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.

Non-extracorporeal circulation for coronary artery bypass graft surgery is more beneficial than extracorporeal circulation.

PubMed

Yang, F-Y; Bao, Y-Z; Liu, F-S; Zhu, Y-C; Zheng, J; Zhang, J-H; Zheng, X-F; Wei, G-C

2015-04-01

The objective of this study was to compare coronary artery bypass graft (CABG) surgery with non-extracorporeal vs. extracorporeal circulation. The study outcomes included operative time, number of graft vessels, pulmonary infection rates, and systemic inflammatory markers. 96 patients received selective CABG, either with non-extracorporeal (study group; n = 48) or extracorporeal circulation (control group; n = 48). Operative time, pulmonary infection rates, and blood levels of inflammatory markers TNF-α, IL-6, and IL-8 before and 4, 24, and 48 hours after the surgery were quantified. Graft vessels were quantified using computed tomography. Operative time was significantly shorter in study group (4.58 ± 0.91 vs. 5.36 ± 1.12 hours in control group; p < 0.05). The number of graft vessels and pulmonary infection rates were comparable between both techniques. However, systemic inflammatory markers were significantly (p < 0.05) lower in study group at 4 and, partly, 24 hours after the surgery. Extracorporeal circulation prolongs operation and can aggravate systemic inflammatory response. Therefore, CABG with non-extracorporeal circulation offers more beneficial outcomes.

[A statement the Polish Cardiac Society Working Group on Pulmonary Circulation on screening for CTEPH patients after acute pulmonary embolism].

PubMed

Ciurzyński, Michał; Kurzyna, Marcin; Kopeć, Grzegorz; Błaszczak, Piotr; Chrzanowski, Łukasz; Kamiński, Karol; Mizia-Stec, Katarzyna; Mularek-Kubzdela, Tatiana; Mroczek, Ewa; Biederman, Andrzej; Pruszczyk, Piotr; Torbicki, Adam

2017-01-01

Both pharmacological and invasive treatment of chronic thromboembolic pulmonary hypertension (CTEPH) is now available in Poland and the awareness of the disease among physicians is growing. Thus, the Polish Cardiac Society's Working Group on Pulmonary Circulation in cooperation with independent experts in this field, have launched the statement on algorithm to guide a CTEPH diagnosis in patients with previous acute pulmonary embolism (APE). In Poland, every year this disease affects about 250 patients. CTEPH should be suspected in individuals after APE with dyspnea, despite at least 3 months period of effective anticoagulation, particularly when specified risk factors are present. Echocardiography is a main screening tool. The authors suggest that a diagnostic process of patients with significant clinical suspicion of CTEPH and right ventricle overload in echocardiography should be performed in reference centres. The document contains a list of Polish centres diagnosing patients with suspected CTEPH. Pulmonary scintigraphy is a safe and highly sensitive screening test for CTEPH. Multi-detector computed tomography with precise detection of thromboembolic residues in pulmonary circulation is important for planning of pulmonary endarterectomy. Right heart catheterisation definitely confirms the presence of pulmonary hypertension and direct pulmonary angiography allows for identification of lesions suitable for thromboendarterectomy or pulmonary balloon angioplasty. In this document a diagnostic algorithm in patients with suspected CTEPH is also proposed. With individualised sequential diagnostic strategy each patient can be finally qualified for a particular mode of therapy by dedicated CTEPH Heart Team. Moreover the document contains short information for the primary care physician about the management of patients after APE.

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

PubMed

Akmal, M; Zulkifle, M; Ansari, Ah

2010-03-01

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

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

PubMed Central

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

2015-01-01

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

Stressed lungs: unveiling the role of circulating stress ...

EPA Pesticide Factsheets

Ozone, a major component of smog generated through the interaction of light and anthropogenic emissions, induces adverse pulmonary, cardiovascular, and systemic health effects upon inhalation. It is generally accepted that ozone-induced lung injury is mediated by its interaction with lung lining components causing local oxidative changes, which then leads to cell damage and recruitment of inflammatory cells. It is postulated that the spillover of reactive intermediates and pro-inflammatory molecules from lung to systemic circulation mediates extra-pulmonary effects. However, recent work from our laboratory supports an alternative hypothesis that circulating stress hormones, such as epinephrine and corticosterone/cortisol, are involved in mediating ozone pulmonary effects. We have shown in rats and humans that ozone increases the levels of circulating stress hormones through activation of the hypothalamus- pituitary-adrenal (HPA) axis before any measurable effects are observed in the lung. The surgical removal of adrenals diminishes circulating stress hormones and at the same time, the pulmonary effects of ozone suggesting a significant contribution of these hormones in ozone-induced lung injury and inflammation. While ozone effects in the lung have been extensively studied, the contribution of central nervous system -mediated hormonal stress response has not been examined. In order to understand the signaling pathways that might be involved in ozone-induced lun

The assisted bidirectional Glenn: a novel surgical approach for first-stage single-ventricle heart palliation.

PubMed

Esmaily-Moghadam, Mahdi; Hsia, Tain-Yen; Marsden, Alison L

2015-03-01

Outcomes after a modified Blalock-Taussig shunt (mBTS) in neonates with single-ventricle physiology remain unsatisfactory. However, initial palliation with a superior cavopulmonary connection, such as a bidirectional Glenn (BDG), is discouraged, owing to potential for inadequate pulmonary blood flow (PBF). We tested the feasibility of a novel surgical approach, adopting the engineering concept of an ejector pump, whereby the flow in the BDG is "assisted" by injection of a high-energy flow stream from the systemic circulation. Realistic 3-dimensional models of the neonatal mBTS and BDG circulations were created. The "assisted" bidirectional Glenn (ABG) consisted of a shunt between the right innominate artery and the superior vena cava (SVC), with a 1.5-mm clip near the SVC anastomosis to create a Venturi effect. The 3 models were coupled to a validated hydraulic circulation model, and 2 pulmonary vascular resistance (PVR) values (7 and 2.3 Wood units) were simulated. The ABG provided the highest systemic oxygen saturation and oxygen delivery at both PVR levels. In addition to achieving higher PBF than the BDG, the ABG produced a lower single-ventricular workload than mBTS. SVC pressure was highest in the ABG model (ABG: 15; Glenn: 11; mBTS: 3 mm Hg; PVR = 7 Wood units), but at low PVR, the SVC pressure was significantly lower (ABG: 8; Glenn: 6; mBTS: <3 mm Hg). Adopting the principle of an ejector pump, with additional flow directed into the SVC in a BDG, the ABG appears to increase PBF with a modest increase in SVC and pulmonary arterial pressure. Although multiscale modeling results demonstrate the conceptual feasibility of the ABG circulation, further technical refinement and investigations are necessary, especially in an appropriate animal model. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Initial in vitro testing of a paediatric continuous-flow total artificial heart.

PubMed

Fukamachi, Kiyotaka; Karimov, Jamshid H; Horvath, David J; Sunagawa, Gengo; Byram, Nicole A; Kuban, Barry D; Moazami, Nader

2018-06-01

Mechanical circulatory support has become standard therapy for adult patients with end-stage heart failure; however, in paediatric patients with congenital heart disease, the options for chronic mechanical circulatory support are limited to paracorporeal devices or off-label use of devices intended for implantation in adults. Congenital heart disease and cardiomyopathy often involve both the left and right ventricles; in such cases, heart transplantation, a biventricular assist device or a total artificial heart is needed to adequately sustain both pulmonary and systemic circulations. We aimed to evaluate the in vitro performance of the initial prototype of our paediatric continuous-flow total artificial heart. The paediatric continuous-flow total artificial heart pump was downsized from the adult continuous-flow total artificial heart configuration by a scale factor of 0.70 (1/3 of total volume) to enable implantation in infants. System performance of this prototype was evaluated using the continuous-flow total artificial heart mock loop set to mimic paediatric circulation. We generated maps of pump performance and atrial pressure differences over a wide range of systemic vascular resistance/pulmonary vascular resistance and pump speeds. Performance data indicated left pump flow range of 0.4-4.7 l/min at 100 mmHg delta pressure. The left/right atrial pressure difference was maintained within ±5 mmHg with systemic vascular resistance/pulmonary vascular resistance ratios between 1.4 and 35, with/without pump speed modulation, verifying expected passive self-regulation of atrial pressure balance. The paediatric continuous-flow total artificial heart prototype met design requirements for self-regulation and performance; in vivo pump performance studies are ongoing.

Challenges of univentricular physiology in heterotaxy.

PubMed

Jacobs, Marshall L; Mavroudis, Constantine

2011-04-01

Patients with heterotaxy syndrome exhibit an extensive constellation of congenital cardiac malformations, making these patients a challenging group to manage surgically. Many of these patients' hearts do not lend themselves to separation of the pulmonary and systemic circulations except by some modification of the Fontan procedure. Palliative procedures early in life are directed at creating a satisfactory balance of pulmonary and systemic blood flow and at the same time ensuring unobstructed pulmonary venous return. Early conversion from parallel pulmonary and systemic circulations to superior cavopulmonary connections is important, to reduce volume work of the systemic ventricle. Heterotaxy patients are generally considered a high-risk population with respect to eventual Fontan procedure. It is important to appreciate the unique and variable anatomy of the sinus node and conduction system and the potential for occult pulmonary venous obstruction, atrioventricular valve regurgitation, and recurrent cyanosis, which may be related to the development of pulmonary arteriovenous malformations.

Pulmonary vasodilator therapy in the failing Fontan circulation: rationale and efficacy.

PubMed

Snarr, Brian S; Paridon, Stephen M; Rychik, Jack; Goldberg, David J

2015-12-01

The Fontan operation is the final step of palliation for patients with a functionally single ventricle. Since its introduction in the 1970s, the Fontan surgery has become part of a successful surgical strategy that has improved single ventricle mortality. In recent years, we have become more aware of the limitations and long-term consequences of the Fontan physiology. Pulmonary vascular resistance plays an important role in total cavopulmonary circulation, and has been identified as a potential therapeutic target to mitigate Fontan sequelae. In this review, we will discuss the results of different pulmonary vasodilator trials and the use of pulmonary vasodilators as a treatment strategy for Fontan patients.

Determinants of pulmonary blood flow distribution.

PubMed

Glenny, Robb W; Robertson, H Thomas

2011-01-01

The primary function of the pulmonary circulation is to deliver blood to the alveolar capillaries to exchange gases. Distributing blood over a vast surface area facilitates gas exchange, yet the pulmonary vascular tree must be constrained to fit within the thoracic cavity. In addition, pressures must remain low within the circulatory system to protect the thin alveolar capillary membranes that allow efficient gas exchange. The pulmonary circulation is engineered for these unique requirements and in turn these special attributes affect the spatial distribution of blood flow. As the largest organ in the body, the physical characteristics of the lung vary regionally, influencing the spatial distribution on large-, moderate-, and small-scale levels. © 2011 American Physiological Society.

Role of circulating granulocytes in sheep lung injury produced by phorbol myristate acetate.

PubMed

Dyer, E L; Snapper, J R

1986-02-01

Phorbol myristate acetate (PMA) and endotoxin cause pulmonary granulocyte sequestration and alteration in lung fluid and solute exchange in awake sheep that are felt to be analogous to the adult respiratory distress syndrome in humans. The basic hypothesis that PMA causes lung injury by activating circulating granulocytes has never been tested. The effects of infused PMA on lung mechanics and the cellular constituents of lung lymph have also not been reported. We therefore characterized the effects of intravenous PMA, 5 micrograms/kg, on lung mechanics, pulmonary hemodynamics, lung fluid and solute exchange, pulmonary gas exchange, blood and lymph leukocyte counts, and plasma and lymph cyclooxygenase products of arachidonate metabolism in 10 awake sheep with normal granulocyte counts and after granulocyte depletion with hydroxyurea. PMA significantly altered lung mechanics from base line in both nongranulocyte depleted and granulocyte-depleted sheep. Dynamic compliance decreased by over 50% and resistance to airflow across the lungs increased over threefold acutely following PMA infusion in both sets of experiments. Changes in lung mechanics, pulmonary hemodynamics, lung fluid and solute exchange, pulmonary gas exchange, and plasma and lymph arachidonate metabolites were not significantly affected by greater than 99% depletion of circulating granulocytes. We conclude that the lung injury caused by PMA in chronically instrumented awake sheep probably is not a result of activation of circulating granulocytes.

Role of Kv7 channels in responses of the pulmonary circulation to hypoxia.

PubMed

Sedivy, Vojtech; Joshi, Shreena; Ghaly, Youssef; Mizera, Roman; Zaloudikova, Marie; Brennan, Sean; Novotna, Jana; Herget, Jan; Gurney, Alison M

2015-01-01

Hypoxic pulmonary vasoconstriction (HPV) is a beneficial mechanism that diverts blood from hypoxic alveoli to better ventilated areas of the lung, but breathing hypoxic air causes the pulmonary circulation to become hypertensive. Responses to airway hypoxia are associated with depolarization of smooth muscle cells in the pulmonary arteries and reduced activity of K(+) channels. As Kv7 channels have been proposed to play a key role in regulating the smooth muscle membrane potential, we investigated their involvement in the development of HPV and hypoxia-induced pulmonary hypertension. Vascular effects of the selective Kv7 blocker, linopirdine, and Kv7 activator, flupirtine, were investigated in isolated, saline-perfused lungs from rats maintained for 3-5 days in an isobaric hypoxic chamber (FiO2 = 0.1) or room air. Linopirdine increased vascular resistance in lungs from normoxic, but not hypoxic rats. This effect was associated with reduced mRNA expression of the Kv7.4 channel α-subunit in hypoxic arteries, whereas Kv7.1 and Kv7.5 were unaffected. Flupirtine had no effect in normoxic lungs but reduced vascular resistance in hypoxic lungs. Moreover, oral dosing with flupirtine (30 mg/kg/day) prevented short-term in vivo hypoxia from increasing pulmonary vascular resistance and sensitizing the arteries to acute hypoxia. These findings suggest a protective role for Kv7.4 channels in the pulmonary circulation, limiting its reactivity to pressor agents and preventing hypoxia-induced pulmonary hypertension. They also provide further support for the therapeutic potential of Kv7 activators in pulmonary vascular disease. Copyright © 2015 the American Physiological Society.

Sustained elevated levels of C-reactive protein and ferritin in pulmonary tuberculosis patients remaining culture positive upon treatment initiation

PubMed Central

Oliveira, Marina G.; Mesquita, Eliene D. D.; Silva, Elisangela; Rauwerdink, Anneloek; Cobelens, Frank; Oliveira, Martha M.; Kritski, Afrânio

2017-01-01

Background Clinical trials that evaluate new anti-tubercular drugs and treatment regimens take years to complete due to the slow clearance of Mycobacterium tuberculosis infection and the lack of early biomarkers that predict treatment outcomes. Host Inflammation markers have been associated with tuberculosis (TB) pathogenesis. In the present study, we tested if circulating levels of C-reactive protein (CRP) and ferritin reflect mycobacterial loads and inflammation in pulmonary TB (PTB) patients undergoing anti-tuberculous therapy (ATT). Methods Prospective measurements of CRP and ferritin, used as readouts of systemic inflammation, were performed in cryopreserved serum samples from 165 Brazilian patients with active PTB initiating ATT. Associations between levels of these laboratory parameters with mycobacterial loads in sputum as well as with sputum conversion at day 60 of ATT were tested. Results Circulating levels of both ferritin and CRP gradually decreased over time on ATT. At pre-treatment, concentrations of these parameters were unable to distinguish patients with positive from those with negative acid-fast bacilli (AFB) in sputum cultures. However, patients who remained with positive cultures at day 60 of ATT exhibited heightened levels of these inflammatory markers compared to those with negative cultures at that time point. Conclusions CRP and Ferritin levels in serum may be useful to identify patients with positive cultures at day 60 of ATT. PMID:28384354

Isolating and Testing Circulating Tumor DNA and Soluble Immune Markers During the Course of Treatment for Lung Cancer

ClinicalTrials.gov

2018-01-08

Lung Cancer; Lung Neoplasms; Cancer of Lung; Cancer of the Lung; Neoplasms, Lung; Neoplasms, Pulmonary; Pulmonary Cancer; Pulmonary Neoplasms; Carcinoma, Non-small-cell Lung; Adenocarcinoma; Squamous Cell Carcinoma

The pulmonary circulation of some domestic animals at high altitude

NASA Astrophysics Data System (ADS)

Anand, I.; Heath, D.; Williams, D.; Deen, M.; Ferrari, R.; Bergel, D.; Harris, P.

1988-03-01

Pulmonary haemodynamics and the histology of the pulmonary vasculature have been studied at high altitude in the yak, in interbreeds between yaks and cattle, and in domestic goats and sheep indigenous to high altitudes together with crosses between them and low-altitude strains. Cattle at high altitude had a higher pulmonary arterial pressure than cattle at low altitude. The yak and two interbreeds with cattle (dzos and stols) had a low pulmonary arterial pressure compared with cattle, while the medial thickness of the small pulmonary arteries was less than would be expected in cattle, suggesting that the yak has a low capacity for hypoxic pulmonary vasoconstriction and that this characteristic is transmitted genetically. Goats and sheep showed haemodynamic evidence of a limited response of the pulmonary circulation to high altitude, but no evidence that the high altitude breeds had lost this response. There were no measurable differences in the thickness of the media of the small pulmonary arteries between high- and low-altitude breeds of goats and sheep. All these species showed prominent intimal protrusions of muscle into the pulmonary veins but no specific effect of high altitude in this respect.

Differential pulmonary and cardiac effects of pulmonary exposure to a panel of PM-associated metals

EPA Science Inventory

Biological mechanisms underlying the epidemiological association between exposure to particulate matter (PM) and increased risk of cardiovascular health effects are under investigation. Water soluble metals reaching systemic circulation following pulmonary exposure are likely exe...

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 in the pulmonary artery may be the cause. This appears important as NO plays a protective role by preventing vasoconstriction, thrombosis and atherosclerosis. PMID:8770860

Influence of Gravity on Blood Volume and Flow Distribution

NASA Technical Reports Server (NTRS)

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

1999-01-01

In our previous experiments during NASA Shuttle flights SLS 1 and 2 (9-15 days) and EUROMIR flights (30-90 days) we observed that pulmonary blood flow (cardiac output) was elevated initially, and surprisingly remained elevated for the duration of the flights. Stroke volume increased initially and then decreased, but was still above 1 Gz values. As venous return was constant, the changes in SV were secondary to modulation of heart rate. Mean blood pressure was at or slightly below 1 Gz levels in space, indicating a decrease in total peripheral resistance. It has been suggested that plasma volume is reduced in space, however cardiac output/venous return do not return to 1 Gz levels over the duration of flight. In spite of the increased cardiac output, central venous pressure was not elevated in space. These data suggest that there is a change in the basic relationship between cardiac output and central venous pressure, a persistent "hyperperfusion" and a re-distribution of blood flow and volume during space flight. Increased pulmonary blood flow has been reported to increase diffusing capacity in space, presumably due to the improved homogeneity of ventilation and perfusion. Other studies have suggested that ventilation may be independent of gravity, and perfusion may not be gravity- dependent. No data for the distribution of pulmonary blood volume were available for flight or simulated microgravity. Recent studies have suggested that the pulmonary vascular tree is influenced by sympathetic tone in a manner similar to that of the systemic system. This implies that the pulmonary circulation is dilated during microgravity and that the distribution of blood flow and volume may be influenced more by vascular control than by gravity. The cerebral circulation is influenced by sympathetic tone similarly to that of the systemic and pulmonary circulations; however its effects are modulated by cerebral autoregulation. Thus it is difficult to predict if cerebral perfusion is increased and if there is edema in space. Anecdotal evidence suggests there may be cerebral edema early in flight. Cerebral artery velocity has been shown to be elevated in simulated microgravity. The elevated cerebral artery velocity during simulated microgravity may reflect vasoconstriction of the arteries and not increased cerebral blood flow. The purpose of our investigations was to evaluate the effects of alterations in simulated gravity (+/-), resulting in changes in cardiac output (+/-), and on the blood flow and volume distribution in the lung and brain of human subjects. The first hypothesis of these studies was that blood flow and volume would be affected by gravity, but their distribution in the lung would be independent of gravity and due to vasoactivity changing vascular resistance in lung vessels. The vasodilitation of the lung vasculature (lower resistance) along with increased "compliance" of the heart could account for the absence of increased central venous pressure in microgravity. Secondly, we postulate that cerebral blood velocity is increased in microgravity due to large artery vasoconstriction, but that cerebral blood flow would be reduced due to autoregulation.

Dor procedure for pulmonary atresia with intact ventricular septum in an infant.

PubMed

Kang, Yoonjin; Kwak, Jae Gun; Kim, Eung Rae; Kim, Woong-Han

2018-02-01

Pulmonary atresia with intact ventricular septum and right ventricle-dependent coronary circulation confers a high risk for myocardial infarction and complications of ischaemia, including left ventricle aneurysms. We describe an infant with pulmonary atresia with intact ventricular septum and right ventricle-dependent coronary circulation and a left ventricle apical aneurysm who successfully underwent the Dor procedure and a subsequent Fontan operation. Surgery for postinfarction left ventricle aneurysm can be considered in infants. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Predicting the Necessity for Extracorporeal Circulation During Lung Transplantation: A Feasibility Study.

PubMed

Hinske, Ludwig Christian; Hoechter, Dominik Johannes; Schröeer, Eva; Kneidinger, Nikolaus; Schramm, René; Preissler, Gerhard; Tomasi, Roland; Sisic, Alma; Frey, Lorenz; von Dossow, Vera; Scheiermann, Patrick

2017-06-01

The factors leading to the implementation of unplanned extracorporeal circulation during lung transplantation are poorly defined. Consequently, the authors aimed to identify patients at risk for unplanned extracorporeal circulation during lung transplantation. Retrospective data analysis. Single-center university hospital. A development data set of 170 consecutive patients and an independent validation cohort of 52 patients undergoing lung transplantation. The authors investigated a cohort of 170 consecutive patients undergoing single or sequential bilateral lung transplantation without a priori indication for extracorporeal circulation and evaluated the predictive capability of distinct preoperative and intraoperative variables by using automated model building techniques at three clinically relevant time points (preoperatively, after endotracheal intubation, and after establishing single-lung ventilation). Preoperative mean pulmonary arterial pressure was the strongest predictor for unplanned extracorporeal circulation. A logistic regression model based on preoperative mean pulmonary arterial pressure and lung allocation score achieved an area under the receiver operating characteristic curve of 0.85. Consequently, the authors developed a novel 3-point scoring system based on preoperative mean pulmonary arterial pressure and lung allocation score, which identified patients at risk for unplanned extracorporeal circulation and validated this score in an independent cohort of 52 patients undergoing lung transplantation. The authors showed that patients at risk for unplanned extracorporeal circulation during lung transplantation could be identified by their novel 3-point score. Copyright © 2017 Elsevier Inc. All rights reserved.

Systemic and Vascular Alterations in Rat models Exposed to Libby Amphibole

EPA Science Inventory

Acute pulmonary injury and chronic diseases can impact systemic vasculature and extra pulmonary organ systems due to the hemodynamic properties of the pulmonary capillary network that allows mediators to release into the circulation. Exposure to Libby amphibole (LA) is associated...

Effects of Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) on Fetal Pulmonary Circulation: An Experimental Study in Fetal Lambs

PubMed Central

Sharma, Dyuti; Aubry, Estelle; Ouk, Thavarak; Houeijeh, Ali; Houfflin-Debarge, Véronique; Besson, Rémi; Deruelle, Philippe; Storme, Laurent

2017-01-01

Background: Persistent pulmonary hypertension of the newborn (PPHN) causes significant morbidity and mortality in neonates. n-3 Poly-unsaturated fatty acids have vasodilatory properties in the perinatal lung. We studied the circulatory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fetal sheep and in fetal pulmonary arterial rings. Methods: At 128 days of gestation, catheters were placed surgically in fetal systemic and pulmonary circulation, and a Doppler probe around the left pulmonary artery (LPA). Pulmonary arterial pressure and LPA flow were measured while infusing EPA or DHA for 120 min to the fetus, to compute pulmonary vascular resistance (PVR). The dose effects of EPA or DHA were studied in vascular rings pre-constricted with serotonin. Rings treated with EPA were separated into three groups: E+ (intact endothelium), E− (endothelium stripped) and LNA E+ (pretreatment of E+ rings with l-nitro-arginine). Results: EPA, but not DHA, induced a significant and prolonged 25% drop in PVR (n = 8, p < 0.001). Incubation of vascular rings with EPA (100 µM) caused a maximum relaxation of 60% in the E+ (n = 6), whereas vessel tone did not change in the E− (n = 6, p < 0.001). The vascular effects of EPA were significantly decreased in LNA E+ (n = 6). Incubation with DHA resulted in only a mild relaxation at the highest concentration of DHA (300 µM) compared to E+. Conclusions: EPA induces a sustained pulmonary vasodilatation in fetal lambs. This effect is endothelium- and dose-dependent and involves nitric oxide (NO) production. We speculate that EPA supplementation may improve pulmonary circulation in clinical conditions with PPHN. PMID:28714905

Effects of Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) on Fetal Pulmonary Circulation: An Experimental Study in Fetal Lambs.

PubMed

Sharma, Dyuti; Aubry, Estelle; Ouk, Thavarak; Houeijeh, Ali; Houfflin-Debarge, Véronique; Besson, Rémi; Deruelle, Philippe; Storme, Laurent

2017-07-16

Background: Persistent pulmonary hypertension of the newborn (PPHN) causes significant morbidity and mortality in neonates. n -3 Poly-unsaturated fatty acids have vasodilatory properties in the perinatal lung. We studied the circulatory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fetal sheep and in fetal pulmonary arterial rings. Methods: At 128 days of gestation, catheters were placed surgically in fetal systemic and pulmonary circulation, and a Doppler probe around the left pulmonary artery (LPA). Pulmonary arterial pressure and LPA flow were measured while infusing EPA or DHA for 120 min to the fetus, to compute pulmonary vascular resistance (PVR). The dose effects of EPA or DHA were studied in vascular rings pre-constricted with serotonin. Rings treated with EPA were separated into three groups: E+ (intact endothelium), E- (endothelium stripped) and LNA E+ (pretreatment of E+ rings with l-nitro-arginine). Results: EPA, but not DHA, induced a significant and prolonged 25% drop in PVR ( n = 8, p < 0.001). Incubation of vascular rings with EPA (100 µM) caused a maximum relaxation of 60% in the E+ ( n = 6), whereas vessel tone did not change in the E- ( n = 6, p < 0.001). The vascular effects of EPA were significantly decreased in LNA E+ ( n = 6). Incubation with DHA resulted in only a mild relaxation at the highest concentration of DHA (300 µM) compared to E+. Conclusions: EPA induces a sustained pulmonary vasodilatation in fetal lambs. This effect is endothelium- and dose-dependent and involves nitric oxide (NO) production. We speculate that EPA supplementation may improve pulmonary circulation in clinical conditions with PPHN.

Perspective: ambient air pollution: inflammatory response and effects on the lung’s vasculature

PubMed Central

Esmaeil, Nafiseh; Reibman, Joan

2014-01-01

Abstract Particulates from air pollution are implicated in causing or exacerbating respiratory and systemic cardiovascular diseases and are thought to be among the leading causes of morbidity and mortality. However, the contribution of ambient particulate matter to diseases affecting the pulmonary circulation, the right heart, and especially pulmonary hypertension is much less documented. Our own work and that of other groups has demonstrated that prolonged exposure to antigens via the airways can cause severe pulmonary arterial remodeling. In addition, vascular changes have been well documented in a typical disease of the airways, asthma. These experimental and clinical findings link responses in the airways with responses in the lung’s vasculature. It follows that particulate air pollution could cause, or exacerbate, diseases in the pulmonary circulation and associated pulmonary hypertension. This perspective details the literature for support of this concept. Data regarding the health effects of particulate matter from air pollution on the lung’s vasculature, with emphasis on the lung’s inflammatory responses to particulate matter deposition and pulmonary hypertension, are discussed. A deeper understanding of the health implications of exposure to ambient particulate matter will improve our knowledge of how to improve the management of lung diseases, including diseases of the pulmonary circulation. As man-made ambient particulate air pollution is typically linked to economic growth, a better understanding of the health effects of exposure to particulate air pollution is expected to integrate the global goal of achieving healthy living for all. PMID:25006418

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

Measurement of cardiac output from dynamic pulmonary circulation time CT

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

Yee, Seonghwan, E-mail: Seonghwan.Yee@Beaumont.edu; Scalzetti, Ernest M.

Purpose: To introduce a method of estimating cardiac output from the dynamic pulmonary circulation time CT that is primarily used to determine the optimal time window of CT pulmonary angiography (CTPA). Methods: Dynamic pulmonary circulation time CT series, acquired for eight patients, were retrospectively analyzed. The dynamic CT series was acquired, prior to the main CTPA, in cine mode (1 frame/s) for a single slice at the level of the main pulmonary artery covering the cross sections of ascending aorta (AA) and descending aorta (DA) during the infusion of iodinated contrast. The time series of contrast changes obtained for DA,more » which is the downstream of AA, was assumed to be related to the time series for AA by the convolution with a delay function. The delay time constant in the delay function, representing the average time interval between the cross sections of AA and DA, was determined by least square error fitting between the convoluted AA time series and the DA time series. The cardiac output was then calculated by dividing the volume of the aortic arch between the cross sections of AA and DA (estimated from the single slice CT image) by the average time interval, and multiplying the result by a correction factor. Results: The mean cardiac output value for the six patients was 5.11 (l/min) (with a standard deviation of 1.57 l/min), which is in good agreement with the literature value; the data for the other two patients were too noisy for processing. Conclusions: The dynamic single-slice pulmonary circulation time CT series also can be used to estimate cardiac output.« less

Pathophysiology of Pulmonary Hypertension in Chronic Parenchymal Lung Disease.

PubMed

Singh, Inderjit; Ma, Kevin Cong; Berlin, David Adam

2016-04-01

Pulmonary hypertension commonly complicates chronic obstructive pulmonary disease and interstitial lung disease. The association of chronic lung disease and pulmonary hypertension portends a worse prognosis. The pathophysiology of pulmonary hypertension differs in the presence or absence of lung disease. We describe the physiological determinants of the normal pulmonary circulation to better understand the pathophysiological factors implicated in chronic parenchymal lung disease-associated pulmonary hypertension. This review will focus on the pathophysiology of 3 forms of chronic lung disease-associated pulmonary hypertension: idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and sarcoidosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Protein S is protective in pulmonary fibrosis.

PubMed

Urawa, M; Kobayashi, T; D'Alessandro-Gabazza, C N; Fujimoto, H; Toda, M; Roeen, Z; Hinneh, J A; Yasuma, T; Takei, Y; Taguchi, O; Gabazza, E C

2016-08-01

Essentials Epithelial cell apoptosis is critical in the pathogenesis of idiopathic pulmonary fibrosis. Protein S, a circulating anticoagulant, inhibited apoptosis of lung epithelial cells. Overexpression of protein S in lung cells reduced bleomycin-induced pulmonary fibrosis. Intranasal therapy with exogenous protein S ameliorated bleomycin-induced pulmonary fibrosis. Background Pulmonary fibrosis is the terminal stage of interstitial lung diseases, some of them being incurable and of unknown etiology. Apoptosis plays a critical role in lung fibrogenesis. Protein S is a plasma anticoagulant with potent antiapoptotic activity. The role of protein S in pulmonary fibrosis is unknown. Objectives To evaluate the clinical relevance of protein S and its protective role in pulmonary fibrosis. Methods and Results The circulating level of protein S was measured in patients with pulmonary fibrosis and controls by the use of enzyme immunoassays. Pulmonary fibrosis was induced with bleomycin in transgenic mice overexpressing human protein S and wild-type mice, and exogenous protein S or vehicle was administered to wild-type mice; fibrosis was then compared in both models. Patients with pulmonary fibrosis had reduced circulating levels of protein S as compared with controls. Inflammatory changes, the levels of profibrotic cytokines, fibrosis score, hydroxyproline content in the lungs and oxygen desaturation were significantly reduced in protein S-transgenic mice as compared with wild-type mice. Wild-type mice treated with exogenous protein S showed significant decreases in the levels of inflammatory and profibrotic markers and fibrosis in the lungs as compared with untreated control mice. After bleomycin infusion, mice overexpressing human protein S showed significantly low caspase-3 activity, enhanced expression of antiapoptotic molecules and enhanced Akt and Axl kinase phosphorylation as compared with wild-type counterparts. Protein S also inhibited apoptosis of alveolar epithelial cells in vitro. Conclusions These observations suggest clinical relevance and a protective role of protein S in pulmonary fibrosis. © 2016 International Society on Thrombosis and Haemostasis.

Does the sequence of pulmonary vasculature ligation have any oncological impact during an anatomical lung resection for non-small-cell lung cancer?

PubMed

Toufektzian, Levon; Attia, Rizwan; Polydorou, Nicolaos; Veres, Lukacs

2015-02-01

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'in patients with primary lung carcinoma, does the sequence of pulmonary vasculature ligation during anatomical lung resection influence the oncological outcomes?' A total of 48 papers were found using the reported search, of which 7 represented the best evidence to answer the question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Among six prospective studies included, five of them randomized patients to either pulmonary vein or artery occlusion first during anatomical lung resection, while one study was retrospective. Two reports did not find any difference between pulmonary vein and artery occlusion first during long-term follow-up in terms of either disease recurrence (51 vs 53%, P = 0.7), or 5-year overall survival (54 vs 50%, P = 0.82). One report did not find any difference with regard to circulating tumour cells either after thoracotomy (5.0 vs 3.9, P = 0.4), or after the completion of lobectomy (38.0 vs 70.0, P = 0.23). One report found a higher expression of CD44v6 (P = 0.008) and CK19 (P = 0.05) in patients undergoing pulmonary arterial occlusion first. One report found that pulmonary vein occlusion before that of the pulmonary arterial branches has a favourable outcome on circulating carcino-embryonic antigen (CEA) mRNA in the peripheral blood, while another one did not find a significant difference in circulating levels of CEA mRNA (P = 0.075) and CK19 mRNA (P = 0.086) with either method. Another study reported no correlation between circulating pin1 mRNA levels in peripheral blood after the completion of the resection and the sequence of ligation of pulmonary vessels (9.95 ± 0.91 vs 14.71 ± 1.64, P > 0.05). Based on the two studies assessing the long-term outcome of patients with primary lung cancer undergoing anatomical curative resection, the sequence of ligation of pulmonary vessels does not seem to influence the oncological outcomes or survival. However, the other studies focusing on the influence of these techniques on circulating tumour cells or their molecular products report conflicting results the clinical consequences of which cannot be predicted. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

A brief history of the discovery of the circulation of blood in the human body.

PubMed

Azizi, Mohammad-Hossein; Nayernouri, Touraj; Azizi, Farzaneh

2008-05-01

The present article describes briefly the development of the theories regarding the circulation of blood in humans, from the time of Galen (second century C.E.) to the work of William Harvey (17th century C.E.).We shall summarize the views of Galen together with those of two prominent Iranian physicians of the Middle Ages (Razi and Ahwazi known in the West as Rhazes and Haly Abbas respectively) as well as that of Ibn-Nafis from Damascus (the discoverer of the pulmonary circulation) and the Spanish physician and cleric Michael Servetus and finally the definitive work of William Harvey, the English physician who described the mechanism of both the systemic and pulmonary circulation of blood in the human body.

Upregulation of Human Endogenous Retrovirus-K Is Linked to Immunity and Inflammation in Pulmonary Arterial Hypertension.

PubMed

Saito, Toshie; Miyagawa, Kazuya; Chen, Shih-Yu; Tamosiuniene, Rasa; Wang, Lingli; Sharpe, Orr; Samayoa, Erik; Harada, Daisuke; Moonen, Jan-Renier A J; Cao, Aiqin; Chen, Pin-I; Hennigs, Jan K; Gu, Mingxia; Li, Caiyun G; Leib, Ryan D; Li, Dan; Adams, Christopher M; Del Rosario, Patricia A; Bill, Matthew; Haddad, Francois; Montoya, Jose G; Robinson, William H; Fantl, Wendy J; Nolan, Garry P; Zamanian, Roham T; Nicolls, Mark R; Chiu, Charles Y; Ariza, Maria E; Rabinovitch, Marlene

2017-11-14

Immune dysregulation has been linked to occlusive vascular remodeling in pulmonary arterial hypertension (PAH) that is hereditary, idiopathic, or associated with other conditions. Circulating autoantibodies, lung perivascular lymphoid tissue, and elevated cytokines have been related to PAH pathogenesis but without a clear understanding of how these abnormalities are initiated, perpetuated, and connected in the progression of disease. We therefore set out to identify specific target antigens in PAH lung immune complexes as a starting point toward resolving these issues to better inform future application of immunomodulatory therapies. Lung immune complexes were isolated and PAH target antigens were identified by liquid chromatography tandem mass spectrometry, confirmed by enzyme-linked immunosorbent assay, and localized by confocal microscopy. One PAH antigen linked to immunity and inflammation was pursued and a link to PAH pathophysiology was investigated by next-generation sequencing, functional studies in cultured monocytes and endothelial cells, and hemodynamic and lung studies in a rat. SAM domain and HD domain-containing protein 1 (SAMHD1), an innate immune factor that suppresses HIV replication, was identified and confirmed as highly expressed in immune complexes from 16 hereditary and idiopathic PAH versus 12 control lungs. Elevated SAMHD1 was localized to endothelial cells, perivascular dendritic cells, and macrophages, and SAMHD1 antibodies were prevalent in tertiary lymphoid tissue. An unbiased screen using metagenomic sequencing related SAMHD1 to increased expression of human endogenous retrovirus K (HERV-K) in PAH versus control lungs (n=4). HERV-K envelope and deoxyuridine triphosphate nucleotidohydrolase mRNAs were elevated in PAH versus control lungs (n=10), and proteins were localized to macrophages. HERV-K deoxyuridine triphosphate nucleotidohydrolase induced SAMHD1 and proinflammatory cytokines (eg, interleukin 6, interleukin 1β, and tumor necrosis factor α) in circulating monocytes, pulmonary arterial endothelial cells, and also activated B cells. Vulnerability of pulmonary arterial endothelial cells (PAEC) to apoptosis was increased by HERV-K deoxyuridine triphosphate nucleotidohydrolase in an interleukin 6-independent manner. Furthermore, 3 weekly injections of HERV-K deoxyuridine triphosphate nucleotidohydrolase induced hemodynamic and vascular changes of pulmonary hypertension in rats (n=8) and elevated interleukin 6. Our study reveals that upregulation of the endogenous retrovirus HERV-K could both initiate and sustain activation of the immune system and cause vascular changes associated with PAH. © 2017 American Heart Association, Inc.

Changes in pulmonary circulation in severe bronchopulmonary dysplasia.

