaronson, Philip I.; Ward, Jeremy P.T.; Knock, Greg A.

    2011-01-01

    Aims The aim of this study was to determine the relative importance of Ca2+ sensitization, ion channels, and intracellular Ca2+ ([Ca2+]i) in the mixed constrictor/relaxation actions of superoxide anion on systemic and pulmonary arteries. Methods and results Pulmonary and mesenteric arteries were obtained from rat. Superoxide was generated in arteries and cells with 6-anilino-5,8-quinolinequinone (LY83583). Following pre-constriction with U46619, 10 μmol/L LY83583 caused constriction in pulmonary and relaxation in mesenteric arteries. Both constrictor and relaxant actions of LY83583 were inhibited by superoxide dismutase and catalase. LY83583 caused Rho-kinase-dependent constriction in α-toxin-permeabilized pulmonary but not mesenteric arteries. Phosphorylation of myosin phosphatase-targeting subunit-1 (MYPT-1; as determined by western blot), was enhanced by LY83583 in pulmonary artery only. However, in both artery types, changes in tension were closely correlated with changes in phosphorylation of the 20 kDa myosin light chain as well as changes in [Ca2+]i (as measured with Fura PE-3), with LY83583 causing increases in pulmonary and decreases in mesenteric arteries. When U46619 was replaced by 30 mmol/L K+, all changes in [Ca2+]i were abolished and LY83583 constricted both artery types. The KV channel inhibitor 4-aminopyridine abolished the LY83583-induced relaxation in mesenteric artery without affecting constriction in pulmonary artery. However, LY83583 caused a similar hyperpolarizing shift in the steady-state activation of KV current in isolated smooth muscle cells of both artery types. Conclusions Superoxide only causes Rho-kinase-dependent Ca2+ sensitization in pulmonary artery, resulting in constriction, and whilst it opens KV channels in both artery types, this only results in relaxation in mesenteric. PMID:20805095

  10. Oxidative stress is associated with increased pulmonary artery systolic pressure in humans.

    PubMed

    Ghasemzadeh, Nima; Patel, Riyaz S; Eapen, Danny J; Veledar, Emir; Al Kassem, Hatem; Manocha, Pankaj; Khayata, Mohamed; Zafari, A Maziar; Sperling, Laurence; Jones, Dean P; Quyyumi, Arshed A

    2014-06-01

    Oxidative stress contributes to the development of pulmonary hypertension in experimental models, but this association in humans is unknown. We investigated the relationship between pulmonary artery systolic pressure measured by echocardiography and plasma aminothiol oxidative stress markers, with the hypothesis that oxidative stress will be higher in those with pulmonary hypertension. A group of 347 patients aged 65±12 years from the Emory Cardiovascular Biobank underwent echocardiographic assessment of left ventricular ejection fraction and pulmonary artery systolic pressure. Plasma aminothiols, cysteine, its oxidized form, cystine, glutathione, and its oxidized disulphide were measured and the redox potentials (Eh) of cysteine/cystine and glutathione/oxidized glutathione couples were calculated. Non-normally distributed variables were log transformed (Ln). Univariate predictors of pulmonary artery systolic pressure included age (P<0.001), sex (P=0.002), mitral regurgitation (P<0.001), left ventricular ejection fraction (P<0.001), left atrial size (P<0.001), diabetes mellitus (P=0.03), plasma Ln cystine (β=9.53; P<0.001), Ln glutathione (β=-5.4; P=0.002), and Eh glutathione (β=0.21; P=0.001). A multivariate linear regression model adjusting for all confounding variables demonstrated that Ln cystine (β=6.56; P=0.007), mitral regurgitation (β=4.52; P<0.001), statin use (β=-3.39; P=0.03), left ventricular ejection fraction (β=-0.26; P=0.003), and age (β=0.17; P=0.003) were independent predictors of pulmonary artery systolic pressure. For each 1% increase in plasma cystine, pulmonary artery systolic pressure increased by 16%. This association persisted in the subgroup with preserved left ventricular ejection fraction (≥50%) and no significant mitral regurgitation. Whether treatment of oxidative stress will improve pulmonary hypertension requires further study.

  11. [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.

  12. Aberrant left subclavian artery occlusion in right-sided aortic artery associated with left cerebral infarction: A case report.

    PubMed

    Tempaku, Akira; Kuroiwa, Terumasa; Nishio, Akimasa

    2018-06-01

    Purpose Right-sided aortic arch is a rare vessel anomaly with an incidence of 0.1% worldwide. Supra-aortic branches form a mirror image of the left-sided aortic arch or an aberrant left subclavian artery associated with Kommerell diverticulum. Most patients are diagnosed by a difference in blood pressure in each upper extremity or by the presence of left subclavian steal syndrome in their younger age. The diagnosis of onset of ischemic stroke in middle age is rare. Methods We present the case of a female patient who presented with an ischemic stroke in the left posterior circulation area. She had no history of congenital heart malformation. We performed head magnetic resonance imaging, cerebral angiography, and enhanced computed tomography of the aortic arch and major branches. Results The patient had a right-sided aortic arch and an aberrant left subclavian artery. The left subclavian artery was occluded at the proximal portion with a fibrous string. Collateral flow in the anterior cervical subcutaneous area supported left limb perfusion. Conclusion An atheromatous change reduced shunt flow via collateral networks at the anterior cervical region. Congenital subclavian steal supported the ischemic stroke.

  13. Anomalous origin of left coronary artery from pulmonary artery in older children and adults: direct aortic implantation.

    PubMed

    Kottayil, Brijesh P; Jayakumar, Karunakaran; Dharan, Baiju S; Pillai, Vivek V; Ajitkumar, Valaparambil; Menon, Sabarinath; Sanjay, Ganapathi

    2011-02-01

    Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) presents rarely in adulthood and is treated by different surgical techniques with varying results. This study was undertaken to evaluate the feasibility of reestablishment of a dual coronary system in older children and adults with emphasis on direct aortic implantation. From 2002 to 2010, 10 patients aged 10 to 51 years (median age, 24 years) underwent surgical correction of ALCAPA. Median weight was 44.5 kg. All the patients except 2 were symptomatic. Two patients were in atrial fibrillation. Eight patients had varying degrees of mitral regurgitation, which was severe in 2. In all patients, the left coronary artery was arising from the facing sinus of the pulmonary artery. Direct left main coronary implantation into the aorta was feasible in all patients. Mitral valve replacement was done in 4 patients. At a median follow-up of 5.5 years there was no new angina or infarction. One patient died 3 months postsurgery due to intracerebral bleed. Echocardiography demonstrated normal antegrade flow in the transferred left coronary artery, with 2 patients having persistent moderate mitral regurgitation. Coronary angiography done on follow-up in one patient revealed a patent transferred left coronary artery with distal development of new atherosclerotic lesion. Direct reimplantation of the ALCAPA is considered technically more difficult and hazardous in adults. With increased experience with coronary transfer technique, direct aortic implantation is feasible in adult cases. This provides a more physiologic correction and reestablishment of a dual coronary system with a better outcome. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

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

    PubMed

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

    2016-06-01

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

  15. Pulmonary arterial dissection in a post-partum patient with patent ductus arteriosus: Case report and review of the literature

    PubMed Central

    Yaman, Mehmet; Arslan, Uğur; Ateş, Ahmet Hakan; Aksakal, Aytekin

    2015-01-01

    Pulmonary arterial dissection is an uncommon but usually a deadly complication of chronic pulmonary hypertension. A 26-year-old female patient was admitted to our clinics with sudden dyspnea and chest discomfort one hour after giving birth to twins by vaginal delivery. An echocardiography was performed with a pre-diagnosis of pulmonary embolism. However, echocardiographic examination revealed a dilated main pulmonary artery and a dissection flap extending from main pulmonary artery to left pulmonary artery. In summary, in this report, we described a very rare case of pulmonary artery dissection in a pregnant patient with a previously un-diagnosed patent ductus arteriosus without an obvious rise in pulmonary artery pressure and reviewed the relevant literature. PMID:25717357

  16. Pulmonary arterial dissection in a post-partum patient with patent ductus arteriosus: Case report and review of the literature.

    PubMed

    Yaman, Mehmet; Arslan, Uğur; Ateş, Ahmet Hakan; Aksakal, Aytekin

    2015-02-26

    Pulmonary arterial dissection is an uncommon but usually a deadly complication of chronic pulmonary hypertension. A 26-year-old female patient was admitted to our clinics with sudden dyspnea and chest discomfort one hour after giving birth to twins by vaginal delivery. An echocardiography was performed with a pre-diagnosis of pulmonary embolism. However, echocardiographic examination revealed a dilated main pulmonary artery and a dissection flap extending from main pulmonary artery to left pulmonary artery. In summary, in this report, we described a very rare case of pulmonary artery dissection in a pregnant patient with a previously un-diagnosed patent ductus arteriosus without an obvious rise in pulmonary artery pressure and reviewed the relevant literature.

  17. Systemic sclerosis patients with and without pulmonary arterial hypertension: a nailfold capillaroscopy study.

    PubMed

    Riccieri, Valeria; Vasile, Massimiliano; Iannace, Nicoletta; Stefanantoni, Katia; Sciarra, Iliana; Vizza, Carmine D; Badagliacca, Roberto; Poscia, Roberto; Papa, Silvia; Mezzapesa, Mario; Nocioni, Martina; Valesini, Guido

    2013-08-01

    Pulmonary arterial hypertension (PAH) is a complication of SSc due to increased vascular resistance, and abnormal vascularity is a well-known feature of the disease as shown by nailfold videocapillaroscopy (NVC). This study investigated for specific NVC changes in SSc patients with and without PAH to assess any useful difference. Twenty-four SSc patients, 12 with PAH and 12 without, entered the study. Evidence of PAH was defined as increased systolic pulmonary artery pressure (PAP) (≥35 mmHg), indirectly assessed by echocardiography and confirmed by right heart catheterization (mPAP > 25 mmHg). NVC was performed, and a semi-quantitative rating scale, a rating system for avascular areas and a specific NVC pattern evaluation, namely early, active and late, were used. An NVC score >1 was more frequently found in patients with PAH than those without, 11 cases (92%) vs 5 cases (42%) (P = 0.03); an avascular areas grade >1 was present in 10 (83%) and 2 (17%) cases, respectively (P = 0.003); and a more severe NC pattern (active/late) was described in 11 (92%) and 5 (42%) patients, respectively (P = 0.03). When we compared the mPAP with NVC parameters, we found significant correlations between mPAP values and the NVC score (P < 0.005) and with the avascular areas score (P < 0.001). Our results underline the relevance of early microvascular assessment in patients at risk of developing a severe complication such as PAH that can amplify the systemic microvascular impairment in SSc. More severe NVC abnormalities should lead to strict cardiopulmonary surveillance and a complete NVC study is indicated.

  18. [Pulmonary arterial hypertension in women].

    PubMed

    Sanchez, O; Marié, E; Lerolle, U; Wermert, D; Israël-Biet, D; Meyer, G

    2008-04-01

    Pulmonary arterial hypertension (PAH) is a rare condition characterized by sustained elevation in pulmonary arterial resistance leading to right heart failure. PAH afflicts predominantly women. Echocardiography is the initial investigation of choice for non-invasive detection of PAH but right-heart catheterization is necessary to confirm the diagnosis. Conventional treatment includes non-specific drugs (warfarin, diuretics, oxygen). The endothelin-1 receptor antagonist bosentan, the phosphodiesterase-5 inhibitor sildenafil, and prostanoids have been shown to improve symptoms, exercise capacity and haemodynamics. Intravenous prostacyclin is the first-line treatment for the most severely affected patients. Despite the most modern treatment the overall mortality rate of pregnant women with severe PAH remains high. Therefore, pregnancy is contraindicated in women with PAH and an effective method of contraception is recommended in women of childbearing age. Therapeutic abortion should be offered, particularly when early deterioration occurs. If this option is not accepted, intravenous prostacyclin should be considered promptly. Recent advances in the management of PAH have markedly improved prognosis and have resulted in more women of childbearing age considering pregnancy. A multidisciplinary approach should give new insights into cardiopulmonary, obstetric and anaesthetic management during pregnancy, delivery and the post-partum period.

  19. Coil embolization for pulmonary artery injury caused by chest tube drainage.

    PubMed

    Shigefuku, Shunsuke; Kudo, Yujin; Saguchi, Toru; Maeda, Junichi

    2017-05-01

    Pulmonary artery injury caused by chest tube drainage is rare, but it requires prompt diagnosis to perform urgent surgical repair. We report that a 53-year-old man who suffered from pulmonary artery injury by chest tube drainage was successfully treated by coil embolization. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  20. Associations between thoracic radiographic changes and severity of pulmonary arterial hypertension diagnosed in 60 dogs via Doppler echocardiography: A retrospective study.

    PubMed

    Adams, Dustin S; Marolf, Angela J; Valdés-Martínez, Alejandro; Randall, Elissa K; Bachand, Annette M

    2017-07-01

    Doppler echocardiography is a noninvasive method for estimating and grading pulmonary arterial hypertension. No current literature associates significance of radiographic findings with severity of pulmonary arterial hypertension. We hypothesized that the number and conspicuity of radiographic findings suggestive of pulmonary arterial hypertension would be greater based on the severity of pulmonary arterial hypertension. Dogs with pulmonary arterial hypertension and normal control dogs were included in this retrospective, case control study. Three radiologists blinded to echocardiographic results scored thoracic radiographs for right ventricular and main pulmonary artery enlargement and pulmonary lobar artery enlargement, tortuosity, and blunting by multiple methods. Presence or absence of each finding was scored in an additive fashion and averaged for each grade of pulmonary arterial hypertension severity. Seventy-one dogs (60 dogs with pulmonary arterial hypertension and 11 control dogs) of which some had multiple studies were included: 20 mild, 21 moderate, 25 severe, and 11 absent pulmonary arterial hypertension. The following radiographic findings were significantly associated with increasing pulmonary arterial hypertension severity: right ventricular enlargement by "reverse D" and "3/5-2/5 cardiac ratio" methods, main pulmonary artery enlargement, and caudal lobar artery enlargement by the "3rd rib" method. Mean scores for severe pulmonary arterial hypertension and normal dogs were significantly different (P-value < 0.0001). Mean scores between different pulmonary arterial hypertension grades increased with severity but were not statistically significant. Individually and in combination, radiographic findings performed poorly in differentiating severity of pulmonary arterial hypertension. Findings indicated that thoracic radiographs should be utilized in conjunction with Doppler echocardiography in a complete diagnostic work-up for dogs with suspected

  1. Takotsubo cardiomyopathy after treatment of pulmonary arterial hypertension

    PubMed Central

    Cork, David P.; Mehrotra, Amit K.; Gomberg-Maitland, Mardi

    2012-01-01

    Pulmonary arterial hypertension is a fatal disease. Intravenous prostanoids are often utilized for long-term management of patients. The therapy requires a significant commitment and change in lifestyle for both the patient and family. Takotsubo cardiomyopathy, transient apical ballooning syndrome, has been reported in association with emotional and physical stress. This case report describes a patient with pulmonary arterial hypertension who developed Takotsubo cardiomyopathy after treatment initiation with intravenous treprostinil. Over time, the syndrome resolved and the patient had return of normal left ventricular function. Takotsubo cardiomyopathy should be recognized as a potential, rare complication of therapy initiation due to the severity of the illness and the emotional stress of the disease. PMID:23130109

  2. Pediatric Perioperative Pulmonary Arterial Hypertension: A Case-Based Primer

    PubMed Central

    Shah, Shilpa; Szmuszkovicz, Jacqueline R.

    2017-01-01

    The perioperative period is an extremely tenuous time for the pediatric patient with pulmonary arterial hypertension. This article will discuss a multidisciplinary approach to preoperative planning, the importance of early identification of pulmonary hypertensive crises, and practical strategies for postoperative management for this unique group of children. PMID:29064445

  3. Isolated Human Pulmonary Artery Structure and Function Pre- and Post-Cardiopulmonary Bypass Surgery.

    PubMed

    Dora, Kim A; Stanley, Christopher P; Al Jaaly, Emad; Fiorentino, Francesca; Ascione, Raimondo; Reeves, Barnaby C; Angelini, Gianni D

    2016-02-23

    Pulmonary dysfunction is a known complication after cardiac surgery using cardiopulmonary bypass, ranging from subclinical functional changes to prolonged postoperative ventilation, acute lung injury, and acute respiratory distress syndrome. Whether human pulmonary arterial function is compromised is unknown. The aim of the present study was to compare the structure and function of isolated and cannulated human pulmonary arteries obtained from lung biopsies after the chest was opened (pre-cardiopulmonary bypass) to those obtained at the end of cardiopulmonary bypass (post-cardiopulmonary bypass) from patients undergoing coronary artery bypass graft surgery. Pre- and post-cardiopulmonary bypass lung biopsies were received from 12 patients undergoing elective surgery. Intralobular small arteries were dissected, cannulated, pressurized, and imaged using confocal microscopy. Functionally, the thromboxane mimetic U46619 produced concentration-dependent vasoconstriction in 100% and 75% of pre- and post-cardiopulmonary bypass arteries, respectively. The endothelium-dependent agonist bradykinin stimulated vasodilation in 45% and 33% of arteries pre- and post-cardiopulmonary bypass, respectively. Structurally, in most arteries smooth muscle cells aligned circumferentially; live cell viability revealed that although 100% of smooth muscle and 90% of endothelial cells from pre-cardiopulmonary bypass biopsies had intact membranes and were considered viable, only 60% and 58%, respectively, were viable from post-cardiopulmonary bypass biopsies. We successfully investigated isolated pulmonary artery structure and function in fresh lung biopsies from patients undergoing heart surgery. Pulmonary artery contractile tone and endothelium-dependent dilation were significantly reduced in post-cardiopulmonary bypass biopsies. The decreased functional responses were associated with reduced cell viability. URL: http://www.isrctn.com/ISRCTN34428459. Unique identifier: ISRCTN 34428459.

  4. Osthole relaxes pulmonary arteries through endothelial phosphatidylinositol 3-kinase/Akt-eNOS-NO signaling pathway in rats.

    PubMed

    Yao, Li; Lu, Ping; Li, Yumei; Yang, Lijing; Feng, Hongxuan; Huang, Yong; Zhang, Dandan; Chen, Jianguo; Zhu, Daling

    2013-01-15

    Pulmonary arterial hypertension is a life-threatening disease lacking effective therapies. Osthole is a natural coumarin compound isolated from Angelica pubescens Maxim., which possesses hypotensive effect. Although its effects on isolated thoracic aorta (systemic circulating system) are clarified, it remains unclear whether Osthole relaxes isolated pulmonary arteries (PAs) (pulmonary circulating system). The aim of this study was to investigate the effects of Osthole on isolated PAs and the underlying mechanisms. We examined PA relaxation induced by Osthole in isolated human and rat PA rings with force-electricity transducers, the expression and activity of endothelial nitric oxide synthase (eNOS) and protein kinase B (Akt) with western blot, and nitric oxide (NO) production using DAF-FM DA fluorescent indicator. The results showed that Osthole elicited a dose-dependent vasorelaxation activity with phenylephrine-precontracted human and rat PA rings, which can be diminished by endothelium denudation and inhibition of eNOS, while having no effect on rat mesenteric arteries. Osthole increased NO release as well as activation of Akt and eNOS, indicated with increased phosphorylations of Akt at Ser-473 and eNOS at Ser-1177 in endothelial cells. PI3K inhibitor LY294002 also blocked Osthole induced vasodilation. In summary, dilative effect of Osthole was dependent on endothelial integrity and NO production, and was mediated by endothelial PI3K/Akt-eNOS-NO pathway. These may provide a new pulmonary vasodilator for the therapy of pulmonary arterial hypertension. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Grape seed procyanidin extract attenuates hypoxic pulmonary hypertension by inhibiting oxidative stress and pulmonary arterial smooth muscle cells proliferation.

    PubMed

    Jin, Haifeng; Liu, Mingcheng; Zhang, Xin; Pan, Jinjin; Han, Jinzhen; Wang, Yudong; Lei, Haixin; Ding, Yanchun; Yuan, Yuhui

    2016-10-01

    Hypoxia-induced oxidative stress and excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) play important roles in the pathological process of hypoxic pulmonary hypertension (HPH). Grape seed procyanidin extract (GSPE) possesses antioxidant properties and has beneficial effects on the cardiovascular system. However, the effect of GSPE on HPH remains unclear. In this study, adult Sprague-Dawley rats were exposed to intermittent chronic hypoxia for 4 weeks to mimic a severe HPH condition. Hemodynamic and pulmonary pathomorphology data showed that chronic hypoxia significantly increased right ventricular systolic pressures (RVSP), weight of the right ventricle/left ventricle plus septum (RV/LV+S) ratio and median width of pulmonary arteries. GSPE attenuated the elevation of RVSP, RV/LV+S, and reduced the pulmonary vascular structure remodeling. GSPE also increased the levels of SOD and reduced the levels of MDA in hypoxia-induced HPH model. In addition, GSPE suppressed Nox4 mRNA levels, ROS production and PASMCs proliferation. Meanwhile, increased expression of phospho-STAT3, cyclin D1, cyclin D3 and Ki67 in PASMCs caused by hypoxia was down-regulated by GSPE. These results suggested that GSPE might potentially prevent HPH via antioxidant and antiproliferative mechanisms. Copyright © 2016. Published by Elsevier Inc.

  6. Prognostic value of exercise pulmonary haemodynamics in pulmonary arterial hypertension.

    PubMed

    Chaouat, Ari; Sitbon, Olivier; Mercy, Magalie; Ponçot-Mongars, Raphaëlle; Provencher, Steeve; Guillaumot, Anne; Gomez, Emmanuel; Selton-Suty, Christine; Malvestio, Pascale; Regent, Denis; Paris, Christophe; Hervé, Philippe; Chabot, François

    2014-09-01

    The aim of the study was to investigate the prognostic value of right heart catheterisation variables measured during exercise. 55 incident patients with idiopathic, familial or anorexigen-associated pulmonary arterial hypertension (PAH) underwent right heart catheterisation at rest and during exercise and 6-min walk testing before PAH treatment initiation. Patients were treated according to recommendations within the next 2 weeks. Right heart catheterisation was repeated 3-5 months into the PAH treatment in 20 patients. Exercise cardiac index decreased gradually as New York Heart Association (NYHA) functional class increased whereas cardiac index at rest was not significantly different across NYHA groups. Baseline 6-min walk distance correlated significantly with exercise and change in cardiac index from rest to exercise (r=0.414 and r=0.481, respectively; p<0.01). Change in 6-min walk distance from baseline to 3-5 months under PAH treatment was highly correlated with change in exercise cardiac index (r=0.746, p<0.001). The most significant baseline covariates associated with survival were change in systolic pulmonary artery pressure from rest to exercise and exercise cardiac index (hazard ratio 0.56 (95% CI 0.37-0.86) and 0.14 (95% CI 0.05-0.43), respectively). Change in pulmonary haemodynamics during exercise is an important tool for assessing disease severity and may help devise optimal treat-to-target strategies. ©ERS 2014.

  7. Rapamycin nanoparticles localize in diseased lung vasculature and prevent pulmonary arterial hypertension.

    PubMed

    Segura-Ibarra, Victor; Amione-Guerra, Javier; Cruz-Solbes, Ana S; Cara, Francisca E; Iruegas-Nunez, David A; Wu, Suhong; Youker, Keith A; Bhimaraj, Arvind; Torre-Amione, Guillermo; Ferrari, Mauro; Karmouty-Quintana, Harry; Guha, Ashrith; Blanco, Elvin

    2017-05-30

    Vascular remodeling resulting from pulmonary arterial hypertension (PAH) leads to endothelial fenestrations. This feature can be exploited by nanoparticles (NP), allowing them to extravasate from circulation and accumulate in remodeled pulmonary vessels. Hyperactivation of the mTOR pathway in PAH drives pulmonary arterial smooth muscle cell proliferation. We hypothesized that rapamycin (RAP)-loaded NPs, an mTOR inhibitor, would accumulate in diseased lungs, selectively targeting vascular mTOR and preventing PAH progression. RAP poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-PCL) NPs were fabricated. NP accumulation and efficacy were examined in a rat monocrotaline model of PAH. Following intravenous (IV) administration, NP accumulation in diseased lungs was verified via LC/MS analysis and confocal imaging. Pulmonary arteriole thickness, right ventricular systolic pressures, and ventricular remodeling were determined to assess the therapeutic potential of RAP NPs. Monocrotaline-exposed rats showed increased NP accumulation within lungs compared to healthy controls, with NPs present to a high extent within pulmonary perivascular regions. RAP, in both free and NP form, attenuated PAH development, with histological analysis revealing minimal changes in pulmonary arteriole thickness and no ventricular remodeling. Importantly, NP-treated rats showed reduced systemic side effects compared to free RAP. This study demonstrates the potential for nanoparticles to significantly impact PAH through site-specific delivery of therapeutics. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Pulmonary Angiography and Embolization for Severe Hemoptysis Due to Cavitary Pulmonary Tuberculosis

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

    Sanyika, Charles; Corr, Peter; Royston, Duncan

    1999-11-15

    Purpose: To identify the role of pulmonary angiography in the diagnosis and treatment of severe hemoptysis due to cavitary pulmonary tuberculosis. Methods: Selective pulmonary angiography was performed on eight patients with severe hemoptysis uncontrolled by previous bronchial and systemic arterial embolization. Results: Three (38%) patients had Rasmussen aneurysms, which were successfully embolized with steel coils. Five patients demonstrated pulmonary arterial hypoperfusion in the diseased lung. Conclusions: We recommend pulmonary angiography in cavitary tuberculous patients with severe hemoptysis who do not respond to systemic arterial embolization. Rasmussen aneurysms are effectively treated by steel coil occlusion.

  9. Pulmonary Artery Aneurysm/Pseudoaneurysm, a Delayed Complication of Lung Abscess: A Case Report.

    PubMed

    Oguma, Tsuyoshi; Morise, Masahiro; Harada, Kazuki; Tanaka, Jun; Sato, Masako; Horio, Yukihiro; Takiguchi, Hiroto; Tomomatsu, Hiromi; Tomomatsu, Katsuyoshi; Takihara, Takahisa; Niimi, Kyoko; Hayama, Naoki; Aoki, Takuya; Urano, Tetsuya; Ito, Chihiro; Koizumi, Jun; Asano, Koichiro

    2015-09-20

    Massive hemoptysis mostly arises from the bronchial arteries; however, bleeding can also occur from a lesion in injured pulmonary arteries, such as pulmonary artery aneurysm/pseudoaneurysm (PAA/PAP), during pulmonary infection. A 66-year-old man was admitted with a diagnosis of lung abscess in the right lower lobe that was complicated with pyothorax. Intravenous administration of antibiotics and thoracic drainage successfully controlled the infection and inflammation until day 16, when the patient began to exhibit hemoptysis and bloody pleural effusion. Enhanced computed tomography (CT) with multi-planer reconstruction (MPR) images showed a highly enhanced mass inside the abscess fed by the pulmonary artery, suggesting PAA/PAP. Pulmonary angiography confirmed PAA/PAP, and embolization with coils successfully stopped both the bleeding into the sputum and pleural effusion, with a collapsed aneurysm visible on chest CT scan. Clinicians should consider the possibility of PAA/PAP in the differential diagnosis of hemoptysis during the treatment of patients with lung abscess. MPR CT is helpful for the diagnosis of PAA/PAP and its feeding vessels.

  10. [Beneficial effects of renal denervation on pulmonary vascular remodeling in experimental pulmonary artery hypertension].

    PubMed

    Zhang, Shujuan; Zhao, Qingyan; Jiang, Xuejun; Yang, Bo; Dai, Zixuan; Wang, Xiaozhan; Wang, Xule; Guo, Zongwen; Yu, Shengbo; Tang, Yanhong; Hu, Wei; Huang, Congxin

    2015-04-14

    To explore the effects of renal sympathetic denervation (RSD) on pulmonary vascular remodeling in a model of pulmonary arterial hypertension (PAH). According to the random number table, 24 beagles were randomized into control, PAH and PAH+RSD groups (n=8 each). The levels of neurohormone, echocardiogram and dynamics parameters were measured. Then 0.1 ml/kg dimethylformamide (control group) or 2 mg/kg dehydromonocrotaline (PAH and PAH+RSD groups) were injected. The PAH+RSD group underwent RSD after injection. At week 8 post-injection, the neurohormone levels, echocardiogram, dynamics parameters and pulmonary tissue morphology were observed. The values of right ventricular systolic pressure (RVSP) and pulmonary arterial systolic pressure (PASP) in PAH and PAH+RSD groups were both significantly higher than those in control group ((42.8±8.7), (30.8±6.8) vs (23.2±5.7) mmHg (1 mmHg=0.133 kPa) and (45.1±11.2), (32.6±7.9) vs (24.7±7.1) mmHg). Meanwhile, the values of RVSP and PASP in PAH group were higher than those in PAH+RSD group (all P<0.01). The levels of serum angiotensin II (Ang II) and endothelin-1 significantly increased after 8 weeks in PAH dogs ((228±41) vs (113±34) pg/ml and (135±15) vs (77±7) pg/ml, all P<0.01). And Ang II and endothelin-1 were higher in lung tissues of PAH group ((65±10) and (96±10) pg/ml) than in those of control group ((38±7) and (54±6) pg/ml) and PAH+RSD group ((46±8) and (67±9) pg/ml) (all P<0.01). Pulmonary tissues had marked collagen hyperplasia and lamellar corpuscles of type 2 alveolar cells were damaged more severely in PAH dogs than in PAH+RSD dogs. RSD suppresses pulmonary vascular remodeling and decreases pulmonary arterial pressure in experimental PAH. And the effect of RSD on PAH may contribute to decreased neurohormone levels.

  11. Diagnostic Value of Transthoracic Echocardiography in Patients With Anomalous Origin of the Left Coronary Artery From the Pulmonary Artery

    PubMed Central

    Li, Rong-Juan; Sun, Zhonghua; Yang, Jiao; Yang, Ya; Li, Yi-Jia; Leng, Zhao-Ting; Liu, Guo-Wen; Pu, Li-Hong

    2016-01-01

    Abstract Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital coronary abnormality associated with early infant mortality and sudden death in adults. Transthoracic echocardiography (TTE) plays an important role in early detection and diagnosis of ALCAPA as a noninvasive modality. However, its diagnostic value is not well studied. The purpose of this study is to determine the performance of TTE in the diagnostic assessment of ALCAPA as compared with coronary CT and invasive coronary angiography. A total of 22 patients (13 women and 9 men, mean age, 12.9 ± 19.5 years) with ALCAPA who underwent echocardiographic examination for clinical diagnosis were retrospectively reviewed and analyzed. Transthoracic echocardiographic features of ALCAPA were analyzed and its diagnostic value was compared with invasive coronary angiography and coronary CT angiography (CTA) with surgical findings serving as the gold standard. Surgery was performed in all of the patients to establish the dual coronary artery system. Five underwent the Takeuchi procedure and 17 had re-implantation of the anomalous left coronary artery. Of 20 patients, echocardiographic diagnoses were in good agreement with findings at surgery, resulting in the diagnostic accuracy of 90.9%. Two cases were misdiagnosed—one as the right coronary artery to pulmonary artery fistula and the other as rheumatic heart disease. The echocardiographic features of these patients with ALCAPA included: abnormal left coronary ostium arising from the pulmonary trunk with retrograde coronary artery flow in 20 patients; enlargement of the right coronary artery in 17 patients; abundant intercoronary septal collaterals in 17 patients; and moderate and significant mitral regurgitation in 14 patients. The diagnostic accuracy of invasive coronary angiography (in 17 patients) and coronary CTA (in 9 patients) was 100%. This study shows that TTE is an accurate, noninvasive imaging modality

  12. Transesophageal Echocardiographic Assessment of Pulmonary Artery-to-Ascending Aorta Ratio for the Detection of Pulmonary Hypertension in Cardiac Surgical Patients.

    PubMed

    Narendra Kumar, Karthik; Singh, Naveen G; P S, Nagaraja; Patil, Thimmangouda A; N, Manjunath

    2017-10-01

    The objective of the study was to investigate if the main pulmonary artery (mPA)-to-ascending aorta (AscAo), (mPA:AscAo) ratio could serve as a screening tool in identifying pulmonary artery hypertension (PAH). A prospective observational study. Tertiary care center, university hospital. Fifty-four adult patients undergoing off-pump coronary artery bypass grafting surgery (OPCAB). mPA and AscAo transverse diameters were measured by transesophageal echocardiography (TEE) and the mean pulmonary arterial pressures (mPAP) were recorded simultaneously using a pulmonary artery catheter. mPA:AscAo ratio demonstrated significant linear correlation with mPAP measured by pulmonary artery catheterization (ie, r = 0.61, confidence interval [CI] = 0.5352-0.6736, p < 0.0001). Receiver operating characteristic curves were performed to evaluate sensitivity and specificity of mPA:AscAo ratio ≥1 for diagnosing PAH (mPAP ≥25 mmHg). Area under the curve for mPA:AscAo ratio was 0.91 (95% CI, 0.869-0.936, p < 0.0001), with a sensitivity of 84.27%, specificity of 83.92%, positive-predictive value of 87.6% and negative-predictive value of 81.1% for a mPAP ≥25 mmHg. The ratio of mPA:AscAo is a simple, reliable, and reproducible method that can be obtained through TEE, which guides the clinician to screen patients with PAH. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Effects of terlipressin on systolic pulmonary artery pressure of patients with liver cirrhosis: An echocardiographic assessment

    PubMed Central

    Altintas, Engin; Akkus, Necdet; Gen, Ramazan; Helvaci, M. Rami; Sezgin, Orhan; Oguz, Dilek

    2004-01-01

    AIM: Portopulmonary hypertension is a serious complication of chronic liver disease. Our aim was to search into the effect of terlipressin on systolic pulmonary artery pressure among cirrhotic patients. METHODS: Twelve patients (6 males and 6 females) with liver cirrhosis were recruited in the study. Arterial blood gas samples were obtained in sitting position at rest. Contrast enhanced echocardiography and measurements of systolic pulmonary artery pressure were performed before and after the intravenous injection of 2 mg terlipressin. RESULTS: Of 12 patients studied, the contrast enhanced echocardiography was positive in 5, and the positive findings in contrast enhanced echocardiography were reversed to normal in two after terlipressin injection. The mean systolic pulmonary artery pressure was 25.5 ± 3.6 mmHg before terlipressin injection, and was 22.5 ± 2.5 mmHg after terlipressin (P = 0.003). The systolic pulmonary artery pressure was above 25 mmHg in seven of these 12 patients. After the terlipressin injection, systolic pulmonary artery pressure was < 25 mmHg in four of these cases (58.3% vs 25%, P = 0.04). CONCLUSION: Terlipressin can decrease the systolic pulmonary artery pressure in patients with liver cirrhosis. PMID:15259082

  14. CT measurement of central pulmonary arteries to diagnose pulmonary hypertension (PHTN): more reliable than valid?

    PubMed

    Terpenning, Silanath; Deng, Matthew; Hong-Zohlman, Susie N; Lin, Cheng Ting; Kligerman, Seth J; Jeudy, Jean; Ketai, Loren H

    2016-01-01

    The association between main pulmonary artery (MPA) size and pulmonary arterial hypertension (PAHTN) is well established; however, the clinical utility of routine measurement of MPA is uncertain due to considerable overlap between normal patients and those with pulmonary hypertension. The lack of diagnostic accuracy could be further degraded by variability among the radiologists. It is unknown whether the addition of right and left pulmonary artery measurements would improve accuracy or further impair it. The purposes of this study are to verify the accuracy of a proposed cutoff value for the size of MPA in the diagnosis PAHTN, to determine the interrater agreement for this measurement, and to determine whether addition of right pulmonary artery (RPA) and left pulmonary artery (LPA) measurement or simple assessment of patient comorbidities can improve the accuracy. Patients undergoing both cardiac catheterization and chest computed tomography (CT) within 3 months of each other at a large university hospital between January 2010 and December 2012 were identified. Patients with prior cardiac surgery or congenital heart disease and critically ill patients were excluded from the study population. Patients with pericardial disease or severe lung disease documented on CT examinations were also excluded. From the remaining patients, 45 patients with normal pulmonary artery pressure and 50 patients with proven pulmonary hypertension were selected. Demographic data and clinical information was collected from medical records of these patients. Three radiologists with different years of experience in cardiothoracic imaging measured the MPA, RPA, and LPA diameters on axial images using an electronic ruler on 3D work stations independently and were masked to the patient clinical symptoms, diagnosis, and each other's measurement to prevent bias. Association between MPA diameter (MPAD) and patient characteristics assessed by one-way analysis of variance for scalar measures. Each

  15. [Study on relationship between blood supply from pulmonary artery and pathological characteristics of patients with primary bronchogenic carcinoma].

    PubMed

    Zhang, Yongkui; Le, Hanbo; Chen, Zhijun; Wang, Chaoye; Zhang, Binjie

    2006-01-01

    At present, it has been known that the bronchogenic artery participates in the blood supply of primary bronchogenic carcinoma, but there is controversy about the blood supply from pulmonary artery in primary bronchogenic carcinoma. The aim of this study is to assess the relationship between the blood supply from pulmonary artery and pathological characteristis of patients with primary bronchogenic carcinoma. The pulmonary arteries in 43 surgical samples of bronchogenic carcinoma were marked, then the iopromide was used to selective pulmonary arteriography in digital subtraction angiography (DSA). The relationship between tumor with blood supply from pulmonary artery and the pathologic characteristics was observed. There were 34 samples with blood supply from pulmonary artery ( 79.07%) , and 9 samples without blood supply from pulmonary artery (20.93%). The development rate of peripheral lung cancer (100.00%) was significantly higher than that of central lung cancer (64.00%) (P < 0.01) . The development rate of squamous cell carcinoma (91.30%) was remarkably higher than that of adenocarcinoma (61.11%) (P < 0.05). The development rate of poorly differentiated lung cancer (95.00%) was remarkably higher than that of well and moderately differentiated lung cancer (65.22%) (P < 0.05). There was a positive relationship between the tumor size and the development rate (P < 0.05). In primary bronchogenic carcinoma, the pulmonary artery blood supply exists in most of tumors. There is relationship between the blood supply from pulmonary artery and general type, histopathology, cell differentiation and tumor size of lung cancer. The blood supply from pulmonary artery doesn't relate to tumor stage.

  16. Pregnancy in pulmonary arterial hypertension.

    PubMed

    Olsson, Karen M; Channick, Richard

    2016-12-01

    Despite advanced therapies, maternal mortality in women with pulmonary arterial hypertension (PAH) remains high in pregnancy and is especially high during the post-partum period. However, recent data indicates that morbidity and mortality during pregnancy and after birth have improved for PAH patients. The current European Society of Cardiology/European Respiratory Society guidelines recommend that women with PAH should not become pregnant. Therefore, the risks associated with pregnancy must be emphasised and counselling offered to women at the time of PAH diagnosis and to women with PAH who become pregnant. Early termination should be discussed. Women who choose to continue with their pregnancy should be treated at specialised pulmonary hypertension centres with experience in managing PAH during and after pregnancy. Copyright ©ERS 2016.

  17. Pulmonary artery perforation by plug anchoring system after percutaneous closure of left appendage.

    PubMed

    Bianchi, Giacomo; Solinas, Marco; Gasbarri, Tommaso; Bevilacqua, Stefano; Tiwari, Kaushal Kishore; Berti, Sergio; Glauber, Mattia

    2013-07-01

    Patients receiving oral anticoagulant therapy for atrial fibrillation who are at high risk of bleeding are increasingly referred for percutaneous left atrial appendage exclusion. Although effective, this procedure is not free from risk. We report a case of pericardial tamponade due to pulmonary artery tear caused by a trespassing anchoring hook of an AGA plug. Intraoperatively, no actual bleeding was found from the left appendage, a proof of its complete occlusion by the device. The patient underwent successful surgical repair and radio-frequency ablation of atrial fibrillation was performed by pulmonary veins encircling. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  18. 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.

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

    NASA Astrophysics Data System (ADS)

    Clarke, Shanelle; Baumgardt, Shelley; Molthen, Robert

    2010-03-01

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

  20. Pulmonary artery occlusion pressure estimation by transesophageal echocardiography: is simpler better?

    PubMed Central

    Voga, Gorazd

    2008-01-01

    The measurement of pulmonary artery occlusion pressure (PAOP) is important for estimation of left ventricular filling pressure and for distinction between cardiac and non-cardiac etiology of pulmonary edema. Clinical assessment of PAOP, which relies on physical signs of pulmonary congestion, is uncertain. Reliable PAOP measurement can be performed by pulmonary artery catheter, but it is possible also by the use of echocardiography. Several Doppler variables show acceptable correlation with PAOP and can be used for its estimation in cardiac and critically ill patients. Noninvasive PAOP estimation should probably become an integral part of transthoracic and transesophageal echocardiographic evaluation in critically ill patients. However, the limitations of both methods should be taken into consideration, and in specific patients invasive PAOP measurement is still unavoidable, if the exact value of PAOP is needed. PMID:18394183

  1. Pulmonary artery occlusion pressure estimation by transesophageal echocardiography: is simpler better?

    PubMed

    Voga, Gorazd

    2008-01-01

    The measurement of pulmonary artery occlusion pressure (PAOP) is important for estimation of left ventricular filling pressure and for distinction between cardiac and non-cardiac etiology of pulmonary edema. Clinical assessment of PAOP, which relies on physical signs of pulmonary congestion, is uncertain. Reliable PAOP measurement can be performed by pulmonary artery catheter, but it is possible also by the use of echocardiography. Several Doppler variables show acceptable correlation with PAOP and can be used for its estimation in cardiac and critically ill patients. Noninvasive PAOP estimation should probably become an integral part of transthoracic and transesophageal echocardiographic evaluation in critically ill patients. However, the limitations of both methods should be taken into consideration, and in specific patients invasive PAOP measurement is still unavoidable, if the exact value of PAOP is needed.

  2. Regression of left ventricular dilation after percutaneous closure of a large intralobar pulmonary sequestration.

    PubMed

    Alvarez, Alejandro; Borgia, Francesco; Guccione, Paolo

    2010-02-01

    We describe an infant of 8 months who presented with left ventricular dilation due to an extensive intralobar sequestration of the right lung. The pulmonary sequestration was associated with a patent arterial duct and a right aortic arch. Percutaneous closure of the anomalous aberrant artery feeding the sequestrated lung resulted in prompt regression of the left ventricular enlargement.

  3. Anomalous Origin of One Pulmonary Artery From the Ascending Aorta: From Diagnosis to Treatment in Angola.

    PubMed

    Manuel, Valdano; Sousa-Uva, Miguel; Morais, Humberto; Magalhães, Manuel P; Pedro, Albino; Miguel, Gade; Nunes, Maria A S; Gamboa, Sebastiana; Júnior, António P F

    2015-10-01

    Anomalous origin of one pulmonary artery is a rare congenital heart disease in which one pulmonary artery branch originates from the ascending aorta. To describe the experience of a cardiothoracic center in an African country to repair anomalous origin of one pulmonary artery in the context of Portugal-Angola collaboration. Between March 2011 and March 2015, four consecutive patients with anomalous origin of pulmonary artery branch underwent surgical correction. The mean age was 1.6 months. The mean weight was 4 kg. All had right pulmonary artery branch originating from the ascending aorta. All patients underwent direct implantation of right pulmonary branch to main pulmonary artery. Two patents had patent ductus arteriosus and one had atrial septal defect. Two patients had pulmonary hypertension. There was no registration of death. The mean cardiopulmonary bypass time was 75.5 ± 4.5 minutes, mean aortic cross-clamping time was 40 ± 5.6 minutes, and mean duration of the postoperative intensive care unit stay was 6.8 ± 5.7 days. At discharge, one patient had residual gradient of 25 mm Hg, the remainder had no significant gradient. The mean follow-up time was 11 months (5-28 months). One week after discharge, one patient presented operative wound dehiscence. At the last follow-up, all patients were alive, and no significant residual gradient or stenosis at site of anastomosis was observed. No reintervention was required. Anomalous origin of one pulmonary artery is a rare but potentially treatable lesion if operated early in life. Direct implantation was a good technique with good short-term results. © The Author(s) 2015.

  4. Biaxial Properties of the Left and Right Pulmonary Arteries in a Monocrotaline Rat Animal Model of Pulmonary Arterial Hypertension.

    PubMed

    Pursell, Erica R; Vélez-Rendón, Daniela; Valdez-Jasso, Daniela

    2016-11-01

    In a monocrotaline (MCT) induced-pulmonary arterial hypertension (PAH) rat animal model, the dynamic stress-strain relation was investigated in the circumferential and axial directions using a linear elastic response model within the quasi-linear viscoelasticity theory framework. Right and left pulmonary arterial segments (RPA and LPA) were mechanically tested in a tubular biaxial device at the early stage (1 week post-MCT treatment) and at the advanced stage of the disease (4 weeks post-MCT treatment). The vessels were tested circumferentially at the in vivo axial length with matching in vivo measured pressure ranges. Subsequently, the vessels were tested axially at the mean pulmonary arterial pressure by stretching them from in vivo plus 5% of their length. Parameter estimation showed that the LPA and RPA remodel at different rates: axially, both vessels decreased in Young's modulus at the early stage of the disease, and increased at the advanced disease stage. Circumferentially, the Young's modulus increased in advanced PAH, but it was only significant in the RPA. The damping properties also changed in PAH; in the LPA relaxation times decreased continuously as the disease progressed, while in the RPA they initially increased and then decreased. Our modeling efforts were corroborated by the restructuring organization of the fibers imaged under multiphoton microscopy, where the collagen fibers become strongly aligned to the 45 deg angle in the RPA from an uncrimped and randomly organized state. Additionally, collagen content increased almost 10% in the RPA from the placebo to advanced PAH.

  5. ASK1 Inhibition Halts Disease Progression in Preclinical Models of Pulmonary Arterial Hypertension.

    PubMed

    Budas, Grant R; Boehm, Mario; Kojonazarov, Baktybek; Viswanathan, Gayathri; Tian, Xia; Veeroju, Swathi; Novoyatleva, Tatyana; Grimminger, Friedrich; Hinojosa-Kirschenbaum, Ford; Ghofrani, Hossein A; Weissmann, Norbert; Seeger, Werner; Liles, John T; Schermuly, Ralph T

    2018-02-01

    Progression of pulmonary arterial hypertension (PAH) is associated with pathological remodeling of the pulmonary vasculature and the right ventricle (RV). Oxidative stress drives the remodeling process through activation of MAPKs (mitogen-activated protein kinases), which stimulate apoptosis, inflammation, and fibrosis. We investigated whether pharmacological inhibition of the redox-sensitive apical MAPK, ASK1 (apoptosis signal-regulating kinase 1), can halt the progression of pulmonary vascular and RV remodeling. A selective, orally available ASK1 inhibitor, GS-444217, was administered to two preclinical rat models of PAH (monocrotaline and Sugen/hypoxia), a murine model of RV pressure overload induced by pulmonary artery banding, and cellular models. Oral administration of GS-444217 dose dependently reduced pulmonary arterial pressure and reduced RV hypertrophy in PAH models. The therapeutic efficacy of GS-444217 was associated with reduced ASK1 phosphorylation, reduced muscularization of the pulmonary arteries, and reduced fibrotic gene expression in the RV. Importantly, efficacy was observed when GS-444217 was administered to animals with established disease and also directly reduced cardiac fibrosis and improved cardiac function in a model of isolated RV pressure overload. In cellular models, GS-444217 reduced phosphorylation of p38 and JNK (c-Jun N-terminal kinase) induced by adenoviral overexpression of ASK1 in rat cardiomyocytes and reduced activation/migration of primary mouse cardiac fibroblasts and human pulmonary adventitial fibroblasts derived from patients with PAH. ASK1 inhibition reduced pathological remodeling of the pulmonary vasculature and the right ventricle and halted progression of pulmonary hypertension in rodent models. These preclinical data inform the first description of a causal role of ASK1 in PAH disease pathogenesis.

  6. The induction of nitric oxide-mediated relaxation of human isolated pulmonary arteries by PACAP

    PubMed Central

    Cardell, Lars Olaf; Hjert, Ola; Uddman, Rolf

    1997-01-01

    The effects of pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) were analysed in human isolated circular segments of pulmonary arteries. Guinea-pig pulmonary arteries were used for comparison. The responses obtained were analysed in relation to the vascular endothelium and the nitric oxide (NO) synthase inhibitor NG-monomethyl L-arginine (L-NMMA).PACAP and VIP induced concentration-dependent relaxations of precontracted pulmonary arteries. The maximal dilator response (Imax,%) and the potency (pEC50 value) were the same for both peptides, and there were no differences in the effects obtained on human and guinea-pig segments. PACAP and VIP were both more potent that acetylcholine (ACh).Removal of the vascular endothelium abolished the PACAP induced dilator response in pulmonary arteries from both species. The VIP induced dilatation was unaffected, whereas the response to ACh was abolished. L-NMMA given before PACAP inhibited the dilatation. Furthermore, L-NMMA also reversed the dilatation already induced by PACAP and excess concentrations of L-arginine restored the dilator response of the L-NMMA treated arteries.PACAP is a potent dilator of human pulmonary arteries. Although the dilator effect seems to be similar in amplitude to the one induced by VIP, the present results suggest differences in the underlying mechanisms of action (endothelium-dependency) between the two peptides. PMID:9134222

  7. Diesel exhaust inhalation exposure induces pulmonary arterial hypertension in mice.

    PubMed

    Liu, Jing; Ye, Xiaoqing; Ji, Dapeng; Zhou, Xiaofei; Qiu, Cong; Liu, Weiping; Yu, Luyang

    2018-06-01

    Diesel exhaust (DE) is one of the main sources of urban air pollution. An increasing number of evidence showed the association of air pollution with cardiovascular diseases. Pulmonary arterial hypertension (PAH) is one of the most disastrous vascular diseases, which results in right ventricular failure and death. However, the relationship of DE inhalation exposure with PAH is still unknown. In this study, male adult mice were exposed by inhalation to filtered ambient air (negative control), 10% O 2 hypoxia (PAH-phenotype positive control), 350 μg/m 3 particulate matter whole DE, or the combination of DE and hypoxic condition. DE inhalation induced PAH-phenotype accompanied with increased right ventricular systolic pressure (RVSP), right ventricle hypertrophy and pulmonary arterial thickening in a mouse model. DE exposure induced the proliferation of vascular smooth muscle cells (VSMCs) and apoptosis of endothelial cells in pulmonary artery. DE inhalation exposure induced an accumulation of CD45 +  lymphocytes and CD68 +  macrophages surrounding and infiltrating pulmonary arteriole. The levels of pro-inflammatory cytokines tumor necrosis factor (TNF-α), interleukin-6 (IL-6) and IL-13 produced by T helper 17 (Th17) and Th2 cells were markedly elevated in lung tissues of mice after DE inhalation exposure. Our findings suggest DE exposure induces PAH by activating Th17-skewed and Th2-droved responses, stimulating VSMCs proliferation and inducing endothelial cell apoptosis by the production of multifunctional pro-inflammatory cytokines, especially IL-6 and TNF-α. Considering the adverse impact of air pollution on health care, it is imperative to understand air pollution-induced susceptibility of progressive cardiopulmonary disease, such as PAH, and also elucidate critical mechanistic pathways which mediate pulmonary artery vascular remodeling and may serve as targets for preventive measures. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. 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

  9. Suture Embolism of the Left Superior Lobar Pulmonary Artery.

    PubMed

    Ahn, Janice Seulgy; Grise, Joy; DelTondo, Joseph A

    2018-05-31

    Endogenous pulmonary thromboemboli are a common cause of noncardiac sudden natural death. Embolism of exogenous material is a rare but potential finding in autopsies following surgeries, medical procedures, penetrating trauma, and nonparenteral drug abuse. This report describes the first case of a suture embolism of the left superior lobar pulmonary artery following complicated abdominal surgery. © 2018 American Academy of Forensic Sciences.

  10. A novel multiscale topo-morphometric approach for separating arteries and veins via pulmonary CT imaging

    NASA Astrophysics Data System (ADS)

    Saha, Punam K.; Gao, Zhiyun; Alford, Sara; Sonka, Milan; Hoffman, Eric

    2009-02-01

    Distinguishing arterial and venous trees in pulmonary multiple-detector X-ray computed tomography (MDCT) images (contrast-enhanced or unenhanced) is a critical first step in the quantification of vascular geometry for purposes of determining, for instance, pulmonary hypertension, using vascular dimensions as a comparator for assessment of airway size, detection of pulmonary emboli and more. Here, a novel method is reported for separating arteries and veins in MDCT pulmonary images. Arteries and veins are modeled as two iso-intensity objects closely entwined with each other at different locations at various scales. The method starts with two sets of seeds -- one for arteries and another for veins. Initialized with seeds, arteries and veins grow iteratively while maintaining their spatial separation and eventually forming two disjoint objects at convergence. The method combines fuzzy distance transform, a morphologic feature, with a topologic connectivity property to iteratively separate finer and finer details starting at a large scale and progressing towards smaller scales. The method has been validated in mathematically generated tubular objects with different levels of fuzziness, scale and noise. Also, it has been successfully applied to clinical CT pulmonary data. The accuracy of the method has been quantitatively evaluated by comparing its results with manual outlining. For arteries, the method has yielded correctness of 81.7% at the cost of 6.7% false positives and 11.6% false negatives. Our method is very promising for automated separation of arteries and veins in MDCT pulmonary images even when there is no mark of intensity variation at conjoining locations.

  11. Anomalous Systemic Artery to the Left Lower Lobe: Literature Review and a New Surgical Technique.

    PubMed

    Miller, Jacob R; Lancaster, Timothy S; Abarbanell, Aaron M; Manning, Peter B; Eghtesady, Pirooz

    2018-05-01

    Anomalous systemic arterial supply to the basal segments of the left lower lobe without coexisting pulmonary artery connection is a rare anomaly. Most feel treatment is necessary; however, the ideal strategy is unclear. Treatments described include embolization, pulmonary resection, or anastomosis to the native pulmonary artery. We recently encountered an infant with this anomaly and present a literature review summarizing all recent reports. Additionally, we describe a novel surgical technique to create a tension-free anastomosis utilizing segmental aortic translocation that we employed in our patient due to a large distance between the anomalous vessel and native left pulmonary artery.

  12. 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

  13. Impact of sildenafil on survival of patients with idiopathic pulmonary arterial hypertension.

    PubMed

    Zeng, Wei-Jie; Sun, Yun-Juan; Gu, Qing; Xiong, Chang-Ming; Li, Jian-Jun; He, Jian-Guo

    2012-09-01

    It has been reported that short-term sildenafil therapy is safe and effective for patients with pulmonary arterial hypertension. However, data regarding the impact of sildenafil on the survival of patients with idiopathic pulmonary arterial hypertension remain limited. The study was conducted on 77 patients with newly diagnosed idiopathic pulmonary arterial hypertension at Fu Wai Hospital between September 2005 and September 2009. Patients were divided into 2 groups: the sildenafil group and the conventional group. Nine patients treated with sildenafil were re-evaluated by right heart catheterization after 3 months. Our data demonstrated that the 6-minute walk distance, World Health Organization functional class, mixed venous oxygen saturation, and hemodynamics significantly improved after 3 months of sildenafil therapy (P < .05). The baseline characteristics of the sildenafil group were similar to those of the conventional group. The 1-, 2-, and 3-year survival rates in the sildenafil group were 88%, 72%, and 68% compared with 61%, 36%, and 27% in the conventional group (P < .001). The absence of sildenafil therapy, lower body mass index, and lower mixed venous oxygen saturation were found to be independent predictors of mortality. In conclusion, sildenafil therapy was found to be associated with improved survival in patients with idiopathic pulmonary arterial hypertension.