PubMed Central

Bush, A; Busst, C M; Knight, W B; Hislop, A A; Haworth, S G; Shinebourne, E A

1990-01-01

Eight patients with severe bronchopulmonary dysplasia underwent cardiac catheterisation. Seven had a pulmonary vascular resistance greater than 3 mm Hg.l-1 min.m2 (mean 8.9, range 2.2-13.8). All had raised intrapulmonary shunts (mean 25.6%, range 5.4-50%, normal less than 5%). Two had a high alveolar dead space, and two had unsuspected congenital heart disease. Epoprostenol (prostacyclin), but not 100% oxygen, caused a significant fall in pulmonary vascular resistance. Death was associated with a high pulmonary vascular resistance and a high shunt. Morphometric studies in three cases showed normal numbers of airways, but increased thickness of bronchial muscle. The numbers of alveoli were reduced and the walls thickened. There was increased medial thickness in small pulmonary arteries with distal extension of muscle. In the oldest child some vessels were obliterated by fibrosis. We speculate that measurements of pulmonary vascular resistance and shunt may have prognostic value; that a trial of pulmonary vasodilators other than oxygen might be worthwhile in patients with poor prognosis; and that abnormalities of the pulmonary circulation contribute to the difficulties of managing patients with bronchopulmonary dysplasia. Images Figure 7 PMID:2117421

Hantaviruses and hantavirus pulmonary syndrome, Maranhao, Brazil.

PubMed

Travassos da Rosa, Elizabeth S; Sampaio de Lemos, Elba R; de Almeida Medeiros, Daniele B; Simith, Darlene B; de Souza Pereira, Armando; Elkhoury, Mauro R; Mendes, Wellington S; Vidigal, José R B; de Oliveira, Renata C; D'Andrea, Paulo S; Bonvicino, Cibele R; Cruz, Ana C R; Nunes, Márcio R T; da Costa Vasconcelos, Pedro F

2010-12-01

To confirm circulation of Anajatuba virus in Maranhao, Brazil, we conducted a serologic survey (immunoglobulin G ELISA) and phylogenetic studies (nucleocapsid gene sequences) of hantaviruses from wild rodents and persons with hantavirus pulmonary syndrome. This virus is transmitted by Oligoryzomys fornesi rodents and is responsible for hantavirus pulmonary syndrome in this region.

Mechanical support of total cavopulmonary connection with an axial flow pump.

PubMed

Riemer, R Kirk; Amir, Gabriel; Reichenbach, Steven H; Reinhartz, Olaf

2005-08-01

Even under optimal circumstances, total cavopulmonary connection is associated with a continuous late risk of death. Hemodynamics are distinctly abnormal, with increased systemic venous pressures and frequent low cardiac output. Our study uses a sheep model of total cavopulmonary connection to test the response to axial flow pump (Thoratec HeartMate II; Thoratec Corporation (Pleasanton, Calif)) support of total cavopulmonary connection, which might be suitable to treat patients with failing Fontan circulation. Eight sheep (42-48 kg) were studied. After pilot studies in 3 animals, 5 underwent both pump-supported and nonsupported total cavopulmonary connection in alternating sequence for up to 2 hours. This was achieved with a 12-mm polytetrafluoroethylene graft from the (distally ligated) superior vena cava to the main pulmonary artery and a cannula placed in the inferior vena cava with an attached 16-mm Dacron graft to the main pulmonary artery. Pressures (arterial, inferior vena cava, left atrium, and pulmonary artery) and flows (ascending aorta and inferior vena cava) were recorded over 1 hour both with unsupported total cavopulmonary connection and after placing an axial flow pump (Thoratec HeartMate II) between the inferior vena caval inflow cannula and the main pulmonary artery. Under nonsupported total cavopulmonary connection circulation, inferior vena caval and aortic blood flow decreased by nearly 50%. Inferior vena caval pressure nearly doubled, whereas arterial pressure decreased by one third. Pulmonary artery pressure became nonpulsatile; however, mean pulmonary artery pressure and left atrial pressure did not change significantly. With pump-supported Fontan circulation, cardiac output, inferior vena caval flow, and arterial pressure returned to baseline. Inferior vena caval pressure decreased to below baseline levels. Mean pulmonary artery pressure and left atrial pressure again remained unchanged. Axial flow pump support from the inferior vena cava to the pulmonary artery can prevent the substantial decrease of aortic flow and pressure associated with total cavopulmonary connection and can reverse its poor hemodynamics. This is a simple model that can be used to further evaluate the potential of mechanical support as a treatment option in failing Fontan circulation.

Computer simulated modeling of healthy and diseased right ventricular and pulmonary circulation.

PubMed

Chou, Jody; Rinehart, Joseph B

2018-01-12

We have previously developed a simulated cardiovascular physiology model for in-silico testing and validation of novel closed-loop controllers. To date, a detailed model of the right heart and pulmonary circulation was not needed, as previous controllers were not intended for use in patients with cardiac or pulmonary pathology. With new development of controllers for vasopressors, and looking forward, for combined vasopressor-fluid controllers, modeling of right-sided and pulmonary pathology is now relevant to further in-silico validation, so we aimed to expand our existing simulation platform to include these elements. Our hypothesis was that the completed platform could be tuned and stabilized such that the distributions of a randomized sample of simulated patients' baseline characteristics would be similar to reported population values. Our secondary outcomes were to further test the system in representing acute right heart failure and pulmonary artery hypertension. After development and tuning of the right-sided circulation, the model was validated against clinical data from multiple previously published articles. The model was considered 'tuned' when 100% of generated randomized patients converged to stability (steady, physiologically-plausible compartmental volumes, flows, and pressures) and 'valid' when the means for the model data in each health condition were contained within the standard deviations for the published data for the condition. A fully described right heart and pulmonary circulation model including non-linear pressure/volume relationships and pressure dependent flows was created over a 6-month span. The model was successfully tuned such that 100% of simulated patients converged into a steady state within 30 s. Simulation results in the healthy state for central venous volume (3350 ± 132 ml) pulmonary blood volume (405 ± 39 ml), pulmonary artery pressures (systolic 20.8 ± 4.1 mmHg and diastolic 9.4 ± 1.8 mmHg), left atrial pressure (4.6 ± 0.8 mmHg), PVR (1.0 ± 0.2 wood units), and CI (3.8 ± 0.5 l/min/m 2 ) all met criteria for acceptance of the model, though the standard deviations of LAP and CI were somewhat narrower than published comparators. The simulation results for right ventricular infarction also fell within the published ranges: pulmonary blood volume (727 ± 102 ml), pulmonary arterial pressures (30 ± 4 mmHg systolic, 12 ± 2 mmHg diastolic), left atrial pressure (13 ± 2 mmHg), PVR (1.6 ± 0.3 wood units), and CI (2.0 ± 0.4 l/min/m 2 ) all fell within one standard deviation of the reported population values and vice-versa. In the pulmonary hypertension model, pulmonary blood volume of 615 ± 90 ml, pulmonary arterial pressures of 80 ± 14 mmHg systolic, 36 ± 7 mmHg diastolic, and the left atrial pressure of 11 ± 2 mmHg all met criteria for acceptance. For CI, the simulated value of 2.8 ± 0.4 l/min/m 2 once again had a narrower spread than most of the published data, but fell inside of the SD of all published data, and the PVR value of 7.5 ± 1.6 wood units fell in the middle of the four published studies. The right-ventricular and pulmonary circulation simulation appears to be a reasonable approximation of the right-sided circulation for healthy physiology as well as the pathologic conditions tested.

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

PubMed

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

2016-12-01

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

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

Thoracic magnetic resonance imaging: pulmonary thromboembolism.

PubMed

Fink, Christian; Henzler, Thomas; Shirinova, Aysel; Apfaltrer, Paul; Wasser, Klaus

2013-05-01

Ongoing technical developments have substantially improved the potential of magnetic resonance imaging (MRI) in the assessment of the pulmonary circulation. These developments includes improved magnet and hardware design, new k-space sampling techniques (ie, parallel imaging), and alternative contrast materials. With these techniques, not only can pulmonary vessels be visualized by MR angiography with high spatial resolution but also the perfusion of the lungs and its changes in relation to pulmonary thromboembolism (PE) can be assessed. Considering venous thromboembolism as a systemic disease, MR venography might be added for the diagnosis of underlying deep venous thrombosis. A unique advantage of MRI over other imaging tests is its potential to evaluate changes in cardiac function as a result of obstruction of the pulmonary circulation, which may have a significant impact on patient monitoring and treatment. Finally, MRI does not involve radiation, which is advantageous, especially in young patients. Over the years, a number of studies have shown promising results not only for MR angiography but also for MRI of lung perfusion and for MR venography. This review article summarizes and discusses the current evidence on pulmonary MRI for patients with suspected PE.

Levosimendan reduces plasma B-type natriuretic peptide and interleukin 6, and improves central hemodynamics in severe heart failure patients.

PubMed

Kyrzopoulos, Stamos; Adamopoulos, Stamatis; Parissis, John T; Rassias, John; Kostakis, George; Iliodromitis, Efstathios; Degiannis, Dimitrios; Kremastinos, Dimitrios Th

2005-03-30

Plasma B-type natriuretic peptide (BNP) and interleukin 6 (IL-6) levels have recently been demonstrated as significant neurohormonal markers associated with the progression of chronic heart failure (CHF). Additionally, clinical studies have shown that the calcium sensitizer, levosimendan, beneficially affects the central hemodynamics of CHF patients and improves their long-term prognosis. This study investigates whether levosimendan-induced hemodynamic improvement of CHF patients is related to the respective changes of NT-proBNP and IL-6 levels. Circulating levels of NT-pro BNP and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA) in 12 patients with decompensated advanced CHF at baseline, immediately after the end of a 24-h levosimendan infusion and 72 h after the initiation of treatment. Hemodynamic parameters of patients (pulmonary wedge and pulmonary artery pressure (PAP), systemic and pulmonary vascular resistance (PVR), stroke volume, and cardiac output and index) were also monitored during the same period. NT-proBNP and IL-6 levels were significantly reduced in severe CHF patients within 72 h after the initiation of levosimendan treatment (p<0.01 and p<0.05, respectively). A significant reduction of pulmonary wedge (p<0.01) and artery pressure values (p<0.05) was also found during the same period. A good correlation between the levosimendan-induced changes in NT-proBNP levels and the respective reduction of pulmonary wedge pressure (r(s)=0.65, p<0.05) was observed. Our results indicate that changes of NT-pro BNP and IL-6 levels may be useful biochemical markers related with the levosimendan-induced improvement in central hemodynamics and the clinical status of decompensated advanced CHF patients.

Pulmonary hypertension in children with congenital heart disease (PAH-CHD, PPHVD-CHD). Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.

PubMed

Kozlik-Feldmann, Rainer; Hansmann, Georg; Bonnet, Damien; Schranz, Dietmar; Apitz, Christian; Michel-Behnke, Ina

2016-05-01

Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) is a complex disease that presents with a broad spectrum of morphological and haemodynamic findings of varying severity. Recently, the aspect of paediatric pulmonary hypertensive vascular disease (PPHVD) has been introduced to expand the understanding of the full spectrum of pulmonary hypertension and increased pulmonary vascular resistance. Evaluation and treatment of PAH-CHD/PPHVD-CHD can be divided into in different topics. First, defining criteria for operability and initiation of advanced therapies preoperatively and postoperatively is an unresolved issue. Second, management of Eisenmenger syndrome is still an important question, with recent evidence on the severity of the disease and a more rapidly progressive course than previously described. Third, the Fontan circulation with no subpulmonary ventricle requires a distinct discussion, definition and classification since even a mild rise in pulmonary vascular resistance may lead to the so-called failing Fontan situation. Patients with CHD and single-ventricle physiology (Fontan/total cavopulmonary anastomosis) require a particularly stepwise and individualised approach. This consensus statement is on the current evidence for the most accurate evaluation and treatment of increased pulmonary artery pressure and resistance, as well as ventricular dysfunction, in children with congenital heart defects, and provides according practical recommendations. To optimise preoperative and postoperative management in patients with PAH-CHD, diagnostic and treatment algorithms are provided. 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/

Total ginsenosides synergize with ulinastatin against septic acute lung injury and acute respir atory distress syndrome

PubMed Central

Sun, Rongju; Li, Yana; Chen, Wei; Zhang, Fei; Li, Tanshi

2015-01-01

Total ginsenosides synergize with ulinastatin (UTI) against septic acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). We randomly divided 80 cases of severe sepsis-induced ALI and ARDS into a UTI group and a ginsenosides (GS)+UTI group. Continuous electrocardiac monitoring of pulse, respiratory rate, blood pressure, and heart rate; invasive hemodynamic monitoring; ventilator-assisted breathing and circulation support; and anti-infection as well as UTI treatment were given in the UTI group with GS treatment added for 7 consecutive days in the GS+UTI group. The indicators of pulmonary vascular permeability, pulmonary circulation, blood gases, and hemodynamics as well as APACHE II and ALI scores were detected on days 1, 3, and 7. The ALI score in the GS+UTI group was significantly decreased (P < 0.05) compared with that of the UTI group, and the indicators of pulmonary capillary permeability such as pulmonary vascular permeability index, extravascular lung water index, and oxygenation index, in the GS+UTI group improved significantly more than that of the UTI group. The indicators of hemodynamics and pulmonary circulation such as cardiac index, intrathoracic blood volume index, and central venous pressure improved significantly (P < 0.05), and the APACHE II score in the GS+UTI group was lower than that of the UTI group. GS can effectively collaborate with UTI against ALI and/or ARDS. PMID:26261640

Airway mechanics and lung tissue viscoelasticity: effects of altered blood hematocrit in the pulmonary circulation.

PubMed

Peták, Ferenc; Fodor, Gergely H; Babik, Barna; Habre, Walid

2016-07-01

The contribution of the hematocrit (Hct) of the blood in the pulmonary vasculature to the overall lung mechanics has not been characterized. We therefore set out to establish how changes of the Hct level in the pulmonary circulation affect the airway and lung tissue viscoelastic properties. The Hct level of the blood in an isolated perfused rat lung model was randomly altered. Intermediate (26.5%), followed by low (6.6%) or normal (43.7%), Hct was set in two consecutive sequences. The pulmonary capillary pressure was maintained constant throughout the experiment, and the pulmonary hemodynamic parameters were monitored continuously. The airway resistance (Raw), the viscous (G) and elastic (H) parameters, and the hysteresivity (η = G/H) of the lung tissues were obtained from measurements of forced oscillatory input impedance data. Raw was not affected by the alterations of the Hct levels. As concerns the lung tissues, the decrease of Hct to intermediate or low levels resulted in close to proportional decreases in the viscoelastic parameters G [16.5 ± 7.7% (SD), 12.1 ± 9.5%, P < 0.005] and H (13.2 ± 8.6%, 10.8 ± 4.7%, P < 0.001). No significant changes in η were detected in a wide range of Hct, which indicates that coupled processes cause alterations in the resistive and elastic properties of the lungs following Hct changes in the pulmonary circulation. The diminishment of the viscous and elastic parameters of the pulmonary parenchyma following a reduction of blood Hct demonstrates the significant contribution of the red blood cells to the overall lung viscoelasticity. Copyright © 2016 the American Physiological Society.

The OregonHeart Total Artificial Heart: Design and Performance on a Mock Circulatory Loop.

PubMed

Glynn, Jeremy; Song, Howard; Hull, Bryan; Withers, Stanley; Gelow, Jill; Mudd, James; Starr, Albert; Wampler, Richard

2017-10-01

Widespread use of heart transplantation is limited by the scarcity of donor organs. Total artificial heart (TAH) development has been pursued to address this shortage, especially to treat patients who require biventricular support. We have developed a novel TAH that utilizes a continuously spinning rotor that shuttles between two positions to provide pulsatile, alternating blood flow to the systemic and pulmonary circulations without artificial valves. Flow rates and pressures generated by the TAH are controlled by adjusting rotor speed, cycle frequency, and the proportion of each cycle spent pumping to either circulation. To validate the design, a TAH prototype was placed in a mock circulatory loop that simulates vascular resistance, pressure, and compliance in normal and pathophysiologic conditions. At a systemic blood pressure of 120/80 mm Hg, nominal TAH output was 7.4 L/min with instantaneous flows reaching 17 L/min. Pulmonary artery, and left and right atrial pressures were all maintained within normal ranges. To simulate implant into a patient with severe pulmonary hypertension, the pulmonary vascular resistance of the mock loop was increased to 7.5 Wood units. By increasing pump speed to the pulmonary circulation, cardiac output could be maintained at 7.4 L/min as mean pulmonary artery pressure increased to 56 mm Hg while systemic blood pressures remained normal. This in vitro testing of a novel, shuttling TAH demonstrated that cardiac output could be maintained across a range of pathophysiologic conditions including pulmonary hypertension. These experiments serve as a proof-of-concept for the design, which has proceeded to in vivo testing. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

THE RELATION OF BACTERIUM PNEUMOSINTES TO INFLUENZA: A STUDY WITH A STRAIN OF THE ORGANISM DERIVED FROM THE NASOPHARYNGEAL WASHINGS OF A CASE OF INFLUENZA

PubMed Central

Hall, Milton W.

1926-01-01

Nasopharyngeal washings from a case of epidemic influenza have proven capable of initiating a pathological change in rabbits and in guinea pigs characterized after an incubation period of 1 or 2 days, by some elevation of temperature, reduction in the number of circulating leucocytes, especially of the mononuclears, and by a pulmonary lesion during the period of reaction, which is distinguishable from those accidentally incurred at the time of death. From one such animal, in the second passage of the virus, an anaerobic coccobacius, corresponding in all respects to Bact. pneumosintes, was isolated by the method employed by Olitsky and Gates. This organism also proved capable of initiating the pathological change in animals found after inoculation with influenzal material. The observation of Olitsky and Gates that the presence of this organism in the lungs of experimental animals predisposes to pulmonary localization of other bacteria with the production of definite pneumonic lesions has been confirmed. Bact. pneumosintes infections may be induced by subcutaneous injection of infected material. PMID:19869205

Hantaviruses and Hantavirus Pulmonary Syndrome, Maranhão, Brazil

PubMed Central

Travassos da Rosa, Elizabeth S.; Sampaio de Lemos, Elba R.; Medeiros, Daniele B. de Almeida; Simith, Darlene B.; Pereira, Armando de Souza; Elkhoury, Mauro R.; Mendes, Wellington S.; Vidigal, José R.B.; de Oliveira, Renata C.; D’Andrea, Paulo S.; Bonvícino, Cibele R.; Cruz, Ana C.R.; Nunes, Márcio R.T.

2010-01-01

To confirm circulation of Anajatuba virus in Maranhão, Brazil, we conducted a serologic survey (immunoglobulin G ELISA) and phylogenetic studies (nucleocapsid gene sequences) of hantaviruses from wild rodents and persons with hantavirus pulmonary syndrome. This virus is transmitted by Oligoryzomys fornesi rodents and is responsible for hantavirus pulmonary syndrome in this region. PMID:21122229

Long term cardiovascular consequences of chronic lung disease of prematurity.

PubMed

Poon, Chuen Yeow; Edwards, Martin Oliver; Kotecha, Sailesh

2013-12-01

Pulmonary arterial (PA) hypertension in preterm infant is an important consequence of chronic lung disease of prematurity (CLD) arising mainly due to impaired alveolar development and dysregulated angiogenesis of the pulmonary circulation. Although PA pressure and resistance in these children normalise by school age, their pulmonary vasculature remains hyper-reactive to hypoxia until early childhood. Furthermore, there is evidence that systemic blood pressure in preterm born children with or without CLD is mildly increased at school age and in young adulthood when compared to term-born children. Arterial stiffness may be increased in CLD survivors due to increased smooth muscle tone of the pre-resistance and resistance vessels rather than the loss of elasticity in the large arteries. This review explores the long term effects of CLD on the pulmonary and systemic circulations along with their clinical correlates and therapeutic approaches. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

PubMed

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

2005-01-01

After cavopulmonary shunt in which the superior vena cava is anastomosed to the right pulmonary artery, the right lung is in a unique condition without flow pulsatility and hepatic venous effluent. In a previous study, we reported that hypoxic pulmonary vasoconstriction disappeared in the pulmonary circulation after cavopulmonary shunt. In this study, however, to investigate the influence of pulsatility and hepatic venous effluent on hypoxic pulmonary vasoconstriction in the pulmonary circulation, we developed an alternative cavopulmonary shunt rabbit model that included hepatic venous effluent in the pulmonary circulation and reduced the pulsatility of the pulmonary arterial blood flow. We then observed the physiologic characteristics of the peripheral pulmonary artery after cavopulmonary shunt, specifically the disappearance of hypoxic pulmonary vasoconstriction. Sixteen Japanese white rabbits (12-16 weeks old) were used in this study. With general anesthesia, a cavopulmonary shunt was established by anastomosing the right superior vena cava to the right pulmonary artery in an end-to-side fashion. Of the 16 rabbits for the study, the proximal right pulmonary artery was completely ligated in 5 (atresia group) and partially ligated in 6 (stenosis group). Sham operation was performed in the remaining 5 rabbits. Two weeks later, we analyzed the response of the pulmonary artery (which was divided into three categories: segmental, lobular, and acinar level artery) to hypoxia (8% oxygen inhalation) with a specially designed video radiographic system. Morphometric analysis of the resistance pulmonary artery was done in each group after angiography. Mean pressure and pulse pressure in the right pulmonary artery were not significantly different between the atresia and stenosis groups. The mean pulmonary artery pressures in the atresia and stenosis groups were 8 and 11 mm Hg, respectively. However, the pulse pressure was less than 2 mm Hg in both groups. The baseline internal diameter of the resistance pulmonary artery of the atresia group was significantly different from those of the stenosis and sham groups. In the atresia group, the resistance pulmonary arteries did not respond to hypoxia. In contrast, significant constriction (as assessed by percentage change of internal diameter of the resistance pulmonary arteries in the acinar and lobular level arteries) was observed in the pulmonary arteries of the sham and stenosis groups (atresia vs stenosis vs sham 0.4% vs - 19.0% vs - 18.8%, P = .01). In our morphometric study, we observed vasodilation of the resistance pulmonary artery with a thinner medial layer in the atresia group, consistent with the result of microangiography. We developed a cavopulmonary shunt rabbit model in which the inferior vena caval blood was derived from the right ventricle. Hypoxic pulmonary vasoconstriction was maintained in the model with the blood flow from the right ventricle. When the blood flow was not maintained, however, hypoxic pulmonary vasoconstriction disappeared. This phenomenon strongly suggests that a substance in hepatic venous effluent partially regulates the physiological pulmonary vascular function in the rabbit lung.

THE RAPID SHALLOW BREATHING RESULTING FROM PULMONARY CONGESTION AND EDEMA

PubMed Central

Churchill, Edward D.; Cope, Oliver

1929-01-01

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

Platelet GPIIb supports initial pulmonary retention but inhibits subsequent proliferation of melanoma cells during hematogenic metastasis

PubMed Central

Echtler, Katrin; Konrad, Ildiko; Lorenz, Michael; Schneider, Simon; Hofmaier, Sebastian; Plenagl, Florian; Stark, Konstantin; Czermak, Thomas; Tirniceriu, Anca; Eichhorn, Martin; Walch, Axel; Enders, Georg; Massberg, Steffen; Schulz, Christian

2017-01-01

Platelets modulate the process of cancer metastasis. However, current knowledge on the direct interaction of platelets and tumor cells is mostly based on findings obtained in vitro. We addressed the role of the platelet fibrinogen receptor glycoprotein IIb (integrin αIIb) for experimental melanoma metastasis in vivo. Highly metastatic B16-D5 melanoma cells were injected intravenously into GPIIb-deficient (GPIIb-/-) or wildtype (WT) mice. Acute accumulation of tumor cells in the pulmonary vasculature was assessed in real-time by confocal videofluorescence microscopy. Arrest of tumor cells was dramatically reduced in GPIIb-/- mice as compared to WT. Importantly, we found that mainly multicellular aggregates accumulated in the pulmonary circulation of WT, instead B16-D5 aggregates were significantly smaller in GPIIb-/- mice. While pulmonary arrest of melanoma was clearly dependent on GPIIb in this early phase of metastasis, we also addressed tumor progression 10 days after injection. Inversely, and unexpectedly, we found that melanoma metastasis was now increased in GPIIb-/- mice. In contrast, GPIIb did not regulate local melanoma proliferation in a subcutaneous tumor model. Our data suggest that the platelet fibrinogen receptor has a differential role in the modulation of hematogenic melanoma metastasis. While platelets clearly support early steps in pulmonary metastasis via GPIIb-dependent formation of platelet-tumor-aggregates, at a later stage its absence is associated with an accelerated development of melanoma metastases. PMID:28253287

Platelet GPIIb supports initial pulmonary retention but inhibits subsequent proliferation of melanoma cells during hematogenic metastasis.

PubMed

Echtler, Katrin; Konrad, Ildiko; Lorenz, Michael; Schneider, Simon; Hofmaier, Sebastian; Plenagl, Florian; Stark, Konstantin; Czermak, Thomas; Tirniceriu, Anca; Eichhorn, Martin; Walch, Axel; Enders, Georg; Massberg, Steffen; Schulz, Christian

2017-01-01

Platelets modulate the process of cancer metastasis. However, current knowledge on the direct interaction of platelets and tumor cells is mostly based on findings obtained in vitro. We addressed the role of the platelet fibrinogen receptor glycoprotein IIb (integrin αIIb) for experimental melanoma metastasis in vivo. Highly metastatic B16-D5 melanoma cells were injected intravenously into GPIIb-deficient (GPIIb-/-) or wildtype (WT) mice. Acute accumulation of tumor cells in the pulmonary vasculature was assessed in real-time by confocal videofluorescence microscopy. Arrest of tumor cells was dramatically reduced in GPIIb-/- mice as compared to WT. Importantly, we found that mainly multicellular aggregates accumulated in the pulmonary circulation of WT, instead B16-D5 aggregates were significantly smaller in GPIIb-/- mice. While pulmonary arrest of melanoma was clearly dependent on GPIIb in this early phase of metastasis, we also addressed tumor progression 10 days after injection. Inversely, and unexpectedly, we found that melanoma metastasis was now increased in GPIIb-/- mice. In contrast, GPIIb did not regulate local melanoma proliferation in a subcutaneous tumor model. Our data suggest that the platelet fibrinogen receptor has a differential role in the modulation of hematogenic melanoma metastasis. While platelets clearly support early steps in pulmonary metastasis via GPIIb-dependent formation of platelet-tumor-aggregates, at a later stage its absence is associated with an accelerated development of melanoma metastases.

Exercise-Induced Pulmonary Hypertension: Translating Pathophysiological Concepts Into Clinical Practice.

PubMed

Naeije, Robert; Saggar, Rajeev; Badesch, David; Rajagopalan, Sanjay; Gargani, Luna; Rischard, Franz; Ferrara, Francesco; Marra, Alberto M; D' Alto, Michele; Bull, Todd M; Saggar, Rajan; Grünig, Ekkehard; Bossone, Eduardo

2018-01-31

Exercise stress testing of the pulmonary circulation for the diagnosis of latent or early-stage pulmonary hypertension (PH) is gaining acceptance. There is emerging consensus to define exercise-induced PH by a mean pulmonary artery pressure > 30 mm Hg at a cardiac output < 10 L/min and a total pulmonary vascular resistance> 3 Wood units at maximum exercise, in the absence of PH at rest. Exercise-induced PH has been reported in association with a bone morphogenetic receptor-2 gene mutation, in systemic sclerosis, in left heart conditions, in chronic lung diseases, and in chronic pulmonary thromboembolism. Exercise-induced PH is a cause of decreased exercise capacity, may precede the development of manifest PH in a proportion of patients, and is associated with a decreased life expectancy. Exercise stress testing of the pulmonary circulation has to be dynamic and rely on measurements of the components of the pulmonary vascular equation during, not after exercise. Noninvasive imaging measurements may be sufficiently accurate in experienced hands, but suffer from lack of precision, so that invasive measurements are required for individual decision-making. Exercise-induced PH is caused either by pulmonary vasoconstriction, pulmonary vascular remodeling, or by increased upstream transmission of pulmonary venous pressure. This differential diagnosis is clinical. Left heart disease as a cause of exercise-induced PH can be further ascertained by a pulmonary artery wedge pressure above or below 20 mm Hg at a cardiac output < 10 L/min or a pulmonary artery wedge pressure-flow relationship above or below 2 mm Hg/L/min during exercise. Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

[Gas embolism in the rat].

PubMed

Lagneaux, D; Bodson, L; Remacle, R

1982-11-01

Gaseous carbon dioxide was used to produce experimental pulmonary embolism in anaesthetized rats, the vagal nerves of which were either intact or severed. 1. Within seconds following intravenous CO2 injection, pulmonary hypertension, moderate systemic hypotension and bradycardia occurred. After a short hyperventilation period, intact rats showed a brief and transient apnea. Vagotomy suppresses (1) apnea presumably by interruption of reflexes from J pulmonary receptors (Paintal, 1967) and (2) bradycardia by the same token or by suppression of a reflex from auricular origin (Thorén, 1976). 2. Following that initial phase, the events were totally dependent on the right ventricular ability to overcome the pulmonary vascular resistance. If it failed, left and right pressures fell and a secondary apnea followed systemic hypotension. Vagotomy had no effect at this stage. Only half of all animals showed these features. 3. Pulmonary hypertension and hyperventilation lasted twenty minutes at least in intact rats, while vagotomized ones showed an evolution toward acute pulmonary oedema and death. 4. With the same amount of CO2/kg, the dogs of Verstappen et al. (1977) showed only minimal cardio-vascular alterations. The mode of effective embolization in the two species was probably different, as a function of the respective circulation times. But this geometrical point of view is not the only one to be considered: in rats, the rise of pulmonary arterial blood pressure remains even when mechanical obstruction by bubbles has dissipated and a local prolonged vasospasm could be advocated. 5. Acute pulmonary oedema rapidly occurring in vagotomized rats seems to be related to the hyperinflation (very large tidal volume) as also seen in this species with other intensive respiratory drives.

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

Design of a hydraulic analog of the circulatory system for evaluating artificial hearts.

PubMed

Donovan, F M

1975-01-01

A major problem in improving artificial heart designs is the absence of methods for accurate in vitro testing of artificial heart systems. A mock circulatory system has been constructed which hydraulically simulates the systemic and pulmonary circulations of the normal human. The device is constructed of 1/2 in. acrylic sheet and has overall dimensions of 24 in. wide, 16 in. tall, and 8 in. deep. The artificial heart to be tested is attached to the front of the device, and pumps fluid from the systemic venous chamber into the pulmonary arterial chamber and from the pulmonary venous chamber into the systemic arterial chamber. Each of the four chambers is hermetically sealed. The compliance of each chamber is determined by the volume of air trapped above the fluid in that chamber. The pulmonary and systemic resistances are set automatically by bellows-operated valves to simulate the barroreceptor response in the systemic arteries and the passive pulmonary resistance response in the pulmonary arteries. Cardiac output is measured by a turbine flowmeter in the systemic circulation. Results using the Kwan-Gett artificial heart show a good comparison between the mock circulatory system response and the calf response.

VASCULAR AND THROMBOGENIC EFFECTS OF PULMONARY EXPOSURE TO LIBBY AMPHIBOLE

EPA Science Inventory

Acute pulmonary injury and chronic disease can impact the systemic vasculature through the release of inflammogenic and vasoactive mediators from the lung into the circulation. Exposure to Libby amphibole (LA) asbestos is associated with increased human cardiovascular mortality a...

New approach in partial cavopulmonary connection.

PubMed

Paulista, P P; Santana, M V; Henriques Neto, A T; Fontes, V F

1998-07-01

The development of pulmonary arteriovenous fistulas after bidirectional cavopulmonary operations, such as the bidirectional Glenn shunt and Kawashima's procedure, has raised concern. Development of these fistulas, which are more frequent than initially thought, can represent a limiting factor in the late outcome of these patients and may even limit the indication for these types of surgery. Whether the fistulas can be reversed by transforming the surgical procedures has yet to be established. In the hope of avoiding this kind of complication, thought to be caused by the lack of passage of a hypothetical hepatic factor through the pulmonary circulation, we have developed an inverted type of bidirectional cavopulmonary connection in which the blood coming from the liver perfuses immediately both lungs. This is made possible by shunting via an intra-atrial tunnel the blood from the superior caval vein directly to the left atrium, and the blood from the inferior caval vein to the right branch of the pulmonary trunk (keeping its bifurcation intact). We describe findings in two patients undergoing successful surgery with this technique. Serial follow-up with contrast echocardiography did not show evidence of arteriovenous pulmonary fistulas. Despite our numbers being small, and the time of follow-up being limited, we believe that it is important to document these and similar cases.

Oxidative injury of the pulmonary circulation in the perinatal period: Short- and long-term consequences for the human cardiopulmonary system

PubMed Central

de Wijs-Meijler, Daphne P.; Duncker, Dirk J.; Tibboel, Dick; Schermuly, Ralph T.; Weissmann, Norbert; Merkus, Daphne; Reiss, Irwin K.M.

2017-01-01

Development of the pulmonary circulation is a complex process with a spatial pattern that is tightly controlled. This process is vulnerable for disruption by various events in the prenatal and early postnatal periods. Disruption of normal pulmonary vascular development leads to abnormal structure and function of the lung vasculature, causing neonatal pulmonary vascular diseases. Premature babies are especially at risk of the development of these diseases, including persistent pulmonary hypertension and bronchopulmonary dysplasia. Reactive oxygen species play a key role in the pathogenesis of neonatal pulmonary vascular diseases and can be caused by hyperoxia, mechanical ventilation, hypoxia, and inflammation. Besides the well-established short-term consequences, exposure of the developing lung to injurious stimuli in the perinatal period, including oxidative stress, may also contribute to the development of pulmonary vascular diseases later in life, through so-called “fetal or perinatal programming.” Because of these long-term consequences, it is important to develop a follow-up program tailored to adolescent survivors of neonatal pulmonary vascular diseases, aimed at early detection of adult pulmonary vascular diseases, and thereby opening the possibility of early intervention and interfering with disease progression. This review focuses on pathophysiologic events in the perinatal period that have been shown to disrupt human normal pulmonary vascular development, leading to neonatal pulmonary vascular diseases that can extend even into adulthood. This knowledge may be particularly important for ex-premature adults who are at risk of the long-term consequences of pulmonary vascular diseases, thereby contributing disproportionately to the burden of adult cardiovascular disease in the future. PMID:28680565

Lineage Analysis in Pulmonary Arterial Hypertension

DTIC Science & Technology

2012-06-01

undergo pneunomectomy followed one week later by intravenous injection of monocrotaline pyrrole . The fate of GFP-expressing cells of endothelial lineage...pneumonectomy followed one week later by jugular vein injection of monocrotaline pyrrole in dimethyl formamide. Expression of smooth muscle alpha actin in...cells. We induced experimental pulmonary hypertension in SM22 Cre x mT/mG mice, by injecting monocrotaline pyrrole into the pulmonary circulation of

Cardio-Pulmonary Response to Shock.

DTIC Science & Technology

1981-02-01

Maryland 21701 ( Contract No. DANID17-78-C-8026 Harvard Medical School 25 Shattuck St. D Boston, Massachusetts 02115 E L - C T E APR 16 1W84 Approved for...Controlling Offce) IS. SECURITY CLASS. (of this repot) ISa. DECL ASSIFICATION/DOWNGRADING SCHEDULE IS. DISTRIBUTION STATEMENT (of AdU Repoft) Approved...Circulating Negative Inotropes 1. Depressed left ventricular function following pulmonary embolism 2. Thromboxane mediation of cardio-pulmonary effects

In Vitro Study of Flow Regulation for Pulmonary Insufficiency

PubMed Central

Camp, T. A.; Stewart, K. C.; Figliola, R. S.; McQuinn, T.

2007-01-01

Given the tolerance of the right heart circulation to mild regurgitation and gradient, we study the potential of using motionless devices to regulate the pulmonary circulation. In addition, we document the flow performance of two mechanical valves. A motionless diode, a nozzle, a mechanical bileaflet valve, and a tilting disk valve were tested in a pulmonary mock circulatory system over the normal human range of pulmonary vascular resistance (PVR). For the mechanical valves, regurgitant fractions (RFs) and transvalvular pressure gradients were found to be weak functions of PVR. On the low end of normal PVR, the bileaflet and tilting disk valves fluttered and would not fully close. Despite this anomaly, the regurgitant fraction of either valve did not change significantly. The values for RF and transvalvular gradient measured varied from 4 to 7% and 4 to 7 mm Hg, respectively, at 5 lpm for all tests. The diode valve was able to regulate flow with mild regurgitant fraction and trivial gradient but with values higher than either mechanical valve tested. Regurgitant fraction ranged from 2 to 17% in tests extending from PVR values of 1 to 4.5 mm Hg/lpm at 5 lpm and with concomitant increases in gradient up to 17 mm Hg. The regurgitant fraction for the nozzle increased from 2 to 23% over the range of PVR with gradients increasing to 18 mm Hg. The significant findings were: (1) the mechanical valves controlled regurgitation at normal physiological cardiac output and PVR even though they failed to close at some normal values of PVR and showed leaflet flutter; and (2) it may be possible to regulate the pulmonary circulation to tolerable levels using a motionless pulmonary valve device. PMID:17408334

Perioperative pharmacological management of pulmonary hypertensive crisis during congenital heart surgery.

PubMed

Brunner, Nathan; de Jesus Perez, Vinicio A; Richter, Alice; Haddad, François; Denault, André; Rojas, Vanessa; Yuan, Ke; Orcholski, Mark; Liao, Xiaobo

2014-03-01

Pulmonary hypertensive crisis is an important cause of morbidity and mortality in patients with pulmonary arterial hypertension secondary to congenital heart disease (PAH-CHD) who require cardiac surgery. At present, prevention and management of perioperative pulmonary hypertensive crisis is aimed at optimizing cardiopulmonary interactions by targeting prostacyclin, endothelin, and nitric oxide signaling pathways within the pulmonary circulation with various pharmacological agents. This review is aimed at familiarizing the practitioner with the current pharmacological treatment for dealing with perioperative pulmonary hypertensive crisis in PAH-CHD patients. Given the life-threatening complications associated with pulmonary hypertensive crisis, proper perioperative planning can help anticipate cardiopulmonary complications and optimize surgical outcomes in this patient population.

Perioperative pharmacological management of pulmonary hypertensive crisis during congenital heart surgery

PubMed Central

2014-01-01

Abstract Pulmonary hypertensive crisis is an important cause of morbidity and mortality in patients with pulmonary arterial hypertension secondary to congenital heart disease (PAH-CHD) who require cardiac surgery. At present, prevention and management of perioperative pulmonary hypertensive crisis is aimed at optimizing cardiopulmonary interactions by targeting prostacyclin, endothelin, and nitric oxide signaling pathways within the pulmonary circulation with various pharmacological agents. This review is aimed at familiarizing the practitioner with the current pharmacological treatment for dealing with perioperative pulmonary hypertensive crisis in PAH-CHD patients. Given the life-threatening complications associated with pulmonary hypertensive crisis, proper perioperative planning can help anticipate cardiopulmonary complications and optimize surgical outcomes in this patient population. PMID:25006417

Pulmonary hypertension and hepatic cirrhosis.

PubMed

Téllez Villajos, L; Martínez González, J; Moreira Vicente, V; Albillos Martínez, A

2015-01-01

Pulmonary hypertension is a relatively common phenomenon in patients with hepatic cirrhosis and can appear through various mechanisms. The most characteristic scenario that binds portal and pulmonary hypertension is portopulmonary syndrome. However, hyperdynamic circulation, TIPS placement and heart failure can raise the mean pulmonary artery pressure without increasing the resistances. These conditions are not candidates for treatment with pulmonary vasodilators and require a specific therapy. A correct assessment of hemodynamic, ultrasound and clinical variables enables the differential diagnosis of each situation that produces pulmonary hypertension in patients with cirrhosis. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Cardiorespiratory Interactions in Paediatrics: 'It's (almost always) the circulation stupid!'

PubMed

Rigby, M L; Rosenthal, M

2017-03-01

The interaction of the heart and lungs is probably the most important aspect of life and survival. Fortunately, it is not difficult to understand the fundamentals. The purpose of the lungs and their ventilation is to present oxygen to the circulation via the alveoli and to receive carbon dioxide from the circulation and then expel it. The relations of the heart and lungs and the matching of blood flow to the various organs with ventilation and lung perfusion may be disrupted by a variety of congenital or acquired heart malformations. They include those giving rise to an increased or reduced pulmonary blood flow, elevated pulmonary venous pressure or external physical pressure on the airways or lung parenchyma. Respiratory disorders which compromise cardiac function include states with reduced alveolar ventilation, those with a barrier to ventilation or perfusion, ventilation/perfusion mismatch and pulmonary vascular disease. There is also a fascinating group in which congenital disorders of the heart and lung co-exist to produce very particular modes of abnormal cardiopulmonary interaction. Copyright © 2016. Published by Elsevier Ltd.

[Oxygen-transporting function of the blood circulation system in sevoflurane anesthesia during myocardial revascularization under extracorporeal circulation].

PubMed

Skopets, A A; Lomivorotov, V V; Karakhalis, N B; Makarov, A A; Duman'ian, E S; Lomivorotova, L V

2009-01-01

The purpose of the study was to evaluate the efficiency of oxygen-transporting function of the circulatory system under sevoflurane anesthesia during myocardial revascularization operations under extracorporeal circulation. Twenty-five patients with coronary heart disease were examined. Mean blood pressure, heart rate, cardiac index, total peripheral vascular resistance index, pulmonary pressure, pulmonary wedge pressure, and central venous pressure were measured. Arterial and mixed venous blood oxygen levels, oxygen delivery and consumption index, arteriovenous oxygen difference, and glucose and lactate concentrations were calculated. The study has demonstrated that sevoflurane is an effective and safe anesthetic for myocardial revascularization operations in patients with coronary heart disease. The use of sevoflurane contributes to steady-state oxygen-transporting function of the circulatory system at all surgical stages.

Identification and Characterization of a Dendritic Cell Precursor in Parenchymal Lung Tissue.

PubMed

von Garnier, Christophe; Blank, Fabian; Rothen-Rutishauser, Barbara; Goethert, Joachim R; Holt, Patrick G; Stumbles, Philip A; Strickland, Deborah H

2017-03-01

The pulmonary parenchymal and mucosal microenvironments are constantly exposed to the external environment and thus require continuous surveillance to maintain steady-state immunological homeostasis. This is achieved by a mobile network of pulmonary dendritic cells (DC) and macrophages (mø) that constantly sample and process microenvironmental antigens into signals that can initiate or dampen inflammation, either locally or after onward migration to draining lymph nodes. The constant steady-state turnover of pulmonary DC and mø requires replenishment from bone marrow precursors; however, the nature of the pulmonary precursor cell (PC) remains unclear, although recent studies suggest that subsets of pulmonary DC may derive from circulating monocytic precursors. In the current study, we describe a population of cells in steady-state mouse lung tissue that has the surface phenotypic and ultrastructural characteristics of a common DC progenitor. Irradiation and reconstitution studies confirmed the bone marrow origins of this PC and showed that it had rapid depletion and reconstitution kinetics that were similar to those of DC, with a 50% repopulation by donor-derived cells by Days 7-9 after reconstitution. This was significantly faster than the rates observed for mø, which showed 50% repopulation by donor-derived cells beyond Days 16-21 after reconstitution. Purified PC gained antigen-presenting function and a cell surface phenotype similar to that of pulmonary DC after maturation in vitro, with light and electron microscopy confirming a myeloid DC morphology. To the best of our knowledge, this is the first study to describe a PC for DC in lung tissue; the findings have implications for the restoration of pulmonary immunological homeostasis after bone marrow transplant.

Evaluation of Pulmonary Nodules: Clinical Practice Consensus Guidelines for Asia.

PubMed

Bai, Chunxue; Choi, Chang-Min; Chu, Chung Ming; Anantham, Devanand; Chung-Man Ho, James; Khan, Ali Zamir; Lee, Jang-Ming; Li, Shi Yue; Saenghirunvattana, Sawang; Yim, Anthony

2016-10-01

American College of Chest Physicians (CHEST) clinical practice guidelines on the evaluation of pulmonary nodules may have low adoption among clinicians in Asian countries. Unique patient characteristics of Asian patients affect the diagnostic evaluation of pulmonary nodules. The objective of these clinical practice guidelines was to adapt those of CHEST to provide consensus-based recommendations relevant to practitioners in Asia. A modified ADAPTE process was used by a multidisciplinary group of pulmonologists and thoracic surgeons in Asia. An initial panel meeting analyzed all CHEST recommendations to achieve consensus on recommendations and identify areas that required further investigation before consensus could be achieved. Revised recommendations were circulated to panel members for iterative review and redrafting to develop the final guidelines. Evaluation of pulmonary nodules in Asia broadly follows those of the CHEST guidelines with important caveats. Practitioners should be aware of the risk of lung cancer caused by high levels of indoor and outdoor air pollution, as well as the high incidence of adenocarcinoma in female nonsmokers. Furthermore, the high prevalence of granulomatous disease and other infectious causes of pulmonary nodules need to be considered. Therefore, diagnostic risk calculators developed in non-Asian patients may not be applicable. Overall, longer surveillance of nodules than those recommended by CHEST should be considered. TB in Asia favors lesser reliance on PET scanning and greater use of nonsurgical biopsy over surgical diagnosis or surveillance. Practitioners in Asia are encouraged to use these adapted consensus guidelines to facilitate consistent evaluation of pulmonary nodules. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Circulating Magnetic Microbubbles for Localized Real-Time Control of Drug Delivery by Ultrasonography-Guided Magnetic Targeting and Ultrasound

PubMed Central

Chertok, Beata; Langer, Robert

2018-01-01

Image-guided and target-selective modulation of drug delivery by external physical triggers at the site of pathology has the potential to enable tailored control of drug targeting. Magnetic microbubbles that are responsive to magnetic and acoustic modulation and visible to ultrasonography have been proposed as a means to realize this drug targeting strategy. To comply with this strategy in vivo, magnetic microbubbles must circulate systemically and evade deposition in pulmonary capillaries, while also preserving magnetic and acoustic activities in circulation over time. Unfortunately, challenges in fabricating magnetic microbubbles with such characteristics have limited progress in this field. In this report, we develop magnetic microbubbles (MagMB) that display strong magnetic and acoustic activities, while also preserving the ability to circulate systemically and evade pulmonary entrapment. Methods: We systematically evaluated the characteristics of MagMB including their pharmacokinetics, biodistribution, visibility to ultrasonography and amenability to magneto-acoustic modulation in tumor-bearing mice. We further assessed the applicability of MagMB for ultrasonography-guided control of drug targeting. Results: Following intravenous injection, MagMB exhibited a 17- to 90-fold lower pulmonary entrapment compared to previously reported magnetic microbubbles and mimicked circulation persistence of the clinically utilized Definity microbubbles (>10 min). In addition, MagMB could be accumulated in tumor vasculature by magnetic targeting, monitored by ultrasonography and collapsed by focused ultrasound on demand to activate drug deposition at the target. Furthermore, drug delivery to target tumors could be enhanced by adjusting the magneto-acoustic modulation based on ultrasonographic monitoring of MagMB in real-time. Conclusions: Circulating MagMB in conjunction with ultrasonography-guided magneto-acoustic modulation may provide a strategy for tailored minimally-invasive control over drug delivery to target tissues. PMID:29290812

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

PubMed

Starck, J Matthias

2009-06-01

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

Cardiopulmonary responses to acute hypoxia, head-down tilt and fluid loading in anesthetized dogs

NASA Technical Reports Server (NTRS)

Loeppky, J. A.; Scotto, P.; Riedel, C.; Avasthi, P.; Koshukosky, V.; Chick, T. W.

1991-01-01

Cardiopulmonary responses to acute hypoxia (HY), fluid loading by saline infusion (FL), and head-down tilt (HD) of mechanically ventilated anesthetized dogs were investigated by measuring thermodynamics and pulmonary gas exchange. It was found that HD decreased the total respiratory compliance both during HY and normoxia (NO) and that the reduction in compliance by FL was twice as large as by HD. Superimposing HD on HY doubled the increase in vascular resistance due to HY alone. In the systemic circulation, HD lowered the resistance to below NO levels. There was a significant positive correlation between the changes in blood volume and in pulmonary artery pressure for experimental transitions, suggesting that a shift in blood volume from systemic to pulmonary circulations and changes in the total blood volume may contribute substantially to these apparent changes in resistance.

[Clinical, hemodynamic and angiographic results of total cavo-pulmonary connection].

PubMed

Jimenez, A C; Neville, P; Chamboux, C; Crenn, R; Vaillant, M C; Marchand, M; Chantepie, A

1998-05-01

The aim of the study was to assess the short and medium term results of total cavo-pulmonary connection based on analysis of the functional status, the cavo-pulmonary circulation and the surgical techniques, and the hepatic consequences. Fifteen patients with congenital defects beyond repair were treated by total cavo-pulmonary connection at Tours between March 1st 1992 and July 30th 1996. There were 12 children (mean age: 6.3 years) and 3 adults aged 25 to 28. Results were assessed by clinical examination, hepatic function tests and cardiovascular investigations including right heart catheterisation with angiography in 14 patients. There were no fatalities. Seven patients were in functional Class I and 8 in Class II at medium term (average follow-up of 33 months). Hepatic function was mildly abnormal in all patients with an increase in serum bilirubin and gamma GT, and a decrease in the coagulation factors. The mean pressures in the atrial channel were 12 mmHg (9-16 mmHg), in the superior vena 13.2 mmHg (10-18 mmHg), in the right pulmonary artery 9.5 mmHg (7-15 mmHg) and 11.6 mmHg (8-16 mmHg) in the left pulmonary artery. Significant residual stenosis of a pulmonary branch was observed in 2 cases. The cavo-pulmonary anastomoses were out of line, one from the other, in all cases. The atrial channel was tubular in 9 cases and dilated with slight stagnation of the contrast medium in its inferior region in 5 cases. Total cavo-pulmonary connection transformed the clinical status of these patients but was associated with minor abnormalities of liver function. The quality of the cavo-pulmonary circulation and the surgical anastomoses was estimated to be satisfactory in the majority of cases.

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

PubMed

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

2012-02-01

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

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

PubMed Central

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

2011-01-01

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

Stressed lungs: unveiling the role of circulating stress hormones in ozone-induced lung injury and inflammation

EPA Science Inventory

Our recent work demonstrated that circulating stress hormones, epinephrine and corticosterone/cortisol, are involved in mediating ozone pulmonary effects through the activation of hypothalamus-pituitary-adrenal (HPA) axis. Adrenalectomy in Wistar Kyoto (WKY) rats diminished circu...

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

Endothelial progenitor cells in chronic obstructive pulmonary disease and emphysema

PubMed Central

Tracy, Russell P.; Parikh, Megha A.; Hoffman, Eric A.; Shimbo, Daichi; Austin, John H. M.; Smith, Benjamin M.; Hueper, Katja; Vogel-Claussen, Jens; Lima, Joao; Gomes, Antoinette; Watson, Karol; Kawut, Steven; Barr, R. Graham

2017-01-01

Endothelial injury is implicated in the pathogenesis of COPD and emphysema; however the role of endothelial progenitor cells (EPCs), a marker of endothelial cell repair, and circulating endothelial cells (CECs), a marker of endothelial cell injury, in COPD and its subphenotypes is unresolved. We hypothesized that endothelial progenitor cell populations would be decreased in COPD and emphysema and that circulating endothelial cells would be increased. Associations with other subphenotypes were examined. The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with COPD and controls age 50–79 years without clinical cardiovascular disease. Endothelial progenitor cell populations (CD34+KDR+ and CD34+KDR+CD133+ cells) and circulating endothelial cells (CD45dimCD31+CD146+CD133-) were measured by flow cytometry. COPD was defined by standard spirometric criteria. Emphysema was assessed qualitatively and quantitatively on CT. Full pulmonary function testing and expiratory CTs were measured in a subset. Among 257 participants, both endothelial progenitor cell populations, and particularly CD34+KDR+ endothelial progenitor cells, were reduced in COPD. The CD34+KDR+CD133+ endothelial progenitor cells were associated inversely with emphysema extent. Both endothelial progenitor cell populations were associated inversely with extent of panlobular emphysema and positively with diffusing capacity. Circulating endothelial cells were not significantly altered in COPD but were inversely associated with pulmonary microvascular blood flow on MRI. There was no consistent association of endothelial progenitor cells or circulating endothelial cells with measures of gas trapping. These data provide evidence that endothelial repair is impaired in COPD and suggest that this pathological process is specific to emphysema. PMID:28291826

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

PubMed Central

2014-01-01

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

The pulmonary vasculature--lessons from Tibetans and from rare diseases of oxygen sensing.

PubMed

Frise, Matthew C; Robbins, Peter A

2015-11-01

What is the topic of this review? This review is principally concerned with results from studies of the pulmonary vasculature in humans, particularly in relation to hypoxia and rare diseases that affect oxygen sensing. What advances does it highlight? This review highlights the degree to which the hypoxia-inducible factor (HIF) transcription system influences human pulmonary vascular responses to hypoxia. Upregulation of the HIF pathway augments hypoxic pulmonary vasoconstriction, while alterations to the pathway found in Tibetans are associated with suppression of the progressive increase in pulmonary artery pressure with sustained hypoxia. It also highlights the potential importance of iron, which modulates the HIF pathway, in modifying the pulmonary vascular response to hypoxia. The human pulmonary circulation loses its natural distensibility during sustained hypoxia, leading to pulmonary arterial hypertension and a much higher workload for the right ventricle. The hypoxia-inducible factor (HIF) pathway is implicated in this pulmonary vascular response to continued hypoxia by animal studies, and additionally, by rare human diseases where the pathway is upregulated. However, there are no known human genetic diseases downregulating HIF. Tibetans, though, demonstrate blunted pulmonary vascular responses to sustained hypoxia. This seems to be accounted for by an altered HIF pathway as a consequence of natural selection over a period of many thousands of years lived at high altitude. In addition to genetic differences, iron is another important modulator of HIF pathway function. Experimental work in humans demonstrates that manipulation of iron stores can influence the behaviour of the pulmonary circulation during hypoxia, in ways analogous to that seen in Tibetans and patients with rare diseases that affect oxygen sensing. The importance of physiological differences in iron bioavailability in modulating hypoxic pulmonary vasoconstriction in health and disease is yet to be established. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Cerebral fat embolism: pulmonary contusion is a more important etiology than long bone fractures.

PubMed

Aydin, M D; Akçay, F; Aydin, N; Gündogdu, C

2005-01-01

Lipid embolism is a serious and life-threatening problem and usually arises as a complication of severe trauma associated with long bone or pelvic fractures. It is generally thought that fat droplets enter the circulation at the site of fracture. In the systemic circulation, they become emboli to brain, kidney and other areas. Lipids are absorbed from the intestinal tract and transported into pulmonary tissue via thoracic duct and exposed to first catabolic procedures in the lungs. We have predicted that systemic lipid embolism may not occur unless bone fractures lead to pulmonary injury. This study was planned to investigate this hypothesis with respect to the role of pulmonary contusion and long bone fractures in the formation of cerebral fat embolism. Twenty male hybrid rabbits were included in this study. Pulmonary contusion was performed on half of the rabbits (n = 10) and femur fracture was applied to the remaining ones (n = 10). Ten days after procedure, all rabbits were sacrificed. Brain specimens were taken by frozen-section method and stained with Sudan black. Intraarteriolar lipid particles in the brain were examined microscopically. Cerebral fat embolism was detected in seven animals exposed to pulmonary contusion and only in one animal exposed to femur fracture. The mean number of branches of middle cerebral artery at midparietal level occluded with fat particles were higher in the pulmonary contusion group than in the long bone fracture group. In conclusion, we found that pulmonary contusion had more deleterious effects than long bone fracture in the formation of cerebral fat embolism.

Distinct right ventricle remodeling in response to pressure overload in the rat.

PubMed

Mendes-Ferreira, P; Santos-Ribeiro, D; Adão, R; Maia-Rocha, C; Mendes-Ferreira, M; Sousa-Mendes, C; Leite-Moreira, A F; Brás-Silva, C

2016-07-01

Pulmonary arterial hypertension (PAH), the most serious chronic disorder of the pulmonary circulation, is characterized by pulmonary vasoconstriction and remodeling, resulting in increased afterload on the right ventricle (RV). In fact, RV function is the main determinant of prognosis in PAH. The most frequently used experimental models of PAH include monocrotaline- and chronic hypoxia-induced PAH, which primarily affect the pulmonary circulation. Alternatively, pulmonary artery banding (PAB) can be performed to achieve RV overload without affecting the pulmonary vasculature, allowing researchers to determine the RV-specific effects of their drugs/interventions. In this work, using two different degrees of pulmonary artery constriction, we characterize, in full detail, PAB-induced adaptive and maladaptive remodeling of the RV at 3 wk after PAB surgery. Our results show that application of a mild constriction resulted in adaptive hypertrophy of the RV, with preserved systolic and diastolic function, while application of a severe constriction resulted in maladaptive hypertrophy, with chamber dilation and systolic and diastolic dysfunction up to the isolated cardiomyocyte level. By applying two different degrees of constriction, we describe, for the first time, a reliable and short-duration PAB model in which RV adaptation can be distinguished at 3 wk after surgery. We characterize, in full detail, structural and functional changes of the RV in its response to moderate and severe constriction, allowing researchers to better study RV physiology and transition to dysfunction and failure, as well as to determine the effects of new therapies. Copyright © 2016 the American Physiological Society.

Pulmonary vascular function and exercise capacity in black sub-Saharan Africans.

PubMed

Simaga, Bamodi; Vicenzi, Marco; Faoro, Vitalie; Caravita, Sergio; Di Marco, Giovanni; Forton, Kevin; Deboeck, Gael; Lalande, Sophie; Naeije, Robert

2015-09-01

Sex and age affect the pulmonary circulation. Whether there may be racial differences in pulmonary vascular function is unknown. Thirty white European Caucasian subjects (15 women) and age and body-size matched 30 black sub-Saharan African subjects (15 women) underwent a cardiopulmonary exercise test and exercise stress echocardiography with measurements of pulmonary artery pressure (PAP) and cardiac output (CO). A pulmonary vascular distensibility coefficient α was mathematically determined from the natural curvilinearity of multipoint mean PAP (mPAP)-CO plots. Maximum oxygen uptake (V̇o2max) and workload were higher in the whites, while maximum respiratory exchange ratio and ventilatory equivalents for CO2 were the same. Pulmonary hemodynamics were not different at rest. Exercise was associated with a higher maximum total pulmonary vascular resistance, steeper mPAP-CO relationships, and lower α-coefficients in the blacks. These differences were entirely driven by higher slopes of mPAP-CO relationships (2.5 ± 0.7 vs. 1.4 ± 0.7 mmHg·l(-1)·min; P < 0.001) and lower α-coefficients (0.85 ± 0.33 vs. 1.35 ± 0.51%/mmHg; P < 0.01) in black men compared with white men. There were no differences in any of the hemodynamic variables between black and white women. In men only, the slopes of mPAP-CO relationships were inversely correlated to V̇o2max (P < 0.01). Thus the pulmonary circulation is intrinsically less distensible in black sub-Saharan African men compared with white Caucasian Europeans men, and this is associated with a lower exercise capacity. This study did not identify racial differences in pulmonary vascular function in women. Copyright © 2015 the American Physiological Society.

Effects of body position on exercise capacity and pulmonary vascular pressure-flow relationships.

PubMed

Forton, Kevin; Motoji, Yoshiki; Deboeck, Gael; Faoro, Vitalie; Naeije, Robert

2016-11-01

There has been revival of interest in exercise testing of the pulmonary circulation for the diagnosis of pulmonary vascular disease, but there still is uncertainty about body position and the most relevant measurements. Doppler echocardiography pulmonary hemodynamic measurements were performed at progressively increased workloads in 26 healthy adult volunteers in supine, semirecumbent, and upright positions that were randomly assigned at 24-h intervals. Mean pulmonary artery pressure (mPAP) was estimated from the maximum tricuspid regurgitation jet velocity. Cardiac output was calculated from the left ventricular outflow velocity-time integral. Pulmonary vascular distensibility α-index, the percent change of vessel diameter per millimeter mercury of mPAP, was calculated from multipoint mPAP-cardiac output plots. Body position did not affect maximum oxygen uptake (Vo 2max ), maximum respiratory exchange ratio, ventilatory equivalent for carbon dioxide, or slope of mPAP-cardiac output relationships, which was on average of 1.5 ± 0.4 mmHg·l -1 ·min -1 Maximum mPAP, cardiac output, and total pulmonary vascular resistance were, respectively, 34 ± 4 mmHg, 18 ± 3 l/min, and 1.9 ± 0.3 Wood units. However, the semirecumbent position was associated with a 10% decrease in maximum workload. Furthermore, cardiac output-workload or cardiac output-Vo 2 relationships were nonlinear and variable. These results suggest that body position does not affect maximum exercise testing of the pulmonary circulation when results are expressed as mPAP-cardiac output or maximum total pulmonary vascular resistance. Maximum workload is decreased in semirecumbent compared with upright exercise. Workload or Vo 2 cannot reliably be used as surrogates for cardiac output. Copyright © 2016 the American Physiological Society.

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.

Measurement of central venous pressure and determination of hormones in blood serum during weightlessness

NASA Technical Reports Server (NTRS)

Kirsch, K.

1981-01-01

A Spacelab experiment is described which proposes to obtain data on the degree of engorgement of the cephalad circulation during weightlessness by recording central venous pressure. Of practical importance is the question of how close the astronauts are to pulmonary edema and whether the pressure falls toward normal during the time of the mission. Another experiment to investigate deviations from normal fluid and mineral metabolism, possibly initiated by the central engorgement of the low pressure system, is discussed. Hormones responsible for the control of water and mineral balance (vasopressin, catecholamines, renin, aldosterone, corticosteroids, and prostaglandin E1) will be analyzed from blood samples.

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

PubMed Central

West, John B.

2008-01-01

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

Pulmonary complications of cirrhosis.

PubMed

Singh, C; Sager, J S

2009-07-01

Advanced liver disease and portal hypertension produce various intrathoracic complications that involve the pleural space, the lung parenchyma, and the pulmonary circulation. Dyspnea and arterial hypoxemia are the most common symptoms and signs in patients with such complications. This article focuses on the diagnosis and management of hepatopulmonary syndrome, portopulmonary hypertension, and hepatic hydrothorax. All are pulmonary processes associated with end-stage liver disease that lead to significant morbidity and affect the quality of life of patients who are suffering from liver cirrhosis.

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.

Lung ventilation studies with technetium-99m Pseudogas

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

Burch, W.M.; Sullivan, P.J.; Lomas, F.E.

1986-06-01

Technetium-99m Pseudogas is an ultrafine near monodisperse aerosol of 0.12-microgram diam particle size. This report describes initial clinical experiences with 27 patients referred for investigation of suspected pulmonary embolism, and in whom Pseudogas ventilation images were compared with a high quality commercial aerosol. An additional group of ten patients with severe COPD was examined in a comparative trial of Pseudogas with 81mKr. Pseudogas was better than a conventional aerosol in reaching a diagnosis of pulmonary embolism using a simple blinded comparison with coded images. In addition, bronchial deposition was minimal unless COPD was severe. Moderately well patients had no difficultymore » inhaling the necessary activity in one or two breaths, and even severely ill and frail aged persons could accomplish the passive breathing maneuver in less than a minute. Clearance of Pseudogas was directly to the systemic circulation with a half-time of 10 min in normal subjects extending up to 100 min in patients with airways disease.« less

Pulsatile operation of a continuous-flow right ventricular assist device (RVAD) to improve vascular pulsatility

PubMed Central

Ng, Boon C.; Timms, Daniel; Cohn, William E.

2018-01-01

Despite the widespread acceptance of rotary blood pump (RBP) in clinical use over the past decades, the diminished flow pulsatility generated by a fixed speed RBP has been regarded as a potential factor that may lead to adverse events such as vasculature stiffening and hemorrhagic strokes. In this study, we investigate the feasibility of generating physiological pulse pressure in the pulmonary circulation by modulating the speed of a right ventricular assist device (RVAD) in a mock circulation loop. A rectangular pulse profile with predetermined pulse width has been implemented as the pump speed pattern with two different phase shifts (0% and 50%) with respect to the ventricular contraction. In addition, the performance of the speed modulation strategy has been assessed under different cardiovascular states, including variation in ventricular contractility and pulmonary arterial compliance. Our results indicated that the proposed pulse profile with optimised parameters (Apulse = 10000 rpm and ωmin = 3000 rpm) was able to generate pulmonary arterial pulse pressure within the physiological range (9–15 mmHg) while avoiding undesirable pump backflow under both co- and counter-pulsation modes. As compared to co-pulsation, stroke work was reduced by over 44% under counter-pulsation, suggesting that mechanical workload of the right ventricle can be efficiently mitigated through counter-pulsing the pump speed. Furthermore, our results showed that improved ventricular contractility could potentially lead to higher risk of ventricular suction and pump backflow, while stiffening of the pulmonary artery resulted in increased pulse pressure. In conclusion, the proposed speed modulation strategy produces pulsatile hemodynamics, which is more physiologic than continuous blood flow. The findings also provide valuable insight into the interaction between RVAD speed modulation and the pulmonary circulation under various cardiovascular states. PMID:29677212

Atrial natriuretic peptide ameliorates hypoxic pulmonary vasoconstriction without influencing systemic circulation.

PubMed

Höhne, C; Drzimalla, M; Krebs, M O; Boemke, W; Kaczmarczyk, G

2003-12-01

Hypoxic pulmonary vasoconstriction (HPV) is encountered during ascent to high altitude. Atrial natriuretic peptide (ANP) could be an option to treat HPV because of its natriuretic, diuretic, and vasodilatory properties. Data on effects of ANP on pulmonary and systemic circulation during HVP are conflicting, partly owing to anesthesia, surgical stress or uncontrolled dietary conditions. Therefore, ten conscious, chronically tracheotomized dogs were studied under standardized dietary conditions. The dogs were trained to breathe spontaneously at a ventilator circuit. 30min of normoxia [inspiratory oxygen fraction (F(i)O(2))=0.21] were followed by 30min of hypoxia without ANP infusion (Hypoxia I, F(i)O(2)=0.1). While maintaining hypoxia an intravenous infusion of atrial natriuretic peptide was started with 50ng x kg body wt(-1) x min(-1) for 30min (Hypoxia+ANP1=low dose), followed by 1000ng x kg body wt(-1) x min(-1) for 30min (Hypoxia+ANP2=high dose). Thereafter, ANP infusion was stopped and hypoxia maintained for a final 30min (Hypoxia II). Compared to normoxia, mean pulmonary arterial pressure (MPAP) (16+/-0.7 vs. 26+/-1.3mmHg) and pulmonary vascular resistance (PVR) (448+/-28 vs. 764+/-89dyn x s(-1) x cm(-5)) increased during Hypoxia I and decreased during Hypoxia+ANP 1 (MPAP 20+/-1mmHg, PVR 542+/-55dyn x s(-1) x cm(-5)) (P<0.05). The higher dose of ANP did not further decrease MPAP or PVR, but started to have a tendency to decrease mean arterial pressure and cardiac output. We conclude that low dose ANP is able to reduce HPV without affecting systemic circulation during acute hypoxia.

Effects of clinically relevant acute hypercapnic and metabolic acidosis on the cardiovascular system: an experimental porcine study

PubMed Central

2013-01-01

Introduction Hypercapnic acidosis (HCA) that accompanies lung-protective ventilation may be considered permissive (a tolerable side effect), or it may be therapeutic by itself. Cardiovascular effects may contribute to, or limit, the potential therapeutic impact of HCA; therefore, a complex physiological study was performed in healthy pigs to evaluate the systemic and organ-specific circulatory effects of HCA, and to compare them with those of metabolic (eucapnic) acidosis (MAC). Methods In anesthetized, mechanically ventilated and instrumented pigs, HCA was induced by increasing the inspired fraction of CO2 (n = 8) and MAC (n = 8) by the infusion of HCl, to reach an arterial plasma pH of 7.1. In the control group (n = 8), the normal plasma pH was maintained throughout the experiment. Hemodynamic parameters, including regional organ hemodynamics, blood gases, and electrocardiograms, were measured in vivo. Subsequently, isometric contractions and membrane potentials were recorded in vitro in the right ventricular trabeculae. Results HCA affected both the pulmonary (increase in mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR)) and systemic (increase in mean arterial pressure (MAP), decrease in systemic vascular resistance (SVR)) circulations. Although the renal perfusion remained unaffected by any type of acidosis, HCA increased carotid, portal, and, hence, total liver blood flow. MAC influenced the pulmonary circulation only (increase in MPAP and PVR). Both MAC and HCA reduced the stroke volume, which was compensated for by an increase in heart rate to maintain (MAC), or even increase (HCA), the cardiac output. The right ventricular stroke work per minute was increased by both MAC and HCA; however, the left ventricular stroke work was increased by HCA only. In vitro, the trabeculae from the control pigs and pigs with acidosis showed similar contraction force and action-potential duration (APD). Perfusion with an acidic solution decreased the contraction force, whereas APD was not influenced. Conclusions MAC preferentially affects the pulmonary circulation, whereas HCA affects the pulmonary, systemic, and regional circulations. The cardiac contractile function was reduced, but the cardiac output was maintained (MAC), or even increased (HCA). The increased ventricular stroke work per minute revealed an increased work demand placed by acidosis on the heart. PMID:24377654

Total Cavopulmonary Connection for Functionally Single Ventricle without Cardiopulmonary Bypass Support.

PubMed

Bangash, Sohail Khan; Pathan, Iqbal Hussain; Zaki, Saad Bader

2016-10-01

A heart with two atriums but one ventricle, an anatomy with a unique physiology, is responsible for many creative surgical and interventional approaches in history. Different surgical techniques have been used to address this strange physiology of parallel circulation. All these attempts met with failure till the concept of Fontan circulation was described. Currently, controversy exists between multistage vs. single stage total cavopulmonary connections. Total cavopulmonary connection is the only definitive procedure performed to provide palliation for patients with complex congenital heart defects which cannot support a biventricular circulation. We report a case with tricuspid atresia with transposition of great arteries and pulmonary stenosis with persistant left-sided superior vena cava and functionally single ventricle. Patient successfully underwent single stage extra-cardiac total cavopulmonary connection. In this case, bilateral Glenn with extra-cardiac inferior vena cava to main pulmonary artery shunt was performed off-pump.

Circulating endothelial and progenitor cells: Evidence from acute and long-term exercise effects

PubMed Central

Koutroumpi, Matina; Dimopoulos, Stavros; Psarra, Katherini; Kyprianou, Theodoros; Nanas, Serafim

2012-01-01

Circulating bone-marrow-derived cells, named endothelial progenitor cells (EPCs), are capable of maintaining, generating, and replacing terminally differentiated cells within their own specific tissue as a consequence of physiological cell turnover or tissue damage due to injury. Endothelium maintenance and restoration of normal endothelial cell function is guaranteed by a complex physiological procedure in which EPCs play a significant role. Decreased number of peripheral blood EPCs has been associated with endothelial dysfunction and high cardiovascular risk. In this review, we initially report current knowledge with regard to the role of EPCs in healthy subjects and the clinical value of EPCs in different disease populations such as arterial hypertension, obstructive sleep-apnea syndrome, obesity, diabetes mellitus, peripheral arterial disease, coronary artery disease, pulmonary hypertension, and heart failure. Recent studies have introduced the novel concept that physical activity, either performed as a single exercise session or performed as part of an exercise training program, results in a significant increase of circulating EPCs. In the second part of this review we provide preliminary evidence from recent studies investigating the effects of acute and long-term exercise in healthy subjects and athletes as well as in disease populations. PMID:23272272

Oxidative stress and reduced responsiveness of challenged circulating leukocytes following pulmonary instillation of metal-rich particulate matter in rats

PubMed Central

2014-01-01

Welding fume is an exposure that consists of a mixture of metal-rich particulate matter with gases (ozone, carbon monoxide) and/or vapors (VOCs). Data suggests that welders are immune compromised. Given the inability of pulmonary leukocytes to properly respond to a secondary infection in animal models, the question arose whether the dysfunction persisted systemically. Our aim was to evaluate the circulating leukocyte population in terms of cellular activation, presence of oxidative stress, and functionality after a secondary challenge, following welding fume exposure. Rats were intratracheally instilled (ITI) with PBS or 2 mg of welding fume collected from a stainless steel weld. Rats were sacrificed 4 and 24 h post-exposure and whole blood was collected. Whole blood was used for cellular differential counts, RNA isolation with subsequent microarray and Ingenuity Pathway Analysis, and secondary stimulation with LPS utilizing TruCulture technology. In addition, mononuclear cells were isolated 24 h post-exposure to measure oxidative stress by flow cytometry and confocal microscopy. Welding fume exposure had rapid effects on the circulating leukocyte population as identified by relative mRNA expression changes. Instillation of welding fume reduced inflammatory protein production of circulating leukocytes when challenged with the secondary stimulus LPS. The effects were not related to transcription, but were observed in conjunction with oxidative stress. These findings support previous studies of an inadequate pulmonary immune response following a metal-rich exposure and extend those findings showing leukocyte dysfunction occurs systemically. PMID:25123171

Oxidative stress and reduced responsiveness of challenged circulating leukocytes following pulmonary instillation of metal-rich particulate matter in rats.

PubMed

Erdely, Aaron; Antonini, James M; Young, Shih-Houng; Kashon, Michael L; Gu, Ja K; Hulderman, Tracy; Salmen, Rebecca; Meighan, Terence; Roberts, Jenny R; Zeidler-Erdely, Patti C

2014-08-15

Welding fume is an exposure that consists of a mixture of metal-rich particulate matter with gases (ozone, carbon monoxide) and/or vapors (VOCs). Data suggests that welders are immune compromised. Given the inability of pulmonary leukocytes to properly respond to a secondary infection in animal models, the question arose whether the dysfunction persisted systemically. Our aim was to evaluate the circulating leukocyte population in terms of cellular activation, presence of oxidative stress, and functionality after a secondary challenge, following welding fume exposure. Rats were intratracheally instilled (ITI) with PBS or 2 mg of welding fume collected from a stainless steel weld. Rats were sacrificed 4 and 24 h post-exposure and whole blood was collected. Whole blood was used for cellular differential counts, RNA isolation with subsequent microarray and Ingenuity Pathway Analysis, and secondary stimulation with LPS utilizing TruCulture technology. In addition, mononuclear cells were isolated 24 h post-exposure to measure oxidative stress by flow cytometry and confocal microscopy. Welding fume exposure had rapid effects on the circulating leukocyte population as identified by relative mRNA expression changes. Instillation of welding fume reduced inflammatory protein production of circulating leukocytes when challenged with the secondary stimulus LPS. The effects were not related to transcription, but were observed in conjunction with oxidative stress. These findings support previous studies of an inadequate pulmonary immune response following a metal-rich exposure and extend those findings showing leukocyte dysfunction occurs systemically.

Development of anatomophysiologic knowledge regarding the cardiovascular system: from Egyptians to Harvey.

PubMed

Bestetti, Reinaldo Bulgarelli; Restini, Carolina Baraldi A; Couto, Lucélio B

2014-12-01

Our knowledge regarding the anatomophysiology of the cardiovascular system (CVS) has progressed since the fourth millennium BC. In Egypt (3500 BC), it was believed that a set of channels are interconnected to the heart, transporting air, urine, air, blood, and the soul. One thousand years later, the heart was established as the center of the CVS by the Hippocratic Corpus in the medical school of Kos, and some of the CVS anatomical characteristics were defined. The CVS was known to transport blood via the right ventricle through veins and the pneuma via the left ventricle through arteries. Two hundred years later, in Alexandria, following the development of human anatomical dissection, Herophilus discovered that arteries were 6 times thicker than veins, and Erasistratus described the semilunar valves, emphasizing that arteries were filled with blood when ventricles were empty. Further, 200 years later, Galen demonstrated that arteries contained blood and not air. With the decline of the Roman Empire, Greco-Roman medical knowledge about the CVS was preserved in Persia, and later in Islam where, Ibn Nafis inaccurately described pulmonary circulation. The resurgence of dissection of the human body in Europe in the 14th century was associated with the revival of the knowledge pertaining to the CVS. The main findings were the description of pulmonary circulation by Servetus, the anatomical discoveries of Vesalius, the demonstration of pulmonary circulation by Colombo, and the discovery of valves in veins by Fabricius. Following these developments, Harvey described blood circulation.

Development of Anatomophysiologic Knowledge Regarding the Cardiovascular System: From Egyptians to Harvey.

PubMed

Bestetti, Reinaldo Bulgarelli; Restini, Carolina Baraldi A; Couto, Lucélio B

2014-10-10

Our knowledge regarding the anatomophysiology of the cardiovascular system (CVS) has progressed since the fourth millennium BC. In Egypt (3500 BC), it was believed that a set of channels are interconnected to the heart, transporting air, urine, air, blood, and the soul. One thousand years later, the heart was established as the center of the CVS by the Hippocratic Corpus in the medical school of Kos, and some of the CVS anatomical characteristics were defined. The CVS was known to transport blood via the right ventricle through veins and the pneuma via the left ventricle through arteries. Two hundred years later, in Alexandria, following the development of human anatomical dissection, Herophilus discovered that arteries were 6 times thicker than veins, and Erasistratus described the semilunar valves, emphasizing that arteries were filled with blood when ventricles were empty. Further, 200 years later, Galen demonstrated that arteries contained blood and not air. With the decline of the Roman Empire, Greco-Roman medical knowledge about the CVS was preserved in Persia, and later in Islam where, Ibn Nafis inaccurately described pulmonary circulation. The resurgence of dissection of the human body in Europe in the 14th century was associated with the revival of the knowledge pertaining to the CVS. The main findings were the description of pulmonary circulation by Servetus, the anatomical discoveries of Vesalius, the demonstration of pulmonary circulation by Colombo, and the discovery of valves in veins by Fabricius. Following these developments, Harvey described blood circulation.

Development of Anatomophysiologic Knowledge Regarding the Cardiovascular System: From Egyptians to Harvey

PubMed Central

Bestetti, Reinaldo Bulgarelli; Restini, Carolina Baraldi A.; Couto, Lucélio B.