  14. Factors affecting the response to exercise in patients with severe pulmonary arterial hypertension.

    PubMed

    Flox-Camacho, Angela; Escribano-Subías, Pilar; Jiménez-López Guarch, Carmen; Fernández-Vaquero, Almudena; Martín-Ríos, Dolores; de la Calzada-Campo, Carlos Sáenz

    2011-01-01

    Ergospirometry objectively quantifies exercise capacity. Up until now, the response to exercise evaluated by ergospirometry in patients with pulmonary arterial hypertension has only been described in recently diagnosed.patients. Our aim is to describe the response to exercise in patients with severe pulmonary arterial hypertension under specific treatment and define which parameters determine their exercise capacity. A cross-sectional study was performed on 80 patients, 57 women, aged 45 (14), with severe pulmonary arterial hypertension (48 idiopathic, 14 related to toxic rapeseed oil, 13 to connective tissue disease, 5 to human immunodeficiency virus), mean pulmonary pressure at diagnosis 61(15)mmHg and after 49(33) months under treatment since diagnosis. Biomarkers were measured and echocardiography and ergospirometry were performed the same day. Our patients, under specific treatment, showed the typical behaviour of patients with pulmonary arterial hypertension with less limitation of both aerobic capacity and ventilatory efficiency. Being male (p=0.004), high ventilatory equivalent for carbon dioxide at anaerobic threshold (p<0.001) or biomarkers (p=0.006) were the strongest predictors of impaired peak oxygen uptake in multivariate analysis, whereas for an impaired percentage achieved of predicted value were right ventricle diastolic diameter (p<0.001), months of treatment (p=0.01) and high ventilatory equivalent for CO(2) (p<0.001). In pulmonary arterial hypertension, right ventricle dysfunction (expressed by its dilation or high NTproBNP) and impaired ventilatory inefficiency as well as being male or a short time under treatment can be considered as determining factors of impaired exercise capacity. Copyright © 2010 SEPAR. Published by Elsevier Espana. All rights reserved.

  15. Targeted Delivery of Pulmonary Arterial Endothelial Cells Overexpressing Interleukin-8 Receptors Attenuates Monocrotaline-Induced Pulmonary Vascular Remodeling

    PubMed Central

    Fu, Jinyan; Chen, Yiu-Fai; Zhao, Xiangmin; Creighton, Judy; Guo, Yuan-Yuan; Hage, Fadi G.; Oparil, Suzanne; Xing, Daisy D.

    2014-01-01

    Objective Interleukin-8 (IL8) receptors IL8RA and IL8RB (ILRA/B) on neutrophil membranes bind to IL8 with high affinity and play a critical role in neutrophil recruitment to sites of injury and/or inflammation. This study tested the hypothesis that administration of rat pulmonary arterial endothelial cells (ECs) overexpressing IL8RA/B can accelerate the adhesion of ECs to the injured lung and inhibit monocrotaline (MCT)-induced pulmonary inflammation, arterial thickening and hypertension, and right ventricular (RV) hypertrophy. Approach and Results The treatment groups included 10-wk-old ovariectomized Sprague-Dawley rats that received s.c. injection of phosphate-buffered-saline (Vehicle); a single injection of MCT (MCT alone, 60 mg/kg, s.c.); MCT followed by i.v. transfusion of ECs transduced with the empty adenoviral vector (Null-EC); and MCT followed by i.v. transfusion of ECs overexpressing IL8RA/B (IL8RA/B-EC, 1.5×106 cells/rat). Two days or 4 wks after MCT treatment, eNOS, iNOS, CINC-2β (IL8 equivalent in rat) and MCP-1 expression; neutrophil and macrophage infiltration into pulmonary arterioles, and arteriolar and alveolar morphology were measured by histological and immunohistochemical techniques. Pro-inflammatory cytokine/chemokine protein levels were measured by Multiplexed rat specific magnetic beads based sandwich immunoassay in total lung homogenates. Transfusion of IL8RA/B-ECs significantly reduced MCT-induced neutrophil infiltration and pro-inflammatory mediator (IL-8, MCP-1, iNOS, CINC and MIP-2) expression in lungs and pulmonary arterioles and alveoli, pulmonary artery pressure, and pulmonary arteriole and RV hypertrophy and remodeling. Conclusion These provocative findings suggest that targeted delivery of ECs overexpressing IL8RA/B is effective in repairing the injured pulmonary vasculature. PMID:24790141

  16. 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.

  17. 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

  18. Contrast Media Delivery in the Assessment of Anomalous Left Coronary Artery From the Pulmonary Artery.

    PubMed

    Saade, Charbel; Al-Hamra, Salam; Al-Mohiy, Hussain; El-Merhi, Fadi

    2016-05-01

    A patient with a history of mitral valve prolapse and regurgitation that was corrected with a mitral ring repair 15 years earlier received a diagnosis of anomalous left coronary artery arising from the pulmonary artery and underwent repair. Coronary computed tomography angiography (CTA) was employed to image the patient before surgical intervention. Synchronizing contrast media administration to opacify the right coronary artery in the arterial phase and the left coronary artery in the venous phase required a test-bolus approach. Matching compromised cardiovascular dynamics with patient-specific contrast media administration protocols was improved considerably with the use of a test-bolus technique during electrocardiography-gated coronary CTA.

  19. Changing demographics, epidemiology, and survival of incident pulmonary arterial hypertension: results from the pulmonary hypertension registry of the United Kingdom and Ireland.

    PubMed

    Ling, Yi; Johnson, Martin K; Kiely, David G; Condliffe, Robin; Elliot, Charlie A; Gibbs, J Simon R; Howard, Luke S; Pepke-Zaba, Joanna; Sheares, Karen K K; Corris, Paul A; Fisher, Andrew J; Lordan, James L; Gaine, Sean; Coghlan, J Gerry; Wort, S John; Gatzoulis, Michael A; Peacock, Andrew J

    2012-10-15

    Incident pulmonary arterial hypertension was underrepresented in most pulmonary hypertension registries and may have a different disease profile to prevalent disease. To determine the characteristics and outcome of a purely incident, treatment-naive cohort of idiopathic, heritable, and anorexigen-associated pulmonary arterial hypertension and to determine the changes in presentations and survival over the past decade in the United Kingdom and Ireland. All consecutive newly diagnosed patients from 2001 to 2009 were identified prospectively. A total of 482 patients (93% idiopathic, 5% heritable, and 2% anorexigen-associated pulmonary arterial hypertension) were diagnosed, giving rise to an estimated incidence of 1.1 cases per million per year and prevalence of 6.6 cases per million in 2009. Younger patients (age ≤ 50 yrs) had shorter duration of symptoms, fewer comorbidities, better functional and exercise capacity, higher percent diffusing capacity of carbon monoxide, more severe hemodynamic impairment, but better survival compared with older patients. In comparison with the earlier cohorts, patients diagnosed in 2007-2009 were older, more obese, had lower percent diffusing capacity of carbon monoxide,(,) and more comorbidities, but better survival. Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) equation, REVEAL risk score, and Pulmonary Hypertension Connection Registry survival equation accurately predicted survival of our incident cohort at 1 year. This study highlights the influence of age on phenotypes of incident pulmonary arterial hypertension and has shown the changes in demographics and epidemiology over the past decade in a national setting. The results suggest that there may be two subtypes of patients: the younger subtype with more severe hemodynamic impairment but better survival, compared with the older subtype who has more comorbidities.

  20. Diverse forms of pulmonary hypertension remodel the arterial tree to a high shear phenotype

    PubMed Central

    Allen, Roblee P.; Schelegle, Edward S.

    2014-01-01

    Pulmonary hypertension (PH) is associated with progressive changes in arterial network complexity. An allometric model is derived that integrates diameter branching complexity between pulmonary arterioles of generation n and the main pulmonary artery (MPA) via a power-law exponent (X) in dn = dMPA2−n/X and the arterial area ratio β = 21–2/X. Our hypothesis is that diverse forms of PH demonstrate early decrements in X independent of etiology and pathogenesis, which alters the arteriolar shear stress load from a low-shear stress (X > 2, β > 1) to a high-shear stress phenotype (X < 2, β < 1). Model assessment was accomplished by comparing theoretical predictions to retrospective morphometric and hemodynamic measurements made available from a total of 221 PH-free and PH subjects diagnosed with diverse forms (World Health Organization; WHO groups I-IV) of PH: mitral stenosis, congenital heart disease, chronic obstructive pulmonary lung disease, chronic thromboembolism, idiopathic pulmonary arterial hypertension (IPAH), familial (FPAH), collagen vascular disease, and methamphetamine exposure. X was calculated from pulmonary artery pressure (PPA), cardiac output (Q) and body weight (M), utilizing an allometric power-law prediction of X relative to a PH-free state. Comparisons of X between PAH-free and PAH subjects indicates a characteristic reduction in area that elevates arteriolar shear stress, which may contribute to mechanisms of endothelial dysfunction and injury before clinically defined thresholds of pulmonary vascular resistance and PH. We conclude that the evaluation of X may be of use in identifying reversible and irreversible phases of PH in the early course of the disease process. PMID:24858853

  1. Ultrasonic Estimation of Mechanical Properties of Pulmonary Arterial Wall Under Normoxic and Hypoxic Conditions

    NASA Astrophysics Data System (ADS)

    Waters, Kendall R.; Mukdadi, Osama M.

    2005-04-01

    Secondary pediatric pulmonary hypertension is a disease that could benefit from improved ultrasonic diagnostic techniques. We perform high-frequency in vitro ultrasound measurements (25 MHz to 100 MHz) on fresh and fixed pulmonary arterial walls excised from normoxic and hypoxic Long-Evans rat models. Estimates of the elastic stiffness coefficients are determined from measurements of the speed of sound. Preliminary results indicate that hypoxia leads to up to increase of 20 % in stiffening of the pulmonary arterial wall.

  2. [Compression of trachea and esophagus by abnormal course of the left pulmonary artery (author's transl)].

    PubMed

    Lang, D; Hofstetter, R; Müssig, G; von Bernuth, G

    1975-11-01

    A three months old infant with abnormal origine and course of the left pulmonary artery is described. The course of the left pulmonary artery between oesophagus and trachea causes narrowing of the distal trachea leading to in- and expiratory stridor. A ventral indentation of the oesophagus, visible on the lateral plane of an oesophageal roentgenogram, is characteristic for the anomaly which can be proven by pulmonary angiography.

  3. 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

  4. Impact of Chronic Hypoxia on Proximal Pulmonary Artery Wave Propagation and Mechanical Properties in Rats.

    PubMed

    Su, Junjing; Logan, Charmilie C; Hughes, Alun D; Parker, Kim H; Dhutia, Niti M; Danielsen, Carl Christian; Simonsen, Ulf

    2018-03-16

    Arterial stiffness and wave reflection are important components of the ventricular afterload. Therefore, we aimed to assess the arterial wave characteristics and mechanical properties of the proximal pulmonary arteries (PAs) in the hypoxic pulmonary hypertensive rat model. After 21 days in normoxic or hypoxic chambers (24 animals in each group), the animals underwent transthoracic echocardiography and pulmonary artery catheterization with a dual-tipped pressure and Doppler flow sensor wire. Wave intensity analysis (WIA) was performed. Artery rings obtained from the pulmonary trunk, right and left PAs and the aorta were subjected to a tensile test to rupture. Collagen and elastin content was determined. In hypoxic rats, proximal PA wall thickness, collagen content, tensile strength per unit collagen, maximal elastic modulus and wall viscosity increased; while the elastin:collagen ratio and arterial distensibility decreased. Arterial pulse wave velocity was also increased and the increase was more prominent in vivo than ex vivo. Wave intensity was similar in the hypoxic and normoxic animals with negligible wave reflection. In contrast, aortic maximal elastic modulus remained unchanged, while the wall viscosity decreased. There was no evidence of altered arterial wave propagation in the proximal PAs of hypoxic rats, while the extracellular matrix protein composition altered and the collagen tensile strength increased. This was accompanied by altered mechanical properties in vivo and ex vivo.

  5. [Right branch pulmonary artery stenosis with supravalvar aortic stenosis as a complication of Lecompte maneuver for tetralogy of Fallot associated with absent pulmonary valve].

    PubMed

    Honda, Yoshihiro; Suzuki, Shoji; Kaga, Shigeaki; Yoshida, Yukiyo; Kimura, Mitsuhiro; Kamiya, Kentaro; Sakakibara, Kenji; Katsu, Masatake

    2015-05-01

    The patient was diagnosed with tetralogy of Fallot associated with absent pulmonary valve syndrome and a low birth weight of 1,912 g. He suffered from respiratory distress on day 14 and received non-invasive positive pressure ventilation. At 5 months of age and 4.1 kg, he underwent intracardiac repair including right ventricular outflow repair with a monocusp patch, patch closure of the ventricular septum defect and right pulmonary transposition to the anterior of the ascending aorta following the Lecompte maneuver for airway decompression. He was subsequently discharged to home and exhibited an uneventful clinical course with non-invasive positive pressure ventilation for 5 months postoperatively. However, right pulmonary artery and supra-aortic stenosis was noted 2 years after the operation. Computed tomography (CT) and angiography showed ascending aorta strangulation by the right pulmonary artery with right ventricular outflow regurgitation. Right pulmonary artery reconstruction using polytetrafluoroethylene graft interposition and repeat right ventricular outflow repair with bicuspid hand-sewn valves was therefore performed;the postoperative course was uneventful. Pre- and post-operative management using non-invasive positive pressure ventilation and airway decompression with pulmonary artery translocation is a useful strategy in patients exhibiting symptomatic tetralogy of Fallot associated with absent pulmonary valve syndrome in the neonatal period.

  6. Determination of lung segments in computed tomography images using the Euclidean distance to the pulmonary artery

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

    Stoecker, Christina; Moltz, Jan H.; Lassen, Bianca

    Purpose: Computed tomography (CT) imaging is the modality of choice for lung cancer diagnostics. With the increasing number of lung interventions on sublobar level in recent years, determining and visualizing pulmonary segments in CT images and, in oncological cases, reliable segment-related information about the location of tumors has become increasingly desirable. Computer-assisted identification of lung segments in CT images is subject of this work.Methods: The authors present a new interactive approach for the segmentation of lung segments that uses the Euclidean distance of each point in the lung to the segmental branches of the pulmonary artery. The aim is tomore » analyze the potential of the method. Detailed manual pulmonary artery segmentations are used to achieve the best possible segment approximation results. A detailed description of the method and its evaluation on 11 CT scans from clinical routine are given.Results: An accuracy of 2–3 mm is measured for the segment boundaries computed by the pulmonary artery-based method. On average, maximum deviations of 8 mm are observed. 135 intersegmental pulmonary veins detected in the 11 test CT scans serve as reference data. Furthermore, a comparison of the presented pulmonary artery-based approach to a similar approach that uses the Euclidean distance to the segmental branches of the bronchial tree is presented. It shows a significantly higher accuracy for the pulmonary artery-based approach in lung regions at least 30 mm distal to the lung hilum.Conclusions: A pulmonary artery-based determination of lung segments in CT images is promising. In the tests, the pulmonary artery-based determination has been shown to be superior to the bronchial tree-based determination. The suitability of the segment approximation method for application in the planning of segment resections in clinical practice has already been verified in experimental cases. However, automation of the method accompanied by an evaluation on a

  7. 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

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

    PubMed

    Bordones, Alifer D; Leroux, Matthew; Kheyfets, Vitaly O; Wu, Yu-An; Chen, Chia-Yuan; Finol, Ender A

    2018-05-21

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

  9. Experimental pulmonary embolism: effects of the thrombus and attenuation of pulmonary artery injury by low-molecular-weight heparin.

    PubMed

    Rectenwald, John E; Deatrick, K Barry; Sukheepod, Pasu; Lynch, Erin M; Moore, Andrea J; Moaveni, Daria M; Dewyer, Nicholas A; Deywer, Nicholas A; Luke, Catherine E; Upchurch, Gilbert R; Wakefield, Thomas W; Kunkel, Steven L; Henke, Peter K

    2006-04-01

    Pulmonary embolism (PE) is a life-threatening condition that is associated with the long-term sequelae of chronic pulmonary hypertension. Prior experimental work has suggested that post-PE inflammation is accompanied by pulmonary artery intimal hyperplasia. This study evaluated the effect of the thrombus and tested the hypothesis that thrombolytic, antiplatelet, and anticoagulant agents would decrease pulmonary injury. Male Sprague-Dawley rats (n = 267) underwent laparotomy and temporary clip occlusion of the infrarenal inferior vena cava for the formation of endogenous thrombus or placement of an inert silicone "thrombus." Two days later, repeat laparotomy was performed, the clip removed, and the thrombus or silicone plug was embolized to the lungs. The endogenous thrombus group received normal saline, low-molecular-weight heparin (LMWH), tissue plasminogen activator (tPA), or a gIIB/IIIA antagonist (abciximab). Lung tissue was harvested at various times over 21 days and assayed for total collagen, monocyte chemoattractant protein-1 (MCP-1), interleukin-13 (IL-13), and transforming growth factor-beta (TGF-beta). Fixed sections were stained with trichrome for intimal hyperplasia determination and ED-1 monocytes and alpha-actin-positive staining. The overall survival for rats undergoing PE was 90%, was not affected by treatment, and 84% of all PE localized to the right pulmonary artery. The PE significantly reduced Pa(O2) in all groups. Compared with controls, the silicone emboli group had an increased level of IL-13 on day 1, an increased level of MCP-1 on day 4, and an increase in the levels of all inflammatory mediators on day 14 (P < .05). Accompanying these differences were greater pulmonary artery intimal hyperplasia at days 4 and 21 in the silicone group compared with controls (P < .05). LMWH treatment in the thrombus of PE rats significantly decreased IL-13 levels at all time points, whereas treatment with abciximab or tPA significantly increased IL-13

  10. ITE inhibits growth of human pulmonary artery endothelial cells.

    PubMed

    Pang, Ling-Pin; Li, Yan; Zou, Qing-Yun; Zhou, Chi; Lei, Wei; Zheng, Jing; Huang, Shi-An

    2017-10-01

    Pulmonary arterial hypertension (PAH), a deadly disorder is associated with excessive growth of human pulmonary artery endothelial (HPAECs) and smooth muscle (HPASMCs) cells. Current therapies primarily aim at promoting vasodilation, which only ameliorates clinical symptoms without a cure. 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) is an endogenous aryl hydrocarbon receptor (AhR) ligand, and mediates many cellular function including cell growth. However, the roles of ITE in human lung endothelial cells remain elusive. Herein, we tested a hypothesis that ITE inhibits growth of human pulmonary artery endothelial cells via AhR. Immunohistochemistry was performed to localize AhR expression in human lung tissues. The crystal violet method and MTT assay were used to determine ITE's effects on growth of HPAECs. The AhR activation in HPAECs was confirmed using Western blotting and RT-qPCR. The role of AhR in ITE-affected proliferation of HPAECs was assessed using siRNA knockdown method followed by the crystal violet method. Immunohistochemistry revealed that AhR was present in human lung tissues, primarily in endothelial and smooth muscle cells of pulmonary veins and arteries, as well as in bronchial and alveolar sac epithelia. We also found that ITE dose- and time-dependently inhibited proliferation of HPAECs with a maximum inhibition of 83% at 20 µM after 6 days of treatment. ITE rapidly decreased AhR protein levels, while it increased mRNA levels of cytochrome P450 (CYP), family 1, member A1 (CYP1A1) and B1 (CYP1B1), indicating activation of the AhR/CYP1A1 and AhR/CYP1B1 pathways in HPAECs. The AhR siRNA significantly suppressed AhR protein expression, whereas it did not significantly alter ITE-inhibited growth of HPAECs. ITE suppresses growth of HPAECs independent of AhR, suggesting that ITE may play an important role in preventing excessive growth of lung endothelial cells.

  11. Decline in arterial partial pressure of oxygen after exercise: a surrogate marker of pulmonary vascular obstructive disease in patients with atrial septal defect and severe pulmonary hypertension.

    PubMed

    Laksmivenkateshiah, Srinivas; Singhi, Anil K; Vaidyanathan, Balu; Francis, Edwin; Karimassery, Sundaram R; Kumar, Raman K

    2011-06-01

    To examine the utility of decline in arterial partial pressure of oxygen after exercise as a marker of pulmonary vascular obstructive disease in patients with atrial septal defect and pulmonary hypertension. Treadmill exercise was performed in 18 patients with atrial septal defect and pulmonary hypertension. Arterial blood gas samples were obtained before and after peak exercise. A decline in the arterial pressure of oxygen of more than 10 millimetres of mercury after exercise was considered significant based on preliminary tests conducted on the controls. Cardiac catheterisation was performed in all patients and haemodynamic data sets were obtained on room air, oxygen, and a mixture of oxygen and nitric oxide (30-40 parts per million). There were 10 patients who had more than a 10 millimetres of mercury drop in arterial partial pressure of oxygen after exercise and who had a basal pulmonary vascular resistance index of more than 7 Wood units per square metre. Out of eight patients who had less than a 10 millimetres of mercury drop in arterial partial pressure of oxygen after exercise, seven had a basal pulmonary vascular resistance index of less than 7 Wood units per square metre, p equals 0.0001. A decline in arterial partial pressure of oxygen of more than 10 millimetres of mercury predicted a basal pulmonary vascular resistance index of more than 7 Wood units per square metre with a specificity of 100% and a sensitivity of 90%. A decline in arterial partial pressure of oxygen following exercise appears to predict a high pulmonary vascular resistance index in patients with atrial septal defect and pulmonary hypertension. This test is a useful non-invasive marker of pulmonary vascular obstructive disease in this subset.

  12. 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.

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

    PubMed Central

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

    1974-01-01

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

  14. Varied response of the pulmonary arterial endothelium in a novel rat model of venous thromboembolism.

    PubMed

    Ji, Ying-qun; Feng, Min; Zhang, Zhong-he; Lu, Wei-xuan; Wang, Chen

    2013-01-01

    The experimental studies of venous thromboembolism (VTE) as an entity and the response of the pulmonary arterial endothelium after VTE are still rare. The objective of this study was to observe changes in the pulmonary arterial endothelium using a novel rat model of VTE. Rats were allocated to the VTE (n = 54) or control groups (n = 9). The left femoral vein was blocked using a microvessel clip to form deep vein thrombosis (DVT). One, four or seven-day-old thrombi were injected into the right femoral vein to induce DVT-pulmonary thromboembolism (DVT-PTE). The rats were sacrificed 1, 4 or 7 days later (D(n(1,4,7)) P(n(1,4,7)) subgroups (n = 6)), and the lungs were examined using light and electron microscopy. On gross dissection, the rate of DVT formation was higher on day 1 (D(1)P(n): 100%, 18/18) than day 4 (D(4)P(n): 83%, 15/18; χ(2) = 5.900, P = 0.015) or day 7 (D(7)P(n): 44%, 8/18; χ(2) = 13.846, P = 0.000). On gross dissection, the positive emboli residue rate in the pulmonary arteries was lower in the D(1)P(n) subgroup (39%, 7/18) than the D(4)P(n) (73%, 11/15; χ(2) = 3.915, P = 0.048) and D(7)P(n) subgroups (100%, 8/8; χ(2) = 8.474, P = 0.004); however, light microscopy indicated the residual emboli rate was similar in all subgroups. Hyperplasia of the pulmonary arterial endothelium was observed 4 and 7 days after the injection of one-day-old or four-day-old thrombi. However, regions without pulmonary arterial endothelial cells and intra-elastic layers were observed one day after injection of seven-day-old thrombi. This novel model closely simulates the clinical situations of thrombus formation and is ideal to study pulmonary endothelial cell activation. The outcome of emboli and pulmonary arterial endothelial alterations are related to the age and nature of the thrombi.

  15. [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

  16. Development of a technique for determination of pulmonary artery pulse wave velocity in horses.

    PubMed

    Silva, Gonçalo Teixeira de Almeida; Guest, Bruce B; Gomez, Diego E; McGregor, Martine; Viel, Laurent; O'Sullivan, M Lynne; Runciman, John; Arroyo, Luis G

    2017-05-01

    Calcification of the tunica media of the axial pulmonary arteries (PA) has been reported in a large proportion of racehorses. In humans, medial calcification is a significant cause of arterial stiffening and is implicated in the pathogenesis of cardiac, cerebral, and renal microvascular diseases. Pulse wave velocity (PWV) provides a measure of arterial stiffness. This study aimed to develop a technique to determine PA-PWV in horses and, secondarily, to investigate a potential association between PA-PWV and arterial fibro-calcification. A dual-pressure sensor catheter (PSC) was placed in the main PA of 10 sedated horses. The pressure waves were used to determine PWV along the PA, using the statistical phase offset method. Histological analysis of the PA was performed to investigate the presence of fibro-calcified lesions. The mean (±SD) PWV was 2.3 ± 0.7 m/s in the proximal PA trunk and 1.1 ± 0.1 m/s further distal (15 cm) in a main PA branch. The mean (±SD) of mean arterial pressures in the proximal PA trunk was 30.1 ± 5.2 mmHg, and 22.0 ± 6.0 mmHg further distal (15 cm) within the main PA branch. The mean (±SD) pulse pressure in the proximal PA trunk was 15.0 ± 4.7 mmHg, and 13.5 ± 3.3 mmHg further distal (15 cm) within the main PA branch. Moderate to severe lesions of the tunica media of the PAs were observed in seven horses, but a correlation with PWV could not be established yet. Pulmonary artery PWV may be determined in standing horses. The technique described may allow further investigation of the effect of calcification of large PAs in the pathogenesis of equine pulmonary circulatory disorders. NEW & NOTEWORTHY Pulmonary artery pulse wave velocity was determined safely in standing sedated horses. The technique described may allow further investigation of the effect of calcification of large pulmonary arteries in the pathogenesis of pulmonary circulatory disorders in horses. Copyright © 2017 the American Physiological Society.

  17. 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

  18. Incentive spirometry for preventing pulmonary complications after coronary artery bypass graft.

    PubMed

    Freitas, E R F S; Soares, B G O; Cardoso, J R; Atallah, A N

    2007-07-18

    Following coronary artery bypass graft (CABG), the main causes of postoperative morbidity and mortality are postoperative pulmonary complications, respiratory dysfunction and arterial hypoxemia. Incentive spirometry is a treatment technique that uses a mechanical device (an incentive spirometer) to reduce such pulmonary complications during postoperative care. To assess the effects of incentive spirometry for preventing postoperative pulmonary complications in adults undergoing CABG. We searched CENTRAL on The Cochrane Library (Issue 2, 2004), MEDLINE (1966 to December 2004), EMBASE (1980 to December 2004), LILACS (1982 to December 2004), the Physiotherapy Evidence Database (PEDro) (1980 to December 2004), Allied & Complementary Medicine (AMED) (1985 to December 2004), CINAHL (1982 to December 2004), and the Database of Abstracts of Reviews of Effects (DARE) (1994 to December 2004). References were checked and authors contacted. No language restrictions were applied. Randomized controlled trials comparing incentive spirometry with any type of prophylactic physiotherapy for prevention of postoperative pulmonary complications in adults undergoing CABG. Two reviewers independently evaluated the quality of trials using the guidelines of the Cochrane Reviewers' Handbook and extracted data from included trials. Four trials with 443 participants contributed to this review. There was no significant difference in pulmonary complications (atelectasis and pneumonia) between treatment with incentive spirometry and treatment with positive pressure breathing techniques (continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP) and intermittent positive pressure breathing (IPPB)) or preoperative patient education. Patients treated with incentive spirometry had worse pulmonary function and arterial oxygenation compared with positive pressure breathing (CPAP, BiPAP, IPPB). Individual small trials suggest that there is no evidence of benefit from incentive

  19. Transcatheter stenting of the right ventricular outflow tract augments pulmonary arterial growth in symptomatic infants with right ventricular outflow tract obstruction and hypercyanotic spells.

    PubMed

    McGovern, Eimear; Morgan, Conall T; Oslizlok, Paul; Kenny, Damien; Walsh, Kevin P; McMahon, Colin J

    2016-10-01

    We retrospectively reviewed all the children with right ventricular outflow tract obstruction, hypoplastic pulmonary annulus, and pulmonary arteries who underwent stenting of the right ventricular outflow tract for hypercyanotic spells at our institution between January, 2008 and December, 2013; nine patients who underwent cardiac catheterisation at a median age of 39 days (range 12-60 days) and weight of 3.6 kg (range 2.6-4.3 kg) were identified. The median number of stents placed was one stent (range 1-4). The median oxygen saturation increased from 60% to 96%. The median right pulmonary artery size increased from 3.3 to 5.5 mm (-2.68 to -0.92 Z-score), and the median left pulmonary artery size increased from 3.4 to 5.5 mm (-1.93 to 0 Z-scores). Among all, one patient developed transient pulmonary haemorrhage, and one patient had pericardial tamponade requiring drainage. Complete repair of tetralogy of Fallot +/- atrioventricular septal defect or double-outlet right ventricle was achieved in all nine patients. Transcatheter stent alleviation of the right ventricular outflow tract obstruction resolves hypercyanotic spells and allows reasonable growth of the pulmonary arteries to facilitate successful surgical repair. This represents a viable alternative to placement of a systemic-to-pulmonary artery shunt, particularly in small neonates.

  20. Unusual Survival of Anomalous Left Coronary Artery From the Pulmonary Artery With Severe Rheumatic Mitral Stenosis in Septuagenarian Women: Foes Becoming Friends?

    PubMed

    Sinha, Santosh Kumar; Khanra, Dibbendhu; Jha, Mukesh Jitendra; Singh, Karandeep; Razi, Mahamdulla; Goel, Amit; Mishra, Vikas; Asif, Mohammad; Sachan, Mohit; Afdaali, Nasar; Kumar, Ashutosh; Thakur, Ramesh; Krishna, Vinay; Pandey, Umeshwar; Varma, Chandra Mohan

    2016-10-01

    ALCAPA syndrome (anomalous origin of the left coronary artery from the pulmonary artery) is a rare disease but lethal with clinical expression from myocardial infarction, congestive heart failure to death during early infancy and unusual survival to adulthood. We report a 73-year-old woman with ALCAPA who presented with exertional dyspnea (NYHA functional class II) over past 2 years. Physical examination revealed soft S, long mid diastolic rumbling murmur and apical pan-systolic murmur. Electrocardiography displayed biatrial enlargement and poor R progression and normal sinus rhythm. Echocardiography established calcified severe mitral stenosis (MS), presence of continuous flow entering the pulmonary trunk, turbulent continuous flow in inter-ventricular septum with left to right shunt in contrast echocardiography and normal systolic function. Coronary angiogram showed absence of left coronary artery (LCA) originating from aorta, dilated and tortuous right coronary artery (RCA) and abundant Rentrop grade 3 intercoronary collateral communicating with LCA originating from pulmonary trunk which was also confirmed on coronary CT angiogram thus establishing diagnosis of ALCAPA. It is exceedingly rare to be associated with severe MS. However, such a long survival in our patient can be explained by the severe pulmonary arterial hypertension which may be contributing to lesser coronary steal.

  1. 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.

  2. A Rare Case of Pulmonary Artery Sling with the VACTERL Association in a 20-Month-Old Infant.

    PubMed

    Ghandi, Yazdan; Shafiee, Akbar; Sharifi, Mehrazad; Bolandnazar, Najmeh Sadat

    2017-07-01

    The VACTERL association, co-occurrence of vertebral, anorectal, cardiac, tracheoesophageal, genitourinary, and limb malformations, is a rare congenital anomaly. Several cardiac anomalies have been reported as a part of the VACTERL association, particularly ventricular and atrial septal defects. Pulmonary artery sling is a rare congenital abnormality in which the left pulmonary artery arises from the right pulmonary artery. This anomaly is not frequently observed in the VACTERL association and has been rarely reported. A 20-month-old girl was admitted to our hospital due to pneumonia in the right lung, which had pulmonary artery sling as a part of the VACTERL association. Barium meal X-ray showed pressure effects on the esophagus, and computed tomography angiography revealed pulmonary artery sling. Pneumonia management was done. However, the parents of our patient refused to give consent for the surgical correction of this vascular anomaly. Three months after discharge from the hospital, the patient was visited, at which time the parents again refused surgery and treatment for their daughter despite our recommendations.

  3. A Rare Case of Pulmonary Artery Sling with the VACTERL Association in a 20-Month-Old Infant

    PubMed Central

    Ghandi, Yazdan; Shafiee, Akbar; Sharifi, Mehrazad; Bolandnazar, Najmeh Sadat

    2017-01-01

    The VACTERL association, co-occurrence of vertebral, anorectal, cardiac, tracheoesophageal, genitourinary, and limb malformations, is a rare congenital anomaly. Several cardiac anomalies have been reported as a part of the VACTERL association, particularly ventricular and atrial septal defects. Pulmonary artery sling is a rare congenital abnormality in which the left pulmonary artery arises from the right pulmonary artery. This anomaly is not frequently observed in the VACTERL association and has been rarely reported. A 20-month-old girl was admitted to our hospital due to pneumonia in the right lung, which had pulmonary artery sling as a part of the VACTERL association. Barium meal X-ray showed pressure effects on the esophagus, and computed tomography angiography revealed pulmonary artery sling. Pneumonia management was done. However, the parents of our patient refused to give consent for the surgical correction of this vascular anomaly. Three months after discharge from the hospital, the patient was visited, at which time the parents again refused surgery and treatment for their daughter despite our recommendations. PMID:29062381

  4. Cardiac and Pulmonary Cystic Echinococcosis with Massive Obstruction of the Pulmonary Vessel System in a 16 Year Old Girl.

    PubMed

    Kohlmaier, Benno; Trobisch, Andreas; Pfurtscheller, Klaus; Knez, Igor; Klepetko, Walter; Pilhatsch, Alexander; Schweintzger, Sabrina; Zenz, Werner

    2018-04-09

    We describe herein the management of a 16-year-old girl with cystic echinococcosis (CE) of the right ventricle and massive obstruction of the pulmonary vessel system by parasitic metastatic dissemination. After resection of the cardiac cyst, pulmonary thromboendarterectomy was performed to remove parts of the obstructive parasitic material. The treatment reduced the elevated pulmonary arterial pressure, improving the patient's overall condition.

  5. A novel mouse model of high flow-induced pulmonary hypertension-surgically induced by right pulmonary artery ligation.

    PubMed

    Zhang, Anchen; Wang, Hongfei; Wang, Shengwei; Huang, Xiaofan; Ye, Ping; Du, Xinling; Xia, Jiahong

    2017-02-01

    This study sought to establish a new model of high-flow pulmonary hypertension (PH) in mice. This model may be useful for studies seeking to reduce the pulmonary vascular resistance and delay the development of PH caused by congenital heart disease. The right pulmonary artery was ligated via a right posterolateral thoracotomy. Pulmonary hemodynamics was evaluated by right heart catheterization immediately after ligation and at 2, 4, 8, and 12 wk postoperatively. The right ventricle (RV) and the left ventricle (LV) with septum (S) were weighed to calculate the RV/(LV + S) ratio as an index of right ventricular hypertrophy. Morphologic changes in the left lungs were analyzed, and percentages of muscularized pulmonary vessels were assessed by hematoxylin and eosin, elastica van Gieson and alpha-smooth muscle actin staining. All the study data were compared with data from a model of PH generated by hypoxic stimulation. A pulmonary hypertensive state was successfully induced by 2 wk after surgery. However, the morphologic analysis demonstrated that pulmonary vascular muscularization, as evaluated using right ventricular systolic pressure and RV/(LV + S), was not significantly increased until 4 wk postoperatively. When mice from the new model and the hypoxic model were compared, no significant differences were observed in any of the evaluated indices. High-flow PH can be induced within 4 wk after ligation of the right pulmonary artery, which is easily performed in mice. Such mice can be used as a model of high-flow PH. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. 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 ( ...

  7. A Mock Circulatory System Incorporating a Compliant 3D-Printed Anatomical Model to Investigate Pulmonary Hemodynamics

    PubMed Central

    Knoops, Paul G.M.; Biglino, Giovanni; Hughes, Alun D.; Parker, Kim H.; Xu, Linzhang; Schievano, Silvia; Torii, Ryo

    2017-01-01

    A realistic mock circulatory system (MCS) could be a valuable in vitro testbed to study human circulatory hemodynamics. The objective of this study was to design a MCS replicating the pulmonary arterial circulation, incorporating an anatomically representative arterial model suitable for testing clinically relevant scenarios. A second objective of the study was to ensure the system's compatibility with magnetic resonance imaging (MRI) for additional measurements. A latex pulmonary arterial model with two generations of bifurcations was manufactured starting from a 3D-printed mold reconstructed from patient data. The model was incorporated into a MCS for in vitro hydrodynamic measurements. The setup was tested under physiological pulsatile flow conditions and results were evaluated using wave intensity analysis (WIA) to investigate waves traveling in the arterial system. Increased pulmonary vascular resistance (IPVR) was simulated as an example of one pathological scenario. Flow split between right and left pulmonary artery was found to be realistic (54 and 46%, respectively). No substantial difference in pressure waveform was observed throughout the various generations of bifurcations. Based on WIA, three main waves were identified in the main pulmonary artery (MPA), that is, forward compression wave, backward compression wave, and forward expansion wave. For IPVR, a rise in mean pressure was recorded in the MPA, within the clinical range of pulmonary arterial hypertension. The feasibility of using the MCS in the MRI scanner was demonstrated with the MCS running 2 h consecutively while acquiring preliminary MRI data. This study shows the development and verification of a pulmonary MCS, including an anatomically correct, compliant latex phantom. The setup can be useful to explore a wide range of hemodynamic questions, including the development of patient- and pathology-specific models, considering the ease and low cost of producing rapid prototyping molds, and the

  8. Superoxide constricts rat pulmonary arteries via Rho-kinase-mediated Ca2+ sensitization

    PubMed Central

    Shaifta, Yasin; Connolly, Michelle; Drndarski, Svetlana; Noah, Anthony; Pourmahram, Ghazaleh E.; Becker, Silke; Aaronson, Philip I.; Ward, Jeremy P.T.

    2018-01-01

    Reactive oxygen species play a key role in vascular disease, pulmonary hypertension, and hypoxic pulmonary vasoconstriction. We investigated contractile responses, intracellular Ca2+ ([Ca2+]i), Rho-kinase translocation, and phosphorylation of the regulatory subunit of myosin phosphatase (MYPT-1) and of myosin light chain (MLC20) in response to LY83583, a generator of superoxide anion, in small intrapulmonary arteries (IPA) of rat. LY83583 caused concentration-dependent constrictions in IPA and greatly enhanced submaximal PGF2α-mediated preconstriction. In small femoral or mesenteric arteries of rat, LY83583 alone was without effect, but it relaxed a PGF2α-mediated preconstriction. Constrictions in IPA were inhibited by superoxide dismutase and tempol, but not catalase, and were endothelium and guanylate cyclase independent. Constrictions were also inhibited by the Rho-kinase inhibitor Y27632 and the Src-family kinase inhibitor SU6656. LY83583 did not raise [Ca2+]i, but caused a Y27632-sensitive constriction in α-toxin-permeabilized IPA. LY83583 triggered translocation of Rho-kinase from the nucleus to the cytosol in pulmonary artery smooth muscle cells and enhanced phosphorylation of MYPT-1 at Thr-855 and of MLC20 at Ser-19 in IPA. This enhancement was inhibited by superoxide dismutase and abolished by Y27632. Hydrogen peroxide did not activate Rho-kinase. We conclude that in rat small pulmonary artery, superoxide triggers Rho-kinase-mediated Ca2+ sensitization and vasoconstriction independent of hydrogen peroxide. PMID:19103285

  9. Transcatheter Arterial Embolization With Spherical Embolic Agent for Pulmonary Metastases From Renal Cell Carcinoma

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

    Seki, Akihiko, E-mail: sekia@igtc.jp; Hori, Shinichi, E-mail: horishin@igtc.jp; Sueyoshi, Satoru, E-mail: sueyoshis@igtc.jp

    2013-12-15

    Purpose: This retrospective study aimed to evaluate the safety and local efficacy of transcatheter arterial embolization (TAE) with superabsorbent polymer microspheres (SAP-MS) in patients with pulmonary metastases from renal cell carcinoma (RCC). Methods: Sixteen patients with unresectable pulmonary metastases from RCC refractory to standard therapy were enrolled to undergo TAE with the purpose of mass reduction and/or palliation. The prepared SAP-MS swell to approximately two times larger than their dry-state size (100-150 {mu}m [n = 14], 50-100 {mu}m [n = 2]). Forty-nine pulmonary nodules (lung n = 22, mediastinal lymph node n = 17, and hilar lymph node n =more » 10) were selected as target lesions for evaluation. Local tumor response was evaluated 3 months after TAE according to Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). The relationship between tumor enhancement ratio by CT during selective angiography and local tumor response was evaluated. Results: The number of TAE sessions per patient ranged from 1 to 5 (median 2.9). Embolized arteries at initial TAE were bronchial arteries in 14 patients (87.5 %) and nonbronchial systemic arteries in 11 patients (68.8 %). Nodule-based evaluation showed that 5 (10.2 %) nodules had complete response, 17 (34.7 %) had partial response, 15 (30.6 %) had stable disease, and 12 (24.5 %) had progressive disease. The response rate was significantly greater in 22 lesions that had a high tumor enhancement ratio than in 27 lesions that had a slight or moderate ratio (90.9 vs. 7.4 %, p = 0.01). Severe TAE-related adverse events did not occur. Conclusion: TAE with SAP-MS might be a well-tolerated and locally efficacious palliative option for patients with pulmonary metastases from RCC.« less

  10. Anomalous origin of the left coronary artery from the pulmonary artery with patent ductus arteriosus: a must to recognize entity.

    PubMed

    Awasthy, Neeraj; Marwah, Ashutosh; Sharma, Rajesh; Dalvi, Bharat

    2010-09-01

    Anomalous left coronary artery from the pulmonary trunk (ALCAPA) presents in early infancy with a clinical picture of congestive heart failure with left ventricular (LV) dysfunction and mitral insufficiency. These manifestations of myocardial ischaemia may be masked in the presence of an associated patent ductus arteriosus (PDA) or ventricular septal defect (VSD) which prevents the fall of pulmonary artery pressures and allows perfusion of the anomalous coronary artery. We present a case of a patient with large PDA-associated ALCAPA and preserved LV function. The importance of such a finding lies in the fact that VSD closure or PDA ligation in such cases would unmask the ALCAPA.

  11. Phasic negative intrathoracic pressures enhance the vascular responses to stimulation of pulmonary arterial baroreceptors in closed-chest anaesthetized dogs

    PubMed Central

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

    2004-01-01

    We investigated whether the reflex responses to stimulation of pulmonary arterial baroreceptors were altered by intrathoracic pressure changes similar to those encountered during normal breathing. Dogs were anaesthetized with α-chloralose, a cardiopulmonary bypass was established, and the pulmonary trunk and its main branches as far as the first lobar arteries were vascularly isolated and perfused with venous blood. The chest was closed following connection to the perfusion circuit and pressures distending the aortic arch, carotid sinus and coronary artery baroreceptors were controlled. Changes in the descending aortic (systemic) perfusion pressure (SPP; flow constant) were used to assess changes in systemic vascular resistance. Values of SPP were plotted against mean pulmonary arterial pressure (PAP) and sigmoid functions applied. From these curves we derived the threshold pressures (corresponding to 5% of the overall response of SPP), the maximum slopes (equivalent to peak gain) and the corresponding PAP (equivalent to ‘set point’). Stimulus–response curves were compared between data obtained with intrathoracic pressure at atmospheric and with a phasic intrathoracic pressure ranging from atmospheric to around −10 mmHg (18 cycles min−1). Results were obtained from seven dogs and are given as means ±s.e.m. Compared to the values obtained when intrathoracic pressure was at atmospheric, the phasic intrathoracic pressure decreased the pulmonary arterial threshold pressure in five dogs; average change from 28.4 ± 5.9 to 19.3 ± 5.9 mmHg (P > 0.05). The inflexion pressure was significantly reduced from 37.8 ± 4.8 to 27.4 ± 4.0 mmHg (P < 0.03), but the slopes of the curves were not consistently changed. These results have shown that a phasic intrathoracic pressure, which simulates respiratory oscillations, displaces the stimulus–response curve of the pulmonary arterial baroreceptors to lower pressures so that it lies within a physiological range of

  12. Flow-related Right Ventricular - Pulmonary Arterial Pressure Gradients during Exercise.

    PubMed

    Wright, Stephen P; Opotowsky, Alexander R; Buchan, Tayler A; Esfandiari, Sam; Granton, John T; Goodman, Jack M; Mak, Susanna

    2018-06-06

    The assumption of equivalence between right ventricular and pulmonary arterial systolic pressure is fundamental to several assessments of right ventricular or pulmonary vascular hemodynamic function. Our aims were to 1) determine whether systolic pressure gradients develop across the right ventricular outflow tract in healthy adults during exercise, 2) examine the potential correlates of such gradients, and 3) consider the effect of such gradients on calculated indices of right ventricular function. Healthy untrained and endurance-trained adult volunteers were studied using right-heart catheterization at rest and during submaximal cycle ergometry. Right ventricular and pulmonary artery pressures were simultaneously transduced, and cardiac output was determined by thermodilution. Systolic pressures, peak and mean gradients, and indices of chamber, vascular, and valve function were analyzed offline. Summary data are reported as mean ± standard deviation or median [interquartile range]. No significant right ventricular outflow tract gradients were observed at rest (mean gradient = 4 [3-5] mmHg), and calculated effective orifice area was 3.6±1.0 cm2. Right ventricular systolic pressure increases during exercise were greater than that of pulmonary artery systolic pressure. Accordingly, mean gradients developed during light exercise (8 [7-9] mmHg) and increased during moderate exercise (12 [9-14] mmHg, p < 0.001). The magnitude of the mean gradient was linearly related to cardiac output (r2 = 0.70, p < 0.001). In healthy adults without pulmonic stenosis, systolic pressure gradients develop during exercise, and the magnitude is related to blood flow rate.

  13. Serum osteoprotegerin is increased and predicts survival in idiopathic pulmonary arterial hypertension

    PubMed Central

    Condliffe, Robin; Pickworth, Josephine A.; Hopkinson, Kay; Walker, Sara J.; Hameed, Abdul G.; Suntharaligam, Jay; Soon, Elaine; Treacy, Carmen; Pepke-Zaba, Joanna; Francis, Sheila E.; Crossman, David C.; Newman, Christopher M. H.; Elliot, Charles A.; Morton, Allison C.; Morrell, Nicholas W.; Kiely, David G.; Lawrie, Allan

    2012-01-01

    We previously reported that osteoprotegerin (OPG) is regulated by pathways associated with pulmonary arterial hypertension (PAH), and is present at elevated levels within pulmonary vascular lesions and sera from patients with idiopathic PAH (IPAH). Since OPG is a naturally secreted protein, we investigated the relationship between serum OPG and disease severity and outcome in patients with IPAH and animal models. OPG mRNA expression was measured in pulmonary artery smooth muscle cells (PASMC) from pulmonary arteries of patients with and without IPAH. Serum concentrations of OPG were measured in a retrospective and prospective group of patients. OPG levels were compared with phenotypic data and other putative PAH biomarkers. Prognostic significance was assessed and levels compared with healthy controls. Correlation of OPG and pulmonary vascular remodeling was also performed in rodent models of PAH. OPG mRNA was significantly increased 2-fold in PASMC isolated from explanted PAH lungs compared with control. Serum OPG concentrations were markedly elevated in IPAH compared with controls. In Cohort 1 OPG levels significantly correlated with mean right atrial pressure and cardiac index, while in Cohort 2 significant correlations existed between age-adjusted OPG levels and gas transfer. In both cohorts an OPG concentration above a ROC-derived threshold of 4728 pg/ml predicted poorer survival. In two rodent models, OPG correlated with the degree of pulmonary vascular remodeling. OPG levels are significantly elevated in patients with idiopathic PAH and are of prognostic significance. The role of OPG as a potential biomarker and therapeutic target merits further investigation. PMID:22558516

  14. Poland syndrome associated with an aberrant subclavian artery and vascular abnormalities of the retina in a child exposed to misoprostol during pregnancy.

    PubMed

    Rosa, Rafael Fabiano Machado; Travi, Giovanni M; Valiatti, Fabiana; Zen, Paulo Ricardo Gazzola; Pinto, Louise Lapagesse; Kiss, Andrea; Graziadio, Carla; Paskulin, Giorgio Adriano

    2007-06-01

    Poland syndrome has been attributed to a process of vascular disruption, and exposure to misoprostol at 6-8 weeks of gestation has been shown to produce defects attributed to vascular disruption. Herein we report the first case of a patient with Poland syndrome associated with an aberrant subclavian artery and vascular abnormalities of the retina, whose mother used misoprostol during pregnancy. A White boy of 1 year and 7 months of age, whose mother used misoprostol during the second month of pregnancy, presented with bilateral epicanthal folds, aplasia of the sternocostal head of the pectoralis major muscle with a hypoplastic nipple on the right side, and asymmetry between the upper limbs. The results of an angiotomographic study showed the presence of an aberrant right subclavian artery. Ultrasonographic evaluation showed turbulence and a high peak in the diastolic velocity in both carotid arteries, suggesting stenosis. Ophthalmologic assessment disclosed an intense bilateral tortuosity of the retinal blood vessels, with arterialnarrowing and rarefaction of the retinal pigment epithelium. This case suggests that the mechanism of vascular disruption of misoprostol could be related to the aberrant subclavian artery and the observed Poland syndrome. His retinal findings are different from those in cases described thus far in the literature, and this pattern of anomaly has never been associated with a gestational exposure to misoprostol. The possibility of a relationship of the aberrant right subclavian artery and the pattern of blood flow verified in the carotid arteries with the eye fundus abnormalities could be causally related or simply coincidental.

  15. Elevated plasma endothelin-1 and pulmonary arterial pressure in children exposed to air pollution.

    PubMed

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

    2007-08-01

    Controlled exposures of animals and humans to particulate matter (PM) or ozone air pollution cause an increase in plasma levels of endothelin-1, a potent vasoconstrictor that regulates pulmonary arterial pressure. The primary objective of this field study was to determine whether Mexico City children, who are chronically exposed to levels of PM and O(3) that exceed the United States air quality standards, have elevated plasma endothelin-1 levels and pulmonary arterial pressures. We conducted a study of 81 children, 7.9 +/- 1.3 years of age, lifelong residents of either northeast (n = 19) or southwest (n = 40) Mexico City or Polotitlán (n = 22), a control city with PM and O(3) levels below the U.S. air quality standards. Clinical histories, physical examinations, and complete blood counts were done. Plasma endothelin-1 concentrations were determined by immunoassay, and pulmonary arterial pressures were measured by Doppler echocardiography. Mexico City children had higher plasma endothelin-1 concentrations compared with controls (p < 0.001). Mean pulmonary arterial pressure was elevated in children from both northeast (p < 0.001) and southwest (p < 0.05) Mexico City compared with controls. Endothelin-1 levels in Mexico City children were positively correlated with daily outdoor hours (p = 0.012), and 7-day cumulative levels of PM air pollution < 2.5 mum in aerodynamic diameter (PM(2.5)) before endothelin-1 measurement (p = 0.03). Chronic exposure of children to PM(2.5) is associated with increased levels of circulating endothelin-1 and elevated mean pulmonary arterial pressure.

  16. Aorta and pulmonary artery segmentation using optimal surface graph cuts in non-contrast CT

    NASA Astrophysics Data System (ADS)

    Sedghi Gamechi, Zahra; Arias-Lorza, Andres M.; Pedersen, Jesper Holst; de Bruijne, Marleen

    2018-03-01

    Accurate measurements of the size and shape of the aorta and pulmonary arteries are important as risk factors for cardiovascular diseases, and for Chronicle Obstacle Pulmonary Disease (COPD).1 The aim of this paper is to propose an automated method for segmenting the aorta and pulmonary arteries in low-dose non-ECGgated non-contrast CT scans. Low contrast and the high noise level make the automatic segmentation in such images a challenging task. In the proposed method, first, a minimum cost path tracking algorithm traces the centerline between user-defined seed points. The cost function is based on a multi-directional medialness filter and a lumen intensity similarity metric. The vessel radius is also estimated from the medialness filter. The extracted centerlines are then smoothed and dilated non-uniformly according to the extracted local vessel radius and subsequently used as initialization for a graph-cut segmentation. The algorithm is evaluated on 225 low-dose non-ECG-gated non-contrast CT scans from a lung cancer screening trial. Quantitatively analyzing 25 scans with full manual annotations, we obtain a dice overlap of 0.94+/-0.01 for the aorta and 0.92+/-0.01 for pulmonary arteries. Qualitative validation by visual inspection on 200 scans shows successful segmentation in 93% of all cases for the aorta and 94% for pulmonary arteries.

  17. Nonenhanced MR angiography of the pulmonary arteries using single-shot radial quiescent-interval slice-selective (QISS): a technical feasibility study.

    PubMed

    Edelman, Robert R; Silvers, Robert I; Thakrar, Kiran H; Metzl, Mark D; Nazari, Jose; Giri, Shivraman; Koktzoglou, Ioannis

    2017-06-30

    For evaluation of the pulmonary arteries in patients suspected of pulmonary embolism, CT angiography (CTA) is the first-line imaging test with contrast-enhanced MR angiography (CEMRA) a potential alternative. Disadvantages of CTA include exposure to ionizing radiation and an iodinated contrast agent, while CEMRA is sensitive to respiratory motion and requires a gadolinium-based contrast agent. The primary goal of our technical feasibility study was to evaluate pulmonary arterial conspicuity using breath-hold and free-breathing implementations of a recently-developed nonenhanced approach, single-shot radial quiescent-interval slice-selective (QISS) MRA. Breath-hold and free-breathing, navigator-gated versions of radial QISS MRA were evaluated at 1.5 Tesla in three healthy subjects and 11 patients without pulmonary embolism or arterial occlusion by CTA. Images were scored by three readers for conspicuity of the pulmonary arteries through the level of the segmental branches. In addition, one patient with pulmonary embolism was imaged. Scan time for a 54-slice acquisition spanning the pulmonary arteries was less than 2 minutes for breath-hold QISS, and less than 3.4 min using free-breathing QISS. Pulmonary artery branches through the segmental level were conspicuous with either approach. Free-breathing scans showed only mild blurring compared with breath-hold scans. For both readers, less than 1% of pulmonary arterial segments were rated as "not seen" for breath-hold and navigator-gated QISS, respectively. In subjects with atrial fibrillation, single-shot radial QISS consistently depicted the pulmonary artery branches, whereas navigator-gated 3D balanced steady-state free precession showed motion artifacts. In one patient with pulmonary embolism, radial QISS demonstrated central pulmonary emboli comparably to CEMRA and CTA. The thrombi were highly conspicuous on radial QISS images, but appeared subtle and were not prospectively identified on scout images acquired

  18. Pulmonary hypertension

    MedlinePlus

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

  19. Outcomes of Percutaneous Closure of Patent Ductus Arteriosus Accompanied With Unilateral Absence of Pulmonary Artery.