2014-01-01

Our knowledge regarding the anatomophysiology of the cardiovascular system (CVS) has progressed since the fourth millennium BC. In Egypt (3500 BC), it was believed that a set of channels are interconnected to the heart, transporting air, urine, air, blood, and the soul. One thousand years later, the heart was established as the center of the CVS by the Hippocratic Corpus in the medical school of Kos, and some of the CVS anatomical characteristics were defined. The CVS was known to transport blood via the right ventricle through veins and the pneuma via the left ventricle through arteries. Two hundred years later, in Alexandria, following the development of human anatomical dissection, Herophilus discovered that arteries were 6 times thicker than veins, and Erasistratus described the semilunar valves, emphasizing that arteries were filled with blood when ventricles were empty. Further, 200 years later, Galen demonstrated that arteries contained blood and not air. With the decline of the Roman Empire, Greco-Roman medical knowledge about the CVS was preserved in Persia, and later in Islam where, Ibn Nafis inaccurately described pulmonary circulation. The resurgence of dissection of the human body in Europe in the 14th century was associated with the revival of the knowledge pertaining to the CVS. The main findings were the description of pulmonary circulation by Servetus, the anatomical discoveries of Vesalius, the demonstration of pulmonary circulation by Colombo, and the discovery of valves in veins by Fabricius. Following these developments, Harvey described blood circulation. PMID:25590934

Microglial priming through the lung–brain axis: the role of air pollution–induced circulating factors

PubMed Central

Mumaw, Christen L.; Levesque, Shannon; McGraw, Constance; Robertson, Sarah; Lucas, Selita; Stafflinger, Jillian E; Campen, Matthew J.; Hall, Pamela; Norenberg, Jeffrey P.; Anderson, Tamara; Lund, Amie K.; McDonald, Jacob D.; Ottens, Andrew K.; Block, Michelle L.

2016-01-01

Air pollution is implicated in neurodegenerative disease risk and progression and in microglial activation, but the mechanisms are unknown. In this study, microglia remained activated 24 h after ozone (O3) exposure in rats, suggesting a persistent signal from lung to brain. Ex vivo analysis of serum from O3-treated rats revealed an augmented microglial proinflammatory response and β-amyloid 42 (Aβ42) neurotoxicity independent of traditional circulating cytokines, where macrophage-1 antigen-mediated microglia proinflammatory priming. Aged mice exhibited reduced pulmonary immune profiles and the most pronounced neuroinflammation and microglial activation in response to mixed vehicle emissions. Consistent with this premise, cluster of differentiation 36 (CD36)−/− mice exhibited impaired pulmonary immune responses concurrent with augmented neuroinflammation and microglial activation in response to O3. Further, aging glia were more sensitive to the proinflammatory effects of O3 serum. Together, these findings outline the lung–brain axis, where air pollutant exposures result in circulating, cytokine-independent signals present in serum that elevate the brain proinflammatory milieu, which is linked to the pulmonary response and is further augmented with age.—Mumaw, C. L., Levesque, S., McGraw, C., Robertson, S., Lucas, S., Stafflinger, J. E., Campen, M. J., Hall, P., Norenberg, J. P., Anderson, T., Lund, A. K., McDonald, J. D., Ottens, A. K., Block, M. L. Microglial priming through the lung–brain axis: the role of air pollution–induced circulating factors. PMID:26864854

Effects of nifedipine and captopril on vascular capacitance of ganglion-blocked anesthetized dogs.

PubMed

Ogilvie, R I; Zborowska-Sluis, D

1990-03-01

The hemodynamic effects of nifedipine and captopril at doses producing similar reductions in arterial pressure were studied in pentobarbital-anesthetized ventilated dogs after splenectomy during ganglion blockade with hexamethonium. Mean circulatory filling pressure (Pmcf) was determined during transient circulatory arrest induced by acetylcholine at baseline circulating blood volumes and after increases of 5 and 10 mL/kg. Central blood volumes (pulmonary artery to aortic root) were determined from transit times, and separately determined cardiac outputs (right atrium to pulmonary artery) were estimated by thermodilution. Nifedipine (n = 5) increased Pmcf at all circulating blood volumes and reduced total vascular capacitance without a change in total vascular compliance. Central blood volume, right atrial pressure, and cardiac output were increased with induced increases in circulating blood volume. In contrast, captopril (n = 5) did not alter total vascular capacitance, central blood volume, right atrial pressure, or cardiac output at baseline or with increased circulating volume. Thus, at doses producing similar reductions in arterial pressure, nifedipine but not captopril increased venous return and cardiac output in ganglion-blocked dogs.

Bronchial circulation in the marsupial opossum, Didelphis marsupialis.

PubMed

Bernard, S L; Luchtel, D L; Glenny, R W; Lakshminarayan, S

1996-08-01

This study characterizes the existence of a bronchial circulation in a marsupial, an animal which does not undergo placental development and does not have a ductus arteriosus. Direct perfusion of the lung by the pulmonary vasculature during the fetal development of opossums may occur, potentially eliminating the need for a bronchial circulation. We used radio- and fluorescent-labeled microspheres in conjunction with postmortem intravascular casting to determine if opossums have a systemic (bronchial) blood supply to the lung (n = 9). Gross postmortem examination of the intravascular casts showed a well-developed common bronchial artery. The histological distribution pattern of fluorescent microspheres was primarily to the airways. A few fluorescent microspheres were observed in the alveolar capillaries, indicating that a precapillary bronchial-to-pulmonary anastomosis exists in the opossum. Using the reference flow technique, total bronchial blood flow to the left lung averaged 0.95 +/- 0.58 SE ml/min. The presence of a bronchial circulation in the opossum suggests that it is more than a vestigial structure from embryonic development, potentially supporting its functional importance for carrying nutrients to the airway.

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

PubMed Central

Kulik, Thomas J.

2012-01-01

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

Exercise-induced Pulmonary Hypertension

PubMed Central

Vanderpool, Rebecca; Dhakal, Bishnu P.; Saggar, Rajeev; Saggar, Rajan; Vachiery, Jean-Luc; Lewis, Gregory D.

2013-01-01

Exercise stresses the pulmonary circulation through increases in cardiac output (Q.) and left atrial pressure. Invasive as well as noninvasive studies in healthy volunteers show that the slope of mean pulmonary artery pressure (mPAP)–flow relationships ranges from 0.5 to 3 mm Hg⋅min⋅L−1. The upper limit of normal mPAP at exercise thus approximates 30 mm Hg at a Q. of less than 10 L⋅min−1 or a total pulmonary vascular resistance at exercise of less than 3 Wood units. Left atrial pressure increases at exercise with an average upstream transmission to PAP in a close to one-for-one mm Hg fashion. Multipoint PAP–flow relationships are usually described by a linear approximation, but present with a slight curvilinearity, which is explained by resistive vessel distensibility. When mPAP is expressed as a function of oxygen uptake or workload, plateau patterns may be observed in patients with systolic heart failure who cannot further increase Q. at the highest levels of exercise. Exercise has to be dynamic to avoid the increase in systemic vascular resistance and abrupt changes in intrathoracic pressure that occur with resistive exercise and can lead to unpredictable effects on the pulmonary circulation. Postexercise measurements are unreliable because of the rapid return of pulmonary vascular pressures and flows to the baseline resting state. Recent studies suggest that exercise-induced increase in PAP to a mean higher than 30 mm Hg may be associated with dyspnea-fatigue symptomatology. PMID:23348976

Missile pulmonary embolus secondary to abdominal gunshot wound.

PubMed

Mctyre, Emory; McGill, Lee; Miller, Nessa

2012-01-01

Missile pulmonary emboli are rare sequelae of traumatic entry of projectile missiles-generally bullets or bullet fragments-in which access to the systemic venous circulation is established by the missile, making it possible for the missile to migrate to the pulmonary arteries. In the case introduced here, a 24-year-old male presented to the ER with a gunshot wound to the abdomen. In the early course of his care, it was determined that he had suffered a missile pulmonary embolus secondary to a large fragment of a bullet penetrating the IVC. Despite the large perfusion defect created by this missile embolus, the patient recovered uneventfully without embolectomy.

The role of nitric oxide in regulation of the cardiovascular system in reptiles.

PubMed

Skovgaard, Nini; Galli, Gina; Abe, Augusto; Taylor, Edwin W; Wang, Tobias

2005-10-01

The roles that nitric oxide (NO) plays in the cardiovascular system of reptiles are reviewed, with particular emphasis on its effects on central vascular blood flows in the systemic and pulmonary circulations. New data is presented that describes the effects on hemodynamic variables in varanid lizards of exogenously administered NO via the nitric oxide donor sodium nitroprusside (SNP) and inhibition of nitric oxide synthase (NOS) by l-nitroarginine methyl ester (l-NAME). Furthermore, preliminary data on the effects of SNP on hemodynamic variables in the tegu lizard are presented. The findings are compared with previously published data from our laboratory on three other species of reptiles: pythons (), rattlesnakes () and turtles (). These five species of reptiles possess different combinations of division of the heart and structural complexity of the lungs. Comparison of their responses to NO donors and NOS inhibitors may reveal whether the potential contribution of NO to vascular tone correlates with pulmonary complexity and/or with blood pressure. All existing studies on reptiles have clearly established a potential role for NO in regulating vascular tone in the systemic circulation and NO may be important for maintaining basal systemic vascular tone in varanid lizards, pythons and turtles, through a continuous release of NO. In contrast, the pulmonary circulation is less responsive to NO donors or NOS inhibitors, and it was only in pythons and varanid lizards that the lungs responded to SNP. Both species have a functionally separated heart, so it is possible that NO may exert a larger role in species with low pulmonary blood pressures, irrespective of lung complexity.

On the origin of microparticles: From “platelet dust” to mediators of intercellular communication

PubMed Central

Hargett, Leslie A.; Bauer, Natalie N.

2013-01-01

Microparticles are submicron vesicles shed from a variety of cells. Peter Wolf first identified microparticles in the midst of ongoing blood coagulation research in 1967 as a product of platelets. He termed them platelet dust. Although initially thought to be useless cellular trash, decades of research focused on the tiny vesicles have defined their roles as participators in coagulation, cellular signaling, vascular injury, and homeostasis. The purpose of this review is to highlight the science leading up to the discovery of microparticles, feature discoveries made by key contributors to the field of microparticle research, and discuss their positive and negative impact on the pulmonary circulation. PMID:24015332

Atrial cardiomyoplasty in a Fontan circulation.

PubMed

Voss, Bernhard; Sack, Falk-Udo; Saggau, Werner; Hagl, Siegfried; Lange, Rüdiger

2002-05-01

The Fontan circulation is a direct connection between the systemic veins and the pulmonary artery (PA). Consequently, the pulmonary flow is passive due to the gradient between the right and left atrial pressure. In patients with increased pulmonary vascular resistance, the surgical procedure of atrio-pulmonary connection is therefore prone to failure. The goal of this experiment was to increase the pulmonary flow in an experimental model of a Fontan circulation by performing a right atrial cardiomyoplasty (ACMP). In 19 Foxhounds the left m. latissimus dorsi (LD) was mobilised and transferred as a pedicle into the chest. After sternotomy a 'Fontan circulation' was created under cardiopulmonary bypass (CPB) by connecting the right atrium (RA) with the PA by a valveless conduit. The tricuspid valve was closed with a patch. In 11 dogs (group 1) a valve was implanted in the inferior vena cava (IVC) and pulmonary inflow impedance was increased by partial occlusion of the conduit to a gradient of 10 mmHg between RA and PA. In the other eight dogs (group 2) no valve was implanted, but flowmeters were placed in the IVC and the superior vena cava (SVC). In all dogs the RA was enlarged by a fascia lata patch before the LD was wrapped over the RA and stimulated synchronously to the R-wave with burst impulses. After coming off CPB, relatively high central venous pressures (22.5+/-5.8 mmHg) were necessary to maintain haemodynamic stability. With LD-stimulation in a 1:3 mode in group 1, RA pressure (P) increased from 23.1+/-7.7 to 45+/-10.5 mmHg (P<0.001), pulmonary atrial pressure (PAP) from 15.5+/-4.3 to 25.5+/-7.6 mmHg (P<0.001) and central venous pressure increased to 33.1+/-11.3 mmHg (P<0.05). Stroke volume increase from 11.4+/-4.7 to 17.2+/-4.3 ml and peak conduit-flow from 1286.3+/-880.3 to 2329+/-1173 ml/min (all P<0.001). In a 1:1 stimulation mode a pulsatile pressure/flow profile was obtained in the PA-conduit. Furthermore, at higher frequencies of about 120 beats/min muscle relaxation was still fast enough as not to interfere with the RA filling. In group 2 caval flow without stimulation occurred mainly during diastole. However, with LD-stimulation, a strong backflow into IVC and SVC was observed resulting in a less pronounced pressure/flow increase in the PA. Our experimental model demonstrates the possibility of a 'ventricularisation' of the RA by using the force of the LD. However, the haemodynamic benefit of ACMP was achieved only, when a valve was implanted in the ICV.

Contribution of the bronchial circulation to lung preservation.

PubMed

LoCicero, J; Massad, M; Matano, J; Greene, R; Dunn, M; Michaelis, L L

1991-05-01

Short preservation time still severely limits lung transplantation. To determine the effect of bronchial arterial flush preservation, we studied 54 dogs using the isolated perfused working lung model. After baseline measurements, lungs were flushed with lactated Ringer's solution (60 ml/kg at 8 degrees C) by one of three methods: pulmonary artery perfusion, bronchial artery perfusion through a 15 cm closed aortic segment, or simultaneous pulmonary-bronchial artery perfusion. These groups were further subdivided and tested after 0, 4, and 17 hours of storage at 4 degrees C (n = 6 each). Lungs were ventilated (flow rate 140 ml/kg/min; inspired oxygen fraction 0.21) and continuously reperfused with normothermic deoxygenated autologous blood in a closed loop. Measured variables were hemodynamics, aerodynamics, and leukocytes in bronchoalveolar lavage. Survival time was determined from initial reperfusion to failure of the lung to oxygenate. After 0 and 4 hours of storage, there was no significant difference in survival times. After 17 hours, lungs subjected to pulmonary-bronchial artery perfusion survived longer than those perfused via either the pulmonary or bronchial arteries alone (120 +/- 24 versus 38 +/- 14 or 52 +/- 16 minutes; p less than 0.01). Pulmonary artery pressure and resistance in all groups except at failure were never different from baseline values in the intact animal. Shunts in the pulmonary-bronchial artery perfusion groups were closest to baseline at onset (8% +/- 4%) and remained lower throughout reperfusion than in the groups subjected to pulmonary or bronchial artery perfusion alone. After 17 hours, static compliance of pulmonary artery-perfused lungs was worse than baseline (1.1 +/- 0.2 x 10(-2) versus 3.2 +/- 0.7 x 10(-2) L/cm H2O/sec; p less than 0.05), whereas compliance in the pulmonary-bronchial artery perfusion groups remained constant (3.6 +/- 1.5 x 10(-2) L/cm H2O/sec). Elastic work performed by lungs subjected to pulmonary-bronchial artery flushing at onset was significantly lower when these lungs were reperfused immediately (201 +/- 14 versus 295 +/- 35 gm-m/min for pulmonary artery-flushed lungs) or after 4 hours of storage (229 +/- 30 versus 290 +/- 24 gm-m/min for pulmonary artery-flushed lungs). Bronchoalveolar lavage after 17 hours in the group subjected to pulmonary bronchial artery flushing demonstrated leukocyte counts similar to those of intact lungs (45 +/- 5 versus 29 +/- 8/mm3) and significantly less than in lungs subjected to pulmonary or bronchial artery flushing (137 +/- 18 or 82 +/- 10/mm3, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Distensibility and pressure-flow relationship of the pulmonary circulation. II. Multibranched model.

PubMed

Bshouty, Z; Younes, M

1990-04-01

The contribution of distensibility and recruitment to the distinctive behavior of the pulmonary circulation is not known. To examine this question we developed a multibranched model in which an arterial vascular bed bifurcates sequentially up to 8 parallel channels that converge and reunite at the venous side to end in the left atrium. Eight resistors representing the capillary bed separate the arterial and venous beds. The elastic behavior of capillaries and extra-alveolar vessels was modeled after Fung and Sobin (Circ. Res. 30: 451-490, 1972) and Smith and Mitzner (J. Appl. Physiol. 48: 450-467, 1980), respectively. Forces acting on each component are modified and calculated individually, thus enabling the user to explore the effects of parallel and longitudinal heterogeneities in applied forces (e.g., gravity, vasomotor tone). Model predictions indicate that the contribution of distensibility to nonlinearities in the pressure-flow (P-F) and atrial-pulmonary arterial pressure (Pla-Ppa) relationships is substantial, whereas gravity-related recruitment contributes very little to these relationships. In addition, Pla-Ppa relationships, obtained at a constant flow, have no discriminating ability in identifying the presence or absence of a waterfall along the circulation. The P-F relationship is routinely shifted in a parallel fashion, within the physiological flow range, whenever extra forces (e.g., lung volume, tone) are applied uniformly at one or more branching levels, regardless of whether a waterfall is created. For a given applied force, the magnitude of parallel shift varies with proportion of the circulation subjected to the added force and with Pla.

Cardiovascular dynamics during the initial period of head-down tilt

NASA Technical Reports Server (NTRS)

Tomaselli, Clare Marie; Kenney, Richard A.; Frey, Mary Anne Bassett; Hoffler, G. Wyckliffe

1987-01-01

The cardiovascular response to 1 h of 60-deg head-down tilt was studied in 12 male subjects, ages 30-39 years, to simulate the early effects of weightlessness. Fluid shifts, hemodynamic variables, and indices of myocardial contractility were evaluated by utilizing electrocardiography, systolic time intervals, impedance cardiography, sphygmomanometry, and measurement of calf circumference. Most cardiovascular variables remained stable throughout the initial 30 min of the protocol, even though translocation of fluid from the legs to the thorax commenced immediately with the onset of head-down tilt. In contrast, minutes 30-60 were characterized by reduced stroke volume, cardiac output, mean stroke ejection rate, and Heather index concomitant with an elevation in mean arterial pressure. Intrathoracic fluid volume continued to increase, while leg volume continued to decrease. This latter physiological response suggests intrathoracic sequestration of fluid volume; blood was apparently redistributed to the pulmonary circulation rather than being retained in the great veins.

Cigarette Smoke Increases Endothelial CXCL16-Leukocyte CXCR6 Adhesion In Vitro and In Vivo. Potential Consequences in Chronic Obstructive Pulmonary Disease

PubMed Central

Marques, Patrice; Collado, Aida; Escudero, Paula; Rius, Cristina; González, Cruz; Servera, Emilio; Piqueras, Laura; Sanz, Maria-Jesus

2017-01-01

Cardiovascular disease (CVD) is a major comorbidity in chronic obstructive pulmonary disease (COPD). Although the mechanism of its development remains largely unknown, it appears to be associated with cigarette consumption and reduced lung function. Therefore, the aim of this study was to investigate the potential link between water-soluble cigarette smoke extract (CSE)-induced endothelial dysfunction and the function of CXCL16/CXCR6 axis on the initial attachment of leukocytes, in addition to its possible impact on COPD-associated systemic inflammation. To do this, we employed several experimental approaches, including RNA silencing and flow cytometry analysis, the dynamic flow chamber technique, and intravital microscopy in the cremasteric arterioles of animals exposed to cigarette smoke (CS). CSE-induced arterial CXCL16 expression, leading to increased platelet–leukocyte and mononuclear cell adhesiveness. CSE-induced CXCL16 expression was dependent on Nox5 expression and subsequent RhoA/p38 MAPK/NF-κB activation. Flow cytometry analysis revealed that COPD patients (n = 35) presented greater numbers of activated circulating platelets (PAC-1+ and P-selectin+) expressing CXCL16 and CXCR6 as compared with age-matched controls (n = 17), with a higher number of CXCR6+-platelets in the smoking COPD group than in ex-smokers. This correlated with enhanced circulating CXCR6+-platelet–leukocyte aggregates in COPD patients. The increase in circulating numbers of CXCR6-expressing platelets and mononuclear cells resulted in enhanced platelet–leukocyte and leukocyte adhesiveness to CSE-stimulated arterial endothelium, which was greater than that found in age-matched controls and was partly dependent on endothelial CXCL16 upregulation. Furthermore, CS exposure provoked CXCL16-dependent leukocyte–arteriolar adhesion in cremasteric arterioles, which was significantly reduced in animals with a nonfunctional CXCR6 receptor. In conclusion, we provide the first evidence that increased numbers of CXCR6-expressing circulating platelets and mononuclear leukocytes from patients with COPD might be a marker of systemic inflammation with potential consequences in CVD development. Accordingly, CXCL16/CXCR6 axis blockade might constitute a new therapeutic approach for decreasing the risk of CVD in COPD patients. PMID:29326688

Cigarette Smoke Increases Endothelial CXCL16-Leukocyte CXCR6 Adhesion In Vitro and In Vivo. Potential Consequences in Chronic Obstructive Pulmonary Disease.

PubMed

Marques, Patrice; Collado, Aida; Escudero, Paula; Rius, Cristina; González, Cruz; Servera, Emilio; Piqueras, Laura; Sanz, Maria-Jesus

2017-01-01

Cardiovascular disease (CVD) is a major comorbidity in chronic obstructive pulmonary disease (COPD). Although the mechanism of its development remains largely unknown, it appears to be associated with cigarette consumption and reduced lung function. Therefore, the aim of this study was to investigate the potential link between water-soluble cigarette smoke extract (CSE)-induced endothelial dysfunction and the function of CXCL16/CXCR6 axis on the initial attachment of leukocytes, in addition to its possible impact on COPD-associated systemic inflammation. To do this, we employed several experimental approaches, including RNA silencing and flow cytometry analysis, the dynamic flow chamber technique, and intravital microscopy in the cremasteric arterioles of animals exposed to cigarette smoke (CS). CSE-induced arterial CXCL16 expression, leading to increased platelet-leukocyte and mononuclear cell adhesiveness. CSE-induced CXCL16 expression was dependent on Nox5 expression and subsequent RhoA/p38 MAPK/NF-κB activation. Flow cytometry analysis revealed that COPD patients ( n  = 35) presented greater numbers of activated circulating platelets (PAC-1 + and P-selectin + ) expressing CXCL16 and CXCR6 as compared with age-matched controls ( n  = 17), with a higher number of CXCR6 + -platelets in the smoking COPD group than in ex-smokers. This correlated with enhanced circulating CXCR6 + -platelet-leukocyte aggregates in COPD patients. The increase in circulating numbers of CXCR6-expressing platelets and mononuclear cells resulted in enhanced platelet-leukocyte and leukocyte adhesiveness to CSE-stimulated arterial endothelium, which was greater than that found in age-matched controls and was partly dependent on endothelial CXCL16 upregulation. Furthermore, CS exposure provoked CXCL16-dependent leukocyte-arteriolar adhesion in cremasteric arterioles, which was significantly reduced in animals with a nonfunctional CXCR6 receptor. In conclusion, we provide the first evidence that increased numbers of CXCR6-expressing circulating platelets and mononuclear leukocytes from patients with COPD might be a marker of systemic inflammation with potential consequences in CVD development. Accordingly, CXCL16/CXCR6 axis blockade might constitute a new therapeutic approach for decreasing the risk of CVD in COPD patients.

LUNG PHYSIOLOGY DURING ECS RESUSCITATION OF DCD DONORS FOLLOWED BY IN-SITU ASSESSMENT OF LUNG FUNCTION

PubMed Central

Reoma, Junewai L.; Rojas, Alvaro; Krause, Eric M.; Obeid, Nabeel R.; Lafayette, Nathan G.; Pohlmann, Joshua R.; Padiyar, Niru P.; Punch, Jeffery D; Cook, Keith E.; Bartlett, Robert H

2009-01-01

Extracorporeal cardiopulmonary support(ECS) of donors following cardiac death(DCD) has been shown to improve abdominal organs for transplantation. This study assesses whether pulmonary congestion occurs during ECS with the heart arrested and describes an in-vivo method to assess if lungs are suitable for transplantation from DCD donors following ECS resuscitation. Cardiac arrest was induced in 30 kg pigs, followed by 10min. of warm ischemia. Cannulas were placed into right atrium (RA) and iliac artery, and veno-arterial ECS was initiated for 90min with lungs inflated, Group 1 (n=5) or deflated Group 2 (n=3). Left atrial pressures were measured as a marker for pulmonary congestion. After 90 min of ECS, lung function was evaluated. Cannulae were placed into the pulmonary artery (PA) and left ventricle (LV). A second pump was included, and ECS was converted to a bi-VAD system. The RVAD drained from the RA and pumped into the PA, and the LVAD drained the LV and pumped into the iliac. This brought the lungs back into circulation for a 1hr assessment period. The oxygenator was turned off, and ventilation restarted. Flows, blood gases, pulmonary artery and left atrial pressures, and compliance were recorded. In both groups: LA pressure was <15mmHg during ECS. During the lung assessment period, PA flows were 1.4−2.2 liter/min. PO2 was >300mmHg, with normal PCO2. ECS resuscitation of DCD donors is feasible and allows for assessment of function prior to procurement. ECS does not cause pulmonary congestion, and lungs retain adequate function for transplantation. Compliance correlated with lung function. PMID:19506464

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

PubMed

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

2016-01-19

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

Hyperthyroidism and pulmonary hypertension: an important association.

PubMed

Vallabhajosula, Sailaja; Radhi, Saba; Cevik, Cihan; Alalawi, Raed; Raj, Rishi; Nugent, Kenneth

2011-12-01

Pulmonary hypertension is a complex disorder with multiple etiologies. The World Health Organization Group 5 (unclear multifactorial mechanisms) includes patients with thyroid disorders. The authors reviewed the literature on the association between hyperthyroidism and pulmonary hypertension and identified 20 publications reporting 164 patients with treatment outcomes. The systolic pulmonary artery (PA) pressures in these patients ranged from 28 to 78 mm Hg. They were treated with antithyroid medications, radioactive iodine and surgery. The mean pretherapy PA systolic pressure was 39 mm Hg; the mean posttreatment pressure was 30 mm Hg. Pulmonary hypertension should be considered in hyperthyroid patients with dyspnea. All patients with pulmonary hypertension should be screened for hyperthyroidism, because the treatment of hyperthyroidism can reduce PA pressures, potentially avoid the side-effects and costs with current therapies for pulmonary hypertension and limit the consequences of untreated hyperthyroidism. However, the long-term outcome in these patients is uncertain, and this issue needs more study. Changes in the pulmonary circulation and molecular regulators of vascular remodeling likely explain this association.

Sickle erythrocytes and platelets augment lung leukotriene synthesis with downregulation of anti-inflammatory proteins: relevance in the pathology of the acute chest syndrome

PubMed Central

Opene, Michael; Kurantsin-Mills, Joseph; Husain, Sumair

2014-01-01

Abstract Initiation, progression, and resolution of vaso-occlusive pain episodes in sickle cell disease (SCD) have been recognized as reperfusion injury, which provokes an inflammatory response in the pulmonary circulation. Some 5-lipoxygenase (5-lox) metabolites are potent vasoconstrictors in the pulmonary circulation. We studied stimulation of production of the inflammatory eicosanoids leukotrienes (LTs) and prostaglandin E2 (PGE2) by isolated rat lungs perfused with sickle (HbSS) erythrocytes. Our hypothesis is that HbSS erythrocytes produce more LTs than normal (HbAA) erythrocytes, which can induce vaso-occlusive episodes in SCD patients. Lung perfusates were collected at specific time points and purified by high-pressure liquid chromatography, and LTC4 and PGE2 contents were measured by enzyme-linked immunosorbent assay (ELISA). Rat lung explants were also cultured with purified HbAA and HbSS peptides, and 5-lox, cyclooxygenase 1/2, and platelet-activating factor receptor (PAFR) proteins were measured by Western blotting, while prostacyclin and LTs produced by cultured lung explants were measured by ELISA. Lung weight gain and blood gas data were not different among the groups. HbSS-perfused lungs produced more LTC4 and PGE2 than HbAA-perfused lungs: 10.40 ± 0.62 versus 0.92 ± 0.2 ng/g dry lung weight (mean ± SEM; P = 0.0001) for LTC4. Inclusion of autologous platelets (platelet-rich plasma) elevated LTC4 production to 12.6 ± 0.96 and 7 ± 0.60 ng/g dry lung weight in HbSS and HbAA perfusates, respectively. HbSS lungs also expressed more 5-lox and PAFR. The data suggest that HbSS erythrocytes and activated platelets in patient’s pulmonary microcirculation will enhance the synthesis and release of the proinflammatory mediators LTC4 and PGE2, both of which may contribute to onset of the acute chest syndrome in SCD. PMID:25621162

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 compliance in both large and small arteries. Results showed, that the effects of decreased compliance in the large arteries far outweigh the effects observed when decreasing the compliance of the small arteries. We further showed that a decrease of compliance in the large arteries results in pressure increases consistent with observations of isolated systolic hypertension, as occurs in ageing. PMID:22962497

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

Modeling bronchial circulation with application to soluble gas exchange: description and sensitivity analysis.

PubMed

Bui, T D; Dabdub, D; George, S C

1998-06-01

The steady-state exchange of inert gases across an in situ canine trachea has recently been shown to be limited equally by diffusion and perfusion over a wide range (0.01-350) of blood solubilities (betablood; ml . ml-1 . atm-1). Hence, we hypothesize that the exchange of ethanol (betablood = 1,756 at 37 degrees C) in the airways depends on the blood flow rate from the bronchial circulation. To test this hypothesis, the dynamics of the bronchial circulation were incorporated into an existing model that describes the simultaneous exchange of heat, water, and a soluble gas in the airways. A detailed sensitivity analysis of key model parameters was performed by using the method of Latin hypercube sampling. The model accurately predicted a previously reported experimental exhalation profile of ethanol (R2 = 0.991) as well as the end-exhalation airstream temperature (34.6 degrees C). The model predicts that 27, 29, and 44% of exhaled ethanol in a single exhalation are derived from the tissues of the mucosa and submucosa, the bronchial circulation, and the tissue exterior to the submucosa (which would include the pulmonary circulation), respectively. Although the concentration of ethanol in the bronchial capillary decreased during inspiration, the three key model outputs (end-exhaled ethanol concentration, the slope of phase III, and end-exhaled temperature) were all statistically insensitive (P > 0.05) to the parameters describing the bronchial circulation. In contrast, the model outputs were all sensitive (P < 0.05) to the thickness of tissue separating the core body conditions from the bronchial smooth muscle. We conclude that both the bronchial circulation and the pulmonary circulation impact soluble gas exchange when the entire conducting airway tree is considered.

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.

'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/.

Increased levels of circulating nitrates and impaired endothelium-mediated vasodilation suggest multiple roles of nitric oxide during acute rejection of pulmonary allografts.

PubMed

Wiklund, L; Lewis, D H; Sjöquist, P O; Nilsson, F; Tazelaar, H; Miller, V M; McGregor, C G

1997-05-01

Experiments were designed to determine whether changes in pulmonary artery function could be reduced by treatment with a lipid peroxidation inhibitor (H 290/51) during acute rejection of pulmonary allografts. Single lung transplantation was performed in three groups of dogs: group 1 was maintained on immunosuppression for 8 days after operation (immunosuppressed, n = 5); in group 2, immunosuppression was discontinued on postoperative day 5, so that rejection occurred on postoperative day 8 (rejecting, n = 6); in group 3, immunosuppression was discontinued after 5 days, and the lipid peroxidation inhibitor H 290/51 (25 mg/kg) was given perorally for 3 days (rejecting + H 290/51, n = 6). Plasma nitric oxide (NO(x)) was measured by use of chemoluminescence. On postoperative day 8 rejection was observed in groups 2 and 3. Contractions to angiotensin I and endothelium-dependent relaxations to adenosine diphosphate were reduced in pulmonary arteries from rejecting lungs. Responses of rings from dogs treated with H 290/51 were similar to those from rejecting lungs. Rejection did not alter relaxations to exogenous nitric oxide. However, plasma levels of NO(x) increased significantly during rejection independently of treatment with H 290/51. Results of this study confirm that endothelium-dependent relaxation of pulmonary arteries is reduced during acute rejection of lung allografts. The result extends these observations to suggest that treatment with a lipid peroxidation inhibitor neither protects the pulmonary artery function nor affects levels of circulating NO(x). Therefore mechanisms other than lipid peroxidation participate in vascular changes associated with allograft rejection.

Omentin protects against LPS-induced ARDS through suppressing pulmonary inflammation and promoting endothelial barrier via an Akt/eNOS-dependent mechanism.

PubMed

Qi, Di; Tang, Xumao; He, Jing; Wang, Daoxin; Zhao, Yan; Deng, Wang; Deng, Xinyu; Zhou, Guoqi; Xia, Jing; Zhong, Xi; Pu, Shenglan

2016-09-08

Acute respiratory distress syndrome (ARDS) is characterized by increased pulmonary inflammation and endothelial barrier permeability. Omentin has been shown to benefit obesity-related systemic vascular diseases; however, its effects on ARDS are unknown. In the present study, the level of circulating omentin in patients with ARDS was assessed to appraise its clinical significance in ARDS. Mice were subjected to systemic administration of adenoviral vector expressing omentin (Ad-omentin) and one-shot treatment of recombinant human omentin (rh-omentin) to examine omentin's effects on lipopolysaccharide (LPS)-induced ARDS. Pulmonary endothelial cells (ECs) were treated with rh-omentin to further investigate its underlying mechanism. We found that a decreased level of circulating omentin negatively correlated with white blood cells and procalcitonin in patients with ARDS. Ad-omentin protected against LPS-induced ARDS by alleviating the pulmonary inflammatory response and endothelial barrier injury in mice, accompanied by Akt/eNOS pathway activation. Treatment of pulmonary ECs with rh-omentin attenuated inflammatory response and restored adherens junctions (AJs), and cytoskeleton organization promoted endothelial barrier after LPS insult. Moreover, the omentin-mediated enhancement of EC survival and differentiation was blocked by the Akt/eNOS pathway inactivation. Therapeutic rh-omentin treatment also effectively protected against LPS-induced ARDS via the Akt/eNOS pathway. Collectively, these data indicated that omentin protects against LPS-induced ARDS by suppressing inflammation and promoting the pulmonary endothelial barrier, at least partially, through an Akt/eNOS-dependent mechanism. Therapeutic strategies aiming to restore omentin levels may be valuable for the prevention or treatment of ARDS.

[Pulmonary thromboembolism. Therapy recommendations of the practice guidelines of the Mexican Society of Cardiology].

PubMed

Jerjes-Sánchez, Carlos; Ramírez-Rivera, Alicia

2007-01-01

Prevalence and incidence of pulmonary thromboembolism (PTE) is very high, and in many cases, remains undiagnosed. In developed countries, it's the third cause of cardiovascular mortality, a fact that is also observed in developing countries. Within the clinical spectrum, PTE is regarded as minor and massive, in between a sub-massive PET, which is characterized by normal arterial pressure, or even hypotension, with compensated systemic perfusion and right ventricle dysfunction (RVD), with presence or not or positive biomarkers. When there is no evidence of severe pulmonary hypertension, or RVD, anticoagulation therapy stands as the pharmacological approach. When RVD is observed, pulmonary reperfusion is advised. According to the guidelines and recommendations for stratification, diagnose, and treatment of PTE, from the Pulmonary Circulation Chapter of the Mexican Society of Cardiology, evidence is established between physiopathology and the degree of vascular pulmonary obstruction.

Systemic inflammation in chronic obstructive pulmonary disease and lung cancer: common driver of pulmonary cachexia?

PubMed

Ceelen, Judith J M; Langen, Ramon C J; Schols, Annemie M W J

2014-12-01

In this article, a putative role of systemic inflammation as a driver of pulmonary cachexia induced by either chronic obstructive pulmonary disease or nonsmall cell lung cancer is reviewed. Gaps in current translational research approaches are discussed and alternative strategies are proposed to provide new insights. Activation of the ubiquitin proteasome system has generally been considered a cause of pulmonary cachexia, but current animal models lack specificity and evidence is lacking in nonsmall cell lung cancer and conflicting in chronic obstructive pulmonary disease patients. Recent studies have shown activation of the autophagy-lysosome pathway in both nonsmall cell lung cancer and chronic obstructive pulmonary disease. Myonuclear loss, as a consequence of increased apoptotic events in myofibers, has been suggested in cancer-cachexia-associated muscle atrophy. Plasma transfer on myotube cultures can be used to detect early inflammatory signals in patients and presence of atrophy-inducing activity within the circulation. Comparative clinical research between nonsmall cell lung cancer and chronic obstructive pulmonary disease in different disease stages is useful to unravel disease-specific versus common denominators of pulmonary cachexia.

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

PubMed

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

2017-03-07

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

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.

Duroquinone reduction during passage through the pulmonary circulation.

PubMed

Audi, Said H; Bongard, Robert D; Dawson, Christopher A; Siegel, David; Roerig, David L; Merker, Marilyn P

2003-11-01

The lungs can substantially influence the redox status of redox-active plasma constituents. Our objective was to examine aspects of the kinetics and mechanisms that determine pulmonary disposition of redox-active compounds during passage through the pulmonary circulation. Experiments were carried out on rat and mouse lungs with 2,3,5,6-tetramethyl-1,4-benzoquinone [duroquinone (DQ)] as a model amphipathic quinone reductase substrate. We measured DQ and durohydroquinone (DQH2) concentrations in the lung venous effluent after injecting, or while infusing, DQ or DQH2 into the pulmonary arterial inflow. The maximum net rates of DQ reduction to DQH2 in the rat and mouse lungs were approximately 4.9 and 2.5 micromol. min(-1).g dry lung wt(-1), respectively. The net rate was apparently the result of freely permeating access of DQ and DQH2 to tissue sites of redox reactions, dominated by dicumarol-sensitive DQ reduction to DQH2 and cyanide-sensitive DQH2 reoxidation back to DQ. The dicumarol sensitivity along with immunodetectable expression of NAD(P)H-quinone oxidoreductase 1 (NQO1) in the rat lung tissue suggest cytoplasmic NQO1 as the dominant site of DQ reduction. The effect of cyanide on DQH2 oxidation suggests that the dominant site of oxidation is complex III of the mitochondrial electron transport chain. If one envisions DQ as a model compound for examining the disposition of amphipathic NQO1 substrates in the lungs, the results are consistent with a role for lung NQO1 in determining the redox status of such compounds in the circulation. For DQ, the effect is conversion of a redox-cycling, oxygen-activating quinone into a stable hydroquinone.

C1q Deficiency Promotes Pulmonary Vascular Inflammation and Enhances the Susceptibility of the Lung Endothelium to Injury.

PubMed

Shah, Dilip; Romero, Freddy; Zhu, Ying; Duong, Michelle; Sun, Jianxin; Walsh, Kenneth; Summer, Ross

2015-12-04

The collectin proteins are innate immune molecules found in high concentrations on the epithelial and endothelial surfaces of the lung. While these proteins are known to have important anti-inflammatory actions in the airways of the lung little is known of their functional importance in the pulmonary circulation. We recently demonstrated that the circulating collectin protein adiponectin has potent anti-inflammatory effects on the lung endothelium, leading us to reason that other structurally related proteins might have similar effects. To test this hypothesis, we investigated the anti-inflammatory actions of C1q in lung endothelial homeostasis and the pulmonary vascular response to LPS or HCl injury. We show that lung endothelium from C1q-deficient (C1q(-/-)) mice expresses higher baseline levels of the vascular adhesion markers ICAM-1, VCAM-1, and E-selectin when compared with wild-type mice. Further, we demonstrate that these changes are associated with enhanced susceptibility of the lung to injury as evident by increased expression of adhesion markers, enhanced production of pro-inflammatory cytokines, and augmented neutrophil recruitment. Additionally, we found that C1q(-/-) mice also exhibited enhanced endothelial barrier dysfunction after injury as manifested by decreased expression of junctional adherens proteins and enhanced vascular leakage. Mechanistically, C1q appears to mediate its effects by inhibiting phosphorylation of p38 mitogen-activated protein kinase (MAPK) and blocking nuclear translocation of the P65 subunit of nuclear factor (NF)-κB. In summary, our findings indicate a previously unrecognized role for C1q in pulmonary vascular homeostasis and provide added support for the hypothesis that circulating collectin proteins have protective effects on the lung endothelium. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

C1q Deficiency Promotes Pulmonary Vascular Inflammation and Enhances the Susceptibility of the Lung Endothelium to Injury*

PubMed Central

Shah, Dilip; Romero, Freddy; Zhu, Ying; Duong, Michelle; Sun, Jianxin; Walsh, Kenneth; Summer, Ross

2015-01-01

The collectin proteins are innate immune molecules found in high concentrations on the epithelial and endothelial surfaces of the lung. While these proteins are known to have important anti-inflammatory actions in the airways of the lung little is known of their functional importance in the pulmonary circulation. We recently demonstrated that the circulating collectin protein adiponectin has potent anti-inflammatory effects on the lung endothelium, leading us to reason that other structurally related proteins might have similar effects. To test this hypothesis, we investigated the anti-inflammatory actions of C1q in lung endothelial homeostasis and the pulmonary vascular response to LPS or HCl injury. We show that lung endothelium from C1q-deficient (C1q−/−) mice expresses higher baseline levels of the vascular adhesion markers ICAM-1, VCAM-1, and E-selectin when compared with wild-type mice. Further, we demonstrate that these changes are associated with enhanced susceptibility of the lung to injury as evident by increased expression of adhesion markers, enhanced production of pro-inflammatory cytokines, and augmented neutrophil recruitment. Additionally, we found that C1q−/− mice also exhibited enhanced endothelial barrier dysfunction after injury as manifested by decreased expression of junctional adherens proteins and enhanced vascular leakage. Mechanistically, C1q appears to mediate its effects by inhibiting phosphorylation of p38 mitogen-activated protein kinase (MAPK) and blocking nuclear translocation of the P65 subunit of nuclear factor (NF)-κB. In summary, our findings indicate a previously unrecognized role for C1q in pulmonary vascular homeostasis and provide added support for the hypothesis that circulating collectin proteins have protective effects on the lung endothelium. PMID:26487714

Elevated Plasma CXCL12α Is Associated with a Poorer Prognosis in Pulmonary Arterial Hypertension

PubMed Central

Li, Lili; O’Connell, Caroline; Codd, Mary; Lawrie, Allan; Morton, Allison; Kiely, David G.; Condliffe, Robin; Elliot, Charles; McLoughlin, Paul; Gaine, Sean

2015-01-01

Rationale Recent work in preclinical models suggests that signalling via the pro-angiogenic and pro-inflammatory cytokine, CXCL12 (SDF-1), plays an important pathogenic role in pulmonary hypertension (PH). The objective of this study was to establish whether circulating concentrations of CXCL12α were elevated in patients with PAH and related to mortality. Methods Plasma samples were collected from patients with idiopathic pulmonary arterial hypertension (IPAH) and PAH associated with connective tissue diseases (CTD-PAH) attending two pulmonary hypertension referral centres (n = 95) and from age and gender matched healthy controls (n = 44). Patients were subsequently monitored throughout a period of five years. Results CXCL12α concentrations were elevated in PAH groups compared to controls (P<0.05) and receiver-operating-characteristic analysis showed that plasma CXCL12α concentrations discriminated patients from healthy controls (AUC 0.80, 95% confidence interval 0.73-0.88). Kaplan Meier analysis indicated that elevated plasma CXCL12α concentration was associated with reduced survival (P<0.01). Multivariate Cox proportional hazards model showed that elevated CXCL12α independently predicted (P<0.05) earlier death in PAH with a hazard ratio (95% confidence interval) of 2.25 (1.01-5.00). In the largest subset by WHO functional class (Class 3, 65% of patients) elevated CXCL12α independently predicted (P<0.05) earlier death, hazard ratio 2.27 (1.05-4.89). Conclusions Our data show that elevated concentrations of circulating CXCL12α in PAH predicted poorer survival. Furthermore, elevated circulating CXCL12α was an independent risk factor for death that could potentially be included in a prognostic model and guide therapy. PMID:25856504

Elevated plasma CXCL12α is associated with a poorer prognosis in pulmonary arterial hypertension.

PubMed

McCullagh, Brian N; Costello, Christine M; Li, Lili; O'Connell, Caroline; Codd, Mary; Lawrie, Allan; Morton, Allison; Kiely, David G; Condliffe, Robin; Elliot, Charles; McLoughlin, Paul; Gaine, Sean

2015-01-01

Recent work in preclinical models suggests that signalling via the pro-angiogenic and pro-inflammatory cytokine, CXCL12 (SDF-1), plays an important pathogenic role in pulmonary hypertension (PH). The objective of this study was to establish whether circulating concentrations of CXCL12α were elevated in patients with PAH and related to mortality. Plasma samples were collected from patients with idiopathic pulmonary arterial hypertension (IPAH) and PAH associated with connective tissue diseases (CTD-PAH) attending two pulmonary hypertension referral centres (n = 95) and from age and gender matched healthy controls (n = 44). Patients were subsequently monitored throughout a period of five years. CXCL12α concentrations were elevated in PAH groups compared to controls (P<0.05) and receiver-operating-characteristic analysis showed that plasma CXCL12α concentrations discriminated patients from healthy controls (AUC 0.80, 95% confidence interval 0.73-0.88). Kaplan Meier analysis indicated that elevated plasma CXCL12α concentration was associated with reduced survival (P<0.01). Multivariate Cox proportional hazards model showed that elevated CXCL12α independently predicted (P<0.05) earlier death in PAH with a hazard ratio (95% confidence interval) of 2.25 (1.01-5.00). In the largest subset by WHO functional class (Class 3, 65% of patients) elevated CXCL12α independently predicted (P<0.05) earlier death, hazard ratio 2.27 (1.05-4.89). Our data show that elevated concentrations of circulating CXCL12α in PAH predicted poorer survival. Furthermore, elevated circulating CXCL12α was an independent risk factor for death that could potentially be included in a prognostic model and guide therapy.

Circulating RNA transcripts identify therapeutic response in cystic fibrosis lung disease.

PubMed

Saavedra, Milene T; Hughes, Grant J; Sanders, Linda A; Carr, Michelle; Rodman, David M; Coldren, Christopher D; Geraci, Mark W; Sagel, Scott D; Accurso, Frank J; West, James; Nick, Jerry A

2008-11-01

Circulating leukocyte RNA transcripts are systemic markers of inflammation, which have not been studied in cystic fibrosis (CF) lung disease. Although the standard assessment of pulmonary treatment response is FEV(1), a measure of airflow limitation, the lack of systemic markers to reflect changes in lung inflammation critically limits the testing of proposed therapeutics. We sought to prospectively identify and validate peripheral blood leukocyte genes that could mark resolution of pulmonary infection and inflammation using a model by which RNA transcripts could increase the predictive value of spirometry. Peripheral blood mononuclear cells were isolated from 10 patients with CF and acute pulmonary exacerbations before and after therapy. RNA expression profiling revealed that 10 genes significantly changed with treatment when compared with matched non-CF and control subjects with stable CF to establish baseline transcript abundance. Peripheral blood mononuclear cell RNA transcripts were prospectively validated, using real-time polymerase chain reaction amplification, in an independent cohort of acutely ill patients with CF (n = 14). Patients who responded to therapy were analyzed using general estimating equations and multiple logistic regression, such that changes in FEV(1)% predicted were regressed with transcript changes. Three genes, CD64, ADAM9, and CD36, were significant and independent predictors of a therapeutic response beyond that of FEV(1) alone (P < 0.05). In both cohorts, receiver operating characteristic analysis revealed greater accuracy when genes were combined with FEV(1). Circulating mononuclear cell transcripts characterize a response to the treatment of pulmonary exacerbations. Even in small patient cohorts, changes in gene expression in conjunction with FEV(1) may enhance current outcomes measures for treatment response.

Air Pollution Exposure with Fine Dust. Responses in the Pulmonary Vasculature and the Right Heart.

PubMed

Durmus, Nedim; Grunig, Gabriele

2018-04-01

Detrimental effects of air pollution with fine dust (particulate matter ≤2.5 μm in aerodynamic diameter, or PM 2.5 ) on the systemic circulation and the left heart have been studied intensely during the past decade. In comparison, knowledge regarding the effects of exposure to air pollution with PM 2.5 on the pulmonary vasculature and the right heart lags far behind. A report on severe lung disease and right heart failure in coal miners was published nearly 170 years ago. However, today, we still do not have a clear picture of how the effect of air pollution on the pulmonary circulation or the right heart should be viewed from a clinical, mechanistic biological, therapeutic, or economic angle. In the laboratory, we have established a model of immune response-induced vascular remodeling that is significantly worsened by adding PM 2.5 to the intranasal antigen challenge solution. Importantly, the PM 2.5 is given at a concentration that by itself does not induce significant inflammation or pulmonary vascular remodeling. However, when added to antigen, this low-dose PM 2.5 exposure induces severe pulmonary vascular remodeling, significantly increased right ventricular pressures, and significant molecular changes in the right heart. Our data also show that these PM 2.5 -exaggerated responses are dependent on interleukin-13, interleukin-17A, and antigen-specific antibody. The experimental model is being used to address a few questions: 1. Which mechanism protects the animals from severe right ventricular failure despite the severity of the pulmonary artery remodeling? 2. What is the mechanism by which PM 2.5 worsens the response to antigen? 3. How does PM 2.5 exert its effects across the small airways to the small blood vessels? In conclusion, further investigation is urgently needed to understand the effects of exposure to ambient or occupational air pollution on the pulmonary vasculature, because better knowledge could lead to immediate beneficial actions for patients with pulmonary hypertension and persons at risk.

Crotalaria-induced pulmonary hypertension. Uptake of 3H-thymidine by the cells of the pulmonary circulation and alveolar walls.

PubMed Central

Meyrick, B. O.; Reid, L. M.

1982-01-01

Feeding with Crotalaria spectabilis seeds induces structural changes in the pulmonary arterial circulation characteristic of pulmonary hypertension: increased medial and adventitial thickness, the appearance of muscle in smaller arteries than normal, and reduction in the number of peripheral arteries. By autoradiographic techniques, after injection of 3H-thymidine into rats fed Crotalaria for 3, 7, 14, 21, 28, or 35 days, the contribution of hyperplasia to these changes has been assessed at two levels of the pulmonary artery--the hilum and the periphery. In the hilar pulmonary artery, a biphasic increase in labeling index (LI) is seen in each cell type. After 3 days of feeding, the medial smooth muscle cells show a slight but significant increase (1.5 times the control value), and, after 7 days, so do the adventitial fibroblasts (3 x) and the endothelial cells (EC) (2 x). After 14 days LI for all three cell types is again at control values, but after 21 days (wall thickness is no increased) each cell type shows at least a fivefold increase; by 35 days all are again near control levels. In the intra-acinar region, by 14 days, "newly" muscularized arteries are identified and increase in number and proportion up to 35 days; 3H-thymidine uptake is not evident in this cell type until 35 days have passed. The ECs of these arteries, however, show a striking increase in LI after 14 days as do those of the alveolar capillaries. The ECs of the intra-acinar veins show a biphasic response being increased after 7, 28, and 35 days. The present study has shown that Crotalaria ingestion induces hyperplasia and hypertrophy of pulmonary arterial cells at pre- and intra-acinar levels. The early increase in LI probably represents a response to the original cell injury, the later changes, a response to continuing damage or, in part, adaptation to the pulmonary hypertension now present. Images Figure 3 Figure 7 PMID:7055214

Intravenous sildenafil in right ventricular dysfunction with pulmonary hypertension following a heart transplant.

PubMed

Bonet, Luis Almenar; Guillén, Rosario Vicente; Lázaro, Ignacio Sánchez; de la Fuente, Carmen; Osseyran, Faisa; Dolz, Luis Martínez; Hernández, Mónica Montero; Sanz, Manuel Portolés; Otero, Miguel Rivera; Sanz, Antonio Salvador

2014-01-01

The objective of the present work is to describe the experience with intravenous (IV) sildenafil in heart transplant (HT) patients with reactive pulmonary hypertension (PH) who developed right ventricular dysfunction (RVD) in the immediate postoperative period. The first 5 patients who received IV sildenafil followinga HT are presented. The HTs took place between March 2011 and September 2012 in patients aged 37 to 64 years; all patients were male. Prior to the HT, mean pulmonary artery pressure (mPAP) was 32-56 mmHg. In all cases, the hemodynamic study demonstrated PH reactivity (positive vasodilator test with nitric oxide). All 5 patients developed RVD with hemodynamic instability immediately after the HT, despite the administration of nitric oxide from the time of intubation prior to the implant, optimal medical treatment in all cases, and a ventricular assist in 2 cases. In all patients, IV sildenafil was initiated at 10 mg/8 h for 48 h and was subsequently increased to 20 mg/8 h. in its oral formulation until discharge from the hospital. The change in pulmonary pressure was assessed using a Swan-Ganz catheter. Ventricular function was assessed using echocardiography. Length of stay in the Resuscitation Unit and mid-term survival were also assessed. Average time of extracorporeal circulation was 200 ± 110 min and organ ischemic time was 210 ± 95 min. All of the patients demonstrated pulmonary and systemic hemodynamic improvement, as well as recovery of right ventricular function after completing the treatment with IV sildenafil. The stay in the Resuscitation Unit lasted 3-25 days. All the patients were discharged from hospital with no mortality to date. Intravenous sildenafil improves right ventricle hemodynamics associated with pulmonary hypertension post-HT. Prophylactic prevention with this drug could be indicated for patients with reactive PH who are about to receive a transplant.

Redox Signaling and Persistent Pulmonary Hypertension of the Newborn.

PubMed

Sharma, Megha; Afolayan, Adeleye J

2017-01-01

Reactive oxygen species (ROS) are redox-signaling molecules that are critically involved in regulating endothelial cell functions, host defense, aging, and cellular adaptation. Mitochondria are the major sources of ROS and important sources of redox signaling in pulmonary circulation. It is becoming increasingly evident that increased mitochondrial oxidative stress and aberrant signaling through redox-sensitive pathways play a direct causative role in the pathogenesis of many cardiopulmonary disorders including persistent pulmonary hypertension of the newborn (PPHN). This chapter highlights redox signaling in endothelial cells, antioxidant defense mechanism, cell responses to oxidative stress, and their contributions to disease pathogenesis.

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

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.

Respiratory exacerbation in a young adult with cystic fibrosis and tricuspid atresia.

PubMed

Wood, Jamie; Sawyer, Abbey; Mulrennan, Siobhain; Bullock, Andrew

2018-07-01

Tricuspid atresia (TAt) is a complex congenital heart defect (CHD) characterized by the absence of the tricuspid valve and right ventricular hypoplasia requiring surgery in childhood, the Fontan procedure. We present a case of a 21-year-old male with TAt and cystic fibrosis (CF), who underwent a Fontan procedure in childhood, presenting to an adult CF clinic with severe deterioration in his respiratory status and multi-organ dysfunction associated with CF. This report describes problems associated with the management of a CF respiratory exacerbation and extrapulmonary manifestations of CF in the unique situation of a Fontan circulation, a circulation with absence of a subpulmonary ventricle and pulsatile pulmonary arterial blood flow where maintenance of systemic cardiac output is totally dependent on good respiratory function and low pulmonary artery pressures.

Effects of an Antioxidant-enriched Multivitamin in Cystic Fibrosis: Randomized, Controlled, Multicenter Trial.

PubMed

Sagel, Scott D; Khan, Umer; Jain, Raksha; Graff, Gavin; Daines, Cori L; Dunitz, Jordan M; Borowitz, Drucy; Orenstein, David M; Abdulhamid, Ibrahim; Noe, Julie; Clancy, John P; Slovis, Bonnie; Rock, Michael J; McCoy, Karen S; Strausbaugh, Steven; Livingston, Floyd R; Papas, Konstantinos A; Shaffer, Michele L

2018-04-24

Cystic fibrosis (CF) is characterized by dietary antioxidant deficiencies, which may contribute to an oxidant-antioxidant imbalance and oxidative stress. Evaluate the effects of an oral antioxidant-enriched multivitamin supplement on antioxidant concentrations, markers of inflammation and oxidative stress, and clinical outcomes. In this investigator-initiated, multicenter, randomized, double-blind, controlled trial, 73 pancreatic insufficient CF subjects 10 years of age and older with an FEV1 between 40-100% predicted were randomized to 16 weeks of an antioxidant-enriched multivitamin or control multivitamin without antioxidant enrichment. Endpoints included systemic antioxidant concentrations, markers of inflammation and oxidative stress, clinical outcomes (pulmonary exacerbations, anthropometric measures, pulmonary function), safety and tolerability. Change in sputum myeloperoxidase concentration over 16 weeks, the primary efficacy endpoint, was not significantly different between the treated and control groups. Systemic antioxidant concentrations (β-carotene, CoQ10, γ-tocopherol, lutein) significantly increased in the antioxidant treated group (p<0.001 for each), while circulating calprotectin and myeloperoxidase decreased in the treated group compared to the control group at week 4. The treated group had a lower risk of first pulmonary exacerbation requiring antibiotics than the control group (adjusted hazard ratio=0.50, p=0.04). Lung function and growth endpoints did not differ between groups. Adverse events and tolerability were similar between groups. Antioxidant supplementation was safe and well tolerated, resulting in increased systemic antioxidant concentrations and modest reductions in systemic inflammation after 4 weeks. Antioxidant treatment was also associated with a lower risk of first pulmonary exacerbation. Clinical trial registration available at www.clinicaltrials.gov, ID NCT01859390.

Massive Ischemic Stroke Due to Pulmonary Barotrauma and Cerebral Artery Air Embolism During Commercial Air Travel

PubMed Central

Zarabi, Sara Farshchi; Parotto, Matteo; Katznelson, Rita; Downar, James

2017-01-01

Patient: Male, 65 Final Diagnosis: Air emboli Symptoms: Short of breath Medication: — Clinical Procedure: — Specialty: Anesthesiology Objective: Unusual setting of medical care Background: Air embolism into the systemic arterial circulation secondary to pulmonary barotrauma has rarely been reported. Herein, we report the clinical course of an extremely rare presentation of cerebral air embolism likely due to ruptured pulmonary bullae during commercial air travel. Case Report: A 65-year-old man suddenly became unconscious during an airplane descent. Upon landing, he was immediately transferred to the nearest emergency department where he was intubated for airway protection. His head CT angiogram showed multiple air pockets in the right parietal lobe suspicious for multiple air emboli. His chest CT scan showed multiple large bullae in the left upper and lower lobes as well as diffusely emphysematous lung tissue. After initial stabilization, he underwent emergent hyperbaric oxygen treatment (HBOT) in the multiplace chamber at 2.8 atmospheres. The patient tolerated HBOT well with no complications. However, his neurologic status deteriorated in the following 24 hours due to progression of his cerebral edema and mass effects. The patient’s clinical status was discussed with his family and the decision was made to withdraw life-sustaining measures. He died shortly after withdrawal of life support. Post-mortem examination confirmed the presence of very large bullae in the lungs bilaterally. Conclusions: Spontaneous cerebral air embolism is a possible complication of ruptured pulmonary bullae during air travel. HBOT is well-tolerated and may be used with caution even in the presence of emphysematous bullae. PMID:28607332

Pulmonary Embolism as the Initial Presentation of Testicular Carcinoma

PubMed Central

Berber, Ilhami; Erkurt, Mehmet Ali; Ulutas, Ozkan; Ediz, Caner; Nizam, Ilknur; Kırıcı Berber, Nurcan; Unlu, Serkan; Koroglu, Reyhan; Koroglu, Mustafa; Akpolat, Nusret

2013-01-01

Objective. The risk of pulmonary embolism is well recognized as showing an increase in oncological patients. We report a case presenting with pulmonary embolism initially, which was then diagnosed with testicular cancer. Clinical Presentation and Intervention. A 25-year-old man was admitted to the emergency department with a complaint of dyspnoea. Thoracic tomography, lung ventilation/perfusion scintigraphy, and an increased D-dimer level revealed pulmonary embolism. For the aetiology of pulmonary embolism, a left orchiectomy was performed and the patient was diagnosed with a germinal cell tumour of the testicle. Conclusion. In this paper, we present a patient for whom pulmonary embolism was the initial presentation, and a germinal cell tumour was diagnosed later during the search for the aetiology. PMID:24383024

Effect of Vandetanib on Andes virus survival in the hamster model of Hantavirus pulmonary syndrome.

PubMed

Bird, Brian H; Shrivastava-Ranjan, Punya; Dodd, Kimberly A; Erickson, Bobbie R; Spiropoulou, Christina F

2016-08-01

Hantavirus pulmonary syndrome (HPS) is a severe disease caused by hantavirus infection of pulmonary microvascular endothelial cells leading to microvascular leakage, pulmonary edema, pleural effusion and high case fatality. Previously, we demonstrated that Andes virus (ANDV) infection caused up-regulation of vascular endothelial growth factor (VEGF) and concomitant downregulation of the cellular adhesion molecule VE-cadherin leading to increased permeability. Analyses of human HPS-patient sera have further demonstrated increased circulating levels of VEGF. Here we investigate the impact of a small molecule antagonist of the VEGF receptor 2 (VEGFR-2) activation in vitro, and overall impact on survival in the Syrian hamster model of HPS. Copyright © 2016. Published by Elsevier B.V.

PD-1/PD-L1 Pathway Mediates the Alleviation of Pulmonary Fibrosis by Human Mesenchymal Stem Cells in Humanized Mice.

PubMed

Ni, Ke; Liu, Ming; Zheng, Jian; Wen, Liyan; Chen, Qingyun; Xiang, Zheng; Lam, Kowk-Tai; Liu, Yinping; Chan, Godfrey Chi-Fung; Lau, Yu-Lung; Tu, Wenwei

2018-06-01

Pulmonary fibrosis is a chronic progressive lung disease with few treatments. Human mesenchymal stem cells (MSCs) have been shown to be beneficial in pulmonary fibrosis because they have immunomodulatory capacity. However, there is no reliable model to test the therapeutic effect of human MSCs in vivo. To mimic pulmonary fibrosis in humans, we established a novel bleomycin-induced pulmonary fibrosis model in humanized mice. With this model, the benefit of human MSCs in pulmonary fibrosis and the underlying mechanisms were investigated. In addition, the relevant parameters in patients with pulmonary fibrosis were examined. We demonstrate that human CD8 + T cells were critical for the induction of pulmonary fibrosis in humanized mice. Human MSCs could alleviate pulmonary fibrosis and improve lung function by suppressing bleomycin-induced human T-cell infiltration and proinflammatory cytokine production in the lungs of humanized mice. Importantly, alleviation of pulmonary fibrosis by human MSCs was mediated by the PD-1/programmed death-ligand 1 pathway. Moreover, abnormal PD-1 expression was found in circulating T cells and lung tissues of patients with pulmonary fibrosis. Our study supports the potential benefit of targeting the PD-1/programmed death-ligand 1 pathway in the treatment of pulmonary fibrosis.

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

PubMed Central

2013-01-01

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

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

PubMed

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

2013-02-28

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

Customized Internal Reference Controls for Improved Assessment of Circulating MicroRNAs in Disease.

PubMed

Schlosser, Kenny; McIntyre, Lauralyn A; White, R James; Stewart, Duncan J

2015-01-01

Altered levels of circulating extracellular miRNA in plasma and serum have shown promise as non-invasive biomarkers of disease. However, unlike the assessment of cellular miRNA levels for which there are accepted housekeeping genes, analogous reference controls for normalization of circulating miRNA are lacking. Here, we provide an approach to identify and validate circulating miRNA reference controls on a de novo basis, and demonstrate the advantages of these customized internal controls in different disease settings. Importantly, these internal controls overcome key limitations of external spike-in controls. Using a global RT-qPCR screen of 1066 miRNAs in plasma from pulmonary hypertension patients (PAH) and healthy subjects as a case example, we identified a large pool of initial candidate miRNAs that were systematically ranked according to their plasma level stability using a predefined algorithm. The performance of the top candidates was validated against multiple comparators, and in a second independent cohort of PAH and control subjects. The broader utility of this approach was demonstrated in a completely different disease setting with 372 miRNAs screened in plasma from septic shock patients and healthy controls. Normalization of data with specific internal reference controls significantly reduced the overall variation in circulating miRNA levels between subjects (relative to raw data), provided a more balanced distribution of up- and down-regulated miRNAs, replicated the results obtained by the benchmark geometric averaging of all detected miRNAs, and outperformed the commonly used external spike-in strategy. We demonstrate the feasibility of identifying circulating reference controls that can reduce extraneous technical variations, and improve the assessment of disease-related changes in plasma miRNA levels. This study provides a novel conceptual framework that addresses a critical and previously unmet need if circulating miRNAs are to advance as reliable diagnostic tools in medicine.

Customized Internal Reference Controls for Improved Assessment of Circulating MicroRNAs in Disease

PubMed Central

Schlosser, Kenny; McIntyre, Lauralyn A.; White, R. James; Stewart, Duncan J.

2015-01-01

Background Altered levels of circulating extracellular miRNA in plasma and serum have shown promise as non-invasive biomarkers of disease. However, unlike the assessment of cellular miRNA levels for which there are accepted housekeeping genes, analogous reference controls for normalization of circulating miRNA are lacking. Here, we provide an approach to identify and validate circulating miRNA reference controls on a de novo basis, and demonstrate the advantages of these customized internal controls in different disease settings. Importantly, these internal controls overcome key limitations of external spike-in controls. Methods Using a global RT-qPCR screen of 1066 miRNAs in plasma from pulmonary hypertension patients (PAH) and healthy subjects as a case example, we identified a large pool of initial candidate miRNAs that were systematically ranked according to their plasma level stability using a predefined algorithm. The performance of the top candidates was validated against multiple comparators, and in a second independent cohort of PAH and control subjects. The broader utility of this approach was demonstrated in a completely different disease setting with 372 miRNAs screened in plasma from septic shock patients and healthy controls. Results Normalization of data with specific internal reference controls significantly reduced the overall variation in circulating miRNA levels between subjects (relative to raw data), provided a more balanced distribution of up- and down-regulated miRNAs, replicated the results obtained by the benchmark geometric averaging of all detected miRNAs, and outperformed the commonly used external spike-in strategy. Conclusions We demonstrate the feasibility of identifying circulating reference controls that can reduce extraneous technical variations, and improve the assessment of disease-related changes in plasma miRNA levels. This study provides a novel conceptual framework that addresses a critical and previously unmet need if circulating miRNAs are to advance as reliable diagnostic tools in medicine. PMID:26010841

USSR Report, Space Biology and Aerospace Medicine, Vol. 18, No. 5, September-October 1984

DTIC Science & Technology

1984-11-20

Exchange and Pulmonary Circulation in Man 34 Regional Circulation During Testing on Isokinetic Dynamometer Following 14-Day Bedrest 39 Primate...Indicator of Animal Adaptation to Altitude Hypoxia . 71 Distinctions of Rat Lymphatic Organ Reactions to Acute Stress Factor During Hypokinesia...14, 40, 51].^ Experimental validation of the energy principle of noise effects made it possible to turn to estimation of its equivalent level. The

Rescue pulmonary vein isolation for hemodynamically unstable atrial fibrillation storm in a patient with an acute extensive myocardial infarction.

PubMed

Morishima, Itsuro; Sone, Takahito; Tsuboi, Hideyuki; Mukawa, Hiroaki

2012-11-26

New-onset atrial fibrillation in patients hospitalized for an acute myocardial infarction often leads to hemodynamic deterioration and has serious adverse prognostic implications; mortality is particularly high in patients with congestive heart failure and/or a reduced left ventricular ejection fraction. The mechanism of atrial fibrillation in the context of an acute myocardial infarction has not been well characterized and an effective treatment other than optimal medical therapy and mechanical hemodynamic support are expected. A 71 year-old male with an acute myocardial infarction due to an occlusion of the left main coronary artery was treated with percutaneous coronary intervention. He had developed severe congestive heart failure with a left ventricular ejection fraction of 34%. The systemic circulation was maintained with an intraaortic balloon pump, continuous hemodiafiltration, and mechanical ventilation until atrial fibrillation occurred on day 3 which immediately led to cardiogenic shock. Because atrial fibrillation was refractory to intravenous amiodarone, beta-blockers, and a total of 15 electrical cardioversions, the patient underwent emergent radiofrequency catheter ablation on day 4. Soon after electrical cardioversion, ectopies from the right superior pulmonary vein triggered the initiation of atrial fibrillation. The right pulmonary veins were isolated during atrial fibrillation. Again, atrial fibrillation was electrically cardioverted, then, sinus rhythm was restored. Subsequently, the left pulmonary veins were isolated. The stabilization of the hemodynamics was successfully achieved with an increase in the blood pressure and urine volume. Hemodiafiltration and amiodarone were discontinued. The patient had been free from atrial fibrillation recurrence until he suddenly died due to ventricular fibrillation on day 9. To the best of our knowledge, this is the first report of pulmonary vein isolation for a rescue purpose applied in a patient with hemodymically unstable atrial fibrillation complicated with an acute myocardial infarction. This case demonstrates that ectopic activity in the pulmonary veins may be responsible for triggering atrial fibrillation in the critical setting of an acute myocardial infarction and thus pulmonary vein isolation could be an effective therapeutic option.

Endothelial and Smooth Muscle Cell Ion Channels in Pulmonary Vasoconstriction and Vascular Remodeling

PubMed Central

Makino, Ayako; Firth, Amy L.; Yuan, Jason X.-J.

2017-01-01

The pulmonary circulation is a low resistance and low pressure system. Sustained pulmonary vasoconstriction and excessive vascular remodeling often occur under pathophysiological conditions such as in patients with pulmonary hypertension. Pulmonary vasoconstriction is a consequence of smooth muscle contraction. Many factors released from the endothelium contribute to regulating pulmonary vascular tone, while the extracellular matrix in the adventitia is the major determinant of vascular wall compliance. Pulmonary vascular remodeling is characterized by adventitial and medial hypertrophy due to fibroblast and smooth muscle cell proliferation, neointimal proliferation, intimal, and plexiform lesions that obliterate the lumen, muscularization of precapillary arterioles, and in situ thrombosis. A rise in cytosolic free Ca2+ concentration ([Ca2+]cyt) in pulmonary artery smooth muscle cells (PASMC) is a major trigger for pulmonary vasoconstriction, while increased release of mitogenic factors, upregulation (or downregulation) of ion channels and transporters, and abnormalities in intracellular signaling cascades are key to the remodeling of the pulmonary vasculature. Changes in the expression, function, and regulation of ion channels in PASMC and pulmonary arterial endothelial cells play an important role in the regulation of vascular tone and development of vascular remodeling. This article will focus on describing the ion channels and transporters that are involved in the regulation of pulmonary vascular function and structure and illustrating the potential pathogenic role of ion channels and transporters in the development of pulmonary vascular disease. PMID:23733654

Novel putative pharmacological therapies to protect the right ventricle in pulmonary hypertension: a review of current literature

PubMed Central

Schulz, Rainer; Sliwa, Karen; Schermuly, Ralph Theo; Lecour, Sandrine

2017-01-01

Pulmonary hypertension (PH) is defined by elevated mean pulmonary artery pressure following the pathological remodelling of small pulmonary arteries. An increase in right ventricular (RV) afterload results in RV hypertrophy and RV failure. The pathophysiology of PH, and RV remodelling in particular, is not well understood, thus explaining, at least in part, why current PH therapies have a limited effect. Existing therapies mostly target the pulmonary circulation. Because the remodelled RV fails to support normal cardiac function, patients eventually succumb from RV failure. Developing novel therapies that directly target the function of the RV may therefore benefit patients with PH. In the past decade, several promising studies have investigated novel cardioprotective strategies in experimental models of PH. This review aims to comprehensively discuss and highlight these novel experimental approaches to confer, in the long‐term, greater health benefit in patients with PH. PMID:28099680

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 patient-specific data. A preliminary study investigating the relationship between outlet diameter and flow distribution in the pulmonary tree offers a potential computationally inexpensive alternative to pressure based outflow boundary conditions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Pulmonary Toxocariasis: Initial and Follow-Up CT Findings in 63 Patients.

PubMed

Lee, Kyung Hee; Kim, Tae Jung; Lee, Kyung Won

2015-06-01

The objective of our study was to describe the characteristic radiologic findings of pulmonary toxocariasis on initial and follow-up chest CT. Between June 2010 and May 2014, 63 patients with serologically proven, clinically diagnosed pulmonary toxocariasis and chest CT examinations performed within 2 months of an enzyme-linked immunosorbent assay for toxocariasis were identified. Two chest radiologists retrospectively analyzed the chest CT examinations in consensus; they focused on the distribution, location, number, and internal characteristics of the pulmonary lesions. The pulmonary lesions tended to involve three or more lobes (49% [31/63]) on the initial CT; predominance of the abnormalities in a subpleural location (81% [51/63]) and in the lower lung zone (98% [62/63]) was noted. The number of pulmonary lesions per patient were from two to five (46% [29/63]), more than five (32% [20/63]), or one (22% [14/63]). The radiologic findings of pulmonary toxocariasis could be categorized into four different patterns: ground-glass opacities (GGOs), solid nodules, consolidations, and linear opacities. The most common pattern was ill-defined GGOs with or without solid portions (84% [53/63]). The solid nodule and patchy consolidation patterns were found in 29% (18/63) and 21% (13/63) of patients, respectively. In addition, linear opacities (1-2 mm thick and 8-25 mm long) were present in 19% of patients (12/63); this finding is a subtle, yet novel, finding. On follow-up CT, the pulmonary lesions had either disappeared or migrated; when they had migrated, they revealed radiologic manifestations similar to the findings on the initial CT. Pulmonary toxocariasis manifested as multiple lesions in four radiologic patterns with subpleural and lower lung predominance on initial and follow-up CT. A linear opacity may be one of many clues in the diagnosis of pulmonary toxocariasis on CT.

Redox Regulation of the Superoxide Dismutases SOD3 and SOD2 in the Pulmonary Circulation.

PubMed

Hernandez-Saavedra, Daniel; Swain, Kalin; Tuder, Rubin; Petersen, Steen V; Nozik-Grayck, Eva

2017-01-01

When evaluating the role of redox-regulating signaling in pulmonary vascular diseases, it is intriguing to consider the modulation of key antioxidant enzymes like superoxide dismutase (SOD) because SOD isoforms are regulated by redox reactions, and, in turn, modulate downstream redox sensitive processes. The emerging field of redox biology is built upon understanding the regulation and consequences of tightly controlled and specific reduction-oxidation reactions that are critical for diverse cellular processes including cell signaling. Of relevance, both the site of production of specific reactive oxygen and nitrogen species and the site of the antioxidant defenses are highly compartmentalized within the cell. For example, superoxide is generated during oxidative phosphorylation in the mitochondria as well as by a number of enzymatic sources within the cytosol and at the cell membrane. In the pulmonary circulation, these sources include the mitochondrial electron transport chain, NADPH oxidases (NOX1-4, Duox1,2), nitric oxide synthases, and xanthine oxidase; this important topic has been thoroughly reviewed recently [1]. In parallel with these different cellular sites of superoxide production, the three SOD isoforms are also specifically localized to the cytosol (SOD1), mitochondria (SOD2) or extracellular compartment (SOD3). This chapter focuses on the role of redox mechanisms regulating SOD2 and SOD3, with an emphasis on these processes in the setting of pulmonary hypertension.

The clinical value of circulating tumour cells (CTCs) in patients undergoing pulmonary metastasectomy for metastatic colorectal cancer.

PubMed

Hashimoto, Masaki; Tanaka, Fumihiro; Yoneda, Kazue; Takuwa, Teruhisa; Kuroda, Ayumi; Matsumoto, Seiji; Okumura, Yoshitomo; Kondo, Nobuyuki; Tsujimura, Tohru; Nakano, Takashi; Hasegawa, Seiki

2018-03-01

Circulating tumour cells (CTCs) are a potential surrogate for distant metastasis and are considered a useful clinical prognostic marker for metastatic colorectal cancer (mCRC). This prospective study evaluated the preoperative CTC count as a prognostic factor for pulmonary metastasectomy in mCRC patients. Seventy-nine mCRC patients who underwent curative-intent pulmonary metastasectomy were included. Preoperatively, 7.5 mL of peripheral blood from each patient was quantitatively evaluated for CTCs with the CellSearch ® system. The clinical significance of CTC count was evaluated according to Kaplan-Meier analyses and log-rank test. Multivariate analyses of the perioperative variables were performed. The distribution of CTC counts were as follows; 0 in 66 patients (83.5%), 1 in eight patients (10.1%), 2 in three patients (3.8%), and 3 and 6 in one patient (1.3%). The patients with multiple CTCs (CTC count ≥2) had significant shorter disease-free survival (DFS) (P=0.005, median DFS; 19.8 vs . 8.6 months) and overall survival (OS) (P=0.035, median DFS; not reached vs. 37.8 months), respectively. Multivariate analysis showed the patients with multiple CTCs had elevated risk of recurrence [hazard ratio (HR), 3.28; 95% confidence interval (CI), 1.24-8.67; P=0.017]. The detected rate of CTCs was quite low in mCRC patients who underwent pulmonary metastasectomy. The patient with multiple CTCs had shorter DFS in this study. The larger prospective clinical study is needed to establish the meaning of CTC in mCRC candidate for pulmonary metastasectomy.

Obesity-related pulmonary arterial hypertension in rats correlates with increased circulating inflammatory cytokines and lipids and with oxidant damage in the arterial wall but not with hypoxia

PubMed Central

Irwin, David C.; Garat, Chrystelle V.; Crossno, Joseph T.; MacLean, Paul S.; Sullivan, Timothy M.; Erickson, Paul F.; Jackman, Matthew R.; Harral, Julie W.; Reusch, Jane E. B.