    PubMed

    Yang, Yankun; Zheng, Hong; Xu, Zhongying; Zhang, Gejun; Jin, Jinglin; Hu, Haibo; Tian, Tao; Zhou, Xianliang

    2017-04-01

    Limited data have reported the outcomes of percutaneous closure of patent ductus arteriosus (PDA) in patients with unilateral absence of pulmonary artery (UAPA). This study aimed to evaluate the symptomatology, diagnosis and therapy, especially the transcatheter closure of PDA in patients with PDA associated with UAPA. Patients diagnosed with PDA and UAPA were retrospectively enrolled from August 2010 through January 2016. Clinical data, treatment and follow-up information were evaluated. Thirteen patients (6 males and 7 females) were diagnosed with PDA associated with UAPA. Percutaneous closure was successfully conducted in 6 patients successfully. The median age was 7 years (7 months to 37 years). The mean diameter of the PDA and occluders were 4.7 ± 1.8mm (2-7mm) and 11.3 ± 3.9mm (6-14mm), respectively. The mean pulmonary artery pressure was 41.5 ± 13.5mmHg (25-62mmHg). The diameter of PDA has no relationship with the degree of pulmonary artery pressure (r = 0.239, P = 0.648). In 4 patients, systolic pulmonary arterial pressure decreased significantly after closure with 69.0 ± 10.7 versus 48.0 ± 11.3mmHg (P = 0.146), and also the mean pulmonary arterial pressure was 54.5 ± 5.7 mm Hg versus 30.5 ± 3.9mmHg (P = 0.04). In all, 1 patient had a trace residual shunt, which disappeared within 24 hours. In appropriate patients with PDA associated with UAPA, transcatheter closure of PDA has the potential to improve the pulmonary artery hypertension. Further follow-up is required to monitor the long-term outcomes. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  20. Patent ductus arteriosus associated with aberrant right subclavian artery: two cases, one successful interventional closure of PDA.

    PubMed

    Gomez, Jorge E; Gentile, Jorge I

    2011-01-01

    Two children were sent to the catheterization laboratory for transcatheter closure of patent ductus arteriosus (PDA). During the intervention, cineangiogram revealed associated aberrant right subclavian artery (ARSA). Both patients had left-sided aortic arch. The first patient was sent to surgery after one unsuccessful attempt to close the PDA due to the proximity of the ARSA and also because of other concomitant cardiac lesions. We successfully treated the second patient by closing the PDA with a Nit-Occlud® PDA occlusion device (Pfm Medical, Carlsbad, California). Similar mirror cases of PDA closure with aberrant left subclavian artery and right aortic arch have been reported. Anatomic features, as well as the technique and management of the procedure, are discussed here.

  1. Clinical and imaging features of pulmonary artery sling in infants without significant hemodynamic changes.

    PubMed

    Wang, Jian-Hua; Ding, Gui-Chun; Zhang, Min-Yu; Liu, Mei; Niu, Hai-Yan

    2011-10-01

    Pulmonary artery sling (PAS) is a rare congenital heart anomaly and may cause unexplained respiratory symptoms in infants. Since the non-specific respiratory symptoms of PAS may lead to misdiagnosis, the aim of this study was to clarify the clinical and imaging features of this disease for timely diagnosis and treatment. Clinical histories, physical examinations and imaging studies were retrospectively evaluated in nine infants with PAS. Chest X-ray, echocardiography and contrast-enhanced computed tomography (CT) with 3-dimensional reconstructions were performed in all patients and three of them received surgical treatment. Nine cases included six males and three females with a mean age of (4.3 ± 2.8) months ranging from 2 to 11 months old. All patients had respiratory symptoms including recurrent cough, stridor and wheezing. The onset of symptoms was within 3 months in all cases and three children had symptoms only a few days after birth. The chest X-ray showed pneumonia in all cases. Contrast-enhanced CT showed the tracheal compression at different lengths in every case. The echocardiograph findings of PAS were anomalous origins of the left pulmonary artery from the posterior aspect of the right pulmonary artery. Of the 9 cases, 8 cases were diagnosed correctly by echocardiography. Of the complicated abnormalities, there were one with secundum atrial septal defect, one with patent foramen ovale and three with persistent left superior vena cava. None of them were complicated with significant blood dynamic changes. Infants with recurrent respiratory symptoms such as chronic cough, stridor and wheezing, should be examined for the possible presence of congenital pulmonary artery sling. As a noninvasive technique, echocardiography is very helpful and should be the first-choice modality for the diagnosis of pulmonary artery sling. Contrast-enhanced CT, clearly demonstrating the anatomy of pulmonary artery sling and the position and extent of trachea compression, is

  2. Immune regulation of systemic hypertension, pulmonary arterial hypertension, and preeclampsia: shared disease mechanisms and translational opportunities.

    PubMed

    Jafri, Salema; Ormiston, Mark L

    2017-12-01

    Systemic hypertension, preeclampsia, and pulmonary arterial hypertension (PAH) are diseases of high blood pressure in the systemic or pulmonary circulation. Beyond the well-defined contribution of more traditional pathophysiological mechanisms, such as changes in the renin-angiotensin-aldosterone system, to the development of these hypertensive disorders, there is substantial clinical evidence supporting an important role for inflammation and immunity in the pathogenesis of each of these three conditions. Over the last decade, work in small animal models, bearing targeted deficiencies in specific cytokines or immune cell subsets, has begun to clarify the immune-mediated mechanisms that drive changes in vascular structure and tone in hypertensive disease. By summarizing the clinical and experimental evidence supporting a contribution of the immune system to systemic hypertension, preeclampsia, and PAH, the current review highlights the cellular and molecular pathways that are common to all three hypertensive disorders. These mechanisms are centered on an imbalance in CD4 + helper T cell populations, defined by excessive Th17 responses and impaired T reg activity, as well as the excessive activation or impairment of additional immune cell types, including macrophages, dendritic cells, CD8 + T cells, B cells, and natural killer cells. The identification of common immune mechanisms in systemic hypertension, preeclampsia, and PAH raises the possibility of new therapeutic strategies that target the immune component of hypertension across multiple disorders. Copyright © 2017 the American Physiological Society.

  3. Pulmonary artery location during microgravity activity: Potential impact for chest-mounted Doppler during space travel

    NASA Technical Reports Server (NTRS)

    Hadley, A. T., III; Conkin, J.; Waligora, J. M.; Horrigan, D. J., Jr.

    1984-01-01

    Doppler, or ultrasonic, monitoring for pain manifestations of decompression sickness (the bends) is accomplished by placing a sensor on the chest over the pulmonary artery and listening for bubbles. Difficulties have arisen because the technician notes that the pulmonary artery seems to move with subject movement in a one-g field and because the sensor output is influenced by only slight degrees of sensor movement. This study used two subjects and mapped the position of the pulmonary artery in one-g, microgravity, and two-g environments using ultrasound. The results showed that the pulmonary artery is fixed in location in microgravity and not affected by subject position change. The optimal position corresponded to where the Doppler signal is best heard with the subject in a supine position in a one-g environment. The impact of this result is that a proposed multiple sensor array on the chest proposed for microgravity use may not be necessary to monitor an astronaut during extravehicular activities. Instead, a single sensor of approximately 1 inch diameter and mounted in the position described above may suffice.

  4. Signal transduction in the development of pulmonary arterial hypertension

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Stewart, Traci

    2016-01-01

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

  6. A coincidental variation of the axillary artery: the brachioradial artery and the aberrant posterior humeral circumflex artery passing under the tendon of the latissimus dorsi muscle

    PubMed Central

    Konarik, Marek; Kachlik, David; Baca, Vaclav

    2014-01-01

    A case of anomalous terminal branching of the axillary artery was encountered and described in a left upper limb of a male cadaver. A series of 214 upper limbs of Caucasian race was dissected. A variant artery, stemming from the very end of the axillary artery followed a superficial course distally. It passed the cubital fossa, ran on the lateral side of the forearm as usual radial artery, crossed ventrally to the palm and terminated in the deep palmar arch. This vessel is a case of the brachioradial artery (incorrectly termed as the “radial artery with high origin”). Moreover, it was associated with another variation, concerning the aberrant posterior humeral circumflex artery passing under the tendon of the latissimus dorsi muscle. The anatomical knowledge of the axillary region is essential for radiodiagnostic, surgical and traumatologic procedures. The superficially located artery brings an elevated danger of heavy bleeding in all unexpected situations, its variant branching can cause problems in radial catheterization procedures and the anomalously coursing other arterial variant poses an elevated danger in surgical procedures concerning the surgical neck of humerus. PMID:25428677

  7. The Effects of Statins on Pulmonary Artery Pressure in Patients with Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial

    PubMed Central

    Arian, Anahita; Moghadam, Sayyed Gholamreza Mortazavi; Kazemi, Toba; Hajihosseini, Morteza

    2017-01-01

    Objective: Pulmonary hypertension is a serious complication in patients suffering from chronic obstructive pulmonary disease (COPD). The aim of this study is to investigate the effects of atorvastatin in reducing pulmonary arterial pressure in COPD patients. Methods: This double-blind, randomized trial was conducted on 42 known cases of COPD with systolic pulmonary arterial pressure of more than 25 mmHg. The patients were randomly assigned into two groups, 21 patients with atorvastatin treatment (40 mg/daily for 6 months) and 21 patients without receiving atorvastatin. All the patients participated voluntarily and provided written informed consent. The trial was registered in the Iranian Registry of Clinical Trials. Pulmonary pressure was also anticipated by Doppler echocardiography with peak pressure gradient of tricuspid regurgitation. Both groups were tested with echocardiography to measure systolic pulmonary pressure at baseline and posttreatment. Statistical analysis includes Chi-square, Student's t-test, and Wilcoxon test. P < 0.05 was considered statistically significant. Findings: The mean age was 65.8 ± 11.5 years for atorvastatin group and 63.7 ± 7.6 years for control group (P = 0.45). Baseline and posttreatment mean systolic pulmonary artery pressure (PAP) levels in the atorvastatin group were 48.9 ± 3.3 and 38.4 ± 1.9 mmHg, respectively (P = 0.007). In the control group, mean systolic PAP levels at baseline and 6 months later were 45.6 ± 3.1 and 38.9 ± 2.4 mmHg, respectively (P = 0.073). The patients treated with atorvastatin showed significant decrease in total cholesterol (P = 0.001) and low-density lipoprotein cholesterol (P = 0.008). Conclusion: A 40 mg dose of atorvastatin daily for 6 months may have beneficial effects in reducing PAP in patients with COPD. Further studies are necessary to find long-term effects of statins in COPD patients. PMID:28331863

  8. The Effects of Statins on Pulmonary Artery Pressure in Patients with Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial.

    PubMed

    Arian, Anahita; Moghadam, Sayyed Gholamreza Mortazavi; Kazemi, Toba; Hajihosseini, Morteza

    2017-01-01

    Pulmonary hypertension is a serious complication in patients suffering from chronic obstructive pulmonary disease (COPD). The aim of this study is to investigate the effects of atorvastatin in reducing pulmonary arterial pressure in COPD patients. This double-blind, randomized trial was conducted on 42 known cases of COPD with systolic pulmonary arterial pressure of more than 25 mmHg. The patients were randomly assigned into two groups, 21 patients with atorvastatin treatment (40 mg/daily for 6 months) and 21 patients without receiving atorvastatin. All the patients participated voluntarily and provided written informed consent. The trial was registered in the Iranian Registry of Clinical Trials. Pulmonary pressure was also anticipated by Doppler echocardiography with peak pressure gradient of tricuspid regurgitation. Both groups were tested with echocardiography to measure systolic pulmonary pressure at baseline and posttreatment. Statistical analysis includes Chi-square, Student's t -test, and Wilcoxon test. P < 0.05 was considered statistically significant. The mean age was 65.8 ± 11.5 years for atorvastatin group and 63.7 ± 7.6 years for control group ( P = 0.45). Baseline and posttreatment mean systolic pulmonary artery pressure (PAP) levels in the atorvastatin group were 48.9 ± 3.3 and 38.4 ± 1.9 mmHg, respectively ( P = 0.007). In the control group, mean systolic PAP levels at baseline and 6 months later were 45.6 ± 3.1 and 38.9 ± 2.4 mmHg, respectively ( P = 0.073). The patients treated with atorvastatin showed significant decrease in total cholesterol ( P = 0.001) and low-density lipoprotein cholesterol ( P = 0.008). A 40 mg dose of atorvastatin daily for 6 months may have beneficial effects in reducing PAP in patients with COPD. Further studies are necessary to find long-term effects of statins in COPD patients.

  9. Resting arterial hypoxaemia in subjects with chronic heart failure, pulmonary hypertension and patent foramen ovale.

    PubMed

    Lovering, Andrew T; Lozo, Mislav; Barak, Otto; Davis, James T; Lojpur, Mihajlo; Lozo, Petar; Čaljkušić, Krešimir; Dujić, Željko

    2016-05-01

    What is the central question of this study? Does a patent foramen ovale contribute to resting arterial hypoxaemia, defined as arterial oxygen saturation <95%, in subjects with chronic heart failure with or without pulmonary arterial hypertension? What is the main finding and its importance? The presence of a patent foramen ovale contributed to resting arterial hypoxaemia only in subjects with chronic heart failure with pulmonary arterial hypertension. These data suggest that the presence of a patent foramen ovale should be considered in chronic heart failure patients with arterial hypoxaemia and pulmonary hypertension. The roles of intrapulmonary and intracardiac shunt in contributing to arterial hypoxaemia at rest in subjects with chronic heart failure (CHF) have not been well investigated. We hypothesized that blood flow through intrapulmonary arteriovenous anastomoses (Q̇ IPAVA ) and/or patent foramen ovale (Q̇ PFO ) could potentially contribute to arterial hypoxaemia and, with pulmonary hypertension (PH) secondary to CHF, this contribution may be exacerbated. Fifty-six subjects with CHF (New York Heart Association Classes I-III), with (+) or without (-) PH [defined as peak tricuspid regurgitation velocity ≥2.9 m s(-1) (CHF PH+, n = 32) and peak tricuspid regurgitation velocity ≤2.8 m s(-1) (CHF PH-, n = 24)], underwent arterial blood gas analysis and transthoracic saline contrast echocardiography concomitant with transcranial Doppler to detect Q̇ IPAVA and Q̇ PFO . Seventeen of 56 subjects with CHF (30%) had Q̇ PFO , but only four of 56 subjects with CHF had Q̇ IPAVA (7%), both similar to age- and sex-matched control subjects. Mean arterial oxygen saturation (SaO2) was lower in subjects with Q̇ PFO . Only CHF PH+ subjects with Q̇ PFO had arterial hypoxaemia (mean SaO2 <95%). Bubble scores assessed using transthoracic saline contrast echocardiography were correlated with microembolic signals detected with transcranial Doppler in subjects with

  10. Pulmonary artery dissection following balloon valvuloplasty in a dog with pulmonic stenosis.

    PubMed

    Grint, K A; Kellihan, H B

    2017-04-01

    A 3-month-old, 9.9 kg, male pit bull cross was referred for evaluation of collapse. A left basilar systolic heart murmur graded V/VI and a grade IV/VI right basilar systolic heart murmur were ausculted. Echocardiography showed severe pulmonic stenosis characterized by annular hypoplasia, leaflet thickening, and leaflet fusion. After 1 month of atenolol therapy, a pulmonic valve balloon valvuloplasty procedure was performed, and the intra-operative right ventricular pressure was reduced by 43%. Echocardiography, performed the following day, showed apparent rupture of a pulmonary valve leaflet and a membranous structure within the pulmonary artery consistent with a dissecting membrane. Short-term follow-up has shown no apparent progression of the pulmonary artery dissection and the patient remains free of clinical signs. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Serotonin Signaling Through the 5-HT1B Receptor and NADPH Oxidase 1 in Pulmonary Arterial Hypertension.

    PubMed

    Hood, Katie Y; Mair, Kirsty M; Harvey, Adam P; Montezano, Augusto C; Touyz, Rhian M; MacLean, Margaret R

    2017-07-01

    Serotonin can induce human pulmonary artery smooth muscle cell (hPASMC) proliferation through reactive oxygen species (ROS), influencing the development of pulmonary arterial hypertension (PAH). We hypothesize that in PASMCs, serotonin induces oxidative stress through NADPH-oxidase-derived ROS generation and reduced Nrf-2 (nuclear factor [erythroid-derived 2]-like 2) antioxidant systems, promoting vascular injury. HPASMCs from controls and PAH patients, and PASMCs from Nox1 -/- mice, were stimulated with serotonin in the absence/presence of inhibitors of Src kinase, the 5-HT 1B receptor, and NADPH oxidase 1 (Nox1). Markers of fibrosis were also determined. The pathophysiological significance of our findings was examined in vivo in serotonin transporter overexpressing female mice, a model of pulmonary hypertension. We confirmed thatserotonin increased superoxide and hydrogen peroxide production in these cells. For the first time, we show that serotonin increased oxidized protein tyrosine phosphatases and hyperoxidized peroxiredoxin and decreased Nrf-2 and catalase activity in hPASMCs. ROS generation was exaggerated and dependent on cellular Src-related kinase, 5-HT 1B receptor, and the serotonin transporter in human pulmonary artery smooth muscle cells from PAH subjects. Proliferation and extracellular matrix remodeling were exaggerated in human pulmonary artery smooth muscle cells from PAH subjects and dependent on 5-HT 1B receptor signaling and Nox1, confirmed in PASMCs from Nox1 -/- mice. In serotonin transporter overexpressing mice, SB216641, a 5-HT 1B receptor antagonist, prevented development of pulmonary hypertension in a ROS-dependent manner. Serotonin can induce cellular Src-related kinase-regulated Nox1-induced ROS and Nrf-2 dysregulation, contributing to increased post-translational oxidative modification of proteins and activation of redox-sensitive signaling pathways in hPASMCs, associated with mitogenic responses. 5-HT 1B receptors contribute to

  12. Serotonin Signaling Through the 5-HT1B Receptor and NADPH Oxidase 1 in Pulmonary Arterial Hypertension

    PubMed Central

    Hood, Katie Y.; Mair, Kirsty M.; Harvey, Adam P.; Montezano, Augusto C.; Touyz, Rhian M.

    2017-01-01

    Objective— Serotonin can induce human pulmonary artery smooth muscle cell (hPASMC) proliferation through reactive oxygen species (ROS), influencing the development of pulmonary arterial hypertension (PAH). We hypothesize that in PASMCs, serotonin induces oxidative stress through NADPH-oxidase–derived ROS generation and reduced Nrf-2 (nuclear factor [erythroid-derived 2]-like 2) antioxidant systems, promoting vascular injury. Approach and Results— HPASMCs from controls and PAH patients, and PASMCs from Nox1−/− mice, were stimulated with serotonin in the absence/presence of inhibitors of Src kinase, the 5-HT1B receptor, and NADPH oxidase 1 (Nox1). Markers of fibrosis were also determined. The pathophysiological significance of our findings was examined in vivo in serotonin transporter overexpressing female mice, a model of pulmonary hypertension. We confirmed thatserotonin increased superoxide and hydrogen peroxide production in these cells. For the first time, we show that serotonin increased oxidized protein tyrosine phosphatases and hyperoxidized peroxiredoxin and decreased Nrf-2 and catalase activity in hPASMCs. ROS generation was exaggerated and dependent on cellular Src-related kinase, 5-HT1B receptor, and the serotonin transporter in human pulmonary artery smooth muscle cells from PAH subjects. Proliferation and extracellular matrix remodeling were exaggerated in human pulmonary artery smooth muscle cells from PAH subjects and dependent on 5-HT1B receptor signaling and Nox1, confirmed in PASMCs from Nox1−/− mice. In serotonin transporter overexpressing mice, SB216641, a 5-HT1B receptor antagonist, prevented development of pulmonary hypertension in a ROS-dependent manner. Conclusions— Serotonin can induce cellular Src-related kinase–regulated Nox1-induced ROS and Nrf-2 dysregulation, contributing to increased post-translational oxidative modification of proteins and activation of redox-sensitive signaling pathways in hPASMCs, associated with

  13. Use of mathematic modeling to compare and predict hemodynamic effects of the modified Blalock-Taussig and right ventricle-pulmonary artery shunts for hypoplastic left heart syndrome.

    PubMed

    Bove, Edward L; Migliavacca, Francesco; de Leval, Marc R; Balossino, Rossella; Pennati, Giancarlo; Lloyd, Thomas R; Khambadkone, Sachin; Hsia, Tain-Yen; Dubini, Gabriele

    2008-08-01

    Stage one reconstruction (Norwood operation) for hypoplastic left heart syndrome can be performed with either a modified Blalock-Taussig shunt or a right ventricle-pulmonary artery shunt. Both methods have certain inherent characteristics. It is postulated that mathematic modeling could help elucidate these differences. Three-dimensional computer models of the Blalock-Taussig shunt and right ventricle-pulmonary artery shunt modifications of the Norwood operation were developed by using the finite volume method. Conduits of 3, 3.5, and 4 mm were used in the Blalock-Taussig shunt model, whereas conduits of 4, 5, and 6 mm were used in the right ventricle-pulmonary artery shunt model. The hydraulic nets (lumped resistances, compliances, inertances, and elastances) were identical in the 2 models. A multiscale approach was adopted to couple the 3-dimensional models with the circulation net. Computer simulations were compared with postoperative catheterization data. Good correlation was found between predicted and observed data. For the right ventricle-pulmonary artery shunt modification, there was higher aortic diastolic pressure, decreased pulmonary artery pressure, lower Qp/Qs ratio, and higher coronary perfusion pressure. Mathematic modeling predicted minimal regurgitant flow in the right ventricle-pulmonary artery shunt model, which correlated with postoperative Doppler measurements. The right ventricle-pulmonary artery shunt demonstrated lower stroke work and a higher mechanical efficiency (stroke work/total mechanical energy). The close correlation between predicted and observed data supports the use of mathematic modeling in the design and assessment of surgical procedures. The potentially damaging effects of a systemic ventriculotomy in the right ventricle-pulmonary artery shunt modification of the Norwood operation have not been analyzed.

  14. Long-term effects of prenatal hypoxia on endothelium-dependent relaxation responses in pulmonary arteries of adult sheep.

    PubMed

    Liu, Jie; Gao, Yuansheng; Negash, Sewite; Longo, Lawrence D; Raj, J Usha

    2009-03-01

    Chronic hypoxia during the course of pregnancy is a common insult to the fetus. However, its long-term effect on the pulmonary vasculature in adulthood has not been described. In this study, the vasorelaxation responses of conduit pulmonary arteries in adult female sheep that were chronically hypoxic as fetuses and raised postnatally at sea level were investigated. Vessel tension studies revealed that endothelium-dependent relaxation responses were attenuated in pulmonary arteries from adult sheep that experienced prenatal hypoxia. Endothelial nitric oxide synthase (eNOS) protein expression was unchanged, but eNOS activity was significantly decreased in pulmonary arteries from prenatally hypoxic sheep. Protein expression of eNOS partners, caveolin-1, calmodulin, and heat shock protein 90 (Hsp90) did not change following prenatal hypoxia. However, the association between eNOS and caveolin-1, its inhibitory binding partner, was significantly increased, whereas association between eNOS and its stimulatory partners calmodulin and Hsp90 was greatly decreased. Furthermore, phosphorylation of Ser(1177) in eNOS decreased, whereas phosphorylation of Thr(495) increased, in the prenatally hypoxic pulmonary arteries, events that are related to eNOS activity. These data demonstrate that prenatal hypoxia results in persistent abnormalities in endothelium-dependent relaxation responses of pulmonary arteries in adult sheep due to decreased eNOS activity resulting from altered posttranslational regulation.

  15. Long-term effects of prenatal hypoxia on endothelium-dependent relaxation responses in pulmonary arteries of adult sheep

    PubMed Central

    Liu, Jie; Gao, Yuansheng; Negash, Sewite; Longo, Lawrence D.; Raj, J. Usha

    2009-01-01

    Chronic hypoxia during the course of pregnancy is a common insult to the fetus. However, its long-term effect on the pulmonary vasculature in adulthood has not been described. In this study, the vasorelaxation responses of conduit pulmonary arteries in adult female sheep that were chronically hypoxic as fetuses and raised postnatally at sea level were investigated. Vessel tension studies revealed that endothelium-dependent relaxation responses were attenuated in pulmonary arteries from adult sheep that experienced prenatal hypoxia. Endothelial nitric oxide synthase (eNOS) protein expression was unchanged, but eNOS activity was significantly decreased in pulmonary arteries from prenatally hypoxic sheep. Protein expression of eNOS partners, caveolin-1, calmodulin, and heat shock protein 90 (Hsp90) did not change following prenatal hypoxia. However, the association between eNOS and caveolin-1, its inhibitory binding partner, was significantly increased, whereas association between eNOS and its stimulatory partners calmodulin and Hsp90 was greatly decreased. Furthermore, phosphorylation of Ser1177 in eNOS decreased, whereas phosphorylation of Thr495 increased, in the prenatally hypoxic pulmonary arteries, events that are related to eNOS activity. These data demonstrate that prenatal hypoxia results in persistent abnormalities in endothelium-dependent relaxation responses of pulmonary arteries in adult sheep due to decreased eNOS activity resulting from altered posttranslational regulation. PMID:19136582

  16. Effect of age on kinetics of nitric oxide release in rat aorta and pulmonary artery.

    PubMed Central

    Tschudi, M R; Barton, M; Bersinger, N A; Moreau, P; Cosentino, F; Noll, G; Malinski, T; Lüscher, T F

    1996-01-01

    Aging is an important determinant of vascular disease. Endothelium-derived nitric oxide (NO) is protective as a vasodilator and inhibitor of platelet function. This study was designed to directly measure effects of prolonged aging on endotheliai NO release in isolated blood vessels and to delineate differences between the systemic and pulmonary circulation. Aortas and pulmonary arteries from 5-6-mo-old (young), 18-19-mo-old (middle-aged), and 32-33-mo-old (old) normotensive female rats were used. Blood pressure and plasma estradiol-17beta (E2) remained unchanged. In isolated blood vessels, NO release was induced by the receptor-independent agonist calcium ionophore A23187 (10 micromol/liter) and measured in situ on the endothelial surface of vessels using a porphyrinic microsensor. In vessels suspended in organ chambers isometric tension was recorded. In the aorta, the initial rate of NO release and peak NO concentration were reduced in middle-aged and old rats (P < 0.0006 vs. young rats, n = 6). Furthermore, endothelium-dependent relaxations to calcium ionophore and acetylcholine (both 10(-10) - 10(-5) mol/liter) were also reduced in aortas from old as compared with young rats (n = 6, P < 0.05). The initial rate of NO release and peak NO concentration significantly correlated with maximal relaxation to calcium ionophore A23187 (correlation coefficients r - 0.916, P < 0.0018 and r = 0.961, P < 0.0001, respectively, n = 7). In pulmonary arteries, however, the initial rate of NO release as well as peak NO concentration did not decrease with age (n = 6 for each age group, NS). In both blood vessels, the NO release was unaffected by superoxide dismutase in all age groups (n = 6, NS). Thus, aging specifically reduces initial rate and peak concentrations of endothelial NO release from aorta but not pulmonary artery indicating reduced NO production. As arterial pressure did not change with aging, the chronic exposure of the aorta to higher pressure and/or pulsatility than

  17. Echocardiographic Assessment of Pulmonary Arterial Hypertension for Pediatricians and Neonatologists.

    PubMed

    Skinner, Gregory James

    2017-01-01

    There is a growing awareness of the role that increased pulmonary vascular resistance (PVR) plays in many pathologies; therefore, assessment of pulmonary artery pressure (PAP) is an increasingly requested investigation in the critical care environment. This article will go through the basic concepts regarding PAP and PVR, then will go on to outline the various echocardiographic parameters which are used to assess them. Finally, an outline of how to undertake this assessment will be presented.

  18. Expert consensus for performing right heart catheterisation for suspected pulmonary arterial hypertension in systemic sclerosis: a Delphi consensus study with cluster analysis.

    PubMed

    Avouac, Jérôme; Huscher, Dörte; Furst, Daniel E; Opitz, Christian F; Distler, Oliver; Allanore, Yannick

    2014-01-01

    To establish an expert consensus on which criteria are the most appropriate in clinical practice to refer patients with systemic sclerosis (SSc) for right heart catheterisation (RHC) when pulmonary hypertension (PH) is suspected. A three stage internet based Delphi consensus exercise involving worldwide PH experts was designed. In the first stage, a comprehensive list of domains and items combining evidence based indications and expert opinions were obtained. In the second and third stages, experts were asked to rate each item selected in the list. After each of stages 2 and 3, the number of items and criteria were reduced according to a cluster analysis. A literature search and the opinions of 47 experts participating in Delphi stage 1 provided a list of seven domains containing 142 criteria. After stages 2 and 3, these domains and tools were reduced to three domains containing eight tools: clinical (progressive dyspnoea over the past 3 months, unexplained dyspnoea, worsening of WHO dyspnoea functional class, any finding on physical examination suggestive of elevated right heart pressures and any sign of right heart failure), echocardiography (systolic pulmonary artery pressure >45 mm Hg and right ventricle dilation) and pulmonary function tests (diffusion lung capacity for carbon monoxide <50% without pulmonary fibrosis). Among experts in pulmonary arterial hypertension-SSc, a core set of criteria for clinical practice to refer SSc patients for RHC has been defined by Delphi consensus methods. Although these indications are recommended by this expert group to be used as an interim tool, it will be necessary to formally validate the present tools in further studies.

  19. 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

  20. Contemporary survival of patients with pulmonary arterial hypertension and congenital systemic to pulmonary shunts

    PubMed Central

    Chungsomprasong, Paweena; Bositthipichet, Densiri; Ketsara, Salisa; Titaram, Yuttapon; Chanthong, Prakul; Kanjanauthai, Supaluck

    2018-01-01

    Objective To compare survival of patients with newly diagnosed pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) according to various clinical classifications with classifications of anatomical-pathophysiological systemic to pulmonary shunts in a single-center cohort. Methods All prevalent cases of PAH-CHD with hemodynamic confirmation by cardiac catheterization in 1995–2015 were retrospectively reviewed. Patients who were younger than three months of age, or with single ventricle following surgery were excluded. Baseline characteristics and clinical outcomes were retrieved from the database. The survival analysis was performed at the end of 2016. Prognostic factors were identified using multivariate analysis. Results A total of 366 consecutive patients (24.5 ± 17.6 years of age, 40% male) with PAH-CHD were analyzed. Most had simple shunts (85 pre-tricuspid, 105 post-tricuspid, 102 combined shunts). Patients with pre-tricuspid shunts were significantly older at diagnosis in comparison to post-tricuspid, combined, and complex shunts. Clinical classifications identified patients as having Eisenmenger syndrome (ES, 26.8%), prevalent left to right shunt (66.7%), PAH with small defect (3%), or PAH following defect correction (3.5%). At follow-up (median = 5.9 years; 0.1–20.7 years), no statistically significant differences in survival rate were seen among the anatomical-pathophysiological shunts (p = 0.1). Conversely, the clinical classifications revealed that patients with PAH-small defect had inferior survival compared to patients with ES, PAH post-corrective surgery, or PAH with prevalent left to right shunt (p = 0.01). Significant mortality risks were functional class III, age < 10 years, PAH-small defect, elevated right atrial pressure > 15 mmHg, and baseline PVR > 8 WU•m.2 Conclusion Patients with PAH-CHD had a modest long-term survival. Different anatomical-pathophysiological shunts affect the natural presentation, while

  1. MicroRNA-27b plays a role in pulmonary arterial hypertension by modulating peroxisome proliferator-activated receptor γ dependent Hsp90-eNOS signaling and nitric oxide production

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

    Bi, Rui; Bao, Chunrong; Jiang, Lianyong

    Pulmonary artery endothelial dysfunction is associated with pulmonary arterial hypertension (PAH). Based on recent studies showing that microRNA (miR)-27b is aberrantly expressed in PAH, we hypothesized that miR-27b may contribute to pulmonary endothelial dysfunction and vascular remodeling in PAH. The effect of miR-27b on pulmonary endothelial dysfunction and the underlying mechanism were investigated in human pulmonary artery endothelial cells (HPAECs) in vitro and in a monocrotaline (MCT)-induced model of PAH in vivo. miR-27b expression was upregulated in MCT-induced PAH and inversely correlated with the levels of peroxisome proliferator-activated receptor (PPAR)-γ, and miR-27b inhibition attenuated MCT-induced endothelial dysfunction and remodeling and prevented PAHmore » associated right ventricular hypertrophy and systolic pressure in rats. PPARγ was confirmed as a direct target of miR-27b in HPAECs and shown to mediate the effect of miR-27b on the disruption of endothelial nitric oxide synthase (eNOS) coupling to Hsp90 and the suppression of NO production associated with the PAH phenotype. We showed that miR-27b plays a role endothelial function and NO release and elucidated a potential mechanism by which miR-27b regulates Hsp90-eNOS and NO signaling by modulating PPARγ expression, providing potential therapeutic targets for the treatment of PAH. - Highlights: • miR-27b plays a role in endothelial function and NO release. • miR-27b inhibition ameliorates MCT-induced endothelial dysfunction and PAH. • miR-27b targets PPARγ in HPAECs. • miR-27b regulates PPARγ dependent Hsp90-eNOS and NO signaling.« less

  2. Bronchial Artery Embolization in the Management of Pulmonary Parenchymal Endometriosis with Hemoptysis

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

    Kervancioglu, Selim, E-mail: skervancioglu@yahoo.com; Andic, Cagatay; Bayram, Nazan

    Pulmonary parenchymal endometriosis is extremely rare and usually manifests itself with a recurrent hemoptysis associated with the menstrual cycle. The therapies proposed for women with endometriosis consist of medical treatments and surgery. Bronchial artery embolization has become a well-established and minimally invasive treatment modality for hemoptysis, and to the best of our knowledge, it has not been reported in pulmonary endometriosis. We report a case of pulmonary parenchymal endometriosis treated with embolotheraphy for hemoptysis.

  3. Perinatal/Neonatal case presentation: pulmonary artery sling associated with respiratory distress.

    PubMed

    Healey, David; Ron, Nitin; Hromada, Andrew; Chhabra, Manoj

    2016-01-01

    Pulmonary artery sling is a very rare cause of pediatric respiratory distress. The estimated prevalence of the disease was first determined by Yu et al. in 2008 as 59 per million school-aged children. Associated symptoms are cough, wheezing, and feeding difficulty, all of which are common in routine outpatient pediatric clinical encounters. We report a case of a premature male neonate twin who was admitted to the neonatal intensive care unit with respiratory distress and pneumothorax. His presentation, as well as the etiology of his pulmonary disease, was felt to be consistent with those of numerous other premature infants. Akin to this was his delayed discharge on account of his slow progress with oral feeding. Parents gave a history of tachypnea and feeding difficulty to his doctors. He presented twice to the emergency room in respiratory distress. At 4 months of age, while in hospital for a pulmonary infection, he had an echocardiogram that revealed a pulmonary artery sling. We review the literature on this vascular anomaly, discuss its diagnosis and management, and critique the clinical thinking that determined this child's course from the perspective of availability heuristics.

  4. Tyrosine kinase inhibitors in pulmonary arterial hypertension: a double-edge sword?

    PubMed

    Godinas, Laurent; Guignabert, Christophe; Seferian, Andrei; Perros, Frederic; Bergot, Emmanuel; Sibille, Yves; Humbert, Marc; Montani, David

    2013-10-01

    New treatments for pulmonary arterial hypertension (PAH) are a crucial need. The increased proliferation, migration, and survival of pulmonary vascular cells within the pulmonary artery wall in PAH have allowed successful transposition of pathophysiological elements from oncologic researches. Next steps will require translation of these biological advances in PAH therapeutic arsenal and guidelines. This review synthesizes recent data concerning the role of receptor tyrosine kinases and their inhibitors in PAH, with implications in animal models and humans. Results of clinical trials are now accumulating to establish beneficial role of tyrosine kinase inhibitors (TKIs) in PAH and further findings are expected in the near future. Beside this curative approach, evidences of a possible TKI-induced cardiotoxicity are emerging. These safety issues raise concern about a potential amplified harmful effect in PAH, a pathology characterized by an underlying cardiac dysfunction. In addition, analyses of PAH registries shed light on a selective pulmonary vascular toxicity triggered by TKIs, especially dasatinib. These possible dual effects of the TKIs in PAH need to be taken in account for future pharmacological development of this therapeutic class in PAH. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  5. A Mock Circulatory System Incorporating a Compliant 3D-Printed Anatomical Model to Investigate Pulmonary Hemodynamics.

    PubMed

    Knoops, Paul G M; Biglino, Giovanni; Hughes, Alun D; Parker, Kim H; Xu, Linzhang; Schievano, Silvia; Torii, Ryo

    2017-07-01

    A realistic mock circulatory system (MCS) could be a valuable in vitro testbed to study human circulatory hemodynamics. The objective of this study was to design a MCS replicating the pulmonary arterial circulation, incorporating an anatomically representative arterial model suitable for testing clinically relevant scenarios. A second objective of the study was to ensure the system's compatibility with magnetic resonance imaging (MRI) for additional measurements. A latex pulmonary arterial model with two generations of bifurcations was manufactured starting from a 3D-printed mold reconstructed from patient data. The model was incorporated into a MCS for in vitro hydrodynamic measurements. The setup was tested under physiological pulsatile flow conditions and results were evaluated using wave intensity analysis (WIA) to investigate waves traveling in the arterial system. Increased pulmonary vascular resistance (IPVR) was simulated as an example of one pathological scenario. Flow split between right and left pulmonary artery was found to be realistic (54 and 46%, respectively). No substantial difference in pressure waveform was observed throughout the various generations of bifurcations. Based on WIA, three main waves were identified in the main pulmonary artery (MPA), that is, forward compression wave, backward compression wave, and forward expansion wave. For IPVR, a rise in mean pressure was recorded in the MPA, within the clinical range of pulmonary arterial hypertension. The feasibility of using the MCS in the MRI scanner was demonstrated with the MCS running 2 h consecutively while acquiring preliminary MRI data. This study shows the development and verification of a pulmonary MCS, including an anatomically correct, compliant latex phantom. The setup can be useful to explore a wide range of hemodynamic questions, including the development of patient- and pathology-specific models, considering the ease and low cost of producing rapid prototyping molds, and the

  6. Pleural and pulmonary involvement in systemic lupus erythematosus.

    PubMed

    Torre, Olga; Harari, Sergio

    2011-01-01

    Systemic lupus erythematosus (SLE) is a rare complex autoimmune disease with a multisystem involvement. The clinical manifestations of this disease include an erythematous rash, oral ulcers, polyarthralgia, nonerosive arthritis, polyserositis, hematologic, renal, neurologic, pulmonary and cardiac abnormalties. The involvement of the respiratory system is frequent. Pleuro-pulmonary manifestations are present in almost half of the patients during the disease course and may be the presenting symptoms in 4-5% of patients with SLE. Complications directly associated to the disease include pleuritis with or without pleural effusion, alveolitis, interstitial lung disease, lupus pneumonitis, pulmonary hemorrhage, pulmonary arterial hypertension, and pulmonary thromboembolic disease. Complications due to secondary causes include pleuro-pulmonary manifestations of cardiac and renal failure, atelectasis due to diaphragmatic dysfunction, opportunistic pneumonia, and drug toxicity. The prevalence, clinical presentation, prognosis and response to treatment vary, depending on the pattern of involvement. As with other connective tissue diseases, early and specific therapeutic intervention may be indicated for many of these pleuro-pulmonary manifestations. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  7. 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.

  8. [Evaluation of exercise capacity in pulmonary arterial hypertension].

    PubMed

    Demir, Rengin; Küçükoğlu, Mehmet Serdar

    2010-12-01

    Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by increased pulmonary vascular resistance that leads to right ventricular failure. The most common clinical features of PAH are dyspnea and exercise intolerance. Measurement of exercise capacity is of considerable importance for the assessment of disease severity as well as routine monitoring of disease. Maximal, symptom-limited, cardiopulmonary exercise test (CPET) is the gold standard for the evaluation of exercise capacity, whereby functions of several systems involved in exercise can be assessed, including cardiovascular, respiratory, and metabolic systems. However, in order to derive the most useful diagnostic information on physiologic limitations to exercise, CPET requires maximal effort of the patient, which can be difficult and risky for some severely ill patients. Moreover, it requires specific exercise equipment and measurement systems, and experienced and trained personnel. Thus, routine clinical use of CPET to assess exercise capacity in patients with PAH may not always be feasible. A practical and simple alternative to CPET to determine exercise capacity is the 6-minute walk test (6MWT). It is simple to perform, safe, and reproducible. In contrast to CPET, the 6MWT reflects a submaximal level of exertion that is more consistent with the effort required for daily physical activities. This review focuses on the role of CPET and 6MWT in patients with PAH.

  9. Single left coronary ostium and an anomalous prepulmonic right coronary artery in 2 dogs with congenital pulmonary valve stenosis.

    PubMed

    Visser, Lance C; Scansen, Brian A; Schober, Karsten E

    2013-06-01

    A coronary artery anomaly characterized by the presence of a single left coronary ostium with absence of the right coronary ostium and an anomalous prepulmonic right coronary artery course was observed in two dogs with concurrent congenital pulmonary valve stenosis. This unique coronary artery anatomy is similar to the previously described single right coronary ostium with anomalous prepulmonic left coronary artery, the so-called type R2A anomaly, in that an anomalous coronary artery encircles the pulmonary valve annulus. Both dogs of this report, a boxer and an English bulldog, were of breeds known to be at risk for the type R2A anomaly. As such, veterinarians should be aware that the echocardiographic presence of a left coronary ostium in a dog with pulmonary valve stenosis does not exclude the possibility of a prepulmonic coronary artery anomaly that may enhance the risk of complications during balloon pulmonary valvuloplasty. A descriptive naming convention for coronary artery anomalies in dogs is also presented, which may be preferable to the older coding classification scheme. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Repair of a Large Main Pulmonary Artery Aneurysm in a 71-Year-Old Jehovah's Witness Patient

    PubMed Central

    Henn, Lucas W.; Esmailian, Fardad

    2013-01-01

    Pulmonary artery aneurysm is a rarely reported and poorly studied entity; most mentions in the literature are in case series and case reports. Cardiac surgery in Jehovah's Witness patients is occurring more frequently because of improved techniques of blood conservation. We report the repair of a large pulmonary artery aneurysm in a 71-year-old woman who was a Jehovah's Witness. Using total cardiopulmonary bypass, we replaced the main pulmonary artery and both branches with Gelweave tube-grafts, because the fragility of a homograft presented possible bleeding problems. The patient recovered rapidly, and her symptoms were greatly improved. We think that a patient's status as a Jehovah's Witness need not preclude potentially life-saving cardiac operations. PMID:23914038

  11. Repair of a large main pulmonary artery aneurysm in a 71-year-old Jehovah's Witness patient.

    PubMed

    Henn, Lucas W; Esmailian, Fardad

    2013-01-01

    Pulmonary artery aneurysm is a rarely reported and poorly studied entity; most mentions in the literature are in case series and case reports. Cardiac surgery in Jehovah's Witness patients is occurring more frequently because of improved techniques of blood conservation. We report the repair of a large pulmonary artery aneurysm in a 71-year-old woman who was a Jehovah's Witness. Using total cardiopulmonary bypass, we replaced the main pulmonary artery and both branches with Gelweave tube-grafts, because the fragility of a homograft presented possible bleeding problems. The patient recovered rapidly, and her symptoms were greatly improved. We think that a patient's status as a Jehovah's Witness need not preclude potentially life-saving cardiac operations.

  12. Dysregulated expression of microRNAs and mRNAs in pulmonary artery remodeling in ascites syndrome in broiler chickens

    PubMed Central

    Zhuang, Yu; Xiao, Qingyang; Cao, Huabin; Zhang, Caiying; Wang, Tiancheng; Lin, Huayuan; Guo, Xiaoquan; Hu, Guoliang

    2017-01-01

    Ascites syndrome (AS), also known as pulmonary artery hypertension, remains a challenging disease that severely affects both humans and broiler chickens. Pulmonary artery remodeling presents a key step in the development of AS. In this study, we obtained pulmonary artery tissues from broilers with and without AS to perform miRNA sequencing analysis, miRNA-mRNA association analysis and pathological examinations. 29 significantly differentially expressed miRNAs were found both in known and novel miRNAs with 18 up-regulated and 11 down-regulated miRNAs. Their predicted potential targets were involved in a wide range of functional clusters as indicated via GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses. The upregulation of miR-155, miR-23b-3p, miR-146b-5p and miR-146b-3p were found closely associated with the pathogenesis of pulmonary artery remodeling in AS progression. The association analysis for the miRNAs-mRNAs showed that these 29 significantly differentially expressed miRNAs regulate 162 differentially expressed target genes. Among them, 20 miRNAs correlated with 18 predicted target genes that appear to be involved in pulmonary artery remodeling, mainly in three broad physiological processes: the hypoxia sensing response (HIF1a, NHE1, STAT5 and STAT3), endothelial permeability dysfunction (CD44, TRAF2, CDK2AP1, LZTFL1, JAZF1, PEBP1, LRP1B, RPS14 and THBS2) and inflammation (MEOX2, STAT5, STAT3, IRF8, MAP3K8, IL-1BETA and TNFRSF1B). Pathological pulmonary artery remodeling in the AS broilers was consistently observed in the present study. Taken together, the current analysis further illuminates the molecular mechanism of pulmonary artery remodeling underlying AS progression. PMID:27791988

  13. Obstruction of the Aorta and Left Pulmonary Artery After Gianturco Coil Occlusion of Patent Ductus Arteriosus

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

    Kuo, H.-Cg; Ko, Sheung-Fat; Wu, Yu-Tsun

    We report an unusual case of simultaneous obstruction of the left pulmonary artery and descending thoracic aorta after Gianturco coil occlusion in a 15-month-old boy. The diagnosis was made by echocardiography and cardiac angiography. At surgery, thrombi coating on the protruded parts of the Gianturco coil in the pulmonary artery and aorta were found.

  14. PCPA protects against monocrotaline-induced pulmonary arterial remodeling in rats: potential roles of connective tissue growth factor.

    PubMed

    Bai, Yang; Li, Zhong-Xia; Zhao, Yue-Tong; Liu, Mo; Wang, Yun; Lian, Guo-Chao; Zhao, Qi; Wang, Huai-Liang

    2017-12-19

    The purpose of this study was to investigate the mechanism of monocrotaline (MCT)-induced pulmonary artery hypertension (PAH) and determine whether 4-chloro-DL-phenylalanine (PCPA) could inhibit pulmonary arterial remodeling associated with connective tissue growth factor (CTGF) expression and downstream signal pathway. MCT was administered to forty Sprague Dawley rats to establish the PAH model. PCPA was administered at doses of 50 and 100 mg/kg once daily for 3 weeks via intraperitoneal injection. On day 22, the pulmonary arterial pressure (PAP), right ventricle hypertrophy index (RVI) and pulmonary artery morphology were assessed and the serotonin receptor-1B (SR-1B), CTGF, p-ERK/ERK were measured by western blot or immunohistochemistry. The concentration of serotonin in plasma was checked by ELISA. Apoptosis and apoptosis-related indexes were detected by TUNEL and western blot. In the MCT-induced PAH models, the PAP, RVI, pulmonary vascular remodeling, SR-1B index, CTGF index, anti-apoptotic factors bcl-xl and bcl-2, serotonin concentration in plasma were all increased and the pro-apoptotic factor caspase-3 was reduced. PCPA significantly ameliorated pulmonary arterial remodeling induced by MCT, and this action was associated with accelerated apoptosis and down-regulation of CTGF, SR-1B and p-ERK/ERK. The present study suggests that PCPA protects against the pathogenesis of PAH by suppressing remodeling and inducing apoptosis, which are likely associated with CTGF and downstream ERK signaling pathway in rats.

  15. Assessment of branch pulmonary artery stenosis in children after repair of tetralogy of Fallot using lung perfusion scintigraphy comparison with echocardiography.

    PubMed

    Chien, Kuang-Jen; Huang, Hurng-Wern; Huang, Ta-Cheng; Lee, Cheng-Liang; Weng, Ken-Pen; Lin, Chu-Chuan; Shieh, Po-Chuen; Wu, Ming-Ting; Hsieh, Kai-Sheng

    2016-01-01

    The aim of this study was to compare the usefulness of lung perfusion scintigraphy and echocardiogram in the evaluation of the branch pulmonary arteries stenosis in children with tetralogy of Fallot (TOF). From February 2006 to November 2008, 74 children (mean age 7.8 years, range 1–18 years) who underwent repair of TOF at ages from 10 months to 13 years were suspected to have unilateral or bilateral branch pulmonary artery stenosis. In all patients, cardiac angiography was performed to confirm the diagnosis of branch pulmonary artery stenosis. Lung perfusion scintigraphy and two-dimensional transthoracic echocardiography were performed in all patients to compare their abilities to diagnose branch pulmonary artery stenosis. Of the 74 patients, 51 cases were found to have branch pulmonary artery stenosis by cardiac angiography. There was agreement between the scintigraphic and angiographic findings in 44 (86%) patients and there were discrepancies in 11 (15%) patients. The positive predictive value of our lung perfusion scintigraphy in detecting the branch pulmonary artery stenosis was 92 %. The positive and negative likelihood ratios of lung perfusion scintigraphy were 4.96 and 0.17, respectively. There was conformity between the echocardiographic and angiographic findings in 40 (78%) patients with discrepancies in 16 (21%) patients. The positive predictive value of our echocardiography in detecting the branch pulmonary artery stenosis was 89%. The positive and negative likelihood ratios of echocardiography were 3.61 and 0.28, respectively. Lung perfusion scintigraphy is a valuable, non-invasive screening tool in the assessment of branch pulmonary artery stenosis in children after TOF.

  16. [Part II: basic hemodynamic monitoring and the use of pulmonary artery catheter].

    PubMed

    Dias, Fernando Suparregui; Rezende, Ederlon; Mendes, Ciro Leite; Réa-Neto, Alvaro; David, Cid Marcos; Schettino, Guilherme; Lobo, Suzana Margareth Ajeje; Barros, Alberto; Silva, Eliézer; Friedman, Gilberto; Amaral, José Luiz Gomes do; Park, Marcelo; Monachini, Maristela; Oliveira, Mirella Cristine de; Assunção, Murillo Santucci César; Akamine, Nelson; Mello, Patrícia Veiga C; Pereira, Renata Andréa Pietro; Costa Filho, Rubens; Araújo, Sebastião; Félix Pinto, Sérgio; Ferreira, Sérgio; Mitushima, Simone Mattoso; Agareno, Sydney; Brilhante, Yuzeth Nóbrega de Assis

    2006-03-01

    Monitoring of vital functions is one of the most important tools in the management of critically ill patients. Nowadays is possible to detect and analyze a great deal of physiologic data using a lot of invasive and non-invasive methods. The intensivist must be able to select and carry out the most appropriate monitoring technique according to the patient requirements and taking into account the benefit/risk ratio. Despite the fast development of non invasive monitoring techniques, invasive hemodynamic monitoring using Pulmonary Artery Catheter still is one of the basic procedures in Critical Care. The aim was to define recommendations about clinical utility of basic hemodynamic monitoring methods and the Use of Pulmonary Artery Catheter. Modified Delphi methodology was used to create and quantify the consensus between the participants. AMIB indicated a coordinator who invited more six experts in the area of monitoring and hemodynamic support to constitute the Consensus Advisory Board. Twenty-five physicians and nurses selected from different regions of the country completed the expert panel, which reviewed the pertinent bibliography listed at the MEDLINE in the period from 1996 to 2004. Recommendations were made based on 55 questions about the use of central venous pressure, invasive arterial pressure, pulmonary artery catheter and its indications in different settings. Evaluation of central venous pressure and invasive arterial pressure, besides variables obtained by the PAC allow the understanding of cardiovascular physiology that is of great value to the care of critically ill patients. However, the correct use of these tools is fundamental to achieve the benefits due to its use.

  17. Digital subtraction angiography of the pulmonary arteries for the diagnosis of pulmonary embolism

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

    Ludwig, J.W.; Verhoeven, L.A.J.; Kersbergen, J.J.

    1983-06-01

    A comparative study of radionuclide scanning (perfusion studies in all 18 patients and ventilation studies in 9) and digital subtraction angiography (DSA) was performed in 18 patients with suspected pulmonary thromboembolism. In 17 patients good visualization of the arteries was obtained with DSA; 10 of these patients had no pre-existing lung disease, and 7 had chronic obstructive pulmonary disease (COPD). The information provided by DSA in this small group was equal to or better than that of scintigraphy, especially in patients with COPD, and the reliability of DSA was superior to that of the radionuclide scintigraphy. Methods for preventing motionmore » artifacts with DSA are also described.« less

  18. Preventive Role of Hilar Parasympathetic Ganglia on Pulmonary Artery Vasospasm in Subarachnoid Hemorrhage: An Experimental Study.

    PubMed

    Araz, Omer; Aydin, Mehmet Dumlu; Gundogdu, Betul; Altas, Ender; Cakir, Murteza; Calikoglu, Cagatay; Atalay, Canan; Gundogdu, Cemal

    2015-01-01

    Pulmonary arteries are mainly innervated by sympathetic vasoconstrictor and parasympathetic vasodilatory fibers. We examined whether there is a relationship between the neuron densities of hilar parasympathetic ganglia and pulmonary vasospasm in subarachnoid hemorrhage (SAH). Twenty-four rabbits were divided into two groups: control (n=8) and SAH (n=16). The animals were observed for 20 days following experimental SAH. The number of hilar parasympathetic ganglia and their neuron densities were determined. Proportion of pulmonary artery ring surface to lumen surface values was accepted as vasospasm index (VSI). Neuron densities of the hilar ganglia and VSI values were compared statistically. Animals in the SAH group experienced either mild (n=6) or severe (n=10) pulmonary artery vasospasm. In the control group, the mean VSI of pulmonary arteries was 0.777±0.048 and the hilar ganglion neuron density was estimated as 12.100±2.010/mm < sup > 3 < /sup > . In SAH animals with mild vasospasm, VSI=1.148±0.090 and neuron density was estimated as 10.110±1.430/mm < sup > 3 < /sup > ; in animals with severe vasospasm, VSI=1.500±0.120 and neuron density was estimated as 7.340±990/mm < sup > 3 < /sup > . There was an inverse correlation between quantity and neuron density of hilar ganglia and vasospasm index value. The low numbers and low density of hilar parasympathetic ganglia may be responsible for the more severe artery vasospasm in SAH.

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

    NASA Astrophysics Data System (ADS)

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

    2010-03-01

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

  20. The effects of levosimendan exposure on oxidant/antioxidant status and trace element levels in the pulmonary artery of rats.