2014-01-01

Abstract Obesity is causally linked to a number of comorbidities, including cardiovascular disease, diabetes, renal dysfunction, and cancer. Obesity has also been linked to pulmonary disorders, including pulmonary arterial hypertension (PAH). It was long believed that obesity-related PAH was the result of hypoventilation and hypoxia due to the increased mechanical load of excess body fat. However, in recent years it has been proposed that the metabolic and inflammatory disturbances of obesity may also play a role in the development of PAH. To determine whether PAH develops in obese rats in the absence of hypoxia, we assessed pulmonary hemodynamics and pulmonary artery (PA) structure in the diet-resistant/diet-induced obesity (DR/DIO) and Zucker lean/fatty rat models. We found that high-fat feeding (DR/DIO) or overfeeding (Zucker) elicited PA remodeling, neomuscularization of distal arterioles, and elevated PA pressure, accompanied by right ventricular (RV) hypertrophy. PA thickening and distal neomuscularization were also observed in DIO rats on a low-fat diet. No evidence of hypoventilation or chronic hypoxia was detected in either model, nor was there a correlation between blood glucose or insulin levels and PAH. However, circulating inflammatory cytokine levels were increased with high-fat feeding or calorie overload, and hyperlipidemia and oxidant damage in the PA wall correlated with PAH in the DR/DIO model. We conclude that hyperlipidemia and peripheral inflammation correlate with the development of PAH in obese subjects. Obesity-related inflammation may predispose to PAH even in the absence of hypoxia. PMID:25610600

Role of splenic reservoir monocytes in pulmonary vascular monocyte accumulation in experimental hepatopulmonary syndrome

PubMed Central

Wu, Wei; Zhang, Junlan; Yang, Wenli; Hu, Bingqian

2016-01-01

Abstract Background and Aim Pulmonary monocyte infiltration plays a significant role in the development of angiogenesis in experimental hepatopulmonary syndrome (HPS) after common bile duct ligation (CBDL). Hepatic monocytes are also increased after CBDL, but the origins remain unclear. Splenic reservoir monocytes have been identified as a major source of monocytes that accumulate in injured tissues. Whether splenic monocytes contribute to monocyte alterations after CBDL is unknown. This study evaluates monocyte distributions and assesses effects of splenectomy on monocyte levels and pulmonary vascular and hepatic abnormalities in experimental HPS. Methods Splenectomy was performed in CBDL animals. Monocyte levels in different tissues and circulation were assessed with CD68. Pulmonary alterations of HPS were evaluated with vascular endothelial growth factor‐A (VEGF‐A) levels, angiogenesis, and alveolar–arterial oxygen gradient (AaPO2). Liver abnormalities were evaluated with fibrosis (Sirius red), bile duct proliferation (CK‐19), and enzymatic changes. Results Monocyte levels increased in the lung and liver after CBDL and were accompanied by elevated circulating monocyte numbers. Splenectomy significantly decreased monocyte accumulation, VEGF‐A levels, and angiogenesis in CBDL animal lung and improved AaPO2 levels. In contrast, hepatic monocyte levels, fibrosis, and functional abnormalities were further exacerbated by spleen removal. Conclusions Splenic reservoir monocytes are a major source for lung monocyte accumulation after CBDL, and spleen removal attenuates the development of experimental HPS. Liver monocytes may have different origins, and accumulation is exacerbated after depletion of splenic reservoir monocytes. Tissue specific monocyte alterations, influenced by the spleen reservoir, have a significant impact on pulmonary complications of liver disease. PMID:27029414

Early Detection of Junctional Adhesion Molecule-1 (JAM-1) in the Circulation after Experimental and Clinical Polytrauma

PubMed Central

Denk, Stephanie; Wiegner, Rebecca; Hönes, Felix M.; Messerer, David A. C.; Radermacher, Peter; Kalbitz, Miriam; Braumüller, Sonja; McCook, Oscar; Gebhard, Florian; Weckbach, Sebastian; Huber-Lang, Markus

2015-01-01

Severe tissue trauma-induced systemic inflammation is often accompanied by evident or occult blood-organ barrier dysfunctions, frequently leading to multiple organ dysfunction. However, it is unknown whether specific barrier molecules are shed into the circulation early after trauma as potential indicators of an initial barrier dysfunction. The release of the barrier molecule junctional adhesion molecule-1 (JAM-1) was investigated in plasma of C57BL/6 mice 2 h after experimental mono- and polytrauma as well as in polytrauma patients (ISS ≥ 18) during a 10-day period. Correlation analyses were performed to indicate a linkage between JAM-1 plasma concentrations and organ failure. JAM-1 was systemically detected after experimental trauma in mice with blunt chest trauma as a driving force. Accordingly, JAM-1 was reduced in lung tissue after pulmonary contusion and JAM-1 plasma levels significantly correlated with increased protein levels in the bronchoalveolar lavage as a sign for alveolocapillary barrier dysfunction. Furthermore, JAM-1 was markedly released into the plasma of polytrauma patients as early as 4 h after the trauma insult and significantly correlated with severity of disease and organ dysfunction (APACHE II and SOFA score). The data support an early injury- and time-dependent appearance of the barrier molecule JAM-1 in the circulation indicative of a commencing trauma-induced barrier dysfunction. PMID:26556956

Lung physiology during ECS resuscitation of DCD donors followed by in situ assessment of lung function.

PubMed

Reoma, Junewai L; Rojas, Alvaro; Krause, Eric M; Obeid, Nabeel R; Lafayette, Nathan G; Pohlmann, Joshua R; Padiyar, Niru P; Punch, Jeffery D; Cook, Keith E; Bartlett, Robert H

2009-01-01

Extracorporeal cardiopulmonary support (ECS) of donors after cardiac death (DCD) has been shown to improve abdominal organs for transplantation. This study assesses whether pulmonary congestion occurs during ECS with the heart arrested and describes an in vivo method to assess if lungs are suitable for transplantation from DCD donors after ECS resuscitation. Cardiac arrest was induced in 30 kg pigs, followed by 10 min of warm ischemia. Cannulae were placed into the right atrium (RA) and iliac artery, and veno-arterial ECS was initiated for 90 min with lungs inflated, group 1 (n = 5) or deflated, group 2 (n = 3). Left atrial pressures were measured as a marker for pulmonary congestion. After 90 min of ECS, lung function was evaluated. Cannulae were placed into the pulmonary artery (PA) and left ventricle (LV). A second pump was included, and ECS was converted to a bi-ventricular (bi-VAD) system. The RVAD drained from the RA and pumped into the PA, and the LVAD drained the LV and pumped into the iliac. This brought the lungs back into circulation for a 1-hr assessment period. The oxygenator was turned off, and ventilation was restarted. Flows, blood gases, PA and left atrial pressures, and compliance were recorded. In both the groups, LA pressure was <15 mm Hg during ECS. During the lung assessment period, PA flows were 1.4-2.2 L/min. PO2 was >300 mm Hg, with normal PCO2. Extracorporeal cardiopulmonary support resuscitation of DCD donors is feasible and allows for assessment of function before procurement. Extracorporeal cardiopulmonary support does not cause pulmonary congestion, and the lungs retain adequate function for transplantation. Compliance correlated with lung function.

A model to simulate the haemodynamic effects of right heart pulsatile flow after modified Fontan procedure.

PubMed

Tamaki, S; Kawazoe, K; Yagihara, T; Abe, T

1992-02-01

The effect of pulsatile pulmonary flow after the modified Fontan procedure was examined in a model that simulated the right heart. An inlet overflow tank (preload), axial pulsatile pump, Wind-Kessel model (afterload), and an outlet overflow tank were connected in series. The standard conditions were flow 2.00 l/min with 12 mm Hg preload pressure, 3.0 Wood units resistance, and an outlet overflow tank pressure at 6 mm Hg. The pump rate was set at 80 beats/min. The simulated pulmonary arterial pressure and pulmonary flow waves produced by this model closely resembled those obtained from patients who had undergone the modified Fontan procedure. All variables except the preload were fixed and changes in pulmonary flow were examined at preload pressures of 8, 12, 15, and 17 mm Hg. As the peak pulmonary arterial pressure increased so did pulmonary flow, until it was greater than during the non-pulsatile state. Because the afterload of this model was fixed, this result suggests that there was a concomitant decrease in resistance. This model indicates that pulsatile pulmonary blood flow is likely to have a beneficial effect on the pulmonary circulation after the modified Fontan procedure.

Determination of fluid extraction and osmotic conductance sigma K in the lung with hypertonic NaCl infusion. I. Theory.

PubMed

Hunter, M; Lee, J

1992-11-01

A dispersion and extraction model of the lung is developed to assess how the infusion of hypertonic saline into the pulmonary artery changes the gravimetric density of pulmonary venous blood. The dispersion analysis is built on the indicator dilution curve measured for the pulmonary circulation. The extraction model consists of microvascular and interstitial compartments separated by a permeable pulmonary endothelium. Because the density of fluid extracted by the hypertonic disturbance is lower than the blood density, the extraction leads to a decrease in blood density. Two cases of fluid extraction are analyzed, a hypertonic infusion to elevate the osmotic pressure in the pulmonary arterial blood in the form of a step function and an infusion performed over a period of 1 sec. Both cases show that the dispersion significantly attenuates the changes in osmotic pressure and density as they are transported by the blood along the pulmonary vasculature. Because the model has taken into account the effect of dispersion and pulmonary blood flow, the equations developed here provide the basis to calculate from the density change in pulmonary venous blood the characteristics of osmotic extraction intrinsic to the lung.

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

PubMed Central

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

2017-01-01

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

Permanent Cortical Blindness After Bronchial Artery Embolization

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

Doorn, Colette S. van, E-mail: cvandoorn@gmail.com; De Boo, Diederick W., E-mail: d.w.deboo@amc.uva.nl; Weersink, Els J. M., E-mail: e.j.m.weersink@amc.uva.nl

2013-12-15

A 35-year-old female with a known medical history of cystic fibrosis was admitted to our institution for massive hemoptysis. CTA depicted a hypertrophied bronchial artery to the right upper lobe and showed signs of recent bleeding at that location. Bronchial artery embolization (BAE) was performed with gelfoam slurry, because pronounced shunting to the pulmonary artery was present. Immediately after BAE, the patient developed bilateral cortical blindness. Control angiography showed an initially not opacified anastomosis between the embolized bronchial artery and the right subclavian artery, near to the origin of the right vertebral artery. Cessation of outflow in the bronchial circulationmore » reversed the flow through the anastomosis and allowed for spill of embolization material into the posterior circulation. Unfortunately the cortical blindness presented was permanent.« less

Ischaemic Strokes in Patients with Pulmonary Arteriovenous Malformations and Hereditary Hemorrhagic Telangiectasia: Associations with Iron Deficiency and Platelets

PubMed Central

Shovlin, Claire L.; Chamali, Basel; Santhirapala, Vatshalan; Livesey, John A.; Angus, Gillian; Manning, Richard; Laffan, Michael A.; Meek, John; Tighe, Hannah C.; Jackson, James E.

2014-01-01

Background Pulmonary first pass filtration of particles marginally exceeding ∼7 µm (the size of a red blood cell) is used routinely in diagnostics, and allows cellular aggregates forming or entering the circulation in the preceding cardiac cycle to lodge safely in pulmonary capillaries/arterioles. Pulmonary arteriovenous malformations compromise capillary bed filtration, and are commonly associated with ischaemic stroke. Cohorts with CT-scan evident malformations associated with the highest contrast echocardiographic shunt grades are known to be at higher stroke risk. Our goal was to identify within this broad grouping, which patients were at higher risk of stroke. Methodology 497 consecutive patients with CT-proven pulmonary arteriovenous malformations due to hereditary haemorrhagic telangiectasia were studied. Relationships with radiologically-confirmed clinical ischaemic stroke were examined using logistic regression, receiver operating characteristic analyses, and platelet studies. Principal Findings Sixty-one individuals (12.3%) had acute, non-iatrogenic ischaemic clinical strokes at a median age of 52 (IQR 41–63) years. In crude and age-adjusted logistic regression, stroke risk was associated not with venous thromboemboli or conventional neurovascular risk factors, but with low serum iron (adjusted odds ratio 0.96 [95% confidence intervals 0.92, 1.00]), and more weakly with low oxygen saturations reflecting a larger right-to-left shunt (adjusted OR 0.96 [0.92, 1.01]). For the same pulmonary arteriovenous malformations, the stroke risk would approximately double with serum iron 6 µmol/L compared to mid-normal range (7–27 µmol/L). Platelet studies confirmed overlooked data that iron deficiency is associated with exuberant platelet aggregation to serotonin (5HT), correcting following iron treatment. By MANOVA, adjusting for participant and 5HT, iron or ferritin explained 14% of the variance in log-transformed aggregation-rate (p = 0.039/p = 0.021). Significance These data suggest that patients with compromised pulmonary capillary filtration due to pulmonary arteriovenous malformations are at increased risk of ischaemic stroke if they are iron deficient, and that mechanisms are likely to include enhanced aggregation of circulating platelets. PMID:24586400

Impulse activity in afferent vagal C-fibres with endings in the intrapulmonary airways of dogs.

PubMed

Coleridge, H M; Coleridge, J C

1977-04-01

We recorded impulses from afferent vagal C-fibres (conduction velocities 0.8-2.4 m/sec) arising from endings in the lungs of anesthetized dogs with open chest. Endings were of two types ('pulmonary' and 'bronchial') distinguished by their response and accessibility to capsaicin and phenyl diguanide injected into the right or left atrium. 'Pulmonary' endings, stimulated only by capsaicin and accessible through the pulmonary circulation, have been described previously. 'Bronchial' endings were stimulated by both capsicin and phenyl diguanide and were accessible through the bronchial circulation. Eight of 28 'bronchial' endings were located in large airways within 4 cm of the hilum, and two were in small airways near the edge of the lung. The precise location of the remaining 'bronchial' endings was not determined but we think that many were in the airways. 'Bronchial' endings had a sparse and irregular spontaneous discharge. They were stimulated by the inhalation of 5% histamine aerosol, the evoked discharge having no obvious relation to the phase of ventilation. A few were weakly stimulated by hyperinflating the lungs; deflation was without effect. The function of these endings is unknown.

Role of ROS signaling in differential hypoxic Ca2+ and contractile responses in pulmonary and systemic vascular smooth muscle cells.

PubMed

Wang, Yong-Xiao; Zheng, Yun-Min

2010-12-31

Hypoxia causes a large increase in [Ca2+]i and attendant contraction in pulmonary artery smooth muscle cells (PASMCs), but not in systemic artery SMCs. The different responses meet the respective functional needs in these two distinct vascular myocytes; however, the underlying molecular mechanisms are not well known. We and other investigators have provided extensive evidence to reveal that voltage-dependent K+ (KV) channels, canonical transient receptor potential (TRPC) channels, ryanodine receptor Ca2+ release channels (RyRs), cyclic adenosine diphosphate-ribose, FK506 binding protein 12.6, protein kinase C, NADPH oxidase and reactive oxygen species (ROS) are the essential effectors and signaling intermediates in the hypoxic increase in [Ca2+]i in PASMCs and HPV, but they may not primarily underlie the diverse cellular responses in pulmonary and systemic vascular myocytes. Hypoxia significantly increases mitochondrial ROS generation in PASMCs, which can induce intracellular Ca2+ release by opening RyRs, and may also cause extracellular Ca2+ influx by inhibiting KV channels and activating TRPC channels, leading to a large increase in [Ca2+]i in PASMCs and HPV. In contrast, hypoxia has no or a minor effect on mitochondrial ROS generation in systemic SMCs, thereby causing no change or a negligible increase in [Ca2+]i and contraction. Further preliminary work indicates that Rieske iron-sulfur protein in the mitochondrial complex III may perhaps serve as a key initial molecular determinant for the hypoxic increase in [Ca2+]i in PASMCs and HPV, suggesting its potential important role in different cellular changes to respond to hypoxic stimulation in pulmonary and systemic artery myocytes. All these findings have greatly improved our understanding of the molecular processes for the differential hypoxic Ca2+ and contractile responses in vascular SMCs from distinct pulmonary and systemic circulation systems. Copyright © 2010 Elsevier B.V. All rights reserved.

A blood circulation model for reference man

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

Leggett, R.W.; Eckerman, K.F.; Williams, L.R.

This paper describes a dynamic blood circulation model that predicts the movement and gradual dispersal of a bolus of material in the circulation after its intravascular injection into an adult human. The main purpose of the model is to improve the dosimetry of internally deposited radionuclides that decay in the circulation to a significant extent. The total blood volume is partitioned into the blood contents of 24 separate organs or tissues, right heart chambers, left heart chambers, pulmonary circulation, arterial outflow to the systemic tissues (aorta and large arteries), and venous return from the systemic tissues (large veins). As amore » compromise between physical reality and computational simplicity, the circulation of blood is viewed as a system of first-order transfers between blood pools, with the delay time depending on the mean transit time across the pool. The model allows consideration of incomplete, tissue-dependent extraction of material during passage through the circulation and return of material from tissues to plasma.« less

Increased circulating fibrocytes are associated with higher reticulocyte percent in children with sickle cell anemia.

PubMed

Karafin, Matthew S; Dogra, Shibani; Rodeghier, Mark; Burdick, Marie; Mehrad, Borna; Rose, C Edward; Strieter, Robert M; DeBaun, Michael R; Strunk, Robert C; Field, Joshua J

2016-03-01

Interstitial lung disease is common in patients with sickle cell anemia (SCA). Fibrocytes are circulating cells implicated in the pathogenesis of pulmonary fibrosis and airway remodeling in asthma. In this study, we tested the hypotheses that fibrocyte levels are: (1) increased in children with SCA compared to healthy controls, and (2) associated with pulmonary disease. Cross-sectional cohort study of children with SCA who participated in the Sleep Asthma Cohort Study. Fibrocyte levels were obtained from 45 children with SCA and 24 controls. Mean age of SCA cases was 14 years and 53% were female. In children with SCA, levels of circulating fibrocytes were greater than controls (P < 0.01). The fibrocytes expressed a hierarchy of chemokine receptors, with CXCR4 expressed on the majority of cells and CCR2 and CCR7 expressed on a smaller subset. Almost half of fibrocytes demonstrated α-smooth muscle actin activation. Increased fibrocyte levels were associated with a higher reticulocyte count (P = 0.03) and older age (P = 0.048) in children with SCA. However, children with increased levels of fibrocytes were not more likely to have asthma or lower percent predicted forced expiratory volume in 1 sec/forced vital capacity (FEV1 /FVC) or FEV1 than those with lower fibrocyte levels. Higher levels of fibrocytes in children with SCA compared to controls may be due to hemolysis. Longitudinal studies may be able to better assess the relationship between fibrocyte level and pulmonary dysfunction. © 2015 Wiley Periodicals, Inc.

In situ cardiac perfusion reveals interspecific variation of intraventricular flow separation in reptiles.

PubMed

Joyce, William; Axelsson, Michael; Altimiras, Jordi; Wang, Tobias

2016-07-15

The ventricles of non-crocodilian reptiles are incompletely divided and provide an opportunity for mixing of oxygen-poor blood and oxygen-rich blood (intracardiac shunting). However, both cardiac morphology and in vivo shunting patterns exhibit considerable interspecific variation within reptiles. In the present study, we develop an in situ double-perfused heart approach to characterise the propensity and capacity for shunting in five reptile species: the turtle Trachemys scripta, the rock python Python sebae, the yellow anaconda Eunectes notaeus, the varanid lizard Varanus exanthematicus and the bearded dragon Pogona vitticeps To simulate changes in vascular bed resistance, pulmonary and systemic afterloads were independently manipulated and changes in blood flow distribution amongst the central outflow tracts were monitored. As previously demonstrated in Burmese pythons, rock pythons and varanid lizards exhibited pronounced intraventricular flow separation. As pulmonary or systemic afterload was raised, flow in the respective circulation decreased. However, flow in the other circulation, where afterload was constant, remained stable. This correlates with the convergent evolution of intraventricular pressure separation and the large intraventricular muscular ridge, which compartmentalises the ventricle, in these species. Conversely, in the three other species, the pulmonary and systemic flows were strongly mutually dependent, such that the decrease in pulmonary flow in response to elevated pulmonary afterload resulted in redistribution of perfusate to the systemic circuit (and vice versa). Thus, in these species, the muscular ridge appeared labile and blood could readily transverse the intraventricular cava. We conclude that relatively minor structural differences between non-crocodilian reptiles result in the fundamental changes in cardiac function. Further, our study emphasises that functionally similar intracardiac flow separation evolved independently in lizards (varanids) and snakes (pythons) from an ancestor endowed with the capacity for large intracardiac shunts. © 2016. Published by The Company of Biologists Ltd.

The effects of oxygen induced pulmonary vasoconstriction on bedside measurement of pulmonary gas exchange.

PubMed

Weinreich, Ulla M; Thomsen, Lars P; Rees, Stephen E; Rasmussen, Bodil S

2016-04-01

In patients with respiratory failure measurements of pulmonary gas exchange are of importance. The bedside automatic lung parameter estimator (ALPE) of pulmonary gas exchange is based on changes in inspired oxygen (FiO2) assuming that these changes do not affect pulmonary circulation. This assumption is investigated in this study. Forty-two out of 65 patients undergoing coronary artery bypass grafting (CABG) had measurements of mean pulmonary arterial pressure (MPAP), cardiac output and pulmonary capillary wedge pressure thus enabling the calculation of pulmonary vascular resistance (PVR) at each FiO2 level. The research version of ALPE was used and FiO2 was step-wise reduced a median of 0.20 and ultimately returned towards baseline values, allowing 6-8 min' steady state period at each of 4-6 levels before recording the oxygen saturation (SpO2). FiO2 reduction led to median decrease in SpO2 from 99 to 92 %, an increase in MPAP of 4 mmHg and an increase in PVR of 36 dyn s cm(-5). Changes were immediately reversed on returning FiO2 towards baseline. In this study changes in MPAP and PVR are small and immediately reversible consistent with small changes in pulmonary gas exchange. This indicates that mild deoxygenation induced pulmonary vasoconstriction does not have significant influences on the ALPE parameters in patients after CABG.

Effects of water immersion to the neck on pulmonary circulation and tissue volume in man

NASA Technical Reports Server (NTRS)

Begin, R.; Epstein, M.; Sackner, M. A.; Levinson, R.; Dougherty, R.; Duncan, D.

1976-01-01

A rapid noninvasive breathing method is used to obtain serial measurements of the pulmonary capillary blood flow, diffusing capacity per unit of alveolar volume, combined pulmonary tissue plus capillary volume, functional residual capacity, and oxygen consumption in five normal subjects undergoing 6 h of sitting, 4 h of sitting while immersed to the neck in thermoneutral water, and 4 h of lying in thermoneutral water to the neck. The rebreathing method employed a test gas mixture containing 0.5% C2H2, 0.3% C(18)O, 10% He, 21% O2, and balance N2. It is shown that immersion to the neck in the seated posture results in significant increases in sodium excretion cardiac output, and diffusing capacity per unit of alveolar volume. The pulmonary tissue plus capillary volume did not change, demonstrating that the central vascular engorgement induced by water immersion is not accompanied by significant extravasation of fluid into the pulmonary interstitial space.

Analysis of Tumor Vessel Supply in Lewis Lung Carcinoma in Mice by Fluorescent Microsphere Distribution and Imaging with Micro- and Flat-Panel Computed Tomography

PubMed Central

Savai, Rajkumar; Wolf, Joachim C.; Greschus, Susanne; Eul, Bastian G.; Schermuly, Ralph T.; Hänze, Jörg; Voswinckel, Robert; Langheinrich, Alexander C.; Grimminger, Friedrich; Traupe, Horst; Seeger, Werner; Rose, Frank

2005-01-01

In lung carcinomas the blood supply varies depending on tumor type and stage and can develop from pulmonary or bronchial circulation, or both. To examine this in vivo, primary bronchogenic Lewis lung carcinoma cells were intratracheally instilled in C57BL/6 mice. Within 7 days, histological examinations showed progressive tumor growth at the peripheral parenchymal region. The relative contribution of tumor blood supply via the pulmonary and systemic arteries was studied in detail using fluorescent microspheres (10 μm). When compared to healthy lung parenchyma (13:1), Lewis lung carcinoma tumor tissue (52:1) showed a fourfold increase in pulmonary to systemic microspheres, indicating that the pulmonary arteries are the predominant tumor-feeding vessels. After filling the vessels with a vascular cast, the microanatomy of vessels being derived from the pulmonary artery was visualized with micro computed tomography. Flat-panel volumetric computed tomography provided longitudinal visualization of tissue bridges between the growing tumor and the pulmonary vasculature. In this model of peripheral parenchymal malignancy, new imaging techniques allowed effective visualization of lung tumor growth and vascularization in living mice, demonstrating a pulmonary blood supply for lung tumors. PMID:16192630

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.

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.

[Diagnosis and surgical treatment of cystic pulmonary hypoplasia with aortic blood supply].

PubMed

Opanasenko, N S; Klimenko, V I; Kshanovskiĭ, A É; Tereshkovich, A V; Kalenichenko, M I; Konik, B N; Demus, R S; Obremskaia, O K; Levanda, L I; Kononenko, V A; Mikitenko, I Iu

2013-12-01

Cystic pulmonary hypoplasia with aortic blood supply--it is a rare inborn failure, in which the part of pulmonary tissue is developing separately from tracheo-bronchial tree and takes blood supply from systemic blood circulation. Diagnosis of the disease is a complicated, and it is necessary to apply modern radiological methods of visualization. The results of treatment of 27 patients, suffering cystic pulmonary hypoplasia with aortic blood supply, in the clinic through 50 yrs, were analyzed. All the patients were operated on.In 17 (63%) patients lobectomy was performed, in 4 (14.8%)--the left-sided lower lobe pyramid was excised, in 1 (3.7%)--the left-sided wedge resection of C(X), in 1 (3.7%)--the left-sided pulmonectomy, in 1 (3.7%)--left-sided resection of C(VIII) - C(IX). The rate of intraoperative complications--14.8%, and postoperative--7.4%. Efficacy of surgical treatment for this period constitutes 100%.

A neurosurgical presentation of patent foramen ovale with atrial septal aneurysm

PubMed Central

Walsh, Katie; Kaliaperumal, Chandrasekaran; Wyse, Gerry; Kaar, George

2011-01-01

We describe a case of cerebral abscess in a 53-year-old lady with a background of congenital heart defect. She has an atrial septal defect with atrial septal aneurysm, which remained undiagnosed until this clinical presentation. She presented with a short history of right-sided hemiplaegia and neuroimaging revealed a heterogeneous lesion in the left frontoparietal region. Neuronavigation-guided left frontoparietal craniotomy was performed to debulk the lesion and preoperatively frank pus was drained, which grew Streptococcus constellatus. She was successfully treated with antibiotics for 6 weeks and her clinical condition improved. We believe that the patients’ previous dental extraction has possibly resulted in a paradoxical embolism through the atrial septal defect bypassing the pulmonary circulation. The MRI scan picture was misleading, as it was initially thought to be a high-grade brain tumour. PMID:22689610

Two alternative models concerning the perialveolar microcirculation in mammalian lungs.

PubMed

Günther, Bruno; Morgado, Enrique; Cociña, Manuela

2005-01-01

Despite the fact that the concept of sheet-flow in the pulmonary microcirculation of mammals was introduced more than three decades ago, the capillary circulatory model still prevails in the physiological literature. Since cardiac output is identical in the systemic and in pulmonary circulations, it is noteworthy that in the former, the resulting arterial pressure is five times higher than that of the latter, which means that the corresponding microcirculations must be radically different. The present study addresses this problem from both morphological and physiological perspectives.

The value of initial cavitation to predict re-treatment with pulmonary tuberculosis.

PubMed

Huang, Qiusheng; Yin, Yongmei; Kuai, Shougang; Yan, Yan; Liu, Jun; Zhang, YingYing; Shan, Zhongbao; Gu, Lan; Pei, Hao; Wang, Jun

2016-05-06

Pulmonary cavitation is the classic hallmark of pulmonary tuberculosis (PTB) and is the site of very high mycobacterial burden associated with antimycobacterial drug resistance and treatment failure. The objective of this study was to investigate the relationship between re-treatment PTB and initial pulmonary cavitation coordinated with other clinical factors. We conducted a case-control study of 291 newly diagnosed cases of pulmonary TB in The Infectious Hospital of Wuxi from Dec 2009 to Dec 2011 with complete follow-up information until December 31st of 2014. 68 patients were followed-up with PTB re-treatment; the rest of the PTB patients (n = 223) had completed anti-TB treatment, and cured without re-treatment were selected as controls. The univariate analysis [hazard ratio (HR) 1.885, 95 % CI 1.170-3.035, P = 0.009] and the multivariable analysis (HR 2.242, 95 % CI 1.294-3.882, P = 0.004) demonstrated that the initial pulmonary cavitation was a prognostic predictor for TB re-treatment. Additionally, the re-treatment rates in PTB patients with cavitation and no-cavitation were 27.1 and 15.5 %, respectively, with significant difference (log-rank test; P = 0.010). Other factors, age of ≥60 and history of smoking, were also prognostic variables. Initial pulmonary cavitation of chest X-ray was a significant predictor for PTB re-treatment.

A Simple Model of the Pulmonary Circulation for Hemodynamic Study and Examination.

ERIC Educational Resources Information Center

Gaar, Kermit A., Jr.

1983-01-01

Describes a computer program allowing students to study such circulatory variables as venus return, cardiac output, mean circulatory filling pressure, resistance to venous return, and equilibrium point. Documentation for this Applesoft program (or diskette) is available from author. (JM)

Systemic and Vascular Alterations in Healthy and Cardiovascular Compromised Rats Exposed to Libby Amphibole

EPA Science Inventory

Rationale: Acute pulmonary injury and chronic disease can impact systemic vasculature because the lung capillary network can release inflammogenic and vasoactive mediators into the circulation. Occupational exposure to Libby amphibole (LA) type asbestos is associated with increas...

Lung vaso-occlusion in sickle cell disease mediated by arteriolar neutrophil-platelet microemboli.

PubMed

Bennewitz, Margaret F; Jimenez, Maritza A; Vats, Ravi; Tutuncuoglu, Egemen; Jonassaint, Jude; Kato, Gregory J; Gladwin, Mark T; Sundd, Prithu

2017-01-12

In patients with sickle cell disease (SCD), the polymerization of intraerythrocytic hemoglobin S promotes downstream vaso-occlusive events in the microvasculature. While vaso-occlusion is known to occur in the lung, often in the context of systemic vaso-occlusive crisis and the acute chest syndrome, the pathophysiological mechanisms that incite lung injury are unknown. We used intravital microscopy of the lung in transgenic humanized SCD mice to monitor acute vaso-occlusive events following an acute dose of systemic lipopolysaccharide sufficient to trigger events in SCD but not control mice. We observed cellular microembolism of precapillary pulmonary arteriolar bottlenecks by neutrophil-platelet aggregates. Blood from SCD patients was next studied under flow in an in vitro microfluidic system. Similar to the pulmonary circulation, circulating platelets nucleated around arrested neutrophils, translating to a greater number and duration of neutrophil-platelet interactions compared with normal human blood. Inhibition of platelet P-selectin with function-blocking antibody attenuated the neutrophil-platelet interactions in SCD patient blood in vitro and resolved pulmonary arteriole microembolism in SCD mice in vivo. These results establish the relevance of neutrophil-platelet aggregate formation in lung arterioles in promoting lung vaso-occlusion in SCD and highlight the therapeutic potential of targeting platelet adhesion molecules to prevent acute chest syndrome.

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

PubMed

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

2017-05-01

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

beta(2)-adrenoceptor antagonist ICI 118,551 decreases pulmonary vascular tone in mice via a G(i/o) protein/nitric oxide-coupled pathway.

PubMed

Wenzel, Daniela; Knies, Ralf; Matthey, Michaela; Klein, Alexandra M; Welschoff, Julia; Stolle, Vanessa; Sasse, Philipp; Röll, Wilhelm; Breuer, Johannes; Fleischmann, Bernd K

2009-07-01

beta(2)-adrenoceptors are important modulators of vascular tone, particularly in the pulmonary circulation. Because neurohormonal activation occurs in pulmonary arterial hypertension, we have investigated the effect of different adrenergic vasoactive substances on tone regulation in large and small pulmonary arteries, as well as in systemic vessels of mice. We found that the beta(2)-adrenoceptor antagonist ICI 118,551 (ICI) evoked a decrease of vascular tone in large pulmonary arteries and reduced the sensitivity of pulmonary arteries toward different contracting agents, eg, norepinephrine, serotonin, or endothelin. ICI proved to act specifically on pulmonary vessels, because it shifted the dose-response curve of norepinephrine to the right in pulmonary arteries, whereas there was no effect in the aorta. Pharmacological experiments proved that the right shift of the norepinephrine dose-response curve by ICI was mediated via a beta(2)-adrenoceptor/G(i/o) protein-dependent pathway enhancing NO production in the endothelium; these results were corroborated in beta-adrenoceptor and endothelial NO synthase knockout mice where ICI had no effect. ICI increased vascular lumen diameter in lung sections and reduced pulmonary arterial pressure under normoxia and under hypoxia in the isolated perfused lung model. These effects were found to be physiologically relevant, because ICI specifically decreased pulmonary but not systemic blood pressure in vivo. Thus, the beta(2)-adrenoceptor antagonist ICI is a pulmonary arterial-specific vasorelaxant and, therefore, a potentially interesting novel therapeutic agent for the treatment of pulmonary arterial hypertension.

Mucosal-Associated Invariant T Cell Deficiency in Chronic Obstructive Pulmonary Disease.

PubMed

Kwon, Yong Soo; Jin, Hye-Mi; Cho, Young-Nan; Kim, Moon-Ju; Kang, Jeong-Hwa; Jung, Hyun-Ju; Park, Ki-Jeong; Kee, Hae Jin; Kee, Seung-Jung; Park, Yong-Wook

2016-01-01

Mucosal-associated invariant T (MAIT) cells have been reported to play an important role in mucosal immunity. However, little is known about the roles of MAIT cells in chronic obstructive pulmonary disease (COPD). The aims of this study were to examine the levels of circulating MAIT cells and their subsets in COPD patients and to investigate the potential relationship between clinical parameters and MAIT cell levels. Forty-five COPD patients and 57 healthy control subjects were enrolled in the study. Circulating MAIT cells and their subset levels in the peripheral blood were measured by flow cytometry. Disease grades were classified according to the GOLD criteria for the assessment of severity of COPD. Circulating MAIT cell levels were found to be significantly reduced in COPD patients. In particular, this MAIT cell deficiency was more prominent in CD8+ and double-negative T cell subsets. Interestingly, elevated serum C-reactive protein level and reduced FEV1/FVC ratio were associated with MAIT cell deficiency in COPD patients. Furthermore, the circulating MAIT levels were found to be significantly lower in patients with moderate to severe COPD than in patients with mild COPD. Our data shows that MAIT cells are numerically deficient in the peripheral blood of patients with COPD. In addition, this MAIT cell deficiency was found to reflect inflammatory activity and disease severity. These findings provide important information for monitoring the changes in MAIT cell levels and for predicting the prognosis during the disease course.

Systemic metabolic derangement, pulmonary effects, and insulin insufficiency following subchronic ozone exposure in rats.

PubMed

Miller, Desinia B; Snow, Samantha J; Henriquez, Andres; Schladweiler, Mette C; Ledbetter, Allen D; Richards, Judy E; Andrews, Debora L; Kodavanti, Urmila P

2016-09-01

Acute ozone exposure induces a classical stress response with elevated circulating stress hormones along with changes in glucose, protein and lipid metabolism in rats, with similar alterations in ozone-exposed humans. These stress-mediated changes over time have been linked to insulin resistance. We hypothesized that acute ozone-induced stress response and metabolic impairment would persist during subchronic episodic exposure and induce peripheral insulin resistance. Male Wistar Kyoto rats were exposed to air or 0.25ppm or 1.00ppm ozone, 5h/day, 3 consecutive days/week (wk) for 13wks. Pulmonary, metabolic, insulin signaling and stress endpoints were determined immediately after 13wk or following a 1wk recovery period (13wk+1wk recovery). We show that episodic ozone exposure is associated with persistent pulmonary injury and inflammation, fasting hyperglycemia, glucose intolerance, as well as, elevated circulating adrenaline and cholesterol when measured at 13wk, however, these responses were largely reversible following a 1wk recovery. Moreover, the increases noted acutely after ozone exposure in non-esterified fatty acids and branched chain amino acid levels were not apparent following a subchronic exposure. Neither peripheral or tissue specific insulin resistance nor increased hepatic gluconeogenesis were present after subchronic ozone exposure. Instead, long-term ozone exposure lowered circulating insulin and severely impaired glucose-stimulated beta-cell insulin secretion. Thus, our findings in young-adult rats provide potential insights into epidemiological studies that show a positive association between ozone exposures and type 1 diabetes. Ozone-induced beta-cell dysfunction may secondarily contribute to other tissue-specific metabolic alterations following chronic exposure due to impaired regulation of glucose, lipid, and protein metabolism. Published by Elsevier Inc.

Systemic metabolic derangement, pulmonary effects, and insulin insufficiency following subchronic ozone exposure in rats☆,☆☆

PubMed Central

Miller, Desinia B.; Snow, Samantha J.; Henriquez, Andres; Schladweiler, Mette C.; Ledbetter, Allen D.; Richards, Judy E.; Andrews, Debora L.; Kodavanti, Urmila P.

2017-01-01

Acute ozone exposure induces a classical stress response with elevated circulating stress hormones along with changes in glucose, protein and lipid metabolism in rats, with similar alterations in ozone-exposed humans. These stress-mediated changes over time have been linked to insulin resistance. We hypothesized that acute ozone-induced stress response and metabolic impairment would persist during subchronic episodic exposure and induce peripheral insulin resistance. Male Wistar Kyoto rats were exposed to air or 0.25 ppm or 1.00 ppm ozone, 5 h/day, 3 consecutive days/week (wk) for 13 wks. Pulmonary, metabolic, insulin signaling and stress endpoints were determined immediately after 13 wk or following a 1 wk recovery period (13 wk + 1 wk recovery). We show that episodic ozone exposure is associated with persistent pulmonary injury and inflammation, fasting hyperglycemia, glucose intolerance, as well as, elevated circulating adrenaline and cholesterol when measured at 13 wk, however, these responses were largely reversible following a 1 wk recovery. Moreover, the increases noted acutely after ozone exposure in non-esterified fatty acids and branched chain amino acid levels were not apparent following a subchronic exposure. Neither peripheral or tissue specific insulin resistance nor increased hepatic gluconeogenesis were present after subchronic ozone exposure. Instead, long-term ozone exposure lowered circulating insulin and severely impaired glucose-stimulated beta-cell insulin secretion. Thus, our findings in young-adult rats provide potential insights into epidemiological studies that show a positive association between ozone exposures and type 1 diabetes. Ozone-induced beta-cell dysfunction may secondarily contribute to other tissue-specific metabolic alterations following chronic exposure due to impaired regulation of glucose, lipid, and protein metabolism. PMID:27368153

Increased CD39 Nucleotidase Activity on Microparticles from Patients with Idiopathic Pulmonary Arterial Hypertension

PubMed Central

Visovatti, Scott H.; Hyman, Matthew C.; Bouis, Diane; Neubig, Richard; McLaughlin, Vallerie V.; Pinsky, David J.