    PubMed

    Ay, Yasin; Aydın, Cemalettin; Basel, Halil; Bektaş, Hava; Bülüt, Gülay; Inan, Bekir; Ay, Nuray Kahraman; Demir, Ismail

    2013-06-01

    We investigated both the effect of levosimendan and the role of oxidant/antioxidant status and trace element levels in the pulmonary artery of rats. Fourteen male Wistar albino rats were randomly divided into two groups of seven animals each. Group 1 was not exposed to levosimendan and served as a control. Levosimendan (12 μg/kg) diluted in 10 ml 0.9 % NaCl was administered intraperitoneally to group 2. Animals of both groups were killed after 3 days, and their pulmonary arteries were harvested to determine changes in tissue oxidant/antioxidant status and trace element levels. The animals in both groups were killed 72 h after the levosimendan exposure treatment, and pulmonary arteries were harvested to determine levels of the lipid peroxidation product MDA and the antioxidant GSH as well as the decreased activity of antioxidant enzymes such as SOD, GSH-Px and CAT. It was found that MDA levels increased in pulmonary artery tissues of rats after levosimendan administration. The GSH level decreased in the pulmonary artery of rats after levosimendan treatment. Co, Mn, Fe, Cd and Pb levels were significantly higher (P < 0.001) and Mg, Zn and Cu levels significantly lower (P < 0.001) in the levosimendan group compared to the control group. These results suggest that levosimendan treatment caused an increase in free radical production and a decrease in antioxidant enzyme activity in the pulmonary artery of levosimendan-treated rats. It also caused a decrease or increase in the levels of many minerals in the pulmonary artery, which is an undesirable condition for normal pharmacological function.

  1. Platelet activation independent of pulmonary inflammation contributes to diesel exhaust particulate-induced promotion of arterial thrombosis.

    PubMed

    Tabor, Caroline M; Shaw, Catherine A; Robertson, Sarah; Miller, Mark R; Duffin, Rodger; Donaldson, Ken; Newby, David E; Hadoke, Patrick W F

    2016-02-09

    Accelerated thrombus formation induced by exposure to combustion-derived air pollution has been linked to alterations in endogenous fibrinolysis and platelet activation in response to pulmonary and systemic inflammation. We hypothesised that mechanisms independent of inflammation contribute to accelerated thrombus formation following exposure to diesel exhaust particles (DEP). Thrombosis in rats was assessed 2, 6 and 24 h after administration of DEP, carbon black (CB; control carbon nanoparticle), DQ12 quartz microparticles (to induce pulmonary inflammation) or saline (vehicle) by either intra-tracheal instillation (0.5 mg, except Quartz; 0.125 mg) or intravenous injection (0.5 mg/kg). Thrombogenicity was assessed by carotid artery occlusion, fibrinolytic variables and platelet-monocyte aggregates. Measures of inflammation were determined in plasma and bronchoalveolar lavage fluid. Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI)-1 were measured following direct in vitro exposure of human umbilical vein endothelial cells (HUVECs) to DEP (10-150 μg/mL). Instillation of DEP reduced the time to thrombotic occlusion in vivo, coinciding with the peak of DEP-induced pulmonary inflammation (6 h). CB and DQ12 produced greater inflammation than DEP but did not alter time to thrombotic occlusion. Intravenous DEP produced an earlier (2 h) acceleration of thrombosis (as did CB) without pulmonary or systemic inflammation. DEP inhibited t-PA and PAI-1 release from HUVECs, and reduced the t-PA/PAI-1 ratio in vivo; similar effects in vivo were seen with CB and DQ12. DEP, but not CB or DQ12, increased platelet-monocyte aggregates. DEP accelerates arterial thrombus formation through increased platelet activation. This effect is dissociated from pulmonary and systemic inflammation and from impaired fibrinolytic function.

  2. A 50-year-old woman with haemoptysis, cough and tachypnea: cholesterol pneumonia accompanying with pulmonary artery hypertension.

    PubMed

    Li, Mengxi; Zhang, Nuofu; Zhou, Ying; Li, Jinhui; Gu, Yingying; Wang, Jian; Liu, Chunli

    2017-03-01

    Lipoid pneumonia is an uncommon disease caused by the presence of lipid in the alveoli. Here we described a case of a 50-year-old woman with haemoptysis, cough and tachypnea, who was diagnosed with cholesterol pneumonia accompanying with pulmonary artery hypertension. The extremely high pulmonary artery pressure achieved, in this case, is alarming and should alert the physicians that the cholesterol pneumonia may be one of the underlying causes of pulmonary artery hypertension. After a treatment of methylprednisolone, her clinical symptoms were significantly improved, which suggested that steroid might be a promising therapeutic for patients with cholesterol pneumonia. © 2015 John Wiley & Sons Ltd.

  3. Severity of Systemic Sclerosis-Associated Pulmonary Arterial Hypertension in African Americans

    PubMed Central

    Blanco, Isabel; Mathai, Stephen; Shafiq, Majid; Boyce, Danielle; M. Kolb, Todd; Chami, Hala; K. Hummers, Laura; Housten, Traci; Chaisson, Neal; L. Zaiman, Ari; M. Wigley, Fredrick; J. Tedford, Ryan; A. Kass, David; Damico, Rachel; E. Girgis, Reda; M. Hassoun, Paul

    2014-01-01

    Abstract African Americans (AA) with systemic sclerosis (SSc) have a worse prognosis compared to Americans of European descent (EA). We conducted the current study to test the hypothesis that AA patients with SSc have more severe disease and poorer outcomes compared to EA patients when afflicted with pulmonary arterial hypertension (PAH). We studied 160 consecutive SSc patients with PAH diagnosed by right heart catheterization, comparing demographics, hemodynamics, and outcomes between AA and EA patients. The cohort included 29 AA and 131 EA patients with similar baseline characteristics except for increased prevalence of diffuse SSc in AA. AA patients had worse functional class (FC) (80% FC III-IV vs 53%; p = 0.02), higher brain natriuretic peptide (NT-pro-BNP) (5729 ± 9730 pg/mL vs 1892 ± 2417 pg/mL; p = 0.02), more depressed right ventricular function, a trend toward lower 6-minute walk distance (263 ± 111  m vs 333 ± 110  m; p = 0.07), and worse hemodynamics (cardiac index 1.95 ± 0.58 L/min/m2 vs 2.62 ± 0.80 L/min/m2; pulmonary vascular resistance 10.3 ± 6.2 WU vs 7.6 ± 5.0 WU; p  < 0.05) compared with EA patients. Kaplan-Meier survival estimates for AA and EA patients, respectively, were 62% vs 73% at 2 years and 26% vs 44% at 5 years (p  > 0.05). In conclusion, AA patients with SSc-PAH are more likely to have diffuse SSc and to present with significantly more severe PAH compared with EA patients. AA patients also appear to have poorer survival, though larger studies are needed to investigate this association definitively. PMID:25181310

  4. Prognostic value of cardiovascular magnetic resonance imaging measurements corrected for age and sex in idiopathic pulmonary arterial hypertension.

    PubMed

    Swift, Andrew J; Rajaram, Smitha; Campbell, Michael J; Hurdman, Judith; Thomas, Steve; Capener, Dave; Elliot, Charlie; Condliffe, Robin; Wild, Jim M; Kiely, David G

    2014-01-01

    There are limited data on the prognostic value of cardiovascular magnetic resonance measurements in idiopathic pulmonary arterial hypertension, with no studies investigating the impact of correction of cardiovascular magnetic resonance indices for age and sex on prognostic value. Consecutive patients with idiopathic pulmonary arterial hypertension underwent cardiovascular magnetic resonance imaging at 1.5T. Steady-state free precession cardiac volumes and mass measurements were corrected for age, sex, and body surface area according to reference data and prognostic significance assessed. A total of 80 patients with idiopathic pulmonary arterial hypertension were identified, and 23 patients died during the mean follow-up of 32±14 months. Corrected for age, sex, and body surface area, right ventricular end-systolic volume (P=0.004) strongly predicted mortality, independent of World Health Organization functional class, mean right atrial pressure, cardiac index, and mixed venous oxygen saturations. Consideration should be given to correcting cardiovascular magnetic resonance measures for age, sex, and body surface area, particularly given the changing demographics of patients with idiopathic pulmonary arterial hypertension. Corrected right ventricular end-systolic volume is a strong prognostic marker in idiopathic pulmonary arterial hypertension, independent of invasively derived measurements, mean right atrial pressure cardiac index, and mixed venous oxygen saturations.

  5. The internal mammary artery as a shunt in a noncyanotic infant with hemitruncus: surgical and anesthetic management.

    PubMed

    Mahan, Vicki L; Stevens, Randy M; Mesia, Cesar I; Schwartz, Roy E; Moulick, Achintya N

    2016-08-01

    The internal mammary artery (IMA) has been used as a systemic-to-pulmonary artery shunt in selected patients with congenital heart disease. Growth and development of hypoplastic pulmonary arteries have been described. We discuss the surgical and anesthetic management of an infant with an atretic-thrombosed right pulmonary artery originating from the ascending aorta in whom the IMA was used to create a systemic-to-pulmonary artery shunt after failure of a previous shunt and later successful pulmonary artery reconstruction. The IMA should be considered as an alternative conduit in patients requiring a systemic-to-pulmonary artery shunt for growth of pulmonary arteries. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Anomalous left coronary artery from the pulmonary artery with a large patent ductus arteriosus: aversion of a catastrophe.

    PubMed

    Aggarwal, Sanjeev; Delius, Ralph E; Pettersen, Michael D

    2013-01-01

    We present an infant who had an anomalous left coronary artery arising from the pulmonary artery (ALCAPA) and a large patent ductus arteriosus (PDA), who was diagnosed before a potentially catastrophic closure of PDA. In the presence of normal left ventricular function and the absence of coronary artery collaterals, it is difficult to diagnose ALCAPA. A disproportionate degree of left ventricular dilation and severity of mitral valve regurgitation relative to the degree of PDA shunt, and echogenic papillary muscles on an echocardiogram should raise a suspicion of coronary artery anomalies. The infant underwent surgical ligation of PDA with translocation of coronary arteries and had an uneventful recovery. © 2012 Wiley Periodicals, Inc.

  7. A semi-automatic framework of measuring pulmonary arterial metrics at anatomic airway locations using CT imaging

    NASA Astrophysics Data System (ADS)

    Jin, Dakai; Guo, Junfeng; Dougherty, Timothy M.; Iyer, Krishna S.; Hoffman, Eric A.; Saha, Punam K.

    2016-03-01

    Pulmonary vascular dysfunction has been implicated in smoking-related susceptibility to emphysema. With the growing interest in characterizing arterial morphology for early evaluation of the vascular role in pulmonary diseases, there is an increasing need for the standardization of a framework for arterial morphological assessment at airway segmental levels. In this paper, we present an effective and robust semi-automatic framework to segment pulmonary arteries at different anatomic airway branches and measure their cross-sectional area (CSA). The method starts with user-specified endpoints of a target arterial segment through a custom-built graphical user interface. It then automatically detect the centerline joining the endpoints, determines the local structure orientation and computes the CSA along the centerline after filtering out the adjacent pulmonary structures, such as veins or airway walls. Several new techniques are presented, including collision-impact based cost function for centerline detection, radial sample-line based CSA computation, and outlier analysis of radial distance to subtract adjacent neighboring structures in the CSA measurement. The method was applied to repeat-scan pulmonary multirow detector CT (MDCT) images from ten healthy subjects (age: 21-48 Yrs, mean: 28.5 Yrs; 7 female) at functional residual capacity (FRC). The reproducibility of computed arterial CSA from four airway segmental regions in middle and lower lobes was analyzed. The overall repeat-scan intra-class correlation (ICC) of the computed CSA from all four airway regions in ten subjects was 96% with maximum ICC found at LB10 and RB4 regions.

  8. Hyperthyroidism enhances 5-HT-induced contraction of the rat pulmonary artery: role of calcium-activated chloride channel activation.

    PubMed

    Oriowo, Mabayoje A; Oommen, Elsie; Khan, Islam

    2011-11-01

    Experimentally-induced hyperthyroidism in rodents is associated with signs and symptoms of pulmonary hypertension. The main objective of the present study was to investigate the effect of thyroxine-induced pulmonary hypertension on the contractile response of the pulmonary artery to 5-HT and the possible underlying signaling pathway. 5-HT concentration-dependently contracted artery segments from control and thyroxine-treated rats with pD(2) values of 5.04 ± 0.19 and 5.34 ± 0.14, respectively. The maximum response was significantly greater in artery segments from thyroxine-treated rats. Neither BW 723C86 (5-HT(2B)-receptor agonist) nor CP 93129 (5-HT(1B)-receptor agonist) contracted ring segments of the pulmonary artery from control and thyroxine-treated rats at concentrations up to 10(-4)M. There was no significant difference in the level of expression of 5-HT(2A)-receptor protein between the two groups. Ketanserin (3 × 10(-8)M) produced a rightward shift of the concentration-response curve to 5-HT in both groups with equal potency (-logK(B) values were 8.1 ± 0.2 and 7.9 ± 0.1 in control and thyroxine-treated rats, respectively). Nifedipine (10(-6)M) inhibited 5-HT-induced contractions in artery segments from control and thyroxine-treated rats and was more effective against 5-HT-induced contraction in artery segments for thyroxine-treated rats. The calcium-activated chloride channel blocker, niflumic acid (10(-4)M) also inhibited 5-HT-induced contractions in artery segments from control and thyroxine-treated rats and was more effective against 5-HT-induced contraction in artery segments for thyroxine-treated rats. It was concluded that hyperthyroidism enhanced 5-HT-induced contractions of the rat pulmonary artery by a mechanism involving increased activity of calcium-activated chloride channels. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Acute pulmonary edema following inflation of arterial tourniquet.

    PubMed

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

    2014-10-01

    Arterial tourniquets are used as one of the methods for reducing blood loss and for allowing blood free surgical field. A 20-year-old, 45 kg healthy female with a sphere shaped pendunculated hemangioma in the popliteal fossa of her left lower limb was applied with arterial tourniquet after exsanguination. The procedure was performed under general anesthesia. Soon after exsanguination and tourniquet inflation, the patient developed pulmonary edema which subsided after deflating the tourniquet. The clinical evolution, treatment and pathophysiology of this complication are described. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  10. Endosonography of a Pulmonary Artery Obstruction in Echinococcosis.

    PubMed

    Schuuring, Mark J; Bonta, Peter I; van Vugt, Michele; Smithuis, Frank; van Delden, Otto M; Annema, Jouke T; Stijnis, Kees

    2016-01-01

    A 44-year-old woman with a history of pulmonary embolism and abdominal echinococcosis complained of sudden thoracic pain and shortness of breath. A D-dimer of 77.5 mg/l (reference ≤0.5 mg/l) was found. Chest CT scan revealed obstruction of the right lower and middle lobe pulmonary artery (PA). Anticoagulation therapy was initiated for the presumed diagnosis of recurrent pulmonary embolism. However, due to persistent symptoms of dyspnea, follow-up CT angiography of the chest was performed 3 months later. A persistent PA obstruction was found and the presumed diagnosis of embolism was questioned. Subsequently, endobronchial ultrasound (EBUS) imaging was performed to support an alternative diagnosis. EBUS imaging showed an inhomogeneous, sharply demarcated, intravascular lesion with round hypoechoic areas compatible with cysts. The diagnosis of embolism was rejected and treatment with albendazole was initiated for pulmonary echinococcosis. Echinococcosis is a parasitic disease and cystic spread in the PA is exceptional. The patient has remained stable for more than 4 years. In case of disease progression, including progressive PA obstruction or life-threatening hemoptysis, surgical resection will be considered. © 2016 S. Karger AG, Basel.

  11. Pulmonary Arterial Hypertension With Abnormal V/Q Single-Photon Emission Computed Tomography.

    PubMed

    Chan, Kenneth; Ioannidis, Stefanos; Coghlan, John G; Hall, Margaret; Schreiber, Benjamin E

    2017-10-16

    This study aimed to evaluate the incidence and clinical outcomes of abnormal ventilation/perfusion (V/Q) single-photon emission computed tomography (SPECT) without thromboembolism, especially in patients with group I pulmonary arterial hypertension (PAH). American Heart Association/American College of Cardiology and European Society of Cardiology guidelines recommend V/Q scan for screening for chronic thromboembolic pulmonary hypertension. The significance of patients with abnormal V/Q SPECT findings but no thromboembolism demonstrated in further investigations remained unclear. A distinct pattern of global patchy changes not typical of thromboembolism is recognized, but guidelines for reporting these in the context of PAH are lacking. A total of 136 patients who underwent V/Q SPECT and right-sided heart catheterization showing mean pulmonary arterial pressure ≥25 mm Hg were included. V/Q SPECT findings were reported using European Association of Nuclear Medicine criteria for pulmonary embolism followed by computed tomography pulmonary angiography screening for positive thromboembolism and further invasive pulmonary angiography for distal thromboembolism. The abnormal V/Q SPECT images were further analyzed according to perfusion pattern into focal or global perfusion defects. V/Q SPECT showed thromboembolic disease in 44 patients, but 19 of these patients had no thromboembolism demonstrated by pulmonary angiography. Among these patients, 15 of 19 (78.9%) had group I PAH, and the majority had diffuse, patchy perfusion defects. After redefining V/Q SPECT images according to the perfusion pattern, those patients with global perfusion defects had higher mean pulmonary arterial pressure compared with patients with focal perfusion defects and normal scans (mean difference +13.9 and +6.2 mm Hg, respectively; p = 0.0002), as well as higher pulmonary vascular resistance (mean difference +316.6 and +226.3 absolute resistance units, respectively; p = 0

  12. STARS knockout attenuates hypoxia-induced pulmonary arterial hypertension by suppressing pulmonary arterial smooth muscle cell proliferation.

    PubMed

    Shi, Zhaoling; Wu, Huajie; Luo, Jianfeng; Sun, Xin

    2017-03-01

    STARS (STriated muscle Activator of Rho Signaling) is a sarcomeric protein, which expressed early in cardiac development and involved in pathological remodeling. Abundant evidence indicated that STARS could regulate cell proliferation, but it's exact function remains unclear. In this study, we aimed to investigate the role of STARS in the proliferation of pulmonary arterial smooth muscle cells (PASMC) and the potential effect on the progression of pulmonary arterial hypertension (PAH). In this study, we established a PAH mouse model through chronic hypoxia exposure as reflected by the increased RVSP and RVHI. Western blot and RT-qPCR detected the increased STARS protein and mRNA levels in PAH mice. Next, we cultured the primary PASMC from PAH mice. After STARS overexpression in PASMC, STARS, SRF and Egr-1 were up-regulated significantly. The MTT assay revealed an increase in cell proliferation. Flow cytometry showed a marked inhibition of cell apoptosis. However, STARS silence in PASMC exerted opposite effects with STARS overexpression. SRF siRNA transfection blocked the effects of STARS overexpression in PASMC. In order to further confirm the role of STARS in PAH mice in vivo, we exposed STARS knockout mice to hypoxia and found lower RVSP and RVHI in knockout mice as compared with controls. Our results not only suggest that STARS plays a crucial role in the development of PAH by increasing the proliferation of PASMC through activation of the SRF/Egr-1 pathway, but also provides a new mechanism for hypoxia-induced PAH. In addition, STARS may represent a potential treatment target. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. Effect of chronic perinatal hypoxia on the role of rho-kinase in pulmonary artery contraction in newborn lambs

    PubMed Central

    Terry, Michael H.; Merritt, Travis A.; Papamatheakis, Demosthenes G.; Blood, Quintin; Ross, Jonathon M.; Power, Gordon G.; Longo, Lawrence D.; Wilson, Sean M.

    2013-01-01

    Exposure to chronic hypoxia during gestation predisposes infants to neonatal pulmonary hypertension, but the underlying mechanisms remain unclear. Here, we test the hypothesis that moderate continuous hypoxia during gestation causes changes in the rho-kinase pathway that persist in the newborn period, altering vessel tone and responsiveness. Lambs kept at 3,801 m above sea level during gestation and the first 2 wk of life were compared with those with gestation at low altitude. In vitro studies of isolated pulmonary arterial rings found a more forceful contraction in response to KCl and 5-HT in high-altitude compared with low-altitude lambs. There was no difference between the effects of blockers of various pathways of extracellular Ca2+ entry in low- and high-altitude arteries. In contrast, inhibition of rho-kinase resulted in significantly greater attenuation of 5-HT constriction in high-altitude compared with low-altitude arteries. High-altitude lambs had higher baseline pulmonary artery pressures and greater elevations in pulmonary artery pressure during 15 min of acute hypoxia compared with low-altitude lambs. Despite evidence for an increased role for rho-kinase in high-altitude arteries, in vivo studies found no significant difference between the effects of rho-kinase inhibition on hypoxic pulmonary vasoconstriction in intact high-altitude and low-altitude lambs. We conclude that chronic hypoxia in utero results in increased vasopressor response to both acute hypoxia and serotonin, but that rho-kinase is involved only in the increased response to serotonin. PMID:23152110

  14. Isolated Anomalous Origin of Left Pulmonary Artery From the Descending Aorta: An Embryologic Ambiguity.

    PubMed

    Gnanappa, Ganesh Kumar; Laohachai, Karina; Orr, Yishay; Ayer, Julian

    2016-11-01

    Anomalous origin of a branch pulmonary artery from the aorta is a rare malformation, accounting for 0.12% of all congenital heart defects. Anomalous origin of the left pulmonary artery from the aorta (ALPA) constitutes a small proportion of these cases. ALPA has been reported to arise from the ascending aorta with various embryologic postulates. We report a case of isolated ALPA arising from the descending aorta in association with a patent ductus arteriosus, to emphasize its embryologic ambiguity. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  15. Status of systemic to pulmonary arterial collateral flow after the fontan procedure.

    PubMed

    Whitehead, Kevin K; Harris, Matthew A; Glatz, Andrew C; Gillespie, Matthew J; DiMaria, Michael V; Harrison, Neil E; Dori, Yoav; Keller, Marc S; Rome, Jonathan J; Fogel, Mark A

    2015-06-15

    The investigators recently validated a method of quantifying systemic-to-pulmonary arterial collateral flow using phase-contrast magnetic resonance imaging velocity mapping. Cross-sectional data suggest decreased collateral flow in patients with total cavopulmonary connections (TCPCs) compared with those with superior cavopulmonary connections (SCPCs). However, no studies have examined serial changes in collateral flow from SCPCs to TCPCs in the same patients. The aim of this study was to examine differences in collateral flow between patients with SCPCs and those with TCPCs. Collateral flow was quantified by 2 independent measures from 250 single-ventricle studies in 219 different patients (115 SCPC and 135 TCPC studies, 31 patients with both) and 18 controls, during routine studies using through-plane phase-contrast magnetic resonance imaging. Collateral flow was indexed to body surface area, aortic flow, and pulmonary venous flow. Regardless of indexing method, SCPC patients had significantly higher collateral flow than TCPC patients (1.64 ± 0.8 vs 1.03 ± 0.8 L/min/m(2), p <0.001). In 31 patients who underwent serial examinations, collateral flow as a fraction of aortic flow increased early after TCPC completion. In TCPC patients, indexed collateral flow demonstrated a significant negative correlation with time from TCPC. In conclusion, SCPC and TCPC patients demonstrate substantial collateral flow, with SCPC patients having higher collateral flow than TCPC patients overall. On the basis of the paired subset analysis, collateral flow does not decrease in the short term after TCPC completion and trends toward an increase. In the long term, however, collateral flow decreases over time after TCPC completion. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Three-Dimensional Right Ventricular Strain Versus Volume Quantification in Heart Transplant Recipients in Relation to Pulmonary Artery Pressure.

    PubMed

    Sade, Leyla Elif; Kozan, Hatice; Eroglu, Serpil; Pirat, Bahar; Aydinalp, Alp; Sezgin, Atilla; Muderrisoglu, Haldun

    2017-02-01

    Residual pulmonary hypertension challenges the right ventricular function and worsens the prognosis in heart transplant recipients. The complex geometry of the right ventricle complicates estimation of its function with conventional transthoracic echocardiography. We evaluated right ventricular function in heart transplant recipients with the use of 3-dimensional echocardiography in relation to systolic pulmonary artery pressure. We performed 32 studies in 26 heart transplant patients, with 6 patients having 2 studies at different time points with different pressures and thus included. Right atrial volume, tricuspid annular plane systolic excursion, peak systolic annular velocity, fractional area change, and 2-dimensional speckle tracking longitudinal strain were obtained by 2-dimensional and tissue Doppler imaging. Three-dimensional right ventricular volumes, ejection fraction, and 3-dimensional right ventricular strain were obtained from the 3-dimensional data set by echocardiographers. Systolic pulmonary artery pressure was obtained during right heart catheterization. Overall mean systolic pulmonary artery pressure was 26 ± 7 mm Hg (range, 14-44 mmHg). Three-dimensional end-diastolic (r = 0.75; P < .001) and end-systolic volumes (r = 0.55; P = .001)correlated well with systolic pulmonary artery pressure. Right ventricular ejection fraction and right atrium volume also significantly correlated with systolic pulmonary artery pressure (r = 0.49 and P = .01 for both). However, right ventricular 2- and 3-dimensional strain, tricuspid annular plane systolic excursion, and tricuspid annular velocity did not. The effects of pulmonary hemodynamic burden on right ventricular function are better estimated by a 3-dimensional volume evaluation than with 3-dimensional longitudinal strain and other 2-dimensional and tissue Doppler measurements. These results suggest that the peculiar anatomy of the right ventricle necessitates 3-dimensional volume quantification in heart

  17. Lung Abscess as Delayed Manifestation of Pulmonary Arterial Narrowing After Sleeve Resection.

    PubMed

    Frenzen, Frederik S; Lesser, Thomas; Platzek, Ivan; Riede, Frank-Thomas; Kolditz, Martin

    2017-08-01

    A patient who had undergone right upper bilobectomy because of a carcinoid experienced lung abscesses 17 months after operation. After recurrences, despite different antibiotic agents, dual-energy computed tomography showed subtotal stenosis of the right lower lobe pulmonary artery with marked pulmonary perfusion-reduction. Rare causes of lung-abscesses should be considered. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  18. When to Offer Genetic Testing for Pulmonary Arterial Hypertension

    PubMed Central

    Chung, Wendy K.; Austin, Eric D.; Best, D. Hunter; Brown, Lynette M.; Elliott, C. Gregory

    2015-01-01

    Genetic testing is poised to play a greater role in the diagnosis and management of pulmonary arterial hypertension (PAH). Physicians who manage PAH should know the heritable PAH phenotypes, inheritance patterns, and responsible genes. They also should know indications, potential risks and benefits, and the issues surrounding genetic counselling and testing for patients with PAH. PMID:25840103

  19. 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

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

    PubMed Central

    Pousada, Guillermo; Baloira, Adolfo; Valverde, Diana

    2016-01-01

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

  1. Establishment of right ventricle-pulmonary artery continuity as the first-stage palliation in older infants with pulmonary atresia with ventricular septal defect may be preferable to use of an arterial shunt.

    PubMed

    Zheng, Shuai; Yang, Keming; Li, Kun; Li, Shoujun

    2014-07-01

    Right ventricle-pulmonary artery (RV-PA) conduit and systemic-to-pulmonary artery (S-PA) shunt in younger infants for the first-stage palliation with pulmonary atresia with ventricular septal defect (PAVSD) obtained good results. However, the pulmonary arteries (PA) grow slow in older infants undergoing an S-PA shunt. We compared the clinical outcomes of the two procedures in older infants with PAVSD. A total of 48 patients with PAVSD underwent the first-stage palliative procedure between January 2010 and July 2012. Patients were divided into the RV-PA group and the S-PA group based on whether they had an RV-PA conduit (n = 24) or an S-PA shunt (n = 24). The early and late outcomes were compared between groups. There was no significant difference in in-hospital mortality, mechanical ventilation time, paediatric intensive care unit stay and hospital stay between groups (all P > 0.05). The RV-PA conduits were associated with better PA growth compared with the S-PA shunts (P < 0.001). The RV-PA group had a higher rate of second-stage biventricular surgery compared with the S-PA group (P = 0.03). The early outcomes among different conduits of the RV-PA conduit were not different (all P > 0.05). A positive correlation was found between the size of conduits and body weight (R(2) = 0.684, P < 0.001). In older infants with PAVSD who underwent the first-stage palliative procedure, early outcomes showed no difference between the RV-PA conduit group and the S-PA shunt group. The RV-PA conduits were associated with better growth of the PA and higher rates of second-stage biventricular repair. Autologous pericardium is a good choice for RV-PA conduits, and there is a correlation between body weight and size of conduit. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  2. [Right-side aortic arch with aberrant left subclavian artery and Kommerell's diverticulum. A cause of vascular ring].

    PubMed

    Tamayo-Espinosa, Tania; Erdmenger-Orellana, Julio; Becerra-Becerra, Rosario; Balderrabano-Saucedo, Norma; Segura-Standford, Begoña

    The right-side aortic arch may be associated with aberrant left subclavian artery, in some cases this artery originates from an aneurismal dilation of the aorta called Kommerell's diverticulum. A report is presented on 2 cases of vascular ring formed by a right-side aortic arch, anomalous left subclavian artery, Kommerell's diverticulum and left patent ductus arteriosus. A review the literature was also performed as regards the embryological development and the imaging methods used to help in the diagnosis of this rare vascular anomaly. Copyright © 2017 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

  3. K(Ca)3.1 channel downregulation and impaired endothelium-derived hyperpolarization-type relaxation in pulmonary arteries from chronically hypoxic rats.

    PubMed

    Kroigaard, Christel; Kudryavtseva, Olga; Dalsgaard, Thomas; Wandall-Frostholm, Christine; Olesen, Søren-Peter; Simonsen, Ulf

    2013-04-01

    Calcium-activated potassium channels of small (K(Ca)2, SK) and intermediate (K(Ca)3.1, IK) conductance are involved in endothelium-dependent relaxation of pulmonary arteries. We hypothesized that the function and expression of K(Ca)2 and K(Ca)3.1 increase as a compensatory mechanism to counteract hypoxia-induced pulmonary hypertension in rats. For functional studies, pulmonary arteries were mounted in microvascular myographs for isometric tension recordings. The K(Ca) channel expression was evaluated by immunoblotting and quantitative PCR. Although ACh induced similar relaxations, the ACh-induced relaxations were abolished by the combined inhibition of nitric oxide synthase (by L-nitro-arginine, L-NOARG), cyclo-oxygenase (by indomethacin) and soluble guanylate cyclase (by ODQ) in pulmonary arteries from hypoxic rats, whereas 20 ± 6% (n = 8) maximal relaxation in response to ACh persisted in arteries from normoxic rats. Inhibiting Na(+),K(+)-ATPase with ouabain or blocking K(Ca)2 and K(Ca)3.1 channels reduced the persisting ACh-induced relaxation. In the presence of L-NOARG and indomethacin, a novel K(Ca)2 and K(Ca)3.1 channel activator, NS4591, induced concentration- and endothelium-dependent relaxations, which were markedly reduced in arteries from chronically hypoxic rats compared with arteries from normoxic rats. The mRNA levels of K(Ca)2.3 and K(Ca)3.1 were unaltered, whereas K(Ca)2.3 protein expression was upregulated and K(Ca)3.1 protein expression downregulated in pulmonary arteries from rats exposed to hypoxia. In conclusion, endothelium-dependent relaxation was conserved in pulmonary arteries from chronically hypoxic rats, while endothelium-derived hyperpolarization (EDH)-type relaxation was impaired in chronically hypoxic pulmonary small arteries despite upregulation of K(Ca)2.3 channels. Since impaired EDH-type relaxation was accompanied by K(Ca)3.1 channel protein downregulation, these findings suggest that K(Ca)3.1 channels are important for the

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

    PubMed

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

    2014-11-15

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

  5. Endobronchial ultrasound-guided transbronchial needle aspiration of pulmonary artery tumors: A systematic review (with video).

    PubMed

    Harris, Kassem; Modi, Kush; Kumar, Abhishek; Dhillon, Samjot Singh

    2015-01-01

    Convex probe endobronchial ultrasound (CP-EBUS) was originally introduced as a diagnostic and staging tool for lung cancer and subsequently utilized for diagnosis of other malignant and benign mediastinal diseases such as melanoma, lymphoma, and sarcoidosis. More recently, CP-EBUS has been successfully used for the visualization and diagnosis of pulmonary emboli and other vascular lesions including primary and metastatic pulmonary artery (PA) tumors. In this review, we will underline the role of EBUS-guided transbronchial needle aspiration (EBUS-TBNA) for the diagnosis of pulmonary arterial tumors such as sarcomas and tumor emboli. We will concisely discuss the clinical applications of EBUS-TBNA and the types of pulmonary arterial tumors and their different diagnostic modalities. We searched the Cochrane Library and PubMed from 2004 to 2014 to provide the most comprehensive review. Only 10 cases of EBUS-TBNA for intravascular lesions were identified in the literature. Although many cases of EBUS and EUS-guided transvascular tumor biopsies were described in the literature, there were no reported cases of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for intravascular tumor biopsies. Except for one paper, all cases were published as case reports.

  6. Right ventricular stroke work correlates with outcomes in pediatric pulmonary arterial hypertension.

    PubMed

    Yang, Weiguang; Marsden, Alison L; Ogawa, Michelle T; Sakarovitch, Charlotte; Hall, Keeley K; Rabinovitch, Marlene; Feinstein, Jeffrey A

    2018-01-01

    Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary artery pressures (PAP) and pulmonary vascular resistance (PVR). Optimizing treatment strategies and timing for transplant remains challenging. Thus, a quantitative measure to predict disease progression would be greatly beneficial in treatment planning. We devised a novel method to assess right ventricular (RV) stroke work (RVSW) as a potential biomarker of the failing heart that correlates with clinical worsening. Pediatric patients with idiopathic PAH or PAH secondary to congenital heart disease who had serial, temporally matched cardiac catheterization and magnetic resonance imaging (MRI) data were included. RV and PA hemodynamics were numerically determined by using a lumped parameter (circuit analogy) model to create pressure-volume (P-V) loops. The model was tuned using optimization techniques to match MRI and catheterization derived RV volumes and pressures for each time point. RVSW was calculated from the corresponding P-V loop and indexed by ejection fraction and body surface area (RVSW EF ) to compare across patients. Seventeen patients (8 boys; median age = 9.4 years; age range = 4.4-16.3 years) were enrolled. Nine were clinically stable; the others had clinical worsening between the time of their initial matched studies and their most recent follow-up (mean time = 3.9 years; range = 1.1-8.0 years). RVSW EF and the ratio of pulmonary to systemic resistance (Rp:Rs) values were found to have more significant associations with clinical worsening within one, two, and five years following the measurements, when compared with PVR index (PVRI). A receiver operating characteristic analysis showed RVSW EF outperforms PVRI, Rp:Rs and ejection fraction for predicting clinical worsening. RVSW EF correlates with clinical worsening in pediatric PAH, shows promising results towards predicting adverse outcomes, and may serve as an indicator of future clinical worsening.

  7. Robust extraction of the aorta and pulmonary artery from 3D MDCT image data

    NASA Astrophysics Data System (ADS)

    Taeprasartsit, Pinyo; Higgins, William E.

    2010-03-01

    Accurate definition of the aorta and pulmonary artery from three-dimensional (3D) multi-detector CT (MDCT) images is important for pulmonary applications. This work presents robust methods for defining the aorta and pulmonary artery in the central chest. The methods work on both contrast enhanced and no-contrast 3D MDCT image data. The automatic methods use a common approach employing model fitting and selection and adaptive refinement. During the occasional event that more precise vascular extraction is desired or the method fails, we also have an alternate semi-automatic fail-safe method. The semi-automatic method extracts the vasculature by extending the medial axes into a user-guided direction. A ground-truth study over a series of 40 human 3D MDCT images demonstrates the efficacy, accuracy, robustness, and efficiency of the methods.

  8. In Situ Fracture of Stents Implanted for Relief of Pulmonary Arterial Stenosis in Patients with Congenitally Malformed Hearts

    PubMed Central

    McElhinney, Doff B.; Bergersen, Lisa; Marshall, Audrey C.

    2014-01-01

    Background One of the most common uses of stents in patients with congenitally malformed hearts is treatment of pulmonary arterial stenosis. Although there are reports of fractured pulmonary arterial stents, little is known about the risk factors for, and implications of, such fractures. Methods We reviewed angiograms to identify fractures in stents previously inserted to relieve stenoses in pulmonary arteries from 1990 through 2001 in patients who also underwent follow-up catheterization at least 3 years after placement of the stent. We undertook matched cohort analysis, matching a ratio of 2 fractured to 1 unfractured stent. Results Overall, 166 stents meeting the criterions of our study had been placed in 120 patients. We identified fractures in 35 stents (21%) in 29 patients. All fractured stents were in the central pulmonary arteries, 24 (69%) in the central part of the right pulmonary artery, and all were complete axial fractures, or complex fractures along at least 2 planes. Stent-related factors associated with increased risk of fracture identified by multivariable logistic regression included placement in close apposition to the ascending aorta (p = 0.001), and a larger expanded diameter (p = 0.002). There was obstruction across 28 of 35 fractured stents, which was severe in 11. We re-stented 21 of the fractured stents, and recurrent fracture was later diagnosed in 3 of these. A fragment of the fractured stent embolized distally in 2 patients, without clinically important effects. Conclusions In situ fracture of pulmonary arterial stents is relatively common, and in most cases is related to compression by the aorta. There is usually recurrent obstruction across the fractured stent, but fractured stents rarely embolize, and are not associated with other significant complications. PMID:18559137

  9. Use of Isolated Mitochondria and Pulmonary Artery Endothelial Cell Systems in Studies of Oxygen Utilization and the Effects of Hemoglobin-Based Oxygen Carriers

    DTIC Science & Technology

    2008-07-16

    mitochondria through the monocarboxylate transporter and feed in to the Kreb’s cycle to yield 34 ATPs via oxidative phosphorylation as follows (assuming a... Krebs (tricarboxylic acid) cycle enzyme, and is found mainly in the mitochondrial matrix (8). Therefore, its measured enzymatic activity serves as an...APPROVAL SHEET Title of Thesis: "Use of Isolated Mitochondria and Pulmonary Artery Endothelial Cell Systems in Studies of Oxygen Utilization and the

  10. Fetal Onset of Aberrant Gene Expression Relevant to Pulmonary Carcinogenesis in Lung Adenocarcinoma Development Induced by In Utero Arsenic Exposure

    PubMed Central

    Shen, Jun; Liu, Jie; Xie, Yaxiong; Diwan, Bhalchandra A.; Waalkes, Michael P.

    2009-01-01

    Arsenic is a human pulmonary carcinogen. Our work indicates that in utero arsenic exposure in mice can induce or initiate lung cancer in female offspring. To define early molecular changes, pregnant C3H mice were given 85 ppm arsenic in drinking water from days 8 to 18 of gestation and expression of selected genes in the fetal lung or in lung tumors developing in adults was examined. Transplacental arsenic exposure increased estrogen receptor-α (ER-α) transcript and protein levels in the female fetal lung. An overexpression of various estrogen-regulated genes also occurred, including trefoil factor-3, anterior gradient-2, and the steroid metabolism genes 17-β-hydroxysteroid dehydrogenase type 5 and aromatase. The insulin growth factor system, which can be influenced by ER and has been implicated in the pulmonary oncogenic process, was activated in fetal lung after gestational arsenic exposure. in utero arsenic exposure also induced overexpression of α-fetoprotein, epidermal growth factor receptor, L-myc, and metallothionein-1 in fetal lung, all of which are associated with lung cancer. Lung adenoma and adenocarcinoma from adult female mice exposed to arsenic in utero showed widespread, intense nuclear ER-α expression. In contrast, normal adult lung and diethylnitrosamine-induced lung adenocarcinoma showed little evidence of ER-α expression. Thus, transplacental arsenic exposure at a carcinogenic dose produced aberrant estrogen-linked pulmonary gene expression. ER-α activation was specifically associated with arsenic-induced lung adenocarcinoma and adenoma but not with nitrosamine-induced lung tumors. These data provide evidence that arsenic-induced aberrant ER signaling could disrupt early life stage genetic programing in the lung leading eventually to lung tumor formation much later in adulthood. PMID:17077188

  11. Fetal onset of aberrant gene expression relevant to pulmonary carcinogenesis in lung adenocarcinoma development induced by in utero arsenic exposure.

    PubMed

    Shen, Jun; Liu, Jie; Xie, Yaxiong; Diwan, Bhalchandra A; Waalkes, Michael P

    2007-02-01

    Arsenic is a human pulmonary carcinogen. Our work indicates that in utero arsenic exposure in mice can induce or initiate lung cancer in female offspring. To define early molecular changes, pregnant C3H mice were given 85 ppm arsenic in drinking water from days 8 to 18 of gestation and expression of selected genes in the fetal lung or in lung tumors developing in adults was examined. Transplacental arsenic exposure increased estrogen receptor-alpha (ER-alpha) transcript and protein levels in the female fetal lung. An overexpression of various estrogen-regulated genes also occurred, including trefoil factor-3, anterior gradient-2, and the steroid metabolism genes 17-beta-hydroxysteroid dehydrogenase type 5 and aromatase. The insulin growth factor system, which can be influenced by ER and has been implicated in the pulmonary oncogenic process, was activated in fetal lung after gestational arsenic exposure. In utero arsenic exposure also induced overexpression of alpha-fetoprotein, epidermal growth factor receptor, L-myc, and metallothionein-1 in fetal lung, all of which are associated with lung cancer. Lung adenoma and adenocarcinoma from adult female mice exposed to arsenic in utero showed widespread, intense nuclear ER-alpha expression. In contrast, normal adult lung and diethylnitrosamine-induced lung adenocarcinoma showed little evidence of ER-alpha expression. Thus, transplacental arsenic exposure at a carcinogenic dose produced aberrant estrogen-linked pulmonary gene expression. ER-alpha activation was specifically associated with arsenic-induced lung adenocarcinoma and adenoma but not with nitrosamine-induced lung tumors. These data provide evidence that arsenic-induced aberrant ER signaling could disrupt early life stage genetic programing in the lung leading eventually to lung tumor formation much later in adulthood.

  12. Elevation of Plasma Cell-Free Hemoglobin in Pulmonary Arterial Hypertension

    PubMed Central

    Janz, David R.; Austin, Eric D.; Bastarache, Julie A.; Wheeler, Lisa A.; Ware, Lorraine B.; Hemnes, Anna R.

    2014-01-01

    BACKGROUND: Cell-free hemoglobin (CFH) is a potent nitric oxide scavenger associated with poor outcomes in several diseases. Pulmonary arterial hypertension (PAH) is characterized by reduced nitric oxide availability. We hypothesized that CFH would be elevated in PAH and would associate with hemodynamics and clinical outcomes. METHODS: We measured CFH in 200 consecutively evaluated patients with PAH, 16 unaffected bone morphogenetic receptor protein type 2 (BMPR2) mutation carriers, 19 healthy subjects, and 29 patients with pulmonary venous hypertension (PVH). CFH values were tested for association with hemodynamics, time to hospitalization, and death. RESULTS: CFH was elevated in patients with PAH and BMPR2 carriers compared with healthy subjects and patients with PVH (P ≤ .01 all comparisons). There were no differences in CFH across PAH subtypes. CFH modestly correlated with mean pulmonary artery pressure (ρ = 0.16, P = .03) and pulmonary vascular resistance (ρ = 0.21, P = .01) and inversely with cardiac index (ρ = −0.18, P = .02) in patients with PAH. CFH was not associated with hemodynamic response to nitric oxide or death. Patients with the highest CFH levels had increased risk of PAH-related hospitalization when adjusted for age, sex, and PAH cause (hazard ratio, 1.69; 95% CI ,1.08-2.66; P = .02). CONCLUSIONS: CFH is elevated in patients with PAH and BMPR2 carriers compared with healthy subjects and patients with PVH. Elevated CFH levels are independently associated with an increased risk of hospitalization. Further study is required to understand the mechanism of CFH elevation and the potential pathologic contribution of CFH in PAH. PMID:24945582

  13. 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.

  14. PULMONARY ARTERIAL DISEASE ASSOCIATED WITH RIGHT-SIDED CARDIAC HYPERTROPHY AND CONGESTIVE HEART FAILURE IN ZOO MAMMALS HOUSED AT 2,100 M ABOVE SEA LEVEL.

    PubMed

    Juan-Sallés, Carles; Martínez, Liliana Sofía; Rosas-Rosas, Arely G; Parás, Alberto; Martínez, Osvaldo; Hernández, Alejandra; Garner, Michael M

    2015-12-01

    Subacute and chronic mountain sickness of humans and the related brisket disease of cattle are characterized by right-sided congestive heart failure in individuals living at high altitudes as a result of sustained hypoxic pulmonary hypertension. Adaptations to high altitude and disease resistance vary among species, breeds, and individuals. The authors conducted a retrospective survey of right-sided cardiac hypertrophy associated with pulmonary arterial hypertrophy or arteriosclerosis in zoo mammals housed at Africam Safari (Puebla, México), which is located at 2,100 m above sea level. Seventeen animals with detailed pathology records matched the study criterion. Included were 10 maras (Dolichotis patagonum), 2 cotton-top tamarins (Saguinus oedipus oedipus), 2 capybaras (Hydrochaeris hydrochaeris), and 1 case each of Bennet's wallaby (Macropus rufogriseus), nilgai antelope (Boselaphus tragocamelus), and scimitar-horned oryx (Oryx dammah). All had right-sided cardiac hypertrophy and a variety of arterial lesions restricted to the pulmonary circulation and causing arterial thickening with narrowing of the arterial lumen. Arterial lesions most often consisted of medial hypertrophy or hyperplasia of small and medium-sized pulmonary arteries. All maras also had single or multiple elevated plaques in the pulmonary arterial trunk consisting of fibrosis, accompanied by chondroid metaplasia in some cases. Both antelopes were juvenile and died with right-sided congestive heart failure associated with severe pulmonary arterial lesions. To the authors' knowledge, this is the first description of cardiac and pulmonary arterial disease in zoo mammals housed at high altitudes.

  15. A pilot study of the effect of spironolactone therapy on exercise capacity and endothelial dysfunction in pulmonary arterial hypertension: study protocol for a randomized controlled trial.

    PubMed

    Elinoff, Jason M; Rame, J Eduardo; Forfia, Paul R; Hall, Mary K; Sun, Junfeng; Gharib, Ahmed M; Abd-Elmoniem, Khaled; Graninger, Grace; Harper, Bonnie; Danner, Robert L; Solomon, Michael A

    2013-04-02

    Pulmonary arterial hypertension is a rare disorder associated with poor survival. Endothelial dysfunction plays a central role in the pathogenesis and progression of pulmonary arterial hypertension. Inflammation appears to drive this dysfunctional endothelial phenotype, propagating cycles of injury and repair in genetically susceptible patients with idiopathic and disease-associated pulmonary arterial hypertension. Therapy targeting pulmonary vascular inflammation to interrupt cycles of injury and repair and thereby delay or prevent right ventricular failure and death has not been tested. Spironolactone, a mineralocorticoid and androgen receptor antagonist, has been shown to improve endothelial function and reduce inflammation. Current management of patients with pulmonary arterial hypertension and symptoms of right heart failure includes use of mineralocorticoid receptor antagonists for their diuretic and natriuretic effects. We hypothesize that initiating spironolactone therapy at an earlier stage of disease in patients with pulmonary arterial hypertension could provide additional benefits through anti-inflammatory effects and improvements in pulmonary vascular function. Seventy patients with pulmonary arterial hypertension without clinical evidence of right ventricular failure will be enrolled in a randomized, double-blinded, placebo-controlled trial to investigate the effect of early treatment with spironolactone on exercise capacity, clinical worsening and vascular inflammation in vivo. Our primary endpoint is change in placebo-corrected 6-minute walk distance at 24 weeks and the incidence of clinical worsening in the spironolactone group compared to placebo. At a two-sided alpha level of 0.05, we will have at least 84% power to detect an effect size (group mean difference divided by standard deviation) of 0.9 for the difference in the change of 6-minute walk distance from baseline between the two groups. Secondary endpoints include the effect of

  16. A pilot study of the effect of spironolactone therapy on exercise capacity and endothelial dysfunction in pulmonary arterial hypertension: study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background Pulmonary arterial hypertension is a rare disorder associated with poor survival. Endothelial dysfunction plays a central role in the pathogenesis and progression of pulmonary arterial hypertension. Inflammation appears to drive this dysfunctional endothelial phenotype, propagating cycles of injury and repair in genetically susceptible patients with idiopathic and disease-associated pulmonary arterial hypertension. Therapy targeting pulmonary vascular inflammation to interrupt cycles of injury and repair and thereby delay or prevent right ventricular failure and death has not been tested. Spironolactone, a mineralocorticoid and androgen receptor antagonist, has been shown to improve endothelial function and reduce inflammation. Current management of patients with pulmonary arterial hypertension and symptoms of right heart failure includes use of mineralocorticoid receptor antagonists for their diuretic and natriuretic effects. We hypothesize that initiating spironolactone therapy at an earlier stage of disease in patients with pulmonary arterial hypertension could provide additional benefits through anti-inflammatory effects and improvements in pulmonary vascular function. Methods/Design Seventy patients with pulmonary arterial hypertension without clinical evidence of right ventricular failure will be enrolled in a randomized, double-blinded, placebo-controlled trial to investigate the effect of early treatment with spironolactone on exercise capacity, clinical worsening and vascular inflammation in vivo. Our primary endpoint is change in placebo-corrected 6-minute walk distance at 24 weeks and the incidence of clinical worsening in the spironolactone group compared to placebo. At a two-sided alpha level of 0.05, we will have at least 84% power to detect an effect size (group mean difference divided by standard deviation) of 0.9 for the difference in the change of 6-minute walk distance from baseline between the two groups. Secondary endpoints include

  17. Identification of a Novel Hybridization from Isosorbide 5-Mononitrate and Bardoxolone Methyl with Dual Activities of Pulmonary Vasodilation and Vascular Remodeling Inhibition on Pulmonary Arterial Hypertension Rats.

    PubMed

    Cheng, Yusheng; Gong, Yan; Qian, Shuai; Mou, Yi; Li, Hanrui; Chen, Xijing; Kong, Hui; Xie, Weiping; Wang, Hong; Zhang, Yihua; Huang, Zhangjian

    2018-02-22

    Given the clinical therapeutic efficacy of oral-dosed bardoxolone methyl (1) and the selective vasodilatory effect caused by inhalation of nitric oxide (NO) on pulmonary arterial hypertension (PAH) patients, a new hybrid (CDDO-NO, 2) from 1 and NO donor isosorbide 5-mononitrate (3) was designed and synthesized. This hybrid could liberate 1 and NO in the lungs of rats after trachea injection. Significantly, 2 lowered mean pulmonary artery pressure (mPAP) and right ventricular systolic pressure (RVSP), decreased right ventricular hypertrophy (RVH), and attenuated pulmonary artery medial thickness (PAMT) and vascular muscularization in monocrotaline (MCT)-induced PAH rats. Meanwhile, 2 inhibited overproliferation of perivascular cells and diminished macrophage infiltration and oxidative stress by inactivation of NOX4. In addition, 2 markedly reduced cardiac hypertrophy and fibrosis in the PAH rats. Overall, 2 exhibited potent dual activities of pulmonary vasodilation and vascular remodeling inhibition, suggesting that it may be a promising agent for PAH intervention.

  18. URBAN PARTICLE-INDUCED PULMONARY ARTERY CONSTRUCTION IS MEDIATED BY SUPEROXIDE PRODUCTION

    EPA Science Inventory

    URBAN PARTICLE-INDUCED PULMONARY ARTERY CONSTRICTION IS MEDIATED BY SUPEROXIDE PRODUCTION.Jacqueline D. Carter, Zhuowei Li, Lisa A. Dailey, Yuh-Chin T. Huang. CEMALB, University of North Carolina, and ORD, US EPA, Chapel Hill, North Carolina.

    Exposure to particulate matter...

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

    PubMed Central

    2013-01-01

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

  20. Neurohormonal axis in patients with pulmonary arterial hypertension: friend or foe?

    PubMed

    de Man, Frances S; Handoko, M Louis; Guignabert, Christophe; Bogaard, Harm J; Vonk-Noordegraaf, Anton

    2013-01-01

    Despite its description some 25 years ago, neurohormonal activation has long been neglected as an important factor in the pathophysiology of pulmonary arterial hypertension (PAH). Neurohormonal activation was interpreted as a necessary compensatory response to maintain cardiac contractility and systemic blood pressure. Therefore, inhibitors of neurohormonal activity (like β-blockers or angiotensin-converting enzyme inhibitors) are considered contraindicated in current PAH management guidelines. However, recent data revealed that sympathetic overstimulation is strongly related to mortality, and blockade of neurohormonal activity in experimental PAH improved survival and cardiac function. These novel insights shed new light on the role of neurohormonal activity in PAH.

  1. Risks of on-pump coronary artery bypass grafting surgery in patients with chronic obstructive pulmonary disease due to sulfur mustard.

    PubMed

    Firoozabadi, Mehdi Dehghani; Sheikhi, Mohammad Ali; Rahmani, Hossein; Ebadi, Ahmad; Heidari, Amanollah; Gholizadeh, Behnam; Sharifi, Khosrow

    2017-10-01

    Sulfur mustard (SM) is a toxic chemical agent that belongs to a class of vesicant compounds. In the 1980s it was used by the Iraqi army against Iranian forces. Sulfur mustard severely irritates the skin, eyes and lungs. The highest side effects seen in patients affected by this gas are pulmonary complications including different types of lung diseases such as bronchiolitis. It has also led to a certain type of chronic obstructive pulmonary disease called mustard lung. Similar extra-pulmonary, molecular and hormonal effects can be observed in these patients and patients with chronic obstructive pulmonary disease. Here cardiovascular complications may be one of the most dangerous visible effects. And atherosclerosis is probable following the direct effects or consequential long-term effects of SM. The development of atherosclerosis in these patients is associated with an increased risk of cardiovascular and coronary artery disease. Coronary artery bypass grafting surgery is the treatment of coronary artery disease. Doing this surgery by bypass pump has its own morbidity and due to local and systemic inflammation changes in patients with SM pulmonary disorders it may have more side effects. Therefore, detailed knowledge of inflammatory diseases as well as the serum level or even the local lung fluid of the inflammatory factors in these patients before surgery are needed so that it would be possible to reduce the rate of morbidity and mortality by normalizing the inflammatory conditions of the patients before cardiac surgery.

  2. 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.

  3. Vasa Vasorum Arteriopathy: Relationship With Systemic Arterial Hypertension and Other Vascular Lesions in Cats.

    PubMed

    Kohnken, R; Scansen, B A; Premanandan, C

    2017-05-01

    The vasa vasorum is a delicate network of small arterioles that supplies nutrients to the adventitia and outer media of large arteries. In humans, dysfunction of the vasa vasorum contributes to the pathogenesis of aortic dissection and atherosclerosis. Twenty-four cats from 1 to 18 years of age were prospectively evaluated. Cases were divided into 3 cohorts-with systemic hypertension, without systemic hypertension, and uncertain. Histologic sections of the aorta and main pulmonary artery, as well as sections of kidney and lung, were blindly examined by 2 pathologists. The severity of vasa vasorum arteriopathy was compared to the presence of renal arteriosclerosis, aortic medial degeneration, subintimal fibroplasia of the main pulmonary artery, and blood pressure. We found that vasa vasorum arteriopathy correlated strongly with hypertensive status, degree of renal arteriosclerosis, and lesions in the great vessels. The positive predictive value of a severe vasa vasorum score for systemic hypertension was 84.6%. Lesions of vasa vasorum arteriopathy were predictive of renal arteriosclerosis with 100% sensitivity and 64.7% specificity. The positive predictive value of a severe vasa vasorum score for the presence of aortic lesions was 69.2% vs 91.6% for lesions in the main pulmonary artery. The vasa vasorum appears to be an important responder to systemic hypertension in cats, and arteriopathy of this vascular bed has significant implications for the integrity of the great vessels.