2012-01-01

Background Idiopathic pulmonary arterial hypertension (IPAH) is a devastating disease characterized by increased pulmonary vascular resistance, smooth muscle and endothelial cell proliferation, perivascular inflammatory infiltrates, and in situ thrombosis. Circulating intravascular ATP, ADP, AMP and adenosine activate purinergic cell signaling pathways and appear to induce many of the same pathologic processes that underlie IPAH. Extracellular dephosphorylation of ATP to ADP and AMP occurs primarily via CD39 (ENTPD1), an ectonucleotidase found on the surface of leukocytes, platelets, and endothelial cells [1]. Microparticles are micron-sized phospholipid vesicles formed from the membranes of platelets and endothelial cells. Objectives: Studies here examine whether CD39 is an important microparticle surface nucleotidase, and whether patients with IPAH have altered microparticle-bound CD39 activity that may contribute to the pathophysiology of the disease. Methodology/ Principal Findings Kinetic parameters, inhibitor blocking experiments, and immunogold labeling with electron microscopy support the role of CD39 as a major nucleotidase on the surface of microparticles. Comparison of microparticle surface CD39 expression and nucleotidase activity in 10 patients with advanced IPAH and 10 healthy controls using flow cytometry and thin layer chromatograph demonstrate the following: 1) circulating platelet (CD39+CD31+CD42b+) and endothelial (CD39+CD31+CD42b−) microparticle subpopulations in patients with IPAH show increased CD39 expression; 2) microparticle ATPase and ADPase activity in patients with IPAH is increased. Conclusions/ Significance We demonstrate for the first time increased CD39 expression and function on circulating microparticles in patients with IPAH. Further research is needed to elucidate whether these findings identify an important trigger for the development of the disease, or reflect a physiologic response to IPAH. PMID:22792409

Operability assessment in CTEPH: Lessons from the CHEST-1 study.

PubMed

Jenkins, David P; Biederman, Andrzej; D'Armini, Andrea M; Dartevelle, Philippe G; Gan, Hui-Li; Klepetko, Walter; Lindner, Jaroslav; Mayer, Eckhard; Madani, Michael M

2016-09-01

Pulmonary endarterectomy is the gold standard treatment for chronic thromboembolic pulmonary hypertension and is potentially curative, although some patients are unsuitable for pulmonary endarterectomy and require alternative management. Lack of standardized assessment of pulmonary endarterectomy eligibility risks suboptimal treatment in some patients. We discuss the implications for future clinical trials and practice of a unique operability assessment in patients who have chronic thromboembolic pulmonary hypertension and were initially screened for inclusion in the CHEST-1 (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase Stimulator Trial-1) study. The CHEST-1 study evaluated riociguat for the treatment of inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy. Screened patients who were initially considered "inoperable" underwent central independent adjudication by a committee of experienced surgeons, or local adjudication in collaboration with an experienced surgeon. Operability decisions were based on accessibility of thrombi and the association between pulmonary vascular resistance (PVR) and the extent of obstruction, using pulmonary angiography/computed tomography with ventilation/perfusion scintigraphy as the minimum diagnostic tests. Of 446 patients screened for CHEST-1, a total of 188 and 124 underwent central and local adjudication, respectively, after being initially considered to be "inoperable." After a second assessment by an experienced surgeon, 69 of these 312 "inoperable" patients were deemed operable. Rigorous measures in CHEST-1 guaranteed that only technically inoperable patients, or patients who had persistent/recurrent pulmonary hypertension, were enrolled, thus ensuring that only patients for whom surgery was not an option were enrolled. This study design sets new standards for future clinical trials and practice in CTEPH, helping to ensure that patients who have CTEPH receive optimal treatment. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Genetic diminution of circulating prothrombin ameliorates multiorgan pathologies in sickle cell disease mice.

PubMed

Arumugam, Paritha I; Mullins, Eric S; Shanmukhappa, Shiva Kumar; Monia, Brett P; Loberg, Anastacia; Shaw, Maureen A; Rizvi, Tilat; Wansapura, Janaka; Degen, Jay L; Malik, Punam

2015-10-08

Sickle cell disease (SCD) results in vascular occlusions, chronic hemolytic anemia, and cumulative organ damage. A conspicuous feature of SCD is chronic inflammation and coagulation system activation. Thrombin (factor IIa [FIIa]) is both a central protease in hemostasis and a key modifier of inflammatory processes. To explore the hypothesis that reduced prothrombin (factor II [FII]) levels in SCD will limit vaso-occlusion, vasculopathy, and inflammation, we used 2 strategies to suppress FII in SCD mice. Weekly administration of FII antisense oligonucleotide "gapmer" to Berkeley SCD mice to selectively reduce circulating FII levels to ∼10% of normal for 15 weeks significantly diminished early mortality. More comprehensive, long-term comparative studies were done using mice with genetic diminution of circulating FII. Here, cohorts of FII(lox/-) mice (constitutively carrying ∼10% normal FII) and FII(WT) mice were tracked in parallel for a year following the imposition of SCD via hematopoietic stem cell transplantation. This genetically imposed suppression of FII levels resulted in an impressive reduction in inflammation (reduction in leukocytosis, thrombocytosis, and circulating interleukin-6 levels), reduced endothelial cell dysfunction (reduced endothelial activation and circulating soluble vascular cell adhesion molecule), and a significant improvement in SCD-associated end-organ damage (nephropathy, pulmonary hypertension, pulmonary inflammation, liver function, inflammatory infiltration, and microinfarctions). Notably, all of these benefits were achieved with a relatively modest 1.25-fold increase in prothrombin times, and in the absence of hemorrhagic complications. Taken together, these data establish that prothrombin is a powerful modifier of SCD-induced end-organ damage, and present a novel therapeutic target to ameliorate SCD pathologies. © 2015 by The American Society of Hematology.

Acute Ozone-Induced Pulmonary and Systemic Metabolic Effects are Diminished in Adrenalectomized Rats#

EPA Science Inventory

Acute ozone exposure increases circulating stress hormones and induces metabolic alterations in animals and humans. We hypothesized that the increase of adrenal-derived stress hormones is necessary for both ozone-induced metabolic effects and lung injury. Male Wistar-Kyoto rats ...

Acute Ozone-Induced Pulmonary and Systemic Metabolic Effects are Diminished in Adrenalectomized Rats

EPA Science Inventory

Acute ozone exposure increases circulating stress hormones and induces peripheral metabolic alterations in animals and humans. We hypothesized that the increase of adrenal-derived stress hormones is necessary for ozone-induced systemic metabolic effects and lung injury. Male Wis...

Experimental measurements of energy augmentation for mechanical circulatory assistance in a patient-specific Fontan model.

PubMed

Chopski, Steven G; Rangus, Owen M; Moskowitz, William B; Throckmorton, Amy L

2014-09-01

A mechanical blood pump specifically designed to increase pressure in the great veins would improve hemodynamic stability in adolescent and adult Fontan patients having dysfunctional cavopulmonary circulation. This study investigates the impact of axial-flow blood pumps on pressure, flow rate, and energy augmentation in the total cavopulmonary circulation (TCPC) using a patient-specific Fontan model. The experiments were conducted for three mechanical support configurations, which included an axial-flow impeller alone in the inferior vena cava (IVC) and an impeller with one of two different protective stent designs. All of the pump configurations led to an increase in pressure generation and flow in the Fontan circuit. The increase in IVC flow was found to augment pulmonary arterial flow, having only a small impact on the pressure and flow in the superior vena cava (SVC). Retrograde flow was neither observed nor measured from the TCPC junction into the SVC. All of the pump configurations enhanced the rate of power gain of the cavopulmonary circulation by adding energy and rotational force to the fluid flow. We measured an enhancement of forward flow into the TCPC junction, reduction in IVC pressure, and only minimally increased pulmonary arterial pressure under conditions of pump support. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Assessment of Pulmonary Capillary Blood Volume, Membrane Diffusing Capacity, and Intrapulmonary Arteriovenous Anastomoses During Exercise.

PubMed

Tedjasaputra, Vincent; van Diepen, Sean; Collins, Sophie É; Michaelchuk, Wade M; Stickland, Michael K

2017-02-20

Exercise is a stress to the pulmonary vasculature. With incremental exercise, the pulmonary diffusing capacity (DLCO) must increase to meet the increased oxygen demand; otherwise, a diffusion limitation may occur. The increase in DLCO with exercise is due to increased capillary blood volume (Vc) and membrane diffusing capacity (Dm). Vc and Dm increase secondary to the recruitment and distension of pulmonary capillaries, increasing the surface area for gas exchange and decreasing pulmonary vascular resistance, thereby attenuating the increase in pulmonary arterial pressure. At the same time, the recruitment of intrapulmonary arteriovenous anastomoses (IPAVA) during exercise may contribute to gas exchange impairment and/or prevent large increases in pulmonary artery pressure. We describe two techniques to evaluate pulmonary diffusion and circulation at rest and during exercise. The first technique uses multiple-fraction of inspired oxygen (FIO2) DLCO breath holds to determine Vc and Dm at rest and during exercise. Additionally, echocardiography with intravenous agitated saline contrast is used to assess IPAVAs recruitment. Representative data showed that the DLCO, Vc, and Dm increased with exercise intensity. Echocardiographic data showed no IPAVA recruitment at rest, while contrast bubbles were seen in the left ventricle with exercise, suggesting exercise-induced IPAVA recruitment. The evaluation of pulmonary capillary blood volume, membrane diffusing capacity, and IPAVA recruitment using echocardiographic methods is useful to characterize the ability of the lung vasculature to adapt to the stress of exercise in health as well as in diseased groups, such as those with pulmonary arterial hypertension and chronic obstructive pulmonary disease.

Assessment of Pulmonary Capillary Blood Volume, Membrane Diffusing Capacity, and Intrapulmonary Arteriovenous Anastomoses During Exercise

PubMed Central

Tedjasaputra, Vincent; van Diepen, Sean; Collins, Sophie É; Michaelchuk, Wade M.; Stickland, Michael K.

2017-01-01

Exercise is a stress to the pulmonary vasculature. With incremental exercise, the pulmonary diffusing capacity (DLCO) must increase to meet the increased oxygen demand; otherwise, a diffusion limitation may occur. The increase in DLCO with exercise is due to increased capillary blood volume (Vc) and membrane diffusing capacity (Dm). Vc and Dm increase secondary to the recruitment and distension of pulmonary capillaries, increasing the surface area for gas exchange and decreasing pulmonary vascular resistance, thereby attenuating the increase in pulmonary arterial pressure. At the same time, the recruitment of intrapulmonary arteriovenous anastomoses (IPAVA) during exercise may contribute to gas exchange impairment and/or prevent large increases in pulmonary artery pressure. We describe two techniques to evaluate pulmonary diffusion and circulation at rest and during exercise. The first technique uses multiple-fraction of inspired oxygen (FIO2) DLCO breath holds to determine Vc and Dm at rest and during exercise. Additionally, echocardiography with intravenous agitated saline contrast is used to assess IPAVAs recruitment. Representative data showed that the DLCO, Vc, and Dm increased with exercise intensity. Echocardiographic data showed no IPAVA recruitment at rest, while contrast bubbles were seen in the left ventricle with exercise, suggesting exercise-induced IPAVA recruitment. The evaluation of pulmonary capillary blood volume, membrane diffusing capacity, and IPAVA recruitment using echocardiographic methods is useful to characterize the ability of the lung vasculature to adapt to the stress of exercise in health as well as in diseased groups, such as those with pulmonary arterial hypertension and chronic obstructive pulmonary disease. PMID:28287506

Pulmonary Hypertension and Vascular Abnormalities in Bronchopulmonary Dysplasia

PubMed Central

Mourani, Peter M.; Abman, Steven H.

2015-01-01

Advances in the care of preterm infants have improved survival of infants born at earlier gestational ages. Yet, these infants remain at risk for the chronic lung disease of infancy, bronchopulmonary dysplasia (BPD), which results in prolonged need for supplemental oxygen, recurrent respiratory exacerbations, and exercise intolerance. Recent investigations have highlighted the important contribution of the developing pulmonary circulation to lung development, demonstrating that these infants are also at risk for pulmonary vascular disease (PVD), including pulmonary hypertension (PH) and pulmonary vascular abnormalities, which contributes significantly to morbidity and mortality. In the past few years, several epidemiological studies have delineated the incidence of PH in preterm infants and the impact on outcomes. However, these studies have also highlighted gaps in our understanding of PVD in BPD, including universally accepted definitions, approaches to diagnosis and treatment, and patient outcomes. Associated pulmonary vascular and cardiac abnormalities are increasingly recognized complications contributing to PH in these infants, but incidence of these lesions and degree of contribution to disease remains unknown. Therapeutic strategies for PVD in BPD are largely untested, but recent evidence presents the rationale for the approach to diagnosis and treatment of BPD infants with PH that can be evaluated in future studies. PMID:26593082

The pathophysiology of pulmonary hypertension in left heart disease.

PubMed

Breitling, Siegfried; Ravindran, Krishnan; Goldenberg, Neil M; Kuebler, Wolfgang M

2015-11-01

Pulmonary hypertension (PH) is characterized by elevated pulmonary arterial pressure leading to right-sided heart failure and can arise from a wide range of etiologies. The most common cause of PH, termed Group 2 PH, is left-sided heart failure and is commonly known as pulmonary hypertension with left heart disease (PH-LHD). Importantly, while sharing many clinical features with pulmonary arterial hypertension (PAH), PH-LHD differs significantly at the cellular and physiological levels. These fundamental pathophysiological differences largely account for the poor response to PAH therapies experienced by PH-LHD patients. The relatively high prevalence of this disease, coupled with its unique features compared with PAH, signal the importance of an in-depth understanding of the mechanistic details of PH-LHD. The present review will focus on the current state of knowledge regarding the pathomechanisms of PH-LHD, highlighting work carried out both in human trials and in preclinical animal models. Adaptive processes at the alveolocapillary barrier and in the pulmonary circulation, including alterations in alveolar fluid transport, endothelial junctional integrity, and vasoactive mediator secretion will be discussed in detail, highlighting the aspects that impact the response to, and development of, novel therapeutics. Copyright © 2015 the American Physiological Society.

Selective upregulation of endothelin B receptor gene expression in severe pulmonary hypertension.

PubMed

Bauer, Michael; Wilkens, Heinrike; Langer, Frank; Schneider, Sven O; Lausberg, Henning; Schäfers, Hans-Joachim

2002-03-05

The pulmonary circulation is an important site for the production and clearance of endothelin (ET)-1, a potent vasoactive and mitogenic peptide. Increased plasma ET-1 levels are observed in pulmonary arterial hypertension (PHT) and may contribute to the regulation of pulmonary vascular resistance, as well as to proliferative changes in the pulmonary vascular bed. We prospectively assessed changes in plasma big ET-1 levels and changes in ET(A) and ET(B) receptor gene expression in 14 consecutive patients undergoing pulmonary thromboendarterectomy for thromboembolic PHT. Plasma big ET-1 levels were higher in patients with PHT (median, 2.2 pg/mL; 25th to 75th percentile, 1.5 to 3.0 pg/mL) compared with age-matched controls (median, 1.2 pg/mL; 25th to 75th percentile, 1.0 to 1.4 pg/mL; P=0.002). In addition to increased plasma big ET-1 levels, selective upregulation of ET(B) receptor mRNA transcripts and immunoreactive protein in the pulmonary artery was observed in the patients; however, ET(A) receptor gene expression was unaffected. These data suggest that changes in the ET signaling system in PHT caused by thromboembolic disease are not limited to an increased production of ET-1: they also affect ET receptor gene expression.

Systemic immune cell response in rats after pulmonary exposure to manganese-containing particles collected from welding aerosols.

PubMed

Antonini, James M; Zeidler-Erdely, Patti C; Young, Shih-Houng; Roberts, Jenny R; Erdely, Aaron

2012-01-01

Welding fume inhalation affects the immune system of exposed workers. Manganese (Mn) in welding fume may induce immunosuppressive effects. The goal was to determine if Mn in welding fume alters immunity by reducing the number of circulating total leukocytes and specific leukocyte sub-populations. Sprague-Dawley rats were treated by intratracheal instillation (ITI) with either a single dose (2.00 mg/rat) or repeated doses (0.125 or 2.00 mg/rat for 7 weeks) with welding fumes that contained different levels of Mn. Additional rats were treated by ITI once a week for 7 weeks with the two doses of manganese chloride (MnCl₂). Bronchoalveolar lavage was performed to assess lung inflammation. Also, whole blood was recovered, and the number of circulating total leukocytes, as well as specific lymphocyte subsets, was determined by flow cytometry. The welding fume highest in Mn content significantly increased lung inflammation, injury, and production of inflammatory cytokines and chemokines compared to all other treatment groups. In addition, the same group expressed significant decreases in the number of circulating CD4⁺ and CD8⁺ T-lymphocytes after a single exposure, and significant reductions in the number of circulating total lymphocytes, primarily CD4⁺ and CD8⁺ T-lymphocytes, after repeated exposures (compared to control values). Repeated MnCl₂ exposure led to a trend of a reduction (but not statistically significant) in circulating total lymphocytes, attributable to the changes in the CD4⁺ T-lymphocyte population levels. The welding fume with the lower concentration of Mn had no significant effect on the numbers of blood lymphocytes and lymphocyte subsets compared to control values. Evidence from this study indicates that pulmonary exposure to certain welding fumes cause decrements in systemic immune cell populations, specifically circulating T-lymphocytes, and these alterations in immune cell number are not dependent exclusively on Mn, but likely a combination of other metals present in welding fume.

Tetralogy of Fallot with absent pulmonary valve syndrome; appropriate surgical strategies.

PubMed

Shahid, Fatima; Siddiqui, Maria Tariq; Amanullah, Muhammad Muneer

2015-05-01

To evaluate patients presenting with Tetralogy of Fallot with absent pulmonary valve syndrome to a tertiary care hospital and their surgical management. The retrospective study was conducted at Congenital Cardiac Services, Aga Khan University Hospital, Karachi, Pakistan, and comprised data of Tetralogy of Fallot patients between April 2007 and June 2012. Data was analysed together with follow-up echocardiography. Variables assessed included demographics, imaging, operative technique, complications, post-operative recovery and follow-up echocardiography. SPSS 17 was used for statistical analysis. Of the 204 patients, 6 (3%) had undergone surgical correction for Tetralogy of Fallot with absent pulmonary valve syndrome. All 6(100%) patients underwent complete repair. Median age for surgery was 8.5 years (range: 0.5-29 years). Of the different surgical strategies used, Contegra and Bioprosthetic valve placement had satisfactory outcome with minimal gradient at Right Ventricular Outflow Tract, good ventricular function and mild valvular regurgitation. One (16.6%) patient with Trans Annular Patch developed post-operative Right Ventricle Outflow Tract gradient of 80mmHg with moderate pulmonary regurgitation. One (16.6%) patient with monocusp valve developed free pulmonary regurgitation at 6 months. The other 4(66.6%) patients are currently free from any complications or re-intervention. Early surgery is preferred in symptomatic patients. The repair depends upon achieving integrity of pulmonary circulation which is best achieved by using right ventricle to pulmonary artery conduit or inserting a pulmonary valve.

Positive correlation between postoperative tumor recurrence and changes in circulating tumor cell counts in pulmonary venous blood (pvCTC) during surgical manipulation in non-small cell lung cancer.

PubMed

Hashimoto, Masaki; Tanaka, Fumihiro; Yoneda, Kazue; Takuwa, Teruhisa; Matsumoto, Seiji; Okumura, Yoshitomo; Kondo, Nobuyuki; Tsujimura, Tohru; Nakano, Takashi; Hasegawa, Seiki

2018-01-01

In non-small cell lung cancer (NSCLC), circulating tumor cells (CTC) are shed and circulate to the peripheral blood through the pulmonary vein. Previously, CTC count in pulmonary venous blood (pvCTC) was shown to significantly increase after surgical manipulation. Therefore, we assessed the correlation between the changes in the pvCTC count (ΔpvCTC) and clinical outcomes. Consecutive patients with peripheral-type, NSCLC, who underwent lobectomy or bi-lobectomy through open thoracotomy, were enrolled prospectively. Before and after lobectomy, 2.5 mL of blood was drawn from the associated lobar pulmonary vein (PV), and was served for the quantitative evaluation of CTC using the CellSearch ® system. The cut-off point of ΔpvCTC was determined according to clinical outcomes and ΔpvCTC using receiver operation characteristic (ROC) curve. Then the correlation between ΔpvCTC and clinical outcomes was evaluated by Kaplan-Meier analyses and log-rank test. In addition, the correlation between ΔpvCTC and perioperative variables was assessed. A total of 30 patients were enrolled, tumor recurrence occurred in 11 patients over a median follow-up of 64.4 months. Of these, 7 patients had distant metastasis and 4 had local recurrence. The median ΔpvCTC was 49 cells/2.5 mL, and pvCTC-count was increased during surgical manipulation in 24 patients (80%). We divided patients into two groups based on ΔpvCTC with the cut-off value as 119 cells/2.5 mL according to ROC curve. Significant shorter time to distant metastasis (TDM) (P=0.0123) was observed in high ΔpvCTC group (ΔpvCTC ≥119 cells/2.5 mL) than low ΔpvCTC group (ΔpvCTC <119 cells/ 2.5mL). Neither disease-free survival (DFS) nor overall survival (OS) was significantly correlated with ΔpvCTC. Increasing pvCTC count during surgical manipulation was significantly correlated with postoperative distant metastasis in completely resected NSCLC patients. Significant shorter TDM was observed in patient with high ΔpvCTC group.

Systemic metabolic derangement, pulmonary effects, and insulin insufficiency following subchronic ozone exposure in rats

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

Miller, Desinia B.

Acute ozone exposure induces a classical stress response with elevated circulating stress hormones along with changes in glucose, protein and lipid metabolism in rats, with similar alterations in ozone-exposed humans. These stress-mediated changes over time have been linked to insulin resistance. We hypothesized that acute ozone-induced stress response and metabolic impairment would persist during subchronic episodic exposure and induce peripheral insulin resistance. Male Wistar Kyoto rats were exposed to air or 0.25 ppm or 1.00 ppm ozone, 5 h/day, 3 consecutive days/week (wk) for 13 wks. Pulmonary, metabolic, insulin signaling and stress endpoints were determined immediately after 13 wk ormore » following a 1 wk recovery period (13 wk + 1 wk recovery). We show that episodic ozone exposure is associated with persistent pulmonary injury and inflammation, fasting hyperglycemia, glucose intolerance, as well as, elevated circulating adrenaline and cholesterol when measured at 13 wk, however, these responses were largely reversible following a 1 wk recovery. Moreover, the increases noted acutely after ozone exposure in non-esterified fatty acids and branched chain amino acid levels were not apparent following a subchronic exposure. Neither peripheral or tissue specific insulin resistance nor increased hepatic gluconeogenesis were present after subchronic ozone exposure. Instead, long-term ozone exposure lowered circulating insulin and severely impaired glucose-stimulated beta-cell insulin secretion. Thus, our findings in young-adult rats provide potential insights into epidemiological studies that show a positive association between ozone exposures and type 1 diabetes. Ozone-induced beta-cell dysfunction may secondarily contribute to other tissue-specific metabolic alterations following chronic exposure due to impaired regulation of glucose, lipid, and protein metabolism. - Highlights: • Subchronic episodic ozone exposure caused pulmonary and metabolic effects. • These effects were largely reversible upon one week recovery. • Ozone exposure did not cause liver or muscle insulin resistance. • Subchronic ozone exposure led to decrease in serum insulin. • Ozone severely impaired beta cell insulin secretion in response to glucose.« less

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

PubMed

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

2015-07-01

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

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

NASA Technical Reports Server (NTRS)

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

2000-01-01

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

Pulmonary hypertensive vasculopathy in parenchymal lung diseases and/or hypoxia: Number 1 in the Series "Pathology for the clinician" Edited by Peter Dorfmüller and Alberto Cavazza.

PubMed

Ghigna, Maria Rosa; Mooi, Wolter J; Grünberg, Katrien

2017-06-30

Pulmonary hypertension (PH) with complicating chronic lung diseases and/or hypoxia falls into group 3 of the updated classification of PH. Patients with chronic obstructive lung disease (COPD), diffuse lung disease (such as idiopathic pulmonary fibrosis (IPF)) and with sleep disordered breathing are particularly exposed to the risk of developing PH. Although PH in such a context is usually mild, a minority of patients exhibit severe haemodynamic impairment, defined by a mean pulmonary arterial pressure (mPAP) of ≥35 mmHg or mPAP values ranging between 25 mmHg and 35 mmHg with a low cardiac index (<2 L·min -1 ·m -2 ). The overlap between lung parenchymal disease and PH heavily affects life expectancy in such a patient population and complicates their therapeutic management. In this review we illustrate the pathological features and the underlying pathophysiological mechanisms of pulmonary circulation in chronic lung diseases, with an emphasis on COPD, IPF and obstructive sleep apnoea syndrome. Copyright ©ERS 2017.

[System analytical approach of lung function and hemodynamics].

PubMed

Naszlady, Attila; Kiss, Lajos

2009-02-15

The authors critically analyse the traditional views in physiology and complete them with new statements based on computer model simulations of lung function and of hemodynamics. Conclusions are derived for the clinical practice as follows: the four-dimensional function curves are similar in both systems; there is a "waterfall" zone in the pulmonary blood perfusion; the various time constants of pulmonary regions can modify the blood gas values; pulmonary capillary pressure is equal to pulmonary arterial diastole pressure; heart is not a pressure pump, but a flow source; ventricles are loaded by the input impedance of the arterial systems and not by the total vascular (ohmlike) resistance; optimum heart rate in rest depends on the length of the aorta; this law of heart rate, based on the principle of resonance is valid along the mammalian allometric line; tachycardia decreases the input impedance; using positive end expiratory pressure respirators the blood gas of pulmonary artery should be followed; coronary circulation should be assessed in beat per milliliter, the milliliter per minute may be false. These statements are compared to related references.

British Thoracic Society Guideline for the initial outpatient management of pulmonary embolism

PubMed Central

Howard, Luke S; Barden, Steven; Condliffe, Robin; Connolly, Vincent; Davies, Chris; Donaldson, James; Everett, Bernard; Free, Catherine; Horner, Daniel; Hunter, Laura; Kaler, Jasvinder; Nelson-Piercy, Catherine; O’Dowd, Emma; Patel, Raj; Preston, Wendy; Sheares, Karen; Tait, Campbell

2018-01-01

The following is a summary of the recommendations and good practice points for the BTS Guideline for the initial outpatient management of pulmonary embolism. Please refer to the full guideline for full information about each section.

Advances in the Diagnosis and Management of Persistent Pulmonary Hypertension of the Newborn (PPHN)

PubMed Central

Konduri, G. Ganesh; Kim, U. Olivia

2009-01-01

Synopsis Rapid evaluation of a neonate who is cyanotic and in respiratory distress is essential for achieving a good outcome. Persistent pulmonary hypertension of the newborn (PPHN) can be a primary cause or a contributing factor to respiratory failure, particularly in neonates born at ≥34 weeks gestation. PPHN represents a failure of normal postnatal adaptation that occurs at birth in the pulmonary circulation. Rapid advances in therapy in recent years have lead to a remarkable decrease in mortality for the affected infants. However, infants who survive PPHN are at a significant risk for long term hearing and neuro-developmental impairments. This review focuses on the diagnosis, recent advances in management and recommendations for the long term follow-up of infants with PPHN. PMID:19501693

An interesting cause of pulmonary emboli: Acute carbon monoxide poisoning

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

Sevinc, A.; Savli, H.; Atmaca, H.

Carbon monoxide poisoning, a public health problem of considerable significance, is a relatively frequent event today, resulting in thousands of hospitalizations annually. A 70-year-old lady was seen in the emergency department with a provisional diagnosis of carbon monoxide poisoning. The previous night, she slept in a tightly closed room heated with coal ember. She was found unconscious in the morning with poor ventilation. She had a rare presentation of popliteal vein thrombosis, pulmonary emboli, and possible tissue necrosis with carbon monoxide poisoning. Oxygen treatment with low-molecular-weight heparin (nadroparine) and warfarin therapy resulted in an improvement in both popliteal and pulmonarymore » circulations. In conclusion, the presence of pulmonary emboli should be sought in patients with carbon monoxide poisoning.« less

Stressed lungs: unveiling the role of circulating stress hormones in ozone-induced lung injury and inflammation.

EPA Science Inventory

Ozone, a major component of smog generated through the interaction of light and anthropogenic emissions, induces adverse pulmonary, cardiovascular, and systemic health effects upon inhalation. It is generally accepted that ozone-induced lung injury is mediated by its interaction ...

AMD3100 treatment attenuates pulmonary angiogenesis by reducing the c-kit (+) cells and its pro-angiogenic activity in CBDL rat lungs.

PubMed

Shen, Cheng-Cheng; Chen, Bing; Gu, Jian-Teng; Ning, Jiao-Lin; Zeng, Jing; Yi, Bin; Lu, Kai-Zhi

2018-03-01

Recent studies have shown that pulmonary angiogenesis is an important pathological process in the development of hepatopulmonary syndrome (HPS), and growing evidence has indicated that Stromal cell-derived factor 1/C-X-C chemokine receptor type 4 (SDF-1/CXCR4) axis is involved in pulmonary vascular disease by mediating the accumulation of c-kit+ cells. This study aimed to test the effect of AMD3100, an antagonist of CXCR4, in HPS pulmonary angiogenesis. Common bile duct ligation (CBDL) rats were used as experimental HPS model and were treated with AMD3100 (1.25mg/kg/day, i.p.) or 0.9% saline for 3weeks. The sham rats underwent common bile duct exposure without ligation. The c-kit+ cells accounts and its angiogenic-related functions, prosurvival signals, pulmonary angiogenesis and arterial oxygenation were analysed in these groups. Our results showed that pulmonary SDF-1/CXCR4, Akt, Erk and VEGF/VEGFR2 were significantly activated in CBDL rats, and the numbers of circulating and pulmonary c-kit+ cells were increased in CBDL rats compared with control rats. Additionally, the angiogenic-related functions of c-kit+ cells and pulmonary microvessel counts were also elevated in CBDL rats. CXCR4 inhibition reduced pulmonary c-kit+ cells and microvessel counts and improved arterial oxygenation within 3weeks in CBDL rats. The pulmonary prosurvival signals and pro-angiogenic activity of c-kit+ cells were also down-regulated in AMD3100-treated rats. In conclusion, AMD3100 treatment attenuated pulmonary angiogenesis in CBDL rats and prevented the development of HPS via reductions in pulmonary c-kit+ cells and inhibition of the prosurvival signals. Our study provides new insights in HPS treatment. Copyright © 2017. Published by Elsevier B.V.

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.

Altered Redox Balance in the Development of Chronic Hypoxia-induced Pulmonary Hypertension.

PubMed

Jernigan, Nikki L; Resta, Thomas C; Gonzalez Bosc, Laura V

2017-01-01

Normally, the pulmonary circulation is maintained in a low-pressure, low-resistance state with little resting tone. Pulmonary arteries are thin-walled and rely heavily on pulmonary arterial distension and recruitment for reducing pulmonary vascular resistance when cardiac output is elevated. Under pathophysiological conditions, however, active vasoconstriction and vascular remodeling lead to enhanced pulmonary vascular resistance and subsequent pulmonary hypertension (PH). Chronic hypoxia is a critical pathological factor associated with the development of PH resulting from airway obstruction (COPD, sleep apnea), diffusion impairment (interstitial lung disease), developmental lung abnormalities, or high altitude exposure (World Health Organization [WHO]; Group III). The rise in pulmonary vascular resistance increases right heart afterload causing right ventricular hypertrophy that can ultimately lead to right heart failure in patients with chronic lung disease. PH is typically characterized by diminished paracrine release of vasodilators, antimitogenic factors, and antithrombotic factors (e.g., nitric oxide and protacyclin) and enhanced production of vasoconstrictors and mitogenic factors (e.g., reactive oxygen species and endothelin-1) from the endothelium and lung parenchyma. In addition, phenotypic changes to pulmonary arterial smooth muscle cells (PASMC), including alterations in Ca 2+ homeostasis, Ca 2+ sensitivity, and activation of transcription factors are thought to play prominent roles in the development of both vasoconstrictor and arterial remodeling components of hypoxia-associated PH. These changes in PASMC function are briefly reviewed in Sect. 1 and the influence of altered reactive oxygen species homeostasis on PASMC function discussed in Sects. 2-4.

Patent ductus arteriosus in a lamb: A case report

PubMed Central

Jafari Dehkordi, Afshin; Hoseini, Farzaneh

2016-01-01

Patent ductus arteriosus (PDA) is a persistent patency of a vessel normally present in the fetus that connects the pulmonary arterial system to the aorta. The ductus arteriosus fails to close at birth when breathing commences and placental blood circulation is removed. Closure of the ductus arteriosus arises in response to decline pulmonary vascular resistance and increased systemic vascular resistance. This report describes a case of PDA in a two-month-old male lamb with clinical signs of machinery murmur, tachycardia, increase respiratory rate, weakness and ill thrift. Echocardiographic examination and necropsy finding confirmed PDA. PMID:27226893

Reduced serum club cell protein as a pulmonary damage marker for chronic fine particulate matter exposure in Chinese population.

PubMed

Wang, Yanhua; Duan, Huawei; Meng, Tao; Shen, Meili; Ji, Qianpeng; Xing, Jie; Wang, Qingrong; Wang, Ting; Niu, Yong; Yu, Tao; Liu, Zhong; Jia, Hongbing; Zhan, Yuliang; Chen, Wen; Zhang, Zhihu; Su, Wenge; Dai, Yufei; Zhang, Xuchun; Zheng, Yuxin

2018-03-01

Exposure to fine particulate matter (PM 2.5 ) pollution is associated with increased morbidity and mortality from respiratory diseases. However, few population-based studies have been conducted to assess the alterations in circulating pulmonary proteins due to long-term PM 2.5 exposure. We designed a two-stage study. In the first stage (training set), we assessed the associations between PM 2.5 exposure and levels of pulmonary damage markers (CC16, SP-A and SP-D) and lung function in a coke oven emission (COE) cohort with 558 coke plant workers and 210 controls. In the second stage (validation set), significant initial findings were validated by an independent diesel engine exhaust (DEE) cohort with 50 DEE exposed workers and 50 controls. Serum CC16 levels decreased in a dose response manner in association with both external and internal PM 2.5 exposures in the two cohorts. In the training set, serum CC16 levels decreased with increasing duration of occupational PM 2.5 exposure history. An interquartile range (IQR) (122.0μg/m 3 ) increase in PM 2.5 was associated with a 5.76% decrease in serum CC16 levels, whereas an IQR (1.06μmol/mol creatinine) increase in urinary 1-hydroxypyrene (1-OHP) concentration was associated with a 5.36% decrease in serum CC16 levels in the COE cohort. In the validation set, the concentration of serum CC16 in the PM 2.5 exposed group was 22.42% lower than that of the controls and an IQR (1.24μmol/mol creatinine) increase in urinary 1-OHP concentration was associated with a 12.24% decrease in serum CC16 levels in the DEE cohort. Serum CC16 levels may be a sensitive marker for pulmonary damage in populations with high PM 2.5 exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

Systemic Metabolic Derangement, Pulmonary Effects, and Insulin Insufficiency following subchronic ozone exposure in rats

EPA Science Inventory

Acute ozone exposure induces a classical stress response with elevated circulating stress hormones along with changes in glucose, protein and lipid metabolism in rats, with similar alterations in ozone-exposed humans. These stress-mediated changes over time have been linked to in...

Effects of Aging on the Respiratory System.

ERIC Educational Resources Information Center

Levitzky, Michael G.

1984-01-01

Relates alterations in respiratory system functions occurring with aging to changes in respiratory system structure during the course of life. Main alterations noted include loss of alveolar elastic recoil, alteration in chest wall structure and decreased respiratory muscle strength, and loss of surface area and changes in pulmonary circulation.…

Cardiac Rehabilitation. A Handbook for Vocational Rehabilitation Counselors.

ERIC Educational Resources Information Center

Brammell, H. L.; And Others

Basic information about heart disease and functional capacity assessment and its application to activity/job counseling are presented in this handbook for vocational rehabilitation counselors. Sections include the following: impact of heart disease; basic anatomy and physiology (e.g., the heart, pulmonary circulation, causes of cardiac pain, and…

Cardiogenic Pulmonary Edema in a Dog Following Initiation of Therapy for Concurrent Hypoadrenocorticism and Hypothyroidism.

PubMed

Paik, Jooyae; Kang, Ji-Houn; Chang, Dongwoo; Yang, Mhan-Pyo

A 5 yr old intact female cocker spaniel dog weighing 7.8 kg was referred with anorexia, vomiting, and depression. At referral, the dog was diagnosed initially with typical hypoadrenocorticism, and 2 d later, concurrent primary hypothyroidism was detected. Hormonal replacement therapies, including fludrocortisone, prednisolone, and levothyroxine, were initiated, but a few days later the dog became abruptly tachypneic, and thoracic radiographs indicated the development of pulmonary edema. Echocardiography showed that there were abnormalities indicating impaired left ventricular function, although the heart valves were normal. Following treatment with pimobendan and furosemide, the pulmonary edema resolved. The dog had no recurrence of the clinical signs after 10 mo of follow-up, despite being off all cardiac medications; consequently, the cardiac failure was transient or reversible in this dog. The case report describes the stepwise diagnosis and successful treatment of cardiogenic pulmonary edema after initiation of hormonal replacement therapy for concurrent hypoadrenocorticism and hypothyroidism in a dog.

Coupling of a 3D Finite Element Model of Cardiac Ventricular Mechanics to Lumped Systems Models of the Systemic and Pulmonic Circulation

PubMed Central

Kerckhoffs, Roy C. P.; Neal, Maxwell L.; Gu, Quan; Bassingthwaighte, James B.; Omens, Jeff H.; McCulloch, Andrew D.

2010-01-01

In this study we present a novel, robust method to couple finite element (FE) models of cardiac mechanics to systems models of the circulation (CIRC), independent of cardiac phase. For each time step through a cardiac cycle, left and right ventricular pressures were calculated using ventricular compliances from the FE and CIRC models. These pressures served as boundary conditions in the FE and CIRC models. In succeeding steps, pressures were updated to minimize cavity volume error (FE minus CIRC volume) using Newton iterations. Coupling was achieved when a predefined criterion for the volume error was satisfied. Initial conditions for the multi-scale model were obtained by replacing the FE model with a varying elastance model, which takes into account direct ventricular interactions. Applying the coupling, a novel multi-scale model of the canine cardiovascular system was developed. Global hemodynamics and regional mechanics were calculated for multiple beats in two separate simulations with a left ventricular ischemic region and pulmonary artery constriction, respectively. After the interventions, global hemodynamics changed due to direct and indirect ventricular interactions, in agreement with previously published experimental results. The coupling method allows for simulations of multiple cardiac cycles for normal and pathophysiology, encompassing levels from cell to system. PMID:17111210

Splenectomy Is Modifying the Vascular Remodeling of Thrombosis

PubMed Central

Frey, Maria K.; Alias, Sherin; Winter, Max P.; Redwan, Bassam; Stübiger, Gerald; Panzenboeck, Adelheid; Alimohammadi, Arman; Bonderman, Diana; Jakowitsch, Johannes; Bergmeister, Helga; Bochkov, Valery; Preissner, Klaus T.; Lang, Irene M.