  4. A different kind of Christmas tree: anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA).

    PubMed

    Afolabi-Brown, Olayinka; Witzke, Christian; Moldovan, Raul; Pressman, Gregg

    2014-02-01

    Anomalous right coronary artery from the pulmonary artery (ARCAPA) is a rare congenital coronary anomaly that has an incidence of 0.002%. We report a case of a previously healthy female who presented to our hospital with pneumonia and was incidentally discovered to have ARCAPA. This was initially diagnosed on echocardiography by the unusual echocardiographic finding of multiple color flow Doppler signals around the right ventricular free wall and apex which were subsequently confirmed by angiography to be due to extensive collateral circulation between the left and right coronary arteries. This represents an unusual echocardiographic manifestation of this very rare condition. © 2013, Wiley Periodicals, Inc.

  5. Anomalous Origin of Coronary Artery From Main Pulmonary Artery in Hypoplastic Left Heart Syndrome.

    PubMed

    Turiy, Yuliya; Douglas, William; Balaguru, Duraisamy

    2015-12-01

    We report a case of anomalous origin of the left anterior descending coronary artery (LAD) from the main pulmonary artery in a child with hypoplastic left heart syndrome (mitral atresia/aortic atresia). Mechanical circulatory support was necessary because of the inability to wean from cardiopulmonary bypass after the Norwood procedure. The patient died at 4 months of age having continued depressed right ventricular function. The diagnosis was made during a catheterization performed 6 weeks after surgery because of concern for stenosis of Blalock-Taussig shunt. We believe his prolonged postoperative recovery and eventual demise can partially be attributed to lack of cardioplegia to the anomalous LAD territory during surgery. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  6. Energy efficiency and pulmonary artery flow after balloon pulmonary angioplasty for inoperable, chronic thromboembolic pulmonary hypertension: Analysis by phase-contrast MRI.

    PubMed

    Nagao, Michinobu; Yamasaki, Yuzo; Abe, Kohtaro; Hosokawa, Kazuya; Kawanami, Satoshi; Kamitani, Takeshi; Yamanouchi, Torahiko; Yabuuchi, Hidetake; Fukushima, Kenji; Honda, Hiroshi

    2017-02-01

    The aims of this study were to propose a new quantitative method for pulmonary artery (PA) flow energetics using phase-contrast magnetic resonance imaging (PC-MRI), and to investigate how balloon pulmonary angioplasty (BPA) impacts energetics in chronic thromboembolic pulmonary hypertension (CTEPH). PC-MRI at 3-Teslar and with a flow sensitive gradient echo was used to examine energetics prior to and following BPA for 24 CTEPH patients. Stroke volume (m; ml) and mean velocity (V; mm/s) for the main pulmonary artery (PA), right PA, and left PA were calculated from a time-flow curve derived from PC-MRI. Based on the Bernoulli principle, PA energy was identified as 1/2mV 2 (μj/kg), and energy loss was defined as the following equation "energy loss=main PA energy-(rt. PA energy+lt. PA energy)". Right PA energy was significantly greater post-BPA than pre-BPA (61±55 vs. 32±40μj/kg). There was no difference in main PA and left PA energies. Energy loss was significantly decreased post-BPA (18±97μj/kg) than pre-BPA (79±125μj/kg). An optimal cutoff of left PA energy of 45μj/kg pre-BPA can be used to predict patients with mPAP≥30mmHg after BPA, with an area under the curve of 0.91, 78% sensitivity, and 92% specificity. Analysis of PA energetics using phase-contrast MRI demonstrates that BPA improves energy loss in CTEPH. In addition, BPA responses can be predicted by PA energy status pre-treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Isolation of pulmonary artery smooth muscle cells from neonatal mice.

    PubMed

    Lee, Keng Jin; Czech, Lyubov; Waypa, Gregory B; Farrow, Kathryn N

    2013-10-19

    Pulmonary hypertension is a significant cause of morbidity and mortality in infants. Historically, there has been significant study of the signaling pathways involved in vascular smooth muscle contraction in PASMC from fetal sheep. While sheep make an excellent model of term pulmonary hypertension, they are very expensive and lack the advantage of genetic manipulation found in mice. Conversely, the inability to isolate PASMC from mice was a significant limitation of that system. Here we described the isolation of primary cultures of mouse PASMC from P7, P14, and P21 mice using a variation of the previously described technique of Marshall et al. that was previously used to isolate rat PASMC. These murine PASMC represent a novel tool for the study of signaling pathways in the neonatal period. Briefly, a slurry of 0.5% (w/v) agarose + 0.5% iron particles in M199 media is infused into the pulmonary vascular bed via the right ventricle (RV). The iron particles are 0.2 μM in diameter and cannot pass through the pulmonary capillary bed. Thus, the iron lodges in the small pulmonary arteries (PA). The lungs are inflated with agarose, removed and dissociated. The iron-containing vessels are pulled down with a magnet. After collagenase (80 U/ml) treatment and further dissociation, the vessels are put into a tissue culture dish in M199 media containing 20% fetal bovine serum (FBS), and antibiotics (M199 complete media) to allow cell migration onto the culture dish. This initial plate of cells is a 50-50 mixture of fibroblasts and PASMC. Thus, the pull down procedure is repeated multiple times to achieve a more pure PASMC population and remove any residual iron. Smooth muscle cell identity is confirmed by immunostaining for smooth muscle myosin and desmin.

  8. Pulmonary embolism after arterial chemoembolization for hepatocellular carcinoma: An autopsy case report

    PubMed Central

    Hatamaru, Keiichi; Azuma, Shunjiro; Akamatsu, Takuji; Seta, Takeshi; Urai, Shunji; Uenoyama, Yoshito; Yamashita, Yukitaka; Ono, Kazuo

    2015-01-01

    We report an extremely rare case of pulmonary lipiodol embolism with acute respiratory distress syndrome (ARDS) after transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). A 77-year-old man who was diagnosed with a huge HCC was admitted for TACE. Immediately after the procedure, this patient experienced severe dyspnea. We suspected that his symptoms were associated with a pulmonary lipiodol embolism after TACE, and we began intensive treatment. However, his condition did not improve, and he died on the following day. A subsequent autopsy revealed that the cause of death was ARDS due to pulmonary lipiodol embolism. No cases have been previously reported for which an autopsy was performed to explain the most probable mechanism of pulmonary lipiodol embolism; thus, ours is the first report for such a rare case. PMID:25632211

  9. Pulmonary embolism after arterial chemoembolization for hepatocellular carcinoma: an autopsy case report.

    PubMed

    Hatamaru, Keiichi; Azuma, Shunjiro; Akamatsu, Takuji; Seta, Takeshi; Urai, Shunji; Uenoyama, Yoshito; Yamashita, Yukitaka; Ono, Kazuo

    2015-01-28

    We report an extremely rare case of pulmonary lipiodol embolism with acute respiratory distress syndrome (ARDS) after transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). A 77-year-old man who was diagnosed with a huge HCC was admitted for TACE. Immediately after the procedure, this patient experienced severe dyspnea. We suspected that his symptoms were associated with a pulmonary lipiodol embolism after TACE, and we began intensive treatment. However, his condition did not improve, and he died on the following day. A subsequent autopsy revealed that the cause of death was ARDS due to pulmonary lipiodol embolism. No cases have been previously reported for which an autopsy was performed to explain the most probable mechanism of pulmonary lipiodol embolism; thus, ours is the first report for such a rare case.

  10. Vascular Ehlers-Danlos Syndrome With a Novel Missense COL3A1 Mutation Present With Pulmonary Complications and Iliac Arterial Dissection.

    PubMed

    Gu, Guangchao; Yang, Hang; Cui, Lijia; Fu, Yuanyuan; Li, Fangda; Zhou, Zhou; Zheng, Yuehong

    2018-02-01

    Vascular Ehlers-Danlos syndrome (vEDS) is a life-threatening connective tissue disorder due to its high tendency of arterial and organ rupture. Pulmonary complications in vEDS are rare. We present a young male patient with vEDS who developed severe pulmonary complications and severe rupture of the iliac artery at different stages of his life. Vascular Ehlers-Danlos syndrome was diagnosed based on clinical manifestations and confirmed by the identification of COL3A1 gene mutation. Due to high bleeding tendency and weak cardiopulmonary capacity, conservative treatment was taken for him. To our knowledge, this is the first report of vEDS case in which the patient developed both pulmonary complications and dissection of large arteries. Our report emphasizes the importance of considering vEDS when an adolescent develops unexplained pulmonary cysts with fragility of lung tissues. Genetic counseling and close monitoring should be performed for earlier diagnosis and prevention of severe complications of large arteries. The typical presentations of vEDS were also discussed by means of a review of case reports on vEDS with pulmonary complications.

  11. 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

  12. 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.

  13. 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

    Background Acute pulmonary exacerbations are associated with progressive lung function decline and increased mortality in cystic fibrosis (CF). The role of pulmonary vascular disease in pulmonary exacerbations is unknown. We investigated the association between pulmonary artery enlargement (PA:A>1), a marker of pulmonary vascular disease, and exacerbations. Methods We analyzed clinical, computed tomography (CT), and prospective exacerbation data in a derivation cohort of 74 adult CF patients, measuring the PA:A at the level of the PA bifurcation. We then replicated our findings in a validation cohort of 190 adult CF patients. Patients were separated into groups based on the presence or absence of a PA:A>1 and were followed for 1-year in the derivation cohort and 2-years in the validation cohort. The primary endpoint was developing ≥1 acute pulmonary exacerbation during follow-up. Linear and logistic regression models were used to determine associations between clinical factors, the PA:A ratio, and pulmonary exacerbations. We used Cox regression to determine time to first exacerbation in the validation cohort. Findings We found that PA:A>1 was present in n=37/74 (50%) of the derivation and n=89/190 (47%) of the validation cohort. In the derivation cohort, n=50/74 (68%) had ≥1 exacerbation at 1 year and n=133/190 (70%) in the validation cohort had ≥1 exacerbation after 2 years. PA:A>1 was associated with younger age in both cohorts and with elevated sweat chloride (100.5±10.9 versus 90.4±19.9mmol/L, difference between groups 10.1mmol/L [95%CI 2.5–17.7], P=0.017) in the derivation group. PA:A>1 was associated with exacerbations in the derivation (OR 3.49, 95%CI 1.18–10.3, P=0.023) and validation (OR 2.41, 95%CI 1.06–5.52, P=0.037) cohorts when adjusted for confounders. Time to first exacerbation was shorter in PA:A>1 versus PA:A<1 [HR 1.66 (95%CI 1.18–2.34), P=0.004] in unadjusted analysis, but not when adjusted for sex, BMI, prior exacerbation

  14. Endothelial cell-dependent relaxation and contraction induced by histamine in the isolated guinea-pig pulmonary artery.

    PubMed

    Satoh, H; Inui, J

    1984-01-27

    Histamine (10(-8)-10(-6) M) relaxed in a concentration-dependent manner the guinea-pig pulmonary artery which had been contracted by noradrenaline (5 X 10(-7) M). After the removal of endothelial cells (ETCs) histamine at the same concentrations did not cause relaxation but induced additional contraction. Both responses to histamine were antagonized by chlorpheniramine (3 X 10(-7) M). These results suggest that in the pulmonary artery histamine simultaneously stimulates H1-receptors located on both ETCs and smooth muscle cells. This results in two opposite effects, relaxation mediated by ETCs, and contraction.

  15. Percutaneous device closure of patent ductus arteriosus with pulmonary artery hypertension: long-term results.

    PubMed

    Vijayalakshmi, Ishwarappa Balekundri; Setty, Natraj; Narasimhan, Chitra; Singla, Vivek; Manjunath, Cholenahalli Nanjappa

    2014-12-01

    Device closure of patent ductus arteriosus (PDA) is treatment of choice. But device closure in presence of pulmonary artery hypertension (PAH) remains a challenge. Data on patient selection, technical considerations, and complications are limited. To know the challenges and efficacy of device closure of PDA with PAH. Out of 1,325 cases of device closure of PDA, 246 (18.6%) with PAH formed the study material. To test the feasibility, chosen device is used to occlude PDA for ten minutes without oxygen inhalation. The device is released only if PAH reduced. PAH decreased in all except in 1 patient after closure with muscular ventricular septal occluder (MVSDO), pulmonary artery pressure (PAP) transiently increased (became supra-systemic), without significant reduction in aortic pressure. Device embolized in 8 patients (3.3%). Percutaneous retrieval was done in 4 (by snare in 2 and by fixing the cable to device in 2) and replaced with bigger devices. The surgical removal of the embolized MVSDO and ligation was done in 4 cases. All patients were on oral sildenafil and bosentan until PAP regressed to normal. Follow up was from 6 months to 9 years. No residual shunt in any patient on follow-up. The PAP regressed to normal in all except 5 cases (2.03%) of Down's syndrome with systemic PAP. Device closure of PDA with PAH is feasible, safe in all age groups. Temporary PDA occlusion with device is effective and time saving for evaluating pulmonary vascular reactivity. Device embolization in aorta is higher with severe PAH. Novel method of retrieval is effective. © 2014, Wiley Periodicals, Inc.

  16. Computed tomography and magnetic resonance angiography in the evaluation of aberrant origin of the external carotid artery branches.

    PubMed

    Cappabianca, Salvatore; Scuotto, Assunta; Iaselli, Francesco; Pignatelli di Spinazzola, Nicoletta; Urraro, Fabrizio; Sarti, Giuseppe; Montemarano, Marcella; Grassi, Roberto; Rotondo, Antonio

    2012-07-01

    Aim of our study was to evaluate the prevalence of aberrant origin of the branches of the external carotid artery (ECA) in 97 patients by computed tomography (CTA) and magnetic resonance angiography (MRA) and to compare the accuracy of these two techniques in the visualization of the ECA system. All patients underwent CTA and MRA examination of the head and neck. Multiplanar and volumetric reformations were obtained in all cases. For each set of images, the presence of aberrant origin of the branches of the external carotid artery was investigated. MRA and CTA images of each patient were compared to define their information content. Anatomical anomalies were found in 88 heminecks, with a prevalence of 53.3%. In the 61 patients in whom the CTA was performed before the MRA, the latter method showed only 92% of abnormalities detected at the first examination; in the 36 patients in whom MRA was performed first, CTA identified all of the anomalies highlighted by the former, adding 12 new. Knowledge of the anomalies of origin of the ECA branches is essential for the head and neck surgeon; the high prevalence of anomalies found in our series as in the previous studies indicates the opportunity to perform a CTA or a MRA of the head and neck before any surgical or interventional procedure. CTA is the method of choice in the evaluation of anomalies of origin of the branches of the ECA and in the definition of their course.

  17. Pulmonary arterial hypertension associated to systemic erythematous lupus: molecular characterization of 3 cases.

    PubMed

    Pousada, Guillermo; Lago-Docampo, Mauro; Baloira, Adolfo; Valverde, Diana

    2018-03-08

    Pulmonary arterial hypertension associated with systemic lupus erythematosus (PAH-SLE) is a rare disease with a low incidence rate. In this study, PAH related genes and genetic modifiers were characterised molecularly in patients with PAH-SLE. Three patients diagnosed with PAH-SLE and 100 control individuals were analysed after signing an informed consent. Two out of the three analysed patients with PAH-SLE were carriers of pathogenic mutations in the genes BMPR2 and ENG. After an in silico analysis, pathogenic mutations were searched for in control individuals and different databases, with negative results, and they were thus functionally analysed. The third patients only showed polymorphisms in the genes BMPR2, ACVRL1 and ENG. Several genetic variants and genetic modifiers were identified in the three analysed patients. These modifiers, along with the pathogenic mutations, could lead to a more severe clinical course in patients with PAH. We present, for the first time, patients with PAH-SLE carrying pathogenic mutations in the main genes related to PAH and alterations in the genetic modifiers. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

  18. Maternal high-altitude hypoxia and suppression of ryanodine receptor-mediated Ca2+ sparks in fetal sheep pulmonary arterial myocytes

    PubMed Central

    Hadley, Scott R.; Blood, Quintin; Rubalcava, Monica; Waskel, Edith; Lumbard, Britney; Le, Petersen; Longo, Lawrence D.; Buchholz, John N.

    2012-01-01

    Ca2+ sparks are fundamental Ca2+ signaling events arising from ryanodine receptor (RyR) activation, events that relate to contractile and dilatory events in the pulmonary vasculature. Recent studies demonstrate that long-term hypoxia (LTH) can affect pulmonary arterial reactivity in fetal, newborn, and adult animals. Because RyRs are important to pulmonary vascular reactivity and reactivity changes with ontogeny and LTH we tested the hypothesis that RyR-generated Ca2+ signals are more active before birth and that LTH suppresses these responses. We examined these hypotheses by performing confocal imaging of myocytes in living arteries and by performing wire myography studies. Pulmonary arteries (PA) were isolated from fetal, newborn, or adult sheep that lived at low altitude or from those that were acclimatized to 3,801 m for > 100 days. Confocal imaging demonstrated preservation of the distance between the sarcoplasmic reticulum, nucleus, and plasma membrane in PA myocytes. Maturation increased global Ca2+ waves and Ca2+ spark activity, with sparks becoming larger, wider, and slower. LTH preferentially depressed Ca2+ spark activity in immature pulmonary arterial myocytes, and these sparks were smaller, wider, and slower. LTH also suppressed caffeine-elicited contraction in fetal PA but augmented contraction in the newborn and adult. The influence of both ontogeny and LTH on RyR-dependent cell excitability shed new light on the therapeutic potential of these channels for the treatment of pulmonary vascular disease in newborns as well as adults. PMID:22962012

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

    PubMed

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

    2015-01-01

    From the advent of the highly effective antiretroviral treatment, the life expectancy of patients with human immunodeficiency virus has increased significantly. At present, the causes of death are non-infectious complications. Between them, the pulmonary arterial hypertension has a special importance. It is important early detection to establish the therapeutic, with the objective of preventing a fatal outcome to future. Copyright © 2013 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

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

    PubMed

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

    2013-12-24

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

  1. Liquid breathing - Prevention of pulmonary arterial-venous shunting during acceleration.

    NASA Technical Reports Server (NTRS)

    Sass, D. J.; Ritman, E. L.; Caskey, P. E.; Banchero, N.; Wood, E. H.

    1972-01-01

    Dependent pulmonary atelectasis, arterial-venous shunting, and downward displacement of the heart caused by the gravitational-inertial force environment were prevented in dogs breathing oxygenated liquid fluorocarbon in a whole-body water-immersion respirator. Partial closure of the major airways during part of the expiratory phase of liquid respiration was a significant problem initially but was minimized in subsequent studies.

  2. [Supervised exercise training in patients with pulmonary arterial hypertension - analyses of the effectiveness and safety].

    PubMed

    Saxer, S; Rhyner, M; Treder, U; Speich, R; van Gestel, A J R

    2012-02-01

    Both in today's scientific research and in clinical practice, there exists a need to address the uncertainty concerning the effectiveness and safety of cardiopulmonary exercise training (CPET) in patients with pulmonary arterial hypertension (PAH). It is commonly believed that CPET may be dangerous for patients with PAH, because increasing pressure on the pulmonary arteries may worsen right-sided heart failure. Recently, the first clinical trials on exercise training in patients with pulmonary hypertension reported promising results. Extension of the walking distance at the 6-minute walk test improved quality of life, endurance capacity and a reduction in symptoms were observed after CPET. Furthermore, CPET was well tolerated by the patients in five clinical trials. In conclusion, it may be postulated that CPET is an effective therapy in patients with PAH and was tendentially well tolerated by the patients.

  3. Current Approaches to the Treatment of Systemic-Sclerosis-Associated Pulmonary Arterial Hypertension (SSc-PAH).

    PubMed

    Sobanski, Vincent; Launay, David; Hachulla, Eric; Humbert, Marc

    2016-02-01

    Pulmonary arterial hypertension (PAH) is a severe condition causing significant morbidity and mortality in patients with systemic sclerosis (SSc). Despite the use of specific treatments, SSc-PAH survival remains poorer than in idiopathic PAH (IPAH). Recent therapeutic advances in PAH show a lower magnitude of response in SSc-PAH and a higher risk of adverse events, as compared to IPAH. The multifaceted underlying mechanisms and the multisystem nature of SSc probably explain part of the worse outcomes in SSc-PAH compared to IPAH. This review describes the current management of SSc-PAH with an emphasis on the impact of the different organ involvements in the prognosis and treatment response. An earlier detection of PAH and a better characterization of the clinical phenotypes of SSc-PAH are warranted in clinical practice and future trials. Determinants of prognosis, surrogate markers of clinical improvement or worsening, and relevance of the common endpoints used in clinical trials should be evaluated in this specific population. A multidisciplinary approach in expert referral centers is mandatory for SSc-PAH management.

  4. The Genetics of Pulmonary Arterial Hypertension

    PubMed Central

    Austin, Eric D.; Loyd, James E.

    2014-01-01

    Pulmonary arterial hypertension (PAH) is a progressive and fatal disease for which there is an ever-expanding body of genetic and related pathophysiological information on disease pathogenesis. A number of germline gene mutations have now been described, including mutations in the gene coding bone morphogenic protein receptor type 2 (BMPR2) and related genes. Recent advanced gene sequencing methods have facilitated the discovery of additional genes with mutations among those with and without familial forms of PAH (CAV1, KCNK3, EIF2AK4). The reduced penetrance, variable expressivity, and female predominance of PAH suggest that genetic, genomic and other factors modify disease expression. These multi-faceted variations are an active area of investigation in the field, including but not limited to common genetic variants and epigenetic processes, and may provide novel opportunities for pharmacologic intervention in the near future. They also highlight the need for a systems-oriented multi-level approach to incorporate the multitude of biologic variations now associated with PAH. Ultimately, improved understanding provides the opportunity for improved patient and family counseling about this devastating disease, but do require in depth understanding of the genetic factors relevant to PAH. PMID:24951767

  5. Dysfunctional BMPR2 signaling drives an abnormal endothelial requirement for glutamine in pulmonary arterial hypertension.

    PubMed

    Egnatchik, Robert A; Brittain, Evan L; Shah, Amy T; Fares, Wassim H; Ford, H James; Monahan, Ken; Kang, Christie J; Kocurek, Emily G; Zhu, Shijun; Luong, Thong; Nguyen, Thuy T; Hysinger, Erik; Austin, Eric D; Skala, Melissa C; Young, Jamey D; Roberts, L Jackson; Hemnes, Anna R; West, James; Fessel, Joshua P

    2017-03-01

    Pulmonary arterial hypertension (PAH) is increasingly recognized as a systemic disease driven by alteration in the normal functioning of multiple metabolic pathways affecting all of the major carbon substrates, including amino acids. We found that human pulmonary hypertension patients (WHO Group I, PAH) exhibit systemic and pulmonary-specific alterations in glutamine metabolism, with the diseased pulmonary vasculature taking up significantly more glutamine than that of controls. Using cell culture models and transgenic mice expressing PAH-causing BMPR2 mutations, we found that the pulmonary endothelium in PAH shunts significantly more glutamine carbon into the tricarboxylic acid (TCA) cycle than wild-type endothelium. Increased glutamine metabolism through the TCA cycle is required by the endothelium in PAH to survive, to sustain normal energetics, and to manifest the hyperproliferative phenotype characteristic of disease. The strict requirement for glutamine is driven by loss of sirtuin-3 (SIRT3) activity through covalent modification by reactive products of lipid peroxidation. Using 2-hydroxybenzylamine, a scavenger of reactive lipid peroxidation products, we were able to preserve SIRT3 function, to normalize glutamine metabolism, and to prevent the development of PAH in BMPR2 mutant mice. In PAH, targeting glutamine metabolism and the mechanisms that underlie glutamine-driven metabolic reprogramming represent a viable novel avenue for the development of potentially disease-modifying therapeutics that could be rapidly translated to human studies.

  6. Rare Anomalous Origin of Superior Left Pulmonary Artery from Left Subclavian Vein

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

    Lv, Tian-shi, E-mail: TerrenceLv@126.com; Wang, Chao, E-mail: wangchaoxs@163.com; Song, Li, E-mail: song9981@163.com

    2013-10-15

    We report for the first time an extremely rare anomalous origin of the superior left pulmonary artery in a 60 year-old man. Although it was occult in clinical indications, such a malformation still ought to be considered, especially during endovascular procedures.

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

    PubMed

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

    2014-01-01

    Inhaled iloprost is a drug from the group of prostacyclins used in the treatment of pulmonary arterial hypertension. Its efficacy and safety have allowed its use as monotherapy and combination therapy. This review describes the product characteristics, amenable to treatment groups, and updated clinical evidence of drug use. Copyright © 2013 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  8. Non-invasive estimation of pulmonary artery pressures in patients with sickle cell anaemia in Ibadan, Nigeria: an echocardiographic study.

    PubMed

    Enakpene, Evbu O; Adebiyi, Adewole A; Ogah, Okechukwu S; Olaniyi, John A; Aje, Akinyemi; Adeoye, Moshood A; Falase, Ayodele O

    2014-10-01

    Pulmonary hypertension is emerging as one of the causes of morbidity and mortality in adults with sickle cell disease. The prevalence of pulmonary hypertension in Nigerian adults with sickle cell anaemia is unknown. We decided to estimate the pulmonary artery systolic and diastolic pressures in subjects with sickle cell anaemia seen at the University College Hospital, Ibadan, Nigeria, and to determine the frequency of pulmonary hypertension among them. Ninety patients (38 males and 52 females) with sickle cell anaemia in steady state and comparable age- and sex-matched normal controls had a clinical evaluation and echocardiographic examination. The mean age of the subjects with sickle cell anaemia was 24.0 (9.00) years while the mean age for the control group was 24.0 (7.00) years. The frequency of pulmonary hypertension as assessed by a tricuspid regurgitant jet velocity of > 2.5 m/s in this study was 12.2%. Larger left ventricular dimensions and volumes, higher stroke volume and increased left ventricular mass indexed by body surface area were found to be associated with pulmonary hypertension. A multivariate analysis of the potential predictors of pulmonary hypertension in this study showed that male sex and lower packed cell volume (PCV) were independent predictors of pulmonary hypertension in patients with sickle cell anaemia. We conclude that pulmonary artery systolic and diastolic pressures are higher in subjects with sickle cell disease than normal controls. Male sex and low PCV are independent determinants of pulmonary arterial pressure in subjects with sickle cell anaemia in Nigeria.

  9. Right Heart End-Systolic Remodeling Index Strongly Predicts Outcomes in Pulmonary Arterial Hypertension: Comparison With Validated Models.

    PubMed

    Amsallem, Myriam; Sweatt, Andrew J; Aymami, Marie C; Kuznetsova, Tatiana; Selej, Mona; Lu, HongQuan; Mercier, Olaf; Fadel, Elie; Schnittger, Ingela; McConnell, Michael V; Rabinovitch, Marlene; Zamanian, Roham T; Haddad, Francois

    2017-06-01

    Right ventricular (RV) end-systolic dimensions provide information on both size and function. We investigated whether an internally scaled index of end-systolic dimension is incremental to well-validated prognostic scores in pulmonary arterial hypertension. From 2005 to 2014, 228 patients with pulmonary arterial hypertension were prospectively enrolled. RV end-systolic remodeling index (RVESRI) was defined by lateral length divided by septal height. The incremental values of RV free wall longitudinal strain and RVESRI to risk scores were determined. Mean age was 49±14 years, 78% were female, 33% had connective tissue disease, 52% were in New York Heart Association class ≥III, and mean pulmonary vascular resistance was 11.2±6.4 WU. RVESRI and right atrial area were strongly connected to the other right heart metrics. Three zones of adaptation (adapted, maladapted, and severely maladapted) were identified based on the RVESRI to RV systolic pressure relationship. During a mean follow-up of 3.9±2.4 years, the primary end point of death, transplant, or admission for heart failure was reached in 88 patients. RVESRI was incremental to risk prediction scores in pulmonary arterial hypertension, including the Registry to Evaluate Early and Long-Term PAH Disease Management score, the Pulmonary Hypertension Connection equation, and the Mayo Clinic model. Using multivariable analysis, New York Heart Association class III/IV, RVESRI, and log NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) were retained (χ 2 , 62.2; P <0.0001). Changes in RVESRI at 1 year (n=203) were predictive of outcome; patients initiated on prostanoid therapy showed the greatest improvement in RVESRI. Among right heart metrics, RVESRI demonstrated the best test-retest characteristics. RVESRI is a simple reproducible prognostic marker in patients with pulmonary arterial hypertension. © 2017 American Heart Association, Inc.

  10. Interventional and surgical therapeutic strategies for pulmonary arterial hypertension: Beyond palliative treatments.

    PubMed

    Sandoval, Julio; Gomez-Arroyo, Jose; Gaspar, Jorge; Pulido-Zamudio, Tomas

    2015-10-01

    Despite significant advances in pharmacological treatments, pulmonary arterial hypertension remains an incurable disease with an unreasonably high morbidity and mortality. Although specific pharmacotherapies have shifted the survival curves of patients and improved exercise endurance as well as quality of life, it is also true that these pharmacological interventions are not always accessible (particularly in developing countries) and, perhaps most importantly, not all patients respond similarly to these drugs. Furthermore, many patients will continue to deteriorate and will eventually require an additional, non-pharmacological, intervention. In this review we analyze the role of atrial septostomy and Potts anastomosis in the management of patients with pulmonary arterial hypertension, we summarize the current worldwide clinical experience (case reports and case series), and discuss why these interventional/surgical strategies might have a therapeutic role beyond that of a "bridge" to transplantation. Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  11. Pulmonary arterial hypertension associated with chronic active Epstein-Barr virus infection.

    PubMed

    Fukuda, Yutaka; Momoi, Nobuo; Akaihata, Mitsuko; Nagasawa, Katsutoshi; Mitomo, Masaki; Aoyagi, Yoshimichi; Endoh, Kisei; Hosoya, Mitsuaki

    2015-08-01

    Chronic active Epstein-Barr virus (EBV) infection (CAEBV), characterized by persistent infectious mononucleosis-like symptoms, can lead to cardiovascular complications including coronary artery aneurysm or myocarditis. Here, we present the case of an 11-year-old boy with pulmonary arterial hypertension (PAH) and junctional ectopic tachycardia associated with CAEBV. The patient did not have any major symptoms attributed to CAEBV, such as fever, lymphadenopathy or splenomegaly when the PAH developed. Mild liver dysfunction was found at the first examination, and it persisted. Two years after the PAH symptoms appeared, CAEBV was evident, based on deteriorated liver function, hepatosplenomegaly, and coronary artery aneurysms. CAEBV should be considered as a cause of secondary PAH, particularly when liver dysfunction coexists. © 2015 Japan Pediatric Society.

  12. Right ventricular to pulmonary artery conduit instead of modified Blalock-Taussig shunt improves postoperative hemodynamics in newborns after the Norwood operation.

    PubMed

    Mair, Rudolf; Tulzer, Gerald; Sames, Eva; Gitter, Roland; Lechner, Evelyn; Steiner, Jürgen; Hofer, Anna; Geiselseder, Gertraud; Gross, Christoph

    2003-11-01

    Perioperative mortality, prolonged postoperative recovery after the Norwood procedure, and mortality between stage I and stage II might be related to shunt physiology. A right ventricular to pulmonary artery conduit offers a banded physiology in contrast to a Blalock-Taussig shunt. The purpose of this study was to assess the hemodynamic differences and their consequences in the postoperative course between Norwood patients with a Blalock-Taussig shunt and those with a right ventricular to pulmonary artery conduit. From October 1999 until May 2002, 32 unselected consecutive patients underwent a Norwood procedure at the General Hospital Linz. The first 18 patients received a Blalock-Taussig shunt. In the remaining 14 patients we performed a right ventricular to pulmonary artery conduit. Both groups were compared. The diastolic blood pressure was significantly higher in the right ventricular to pulmonary artery conduit group (P <.001). Despite a higher FIO(2), PO(2) levels tended to be lower in the first 5 postoperative days. At the age of 3 months, catheterization laboratory data showed a lower Qp/Qs ratio in the same group (0.86 [0.78; 1] versus 1.55 [1.15; 1.6]; P =.005) and a higher dp/dt (955 [773; 1110] vs 776 [615; 907]; P =.018). (Descriptive data reflect medians and quartiles [in brackets].) Hospital survival was 72% in the Blalock-Taussig shunt group versus 93% in the right ventricular to pulmonary artery conduit group. Mortality between stage I and stage II was 23% in the Blalock-Taussig shunt group versus 0% in the right ventricular to pulmonary artery conduit group. A higher diastolic blood pressure and a lower Qp/Qs ratio were associated with a more stable and efficient circulation in patients with a right ventricular to pulmonary artery conduit. More intensive ventilatory support was necessary during the first postoperative days. We did not note any adverse effects of the ventriculotomy on ventricular performance.

  13. Two congenital coronary abnormalities affecting heart function: anomalous origin of the left coronary artery from the pulmonary artery and congenital left main coronary artery atresia.

    PubMed

    Xiao, Yanyan; Jin, Mei; Han, Ling; Ding, Wenhong; Zheng, Jianyong; Sun, Chufan; Lyu, Zhenyu

    2014-01-01

    The anomalous origin of the left coronary artery (LCA) from the pulmonary artery (ALCAPA) and congenital left main coronary artery atresia (CLMCA-A) are two kinds of very rare coronary heart diseases which affect heart function profoundly. This study aimed to retrospectively illustrate the clinical features and therapy experience of ALCAPA and CLMCA-A patients. From April 1984 to July 2012, in Beijing Anzhen Hospital, 23 patients were diagnosed with ALCAPA and 4 patients with CLMCA-A. We summarized the clinical data of the 27 cases and retrospectively analyzed the clinical manifestation, diagnosis, and treatments of these two kinds of congenital coronary abnormalities. The 23 patients (13 males and 10 females, aged ranging from 2.5 months to 65 years) identified with ALCAPA were classified into infantile type (age of onset younger than 12 months, 16 cases) and adult type (age of onset older than 12 months, 7 cases). Four patients were diagnosed with CLMCA-A (three males and one female, aged ranging from 3 months to 2 years). The main clinical manifestations of infantile-type ALCAPA and CLMCA-A include repeated respiratory tract infection, heart failure, dyspnea, feeding intolerance, diaphoresis, and failure to thrive. And these two congenital coronary abnormalities might be misdiagnosed as endocardial fibroelastosis, dilated cardiomyopathy, and acute myocardial infarction. As for the adult-type ALCAPA, cardiac murmurs and discomfort of the precordial area are the most common presentations and might be misdiagnosed as coronary heart disease, myocarditis, or patent ductus arteriosus. In ECG examination: Infantile-type ALCAPA and CLMCA-A showed abnormal Q waves with T wave inversion in leads I, avL, and V4-V6, especially in lead avL. However, ECG of adult-type ALCAPA lacked distinct features. In chest radiography: pulmonary congestion and cardiomegaly were the most common findings in infantile-type ALCAPA and CLMCA-A, while pulmonary artery segment dilation was more

  14. A four-tier classification system of pulmonary artery metrics on computed tomography for the diagnosis and prognosis of pulmonary hypertension.

    PubMed

    Truong, Quynh A; Bhatia, Harpreet Singh; Szymonifka, Jackie; Zhou, Qing; Lavender, Zachary; Waxman, Aaron B; Semigran, Marc J; Malhotra, Rajeev

    We aimed to develop a severity classification system of the main pulmonary artery diameter (mPA) and its ratio to the ascending aorta diameter (ratio PA) for the diagnosis and prognosis of pulmonary hypertension (PH) on computed tomography (CT) scans. In 228 patients (136 with PH) undergoing right heart catheterization (RHC) and CT for dyspnea, we measured mPA and ratio PA. In a derivation cohort (n = 114), we determined cutpoints for a four-tier severity grading system that would maximize sensitivity and specificity, and validated it in a separate cohort (n = 114). Cutpoints for mPA were defined with ≤27 mm(F) and ≤29 mm(M) as the normal reference range; mild as >27 to <31 mm(F) and >29 to <31 mm(M); moderate≥31-34 mm; and severe>34 mm. Cutpoints for ratio PA were defined as normal ≤0.9; mild>0.9 to 1.0; moderate>1.0 to 1.1; and severe>1.1. Sensitivities for normal tier were 99% for mPA and 93% for ratio PA; while specificities for severe tier were 98% for mPA>34 mm and 100% for ratio PA>1.1. C-statistics for four-tier mPA and ratio PA were both 0.90 (derivation) and both 0.85 (validation). Severity of mPA and ratio PA corresponded to hemodynamics by RHC and echocardiography (both p < 0.001). Moderate-severe mPA values of ≥31 mm and ratio PA>1.1 had worse survival than normal values (all p ≤ 0.01). A CT-based four-tier severity classification system of PA diameter and its ratio to the aortic diameter has high accuracy for PH diagnosis with increased mortality in patients with moderate-severe severity grades. These results may support clinical utilization on chest and cardiac CT reports. Copyright © 2018 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

  15. A Novel Therapeutic Approach in the Treatment of Pulmonary Arterial Hypertension: Allium ursinum Liophylisate Alleviates Symptoms Comparably to Sildenafil

    PubMed Central

    Bombicz, Mariann; Priksz, Daniel; Varga, Balazs; Kurucz, Andrea; Kertész, Attila; Takacs, Akos; Posa, Aniko; Kiss, Rita; Szilvassy, Zoltan; Juhasz, Bela

    2017-01-01

    Right-sided heart failure—often caused by elevated pulmonary arterial pressure—is a chronic and progressive condition with particularly high mortality rates. Recent studies and our current findings suggest that components of Wild garlic (Allium ursinum, AU) may play a role in reducing blood pressure, inhibiting angiotensin-converting enzyme (ACE), as well as improving right ventricle function in rabbit models with heart failure. We hypothesize that AU may mitigate cardiovascular damage caused by pulmonary arterial hypertension (PAH) and has value in the supplementary treatment of the complications of the disease. In this present investigation, PAH was induced by a single dose of monocrotaline (MCT) injection in Sprague-Dawley rats, and animals were divided into 4 treatment groups as follows: I. healthy control animals (Control group); II. pulmonary hypertensive rats (PAH group); III. pulmonary hypertensive rats + daily sildenafil treatment (Sildenafil group); and IV. pulmonary hypertensive rats + Wild garlic liophylisate-enriched chow (WGLL group), for 8 weeks. Echocardiographic measurements were obtained on the 0 and 8 weeks with fundamental and Doppler imaging. Isolated working heart method was used to determinate cardiac functions ex vivo after thoracotomy on the 8th week. Histological analyses were carried out on excised lung samples, and Western blot technique was used to determine Phosphodiesterase type 5 enzyme (PDE5) expression in both myocardial and pulmonary tissues. Our data demonstrate that right ventricle function measured by echocardiography was deteriorated in PAH animals compared to controls, which was counteracted by AU treatment. Isolated working heart measurements showed elevated aortic flow in WGLL group compared to PAH animals. Histological analysis revealed dramatic increase in medial wall thickness of pulmonary arteries harvested from PAH animals, but arteries of animals in sildenafil- and WGLL-treated groups showed physiological status

  16. Differential sensitivities of pulmonary and coronary arteries to hemoglobin-based oxygen carriers and nitrovasodilators: study in a bovine ex vivo model of vascular strips.

    PubMed

    Fonseca, Vera; Avizinis, Jessica; Moon-Massat, Paula; Freilich, Daniel; Kim, Hae Won; Hai, Chi-Ming

    2010-01-01

    Vasoconstriction is a major adverse effect of first and second generation hemoglobin-based oxygen carriers (HBOCs) that hinders their development as blood substitute. However, intravenous infusion of HBOC-201 (second generation) to patients induces significant pulmonary hypertension without significant coronary vasoconstriction. We compared contractile responses of isolated bovine pulmonary and coronary arterial strips to HBOC-201 and HBOC-205LL.LT.MW600 (third generation), polymerized bovine hemoglobins of different molecular weight, and their attenuation by nitroglycerin, sodium nitroprusside (SNP), and sodium nitrite. Pulmonary arteries developed negligible basal tone, but exhibited HBOC-dependent amplification of phenylephrine-induced contractions. In contrast, coronary arteries developed significant basal tone, and exhibited HBOC-dependent constant force increment to serotonin-induced contractions. Therefore, relative to basal tone, HBOC-induced contractions were greater in pulmonary than coronary arteries. Furthermore, HBOC-205LL.LT.MW600 appeared to be less vasoactive than HBOC-201. Unexpectedly, pulmonary and coronary arteries exhibited differential sensitivities to nitrovasodilators in parallel with their differential sensitivities to HBOC. However, SNP and sodium nitrite induced significant methemoglobin formation from HBOC, whereas nitroglycerin did not. These results suggest that phenotypic differences between pulmonary and coronary vascular smooth muscle cells could explain the differential hypertensive effects of HBOC on pulmonary and coronary circulation in patients. Among the three nitrovasodilators investigated, nitroglycerin appears to be the most promising candidate for attenuating HBOC-induced pulmonary hypertension in older HBOCs.

  17. Asthma causes inflammation of human pulmonary arteries and decreases vasodilatation induced by prostaglandin I2 analogs.

    PubMed

    Foudi, Nabil; Badi, Aouatef; Amrane, Mounira; Hodroj, Wassim

    2017-12-01

    Asthma is a chronic inflammatory disease associated with increased cardiovascular events. This study assesses the presence of inflammation and the vascular reactivity of pulmonary arteries in patients with acute asthma. Rings of human pulmonary arteries obtained from non-asthmatic and asthmatic patients were set up in organ bath for vascular tone monitoring. Reactivity was induced by vasoconstrictor and vasodilator agents. Protein expression of inflammatory markers was detected by western blot. Prostanoid releases and cyclic adenosine monophosphate (cAMP) levels were quantified using specific enzymatic kits. Protein expression of cluster of differentiation 68, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and cyclooxygenase-2 was significantly increased in arteries obtained from asthmatic patients. These effects were accompanied by an alteration of vasodilatation induced by iloprost and treprostinil, a decrease in cAMP levels and an increase in prostaglandin (PG) E 2 and PGI 2 synthesis. The use of forskolin (50 µmol/L) has restored the vasodilatation and cAMP release. No difference was observed between the two groups in reactivity induced by norepinephrine, angiotensin II, PGE 2 , KCl, sodium nitroprusside, and acetylcholine. Acute asthma causes inflammation of pulmonary arteries and decreases vasodilation induced by PGI 2 analogs through the impairment of cAMP pathway.

  18. Impact of Pre-Stage II Hemodynamics and Pulmonary Artery Anatomy on 12-Month Outcome in the Single Ventricle Reconstruction Trial

    PubMed Central

    Aiyagari, Ranjit; Rhodes, John F.; Shrader, Peter; Radtke, Wolfgang A.; Bandisode, Varsha M.; Bergersen, Lisa; Gillespie, Matthew J.; Gray, Robert G.; Guey, Lin T.; Hill, Kevin D.; Hirsch, Russel; Kim, Dennis W.; Lee, Kyong-Jin; Pelech, Andrew N.; Ringewald, Jeremy; Takao, Cheryl; Vincent, Julie A.; Ohye, Richard G.

    2014-01-01

    Objective To compare interstage cardiac catheterization hemodynamic and angiographic findings between shunt types for Single Ventricle Reconstruction (SVR) trial. Background The SVR trial, which randomized subjects to modified Blalock-Taussig shunt (MBTS) or right ventricle-to-pulmonary artery shunt (RVPAS) for the Norwood procedure, demonstrated RVPAS was associated with smaller pulmonary artery diameter, but superior 12-month transplant-free survival. Methods We analyzed pre-stage II catheterization data for SVR trial subjects. Hemodynamic variables and shunt and pulmonary angiography were compared between shunt types; their association with 12-month transplant-free survival was also evaluated. Results Of 549 randomized subjects, 389 underwent pre-stage II catheterization. Smaller size, lower aortic and superior vena cava saturation, and higher ventricular end-diastolic pressure (EDP) were associated with worse 12-month transplant-free survival. MBTS subjects had lower coronary perfusion pressure (27mmHg vs. 32mmHg, P<0.001) and higher Qp:Qs ratio (1.1 vs. 1.0, P=0.009). Higher Qp:Qs ratio increased the risk of death or transplant only in the RVPAS group (P=0.01). MBTS subjects had fewer shunt (14% vs. 28%, P=0.004) and severe left pulmonary artery stenoses (0.7% vs. 9.2%, P=0.003), larger mid-main branch pulmonary artery diameters and higher Nakata index (164 vs. 134, P<0.001). Conclusions Compared with RVPAS subjects, MBTS subjects had more hemodynamic abnormalities related to shunt physiology, while RVPAS subjects had more shunt or pulmonary obstruction of a severe degree, and inferior pulmonary artery growth at pre-stage II catheterization. Lower BSA, higher ventricular EDP, and lower SVC saturation were associated with worse 12-month transplant-free survival. PMID:24332668

  19. Surgical treatment for the aberrant internal carotid artery in the middle ear with pulsatile tinnitus.

    PubMed

    Honkura, Yohei; Hidaka, Hiroshi; Ohta, Jun; Gorai, Shigeki; Katori, Yukio; Kobayashi, Toshimitsu

    2014-04-01

    Many previous reports have indicated that pulsatile tinnitus caused by an aberrant internal carotid artery (ICA) should not be treated surgically because of the risk of infection or aneurysm formation. We herein describe a case of aberrant ICA treated by middle ear surgery for which we introduced a novel approach. An 84-year-old man was presented with a one-year history of tinnitus in his right ear. Otoscopic examination demonstrated a whitish mass in the antero-inferior quadrant of the tympanic membrane associated with rhythmic pulsation. Images obtained by CT, MRI and MRA revealed protrusion of the ICA into the tympanic cavity, making contact with the tympanic membrane. Surgery to separate the tympanic membrane from the ICA was performed in order to relieve the pulsatile tinnitus. After the operation, the patient's aural activity was preserved and the tinnitus did not recur within a follow-up period of one year. In the present case, delicate middle ear surgery was effective for relief of the tinnitus. When treating patients with aberrant IAC showing features similar to the present case, the surgical approach we have described is worth attempting. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. Septic pulmonary arteriovenous fistula. An unusual conduit for systemic embolization in right-sided valvular endocarditis.

    PubMed

    Stagaman, D J; Presti, C; Rees, C; Miller, D D

    1990-06-01

    Right-sided valvular (tricuspid, pulmonic) endocarditis is frequently complicated by septic pulmonary embolization. Systemic embolization may also rarely occur due to associated left-sided endocarditis or right-to-left shunting in patients with septal defects. This report documents the occurrence of systemic embolization causing a cerebrovascular accident in an intravenous drug abuser with recurrent tricuspid valve endocarditis due to an isolated peripheral septic pulmonary arteriovenous fistula. Noninvasive diagnosis of the fistula by cardiac auscultation, contrast echocardiography, and nuclear magnetic resonance imaging was confirmed by selective pulmonary angiography. Subselective balloon embolization of the pulmonary arteries feeding this fistula was accomplished.

  1. Adenosine monophosphate-activated protein kinase is required for pulmonary artery smooth muscle cell survival and the development of hypoxic pulmonary hypertension.

    PubMed

    Ibe, Joyce Christina F; Zhou, Qiyuan; Chen, Tianji; Tang, Haiyang; Yuan, Jason X-J; Raj, J Usha; Zhou, Guofei

    2013-10-01

    Human pulmonary artery smooth muscle cells (HPASMCs) express both adenosine monophosphate-activated protein kinase (AMPK) α1 and α2. We investigated the distinct roles of AMPK α1 and α2 in the survival of HPASMCs during hypoxia and hypoxia-induced pulmonary hypertension (PH). The exposure of HPASMCs to hypoxia (3% O2) increased AMPK activation and phosphorylation, and the inhibition of AMPK with Compound C during hypoxia decreased their viability and increased lactate dehydrogenase activity and apoptosis. Although the suppression of either AMPK α1 or α2 expression led to increased cell death, the suppression of AMPK α2 alone increased caspase-3 activity and apoptosis in HPASMCs exposed to hypoxia. It also resulted in the decreased expression of myeloid cell leukemia sequence 1 (MCL-1). The knockdown of MCL-1 or MCL-1 inhibitors increased caspase-3 activity and apoptosis in HPASMCs exposed to hypoxia. On the other hand, the suppression of AMPK α1 expression alone prevented hypoxia-mediated autophagy. The inhibition of autophagy induced cell death in HPASMCs. Our results suggest that AMPK α1 and AMPK α2 play differential roles in the survival of HPASMCs during hypoxia. The activation of AMPK α2 maintains the expression of MCL-1 and prevents apoptosis, whereas the activation of AMPK α1 stimulates autophagy, promoting HPASMC survival. Moreover, treatment with Compound C, which inhibits both isoforms of AMPK, prevented and partly reversed hypoxia-induced PH in mice. Taking these results together, our study suggests that AMPK plays a key role in the pathogenesis of pulmonary arterial hypertension, and AMPK may represent a novel therapeutic target for the treatment of pulmonary arterial hypertension.

  2. Adenosine Monophosphate–Activated Protein Kinase Is Required for Pulmonary Artery Smooth Muscle Cell Survival and the Development of Hypoxic Pulmonary Hypertension

    PubMed Central

    Ibe, Joyce Christina F.; Zhou, Qiyuan; Chen, Tianji; Tang, Haiyang; Yuan, Jason X.-J.; Raj, J. Usha

    2013-01-01

    Human pulmonary artery smooth muscle cells (HPASMCs) express both adenosine monophosphate–activated protein kinase (AMPK) α1 and α2. We investigated the distinct roles of AMPK α1 and α2 in the survival of HPASMCs during hypoxia and hypoxia-induced pulmonary hypertension (PH). The exposure of HPASMCs to hypoxia (3% O2) increased AMPK activation and phosphorylation, and the inhibition of AMPK with Compound C during hypoxia decreased their viability and increased lactate dehydrogenase activity and apoptosis. Although the suppression of either AMPK α1 or α2 expression led to increased cell death, the suppression of AMPK α2 alone increased caspase-3 activity and apoptosis in HPASMCs exposed to hypoxia. It also resulted in the decreased expression of myeloid cell leukemia sequence 1 (MCL-1). The knockdown of MCL-1 or MCL-1 inhibitors increased caspase-3 activity and apoptosis in HPASMCs exposed to hypoxia. On the other hand, the suppression of AMPK α1 expression alone prevented hypoxia-mediated autophagy. The inhibition of autophagy induced cell death in HPASMCs. Our results suggest that AMPK α1 and AMPK α2 play differential roles in the survival of HPASMCs during hypoxia. The activation of AMPK α2 maintains the expression of MCL-1 and prevents apoptosis, whereas the activation of AMPK α1 stimulates autophagy, promoting HPASMC survival. Moreover, treatment with Compound C, which inhibits both isoforms of AMPK, prevented and partly reversed hypoxia-induced PH in mice. Taking these results together, our study suggests that AMPK plays a key role in the pathogenesis of pulmonary arterial hypertension, and AMPK may represent a novel therapeutic target for the treatment of pulmonary arterial hypertension. PMID:23668615

  3. Baseline Characteristics of the Korean Registry of Pulmonary Arterial Hypertension.

    PubMed

    Chung, Wook-Jin; Park, Yong Bum; Jeon, Chan Hong; Jung, Jo Won; Ko, Kwang-Phil; Choi, Sung Jae; Seo, Hye Sun; Lee, Jae Seung; Jung, Hae Ok

    2015-10-01

    Despite recent advances in understanding of the pathobiology and targeted treatments of pulmonary arterial hypertension (PAH), epidemiologic data from large populations have been limited to western countries. The aim of the Korean Registry of Pulmonary Arterial Hypertension (KORPAH) was to examine the epidemiology and prognosis of Korean patients with PAH. KORPAH was designed as a nationwide, multicenter, prospective data collection using an internet webserver from September 2008 to December 2011. A total of 625 patients were enrolled. The patients' mean age was 47.6 ± 15.7 yr, and 503 (80.5%) were women. The diagnostic methods included right heart catheterization (n = 249, 39.8%) and Doppler echocardiography (n = 376, 60.2%). The etiologies, in order of frequency, were connective tissue disease (CTD), congenital heart disease, and idiopathic PAH (IPAH) (49.8%, 25.4%, and 23.2%, respectively). Patients with WHO functional class III or IV at diagnosis were 43.4%. In total, 380 (60.8%) patients received a single PAH-specific treatment at the time of enrollment, but only 72 (18.9%) patients received combination therapy. Incident cases during the registry represented 297 patients; therefore, the incidence rate of PAH was 1.9 patients/yr/million people. The 1st-, 2nd-, and 3rd-yr estimated survival rates were 90.8%, 87.8%, and 84.4%, respectively. Although Korean PAH patients exhibited similar age, gender, and survival rate compared with western registries, they showed relatively more CTD-PAH in the etiology and also systemic lupus erythematosus among CTD-PAH. The data suggest that earlier diagnosis and more specialized therapies should be needed to improve the survival of PAH patients.

  4. 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.

  5. [Treatment of pulmonary arterial hypertension].

    PubMed

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

    2015-06-22

    Treatment of pulmonary arterial hypertension has achieved significant progress over the past 20 years. Currently, 3 groups of drugs have proven useful for the treatment of this disease: endothelin receptor antagonist, phosphodiesterase inhibitors and prostacyclin and its analogues. It is recommended to initiate treatment with one of these drugs, the choice depending on the initial severity of patient disease and the preferences of the treating physician. When the patient does not have a satisfactory response, new drugs acting at a different pathway are most commonly added. At this time, considering referral for lung transplantation could be an alternative. Most experts recommend grouping maximum experience in what is known as expert centers. Treatment has led to better survival in these patients, but there is still a long way to cure this life-threatening disease. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  6. Pulmonary MRA: differentiation of pulmonary embolism from truncation artefact.

    PubMed

    Bannas, Peter; Schiebler, Mark L; Motosugi, Utaroh; François, Christopher J; Reeder, Scott B; Nagle, Scott K

    2014-08-01

    Truncation artefact (Gibbs ringing) causes central signal drop within vessels in pulmonary magnetic resonance angiography (MRA) that can be mistaken for emboli, reducing diagnostic accuracy for pulmonary embolism (PE). We propose a quantitative approach to differentiate truncation artefact from PE. Twenty-eight patients who underwent pulmonary computed tomography angiography (CTA) for suspected PE were recruited for pulmonary MRA. Signal intensity drops within pulmonary arteries that persisted on both arterial-phase and delayed-phase MRA were identified. The percent signal loss between the vessel lumen and central drop was measured. CTA served as the reference standard for presence of pulmonary emboli. A total of 65 signal intensity drops were identified on MRA. Of these, 48 (74%) were artefacts and 17 (26%) were PE, as confirmed by CTA. Truncation artefacts had a significantly lower median signal drop than PE on both arterial-phase (26% [range 12-58%] vs. 85% [range 53-91%]) and delayed-phase MRA (26% [range 11-55%] vs. 77% [range 47-89%]), p < 0.0001 for both. Receiver operating characteristic (ROC) analyses revealed a threshold value of 51% (arterial phase) and 47% signal drop (delayed phase) to differentiate between truncation artefact and PE with 100% sensitivity and greater than 90% specificity. Quantitative signal drop is an objective tool to help differentiate truncation artefact and pulmonary embolism in pulmonary MRA. • Inexperienced readers may mistake truncation artefacts for emboli on pulmonary MRA • Pulmonary emboli have non-uniform signal drop • 51% (arterial phase) and 47% (delayed phase) cut-off differentiates truncation artefact from PE • Quantitative signal drop measurement enables more accurate pulmonary embolism diagnosis with MRA.

  7. Sixth-order wave aberration theory of ultrawide-angle optical systems.

    PubMed

    Lu, Lijun; Cao, Yiqing

    2017-10-20

    In this paper, we develop sixth-order wave aberration theory of ultrawide-angle optical systems like fisheye lenses. Based on the concept and approach to develop wave aberration theory of plane-symmetric optical systems, we first derive the sixth-order intrinsic wave aberrations and the fifth-order ray aberrations; second, we present a method to calculate the pupil aberration of such kind of optical systems to develop the extrinsic aberrations; third, the relation of aperture-ray coordinates between adjacent optical surfaces is fitted with the second-order polynomial to improve the calculation accuracy of the wave aberrations of a fisheye lens with a large acceptance aperture. Finally, the resultant aberration expressions are applied to calculate the aberrations of two design examples of fisheye lenses; the calculation results are compared with the ray-tracing ones with Zemax software to validate the aberration expressions.

  8. Oral therapies for pulmonary arterial hypertension: endothelin receptor antagonists and phosphodiesterase-5 inhibitors.

    PubMed

    Channick, Richard; Preston, Iona; Klinger, James R

    2013-12-01

    The development of orally active pulmonary vasodilators has been a major breakthrough in the treatment of pulmonary arterial hypertension (PAH). Orally active medications greatly enhanced patient access to PAH treatment and increased an interest in the diagnosis and treatment of this disease that still continues. Four different orally active drugs are currently available for the treatment of PAH and several more are undergoing evaluation. This article discusses the mechanisms by which endothelin receptor antagonists and phosphodiesterase-5 inhibitors mitigate pulmonary hypertensive responses, and reviews the most recent data concerning their efficacy and limitations in the treatment of PAH. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Liver hydatid cyst leading to bilateral pulmonary artery embolism and bilateral multiple pulmonar echinococcosis via inferior vena cava: report of a case.

    PubMed

    Bayaroğullari, Hanifi; Davran, Ramazan; Cavuş, Yeliz; Yetim, Tülin Durgun; Evirgen, Ömer

    2013-01-01

    Hydatid disease (HD) is a worldwide parasitic disease. Echinococcosis may involve many organs but affect most commonly liver and lungs. The location of echinococcal cysts inside pulmonary artery is extremely rare. Radiologic findings range from purely cystic lesions to a completely solid appearance. Hydatid cysts (HC) can be solitary or multiple and varies size. Pulmonary artery embolism of HC can be symptomatic or asymptomatic. When symptomatic, we see the chest pain, dyspnea, cough, hemoptysis and sometimes acute cor pulmonale or sudden death secondary to massive giant pulmonary artery embolism of HC. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Losartan attenuates chronic cigarette smoke exposure-induced pulmonary arterial hypertension in rats: possible involvement of angiotensin-converting enzyme-2.

    PubMed

    Han, Su-Xia; He, Guang-Ming; Wang, Tao; Chen, Lei; Ning, Yun-Ye; Luo, Feng; An, Jin; Yang, Ting; Dong, Jia-Jia; Liao, Zeng-Lin; Xu, Dan; Wen, Fu-Qiang

    2010-05-15

    Chronic cigarette smoking induces pulmonary arterial hypertension (PAH) by largely unknown mechanisms. Renin-angiotensin system (RAS) is known to function in the development of PAH. Losartan, a specific angiotensin II receptor antagonist, is a well-known antihypertensive drug with a potential role in regulating angiotensin-converting enzyme-2 (ACE2), a recently found regulator of RAS. To determine the effect of losartan on smoke-induced PAH and its possible mechanism, rats were daily exposed to cigarette smoke for 6months in the absence and in the presence of losartan. Elevated right ventricular systolic pressure (RVSP), thickened wall of pulmonary arteries with apparent medial hypertrophy along with increased angiotensin II (Ang II) and decreased ACE2 levels were observed in smoke-exposed-only rats. Losartan administration ameliorated pulmonary vascular remodeling, inhibited the smoke-induced RVSP and Ang II elevation and partially reversed the ACE2 decrease in rat lungs. In cultured primary pulmonary artery smooth muscle cells (PASMCs) from 3- and 6-month smoke-exposed rats, ACE2 levels were significantly lower than in those from the control rats. Moreover, PASMCs from 6-month exposed rats proliferated more rapidly than those from 3-month exposed or control rats, and cells grew even more rapidly in the presence of DX600, an ACE2 inhibitor. Consistent with the in vivo study, in vitro losartan pretreatment also inhibited cigarette smoke extract (CSE)-induced cell proliferation and ACE2 reduction in rat PASMCs. The results suggest that losartan may be therapeutically useful in the chronic smoking-induced pulmonary vascular remodeling and PAH and ACE2 may be involved as part of its mechanism. Our study might provide insight into the development of new therapeutic interventions for PAH smokers.

  11. Losartan attenuates chronic cigarette smoke exposure-induced pulmonary arterial hypertension in rats: Possible involvement of angiotensin-converting enzyme-2

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

    Han Suxia; He Guangming; Wang Tao

    Chronic cigarette smoking induces pulmonary arterial hypertension (PAH) by largely unknown mechanisms. Renin-angiotensin system (RAS) is known to function in the development of PAH. Losartan, a specific angiotensin II receptor antagonist, is a well-known antihypertensive drug with a potential role in regulating angiotensin-converting enzyme-2 (ACE2), a recently found regulator of RAS. To determine the effect of losartan on smoke-induced PAH and its possible mechanism, rats were daily exposed to cigarette smoke for 6 months in the absence and in the presence of losartan. Elevated right ventricular systolic pressure (RVSP), thickened wall of pulmonary arteries with apparent medial hypertrophy along withmore » increased angiotensin II (Ang II) and decreased ACE2 levels were observed in smoke-exposed-only rats. Losartan administration ameliorated pulmonary vascular remodeling, inhibited the smoke-induced RVSP and Ang II elevation and partially reversed the ACE2 decrease in rat lungs. In cultured primary pulmonary artery smooth muscle cells (PASMCs) from 3- and 6-month smoke-exposed rats, ACE2 levels were significantly lower than in those from the control rats. Moreover, PASMCs from 6-month exposed rats proliferated more rapidly than those from 3-month exposed or control rats, and cells grew even more rapidly in the presence of DX600, an ACE2 inhibitor. Consistent with the in vivo study, in vitro losartan pretreatment also inhibited cigarette smoke extract (CSE)-induced cell proliferation and ACE2 reduction in rat PASMCs. The results suggest that losartan may be therapeutically useful in the chronic smoking-induced pulmonary vascular remodeling and PAH and ACE2 may be involved as part of its mechanism. Our study might provide insight into the development of new therapeutic interventions for PAH smokers.« less

  12. Early detection and management of pulmonary arterial hypertension.

    PubMed

    Humbert, Marc; Gerry Coghlan, J; Khanna, Dinesh

    2012-12-01

    The long-term prognosis for patients with pulmonary arterial hypertension (PAH) remains poor, despite advances in treatment options that have been made in the past few decades. Recent evidence suggests that World Health Organization functional class I or II patients have significantly better long-term survival rates than patients in higher functional classes, thus providing a rationale for earlier diagnosis and treatment of PAH. However, early diagnosis is challenging and there is frequently a delay between symptom onset and diagnosis. Screening programmes play an important role in PAH detection and expert opinion favours echocardiographic screening of asymptomatic patients who may be predisposed to the development of PAH (i.e. those with systemic sclerosis or sickle cell disease), although current guidelines only recommend annual echocardiographic screening in symptomatic patients. This article reviews the currently available screening programmes, including their limitations, and describes alternative screening approaches that may identify more effectively those patients who require right heart catheterisation for a definitive PAH diagnosis.

  13. Is CT angiography of the pulmonary arteries indicated in patients with high clinical probability of pulmonary embolism?

    PubMed

    Martínez Montesinos, L; Plasencia Martínez, J M; García Santos, J M

    When a diagnostic test confirms clinical suspicion, the indicated treatment can be administered. A problem arises when the diagnostic test does not confirm the initially suspected diagnosis; when the suspicion is grounded in clinically validated predictive rules and is high, the problem is even worse. This situation arises in up to 40% of patients with high suspicion for acute pulmonary embolism, raising the question of whether CT angiography of the pulmonary arteries should be done systematically. This paper reviews the literature about this issue and lays out the best evidence about the relevant recommendations for patients with high clinical suspicion of acute pulmonary embolism and negative findings on CT angiography. It also explains the probabilistic concepts derived from Bayes' theorem that can be useful for ascertaining the most appropriate approach in these patients. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Pulmonary arterial hypertension associated with chronic active Epstein-Barr virus infection.

    PubMed

    Hashimoto, Takahiro; Sakata, Yasushi; Fukushima, Kentaro; Maeda, Tetsuo; Arita, Yoh; Shioyama, Wataru; Nakaoka, Yoshikazu; Hori, Yumiko; Morii, Eiichi; Aozasa, Katsuyuki; Kanakura, Yuzuru; Yamauchi-Takihara, Keiko; Komuro, Issei

    2011-01-01

    A 45-year-old man with chronic active Epstein-Barr virus (EBV) infection (CAEBV) with natural killer cell type developed pulmonary arterial hypertension (PAH). After chemotherapy, he showed marked depression of the EBV DNA genome in the peripheral blood, but PAH sustained. He died of heart failure due to PAH, and the histo-pathological examination revealed pulmonary vascular abnormalities without lung disease on autopsy. Although the EBV DNA genome and the infiltrating lymphocytes were not detected in the lung, his clinical course suggested that his PAH might be caused by CAEBV. This is the first reported case of PAH associated CAEBV in an adult.

  15. Zero-stress states of human pulmonary arteries and veins.

    PubMed

    Huang, W; Yen, R T

    1998-09-01

    The zero-stress states of the pulmonary arteries and veins from order 3 to order 9 were determined in six normal human lungs within 15 h postmortem. The zero-stress state of each vessel was obtained by cutting the vessel transversely into a series of short rings, then cutting each ring radially, which caused the ring to spring open into a sector. Each sector was characterized by its opening angle. The mean opening angle varied between 92 and 163 degrees in the arterial tree and between 89 and 128 degrees in the venous tree. There was a tendency for opening angles to increase as the sizes of the arteries and veins increased. We computed the residual strains based on the experimental measurements and estimated the residual stresses according to Hooke's law. We found that the inner wall of a vessel at the state in which the internal pressure, external pressure, and longitudinal stress are all zero was under compression and the outer wall was in tension, and that the magnitude of compressive stress was greater than the magnitude of tensile stress.

  16. Use of a Doppler pulmonary artery catheter for continuous measurement of right ventricular pump function and contractility during single lung transplantation.

    PubMed

    Heerdt, P M; Pond, C G; Kussman, M K; Triantafillou, A N

    1993-01-01

    Despite numerous technologic advances in intraoperative monitoring, the only methods routinely available for assessment of right ventricular function in lung transplant recipients are continuous measurement of right heart pressures and intermittent thermodilution determination of cardiac output and ejection fraction. Additional data may now be obtained with transesophageal echocardiography, although this technology is expensive and not widely available and requires diverting attention from a potentially unstable patient for data acquisition and analysis. Recently, a Doppler pulmonary artery catheter was introduced that measures beat-to-beat pulmonary artery blood flow-velocity, cross sectional area, and volume flow. Because of data indicating that acceleration of blood in the pulmonary artery (measured as the first derivative of either the velocity or flow waveform) is a sensitive indicator of right ventricular contractility, we have used waveforms obtained with the catheter for assessment of right ventricular pump function (stroke volume and peak pulmonary artery flow rate) and contractility in heart surgery patients. We report here our experience with this method in two patients undergoing left single lung transplantation.

  17. 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.

  18. Estimation of pulmonary artery pressure in patients with primary pulmonary hypertension by quantitative analysis of magnetic resonance images.

    PubMed

    Murray, T I; Boxt, L M; Katz, J; Reagan, K; Barst, R J

    1994-01-01

    The use of magnetic resonance (MR) images for estimating mean pulmonary artery pressure (PAP) was tested by comparing main pulmonary artery (MPA) and middescending thoracic aorta (AO) caliber in 12 patients with primary pulmonary hypertension (PPH) with measurements made in eight other patients who were observed for diseases other than heart disease (controls). The ratio MPA/AO and the ratios of vessel caliber normalized to body surface area (MPAI and AOI, respectively) were computed. The PAP was obtained in all PPH patients and compared with caliber measurements. The PPH MPA (3.6 +/- 0.8 cm) was significantly larger than the control MPA (2.9 +/- 0.3 cm, p = 0.02); the PPH MPAI (2.8 +/- 0.7 cm/M2) was significantly greater than the control MPA (1.7 +/- 0.2 cm/M2, p < 0.0001). Control AO (2.2 +/- 0.3 cm) was significantly greater than PPH AO (1.6 +/- 0.4 cm, p < 0.0001); there was no significant difference between control AOI (1.3 +/- 0.2 cm/M2) and PPH AOI (1.2 +/- 0.2 cm/M2, p = 0.25). The PPH MPA/AO (2.3 +/- 0.6) was significantly greater than the control MPA/AO (1.3 +/- 0.1, p < 0.0001); overlap between MPA in the two groups was eliminated by indexing values to AO caliber (MPA/AO). Among PPH patients there was strong correlation between PAP and MPA/AO (PAP = 24 x MPA/AO + 3.7, r = 0.7, p < 0.01). Increased MPA/AO denotes the presence of pulmonary hypertension and may be used to estimate PAP.

  19. Do pulmonary artery catheters cause or increase tricuspid or pulmonic valvular regurgitation?

    PubMed

    Sherman, S V; Wall, M H; Kennedy, D J; Brooker, R F; Butterworth, J

    2001-05-01

    There are few quantitative data on the extent or mechanism of pulmonary artery catheter (PAC)-induced valvular dysfunction. We hypothesized that PACs cause or worsen tricuspid and pulmonic valvular regurgitation, and tested this hypothesis by using transesophageal echocardiography. In 54 anesthetized adult patients, we measured color Doppler jet areas of tricuspid regurgitation (TR) in two planes (midesophageal [ME] 4-chamber and right ventricular inflow-outflow views) and pulmonic insufficiency (PI) in one plane (ME aortic valve long-axis view), both before and after we advanced a PAC into the pulmonary artery. Regurgitant jet areas and hemodynamic measurements were compared by using paired t-test. There were no significant changes in blood pressure or heart rate after passage of the PAC. After PAC placement, the mean PI jet area was not significantly increased. The mean TR jet area increased significantly in the right ventricular inflow-outflow view (+0.37 +/- 0.11 cm(2)) (P = 0.0014), but did not increase at the ME 4-chamber view. Seventeen percent of patients had an increase in TR jet area > or =1 cm(2); 8% of patients had an increase in PI jet area >/=1 cm(2). In patients without pulmonic or tricuspid valvular pathology, placement of a pulmonary artery catheter (PAC) worsened tricuspid regurgitation, which is consistently visualized in the right ventricular inflow-outflow view, and often not seen in the midesophageal 4-chamber view. This is consistent with malcoaptation of the anterior and posterior leaflets. PAC-induced pulmonic insufficiency was rarely detected in the midesophageal aortic valve long-axis view. We conclude that a PAC is very unlikely to be the sole cause of severe tricuspid regurgitation or pulmonic insufficiency.

  20. Right heart function during simulated altitude in patients with pulmonary arterial hypertension

    PubMed Central

    Seccombe, Leigh M; Chow, Vincent; Zhao, Wei; Lau, Edmund M T; Rogers, Peter G; Ng, Austin C C; Veitch, Elizabeth M; Peters, Matthew J; Kritharides, Leonard

    2017-01-01

    Objective Patients with pulmonary arterial hypertension (PAH) are often recommended supplemental oxygen for altitude travel due to the possible deleterious effects of hypoxia on pulmonary haemodynamics and right heart function. This includes commercial aircraft travel; however, the direct effects and potential risks are unknown. Methods Doppler echocardiography and gas exchange measures were investigated in group 1 patients with PAH and healthy patients at rest breathing room air and while breathing 15.1% oxygen, at rest for 20 min and during mild exertion. Results The 14 patients with PAH studied were clinically stable on PAH-specific therapy, with functional class II (n=11) and III (n=3) symptoms when tested. Measures of right ventricular size and function were significantly different in the PAH group at baseline as compared to 7 healthy patients (p<0.04). There was no evidence of progressive right ventricular deterioration during hypoxia at rest or under exertion. Pulmonary arterial systolic pressure (PASP) increased in both groups during hypoxia (p<0.01). PASP in hypoxia correlated strongly with baseline PASP (p<0.01). Pressure of arterial oxygen correlated with PASP in hypoxia (p<0.03) but not at baseline, with three patients with PAH experiencing significant desaturation. The duration and extent of hypoxia in this study was tolerated well despite a mild increase in symptoms of breathlessness (p<0.01). Conclusions Non-invasive measures of right heart function in group 1 patients with PAH on vasodilator treatment demonstrated a predictable rise in PASP during short-term simulated hypoxia that was not associated with a deterioration in right heart function. PMID:28123765

  1. Collagen Matrix Remodeling in Stented Pulmonary Arteries after Transapical Heart Valve Replacement.

    PubMed

    Ghazanfari, Samaneh; Driessen-Mol, Anita; Hoerstrup, Simon P; Baaijens, Frank P T; Bouten, Carlijn V C

    2016-01-01

    The use of valved stents for minimally invasive replacement of semilunar heart valves is expected to change the extracellular matrix and mechanical function of the native artery and may thus impair long-term functionality of the implant. Here we investigate the impact of the stent on matrix remodeling of the pulmonary artery in a sheep model, focusing on matrix composition and collagen (re)orientation of the host tissue. Ovine native pulmonary arteries were harvested 8 (n = 2), 16 (n = 4) and 24 (n = 2) weeks after transapical implantation of self-expandable stented heart valves. Second harmonic generation (SHG) microscopy was used to assess the collagen (re)orientation of fresh tissue samples. The collagen and elastin content was quantified using biochemical assays. SHG microscopy revealed regional differences in collagen organization in all explants. In the adventitial layer of the arterial wall far distal to the stent (considered as the control tissue), we observed wavy collagen fibers oriented in the circumferential direction. These circumferential fibers were more straightened in the adventitial layer located behind the stent. On the luminal side of the wall behind the stent, collagen fibers were aligned along the stent struts and randomly oriented between the struts. Immediately distal to the stent, however, fibers on both the luminal and the adventitial side of the wall were oriented in the axial direction, demonstrating the stent impact on the collagen structure of surrounding arterial tissues. Collagen orientation patterns did not change with implantation time, and biochemical analyses showed no changes in the trend of collagen and elastin content with implantation time or location of the vascular wall. We hypothesize that the collagen fibers on the adventitial side of the arterial wall and behind the stent straighten in response to the arterial stretch caused by oversizing of the stent. However, the collagen organization on the luminal side suggests that

  2. Dynamic contrast–enhanced magnetic resonance imaging in patients with pulmonary arterial hypertension

    PubMed Central

    Condliffe, Robin; Marshall, Helen; Elliot, Charlie; Kiely, David G.; Wild, Jim M.

    2014-01-01

    Abstract Dynamic contrast–enhanced (DCE) time-resolved magnetic resonance (MR) imaging is a technique whereby the passage of an intravenous contrast bolus can be tracked through the pulmonary vascular system. The aim of this study was to investigate the prognostic significance of DCE-MR pulmonary blood transit times in patients with pulmonary arterial hypertension (PAH). Seventy-nine patients diagnosed with PAH underwent pulmonary DCE imaging at 1.5 T using a time-resolved three-dimensional spoiled gradient echo sequence. The prognostic significance of two DCE parameters, full width at half maximum (FWHM) of the first-pass clearance curve and pulmonary transit time (PTT), along with demographic and invasive catheter measurements, was evaluated by univariate and bivariate Cox proportional hazards regression and Kaplan-Meier analysis. DCE-MR transit times were most closely correlated with cardiac index (CI) and pulmonary vascular resistance index (PVRI) and were both found to be accurate for detecting reduced CI (FWHM area under the curve [AUC] at receiver operating characteristic analysis = 0.91 and PTT AUC = 0.92, respectively) and for detecting elevated PVRI (FWHM AUC = 0.88 and PTT AUC = 0.84, respectively). During the follow-up period, 25 patients died. Patients with longer measurements of FWHM (P = 0.0014) and PTT (P = 0.004) were associated with poor outcome at Kaplan-Meier analysis, and both parameters were strong predictors of adverse outcome from Cox proportional hazards analysis (P = 0.013 and 0.010, respectively). At bivariate analysis, DCE measurements predicted mortality independent of age, gender, and World Health Organization functional class; however, invasive hemodynamic indexes CI, PVRI, and DCE measurements were not independent of one another. In conclusion, DCE-MR transit times predict mortality in patients with PAH and are closely associated with clinical gold standards CI and PVRI. PMID:25006422

  3. Dynamic contrast-enhanced magnetic resonance imaging in patients with pulmonary arterial hypertension.

    PubMed

    Swift, Andrew J; Telfer, Adam; Rajaram, Smitha; Condliffe, Robin; Marshall, Helen; Capener, Dave; Hurdman, Judith; Elliot, Charlie; Kiely, David G; Wild, Jim M

    2014-03-01

    Dynamic contrast-enhanced (DCE) time-resolved magnetic resonance (MR) imaging is a technique whereby the passage of an intravenous contrast bolus can be tracked through the pulmonary vascular system. The aim of this study was to investigate the prognostic significance of DCE-MR pulmonary blood transit times in patients with pulmonary arterial hypertension (PAH). Seventy-nine patients diagnosed with PAH underwent pulmonary DCE imaging at 1.5 T using a time-resolved three-dimensional spoiled gradient echo sequence. The prognostic significance of two DCE parameters, full width at half maximum (FWHM) of the first-pass clearance curve and pulmonary transit time (PTT), along with demographic and invasive catheter measurements, was evaluated by univariate and bivariate Cox proportional hazards regression and Kaplan-Meier analysis. DCE-MR transit times were most closely correlated with cardiac index (CI) and pulmonary vascular resistance index (PVRI) and were both found to be accurate for detecting reduced CI (FWHM area under the curve [AUC] at receiver operating characteristic analysis = 0.91 and PTT AUC = 0.92, respectively) and for detecting elevated PVRI (FWHM AUC = 0.88 and PTT AUC = 0.84, respectively). During the follow-up period, 25 patients died. Patients with longer measurements of FWHM (P = 0.0014) and PTT (P = 0.004) were associated with poor outcome at Kaplan-Meier analysis, and both parameters were strong predictors of adverse outcome from Cox proportional hazards analysis (P = 0.013 and 0.010, respectively). At bivariate analysis, DCE measurements predicted mortality independent of age, gender, and World Health Organization functional class; however, invasive hemodynamic indexes CI, PVRI, and DCE measurements were not independent of one another. In conclusion, DCE-MR transit times predict mortality in patients with PAH and are closely associated with clinical gold standards CI and PVRI.

  4. Stent Implantation for Malignant Pulmonary Artery Stenosis in a Metastasizing Non-Small Cell Bronchial Carcinoma

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

    Gutzeit, A., E-mail: andreas.gutzeit@ksw.c; Koch, S.; Meier, U. R.

    2008-07-15

    A 58-year-old patient with recently diagnosed non-small cell bronchial carcinoma was referred to us with increasing shortness of breath and orthopnea by her family practitioner. To exclude the possibility of a pulmonary embolism, contrast medium-enhanced angio-CT of the thorax was performed. This showed a large mediastinal tumor, which, on the one hand, infiltrated and occluded the left upper lobe bronchus and, on the other, constricted the left pulmonary artery over a considerable part of its length. In view of the palliative situation and massively increasing dyspnea, balloon dilatation of the obstructed left pulmonary artery followed by stent placement was performed.more » This resulted in an immediate improvement of the symptoms. The originally strongly oxygen-dependent and heavily dyspneic patient could be relieved of the external supply of oxygen and was able to sleep normally without additional medication within 24 h. The patient was able ambulate freely within 2 days, with a markedly improved quality of life.« less

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  7. 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

  8. Extending the use of the pacing pulmonary artery catheter for safe minimally invasive cardiac surgery.

    PubMed

    Levin, Ricardo; Leacche, Marzia; Petracek, Michael R; Deegan, Robert J; Eagle, Susan S; Thompson, Annemarie; Pretorius, Mias; Solenkova, Nataliya V; Umakanthan, Ramanan; Brewer, Zachary E; Byrne, John G

    2010-08-01

    In this study, the therapeutic use of pacing pulmonary artery catheters in association with minimally invasive cardiac surgery was evaluated. A retrospective study. A single institutional university hospital. Two hundred twenty-four consecutive patients undergoing minimally invasive cardiac surgery through a small (5-cm) right anterolateral thoracotomy using fibrillatory arrest without aortic cross-clamping. Two hundred eighteen patients underwent mitral valve surgery (97%) alone or in combination with other procedures. Six patients underwent other cardiac operations. In all patients, the pacing pulmonary artery catheter was used intraoperatively to induce ventricular fibrillation during the cooling period, and in the postoperative period it also was used in 37 (17%) patients who needed to be paced, mainly for bradyarrhythmias (51%). There were no complications related to the insertion of the catheters. Six (3%) patients experienced a loss of pacing capture, and 2 (1%) experienced another complication requiring the surgical removal of the catheter. Seven (3%) patients needed postoperative implantation of a permanent pacemaker. In combination with minimally invasive cardiac surgery, pacing pulmonary artery catheters were therapeutically useful to induce ventricular fibrillatory arrest intraoperatively and for obtaining pacing capability in the postoperative period. Their use was associated with a low number of complications. Copyright 2010 Elsevier Inc. All rights reserved.

  9. Measurement of pulmonary arterial elastance in patients with systolic heart failure using Doppler echocardiography

    PubMed Central

    Taghavi, Sepideh; Esmaeilzadeh, Maryam; Amin, Ahmad; Naderi, Nasim; Abkenar, Hooman Bakhshandeh; Maleki, Majid; Mitra, Chitsazan

    2016-01-01

    Objective: A reliable and easy-to-perform method for measuring right ventricular (RV) afterload is desirable when scheduling patients with systolic heart failure to undergo heart transplantation. The present study aimed to investigate the accuracy of echocardiographically-derived pulmonary arterial elastance as a measurement of pulmonary vascular resistance by comparing it with invasive measures. Methods: Thirty-one patients with moderate to severe systolic heart failure, including 22 (71%) male patients, with a mean age of 41.16±15.9 years were enrolled in the study. Right heart catheterization and comprehensive echocardiography during the first hour after completion of cardiac catheterization were performed in all the patients. The pulmonary artery elastance was estimated using the ratio of end-systolic pressure (Pes) over the stroke volume (SV) by both cardiac catheterization [Ea (PV)-C] and echocardiography [Ea (PV)-E]. Results: The mean Ea (PV)-C and Ea (PV)-E were estimated to be 0.73±0.49 mm Hg/mL and 0.67±0.44 mm Hg/mL, respectively. There was a significant relation between Ea (PV)-E and Ea (PV)-C (r=0.897, p<0.001). Agreement between echocardiography and catheterization methods for estimating Ea (PV), investigated by the Bland-Altman method, showed a mean bias of -0.06, with 95% limits of agreement from -0.36 mm Hg/mL to 0.48 mm Hg/mL. Conclusion: Doppler echocardiography is an easy, non-invasive, and inexpensive method for measuring pulmonary arterial elastance, which provides accurate and reliable estimation of RV afterload in patients with systolic heart failure. PMID:26467379

  10. Left atrium and pulmonary artery compression due to aortic aneurysm causing heart failure symptoms.

    PubMed

    Jorge, Antonio José Lagoeiro; Martins, Wolney de Andrade; Moutinho, Victor M; Rezende, Juliano M; Alves, Patricia Y; Villacorta, Humberto; Silveira, Pedro F; Couto, Antonio A

    2018-06-01

    Patients with thoracic aortic aneurysm (TAA) are mostly asymptomatic and TAA is rarely related to heart failure (HF). We report the case of an 80-year-old female patient, with type A TAA without dissection, with right pulmonary artery and left atrium compression, who presented with HF, preserved ejection fraction and acute pulmonary edema. Copyright © 2018 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Ischemic preconditioning of the lower extremity attenuates the normal hypoxic increase in pulmonary artery systolic pressure.

    PubMed

    Foster, Gary P; Westerdahl, Daniel E; Foster, Laura A; Hsu, Jeffrey V; Anholm, James D

    2011-12-15

    Ischemic pre-condition of an extremity (IPC) induces effects on local and remote tissues that are protective against ischemic injury. To test the effects of IPC on the normal hypoxic increase in pulmonary pressures and exercise performance, 8 amateur cyclists were evaluated under normoxia and hypoxia (13% F(I)O(2)) in a randomized cross-over trial. IPC was induced using an arterial occlusive cuff to one thigh for 5 min followed by deflation for 5 min for 4 cycles. In the control condition, the resting pulmonary artery systolic pressure (PASP) increased from a normoxic value of 25.6±2.3 mmHg to 41.8±7.2 mmHg following 90 min of hypoxia. In the IPC condition, the PASP increased to only 32.4±3.1 mmHg following hypoxia, representing a 72.8% attenuation (p=0.003). No significant difference was detected in cycle ergometer time trial duration between control and IPC conditions with either normoxia or hypoxia. IPC administered prior to hypoxic exposure was associated with profound attenuation of the normal hypoxic increase of pulmonary artery systolic pressure. Published by Elsevier B.V.

  12. Temperature measurement in intensive care patients: comparison of urinary bladder, oesophageal, rectal, axillary, and inguinal methods versus pulmonary artery core method.

    PubMed

    Lefrant, J-Y; Muller, L; de La Coussaye, J Emmanuel; Benbabaali, M; Lebris, C; Zeitoun, N; Mari, C; Saïssi, G; Ripart, J; Eledjam, J-J

    2003-03-01

    Comparisons of urinary bladder, oesophageal, rectal, axillary, and inguinal temperatures versus pulmonary artery temperature. Prospective cohort study. Intensive Care Unit of a University-Hospital. Forty-two intensive care patients requiring a pulmonary artery catheter (PAC). Patients requiring PAC and without oesophageal, urinary bladder, and/or rectal disease or recent surgery were included in the study. Temperature was simultaneously monitored with PAC, urinary, oesophageal, and rectal electronic thermometers and with axillary and inguinal gallium-in-glass thermometers. Comparisons used a Bland and Altman method. The pulmonary arterial temperature ranged from 33.7 degrees C to 40.2 degrees C. Urinary bladder temperature was assessed in the last 22 patients. A total of 529 temperature measurement comparisons were carried out (252 comparisons of esophageal, rectal, inguinal, axillary, and pulmonary artery temperature measurements in the first 20 patients, and 277 comparisons with overall methods in the last patients). Nine to 18 temperature measurement comparisons were carried out per patient (median = 13). The mean differences between pulmonary artery temperatures and those of the different methods studied were: oesophageal (0.11+/-0.30 degrees C), rectal (-0.07+/-0.40 degrees C), axillary (0.27+/-0.45 degrees C), inguinal (0.17+/-0.48 degrees C), urinary bladder (-0.21+/-0.20 degrees C). In critically ill patients, urinary bladder and oesophageal electronic thermometers are more reliable than the electronic rectal thermometer which is better than inguinal and axillary gallium-in-glass thermometers to measure core temperature.

  13. Incentive spirometry for preventing pulmonary complications after coronary artery bypass graft.

    PubMed

    Freitas, Eliane R F S; Soares, Bernardo G O; Cardoso, Jefferson R; Atallah, Álvaro N

    2012-09-12

    Incentive spirometry (IS) is a treatment technique that uses a mechanical device to reduce pulmonary complications during postoperative care. This is an update of a Cochrane review first published in 2007. Update the previously published systematic review to compare the effects of IS for preventing postoperative pulmonary complications in adults undergoing coronary artery bypass graft (CABG). We searched CENTRAL and DARE on The Cochrane Library (Issue 2 of 4 2011), MEDLINE OVID (1948 to May 2011), EMBASE (1980 to Week 20 2011), LILACS (1982 to July 2011) , the Physiotherapy Evidence Database (PEDro) (1980 to July 2011), Allied & Complementary Medicine (AMED) (1985 to May 2011), CINAHL (1982 to May 2011). Randomised controlled trials comparing IS with any type of prophylactic physiotherapy for prevention of postoperative pulmonary complications in adults undergoing CABG. Two reviewers independently evaluated trial quality using the guidelines of the Cochrane Handbook for Systematic Reviews and extracted data from included trials. For continuous outcomes, we used the generic inverse variance method for meta-analysis and for dichotomous data we used the Peto Odds Ratio. This update included 592 participants from seven studies (two new and one that had been excluded in the previous review in 2007. There was no evidence of a difference between groups in the incidence of any pulmonary complications and functional capacity between treatment with IS and treatment with physical therapy, positive pressure breathing techniques (including continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP) and intermittent positive pressure breathing (IPPB), active cycle of breathing techniques (ACBT) or preoperative patient education. Patients treated with IS had worse pulmonary function and arterial oxygenation compared with positive pressure breathing. Based on these studies there was no improvement in the muscle strength between groups who received IS

  14. Role for miR-204 in human pulmonary arterial hypertension

    PubMed Central

    Courboulin, Audrey; Paulin, Roxane; Giguère, Nellie J.; Saksouk, Nehmé; Perreault, Tanya; Meloche, Jolyane; Paquet, Eric R.; Biardel, Sabrina; Provencher, Steeve; Côté, Jacques; Simard, Martin J.

    2011-01-01

    Pulmonary arterial hypertension (PAH) is characterized by enhanced proliferation and reduced apoptosis of pulmonary artery smooth muscle cells (PASMCs). Because microRNAs have been recently implicated in the regulation of cell proliferation and apoptosis, we hypothesized that these regulatory molecules might be implicated in the etiology of PAH. In this study, we show that miR-204 expression in PASMCs is down-regulated in both human and rodent PAH. miR-204 down-regulation correlates with PAH severity and accounts for the proliferative and antiapoptotic phenotypes of PAH-PASMCs. STAT3 activation suppresses miR-204 expression, and miR-204 directly targets SHP2 expression, thereby SHP2 up-regulation, by miR-204 down-regulation, activates the Src kinase and nuclear factor of activated T cells (NFAT). STAT3 also directly induces NFATc2 expression. NFAT and SHP2 were needed to sustain PAH-PASMC proliferation and resistance to apoptosis. Finally, delivery of synthetic miR-204 to the lungs of animals with PAH significantly reduced disease severity. This study uncovers a new regulatory pathway involving miR-204 that is critical to the etiology of PAH and indicates that reestablishing miR-204 expression should be explored as a potential new therapy for this disease. PMID:21321078

  15. Survival of adults with systemic autoimmune rheumatic diseases and pulmonary arterial hypertension after lung transplantation.

    PubMed

    Bernstein, Elana J; Bathon, Joan M; Lederer, David J

    2018-05-01

    Pulmonary arterial hypertension (PAH) is a major cause of morbidity and mortality in adults with systemic autoimmune rheumatic diseases (ARDs). The aim of this study was to determine whether adults with ARDs and PAH on right-sided heart catheterization (ARD-PAH) have increased mortality following lung transplantation compared with those with PAH not due to an ARD. We conducted a retrospective cohort study of 93 adults with ARD-PAH and 222 adults with PAH who underwent lung transplantation in the USA between 4 May 2005 and 9 March 2015 using data from the United Network for Organ Sharing. We examined associations between diagnosis and survival after lung transplantation using stratified Cox models adjusted for potential confounding recipient factors. Among adults undergoing lung transplantation in the USA, we did not detect a difference in the multivariable-adjusted mortality rate between those with ARD-PAH and those with PAH [hazard ratio 0.75 (95% CI 0.47, 1.19)]. The presence of an ARD was not associated with increased mortality after lung transplantation in adults with PAH.

  16. [Horseshoe lung with normal pulmonary venous return].

    PubMed

    Gondra Sangroniz, A; Elorz Lambarri, J; Villar Alvarez, M A; Lecumberri Cortes, I; Ayala Curiel, J

    2010-09-01

    Horseshoe lung is a rare congenital anomaly characterised by a midline isthmus of pulmonary parenchyma connecting the posterior basal segments of the lungs behind the heart in conjunction with unilateral pulmonary hypoplasia. Of all cases, 80% are associated with scimitar syndrome, consisting of right anomalous pulmonary venous drainage, pulmonary hypoplasia of the right lung and systemic arterial perfusion to some lung areas. A six year old girl who had recurrent lower respiratory infections since birth. Chest Rx, angioCT and MR showed: hypoplasia of the right lung, dextrocardia and pulmonary isthmus bridging both lungs behind the pericardium. The right hypoplastic lung had little systemic supply coming from the abdominal aorta. The right pulmonary artery was hypoplastic. The right pulmonary venous drainage was normal. We present a case of horseshoe lung without abnormal venous drainage. 2010 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  17. Selective Embolization of Systemic Collaterals for the Treatment of Recurrent Hemoptysis Secondary to the Unilateral Absence of a Pulmonary Artery in a Child

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

    Zhou, Yin, E-mail: zhouyin502@163.com; Tsauo, Jiaywei, E-mail: 80732059@qq.com; Li, Yuan, E-mail: liyuanletters@163.com

    The unilateral absence of the pulmonary artery (UAPA) is a rare anomaly. Hemoptysis due to systemic collaterals is one of the most common complications of UAPA. To the best of the authors’ knowledge, the utility of selective embolization for the treatment of this condition in children has not been reported previously. This report describes a 6-year-old girl with isolated UAPA (IUAPA) admitted for a 10-month history of recurrent hemoptysis that had worsened during the previous 2 months. Selective embolization of the bronchial systemic collaterals was performed. The patient remained asymptomatic with no recurrence of hemoptysis 8 months after the procedure.

  18. Long-term treatment with oral sildenafil is safe and improves functional capacity and hemodynamics in patients with pulmonary arterial hypertension.

    PubMed

    Michelakis, Evangelos D; Tymchak, Wayne; Noga, Michelle; Webster, Linda; Wu, Xi-Chen; Lien, Dale; Wang, Shao-Hua; Modry, Dennis; Archer, Stephen L

    2003-10-28

    The prognosis and functional capacity of patients with pulmonary arterial hypertension (PAH) is poor, and there is a need for safe, effective, inexpensive oral treatments. A single dose of sildenafil, an oral phosphodiesterase type-5 (PD-5) inhibitor, is an effective and selective pulmonary vasodilator in PAH. However, the long-term effects of PD-5 inhibition and its mechanism of action in human pulmonary arteries (PAs) are unknown. We hypothesized that 3 months of sildenafil (50 mg orally every 8 hours) added to standard treatment would be safe and improve functional capacity and hemodynamics in PAH patients. We studied 5 consecutive patients (4 with primary pulmonary hypertension, 1 with Eisenmenger's syndrome; New York Heart Association class II to III). Functional class improved by > or =1 class in all patients. Pretreatment versus posttreatment values (mean+/-SEM) were as follows: 6-minute walk, 376+/-30 versus 504+/-27 m, P<0.0001; mean PA pressure, 70+/-3 versus 52+/-3 mm Hg, P<0.007; pulmonary vascular resistance index 1702+/-151 versus 996+/-92 dyne x s x cm(-5) x m(-2), P<0.006. The systemic arterial pressure was unchanged, and no adverse effects occurred. Sildenafil also reduced right ventricular mass measured by MRI. In 7 human PAs (6 cardiac transplant donors and 1 patient with PAH on autopsy), we showed that PD-5 is present in PA smooth muscle cells and that sildenafil causes relaxation by activating large-conductance, calcium-activated potassium channels. This small pilot study suggests that long-term sildenafil therapy might be a safe and effective treatment for PAH. At a monthly cost of 492 dollars Canadian, sildenafil is more affordable than most approved PAH therapies. A large multicenter trial is indicated to directly compare sildenafil with existing PAH treatments.

  19. Rehabilitation in patients with pulmonary arterial hypertension.

    PubMed

    Keusch, Stephan; Turk, Alexander; Saxer, Stéphanie; Ehlken, Nicola; Grunig, Ekkehard; Ulrich, Silvia; On Behalf Of The Swiss Society Of Pulmonary Hypertension

    2017-07-11

    Exertional dyspnoea is a leading symptom in patients with pulmonary arterial hypertension (PAH). Patients suffering from PAH report poor quality of life, have skeletal muscle dysfunction and in the absence of advanced medical therapy deteriorate progressively due to right heart failure which can lead to death. For decades, patients with PAH were advised to avoid exercise in fear of exacerbated right heart failure. Recently, it has been shown that a highly supervised rehabilitation programme in expert centres leads to significant improvements in symptoms, quality of life, exercise capacity and may even enhance haemodynamics in selected stable patients treated with advanced regimens of PAH-targeted drugs. As a consequence of these promising results, pulmonary rehabilitation performed in an expert centre has been included in recent guidelines. The underlying mechanisms are not completely understood, but positive effects can be measured in different organ systems such as skeletal muscles, the cardiopulmonary system and immune system (inflammation), and also on the psychological level. Thus, improvements in 6-minute walking distance (6MWD), peak oxygen uptake (VO2 peak), muscle strength and muscle endurance, as well as physical and mental quality of life scores (SF-36 questionnaire) have been shown. Different training protocols have been used. Essential are qualified patient selection in expert centres, a low workload endurance and dumbbell (weight lifting) training avoiding strenuous exercise and exhaustion, thorough patient education and close supervision by experts especially during the first weeks. Adverse events may occur (e.g., pre-/syncope, arrhythmia, respiratory infections). PAH patients tend to overestimate their physical capacity, not perceiving their own limits properly, which makes education and expert advice even more important as exercise training can also worsen the right heart failure. Therefore, a core issue of the multidisciplinary rehabilitation is

  20. Relationship between interatrial communication, ductus arteriosus, and pulmonary flow patterns in fetuses with transposition of the great arteries: prediction of neonatal desaturation.

    PubMed

    Vaujois, Laurence; Boucoiran, Isabelle; Preuss, Christophe; Brassard, Myriam; Houde, Christine; Fouron, Jean C; Raboisson, Marie-Josée

    2017-09-01

    The relationship between interatrial communication, ductus arteriosus, and pulmonary flow in transposition of the great arteries and intact ventricular septum may help predict postnatal desaturation. Echocardiographic data of 45 fetuses with transposition of the great arteries and intact ventricular septum and 50 age-matched controls were retrospectively reviewed. Interatrial communication, left and right ventricular output, flow in the ductus arteriosus, as well as effective pulmonary flow were measured. Patients were divided into two groups on the basis of postnatal saturations: group 1 had saturations ⩽50% and group 2 >50%. Of 45 fetuses, 13 (26.7%) were classified into group 1. Compared with fetuses in group 2, they had a smaller interatrial communication (2.9 versus 4.0 mm, p=0.004) and more retrograde diastolic flow in the ductus arteriosus (92 versus 23%, p=0.002). Both groups showed a significant decrease in ductal flow compared with controls. Patients in group 2 had a higher effective pulmonary flow compared with controls. There was a mild correlation between left ventricular output and size of the interatrial communication (Spearman's rank correlation 0.44). A retrograde diastolic flow is present in most of the fetuses with postnatal desaturation. Fetuses with transposition of the great arteries have a lower flow through the ductus arteriosus compared with controls. Fetuses without restrictive foramen ovale have higher effective pulmonary flow. Peripheral pulmonary vasodilatation due to higher oxygen saturation in pulmonary arteries in the case of transposition of the great arteries could be one possible cause.

  1. KCNA5 gene is not confirmed as a systemic sclerosis-related pulmonary arterial hypertension genetic susceptibility factor

    PubMed Central

    2012-01-01

    Introduction Potassium voltage-gated channel shaker-related subfamily member 5 (KCNA5) is implicated in vascular tone regulation, and its inhibition during hypoxia produces pulmonary vasoconstriction. Recently, a protective association of the KCNA5 locus with systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) was reported. Hence, the aim of this study was to replicate these findings in an independent multicenter Caucasian SSc cohort. Methods The 2,343 SSc cases (179 PAH positive, confirmed by right-heart catheterization) and 2,690 matched healthy controls from five European countries were included in this study. Rs10744676 single-nucleotide polymorphism (SNP) was genotyped by using a TaqMan SNP genotyping assay. Results Individual population analyses of the selected KCNA5 genetic variant did not show significant association with SSc or any of the defined subsets (for example, limited cutaneous SSc, diffuse cutaneous SSc, anti-centromere autoantibody positive and anti-topoisomerase autoantibody positive). Furthermore, pooled analyses revealed no significant evidence of association with the disease or any of the subsets, not even the PAH-positive group. The comparison of PAH-positive patients with PAH-negative patients showed no significant differences among patients. Conclusions Our data do not support an important role of KCNA5 as an SSc-susceptibility factor or as a PAH-development genetic marker for SSc patients. PMID:23270786

  2. Aberration design of zoom lens systems using thick lens modules.

    PubMed

    Zhang, Jinkai; Chen, Xiaobo; Xi, Juntong; Wu, Zhuoqi

    2014-12-20

    A systematic approach for the aberration design of a zoom lens system using a thick lens module is presented. Each component is treated as a thick lens module at the beginning of the design. A thick lens module refers to a thick lens component with a real lens structure, like lens materials, lens curvatures, lens thicknesses, and lens interval distances. All nine third-order aberrations of a thick lens component are considered during the design. The relationship of component aberrations in different zoom positions can be approximated from the aberration shift. After minimizing the aberrations of the zoom lens system, the nine third-order aberrations of every lens component can be determined. Then the thick lens structure of every lens component can be determined after optimization according to their first-order properties and third-order aberration targets. After a third optimization for minimum practical third-order aberrations of a zoom lens system, the aberration design using the thick lens module is complete, which provides a practical zoom lens system with thick lens structures. A double-sided telecentric zoom lens system is designed using the thick lens module in this paper, which shows that this method is practical for zoom lens design.

  3. Nodal aberration theory for wild-filed asymmetric optical systems

    NASA Astrophysics Data System (ADS)

    Chen, Yang; Cheng, Xuemin; Hao, Qun

    2016-10-01

    Nodal Aberration Theory (NAT) was used to calculate the zero field position in Full Field Display (FFD) for the given aberration term. Aiming at wide-filed non-rotational symmetric decentered optical systems, we have presented the nodal geography behavior of the family of third-order and fifth-order aberrations. Meanwhile, we have calculated the wavefront aberration expressions when one optical element in the system is tilted, which was not at the entrance pupil. By using a three-piece-cellphone lens example in optical design software CodeV, the nodal geography is testified under several situations; and the wavefront aberrations are calculated when the optical element is tilted. The properties of the nodal aberrations are analyzed by using Fringe Zernike coefficients, which are directly related with the wavefront aberration terms and usually obtained by real ray trace and wavefront surface fitting.

  4. Pulmonary MRA: Differentiation of pulmonary embolism from truncation artifact

    PubMed Central

    Bannas, Peter; Schiebler, Mark L; Motosugi, Utaroh; François, Christopher J; Reeder, Scott B; Nagle, Scott K

    2015-01-01

    Purpose Truncation artifact (Gibbs ringing) causes central signal drop within vessels in pulmonary MRA that can be mistaken for emboli, reducing the diagnostic accuracy for pulmonary embolism (PE). We propose a quantitative approach to differentiate truncation artifact from PE. Methods Twenty-eight patients who underwent pulmonary CTA for suspected PE were recruited for pulmonary MRA. Signal intensity drops within pulmonary arteries that persisted on both arterial-phase and delayed-phase MRA were identified. The percent signal loss between the vessel lumen and central drop was measured. CTA served as the reference standard for presence of pulmonary emboli. Results A total of 65 signal intensity drops were identified on MRA. 48 (74%) of these were artifact and 17 (26%) were PE, as confirmed by CTA. Truncation artifacts had a significantly lower median signal drop than PE at both arterial-phase (26% [range 12–58%] vs. 85% [range 53–91%]) and at delayed-phase MRA (26% [range 11–55%] vs. 77% [range 47–89%]), p<0.0001 for both. ROC analyses revealed a threshold value of 51% (arterial-phase) and 47%-signal drop (delayed-phase) to differentiate between truncation artifact and PE with 100% sensitivity and >90% specificity. Conclusion Quantitative signal drop is an objective tool to help differentiate truncation artifact and pulmonary embolism in pulmonary MRA. PMID:24863886

  5. 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.

  6. 2013 ACR/EULAR systemic sclerosis classification criteria in patients with associated pulmonary arterial hypertension.

    PubMed

    Joven, Beatriz E; Escribano, Pilar; Andreu, Jose Luis; Loza, Estibaliz; Jimenez, Carmen; de Yebenes, M Jesus Garcia; Ruiz-Cano, M Jose; Carmona, Loreto; Carreira, Patricia E

    2018-06-01

    To analyze the performance of the 1980 ACR and new 2013 ACR/EULAR criteria for systemic sclerosis (SSc) in cutaneous SSc (lcSSc) patients, especially those affected by lcSSc and pulmonary arterial hypertension (PAH). All patients with a clinical lcSSc diagnosis from a prospective observational SSc cohort were included. Sociodemographic and disease-related variables were collected, and PAH confirmed by right heart catheterization (RHC). Performance of the 2013 and 1980 SSc criteria was analyzed in terms of clinical diagnosis. Descriptive and between-group analyses were performed as to the fulfillment of criterion sets, including comparison of survival. Overall, 321 patients were included, 63% of whom fulfilled the 1980 ACR and 93% the 2013 ACR/EULAR criteria. Agreement between both criteria sets proved poor (κ = 0.23). LcSSC patients fulfilling both criterion sets were significantly younger at diagnosis, whilst presenting organ involvement, calcinosis, fingertip digital ulcers, and pitting scars more frequently than those who met the 2013 criteria only. Patients who fulfilled the 2013 but not the 1980 criteria presented a higher degree of ACA positivity and PAH. Nearly 12% of patients developed PAH. Patients who did not meet the 1980 criteria were affected by a milder disease from but demonstrated higher pulmonary vascular resistance and lower cardiac index than those fulfilling both criterion sets. Whereas patients with PAH met the 2013 criteria, only 47% fulfilled the 1980 criteria. Regardless of criterion set fulfillment, high mortality was observed in PAH patients, with no significant between-patient difference based on criterion set. The new 2013 ARC/EULAR criteria prove more accurate than the former 1980 ACR criteria in identifying and differentiating patients with lcSSc, especially those with associated PAH. Since PAH exhibits a better prognosis if treated early, all SSc patients should undergo PAH screening. Copyright © 2018 Elsevier Inc. All rights

  7. MIP-2 causes differential activation of RhoA in mouse aortic versus pulmonary artery endothelial cells

    PubMed Central

    Moldobaeva, Aigul; Baek, Amy; Wagner, Elizabeth M.

    2008-01-01

    Previously, we have shown that endothelial cell chemotaxis to the proangiogenic chemokine MIP-2 (macrophage inflammatory protein-2), is much greater in mouse aortic endothelial cells (EC) than pulmonary arterial endothelial cells (PA EC). This was true despite the observation that both cell types display comparable levels of the ligand receptor, CXCR2 (8). Since the systemic arterial circulation is proangiogenic in the adult lung and the pulmonary circulation is relatively resistant to neovascularization, we questioned whether the observed functional heterogeneity is related to inherent differences in cell signaling cascades of the two EC subtypes. Specifically, we measured activation of Rac1 and RhoA, both thought to be involved in EC cell migration. Rac1 showed inconsistent and minimal changes in both cell types after MIP-2 treatment (p>0.05). However, activated RhoA was increased upon exposure to MIP-2 only in aortic EC (61% increase; p<0.05). Decreased RhoA activation after treatment of aortic EC with specific siRNA for RhoA resulted in a functional decrease in EC chemotaxis to MIP-2 (17% increase; p<0.05). Additionally, increased RhoA activation in PA EC with adenoviral infection of RhoA caused an increase in PA EC chemotaxis to MIP-2 (46% increase; p<0.05). Inhibition of RhoA activity with the Rho kinase inhibitor, Y27632 blocked aortic EC chemotaxis and stress fiber formation. Thus, RhoA activation is increased after MIP-2 treatment in mouse aortic endothelial cells but not in pulmonary artery endothelial cells. We conclude that RhoA is part of a signaling pathway essential for aortic cell migration after CXCR2 ligation. This result provides one explanation for the difference in chemotaxis observed in these two endothelial subtypes that express similar levels of CXCR2. PMID:17662312

  8. Covered Stent and Coils Embolization of a Pulmonary Artery Pseudoaneurysm After Gunshot Wound

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

    Huet, Nicolas, E-mail: nhuet@chu-grenoble.fr; Rodiere, Mathieu, E-mail: mrodiere@chu-grenoble.fr; Badet, Michel, E-mail: michel.badet@ch-chambery.fr

    We report the first case of endovascular covered stent implantation for the treatment of a large pulmonary artery pseudoaneurysm (PAPA) following a right thoracic gunshot wound. After resuscitation and hemodynamic stabilization, a CT angiography was performed to analyze the neck size of the PAPA and its position relative to the branches of the parent artery. Covered stent implantation with additional coil embolization was successfully performed. At the 4-year follow-up, the stents remained patent and there was neither pseudoaneurysm recurrence nor treatment-related complication.

  9. Exercise training in pulmonary arterial hypertension associated with connective tissue diseases

    PubMed Central

    2012-01-01

    Introduction The objective of this prospective study was to assess short- and long-term efficacy of exercise training (ET) as add-on to medical therapy in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-APAH). Methods Patients with invasively confirmed CTD-APAH received ET in-hospital for 3 weeks and continued at home for 12 weeks. Efficacy parameters have been evaluated at baseline and after 15 weeks by blinded-observers. Survival rate has been evaluated in a follow-up period of 2.9 ± 1.9 years. Results Twenty-one consecutive patients were included and assessed at baseline, and after 3 weeks, 14 after 15 weeks. Patients significantly improved the mean distance walked in 6 minutes compared to baseline by 67 ± 52 meters after 3 weeks (p < 0.001) and by 71 ± 35 meters after 15 weeks (p = 0.003), scores of quality of life (p < 0.05), heart rate at rest, peak oxygen consumption, oxygen saturation and maximal workload. Systolic pulmonary artery pressure and diastolic systemic blood pressure improved significantly after 3 weeks of ET. The 1- and 2-year overall-survival rates were 100%, the 3-year survival 73%. In one patient lung transplantation was performed 6 months after ET. Conclusion ET as add-on to medical therapy is highly effective in patients with CTD-APAH to improve work capacity, quality of life and further prognostic relevant parameters and possibly improves the 1-, 2- and 3-year survival rate. Further randomized controlled studies are needed to confirm these results. Trial registration ClinicalTrials.gov: NCT00491309. PMID:22709477

  10. Prognostication in Pulmonary Arterial Hypertension with Submaximal Exercise Testing.

    PubMed

    Khatri, Vinod; Neal, Jennifer E; Burger, Charles D; Lee, Augustine S

    2015-02-06

    The submaximal exercise test (SET), which gives both a measure of exercise tolerance, as well as disease severity, should be a more robust functional and prognostic marker than the six-minute walk test (6MWT). This study aimed to determine the prognostic value of SET as predicted by the validated REVEAL (Registry to Evaluate Early and Long-Term Pulmonary Artery Hypertension Disease Management) registry risk score (RRRS). Sixty-five consecutive patients with idiopathic and associated pulmonary arterial hypertension (PAH) underwent right-heart catheterization, echocardiogram, 6MWT and a three-minute SET (Shape-HF™). Analyses explored the association between SET variables and prognosis predicted by the RRRS. Although multiple SET variables correlated with the RRRS on univariate analyses, only V E /V CO2 (r = 0.57, p < 0.0001) remained an independent predictor in multivariate analysis (β = 0.05, p = 0.0371). Additionally, the V E /V CO2 was the most discriminatory (area under receiver operating characteristic curve, 0.84) in identifying the highest-risk category (RRRS ≥ 10), with an optimal cut-off of 40.6, resulting in a high sensitivity (92%) and negative-predictive value (97%), but a lower specificity (67%). SETs, particularly the V E /V CO2 , appear to have prognostic value when compared to the RRRS. If validated in prospective trials, SET should prove superior to the 6MWT or the RRRS, with significant implications for both future clinical trials and clinical practice.

  11. Prospective, open-label, uncontrolled pilot study to study safety and efficacy of sildenafil in systemic sclerosis-related pulmonary artery hypertension and cutaneous vascular complications.

    PubMed

    Kumar, Uma; Sankalp, Gokhale; Gokhle, Sankalp S; Sreenivas, V; Kaur, Satbir; Misra, Durgaprasanna

    2013-04-01

    Pulmonary artery hypertension (PAH) remains the leading cause of morbidity and mortality in systemic sclerosis, while Raynaud's phenomenon and digital ulcers significantly add to the morbidity in systemic sclerosis (SSc). This study was undertaken to evaluate the role of sildenafil in PAH, Raynaud's phenomenon, and digital ulcers in systemic sclerosis patients. A prospective, open-label, uncontrolled pilot study was done at a tertiary care centre in India to study the safety and efficacy of oral sildenafil in PAH, Raynaud's phenomenon, digital infarcts, and ulcers in SSc. Seventeen patients fulfilling ACR classification criteria for scleroderma and having PAH were recruited. Six-minute walk test, WHO class of dyspnoea, severity of Raynaud's phenomenon, and 2D ECHO were performed in all the study subjects at baseline and at 3 months post-treatment. All patients were treated with oral sildenafil 25 mg three times a day for a period of 3 months. The pre- and post-treatment values of mean pulmonary artery pressure (PAP), 6-min walk test, WHO class of dyspnoea, and severity of Raynaud's phenomenon were compared to look for any significant change. Sixteen patients who completed 3-month follow-up had shown statistically significant improvement in 6-min walk test, WHO class of dyspnoea, severity of Raynaud's phenomenon, and mPAP. Also, there was no occurrence of new digital infarcts or ulcers, and existing ulcers showed signs of healing. Sildenafil is highly efficacious cheaper and safe alternative to other available therapies for SSc-associated PAH, Raynaud's phenomenon, and digital infarcts/ulcers.

  12. [Pulmonary artery pressure evaluation in adults by Doppler echocardiography].

    PubMed

    Campos Filho, O; Andrade, J L; Carvalho, A C; Luna Filho, B; Pfeferman, A; Arroyo, J B; Leão, L E; Martinez Filho, E E

    1991-04-01

    To assess the role of pulsed Doppler echocardiography (PDE) in the indirect assessment of pulmonary artery (PA) pressure (P), analysing the pulmonary velocity blood flow curves (PVBFC) profile. Sixty-one adults with several kinds of heart disease were submitted to heart catheterization to obtain PAP (systolic, diastolic, mean), and other hemodynamic variables. A PDE examination was performed in all to obtain the PVBFC at the level of the pulmonic annulus. Qualitative features of the curve were analysed (morphological pattern, presence of pulmonic regurgitation) as well as quantitative data (acceleration time = AT, right ventricle ejection time = RVET index, AT/RVET index AT corrected for heart rate = ATC), which were compared to the invasive measurements. An abnormal rapid acceleration of the PVBFC, with triangular configuration, was noted in patient with pulmonary hypertension (PH), in contrast to the dome-like shape of the PVBFC in normal PAP. Pulmonary regurgitation was more frequent (p less than 0.05) in patients with severe PH (mean PAP greater than or equal to 40 mmHg), comparing with patients with PAP less than 40 mmHg. Inverse linear correlations were observed between AT and mean PAP, particularly when sinus rhythm was present (r = 0.89; p less than 0.05) excluding patients with atrial fibrilation (19 cases). PDE is an useful and noninvasive method for indirect evaluation of PAP in adults, especially during stable sinus rhythm, in heart rate range from 60 to 115 bpm.

  13. Automatic multiscale enhancement and segmentation of pulmonary vessels in CT pulmonary angiography images for CAD applications

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

    Zhou Chuan; Chan, H.-P.; Sahiner, Berkman

    2007-12-15

    The authors are developing a computerized pulmonary vessel segmentation method for a computer-aided pulmonary embolism (PE) detection system on computed tomographic pulmonary angiography (CTPA) images. Because PE only occurs inside pulmonary arteries, an automatic and accurate segmentation of the pulmonary vessels in 3D CTPA images is an essential step for the PE CAD system. To segment the pulmonary vessels within the lung, the lung regions are first extracted using expectation-maximization (EM) analysis and morphological operations. The authors developed a 3D multiscale filtering technique to enhance the pulmonary vascular structures based on the analysis of eigenvalues of the Hessian matrix atmore » multiple scales. A new response function of the filter was designed to enhance all vascular structures including the vessel bifurcations and suppress nonvessel structures such as the lymphoid tissues surrounding the vessels. An EM estimation is then used to segment the vascular structures by extracting the high response voxels at each scale. The vessel tree is finally reconstructed by integrating the segmented vessels at all scales based on a 'connected component' analysis. Two CTPA cases containing PEs were used to evaluate the performance of the system. One of these two cases also contained pleural effusion disease. Two experienced thoracic radiologists provided the gold standard of pulmonary vessels including both arteries and veins by manually tracking the arterial tree and marking the center of the vessels using a computer graphical user interface. The accuracy of vessel tree segmentation was evaluated by the percentage of the 'gold standard' vessel center points overlapping with the segmented vessels. The results show that 96.2% (2398/2494) and 96.3% (1910/1984) of the manually marked center points in the arteries overlapped with segmented vessels for the case without and with other lung diseases. For the manually marked center points in all vessels including

  14. 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

  15. 2014 Guidelines of Taiwan Society of Cardiology (TSOC) for the Management of Pulmonary Arterial Hypertension

    PubMed Central

    Hsu, Chih-Hsin; Ho, Wan-Jing; Huang, Wei-Chun; Chiu, Yu-Wei; Hsu, Tsu-Shiu; Kuo, Ping-Hung; Hsu, Hsao-Hsun; Chang, Jia-Kan; Cheng, Chin-Chang; Lai, Chao-Lun; Liang, Kae-Woei; Lin, Shoa-Lin; Sung, Hsao-Hsun; Tsai, Wei-Chuan; Weng, Ken-Pen; Hsieh, Kai-Sheng; Yin, Wei-Hsian; Lin, Shing-Jong; Wang, Kuo-Yang

    2014-01-01

    Pulmonary hypertension (PH) is a hemodynamic and pathophysiologic condition, defined as a mean pulmonary arterial pressure exceeding 25 mmHg at rest. According to the recent classifications, it is grouped into pulmonary arterial hypertension (PAH), heart-related, lung-related, thromboembolic, and miscellaneous PH. In the past two decades, tremendous advances have occurred in the field of PH. These include (1) development of clinical diagnostic algorithm and a monitoring strategy dedicated to PAH, (2) defining strong rationales for screening at-risk populations, (3) advent of pulmonary specific drugs which makes PAH manageable, (4) recognition of needs of having proper strategy of combining existing pulmonary specific drugs, and/or potential novel drugs, (5) pursuit of clinical trials with optimal surrogate endpoints and study durations, (6) recognition of critical roles of PH/right ventricular function, as well as interdependence of ventricles in different conditions, especially those with various phenotypes of heart failure, and (7) for rare diseases, putting equal importance on carefully designed observation studies, various registries, etc., besides double blind randomized studies. In addition, ongoing basic and clinical research has led to further understanding of relevant physiology, pathophysiology, epidemiology and genetics of PH/PAH. This guidelines from the working group of Pulmonary Hypertension of the Taiwan Society of Cardiology is to provide updated guidelines based on the most recent international guidelines as well as Taiwan’s domestic research on PH. The guidelines are mainly for the management of PAH (Group 1) ; however the majority of content can be helpful for managing other types of PH. PMID:27122817

  16. Unraveling endothelin-1 induced hypercontractility of human pulmonary artery smooth muscle cells from patients with pulmonary arterial hypertension

    PubMed Central

    Warburton, Rod; Taylor, Linda; Toksoz, Deniz; Hill, Nicholas; Polgar, Peter

    2018-01-01

    Contraction of human pulmonary artery smooth muscle cells (HPASMC) isolated from pulmonary arterial hypertensive (PAH) and normal (non-PAH) subject lungs was determined and measured with real-time electrical impedance. Treatment of HPASMC with vasoactive peptides, endothelin-1 (ET-1) and bradykinin (BK) but not angiotensin II, induced a temporal decrease in the electrical impedance profile mirroring constrictive morphological change of the cells which typically was more robust in PAH as opposed to non-PAH cells. Inhibition with LIMKi3 and a cofilin targeted motif mimicking cell permeable peptide (MMCPP) had no effect on ET-1 induced HPASMC contraction indicating a negligible role for these actin regulatory proteins. On the other hand, a MMCPP blocking the activity of caldesmon reduced ET-1 promoted contraction pointing to a regulatory role of this protein and its activation pathway in HPASMC contraction. Inhibition of this MEK/ERK/p90RSK pathway, which is an upstream regulator of caldesmon phosphorylation, reduced ET-1 induced cell contraction. While the regulation of ET-1 induced cell contraction was found to be similar in PAH and non-PAH cells, a key difference was the response to pharmacological inhibitors and to siRNA knockdown of Rho kinases (ROCK1/ROCK2). The PAH cells required much higher concentrations of inhibitors to abrogate ET-1 induced contractions and their contraction was not affected by siRNA against either ROCK1 or ROCK2. Lastly, blocking of L-type and T-type Ca2+ channels had no effect on ET-1 or BK induced contraction. However, inhibiting the activity of the sarcoplasmic reticulum Ca2+ ATPase blunted ET-1 and BK induced HPASMC contraction in both PAH and non-PAH derived HPASMC. In summary, our findings here together with previous communications illustrate similarities and differences in the regulation PAH and non-PAH smooth muscle cell contraction relating to calcium translocation, RhoA/ROCK signaling and the activity of caldesmon. These findings

  17. Embolization of the Systemic Arterial Supply via a Detachable Silicon Balloon in a Child with Scimitar Syndrome

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

    Sahin, Sinan; Celebi, Ahmet; Yalcin, Yalim

    2005-04-15

    Scimitar syndrome is a rare congenital disorder. It is characterized by partial or total abnormal venous drainage of the right lung into the inferior vena cava, which is often associated with anomalous systemic arterial supply to the right lung, congenital cardiac anomalies, hypoplasia of the right lung and bronchial anomalies. Symptoms depend on the degree of the shunt and severity of the associated anomalies, which determine the treatment. We present a 6-year-old boy who was diagnosed as having the adult form of scimitar syndrome during evaluation for recurrent pulmonary infections, and underwent embolization with a detachable silicon balloon of themore » anomalous systemic arterial supply from the abdominal aorta to the right lower lung lobe. Successful elective surgery was performed 6 months later, in which right pulmonary veins were directed to the left atrium using a Gore-Tex patch by creating an intra-atrial tunnel. The patient has been symptom-free period during 6 months of follow-up, which supports the idea that recurrent pulmonary infections can be eliminated by embolization of the anomalous arterial supply.« less

  18. The importance of preoperative oxygen saturation as a predictor of pulmonary arterial hypertension after surgery of atrial septal defects.

    PubMed

    Park, Han Ki; Shin, Hong Ju; Park, Young Hwan; Ma, Bo Gyoung

    2016-09-01

    There is no concrete predictor of the change of pulmonary arterial pressure after surgical closure of an atrial septal defect (ASD) in patients with pulmonary arterial hypertension (PAH). The aim of this study was to investigate the role of preoperative room air arterial oxygen saturation (SaO2) (arterial blood gas data) as a predictor of postoperative PAH. The medical records of 36 patients [>20 years, mean pulmonary arterial pressure (mPAP) ≥25 mmHg] who underwent surgical closure of an ASD between March 2004 and January 2014 were retrospectively reviewed. The median age was 47 years (range, 24.6-65.9 years) and mPAP was 38 ± 14 mmHg. The mean pulmonary vascular resistance (Rp) was 3.9 ± 4.2 Wood units, and fenestration was performed in 12 (33%) patients. Only 1 patient received anti-PAH medication preoperatively. The median follow-up period was 4 years (range, 0-10 years). There were two hospital deaths, one of which was related to PAH. At the last follow-up, PAH (estimated tricuspid regurgitation velocity >3 m/s) existed in 7 patients (19%), and 10 patients (28%) were receiving anti-PAH medications (considered as clinical PAH). Univariate analysis for persistent clinical PAH revealed that mPAP, Qp/Qs, Rp, room air arterial oxygen saturation and postoperative functional class were significant risk factors. Only SaO2 remained a significant risk factor in multivariate analysis (P = 0.03). Preoperative room air SaO2 is a useful predictor of persistent PAH in adult patients undergoing surgical closure of an ASD. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  19. Systemic elastin degradation in chronic obstructive pulmonary disease.

    PubMed

    Maclay, John D; McAllister, David A; Rabinovich, Roberto; Haq, Imran; Maxwell, Scott; Hartland, Stephen; Connell, Martin; Murchison, John T; van Beek, Edwin J R; Gray, Robert D; Mills, Nicholas L; Macnee, William

    2012-07-01

    Development of emphysema and vascular stiffness in chronic obstructive pulmonary disease (COPD) may be due to a common mechanism of susceptibility to pulmonary and systemic elastin degradation. To investigate whether patients with COPD have evidence of systemic elastin degradation in the skin. The authors measured cutaneous elastin degradation using immunohistochemistry (percentage area of elastin fibres) in sun-exposed (exposed) and non-sun-exposed (non-exposed) skin biopsies in 16 men with COPD and 15 controls matched for age and cigarette smoke exposure. Quantitative PCR of matrix metalloproteinase (MMP)-2, -9, -12 and tissue inhibitor of metalloproteinase-1 mRNA and zymography for protein expression of MMP-2 and -9 were performed on homogenised skin. Arterial stiffness and emphysema severity were measured using carotid-femoral pulse wave velocity and quantitative CT scanning. Skin elastin degradation was greater in exposed and non-exposed skin of patients with COPD compared with controls (exposed, mean (SD); 43.5 (12.1)% vs 26.3 (6.9)%, p<0.001; non-exposed 22.4 (5.2)% vs 18.1 (4.3)%, p=0.02). Cutaneous expression of MMP-9 mRNA and proMMP-9 concentrations was increased in exposed skin of COPD patients (p=0.004 and p=0.02, respectively) and was also associated with increased skin elastin degradation (r=0.62, p<0.001 and r=0.47, p=0.01, respectively). In the entire cohort of ex-smokers, cutaneous elastin degradation was associated with emphysema severity, FEV(1) and pulse wave velocity. Patients with COPD have increased skin elastin degradation compared with controls, which is related to emphysema severity and arterial stiffness. Systemic elastin degradation due to increased proteolytic activity may represent a novel shared mechanism for the pulmonary, vascular and cutaneous features of COPD.

  20. Presence of reduced regional left ventricular function even in the absence of left ventricular wall scar tissue in the long term after repair of an anomalous left coronary artery from the pulmonary artery.

    PubMed

    Nordmeyer, Sarah; Schmitt, Boris; Nasseri, Boris; Alexi-Meskishvili, Vladimir; Kuehne, Titus; Berger, Felix; Nordmeyer, Johannes

    2018-02-01

    We sought to assess left ventricular regional function in patients with and without left ventricular wall scar tissue in the long term after repair of an anomalous origin of the left coronary artery from the pulmonary artery. A total of 20 patients aged 12.8±7.4 years were assessed 10 (0.5-17) years after the repair of an anomalous origin of the left coronary artery from the pulmonary artery; of them, 10 (50%) patients showed left ventricular wall scar tissue on current cardiac MRI. Left ventricular regional function was assessed by two-dimensional speckle-tracking echocardiography in 10 patients with scar tissue and 10 patients without scar tissue and in 10 age-matched controls. In patients with scar tissue, MRI-derived left ventricular ejection fraction was significantly reduced compared with that in patients without scar tissue (51 versus 61%, p<0.05), and echocardiography-derived longitudinal strain was significantly reduced in five of six left ventricular areas compared with that in healthy controls (average relative reduction, 46%; p<0.05). In patients without scar tissue, longitudinal strain was significantly reduced in two of six left ventricular areas (average relative reduction, 23%; p<0.05) and circumferential strain was reduced in one of six left ventricular areas (relative reduction, 56%; p<0.05) compared with that in healthy controls. Regional left ventricular function is reduced even in patients without left ventricular wall scar tissue late after successful repair of an anomalous origin of the left coronary artery from the pulmonary artery. This highlights the need for meticulous lifelong follow-up in all patients with a repaired anomalous origin of the left coronary artery from the pulmonary artery.

  1. Interstage evaluation of homograft-valved right ventricle to pulmonary artery conduits for palliation of hypoplastic left heart syndrome.

    PubMed

    Sandeep, Nefthi; Punn, Rajesh; Balasubramanian, Sowmya; Smith, Shea N; Reinhartz, Olaf; Zhang, Yulin; Wright, Gail E; Peng, Lynn F; Wise-Faberowski, Lisa; Hanley, Frank L; McElhinney, Doff B

    2018-04-01

    Palliation of hypoplastic left heart syndrome with a standard nonvalved right ventricle to pulmonary artery conduit results in an inefficient circulation in part due to diastolic regurgitation. A composite right ventricle pulmonary artery conduit with a homograft valve has a hypothetical advantage of reducing regurgitation, but may differ in the propensity for stenosis because of valve remodeling. This retrospective cohort study included 130 patients with hypoplastic left heart syndrome who underwent a modified stage 1 procedure with a right ventricle to pulmonary artery conduit from 2002 to 2015. A composite valved conduit (cryopreserved homograft valve anastomosed to a polytetrafluoroethylene tube) was placed in 100 patients (47 aortic, 32 pulmonary, 13 femoral/saphenous vein, 8 unknown), and a nonvalved conduit was used in 30 patients. Echocardiographic functional parameters were evaluated before and after stage 1 palliation and before the bidirectional Glenn procedure, and interstage interventions were assessed. On competing risk analysis, survival over time was better in the valved conduit group (P = .040), but this difference was no longer significant after adjustment for surgical era. There was no significant difference between groups in the cumulative incidence of bidirectional Glenn completion (P = .15). Patients with a valved conduit underwent more interventions for conduit obstruction in the interstage period, but this difference did not reach significance (P = .16). There were no differences between groups in echocardiographic parameters of right ventricle function at baseline or pre-Glenn. In this cohort of patients with hypoplastic left heart syndrome, inclusion of a valved right ventricle to pulmonary artery conduit was not associated with any difference in survival on adjusted analysis and did not confer an identifiable benefit on right ventricle function. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier

  2. Echinacoside induces rat pulmonary artery vasorelaxation by opening the NO-cGMP-PKG-BKCa channels and reducing intracellular Ca2+ levels

    PubMed Central

    Gai, Xiang-yun; Wei, Yu-hai; Zhang, Wei; Wuren, Ta-na; Wang, Ya-ping; Li, Zhan-qiang; Liu, Shou; Ma, Lan; Lu, Dian-xiang; Zhou, Yi; Ge, Ri-li

    2015-01-01

    Aim: Sustained pulmonary vasoconstriction as experienced at high altitude can lead to pulmonary hypertension (PH). The main purpose of this study is to investigate the vasorelaxant effect of echinacoside (ECH), a phenylethanoid glycoside from the Tibetan herb Lagotis brevituba Maxim and Cistanche tubulosa, on the pulmonary artery and its potential mechanism. Methods: Pulmonary arterial rings obtained from male Wistar rats were suspended in organ chambers filled with Krebs-Henseleit solution, and isometric tension was measured using a force transducer. Intracellular Ca2+ levels were measured in cultured rat pulmonary arterial smooth muscle cells (PASMCs) using Fluo 4-AM. Results: ECH (30–300 μmol/L) relaxed rat pulmonary arteries precontracted by noradrenaline (NE) in a concentration-dependent manner, and this effect could be observed in both intact endothelium and endothelium-denuded rings, but with a significantly lower maximum response and a higher EC50 in endothelium-denuded rings. This effect was significantly blocked by L-NAME, TEA, and BaCl2. However, IMT, 4-AP, and Gli did not inhibit ECH-induced relaxation. Under extracellular Ca2+-free conditions, the maximum contraction was reduced to 24.54%±2.97% and 10.60%±2.07% in rings treated with 100 and 300 μmol/L of ECH, respectively. Under extracellular calcium influx conditions, the maximum contraction was reduced to 112.42%±7.30%, 100.29%±8.66%, and 74.74%±4.95% in rings treated with 30, 100, and 300 μmol/L of ECH, respectively. After cells were loaded with Fluo 4-AM, the mean fluorescence intensity was lower in cells treated with ECH (100 μmol/L) than with NE. Conclusion: ECH suppresses NE-induced contraction of rat pulmonary artery via reducing intracellular Ca2+ levels, and induces its relaxation through the NO-cGMP pathway and opening of K+ channels (BKCa and KIR). PMID:25864652

  3. Optimal treatment of coronary-to-pulmonary artery fistula: surgery, coil or stent graft?

    PubMed Central

    Lipiec, Piotr; Peruga, Jan Zbigniew; Jaszewski, Ryszard; Pawłowski, Witold; Kasprzak, Jarosław

    2013-01-01

    We report a case of a 57-year-old man with typical angina due to a coronary artery-to-pulmonary artery fistula, which was evident on transthoracic and transesophageal echocardiography with color Doppler flow mapping. The diagnosis was confirmed by coronary angiography. The patient underwent surgical ligation of the fistula. However, repeated transesophageal echocardiography and coronary angiography revealed persistence of the fistula with significant left-to-right shunt. The orifice of the fistula was then obliterated by stent-graft implantation, which was proven successful by angiography and echocardiography. PMID:24570733

  4. miR-1 is increased in pulmonary hypertension and downregulates Kv1.5 channels in rat pulmonary arteries.

    PubMed

    Mondejar-Parreño, Gema; Callejo, María; Barreira, Bianca; Morales-Cano, Daniel; Esquivel-Ruiz, Sergio; Moreno, Laura; Cogolludo, Angel; Perez-Vizcaino, Francisco

    2018-05-02

    ■The expression of miR-1 is increased in lungs from the Hyp/Su5416 PAH rat model. ■PASMC from this animal model are more depolarised and show decreased expression and activity of Kv1.5. ■miR-1 directly targets Kv1.5 channels, reduces Kv1.5 activity and induces membrane depolarization. ■Antagomir-1 prevents Kv1.5 channel downregulation and the depolarization induced by hypoxia/Su5416 exposition. Impairment of voltage-dependent potassium channel (Kv) plays a central role in the development of cardiovascular diseases, including pulmonary arterial hypertension (PAH). MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression by binding to the 3'-UTR region of specific mRNAs. The aim of this study was to analyze the effects of miR-1 on Kv channel function in pulmonary arteries (PA). Kv channel activity was studied in PA from healthy animals transfected with miR-1 or scrambled-miR. Kv currents were studied using the whole-cell configuration of patch-clamp technique. The characterization of the Kv1.5 currents was performed with the selective inhibitor DPO-1. miR-1 expression was increased and Kv1.5 channels were decreased in lungs from a rat model of PAH induced by hypoxia and Su5416. miR-1 transfection increased cell capacitance, reduced Kv1.5 currents and induced membrane depolarization in isolated pulmonary artery smooth muscle cells (PASMCs). Luciferase reporter assay indicated that KCNA5, which encodes Kv1.5 channels, is a direct target gene of miR-1. Incubation of PA with Su5416 and hypoxia (3% O 2 ) increased miR-1 and induced a decline in Kv1.5 currents, which was prevented by antagomiR-1. In conclusion, these data indicate that miR-1 induces PASMC hypertrophy and reduces the activity and expression of Kv channels, suggesting a pathophysiological role in PAH. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. Pulmonary arterial pressure and right ventricular dilatation independently determine tricuspid valve insufficiency severity in pre-capillary pulmonary hypertension.

    PubMed

    De Meester, Pieter; Van De Bruaene, Alexander; Delcroix, Marion; Belmans, Ann; Herijgers, Paul; Voigt, Jens-Uwe; Budts, Werner

    2012-11-01

    Elevated pulmonary artery systolic pressure (PASP) causes functional tricuspid valve insufficiency (TI). However, the differential contribution of pressure load and right ventricular (RV) dilatation is not well established. The study aim was to evaluate both variables in relation to TI. A cross-sectional study was performed of consecutive transthoracic echocardiographic studies of patients with pre-capillary pulmonary hypertension (PH). Both, demographic data and echocardiographic RV parameters were reviewed. TI was graded semi-quantitatively with color Doppler flow imaging. Trend analyses for TI severity (TI grade 0/4, 1/4, 2/4, 3/4, or 4/4) were performed. A proportional odds logistic regression analysis was carried out to identify independent predictors of TI severity. Eighty-one patients (56 females, 25 males; mean age 60 +/- 15 years) with pre-capillary PH were evaluated. Patients with more severe TI had a significantly lower body mass index, a lower mean systemic blood pressure, a shorter pulmonary acceleration time, a higher tricuspid regurgitant gradient, and a more dilated right ventricle. From the echocardiographic parameters, RV dilatation (p = 0.0143) and the tricuspid regurgitant gradient (p = 0.0026) were independently related to the degree of TI. In patients with pre-capillary PH, PASP and RV dilatation were both related to the increasing severity of TI. When focusing on TI to improve the prognosis of patients with pre-capillary PH, both PASP and RV dimensions should be taken into consideration.

  6. Theory of aberration fields for general optical systems with freeform surfaces.

    PubMed

    Fuerschbach, Kyle; Rolland, Jannick P; Thompson, Kevin P

    2014-11-03

    This paper utilizes the framework of nodal aberration theory to describe the aberration field behavior that emerges in optical systems with freeform optical surfaces, particularly φ-polynomial surfaces, including Zernike polynomial surfaces, that lie anywhere in the optical system. If the freeform surface is located at the stop or pupil, the net aberration contribution of the freeform surface is field constant. As the freeform optical surface is displaced longitudinally away from the stop or pupil of the optical system, the net aberration contribution becomes field dependent. It is demonstrated that there are no new aberration types when describing the aberration fields that arise with the introduction of freeform optical surfaces. Significantly it is shown that the aberration fields that emerge with the inclusion of freeform surfaces in an optical system are exactly those that have been described by nodal aberration theory for tilted and decentered optical systems. The key contribution here lies in establishing the field dependence and nodal behavior of each freeform term that is essential knowledge for effective application to optical system design. With this development, the nodes that are distributed throughout the field of view for each aberration type can be anticipated and targeted during optimization for the correction or control of the aberrations in an optical system with freeform surfaces. This work does not place any symmetry constraints on the optical system, which could be packaged in a fully three dimensional geometry, without fold mirrors.

  7. Endothelium-dependent relaxation induced by cathepsin G in porcine pulmonary arteries

    PubMed Central

    Glusa, Erika; Adam, Christine

    2001-01-01

    Serine proteinases elicit profound cellular effects in various tissues mediated by activation of proteinase-activated receptors (PAR). In the present study, we investigated the vascular effects of cathepsin G, a serine proteinase that is present in the azurophil granules of leukocytes and is known to activate several cells that express PARs. In prostaglandin F2α (3 μM)-precontracted rings from porcine pulmonary arteries with intact endothelium, cathepsin G caused concentration-dependent relaxant responses (pEC50=9.64±0.12). The endothelium-dependent relaxant effect of cathepsin G could also be demonstrated in porcine coronary arteries (pEC50=9.23±0.07). In pulmonary arteries the cathepsin G-induced relaxation was inhibited after blockade of nitric oxide synthesis by L-NAME (200 μM) and was absent in endothelium-denuded vessels. Bradykinin- and cathepsin G-induced relaxant effects were associated with a 5.7 fold and 2.4 fold increase in the concentration of cyclic GMP, respectively. Compared with thrombin and trypsin, which also produced an endothelium-dependent relaxation in pulmonary arteries, cathepsin G was 2.5 and four times more potent, respectively. Cathepsin G caused only small homologous desensitization. In cathepsin G-challenged vessels, thrombin was still able to elicit a relaxant effect. The effects of cathepsin G were blocked by soybean trypsin inhibitor (IC50=0.043 μg ml−1), suggesting that proteolytic activity is essential for induction of relaxation. Recombinant acetyl-eglin C proved to be a potent inhibitor (IC50=0.14 μg ml−1) of the cathepsin G effect, whereas neither indomethacin (3 μM) nor the thrombin inhibitor hirudin (5 ATU ml−1) elicited any inhibitory activity. Due to their polyanionic structure defibrotide (IC50=0.11 μg ml−1), heparin (IC50=0.48 μg ml−1) and suramin (IC50=1.85 μg ml−1) diminished significantly the relaxation in response to the basic protein cathepsin G. In conclusion, like

  8. 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.

  9. Magnetic Resonance Imaging in the Prognostic Evaluation of Patients with Pulmonary Arterial Hypertension

    PubMed Central

    Capener, Dave; Johns, Chris; Hamilton, Neil; Rothman, Alex; Elliot, Charlie; Condliffe, Robin; Charalampopoulos, Athanasios; Rajaram, Smitha; Lawrie, Allan; Campbell, Michael J.; Wild, Jim M.; Kiely, David G.

    2017-01-01

    Rationale: Prognostication is important when counseling patients and defining treatment strategies in pulmonary arterial hypertension (PAH). Objectives: To determine the value of magnetic resonance imaging (MRI) metrics for prediction of mortality in PAH. Methods: Consecutive patients with PAH undergoing MRI were identified from the ASPIRE (Assessing the Spectrum of Pulmonary Hypertension Identified at a Referral Centre) pulmonary hypertension registry. Measurements and Main Results: During the follow-up period of 42 (range, 17–142) months 576 patients were studied and 221 (38%) died. A derivation cohort (n = 288; 115 deaths) and validation cohort (n = 288; 106 deaths) were identified. We used multivariate Cox regression and found two independent MRI predictors of death (P < 0.01): right ventricular end-systolic volume index adjusted for age and sex, and the relative area change of the pulmonary artery. A model of MRI and clinical data constructed from the derivation cohort predicted mortality in the validation cohort at 1 year (sensitivity, 70 [95% confidence interval (CI), 53–83]; specificity, 62 [95% CI, 62–68]; positive predictive value [PPV], 24 [95% CI, 16–32]; negative predictive value [NPV], 92 [95% CI, 87–96]) and at 3 years (sensitivity, 77 [95% CI, 67–85]; specificity, 73 [95% CI, 66–85]; PPV, 56 [95% CI, 47–65]; and NPV, 87 [95% CI, 81–92]). The model was more accurate in patients with idiopathic PAH at 3 years (sensitivity, 89 [95% CI, 65–84]; specificity, 76 [95% CI, 65–84]; PPV, 60 [95% CI, 46–74]; and NPV, 94 [95% CI, 85–98]). Conclusions: MRI measurements reflecting right ventricular structure and stiffness of the proximal pulmonary vasculature are independent predictors of outcome in PAH. In combination with clinical data MRI has moderate prognostic accuracy in the evaluation of patients with PAH. PMID:28328237

  10. Assessment of proximal pulmonary arterial stiffness using magnetic resonance imaging: effects of technique, age and exercise

    PubMed Central

    Kamalasanan, Anu; Cassidy, Deidre B; Struthers, Allan D; Lipworth, Brian J; Houston, J Graeme

    2016-01-01

    Introduction To compare the reproducibility of pulmonary pulse wave velocity (PWV) techniques, and the effects of age and exercise on these. Methods 10 young healthy volunteers (YHV) and 20 older healthy volunteers (OHV) with no cardiac or lung condition were recruited. High temporal resolution phase contrast sequences were performed through the main pulmonary arteries (MPAs), right pulmonary arteries (RPAs) and left pulmonary arteries (LPAs), while high spatial resolution sequences were obtained through the MPA. YHV underwent 2 MRIs 6 months apart with the sequences repeated during exercise. OHV underwent an MRI scan with on-table repetition. PWV was calculated using the transit time (TT) and flow area techniques (QA). 3 methods for calculating QA PWV were compared. Results PWV did not differ between the two age groups (YHV 2.4±0.3/ms, OHV 2.9±0.2/ms, p=0.1). Using a high temporal resolution sequence through the RPA using the QA accounting for wave reflections yielded consistently better within-scan, interscan, intraobserver and interobserver reproducibility. Exercise did not result in a change in either TT PWV (mean (95% CI) of the differences: −0.42 (−1.2 to 0.4), p=0.24) or QA PWV (mean (95% CI) of the differences: 0.10 (−0.5 to 0.9), p=0.49) despite a significant rise in heart rate (65±2 to 87±3, p<0.0001), blood pressure (113/68 to 130/84, p<0.0001) and cardiac output (5.4±0.4 to 6.7±0.6 L/min, p=0.004). Conclusions QA PWV performed through the RPA using a high temporal resolution sequence accounting for wave reflections yields the most reproducible measurements of pulmonary PWV. PMID:27843548

  11. EIF2AK4 Mutations in Patients Diagnosed With Pulmonary Arterial Hypertension.

    PubMed

    Best, D Hunter; Sumner, Kelli L; Smith, Benjamin P; Damjanovich-Colmenares, Kristy; Nakayama, Ikue; Brown, Lynette M; Ha, Youna; Paul, Eleri; Morris, Ashley; Jama, Mohamed A; Dodson, Mark W; Bayrak-Toydemir, Pinar; Elliott, C Gregory

    2017-04-01

    Differentiating pulmonary venoocclusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) from idiopathic pulmonary arterial hypertension (IPAH) or heritable pulmonary arterial hypertension (HPAH) is important clinically. Mutations in eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) cause heritable PVOD and PCH, whereas mutations in other genes cause HPAH. The aim of this study was to describe the frequency of pathogenic EIF2AK4 mutations in patients diagnosed clinically with IPAH or HPAH. Sanger sequencing and deletion/duplication analysis were performed to detect mutations in the bone morphogenetic protein receptor type II (BMPR2) gene in 81 patients diagnosed at 30 North American medical centers with IPAH (n = 72) or HPAH (n = 9). BMPR2 mutation-negative patients (n = 67) were sequenced for mutations in four other genes (ACVRL1, ENG, CAV1, and KCNK3) known to cause HPAH. Patients negative for mutations in all known PAH genes (n = 66) were then sequenced for mutations in EIF2AK4. We assessed the pathogenicity of EIF2AK4 mutations and reviewed clinical characteristics of patients with pathogenic EIF2AK4 mutations. Pathogenic BMPR2 mutations were identified in 8 of 72 (11.1%) patients with IPAH and 6 of 9 (66.7%) patients with HPAH. A novel homozygous EIF2AK4 mutation (c.257+4A>C) was identified in 1 of 9 (11.1%) patients diagnosed with HPAH. The novel EIF2AK4 mutation (c.257+4A>C) was homozygous in two sisters with severe pulmonary hypertension. None of the 72 patients with IPAH had biallelic EIF2AK4 mutations. Pathogenic biallelic EIF2AK4 mutations are rarely identified in patients diagnosed with HPAH. Identification of pathogenic biallelic EIF2AK4 mutations can aid clinicians in differentiating HPAH from heritable PVOD or PCH. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  12. Variations in pulmonary artery occlusion pressure to estimate changes in pleural pressure.

    PubMed

    Bellemare, Patrick; Goldberg, Peter; Magder, Sheldon A

    2007-11-01

    A readily available assessment of changes in pleural pressure would be useful for ventilator and fluid management in critically ill patients. We examined whether changes in pulmonary artery occlusion pressure (Ppao) adequately reflect respiratory changes in pleural pressure as assessed by changes in intraesophageal balloon pressure (Peso). We studied patients who had a pulmonary catheter and esophageal balloon surrounding a nasogastric tube as part of their care (n=24). We compared changes in Ppao (dPpao) to changes in Peso (dPeso) by Bland-Altman and regression analysis. Adequacy of balloon placement was assessed by performing Mueller maneuvers and adjusting the position to achieve a ratio of dPeso to change in tracheal pressure (dPtr) of 0.85 or higher. This was achieved in only 14 of the 24 subjects. We also compared dCVP to dPeso. The dPpao during spontaneous breaths and positive pressure breaths gave a good estimate of Peso but generally underestimated dPeso (bias=2.2 +8.2 and -3.9 cmH2O for the whole group). The dCVP was not as good a predictor (bias=2.9 +10.3 and -4.6). In patients who have a pulmonary artery catheter in place dPpao gives a lower estimate of changes in pleural pressure and may be more reliable than dPeso. The dCVP is a less reliable predictor than changes in pleural pressure.

  13. The value of transthoracic echocardiography in the diagnosis of anomalous origin of the right pulmonary artery from the ascending aorta: A single center experience from China.

    PubMed

    Wang, Jing; Song, Yue; Cheng, Tsung O; Xie, Mingxing; Wang, Xinfang; Yuan, Li; Yang, Yali; Wang, Lei

    2015-04-01

    Anomalous origin of pulmonary artery (AOPA) from the ascending aorta is a rare but serious congenital cardiac malformation, which frequently involves the right pulmonary artery (RPA). We retrospectively analyzed the echocardiographic characteristics of 9 cases with anomalous origin of the right pulmonary artery from the ascending aorta (AORPA) studied from 2007 to 2014 in our institution. The results were compared with the findings at surgery. The corrective surgery was performed in all 9 cases with AORPA. The diagnosis by transthoracic echocardiography (TTE) of 8 cases with AORPA was confirmed at surgery. The coincidence rate for TTE and surgical findings was 88.9%. One case was misdiagnosed as anomalous origin of the left pulmonary artery from the ascending aorta. The anomalous RPA in all cases had a proximal origin from the posterior or lateral part of the ascending aorta in our series. The mean distance from the aortic valve to the site of origin of pulmonary artery was 16.1 ± 6.6 mm (range: 7.0 mm-24.0 mm). The mean diameter of the anomalous pulmonary artery was 9.6 ± 4.5 mm (range: 4.5 mm-17.0 mm). In 4 of 9 (44.5%) cases there were associated aortopulmonary septal defect, intact ventricular septum, patent ductus arteriosus and interruption of aortic arch (Type A), also known as the Berry's syndrome. Other associated cardiovascular abnormalities included patent ductus arteriosus, ventricular septal defect and atrial septal defect. Severe pulmonary arterial hypertension was noted in all cases. TTE plays an important role in the non-invasive and accurate diagnosis of AORPA. TTE can clearly display its site of origin and course, as well as other associated malformations and hemodynamic changes. TTE also plays an important role in the preoperative diagnosis of AORPA. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Pulmonary hypertension in patients with congenital portosystemic venous shunt: a previously unrecognized association.

    PubMed

    Ohno, Takuro; Muneuchi, Jun; Ihara, Kenji; Yuge, Tetsuji; Kanaya, Yoshiaki; Yamaki, Shigeo; Hara, Toshiro

    2008-04-01

    Pulmonary arterial hypertension has been reported to be observed in association with acquired portal hypertension. However, the contribution of congenital anomalies occurring in the portal system to the development of pulmonary arterial hypertension remains to be elucidated. Nine patients with congenital portosystemic venous shunt were studied from January 1990 through September 2005. Patent ductus venosus was detected in 5 patients, including 3 patients with an absence of the portal vein. The presence of either a gastrorenal or splenorenal shunt was evident in another 4 patients. Six patients had a history of hypergalactosemia with normal enzyme activities, as seen during neonatal screening. Six (66.7%) of the 9 patients were identified to have clinically significant pulmonary arterial hypertension (mean pulmonary artery pressure: 34-79 mm Hg; pulmonary vascular resistances: 5.12-38.07 U). The median age at the onset of pulmonary arterial hypertension was 12 years and 3 months. Histologic studies of lung specimens, which were available in 4 of the 9 patients with congenital portosystemic venous shunt, showed small arterial microthrombotic lesions in 3 patients. This characteristic finding was recognized even in the congenital portosystemic venous shunt patients without PAH. This study demonstrated thromboembolic pulmonary arterial hypertension to be a crucial complication in congenital portosystemic venous shunt, and this pathologic state may be latently present in patients with pulmonary arterial hypertension of unknown etiology.

  15. Asymptomatic peripheral artery disease can limit maximal exercise capacity in chronic obstructive pulmonary disease patients regardless of airflow obstruction and lung hyperinflation.

    PubMed

    Crisafulli, Ernesto; Scelfo, Chiara; Tzani, Panagiota; Aiello, Marina; Bertorelli, Giuseppina; Chetta, Alfredo

    2017-06-01

    Background Silent/asymptomatic peripheral artery disease may occur in patients with chronic obstructive pulmonary disease, but it is poorly investigated. The primary aim of this study was to evaluate in chronic obstructive pulmonary disease patients the impact of asymptomatic/silent peripheral artery disease on maximal exercise capacity; the secondary aim was to search for predictors of peripheral artery disease. Methods We prospectively enrolled chronic obstructive pulmonary disease outpatients. Data on anthropometric characteristics, lung function, cardiopulmonary exercise test and ankle-brachial index were recorded. The cut-off of ankle-brachial index used to define patients with peripheral artery disease was ≤0.90. Results We studied 47 patients and found 24 patients (51%) who showed peripheral artery disease. As compared to patients without peripheral artery disease, patients with peripheral artery disease had lower values of peak oxygen uptake, peak workload, energy expenditure (metabolic equivalents) and heart rate recovery, but showed the same degree of airflow obstruction and static and dynamic hyperinflation. In a multivariate linear regression model performed to identify variables predicting metabolic equivalents, ankle-brachial index (β 2.59; 95% confidence interval 0.51-4.67; p = 0.016) was an independent variable. In the search for predictors of peripheral artery disease, heart rate recovery (odds ratio 8.80; 95% confidence interval 1.30-59.35; p = 0.026) increased the risk of peripheral artery disease, whereas metabolic equivalents (odds ratio 0.50; 95% confidence interval 0.26-0.94, p = 0.033) and inhaled corticosteroids+long-acting β 2 agonists (odds ratio 0.13; 95% confidence interval 0.02-0.83; p = 0.030) reduced this risk. Conclusions In chronic obstructive pulmonary disease outpatients, asymptomatic/silent peripheral artery disease affects the maximal exercise capacity regardless of airflow obstruction and lung

  16. 'End-stage' heart failure therapy: potential lessons from congenital heart disease: from pulmonary artery banding and interatrial communication to parallel circulation.

    PubMed

    Schranz, Dietmar; Akintuerk, Hakan; Voelkel, Norbert F

    2017-02-15

    The final therapy of 'end-stage heart failure' is orthotopic heart, lung or heart-lung transplantation. However, these options are not available for many patients worldwide. Therefore, novel therapeutical strategies are needed. Based on pathophysiological insights regarding (1) the long-term impact of an obstructive pulmonary outflow tract in neonates with congenitally corrected transposition of the great arteries, (2) the importance of a restrictive versus a non-restrictive atrial septum in neonates born with a borderline left ventricle and (3) the significance of both, a patent foramen ovale and/or open ductus arteriosus for survival of newborns with persistent pulmonary hypertension, the current review introduces some therapeutical strategies that may be applicable to selected patients with heart failure. These strategies include (1) reversible pulmonary artery banding in left ventricular-dilated cardiomyopathy with preserved right ventricular function, (2) the creation of restrictive interatrial communication to treat diastolic (systolic) heart failure, (3) atrioseptostomy or reverse Potts shunt in pulmonary arterial hypertension and (4) return to a fetal, parallel circulation by combining atrioseptostomy and reversed Potts shunt with or without placement of a bilateral pulmonary artery banding. While still being experimental, it is hoped that the procedures presented in the current overview will inspire future novel therapeutic strategies that may be applicable to selected patients with heart failure. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  17. Endothelin-1-induced contraction of pulmonary arteries from endotoxemic rats is attenuated by the endothelin-A receptor antagonist, BQ123.

    PubMed

    Curzen, N P; Mitchell, J A; Jourdan, K B; Griffiths, M J; Evans, T W

    1996-12-01

    Sepsis is characterized by systemic vasodilation and hyporesponsiveness to constrictor agents, at a time when the pulmonary circulation exhibits varying degrees of vasoconstriction. Plasma endothelin-1 concentrations are increased, but the role of this potent vasoconstrictor peptide in modulating the vascular response to sepsis is unknown. Therefore, we assessed the effect of endothelin-A receptor antagonism in the response of pulmonary arteries from rats treated with lipopolysaccharide to endothelin-1, and determined the vasomotor role of the endothelin-B receptors that are known to be located on rat pulmonary artery smooth muscle and endothelium. Prospective, controlled study. Animal research laboratory. Male Wistar rats (275 to 300 g). Animals were injected with either lipopolysaccharide (20 mg/kg i.p.) or saline (1 mL i.p.) 4 hrs before being killed. The main pulmonary arteries were cut into 2-mm rings, and suspended in an organ bath. In the first set of experiments, half of the rings underwent a procedure that removed the endothelium, and the contractile response to cumulative doses of endothelin-1 (10(-11) to 10(-6) M) was measured. Half of the rings were pretreated with the endothelin-A receptor antagonist, BQ123 (10(-5) M or 10(-6) M), and the other half of the rings were treated with vehicle. In a separate group of experiments, the contractile response to cumulative concentrations of the selective endothelin-B agonist, sarafotoxin S6c (10(-11) to 10(-6) M), was measured in rings at baseline tension. Second, the possible dilator effect of endothelin-B receptor activation was tested by the administration of sarafotoxin S6c (10(-7) to 10(-6) M) to rings preconstricted by 10(-6) M of U46619, a thromboxane receptor agonist, either in the presence or absence of the nitric oxide synthase inhibitor, N omega-nitro-L-arginine-methylester (10(-4) M). Acetylcholine-induced (10(-4) M), endothelium-dependent vasodilation was also measured. BQ123 (10(-5) or 10(-6) M

  18. Type II single umbilical artery (persistent vitelline artery) in an otherwise normal fetus.

    PubMed

    Gamzu, Ronni; Zalel, Yaron; Jacobson, Jeffrey M; Screiber, Leticia; Achiron, Reuven

    2002-11-01

    A single umbilical artery resulting from absence of the umbilical arteries and persistence of the vitelline artery that arises directly from the abdominal aorta has been described only in malformed fetuses with sirenomelia or caudal regression. Such an aberrant artery was suggested to be the etiology of sirenomelia caused by a 'steal' mechanism of blood flow from the caudal end of the embryo. We present a case in which prenatal ultrasound showed a similar aberrant single artery arising from the abdominal aorta in an otherwise normal fetus with a normal course of pregnancy. This vessel, a continuation of the superior mesenteric artery (SMA), corresponds to a persistent vitelline artery assuming the function of the umbilical arteries. The etiology of such a finding and its possible consequences are discussed. Copyright 2002 John Wiley & Sons, Ltd.

  19. Mutations of NOTCH3 in childhood pulmonary arterial hypertension

    PubMed Central

    Chida, Ayako; Shintani, Masaki; Matsushita, Yoshihisa; Sato, Hiroki; Eitoku, Takahiro; Nakayama, Tomotaka; Furutani, Yoshiyuki; Hayama, Emiko; Kawamura, Yoichi; Inai, Kei; Ohtsuki, Shinichi; Saji, Tsutomu; Nonoyama, Shigeaki; Nakanishi, Toshio

    2014-01-01

    Mutations of BMPR2 and other TGF-β superfamily genes have been reported in pulmonary arterial hypertension (PAH). However, 60–90% of idiopathic PAH cases have no mutations in these genes. Recently, the expression of NOTCH3 was shown to be increased in the pulmonary artery smooth muscle cells of PAH patients. We sought to investigate NOTCH3 and its target genes in PAH patients and clarify the role of NOTCH3 signaling. We screened for mutations in NOTCH3, HES1, and HES5 in 41 PAH patients who had no mutations in BMPR2, ALK1, endoglin, SMAD1/4/8, BMPR1B, or Caveolin-1. Two novel missense mutations (c.2519 G>A p.G840E, c.2698 A>C p.T900P) in NOTCH3 were identified in two PAH patients. We performed functional analysis using stable cell lines expressing either wild-type or mutant NOTCH3. The protein-folding chaperone GRP78/BiP was colocalized with wild-type NOTCH3 in the endoplasmic reticulum, whereas the majority of GRP78/BiP was translocated into the nuclei of cells expressing mutant NOTCH3. Cell proliferation and viability were higher for cells expressing mutant NOTCH3 than for those expressing wild-type NOTCH3. We identified novel NOTCH3 mutations in PAH patients and revealed that these mutations were involved in cell proliferation and viability. NOTCH3 mutants induced an impairment in NOTCH3-HES5 signaling. The results may contribute to the elucidation of PAH pathogenesis. PMID:24936512

  20. Cytoskeletal defects in Bmpr2-associated pulmonary arterial hypertension.

    PubMed

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

    2012-03-01

    The heritable form of pulmonary arterial hypertension (PAH) is typically caused by a mutation in bone morphogenic protein receptor type 2 (BMPR2), and mice expressing Bmpr2 mutations develop PAH with features similar to human disease. BMPR2 is known to interact with the cytoskeleton, and human array studies in PAH patients confirm alterations in cytoskeletal pathways. The goal of this study was to evaluate cytoskeletal defects in BMPR2-associated PAH. Expression arrays on our Bmpr2 mutant mouse lungs revealed cytoskeletal defects as a prominent molecular consequence of universal expression of a Bmpr2 mutation (Rosa26-Bmpr2(R899X)). Pulmonary microvascular endothelial cells cultured from these mice have histological and functional cytoskeletal defects. Stable transfection of different BMPR2 mutations into pulmonary microvascular endothelial cells revealed that cytoskeletal defects are common to multiple BMPR2 mutations and are associated with activation of the Rho GTPase, Rac1. Rac1 defects are corrected in cell culture and in vivo through administration of exogenous recombinant human angiotensin-converting enzyme 2 (rhACE2). rhACE2 reverses 77% of gene expression changes in Rosa26-Bmpr2(R899X) transgenic mice, in particular, correcting defects in cytoskeletal function. Administration of rhACE2 to Rosa26-Bmpr2(R899X) mice with established PAH normalizes pulmonary pressures. Together, these findings suggest that cytoskeletal function is central to the development of BMPR2-associated PAH and that intervention against cytoskeletal defects may reverse established disease.

  1. Analysis of volatile compounds in exhaled breath condensate in patients with severe pulmonary arterial hypertension.

    PubMed

    Mansoor, J K; Schelegle, Edward S; Davis, Cristina E; Walby, William F; Zhao, Weixiang; Aksenov, Alexander A; Pasamontes, Alberto; Figueroa, Jennifer; Allen, Roblee

    2014-01-01

    An important challenge to pulmonary arterial hypertension (PAH) diagnosis and treatment is early detection of occult pulmonary vascular pathology. Symptoms are frequently confused with other disease entities that lead to inappropriate interventions and allow for progression to advanced states of disease. There is a significant need to develop new markers for early disease detection and management of PAH. Exhaled breath condensate (EBC) samples were compared from 30 age-matched normal healthy individuals and 27 New York Heart Association functional class III and IV idiopathic pulmonary arterial hypertenion (IPAH) patients, a subgroup of PAH. Volatile organic compounds (VOC) in EBC samples were analyzed using gas chromatography/mass spectrometry (GC/MS). Individual peaks in GC profiles were identified in both groups and correlated with pulmonary hemodynamic and clinical endpoints in the IPAH group. Additionally, GC/MS data were analyzed using autoregression followed by partial least squares regression (AR/PLSR) analysis to discriminate between the IPAH and control groups. After correcting for medicaitons, there were 62 unique compounds in the control group, 32 unique compounds in the IPAH group, and 14 in-common compounds between groups. Peak-by-peak analysis of GC profiles of IPAH group EBC samples identified 6 compounds significantly correlated with pulmonary hemodynamic variables important in IPAH diagnosis. AR/PLSR analysis of GC/MS data resulted in a distinct and identifiable metabolic signature for IPAH patients. These findings indicate the utility of EBC VOC analysis to discriminate between severe IPAH and a healthy population; additionally, we identified potential novel biomarkers that correlated with IPAH pulmonary hemodynamic variables that may be important in screening for less severe forms IPAH.

  2. Analysis of Volatile Compounds in Exhaled Breath Condensate in Patients with Severe Pulmonary Arterial Hypertension

    PubMed Central

    Mansoor, J. K.; Schelegle, Edward S.; Davis, Cristina E.; Walby, William F.; Zhao, Weixiang; Aksenov, Alexander A.; Pasamontes, Alberto; Figueroa, Jennifer; Allen, Roblee

    2014-01-01

    Background An important challenge to pulmonary arterial hypertension (PAH) diagnosis and treatment is early detection of occult pulmonary vascular pathology. Symptoms are frequently confused with other disease entities that lead to inappropriate interventions and allow for progression to advanced states of disease. There is a significant need to develop new markers for early disease detection and management of PAH. Methodolgy and Findings Exhaled breath condensate (EBC) samples were compared from 30 age-matched normal healthy individuals and 27 New York Heart Association functional class III and IV idiopathic pulmonary arterial hypertenion (IPAH) patients, a subgroup of PAH. Volatile organic compounds (VOC) in EBC samples were analyzed using gas chromatography/mass spectrometry (GC/MS). Individual peaks in GC profiles were identified in both groups and correlated with pulmonary hemodynamic and clinical endpoints in the IPAH group. Additionally, GC/MS data were analyzed using autoregression followed by partial least squares regression (AR/PLSR) analysis to discriminate between the IPAH and control groups. After correcting for medicaitons, there were 62 unique compounds in the control group, 32 unique compounds in the IPAH group, and 14 in-common compounds between groups. Peak-by-peak analysis of GC profiles of IPAH group EBC samples identified 6 compounds significantly correlated with pulmonary hemodynamic variables important in IPAH diagnosis. AR/PLSR analysis of GC/MS data resulted in a distinct and identifiable metabolic signature for IPAH patients. Conclusions These findings indicate the utility of EBC VOC analysis to discriminate between severe IPAH and a healthy population; additionally, we identified potential novel biomarkers that correlated with IPAH pulmonary hemodynamic variables that may be important in screening for less severe forms IPAH. PMID:24748102

  3. CD38 Mediates Angiotensin II–Induced Intracellular Ca2+ Release in Rat Pulmonary Arterial Smooth Muscle Cells

    PubMed Central

    Lee, Suengwon; Paudel, Omkar; Jiang, Yongliang; Yang, Xiao-Ru

    2015-01-01

    CD38 is a multifunctional enzyme that catalyzes the formation of the endogenous Ca2+-mobilizing messengers cyclic ADP-ribose (cADPR) and nicotinic acid adenosine dinucleotide phosphate (NAADP) for the activation of ryanodine receptors (RyRs) of sarcoplasmic reticulum and NAADP-sensitive Ca2+ release channels in endolysosomes, respectively. It plays important roles in systemic vascular functions, but there is little information on CD38 in pulmonary arterial smooth muscle cells (PASMCs). Earlier studies suggested a redox-sensing role of CD38 in hypoxic pulmonary vasoconstriction. This study sought to characterize its roles in angiotensin II (Ang II)–induced Ca2+ release (AICR) in PASMCs. Examination of CD38 expression in various rat arteries found high levels of CD38 mRNA and protein in pulmonary arteries. The Ang II–elicited Ca2+ response consisted of extracellular Ca2+ influx and intracellular Ca2+ release in PASMCs. AICR activated in the absence of extracellular Ca2+ was reduced by pharmacological or siRNA inhibition of CD38, by the cADPR antagonist 8-bromo-cADPR or ryanodine, and by the NAADP antagonist Ned-19 or disruption of endolysosomal Ca2+ stores with the vacuolar H+-ATPase inhibitor bafilomycin A1. Suppression of AICR by the inhibitions of cADPR- and NAADP-dependent pathways were nonadditive, indicating interdependence of RyR- and NAADP-gated Ca2+ release. Furthermore, AICR was inhibited by the protein kinase C inhibitor staurosporine, the nonspecific NADPH oxidase (NOX) inhibitors apocynin and diphenyleneiodonium, the NOX2-specific inhibitor gp91ds-tat, and the scavenger of reactive oxygen species (ROS) tempol. These results provide the first evidence that Ang II activates CD38-dependent Ca2+ release via the NOX2-ROS pathway in PASMCs. PMID:25078456

  4. Cardiovascular effects of right ventricle-pulmonary artery valved conduit implantation in experimental pulmonic stenosis.

    PubMed

    Saida, Yuuto; Tanaka, Ryou; Fukushima, Ryuji; Hoshi, Katsuichiro; Hira, Satoshi; Soda, Aiko; Iizuka, Tomoya; Ishikawa, Taisuke; Nishimura, Taiki; Yamane, Yoshihisa

    2009-04-01

    Right ventricle (RV)-pulmonary artery (PA) valved conduit (RPVC) implantation decreases RV systolic pressure in pulmonic stenosis (PS) by forming a bypass route between the RV and the PA. The present study evaluates valved conduits derived from canine aortae in a canine model of PS produced by pulmonary artery banding (PAB). Pulmonary stenosis was elicited using PAB in 10 conditioned beagles aged 8 months. Twelve weeks after PAB, the dogs were assigned to one group that did not undergo surgical intervention and another that underwent RPVC using denacol-treated canine aortic valved grafts (PAB+RPVC). Twelve weeks later, the rate of change in the RV-PA systolic pressure gradient was significantly decreased in the PAB+RPVC, compared with the PAB group (60.5 +/- 16.7% vs. 108.9 +/- 22.9%; p<0.01). In addition, the end-diastolic RV free wall thickness (RVFWd) was significantly reduced in the PAB+RPVC, compared with the PAB group (8.2 +/- 0.2 vs. 9.4 +/- 0.7 mm; p<0.05). Thereafter, regurgitation was not evident beyond the conduit valve and the decrease in RV pressure overload induced by RPVC was confirmed. The present results indicate that RPVC can be performed under a beating heart without cardiopulmonary bypass and adapted to dogs with various types of PS, including "supra valvular" PS or PS accompanied by dysplasia of the pulmonary valve. Therefore, we consider that this method is useful for treating PS in small animals.

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

    PubMed Central

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

    2015-01-01

    Key points Lung ventilation and pulmonary artery pressure rise progressively in response to 8 h of hypoxia, changes described as ‘acclimatization to hypoxia’. Acclimatization responses differ markedly between humans for unknown reasons.We explored whether the magnitudes of the ventilatory and vascular responses were related, and whether the degree of acclimatization could be predicted by acute measurements of ventilatory and vascular sensitivities.In 80 healthy human volunteers measurements of acclimatization were made before, during, and after a sustained exposure to 8 h of isocapnic hypoxia.No correlation was found between measures of ventilatory and pulmonary vascular acclimatization.The ventilatory chemoreflex sensitivities to acute hypoxia and hypercapnia all increased in proportion to their pre‐acclimatization values following 8 h of hypoxia. The peripheral (rapid) chemoreflex sensitivity to CO2, measured before sustained hypoxia against a background of hyperoxia, was a modest predictor of ventilatory acclimatization to hypoxia. This finding has relevance to predicting human acclimatization to the hypoxia of altitude. Abstract Pulmonary ventilation and pulmonary arterial pressure both rise progressively during the first few hours of human acclimatization to hypoxia. These responses are highly variable between individuals, but the origin of this variability is unknown. Here, we sought to determine whether the variabilities between different measures of response to sustained hypoxia were related, which would suggest a common source of variability. Eighty volunteers individually underwent an 8‐h isocapnic exposure to hypoxia (end‐tidal P O2=55 Torr) in a purpose‐built chamber. Measurements of ventilation and pulmonary artery systolic pressure (PASP) assessed by Doppler echocardiography were made during the exposure. Before and after the exposure, measurements were made of the ventilatory sensitivities to acute isocapnic hypoxia (GpO2) and

  6. Proximal pulmonary vascular stiffness as a prognostic factor in children with pulmonary arterial hypertension.

    PubMed

    Friesen, Richard M; Schäfer, Michal; Ivy, D Dunbar; Abman, Steven H; Stenmark, Kurt; Browne, Lorna P; Barker, Alex J; Hunter, Kendall S; Truong, Uyen

    2018-05-16

    Main pulmonary artery (MPA) stiffness and abnormal flow haemodynamics in pulmonary arterial hypertension (PAH) are strongly associated with elevated right ventricular (RV) afterload and associated with disease severity and poor clinical outcomes in adults with PAH. However, the long-term effects of MPA stiffness on RV function in children with PAH remain poorly understood. This study is the first comprehensive evaluation of MPA stiffness in children with PAH, delineating the mechanistic relationship between flow haemodynamics and MPA stiffness as well as the prognostic ability of these measures regarding clinical outcomes. Fifty-six children diagnosed with PAH underwent baseline cardiac magnetic resonance (CMR) acquisition and were compared with 23 control subjects. MPA stiffness and wall shear stress (WSS) were evaluated using phase contrast CMR and were evaluated for prognostic potential along with standard RV volumetric and functional indices. Pulse wave velocity (PWV) was significantly increased (2.8 m/s vs. 1.4 m/s, P < 0.0001) and relative area change (RAC) was decreased (25% vs. 37%, P < 0.0001) in the PAH group, correlating with metrics of RV performance. Decreased WSS was associated with a decrease in RAC over time (r = 0.679, P < 0.001). For each unit increase in PWV, there was approximately a 3.2-fold increase in having a moderate clinical event. MPA stiffness assessed by non-invasive CMR was increased in children with PAH and correlated with RV performance, suggesting that MPA stiffness is a major contribution to RV dysfunction. PWV is predictive of moderate clinical outcomes, and may be a useful prognostic marker of disease activity in children with PAH.

  7. 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

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

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

    Guo, Haipeng; Zhang, Xin; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan 250012

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

  9. Validation of a brief telephone battery for neurocognitive assessment of patients with pulmonary arterial hypertension.

    PubMed

    Taichman, Darren B; Christie, Jason; Biester, Rosette; Mortensen, Jennifer; White, Joanne; Kaplan, Sandra; Hansen-Flaschen, John; Palevsky, Harold I; Elliott, C Gregory; Hopkins, Ramona O

    2005-04-25

    The effects of pulmonary arterial hypertension on brain function are not understood, despite patients' frequent complaints of cognitive difficulties. Using clinical instruments normally administered during standard in-person assessment of neurocognitive function in adults, we assembled a battery of tests designed for administration over the telephone. The purpose was to improve patient participation, facilitate repeated test administration, and reduce the cost of research on the neuropsychological consequences of acute and chronic cardiorespiratory diseases. We undertook this study to validate telephone administration of the tests. 23 adults with pulmonary arterial hypertension underwent neurocognitive assessment using both standard in-person and telephone test administration, and the results of the two methods compared using interclass correlations. For most of the tests in the battery, scores from the telephone assessment correlated strongly with those obtained by in-person administration of the same tests. Interclass correlations between 0.5 and 0.8 were observed for tests that assessed attention, memory, concentration/working memory, reasoning, and language/crystallized intelligence (p < or = 0.05 for each). Interclass correlations for the Hayling Sentence Completion test of executive function approached significance (p = 0.09). All telephone tests were completed within one hour. Administration of this neurocognitive test battery by telephone should facilitate assessment of neuropsychological deficits among patients with pulmonary arterial hypertension living across broad geographical areas, and may be useful for monitoring changes in neurocognitive function in response to PAH-specific therapy or disease progression.

  10. Micro-CT image-derived metrics quantify arterial wall distensibility reduction in a rat model of pulmonary hypertension

    NASA Astrophysics Data System (ADS)

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

    2000-04-01

    We developed methods to quantify arterial structural and mechanical properties in excised rat lungs and applied them to investigate the distensibility decrease accompanying chronic hypoxia-induced pulmonary hypertension. Lungs of control and hypertensive (three weeks 11% O2) animals were excised and a contrast agent introduced before micro-CT imaging with a special purpose scanner. For each lung, four 3D image data sets were obtained, each at a different intra-arterial contrast agent pressure. Vessel segment diameters and lengths were measured at all levels in the arterial tree hierarchy, and these data used to generate features sensitive to distensibility changes. Results indicate that measurements obtained from 3D micro-CT images can be used to quantify vessel biomechanical properties in this rat model of pulmonary hypertension and that distensibility is reduced by exposure to chronic hypoxia. Mechanical properties can be assessed in a localized fashion and quantified in a spatially-resolved way or as a single parameter describing the tree as a whole. Micro-CT is a nondestructive way to rapidly assess structural and mechanical properties of arteries in small animal organs maintained in a physiological state. Quantitative features measured by this method may provide valuable insights into the mechanisms causing the elevated pressures in pulmonary hypertension of differing etiologies and should become increasingly valuable tools in the study of complex phenotypes in small-animal models of important diseases such as hypertension.

  11. 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

  12. Impact of severe tricuspid regurgitation on accuracy of systolic pulmonary arterial pressure measured by Doppler echocardiography: Analysis in an unselected patient population.

    PubMed

    Fei, Beini; Fan, Ting; Zhao, Ling; Pei, Xiaoli; Shu, Xianhong; Fang, Xiaoyan; Cheng, Leilei

    2017-07-01

    Pulmonary arterial pressure is an important index in cardiovascular disorders, especially for pulmonary hypertension (PH). Doppler echocardiography (DE) is widely used as a noninvasive method to assess pulmonary arterial pressure. However, recent studies have found several hemodynamic factors that affect its accuracy in estimating systolic pulmonary arterial pressure (sPAP). But the effect of tricuspid regurgitation (TR) has not been investigated. Therefore, our study is aimed to determine whether the severity of TR will affect the accuracy of sPAP measured by DE in an unselected patient population. We retrospectively studied 177 patients who underwent DE and right heart catheterization (RHC) examinations. Patients were categorized into 3 groups according to the severity of TR (mild, moderate, and severe). The discrepancy in sPAP measured by DE and RHC was calculated and compared in each group. Determinants of discordant results between two methods were also evaluated. Age, gender, interval between DE and RHC, sequence of DE and RHC were similar among groups (all P>.05). Differences in sPAP, RAP, and tricuspid regurgitation pressure gradient (TR-PG) were similar in group 1 and 2 (all P>.05), while all significantly higher in group 3 (all P<.05). The difference in sPAP between DE and RHC was affected independently by severe TR and severe PH (both P<.05). Severe TR and severe PH affect the accuracy of sPAP measured by DE. Modification of echocardiographic sPAP measurements by taking into consideration of these factors may lead to reduced systemic errors. © 2017, Wiley Periodicals, Inc.

  13. PAR-2 inhibition reverses experimental pulmonary hypertension.

    PubMed

    Kwapiszewska, Grazyna; Markart, Philipp; Dahal, Bhola Kumar; Kojonazarov, Baktybek; Marsh, Leigh Matthew; Schermuly, Ralph Theo; Taube, Christian; Meinhardt, Andreas; Ghofrani, Hossein Ardeschir; Steinhoff, Martin; Seeger, Werner; Preissner, Klaus Theo; Olschewski, Andrea; Weissmann, Norbert; Wygrecka, Malgorzata

    2012-04-27

    A hallmark of the vascular remodeling process underlying pulmonary hypertension (PH) is the aberrant proliferation and migration of pulmonary arterial smooth muscle cells (PASMC). Accumulating evidence suggests that mast cell mediators play a role in the pathogenesis of PH. In the present study we investigated the importance of protease-activated receptor (PAR)-2 and its ligand mast cell tryptase in the development of PH. Our results revealed strong increase in PAR-2 and tryptase expression in the lungs of idiopathic pulmonary arterial hypertension (IPAH) patients, hypoxia-exposed mice, and monocrotaline (MCT)-treated rats. Elevated tryptase levels were also detected in plasma samples from IPAH patients. Hypoxia and platelet-derived growth factor (PDGF)-BB upregulated PAR-2 expression in PASMC. This effect was reversed by HIF (hypoxia inducible factor)-1α depletion, PDGF-BB neutralizing antibody, or the PDGF-BB receptor antagonist Imatinib. Attenuation of PAR-2 expression was also observed in smooth muscle cells of pulmonary vessels of mice exposed to hypoxia and rats challenged with MCT in response to Imatinib treatment. Tryptase induced PASMC proliferation and migration as well as enhanced synthesis of fibronectin and matrix metalloproteinase-2 in a PAR-2- and ERK1/2-dependent manner, suggesting that PAR-2-dependent signaling contributes to vascular remodeling by various mechanisms. Furthermore, PAR-2(-/-) mice were protected against hypoxia-induced PH, and PAR-2 antagonist application reversed established PH in the hypoxia mouse model. Our study identified a novel role of PAR-2 in vascular remodeling in the lung. Interference with this pathway may offer novel therapeutic options for the treatment of PH.

  14. IREB2 and GALC are associated with pulmonary artery enlargement in chronic obstructive pulmonary disease.

    PubMed

    Lee, Jin Hwa; Cho, Michael H; Hersh, Craig P; McDonald, Merry-Lynn N; Wells, J Michael; Dransfield, Mark T; Bowler, Russell P; Lynch, David A; Lomas, David A; Crapo, James D; Silverman, Edwin K

    2015-03-01

    Pulmonary hypertension is associated with advanced chronic obstructive pulmonary disease (COPD), although pulmonary vascular changes occur early in the course of the disease. Pulmonary artery (PA) enlargement (PAE) measured by computed tomography correlates with pulmonary hypertension and COPD exacerbation frequency. Genome-wide association studies of PAE in subjects with COPD have not been reported. To investigate whether genetic variants are associated with PAE within subjects with COPD, we investigated data from current and former smokers from the COPDGene Study and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study. The ratio of the diameter of the PA to the diameter of the aorta (A) was measured using computed tomography. PAE was defined as PA/A greater than 1. A genome-wide association study for COPD with PAE was performed using subjects with COPD without PAE (PA/A ≤ 1) as a control group. A secondary analysis used smokers with normal spirometry as a control group. Genotyping was performed on Illumina platforms. The results were summarized using fixed-effect meta-analysis. Both meta-analyses revealed a genome-wide significant locus on chromosome 15q25.1 in IREB2 (COPD with versus without PAE, rs7181486; odds ratio [OR] = 1.32; P = 2.10 × 10(-8); versus smoking control subjects, rs2009746; OR = 1.42; P = 1.32 × 10(-9)). PAE was also associated with a region on 14q31.3 near the GALC gene (rs7140285; OR = 1.55; P = 3.75 × 10(-8)). Genetic variants near IREB2 and GALC likely contribute to genetic susceptibility to PAE associated with COPD. This study provides evidence for genetic heterogeneity associated with a clinically important COPD vascular subtype.

  15. IREB2 and GALC Are Associated with Pulmonary Artery Enlargement in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Lee, Jin Hwa; Cho, Michael H.; Hersh, Craig P.; McDonald, Merry-Lynn N.; Wells, J. Michael; Dransfield, Mark T.; Bowler, Russell P.; Lynch, David A.; Lomas, David A.; Crapo, James D.

    2015-01-01

    Pulmonary hypertension is associated with advanced chronic obstructive pulmonary disease (COPD), although pulmonary vascular changes occur early in the course of the disease. Pulmonary artery (PA) enlargement (PAE) measured by computed tomography correlates with pulmonary hypertension and COPD exacerbation frequency. Genome-wide association studies of PAE in subjects with COPD have not been reported. To investigate whether genetic variants are associated with PAE within subjects with COPD, we investigated data from current and former smokers from the COPDGene Study and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study. The ratio of the diameter of the PA to the diameter of the aorta (A) was measured using computed tomography. PAE was defined as PA/A greater than 1. A genome-wide association study for COPD with PAE was performed using subjects with COPD without PAE (PA/A ≤ 1) as a control group. A secondary analysis used smokers with normal spirometry as a control group. Genotyping was performed on Illumina platforms. The results were summarized using fixed-effect meta-analysis. Both meta-analyses revealed a genome-wide significant locus on chromosome 15q25.1 in IREB2 (COPD with versus without PAE, rs7181486; odds ratio [OR] = 1.32; P = 2.10 × 10−8; versus smoking control subjects, rs2009746; OR = 1.42; P = 1.32 × 10−9). PAE was also associated with a region on 14q31.3 near the GALC gene (rs7140285; OR = 1.55; P = 3.75 × 10−8). Genetic variants near IREB2 and GALC likely contribute to genetic susceptibility to PAE associated with COPD. This study provides evidence for genetic heterogeneity associated with a clinically important COPD vascular subtype. PMID:25101718

  16. Hypoxia increases pulmonary arterial thromboxane receptor internalization independent of receptor sensitization.

    PubMed

    Fediuk, J; Sikarwar, A S; Lizotte, P P; Hinton, M; Nolette, N; Dakshinamurti, S

    2015-02-01

    Persistent Pulmonary Hypertension of the Newborn (PPHN) is characterized by sustained vasospasm and an increased thromboxane:prostacyclin ratio. Thromboxane (TP) receptors signal via Gαq to mobilize IP3 and Ca(2+), causing pulmonary arterial constriction. We have previously reported increased TP internalization in hypoxic pulmonary arterial (PA) myocytes. Serum-deprived PA myocytes were grown in normoxia (NM) or hypoxia (HM) for 72 h. TP localization was visualized in agonist-naïve and -challenged NM and HM by immunocytochemistry. Pathways for agonist-induced TP receptor internalization were determined by inhibiting caveolin- or clathrin-mediated endocytosis, and caveolar fractionation. Roles of actin and tubulin in TP receptor internalization were assessed using inhibitors of tubulin, actin-stabilizing or -destabilizing agents. PKA, PKC or GRK activation and inhibition were used to determine the kinase responsible for post-agonist receptor internalization. Agonist-naïve HM had decreased cell surface TP, and greater TP internalization after agonist challenge. TP protein did not sort with caveolin-rich fractions. Inhibition of clathrin prevented TP internalization. Both actin-stabilizing and -destabilizing agents prevented TP endocytosis in NM, while normalizing TP internalization in HM. Velocity of TP internalization was unaffected by PKA activity, but PKC activation normalized TP receptor internalization in HM. GRK inhibition had no effect. We conclude that in hypoxic myocytes, TP is internalized faster and to a greater extent than in normoxic controls. Internalization of the agonist-challenged TP requires clathrin, dynamic actin and is sensitive to PKC activity. TP receptor trafficking and signaling in hypoxia are pivotal to understanding increased vasoconstrictor sensitivity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Enhanced pulmonary vasodilator reserve and abnormal right ventricular: pulmonary artery coupling in heart failure with preserved ejection fraction.

    PubMed

    Andersen, Mads J; Hwang, Seok-Jae; Kane, Garvan C; Melenovsky, Vojtech; Olson, Thomas P; Fetterly, Kenneth; Borlaug, Barry A

    2015-05-01

    Pulmonary hypertension and right ventricular (RV) dysfunction are common in patients with advanced heart failure with preserved ejection fraction (HFpEF), yet their underlying mechanisms remain poorly understood. We sought to examine RV-pulmonary artery (PA) functional reserve responses and RV-PA coupling at rest and during β-adrenergic stimulation in subjects with earlier stage HFpEF. In a prospective trial, subjects with HFpEF (n=39) and controls (n=18) underwent comprehensive invasive and noninvasive hemodynamic assessment using high fidelity micromanometer catheters, echocardiography, and expired gas analysis at rest and during dobutamine infusion. HFpEF subjects displayed similar RV structure but significantly impaired RV systolic (lower RV dP/dtmax/IP and s') and diastolic function (higher RV τ) coupled with more severe pulmonary vascular disease, manifest by higher PA pressures, higher PA resistance, and lower PA compliance compared with controls. Dobutamine infusion caused greater pulmonary vasodilation in HFpEF compared with controls, with enhanced reductions in PA resistance, greater increase in PA compliance, and a more negative slope in the PA pressure-flow relationship when compared with controls (all P<0.001). RV-PA coupling analysis revealed that dobutamine improved RV ejection in HFpEF subjects through afterload reduction alone, rather than through enhanced contractility, indicating RV systolic reserve dysfunction. Pulmonary hypertension in early stage HFpEF is related to partially reversible pulmonary vasoconstriction coupled with RV systolic and diastolic dysfunction, even in the absence of RV structural remodeling. Pulmonary vascular tone is more favorably responsive to β-adrenergic stimulation in HFpEF than controls, suggesting a potential role for β-agonists in the treatment of patients with HFpEF and pulmonary hypertension. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01418248. © 2015 American Heart Association, Inc.

  18. Key articles and guidelines in the management of pulmonary arterial hypertension: 2011 update.

    PubMed

    Johnson, Samuel G; Kayser, Steven R; Attridge, Rebecca L; Duvall, Laura; Kiser, Tyree H; Moote, Rebecca; Reed, Brent N; Rodgers, Jo E; Erstad, Brian

    2012-06-01

    Pharmacotherapeutic approaches for the management of pulmonary arterial hypertension (PAH) have expanded greatly in the last 10 years. Pulmonary arterial hypertension is a relatively rare disease and is associated with myriad disease processes. The older term for PAH, primary PAH, has been changed to represent these differences and to distinguish it from postcapillary PAH associated with left-sided heart failure. Limitations in evaluating treatment approaches for PAH include its rarity, the small number of patients included in clinical trials, and issues regarding the use of placebo-controlled trials in a disease with such a high mortality rate if left untreated. Management options include the use of prostacyclin and prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase inhibitors, as well as traditional background therapy with diuretics, digoxin, calcium channel blockers, and warfarin. Numerous drugs are under investigation to evaluate their possible roles in management. Combination therapy is increasingly becoming a standard approach to therapy, with mounting literature to document effectiveness. Current or emerging roles for the pharmacist in the management of PAH largely involves ensuring access to drug therapy, facilitating specialty pharmacy dispensing, and providing patient counseling. Newer roles may include future drug development, optimized use of investigational drugs, and specialized disease management programs. This compilation includes a series of articles identifying important literature in cardiovascular pharmacotherapy. This bibliography focuses on pharmacotherapeutic management of pulmonary arterial hypertension (PAH). Most of the cited works present the results of significant human clinical studies that have shaped the management of patients with PAH. Limited primary literature is available for some topics, so in addition, consensus documents prepared by expert panels are reviewed. This compilation may serve as a

  19. Saline contrast echocardiography for the detection of anomalous origin of pulmonary artery from aorta.

    PubMed

    Gupta, Saurabh Kumar; Gupta, Abhishek

    2017-01-01

    Saline contrast echocardiography is a well-established modality for the diagnosis of right-to-left shunt lesions. In this brief report, we demonstrate, for the first time, its usefulness in the diagnosis of anomalous origin of right pulmonary artery from aorta. © 2016, Wiley Periodicals, Inc.

  20. Hemodynamic heterogeneity of connective tissue disease patients with borderline mean pulmonary artery pressure and its distinctive characters from those with normal pulmonary artery pressure: a retrospective study.

    PubMed

    Asari, Yusa; Yamasaki, Yoshioki; Tsuchida, Kosei; Suzuki, Kengo; Akashi, Yoshihiro J; Okazaki, Takahiro; Ozaki, Shoichi; Yamada, Hidehiro; Kawahata, Kimito

    2018-05-18

    To clarify whether patients with connective tissue disease (CTD)-associated borderline mean pulmonary artery pressure (mPAP) have distinctive hemodynamic characteristics from those with normal mPAP and whether pathogenesis is as heterogeneous as manifest pulmonary hypertension (PH). Seventy-five CTD patients who underwent right heart catheterization (RHC) from 2008 through 2016 were retrospectively analyzed. We compared between-group differences in clinical and hemodynamic findings: normal mPAP (n = 35), borderline mPAP (n = 15), and PH (n = 25). A therapeutic intervention trial based on RHC results was performed in nine patients. The values of tricuspid regurgitation pressure gradient (TRPG) in patients with borderline mPAP were comparable at rest but became higher after exercise compared to those with a normal mPAP (P = 0.01). Pulmonary artery wedge pressure in patients with borderline mPAP was higher than in those with normal mPAP (P < 0.0001) and comparable to those with PH. Each of the three patients was treated for pre-capillary and post-capillary disease and two for interstitial lung disease (ILD). During the mean follow-up period of 40 months, mPAP or TRPG normalized in all patients treated for pre-capillary and post-capillary disease. One patient with severe ILD developed to PH and died from it. CTD patients with borderline mPAP, the underlining pathogenesis of which is heterogeneous as PH, have distinctive hemodynamic characteristics from those with normal mPAP. Whether a specific treatment targeting the inflammatory process or local hemodynamics may alter the clinical course to PH is a topic for future research.

  1. Causes and circumstances of death in pulmonary arterial hypertension.

    PubMed

    Tonelli, Adriano R; Arelli, Vineesha; Minai, Omar A; Newman, Jennie; Bair, Nancy; Heresi, Gustavo A; Dweik, Raed A

    2013-08-01

    The causes and circumstances surrounding death are understudied in patients with pulmonary arterial hypertension (PAH). We sought to determine the specific reasons and characteristics surrounding the death of patients with PAH. All deaths of patients with pulmonary hypertension (PH) followed in the Cleveland Clinic Pulmonary Vascular Program were prospectively reviewed by the PH team. A total of 84 patients with PAH (age 58 ± 14 yr; 73% females) who died between June 2008 and May 2012 were included. PH was determined to be the direct cause of death (right heart failure or sudden death) in 37 (44%) patients; PH contributed to but did not directly cause death in 37 (44%) patients; and the death was not related to PH in the remaining cases (n = 7; 8.3%). In three (3.6%) patients the final cause of death could not be adequately assessed. Most patients died in a healthcare environment and most received PH-specific therapies. In our cohort, 50% of all patients with PAH and 75.7% of those who died of right heart failure received parenteral prostanoid therapy. Less than half of patients had advanced healthcare directives. Most patients with PAH in our cohort died of their disease; however, right ventricular failure or sudden death was the sole cause of death in less than half of patients.

  2. Evidence for the involvement of type I interferon in pulmonary arterial hypertension.

    PubMed

    George, Peter M; Oliver, Eduardo; Dorfmuller, Peter; Dubois, Olivier D; Reed, Daniel M; Kirkby, Nicholas S; Mohamed, Nura A; Perros, Frederic; Antigny, Fabrice; Fadel, Elie; Schreiber, Benjamin E; Holmes, Alan M; Southwood, Mark; Hagan, Guy; Wort, Stephen J; Bartlett, Nathan; Morrell, Nicholas W; Coghlan, John G; Humbert, Marc; Zhao, Lan; Mitchell, Jane A

    2014-02-14

    Evidence is increasing of a link between interferon (IFN) and pulmonary arterial hypertension (PAH). Conditions with chronically elevated endogenous IFNs such as systemic sclerosis are strongly associated with PAH. Furthermore, therapeutic use of type I IFN is associated with PAH. This was recognized at the 2013 World Symposium on Pulmonary Hypertension where the urgent need for research into this was highlighted. To explore the role of type I IFN in PAH. Cells were cultured using standard approaches. Cytokines were measured by ELISA. Gene and protein expression were measured using reverse transcriptase polymerase chain reaction, Western blotting, and immunohistochemistry. The role of type I IFN in PAH in vivo was determined using type I IFN receptor knockout (IFNAR1(-/-)) mice. Human lung cells responded to types I and II but not III IFN correlating with relevant receptor expression. Type I, II, and III IFN levels were elevated in serum of patients with systemic sclerosis associated PAH. Serum interferon γ inducible protein 10 (IP10; CXCL10) and endothelin 1 were raised and strongly correlated together. IP10 correlated positively with pulmonary hemodynamics and serum brain natriuretic peptide and negatively with 6-minute walk test and cardiac index. Endothelial cells grown out of the blood of PAH patients were more sensitive to the effects of type I IFN than cells from healthy donors. PAH lung demonstrated increased IFNAR1 protein levels. IFNAR1(-/-) mice were protected from the effects of hypoxia on the right heart, vascular remodeling, and raised serum endothelin 1 levels. These data indicate that type I IFN, via an action of IFNAR1, mediates PAH.

  3. A new variant of aberrant left brachiocephalic trunk in mam: case report and literature review.

    PubMed

    Szpinda, Michał

    2005-02-01

    Importance is placed on aberrant arteries in the radiological and surgical literature. A normal left brachiocephalic trunk is characteristic for the right aortic arch. However, an aberrant left brachiocephalic trunk arising as the last branch of the aortic arch on the left side has not yet been described in the literature. Described here is a new variant of the retro-oesophageal aberrant left brachiocephalic trunk, occasionally observed in a patient during diagnostic investigation or surgical treatment for steno-obstructive involvement of the carotid district. The triple anomaly of the left aortic arch consisted of: 1. the presence of a hypoplastic left brachiocephalic trunk behind the oesophagus, 2. the absence of a brachiocephalic trunk on the right side and 3. separate origins of the arteries on the right side, with the right common artery preceding the right subclavian artery. In front of the trachea an 8-mm prosthetic PTFE was implanted from the proximal segment of the right subclavian artery to the junction of the left common carotid and left subclavian arteries. The author demonstrates the inadequacy of auxiliary investigations to detect aberrant arteries, which may only be identified precisely intra-operatively.

  4. Indexing Guidelines: Applications in Use of Pulmonary Artery Catheters and Pressure Ulcer Prevention

    PubMed Central

    Jenders, Robert A.; Estey, Greg; Martin, Martha; Hamilton, Glenys; Ford-Carleton, Penny; Thompson, B. Taylor; Oliver, Diane E.; Eccles, Randy; Barnett, G. Octo; Zielstorff, Rita D.; Fitzmaurice, Joan B.

    1994-01-01

    In a busy clinical environment, access to knowledge must be rapid and specific to the clinical query at hand. This requires indices which support easy navigation within a knowledge source. We have developed a computer-based tool for trouble-shooting pulmonary artery waveforms using a graphical index. Preliminary results of domain knowledge tests for a group of clinicians exposed to the system (N=33) show a mean improvement on a 30-point test of 5.33 (p<0.001) compared to a control group (N=19) improvement of 0.47 (p=0.61). Survey of the experimental group (N=25) showed 84% (p=0.001) found the system easy to use. We discuss lessons learned in indexing this domain area to computer-based indexing of guidelines for pressure ulcer prevention. PMID:7950035

  5. Drug-Coated Balloon Angioplasty: A Novel Treatment for Pulmonary Artery In-Stent Stenosis in a Patient with Williams Syndrome.

    PubMed

    Cohen, Jennifer L; Glickstein, Julie S; Crystal, Matthew A

    2017-12-01

    A 20-month-old boy with Williams syndrome had undergone multiple surgical and catheter-based interventions for resistant peripheral pulmonary arterial stenoses with eventual bilateral stent placement and conventional balloon angioplasty. He persistently developed suprasystemic right ventricular (RV) pressure. Angioplasty with a drug-coated balloon (DCB) was performed for in-stent restenosis and to remodel his distal pulmonary vessels bilaterally. This resulted in immediate improvement in the in-stent stenosis and resultant decrease in RV pressure. Follow-up catheterization two months later continued to show long-lasting improvement in the in-stent stenosis. We hypothesize that the anti-proliferative effects of DCBs may be of benefit in the arteriopathy associated with Williams syndrome. We report this as a novel use of a DCB in the pulmonary arterial circulation in a patient with Williams syndrome.

  6. Pulmonary hypertension in rheumatic diseases: epidemiology and pathogenesis.

    PubMed

    Shahane, Anupama

    2013-07-01

    The focus of this review is to increase awareness of pulmonary arterial hypertension (PAH) in patients with rheumatic diseases. Epidemiology and pathogenesis of PAH in rheumatic diseases is reviewed, with recommendations for early screening and diagnosis and suggestion of possible role of immunosuppressive therapy in treatment for PAH in rheumatic diseases. A MEDLINE search for articles published between January 1970 and June 2012 was conducted using the following keywords: pulmonary hypertension, scleroderma, systemic sclerosis, pulmonary arterial hypertension, connective tissues disease, systemic lupus erythematosus, mixed connective tissue disease, rheumatoid arthritis, Sjogren's syndrome, vasculitis, sarcoidosis, inflammatory myopathies, dermatomyositis, ankylosing spondylitis, spondyloarthropathies, diagnosis and treatment. Pathogenesis and disease burden of PAH in rheumatic diseases was highlighted, with emphasis on early consideration and workup of PAH. Screening recommendations and treatment were touched upon. PAH is most commonly seen in systemic sclerosis and may be seen in isolation or in association with interstitial lung disease. Several pathophysiologic processes have been identified including an obliterative vasculopathy, veno-occlusive disease, formation of microthrombi and pulmonary fibrosis. PAH in systemic lupus erythematosus is associated with higher prevalence of antiphospholipid and anticardiolipin antibodies and the presence of Raynaud's phenomenon. Endothelial proliferation with vascular remodeling, abnormal coagulation with thrombus formation and immune-mediated vasculopathy are the postulated mechanisms. Improvement with immunosuppressive medications has been reported. Pulmonary fibrosis, extrinsic compression of pulmonary arteries and granulomatous vasculitis have been reported in patients with sarcoidosis. Intimal and medial hyperplasia with luminal narrowing has been observed in Sjogren's syndrome, mixed connective tissue disease and

  7. 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.

  8. The use of iloprost in early pregnancy in patients with pulmonary arterial hypertension.

    PubMed

    Elliot, C A; Stewart, P; Webster, V J; Mills, G H; Hutchinson, S P; Howarth, E S; Bu'lock, F A; Lawson, R A; Armstrong, I J; Kiely, D G

    2005-07-01

    In patients with pulmonary hypertension, pregnancy is associated with a high risk of maternal death. Such patients are counselled to avoid pregnancy, or if it occurs, are offered early interruption. Some patients, however, decide to continue with their pregnancy and others may present with symptoms for the first time whilst pregnant. Pulmonary vasodilator therapy provides a treatment option for these high-risk patients. The present study describes three patients with pulmonary arterial hypertension of various aetiologies who were treated with the prostacyclin analogue iloprost during pregnancy, and the post-partum period. Nebulised iloprost commenced as early as 8 weeks of gestation and patients were admitted to hospital between 24-36 weeks of gestation. All pregnancies were completed with a duration of between 25-36 weeks and all deliveries were by caesarean section under local anaesthetic. All patients delivered children free from congenital abnormalities, and there was no post-partum maternal or infant mortality. In conclusion, although pregnancy is strongly advised against in those with pulmonary hypertension, the current authors have achieved a successful outcome for mother and foetus with a multidisciplinary approach and targeted pulmonary vascular therapy.

  9. Orthonormal aberration polynomials for anamorphic optical imaging systems with rectangular pupils.

    PubMed

    Mahajan, Virendra N

    2010-12-20

    The classical aberrations of an anamorphic optical imaging system, representing the terms of a power-series expansion of its aberration function, are separable in the Cartesian coordinates of a point on its pupil. We discuss the balancing of a classical aberration of a certain order with one or more such aberrations of lower order to minimize its variance across a rectangular pupil of such a system. We show that the balanced aberrations are the products of two Legendre polynomials, one for each of the two Cartesian coordinates of the pupil point. The compound Legendre polynomials are orthogonal across a rectangular pupil and, like the classical aberrations, are inherently separable in the Cartesian coordinates of the pupil point. They are different from the balanced aberrations and the corresponding orthogonal polynomials for a system with rotational symmetry but a rectangular pupil.

  10. Repeatability and responsiveness of exercise tests in pulmonary arterial hypertension.

    PubMed

    Mainguy, Vincent; Malenfant, Simon; Neyron, Anne-Sophie; Bonnet, Sébastien; Maltais, François; Saey, Didier; Provencher, Steeve

    2013-08-01

    Exercise tolerance in pulmonary arterial hypertension (PAH) is most commonly assessed by the 6-min walk test (6MWT). Whether endurance exercise tests are more responsive than the 6MWT remains unknown. 20 stable PAH patients (mean±sd age 53±15 years and mean pulmonary arterial pressure 44±16 mmHg) already on PAH monotherapy completed the 6MWT, the endurance shuttle walk test (ESWT) and the cycle endurance test (CET) before and after the addition of sildenafil citrate 20 mg three times daily or placebo for 28 days in a randomised double-blind crossover setting. Pre- or post-placebo tests were used to assess repeatability of each exercise test, whereas pre- or post-sildenafil citrate tests were used to assess their responsiveness. Sildenafil citrate led to placebo-corrected changes in exercise capacity of 18±25 m (p = 0.02), 58±235 s (p = 0.58) and 29±77 s (p = 0.09) for the 6MWT, the ESWT and the CET, respectively. The 6MWT was associated with a lower coefficient of variation between repeated measures (3% versus 18% versus 13%), resulting in a higher standardised response mean compared with endurance tests (0.72, 0.25 and 0.38 for the 6MWT, the ESWT and the CET, respectively). The 6MWT had the best ability to capture changes in exercise capacity when sildenafil citrate was combined with patients' baseline monotherapy, supporting its use as an outcome measure in PAH.

  11. 3-Bromopyruvate reverses hypoxia-induced pulmonary arterial hypertension through inhibiting glycolysis: In vitro and in vivo studies.

    PubMed

    Chen, Fangzheng; Wang, Heng; Lai, Jiadan; Cai, Shujing; Yuan, Linbo

    2018-05-04

    Pulmonary arterial smooth muscle cell (PASMC) proliferation is vital to pulmonary vascular remodeling in pulmonary arterial hypertension (PAH) pathogenesis, and inhibiting PASMC metabolism could serve as a new possible therapy to reverse the process. 3-Bromopyruvate (3-BrPA) is an effective glycolysis inhibitor with its effect in PAH remains unclear. Our study aims to assess the therapeutic effect of 3-BrPA in PAH rats and investigate the possible mechanism of 3-BrPA in PASMC proliferation and apoptosis. 27 healthy SD rats were grouped and treated with hypoxia/normoxia and administration of 3-BrPA/physiological saline. Mean pulmonary artery pressure (mPAP) and cardiac output (CO) were measured and pulmonary vascular resistance (PVR) was calculated. Right ventricular hypertrophy index (RVHI) was calculated to evaluate the right ventricular hypertrophy degree. The percentage of medial wall area (WA%) and medial wall thickness (WT%) were measured by image analysis. PASMCs groups received hypoxia/normoxia treatments and 3-BrPA/physiological saline. PASMC proliferation and migration were respectively detected by CCK-8 and cell wound scratch assay. Hexokinase II (HK-2) expression and lactate level were respectively measured by Western Blotting and lactate test kit to detect glycolysis. mPAP, PVR, PVHI, WA% and WT% in rats increased after the hypoxia treatment, but were lower compared to rats received 3-BrPA in hypoxia environment. HK-2 expression, lactate concentration, OD value and scratch areas in PASMCs increased after the hypoxia treatment, but were decreased after the administration of 3-BrPA. 3-BrPA can inhibit PASMC proliferation and migration by inhibiting glycolysis, and is effective in reversing the vascular remodeling in hypoxia-induced PAH rats. Copyright © 2017. Published by Elsevier B.V.

  12. Heterogeneous distribution of type I nitric oxide synthase in pulmonary vasculature of ovine fetus.

    PubMed

    Tzao, C; Nickerson, P A; Russell, J A; Noble, B K; Steinhorn, R H

    2000-11-01

    The nitric oxide/guanosine 3',5'-cyclic monophosphate pathway plays an essential role in mediating pulmonary vasodilation at birth. Small resistance arteries in the fetal lung are vessels of major significance in the regulation of pulmonary vascular tone. The present study is to determine that type I nitric oxide synthase (NOS-I) is present in ovine fetal pulmonary vasculature and that NOS-I is distributed heterogeneously in ovine fetal pulmonary circulation. We used reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry and NOS-I immunohistochemistry to localize NOS-I in fetal sheep lungs and showed a colocalization for NADPH-d activity with NOS-I immunoreactivity. Strong NOS-I immunoreactivity was observed exclusively in the endothelium of the terminal bronchiole and respiratory bronchiole-associated arteries. As a comparison, adult sheep lung did not show positive immunoreactivity in the pulmonary endothelium. NOS-I was absent in the umbilical or systemic arteries from the ovine fetus, whereas abundant NOS-III immunoreactivity was present in these arteries. We conclude that NOS-I is present uniquely in the ovine fetal pulmonary circulation as opposed to the adult pulmonary or the fetal systemic circulation. NOS-I is distributed heterogeneously in the ovine pulmonary vasculature. We speculate that NOS-I plays an active role in the regulation of perinatal pulmonary circulation.

  13. Ventriculo-arterial coupling detects occult RV dysfunction in chronic thromboembolic pulmonary vascular disease.

    PubMed

    Axell, Richard G; Messer, Simon J; White, Paul A; McCabe, Colm; Priest, Andrew; Statopoulou, Thaleia; Drozdzynska, Maja; Viscasillas, Jamie; Hinchy, Elizabeth C; Hampton-Till, James; Alibhai, Hatim I; Morrell, Nicholas; Pepke-Zaba, Joanna; Large, Stephen R; Hoole, Stephen P

    2017-04-01

    Chronic thromboembolic disease (CTED) is suboptimally defined by a mean pulmonary artery pressure (mPAP) <25 mmHg at rest in patients that remain symptomatic from chronic pulmonary artery thrombi. To improve identification of right ventricular (RV) pathology in patients with thromboembolic obstruction, we hypothesized that the RV ventriculo-arterial (Ees/Ea) coupling ratio at maximal stroke work (Ees/Ea max sw ) derived from an animal model of pulmonary obstruction may be used to identify occult RV dysfunction (low Ees/Ea) or residual RV energetic reserve (high Ees/Ea). Eighteen open chested pigs had conductance catheter RV pressure-volume (PV)-loops recorded during PA snare to determine Ees/Ea max sw This was then applied to 10 patients with chronic thromboembolic pulmonary hypertension (CTEPH) and ten patients with CTED, also assessed by RV conductance catheter and cardiopulmonary exercise testing. All patients were then restratified by Ees/Ea. The animal model determined an Ees/Ea max sw  = 0.68 ± 0.23 threshold, either side of which cardiac output and RV stroke work fell. Two patients with CTED were identified with an Ees/Ea well below 0.68 suggesting occult RV dysfunction whilst three patients with CTEPH demonstrated Ees/Ea ≥ 0.68 suggesting residual RV energetic reserve. Ees/Ea > 0.68 and Ees/Ea < 0.68 subgroups demonstrated constant RV stroke work but lower stroke volume (87.7 ± 22.1 vs. 60.1 ± 16.3 mL respectively, P  = 0.006) and higher end-systolic pressure (36.7 ± 11.6 vs. 68.1 ± 16.7 mmHg respectively, P  < 0.001). Lower Ees/Ea in CTED also correlated with reduced exercise ventilatory efficiency. Low Ees/Ea aligns with features of RV maladaptation in CTED both at rest and on exercise. Characterization of Ees/Ea in CTED may allow for better identification of occult RV dysfunction. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American

  14. 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.

  15. Increased pulmonary artery pressures during exercise are related to persistent tricuspid regurgitation after atrial septal defect closure.

    PubMed

    De Meester, Pieter; Van De Bruaene, Alexander; Herijgers, Paul; Voigt, Jens-Uwe; Vanhees, Luc; Budts, Werner

    2013-08-01

    Although closure of an atrial septal defect type secundum often normalizes right heart dimensions and pressures, mild tricuspid insufficiency might persist. This study aimed at (1) identification of determinants explaining the persistence of tricuspid insufficiency after atrial septal defect closure, and (2) evaluation of functional capacity of patients with persistent mild tricuspid insufficiency. Twenty-five consecutive patients (age 42+17 y) were included from the outpatient clinic of congenital heart disease at the University Hospitals of Leuven. All underwent transthoracic echocardiography, semi-supine bicycle stress echocardiography and cardio-pulmonary exercise testing. Six patients (24%) had mild tricuspid insufficiency (2/4) compared to 19 patients (76%) with no or minimal tricuspid insufficiency ( 1/4) as assessed by semi-quantitative colour Doppler echocardiography. Mann-Whitney U and Fisher's exact tests were performed where applicable. Patients with persistent mild tricuspid insufficiency were significantly older than those with no or minimal tricuspid insufficiency (P = 0.042). At rest, no differences in right heart configuration, mean pulmonary artery pressure or right ventricular function were found. At peak exercise, mean pulmonary artery pressure was significantly higher in patients with mild persistent tricuspid insufficiency (P = 0.026). Peak oxygen uptake was significantly lower in patients with mild persistent tricuspid insufficiency (P = 0.019). Mild tricuspid insufficiency after atrial septal defect repair occurs more frequently in older patients and in patients with higher mean pulmonary artery pressure at peak exercise. In patients with mild tricuspid insufficiency, functional capacity was more reduced. Mild tricuspid insufficiency could be a marker of subclinical persistent pressure load on the right ventricle.

  16. GDF-15 is abundantly expressed in plexiform lesions in patients with pulmonary arterial hypertension and affects proliferation and apoptosis of pulmonary endothelial cells

    PubMed Central

    2011-01-01

    Background Growth-differentiation factor-15 (GDF-15) is a stress-responsive, transforming growth factor-β-related cytokine, which has recently been reported to be elevated in serum of patients with idiopathic pulmonary arterial hypertension (IPAH). The aim of the study was to examine the expression and biological roles of GDF-15 in the lung of patients with pulmonary arterial hypertension (PAH). Methods GDF-15 expression in normal lungs and lung specimens of PAH patients were studied by real-time RT-PCR and immunohistochemistry. Using laser-assisted micro-dissection, GDF-15 expression was further analyzed within vascular compartments of PAH lungs. To elucidate the role of GDF-15 on endothelial cells, human pulmonary microvascular endothelial cells (HPMEC) were exposed to hypoxia and laminar shear stress. The effects of GDF-15 on the proliferation and cell death of HPMEC were studied using recombinant GDF-15 protein. Results GDF-15 expression was found to be increased in lung specimens from PAH patients, com-pared to normal lungs. GDF-15 was abundantly expressed in pulmonary vascular endothelial cells with a strong signal in the core of plexiform lesions. HPMEC responded with marked upregulation of GDF-15 to hypoxia and laminar shear stress. Apoptotic cell death of HPMEC was diminished, whereas HPMEC proliferation was either increased or decreased depending of the concentration of recombinant GDF-15 protein. Conclusions GDF-15 expression is increased in PAH lungs and appears predominantly located in vascular endothelial cells. The expression pattern as well as the observed effects on proliferation and apoptosis of pulmonary endothelial cells suggest a role of GDF-15 in the homeostasis of endothelial cells in PAH patients. PMID:21548946

  17. Colchicine Depolymerizes Microtubules, Increases Junctophilin-2, and Improves Right Ventricular Function in Experimental Pulmonary Arterial Hypertension.

    PubMed

    Prins, Kurt W; Tian, Lian; Wu, Danchen; Thenappan, Thenappan; Metzger, Joseph M; Archer, Stephen L

    2017-05-31

    Pulmonary arterial hypertension (PAH) is a lethal disease characterized by obstructive pulmonary vascular remodeling and right ventricular (RV) dysfunction. Although RV function predicts outcomes in PAH, mechanisms of RV dysfunction are poorly understood, and RV-targeted therapies are lacking. We hypothesized that in PAH, abnormal microtubular structure in RV cardiomyocytes impairs RV function by reducing junctophilin-2 (JPH2) expression, resulting in t-tubule derangements. Conversely, we assessed whether colchicine, a microtubule-depolymerizing agent, could increase JPH2 expression and enhance RV function in monocrotaline-induced PAH. Immunoblots, confocal microscopy, echocardiography, cardiac catheterization, and treadmill testing were used to examine colchicine's (0.5 mg/kg 3 times/week) effects on pulmonary hemodynamics, RV function, and functional capacity. Rats were treated with saline (n=28) or colchicine (n=24) for 3 weeks, beginning 1 week after monocrotaline (60 mg/kg, subcutaneous). In the monocrotaline RV, but not the left ventricle, microtubule density is increased, and JPH2 expression is reduced, with loss of t-tubule localization and t-tubule disarray. Colchicine reduces microtubule density, increases JPH2 expression, and improves t-tubule morphology in RV cardiomyocytes. Colchicine therapy diminishes RV hypertrophy, improves RV function, and enhances RV-pulmonary artery coupling. Colchicine reduces small pulmonary arteriolar thickness and improves pulmonary hemodynamics. Finally, colchicine increases exercise capacity. Monocrotaline-induced PAH causes RV-specific derangement of microtubules marked by reduction in JPH2 and t-tubule disarray. Colchicine reduces microtubule density, increases JPH2 expression, and improves both t-tubule architecture and RV function. Colchicine also reduces adverse pulmonary vascular remodeling. These results provide biological plausibility for a clinical trial to repurpose colchicine as a RV-directed therapy for PAH

  18. Gene Therapy by Targeted Adenovirus-mediated Knockdown of Pulmonary Endothelial Tph1 Attenuates Hypoxia-induced Pulmonary Hypertension

    PubMed Central

    Morecroft, Ian; White, Katie; Caruso, Paola; Nilsen, Margaret; Loughlin, Lynn; Alba, Raul; Reynolds, Paul N; Danilov, Sergei M; Baker, Andrew H; MacLean, Margaret R

    2012-01-01

    Serotonin is produced by pulmonary arterial endothelial cells (PAEC) via tryptophan hydroxylase-1 (Tph1). Pathologically, serotonin acts on underlying pulmonary arterial cells, contributing to vascular remodeling associated with pulmonary arterial hypertension (PAH). The effects of hypoxia on PAEC-Tph1 activity are unknown. We investigated the potential of a gene therapy approach to PAH using selective inhibition of PAEC-Tph1 in vivo in a hypoxic model of PAH. We exposed cultured bovine pulmonary arterial smooth muscle cells (bPASMCs) to conditioned media from human PAECs (hPAECs) before and after hypoxic exposure. Serotonin levels were increased in hypoxic PAEC media. Conditioned media evoked bPASMC proliferation, which was greater with hypoxic PAEC media, via a serotonin-dependent mechanism. In vivo, adenoviral vectors targeted to PAECs (utilizing bispecific antibody to angiotensin-converting enzyme (ACE) as the selective targeting system) were used to deliver small hairpin Tph1 RNA sequences in rats. Hypoxic rats developed PAH and increased lung Tph1. PAEC-Tph1 expression and development of PAH were attenuated by our PAEC-Tph1 gene knockdown strategy. These results demonstrate that hypoxia induces Tph1 activity and selective knockdown of PAEC-Tph1 attenuates hypoxia-induced PAH in rats. Further investigation of pulmonary endothelial-specific Tph1 inhibition via gene interventions is warranted. PMID:22525513

  19. [Effects of recombinant human morphogenetic protein-2 on pulmonary artery pressure in acute lung injury caused by endotoxin and mechanism thereof: experiment with rats].

    PubMed

    Shan, Shi-min; Pei, Ling; Wang, Jun-ke

    2006-12-05

    To investigate the effects of recombinant human morphogenetic protein-2 (rhBMP-2) on pulmonary artery pressure in acute lung injury (ALI) caused by endotoxin and mechanism thereof: Sixty Wistar rats were randomly divided into 3 equal groups: control group (Group C), receiving intravenous drip of normal saline (NS) through the femoral vein for 1.5 h; lipopolysaccharide (LPS) control group (Group L), receiving intravenous drip of NS and then LPS; and rhBMP-2 group (Group L(T)), receiving intravenous drip of rhBMP-2 solution and LPS solution successively through the femoral vein,, and then injected with rhBMP-2 through a detaining catheter after 24 and 48 hours respectively. Seventy-two hours later the pulmonary artery pressure (P(pa)) was detected and then all the rats were killed with their left lung taken out. Four hours before the collection of lung tissues 5-bromodeoxyuridine (BrDU) was injected intraperitoneally. Pathological examination was conducted. TUNEL was used to examine the proliferation/apoptosis of the pulmonary artery smooth muscle cells (PASMC). The thickness of pulmonary artery media was measured by microphotography system. RT-PCR and Western blotting were used to detect the mRNA and protein expression of the K(V 1.5) gene. PASMCs were collected to undergo electric physiologic examination of the activity of voltage gated potassium channel (K(V)). The PPa of Group L was (25.1 +/- 3.5) mmHg, significantly higher than those of Groups C and L(T) [(14.9 +/- 1.9) and (15.3 +/- 1.2) mmHg respectively, both P < 0.01]. The mitotic index of Group L was 3.1% +/- 0.6%, significantly higher than those of Group C and LT (0.4% +/- 0.1% and 0.5% +/- 0.6% respectively, both P < 0.01). The thickness of the pulmonary artery media of Group L was 9.7% +/- 2.8%, significantly greater than those of Groups C and L(T) (5.0% +/- 1.5% and 5.2 +/- 1.7% respectively, both P < 0.01). When the reference voltage was + 70 mV, the current value of the PASMC of Group L was (0

  20. High-resolution computed tomography evaluation of the bronchial lumen to vertebral body diameter and pulmonary artery to vertebral body diameter ratios in anesthetized ventilated normal cats.

    PubMed

    Lee-Fowler, Tekla M; Cole, Robert C; Dillon, A Ray; Tillson, D Michael; Garbarino, Rachel; Barney, Sharron

    2017-10-01

    Objectives Bronchial lumen to pulmonary artery diameter (BA) ratio has been utilized to investigate pulmonary pathology on high-resolution CT images. Diseases affecting both the bronchi and pulmonary arteries render the BA ratio less useful. The purpose of the study was to establish bronchial lumen diameter to vertebral body diameter (BV) and pulmonary artery diameter to vertebral body diameter (AV) ratios in normal cats. Methods Using high-resolution CT images, 16 sets of measurements (sixth thoracic vertebral body [mid-body], each lobar bronchi and companion pulmonary artery diameter) were acquired from young adult female cats and 41 sets from pubertal female cats. Results Young adult and pubertal cat BV ratios were not statistically different from each other in any lung lobe. Significant differences between individual lung lobe BV ratios were noted on combined age group analysis. Caudal lung lobe AV ratios were significantly different between young adult and pubertal cats. All other lung lobe AV ratios were not significantly different. Caudal lung lobe AV ratios were significantly different from all other lung lobes but not from each other in both the young adult and pubertal cats. Conclusions and relevance BV ratio reference intervals determined for individual lung lobes could be applied to both young adult and pubertal cats. Separate AV ratios for individual lung lobes would be required for young adult and pubertal cats. These ratios should allow more accurate evaluation of cats with concurrent bronchial and pulmonary arterial disease.