2014-01-01

Background Splenectomy is a clinical risk factor for complicated thrombosis. We hypothesized that the loss of the mechanical filtering function of the spleen may enrich for thrombogenic phospholipids in the circulation, thereby affecting the vascular remodeling of thrombosis. Methods and Results We investigated the effects of splenectomy both in chronic thromboembolic pulmonary hypertension (CTEPH), a human model disease for thrombus nonresolution, and in a mouse model of stagnant flow venous thrombosis mimicking deep vein thrombosis. Surgically excised thrombi from rare cases of CTEPH patients who had undergone previous splenectomy were enriched for anionic phospholipids like phosphatidylserine. Similar to human thrombi, phosphatidylserine accumulated in thrombi after splenectomy in the mouse model. A postsplenectomy state was associated with larger and more persistent thrombi. Higher counts of procoagulant platelet microparticles and increased leukocyte–platelet aggregates were observed in mice after splenectomy. Histological inspection revealed a decreased number of thrombus vessels. Phosphatidylserine‐enriched phospholipids specifically inhibited endothelial proliferation and sprouting. Conclusions After splenectomy, an increase in circulating microparticles and negatively charged phospholipids is enhanced by experimental thrombus induction. The initial increase in thrombus volume after splenectomy is due to platelet activation, and the subsequent delay of thrombus resolution is due to inhibition of thrombus angiogenesis. The data illustrate a potential mechanism of disease in CTEPH. PMID:24584745

Chitinase 1 Is a Biomarker for and Therapeutic Target in Scleroderma-Associated Interstitial Lung Disease That Augments TGF-β1 Signaling

PubMed Central

Lee, Chun Geun; Herzog, Erica L.; Ahangari, Farida; Zhou, Yang; Gulati, Mridu; Lee, Chang-Min; Peng, Xueyan; Feghali-Bostwick, Carol; Jimenez, Sergio A.; Varga, John; Elias, Jack A.

2014-01-01

Interstitial lung disease (ILD) with pulmonary fibrosis is an important manifestation in systemic sclerosis (SSc, scleroderma) where it portends a poor prognosis. However, biomarkers that predict the development and or severity of SSc-ILD have not been validated, and the pathogenetic mechanisms that engender this pulmonary response are poorly understood. In this study, we demonstrate in two different patient cohorts that the levels of chitotriosidase (Chit1) bioactivity and protein are significantly increased in the circulation and lungs of SSc patients compared with demographically matched controls. We also demonstrate that, compared with patients without lung involvement, patients with ILD show high levels of circulating Chit1 activity that correlate with disease severity. Murine modeling shows that in comparison with wild-type mice, bleomycin-induced pulmonary fibrosis was significantly reduced in Chit1−/− mice and significantly enhanced in lungs from Chit1 overexpressing transgenic animals. In vitro studies also demonstrated that Chit1 interacts with TGF-β1 to augment fibroblast TGF-β receptors 1 and 2 expression and TGF-β–induced Smad and MAPK/ERK activation. These studies indicate that Chit1 is potential biomarker for ILD in SSc and a therapeutic target in SSc-associated lung fibrosis and demonstrate that Chit1 augments TGF-β1 effects by increasing receptor expression and canonical and noncanonical TGF-β1 signaling. PMID:22826322

Uncoupling protein 2 deficiency mimics the effects of hypoxia and endoplasmic reticulum stress on mitochondria and triggers pseudohypoxic pulmonary vascular remodeling and pulmonary hypertension.

PubMed

Dromparis, Peter; Paulin, Roxane; Sutendra, Gopinath; Qi, Andrew C; Bonnet, Sébastien; Michelakis, Evangelos D

2013-07-05

Mitochondrial signaling regulates both the acute and the chronic response of the pulmonary circulation to hypoxia, and suppressed mitochondrial glucose oxidation contributes to the apoptosis-resistance and proliferative diathesis in the vascular remodeling in pulmonary hypertension. Hypoxia directly inhibits glucose oxidation, whereas endoplasmic reticulum (ER)-stress can indirectly inhibit glucose oxidation by decreasing mitochondrial calcium (Ca²⁺m levels). Both hypoxia and ER stress promote proliferative pulmonary vascular remodeling. Uncoupling protein 2 (UCP2) has been shown to conduct calcium from the ER to mitochondria and suppress mitochondrial function. We hypothesized that UCP2 deficiency reduces Ca²⁺m in pulmonary artery smooth muscle cells (PASMCs), mimicking the effects of hypoxia and ER stress on mitochondria in vitro and in vivo, promoting normoxic hypoxia inducible factor-1α activation and pulmonary hypertension. Ucp2 knockout (KO)-PASMCs had lower mitochondrial calcium than Ucp2 wildtype (WT)-PASMCs at baseline and during histamine-stimulated ER-Ca²⁺ release. Normoxic Ucp2KO-PASMCs had mitochondrial hyperpolarization, lower Ca²⁺-sensitive mitochondrial enzyme activity, reduced levels of mitochondrial reactive oxygen species and Krebs' cycle intermediates, and increased resistance to apoptosis, mimicking the hypoxia-induced changes in Ucp2WT-PASMC. Ucp2KO mice spontaneously developed pulmonary vascular remodeling and pulmonary hypertension and exhibited a pseudohypoxic state with pulmonary vascular and systemic hypoxia inducible factor-1α activation (increased hematocrit), not exacerbated further by chronic hypoxia. This first description of the role of UCP2 in oxygen sensing and in pulmonary hypertension vascular remodeling may open a new window in biomarker and therapeutic strategies.

Microembolism and catheter ablation I: a comparison of irrigated radiofrequency and multielectrode-phased radiofrequency catheter ablation of pulmonary vein ostia.

PubMed

Haines, David E; Stewart, Mark T; Dahlberg, Sarah; Barka, Noah D; Condie, Cathy; Fiedler, Gary R; Kirchhof, Nicole A; Halimi, Franck; Deneke, Thomas

2013-02-01

Cerebral diffusion-weighted MRI lesions have been observed after catheter ablation of atrial fibrillation. We hypothesized that conditions predisposing to microembolization could be identified using a porcine model of pulmonary vein ablation and an extracorporeal circulation loop. Ablations of the pulmonary veins were performed in 18 swine with echo monitoring. The femoral artery and vein were cannulated and an extracorporeal circulation loop with 2 ultrasonic bubble detectors and a 73-μm filter were placed in series. Microemboli and microbubbles were compared between ablation with an irrigated radiofrequency system (Biosense-Webster) and a phased radiofrequency multielectrode system (pulmonary vein ablation catheter [PVAC], Medtronic, Inc, Carlsbad, CA) in unipolar and 3 blended unipolar/bipolar modes. Animal pathology was examined. The size and number of microbubbles observed during ablation ranged from 30 to 180 μm and 0 to 3253 bubbles per ablation. Microbubble volumes with PVAC (29.1 nL) were greater than with irrigated radiofrequency (0.4 nL; P=0.045), and greatest with type II or III microbubbles on transesophageal echocardiography. Ablation with the PVAC showed fewest microbubbles in the unipolar mode (P=0.012 versus bipolar). The most occurred during bipolar energy delivery with overlap of proximal and distal electrodes (median microbubble volume, 1744 nL; interquartile range, 737-4082 nL; maximum, 19 516 nL). No cerebral MRI lesions were seen, but 2 animals had renal embolization. Left atrial ablation with irrigated radiofrequency and PVAC catheters in swine is associated with microbubble and microembolus production. Avoiding overlap of electrodes 1 and 10 on PVAC should reduce the microembolic burden associated with this procedure.

Autoimmunity to Vimentin Is Associated with Outcomes of Patients with Idiopathic Pulmonary Fibrosis.

PubMed

Li, Fu Jun; Surolia, Ranu; Li, Huashi; Wang, Zheng; Kulkarni, Tejaswini; Liu, Gang; de Andrade, Joao A; Kass, Daniel J; Thannickal, Victor J; Duncan, Steven R; Antony, Veena B

2017-09-01

Autoimmunity has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF); however, the repertoire of autoantigens involved in this disease and the clinical relevance of these autoimmune responses are still being explored. Our initial discovery assays demonstrated that circulating and intrapulmonary vimentin levels are increased in IPF patients. Subsequent studies showed native vimentin induced HLA-DR-dependent in vitro proliferation of CD4 T cells from IPF patients and enhanced the production of IL-4, IL-17, and TGF-β1 by these lymphocytes in contrast to normal control specimens. Vimentin supplementation of IPF PBMC cultures also resulted in HLA-DR-dependent production of IgG with anti-vimentin specificities. Circulating anti-vimentin IgG autoantibody levels were much greater in IPF subjects from the University of Alabama at Birmingham ( n = 102) and the University of Pittsburgh (U. Pitt., n = 70) than in normal controls. Anti-vimentin autoantibody levels in IPF patients were HLA biased and inversely correlated with physiological measurements of lung function (i.e., forced expiratory volumes and diffusing capacities). Despite considerable intergroup differences in transplant-free survival between these two independent IPF cohorts, serious adverse outcomes were most frequent among the patients within each population that had the highest anti-vimentin autoantibody levels (University of Alabama at Birmingham: hazard ratio 2.5, 95% confidence interval 1.2-5.3, p = 0.012; University of Pittsburgh: hazard ratio 2.7, 95% confidence interval 1.3-5.5, p = 0.006). These data show that anti-vimentin autoreactivity is prevalent in IPF patients and is strongly associated with disease manifestations. These findings have implications with regard to the pathogenesis of this enigmatic disease and raise the possibility that therapies specifically directed at these autoimmune processes could have therapeutic efficacy. Copyright © 2017 by The American Association of Immunologists, Inc.

[MRI methods for pulmonary ventilation and perfusion imaging].

PubMed

Sommer, G; Bauman, G

2016-02-01

Separate assessment of respiratory mechanics, gas exchange and pulmonary circulation is essential for the diagnosis and therapy of pulmonary diseases. Due to the global character of the information obtained clinical lung function tests are often not sufficiently specific in the differential diagnosis or have a limited sensitivity in the detection of early pathological changes. The standard procedures of pulmonary imaging are computed tomography (CT) for depiction of the morphology as well as perfusion/ventilation scintigraphy and single photon emission computed tomography (SPECT) for functional assessment. Magnetic resonance imaging (MRI) with hyperpolarized gases, O2-enhanced MRI, MRI with fluorinated gases and Fourier decomposition MRI (FD-MRI) are available for assessment of pulmonary ventilation. For assessment of pulmonary perfusion dynamic contrast-enhanced MRI (DCE-MRI), arterial spin labeling (ASL) and FD-MRI can be used. Imaging provides a more precise insight into the pathophysiology of pulmonary function on a regional level. The advantages of MRI are a lack of ionizing radiation, which allows a protective acquisition of dynamic data as well as the high number of available contrasts and therefore accessible lung function parameters. Sufficient clinical data exist only for certain applications of DCE-MRI. For the other techniques, only feasibility studies and case series of different sizes are available. The clinical applicability of hyperpolarized gases is limited for technical reasons. The clinical application of the techniques described, except for DCE-MRI, should be restricted to scientific studies.

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.

Clinical application of three-dimensional printing to the management of complex univentricular hearts with abnormal systemic or pulmonary venous drainage.

PubMed

McGovern, Eimear; Kelleher, Eoin; Snow, Aisling; Walsh, Kevin; Gadallah, Bassem; Kutty, Shelby; Redmond, John M; McMahon, Colin J

2017-09-01

In recent years, three-dimensional printing has demonstrated reliable reproducibility of several organs including hearts with complex congenital cardiac anomalies. This represents the next step in advanced image processing and can be used to plan surgical repair. In this study, we describe three children with complex univentricular hearts and abnormal systemic or pulmonary venous drainage, in whom three-dimensional printed models based on CT data assisted with preoperative planning. For two children, after group discussion and examination of the models, a decision was made not to proceed with surgery. We extend the current clinical experience with three-dimensional printed modelling and discuss the benefits of such models in the setting of managing complex surgical problems in children with univentricular circulation and abnormal systemic or pulmonary venous drainage.

Obesity-induced adipokine imbalance impairs mouse pulmonary vascular endothelial function and primes the lung for injury.

PubMed

Shah, Dilip; Romero, Freddy; Duong, Michelle; Wang, Nadan; Paudyal, Bishnuhari; Suratt, Benjamin T; Kallen, Caleb B; Sun, Jianxin; Zhu, Ying; Walsh, Kenneth; Summer, Ross

2015-06-12

Obesity is a risk factor for the development of acute respiratory distress syndrome (ARDS) but mechanisms mediating this association are unknown. While obesity is known to impair systemic blood vessel function, and predisposes to systemic vascular diseases, its effects on the pulmonary circulation are largely unknown. We hypothesized that the chronic low grade inflammation of obesity impairs pulmonary vascular homeostasis and primes the lung for acute injury. The lung endothelium from obese mice expressed higher levels of leukocyte adhesion markers and lower levels of cell-cell junctional proteins when compared to lean mice. We tested whether systemic factors are responsible for these alterations in the pulmonary endothelium; treatment of primary lung endothelial cells with obese serum enhanced the expression of adhesion proteins and reduced the expression of endothelial junctional proteins when compared to lean serum. Alterations in pulmonary endothelial cells observed in obese mice were associated with enhanced susceptibility to LPS-induced lung injury. Restoring serum adiponectin levels reversed the effects of obesity on the lung endothelium and attenuated susceptibility to acute injury. Our work indicates that obesity impairs pulmonary vascular homeostasis and enhances susceptibility to acute injury and provides mechanistic insight into the increased prevalence of ARDS in obese humans.

Obesity-induced adipokine imbalance impairs mouse pulmonary vascular endothelial function and primes the lung for injury

PubMed Central

Shah, Dilip; Romero, Freddy; Duong, Michelle; Wang, Nadan; Paudyal, Bishnuhari; Suratt, Benjamin T.; Kallen, Caleb B.; Sun, Jianxin; Zhu, Ying; Walsh, Kenneth; Summer, Ross

2015-01-01

Obesity is a risk factor for the development of acute respiratory distress syndrome (ARDS) but mechanisms mediating this association are unknown. While obesity is known to impair systemic blood vessel function, and predisposes to systemic vascular diseases, its effects on the pulmonary circulation are largely unknown. We hypothesized that the chronic low grade inflammation of obesity impairs pulmonary vascular homeostasis and primes the lung for acute injury. The lung endothelium from obese mice expressed higher levels of leukocyte adhesion markers and lower levels of cell-cell junctional proteins when compared to lean mice. We tested whether systemic factors are responsible for these alterations in the pulmonary endothelium; treatment of primary lung endothelial cells with obese serum enhanced the expression of adhesion proteins and reduced the expression of endothelial junctional proteins when compared to lean serum. Alterations in pulmonary endothelial cells observed in obese mice were associated with enhanced susceptibility to LPS-induced lung injury. Restoring serum adiponectin levels reversed the effects of obesity on the lung endothelium and attenuated susceptibility to acute injury. Our work indicates that obesity impairs pulmonary vascular homeostasis and enhances susceptibility to acute injury and provides mechanistic insight into the increased prevalence of ARDS in obese humans. PMID:26068229

Endothelin B receptor blockade attenuates pulmonary vasodilation in oxygen-ventilated fetal lambs.

PubMed

Ivy, D Dunbar; Lee, Dong-Seok; Rairigh, Robyn L; Parker, Thomas A; Abman, Steven H

2004-01-01

Endothelin-1 (ET-1) contributes to the regulation of pulmonary vascular tone in the normal ovine fetus and in models of perinatal pulmonary hypertension. In the fetal lamb lung, the effects of ET-1 depend on the balance of at least two endothelin receptor subtypes: ETA and ETB. ETA receptors are located on smooth muscle cells and mediate vasoconstriction and smooth muscle proliferation. Stimulation of endothelial ETB receptors causes vasodilation through release of nitric oxide and also functions to remove ET-1 from the circulation. However, whether activation of ETB receptors contributes to the fall in pulmonary vascular tone at birth is unknown. To determine the role of acute ETB receptor blockade in pulmonary vasodilation in response to birth-related stimuli, we studied the hemodynamic effects of selective ETB receptor blockade with BQ-788 during mechanical ventilation with low (<10%) and high FiO2 (100%) in near-term fetal sheep. Intrapulmonary infusion of BQ-788 did not change left pulmonary artery (LPA) blood flow and pulmonary vascular resistance (PVR) at baseline. In comparison with controls, BQ-788 treatment attenuated the rise in LPA flow with low and high FiO2 ventilation (p <0.001 vs. control for each FiO2 concentration). PVR progressively decreased during mechanical ventilation with low and high FiO2 in both groups, but PVR remained higher after BQ-788 treatment throughout the study period (p <0.001). We conclude that selective ETB receptor blockade attenuates pulmonary vasodilation at birth. We speculate that ETB receptor stimulation contributes to pulmonary vasodilation at birth in the ovine fetus.

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

PubMed Central

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

2011-01-01

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

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

PubMed Central

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

2012-01-01

Pulmonary hypertension (PH) is characterized by pulmonary arteriolar remodeling with excessive pulmonary vascular smooth muscle cell (VSMC) proliferation. This results in decreased responsiveness of pulmonary circulation to vasodilator therapies. We have shown that extracellular acidosis inhibits VSMC proliferation and migration in vitro. Here we tested whether induction of nonhypercapnic acidosis in vivo ameliorates PH and the underlying pulmonary vascular remodeling and dysfunction. Adult male Sprague-Dawley rats were exposed to hypoxia (8.5% O2) for 2 wk, or injected subcutaneously with monocrotaline (MCT, 60 mg/kg) to develop PH. Acidosis was induced with NH4Cl (1.5%) in the drinking water 5 days prior to and during the 2 wk of hypoxic exposure (prevention protocol), or after MCT injection from day 21 to 28 (reversal protocol). Right ventricular systolic pressure (RVSP) and Fulton's index were measured, and pulmonary arteriolar remodeling was analyzed. Pulmonary and mesenteric artery contraction to phenylephrine (Phe) and high KCl, and relaxation to acetylcholine (ACh) and sodium nitroprusside (SNP) were examined ex vivo. Hypoxic and MCT-treated rats demonstrated increased RVSP, Fulton's index, and pulmonary arteriolar thickening. In pulmonary arteries of hypoxic and MCT rats there was reduced contraction to Phe and KCl and reduced vasodilation to ACh and SNP. Acidosis prevented hypoxia-induced PH, reversed MCT-induced PH, and resulted in reduction in all indexes of PH including RVSP, Fulton's index, and pulmonary arteriolar remodeling. Pulmonary artery contraction to Phe and KCl was preserved or improved, and relaxation to ACh and SNP was enhanced in NH4Cl-treated PH animals. Acidosis alone did not affect the hemodynamics or pulmonary vascular function. Phe and KCl contraction and ACh and SNP relaxation were not different in mesenteric arteries of all groups. Thus nonhypercapnic acidosis ameliorates experimental PH, attenuates pulmonary arteriolar thickening, and enhances pulmonary vascular responsiveness to vasoconstrictor and vasodilator stimuli. Together with our finding that acidosis decreases VSMC proliferation, the results are consistent with the possibility that nonhypercapnic acidosis promotes differentiation of pulmonary VSMCs to a more contractile phenotype, which may enhance the effectiveness of vasodilator therapies in PH. PMID:22287610

REACTIVE OXYGEN AND NITROGEN SPECIES IN PULMONARY HYPERTENSION

PubMed Central

Tabima, Diana M.; Frizzell, Sheila; Gladwin, Mark T.

2013-01-01

Pulmonary vascular disease can be defined as either a disease affecting the pulmonary capillaries and pulmonary arterioles, termed pulmonary arterial hypertension, or as a disease affecting the left ventricle, called pulmonary venous hypertension. Pulmonary arterial hypertension (PAH) is a disorder of the pulmonary circulation characterized by endothelial dysfunction, as well as intimal and smooth muscle proliferation. Progressive increases in pulmonary vascular resistance and pressure impair the performance of the right ventricle, resulting in declining cardiac output, reduced exercise capacity, right heart failure, and ultimately death. While the primary and heritable forms of the disease are thought to affect over 5,000 patients in the U.S., the disease can occur secondary to congenital heart disease, most advanced lung diseases, and many systemic diseases. Multiple studies implicate oxidative stress in the development of PAH. Further, this oxidative stress has been shown to be associated with alterations in reactive oxygen species (ROS), reactive nitrogen species (RNS) and nitric oxide (NO) signaling pathways, whereby bioavailable NO is decreased and ROS and RNS production are increased. Many canonical ROS and NO signaling pathways are simultaneously disrupted in PAH, with increased expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and xanthine oxidoreductase, uncoupling of endothelial NO synthase (eNOS), and reduction in mitochondrial number, as well as impaired mitochondrial function. Upstream dysregulation of ROS/NO redox homeostasis impairs vascular tone and contributes to the pathological activation of anti-apoptotic and mitogenic pathways, leading to cell proliferation and obliteration of the vasculature. This manuscript will review the available data regarding the role of oxidative and nitrosative stress and endothelial dysfunction in the pathophysiology of pulmonary hypertension, and provide a description of targeted therapies for this disease. PMID:22401856

Transport mechanisms at the pulmonary mucosa: implications for drug delivery.

PubMed

Nickel, Sabrina; Clerkin, Caoimhe G; Selo, Mohammed Ali; Ehrhardt, Carsten

2016-01-01

Over the past years, a significant number of papers have substantiated earlier findings proposing a role for drug transporter proteins in pulmonary drug disposition. Whilst the majority of reports present data from in vitro models, a growing number of publications advance the field by introducing sophisticated ex vivo and in vivo techniques. In a few cases, evidence from clinical studies in human volunteers is complementing the picture. In this review, recent advances in pulmonary drug transporter research are critically evaluated. Transporter expression data in tissues and cell-based in vitro models is summarized and information on transport activity assessed. Novel techniques allowing for better quantification of transporter-related effects following pulmonary delivery are also described. Different tissue and cell populations of the lung have distinct transporter expression patterns. Whether these patterns are affected by disease, gender and smoking habits requires further clarification. Transporters have been found to have an impact on drug absorption processes, at least in vitro. Recent ex vivo experiments using isolated, perfused lung models, however, suggest that mainly efflux pumps have significant effects on absorption into the pulmonary circulation. Whether these rodent-based ex vivo models predict the human situation is basis for further research.

Lack of Correlation Between Pulmonary and Systemic Inflammation Markers in Patients with Chronic Obstructive Pulmonary Disease: A Simultaneous, Two-Compartmental Analysis.

PubMed

Núñez, Belen; Sauleda, Jaume; Garcia-Aymerich, Judith; Noguera, Aina; Monsó, Eduard; Gómez, Federico; Barreiro, Esther; Marín, Alicia; Antó, Josep Maria; Agusti, Alvar

2016-07-01

The origin of systemic inflammation in chronic obstructive pulmonary disease (COPD) patients remains to be defined, but one of the most widely accepted hypothesis is the 'spill over' of inflammatory mediators from the lung to the circulation. To evaluate the relationship between pulmonary and systemic inflammation in COPD quantifying several inflammatory markers in sputum and serum determined simultaneously. Correlations between various inflammatory variables (TNF-α, IL6, IL8) in sputum and serum were evaluated in 133 patients from the PAC-COPD cohort study. A secondary objective was the evaluation of relationships between inflammatory variables and lung function. Inflammatory markers were clearly higher in sputum than in serum. No significant correlation was found (absolute value, r=0.03-0.24) between inflammatory markers in blood and in sputum. There were no significant associations identified between those markers and lung function variables, such as FEV1, DLCO and PaO2 neither. We found no correlation between pulmonary and systemic inflammation in patients with stable COPD, suggesting different pathogenic mechanisms. Copyright © 2016 SEPAR. Published by Elsevier Espana. All rights reserved.

Acute resolution of pulmonary alveolar infiltrates in 10 dogs with pulmonary hypertension treated with sildenafil citrate: 2005-2014.

PubMed

Kellihan, Heidi B; Waller, Kenneth R; Pinkos, Alyssa; Steinberg, Howard; Bates, Melissa L

2015-09-01

To describe clinical canine patients with naturally occurring pulmonary hypertension and radiographic pulmonary alveolar infiltrates before and after treatment with sildenafil. Ten client-owned dogs. A retrospective analysis of dogs with echocardiographically-determined pulmonary hypertension and pulmonary alveolar infiltrates on thoracic radiographs was performed before (PRE) and after (POST) sildenafil therapy. Clinical scores, pulmonary alveolar infiltrate scores and tricuspid regurgitation gradients were analyzed PRE and POST sildenafil. Pulmonary alveolar infiltrates associated with pulmonary hypertension developed in a diffusely patchy distribution (10/10). Sixty percent of dogs had a suspected diagnosis of interstitial pulmonary fibrosis as the etiology of pulmonary hypertension. Median PRE clinical score was 4 (range: 3-4) compared to POST score of 0 (0-2) (p = 0.005). Median alveolar infiltrate score PRE was 10 (5-12) compared to POST score of 4 (0-6) (p = 0.006). Median tricuspid regurgitation gradient PRE was 83 mmHg (57-196) compared to 55 mmHg POST (33-151) (p = 0.002). A subset of dogs with moderate to severe pulmonary hypertension present with diffuse, patchy alveolar infiltrates consistent with non-cardiogenic pulmonary edema. The typical clinical presentation is acute dyspnea and syncope, often in conjunction with heart murmurs suggestive of valvular insufficiency. This constellation of signs may lead to an initial misdiagnosis of congestive heart failure or pneumonia; however, these dogs clinically and radiographically improve with the initiation of sildenafil. Copyright © 2015 Elsevier B.V. All rights reserved.

Cardiovascular tissue engineering: where we come from and where are we now?

PubMed

Smit, Francis E; Dohmen, Pascal M

2015-01-27

Abstract Tissue engineering was introduced by Vacanti and Langer in the 80's, exploring the potential of this new technology starting with the well-known "human ear on the mouse back". The goal is to create a substitute which supplies an individual therapy for patients with regeneration, remodeling and growth potential. The growth potential of these subjects is of special interest in congenital cardiac surgery, avoiding repeated interventions and surgery. Initial applications of tissue engineered created substitutes were relatively simple cardiovascular grafts seeded initially by end-differentiated autologous endothelial cells. Important data were collected from these initial clinical autologous endothelial cell seeded grafts in peripheral and coronary vessel disease. After these initial successfully implantation bone marrow cell were used to seed patches and pulmonary conduits were implanted in patients. Driven by the positive results of tissue engineered material implanted under low pressure circumstances, first tissue engineered patches were implanted in the systemic circulation followed by the implantation of tissue engineered aortic heart valves. Tissue engineering is an extreme dynamic technology with continuously modifications and improvements to optimize clinical products. New technologies are unified and so this has also be done with tissue engineering and new application features, so called transcatheter valve intervention. First studies are initiated to apply tissue engineered heart valves with this new transcatheter delivery system less invasive. Simultaneously studies have been started on tissue engineering of so-called whole organs since organ transplantation is restricted due to donor shortage and tissue engineering could overcome this problem. Initial studies of whole heart engineering in the rat model are promising and larger size models are initiated.

Pulmonary Function in Middle-Aged Patients With Idiopathic Scoliosis With Onset Before the Age of 10 Years.

PubMed

Danielsson, Aina J; Ekerljung, Linda; Hallerman, Kerstin Lofdahl

2015-09-01

Consecutive patients with idiopathic scoliosis diagnosed before age 10 attended a clinical follow-up at least 10 years after treatment. To evaluate the pulmonary function in adulthood after treatment with brace or surgery before maturity. Long-term studies of these patients have not been published. One hundred twenty-four patients (69% of the original group) underwent radiography, spirometry, and answered symptom questionnaires. A total of 73 patients had spirometries before treatment enabling longitudinal evaluation. Overall, 68 braced only (BT) and 56 surgically treated (ST) were analyzed in detail. A population-based control group was used. At follow-up, the mean age was 41.5 years and the mean curve size 36 degrees (26% of the curves >45 degrees). The full patient group had a significantly reduced pulmonary function (as measured by the forced vital capacity [FVC], percentage of predicted) compared with the control group, mean 85% versus 102% (p < .0001). Both subgroups of BT and ST patients showed a significant reduction, more in the ST than the BT group (means 79% and 90%, respectively, p = .0003). The most important risk factor for a low lung function at follow-up was a low initial FVC value. Initial curve size correlated with pulmonary function both before treatment and at follow-up. Most surgically treated patients, who had larger curves before treatment, did not improve their pulmonary function after surgery. Both braced and surgically treated patients had reduced pulmonary function at the age of around 40 years. The pulmonary function did not worsen over time in most patients. There was no difference in terms of symptoms between patient groups and controls. Initial curve size was found to be of great importance for pulmonary function. Initial spirometry and follow-up in selected patients is important. III. Copyright © 2015 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.

Neutral lipid trafficking regulates alveolar type II cell surfactant phospholipid and surfactant protein expression.

PubMed

Torday, John; Rehan, Virender

2011-08-01

Adipocyte differentiation-related protein (ADRP) is a critically important protein that mediates lipid uptake, and is highly expressed in lung lipofibroblasts (LIFs). Triacylglycerol secreted from the pulmonary circulation and stored in lipid storage droplets is a robust hormonal-, growth factor-, and stretch-regulated precursor for surfactant phospholipid synthesis by alveolar type II epithelial (ATII) cells. A549 lung epithelial cells rapidly take up green fluorescent protein (GFP)-ADRP fusion protein-associated lipid droplets (LDs) in a dose-dependent manner. The LDs initially localize to the perinuclear region of the cell, followed by localization in the cytoplasm. Uptake of ADRP-LDs causes a time- and dose-dependent increase in surfactant protein-B (SP-B) expression. This mechanism can be inhibited by either actinomycin D or cycloheximide, indicating that ADRP-LDs induce newly synthesized SP-B. ADRP-LDs concomitantly stimulate saturated phosphatidylcholine (satPC) synthesis by A549 cells, which is inhibited by ADRP antibody, indicating that this is a receptor-mediated mechanism. Intravenous administration of GFP-ADRP LDs to adult rats results in dose-dependent increases in lung ADRP and SP-B expression. These data indicate that lipofibroblast-derived ADRP coordinates ATII cells' synthesis of the surfactant phospholipid-protein complex by stimulating both satPC and SP-B. The authors propose, therefore, that ADRP is the physiologic determinant for the elusive coordinated, stoichiometric synthesis of surfactant phospholipid and protein by pulmonary ATII cells.

Model of complete separation of the hepatic veins from the systemic venous system.

PubMed

Brizard, C P; Goussef, N; Chachques, J C; Carpentier, A F

2000-12-01

In patients undergoing a Fontan operation, partial diversion of the hepatic veins to the pulmonary venous atrium has been tried with various techniques. They failed because of the development of intrahepatic collaterals leading to an unacceptable right-to-left shunting. We postulate that to avoid the formation of intrahepatic collaterals, the totality of the liver has to be drained into the same pressure compartment. We have designed a model of cavopulmonary anastomosis in which a prosthetic conduit reproduces an azygos continuation, associated with the diversion of the totality of the hepatic venous return. This article reports on the early hemodynamics and the fate of the separation of the two venous compartments in long-term survivors. Eighteen goats were operated on; the pulmonary artery and hepatic vein pressures were recorded. During month 2, an opacification of the inferior vena cava and the cavopulmonary connection was performed. Between months 6 and 14, another opacification was performed, together with pressure recording at both ends of the conduit. Postoperatively the pulmonary artery pressure was pulsatile with a mean of 10 mm Hg and the hepatic vein pressure was 0 mm Hg. The first angiogram showed patent tubes with fast progression of the contrast. Throughout the inferior vena cava injection, there was no opacification of the portal or hepatic veins. The late study showed a narrowed conduit in all animals. During the injection, a collateral was injected, feeding into the inferior mesenteric vein. No collateral circulation could be seen draining directly into the liver. The median gradient between the two ends of the conduit was 11 mm Hg. The isolation of the entire hepatic venous drainage is feasible and efficient for the separation of two pressure compartments. No intrahepatic collaterals are observed with this model at short- or long-term follow-up. The separation of the hepatic venous drainage should persist without collateral circulation as long as the inferior vena cava pressure stays at the levels observed in Fontan circulation.

Inhaled concentrated ambient particles are associated with hematologic and bronchoalveolar lavage changes in canines.

PubMed Central

Clarke, R W; Coull, B; Reinisch, U; Catalano, P; Killingsworth, C R; Koutrakis, P; Kavouras, I; Murthy, G G; Lawrence, J; Lovett, E; Wolfson, J M; Verrier, R L; Godleski, J J

2000-01-01

Pulmonary inflammatory and hematologic responses of canines were studied after exposure to concentrated ambient particles (CAPs) using the Harvard ambient particle concentrator (HAPC). For pulmonary inflammatory studies, normal dogs were exposed in pairs to either CAPs or filtered air (paired studies) for 6 hr/day on 3 consecutive days. For hematologic studies, dogs were exposed for 6 hr/day for 3 consecutive days with one receiving CAPs while the other was simultaneously exposed to filtered air; crossover of exposure took place the following week (crossover studies). Physicochemical characterization of CAPs exposure samples included measurements of particle mass, size distribution, and composition. No statistical differences in biologic responses were found when all CAPs and all sham exposures were compared. However, the variability in biologic response was considerably higher with CAPs exposure. Subsequent exploratory graphical analyses and mixed linear regression analyses suggested associations between CAPs constituents and biologic responses. Factor analysis was applied to the compositional data from paired and crossover experiments to determine elements consistently associated with each other in CAPs samples. In paired experiments, four factors were identified; in crossover studies, a total of six factors were observed. Bronchoalveolar lavage (BAL) and hematologic data were regressed on the factor scores. Increased BAL neutrophil percentage, total peripheral white blood cell (WBC) counts, circulating neutrophils, and circulating lymphocytes were associated with increases in the aluminum/silicon factor. Increased circulating neutrophils and increased BAL macrophages were associated with the vanadium/nickel factor. Increased BAL neutrophils were associated with the bromine/lead factor when only the compositional data from the third day of CAPs exposure were used. Significant decreases in red blood cell counts and hemoglobin levels were correlated with the sulfur factor. BAL or hematologic parameters were not associated with increases in total CAPs mass concentration. These data suggest that CAPs inhalation is associated with subtle alterations in pulmonary and systemic cell profiles, and specific components of CAPs may be responsible for these biologic responses. PMID:11133399

Rare presentation of intralobar pulmonary sequestration associated with repeated episodes of ventricular tachycardia

PubMed Central

Rao, D Sheshagiri; Barik, Ramachandra

2016-01-01

Arterial supply of an intralobar pulmonary sequestration (IPS) from the coronary circulation is extremely rare. A significant coronary steal does not occur because of dual or triple sources of blood supply to sequestrated lung tissue. We present a 60-year-old woman who presented to us with repeated episodes of monomorphic ventricular tachycardia (VT) in last 3 mo. Radio frequency ablation was ineffective. On evaluation, she had right lower lobe IPS with dual arterial blood supply, i.e., right pulmonary artery and the systemic arterial supply from the right coronary artery (RCA). Stress myocardial perfusion scan revealed significant inducible ischemia in the RCA territory. Coronary angiogram revealed critical stenosis of proximal RCA just after the origin of the systemic artery supplying IPS. The critical stenosis in the RCA was stented. At 12 mo follow-up, she had no further episodes of VT or angina. PMID:27468336

Rare presentation of intralobar pulmonary sequestration associated with repeated episodes of ventricular tachycardia.

PubMed

Rao, D Sheshagiri; Barik, Ramachandra

2016-07-26

Arterial supply of an intralobar pulmonary sequestration (IPS) from the coronary circulation is extremely rare. A significant coronary steal does not occur because of dual or triple sources of blood supply to sequestrated lung tissue. We present a 60-year-old woman who presented to us with repeated episodes of monomorphic ventricular tachycardia (VT) in last 3 mo. Radio frequency ablation was ineffective. On evaluation, she had right lower lobe IPS with dual arterial blood supply, i.e., right pulmonary artery and the systemic arterial supply from the right coronary artery (RCA). Stress myocardial perfusion scan revealed significant inducible ischemia in the RCA territory. Coronary angiogram revealed critical stenosis of proximal RCA just after the origin of the systemic artery supplying IPS. The critical stenosis in the RCA was stented. At 12 mo follow-up, she had no further episodes of VT or angina.

Circulating big endothelin-1: an active role in pulmonary thromboendarterectomy?

PubMed

Langer, Frank; Bauer, Michael; Tscholl, Dietmar; Schramm, Rene; Kunihara, Takashi; Lausberg, Henning; Georg, Thomas; Wilkens, Heinrike; Schäfers, Hans-Joachim

2005-11-01

Pulmonary thromboendarterectomy is an effective treatment for patients with chronic thromboembolic pulmonary hypertension. The early postoperative course may be associated with pulmonary vasoconstriction and profound systemic vasodilation. We investigated the potential involvement of endothelins in these hemodynamic alterations. Seventeen patients with chronic thromboembolic pulmonary hypertension (pulmonary vascular resistance, 1015 +/- 402 dyne x s x cm(-5) [mean +/- SD]) underwent pulmonary thromboendarterectomy with cardiopulmonary bypass and deep hypothermic circulatory arrest. Peripheral arterial blood samples were drawn before sternotomy, during cardiopulmonary bypass before and after deep hypothermic circulatory arrest, and 0, 8, 16, and 24 hours after surgery and were analyzed for big endothelin-1. The patients were divided into 2 groups according to whether their preoperative big endothelin-1 plasma level was above or below the cutoff point of 2.1 pg/mL, as determined by receiver operating characteristic curve analysis (group A, big endothelin-1 <2.1 pg/mL, n = 8; group B, big endothelin-1 > or =2.1 pg/mL, n = 9). Patients in group B, with higher preoperative big endothelin-1 levels (3.2 +/- 1.0 pg/mL vs 1.5 +/- 0.4 pg/mL; P < .001), were poorer operative candidates (preoperative mean pulmonary artery pressure, 51.3 +/- 7.1 mm Hg vs 43.6 +/- 6.2 mm Hg; P = .006) and had a poorer outcome (mean pulmonary artery pressure 24 hours after surgery, 32.6 +/- 9.5 mm Hg vs 21.8 +/- 6.2 mm Hg; P < .001). Positive correlations were found between preoperative big endothelin-1 levels and preoperative mean pulmonary artery pressure (r = 0.56; P = .02) as well as postoperative mean pulmonary artery pressure at 0 hours (r = 0.70; P = .002) and 24 hours (r = 0.63; P = .006) after surgery. Preoperative big endothelin-1 levels predicted outcome (postoperative mean pulmonary artery pressure at 24 hours after surgery) after pulmonary thromboendarterectomy (area under the receiver operating characteristic curve, 0.85). Peak big endothelin-1 levels also correlated with maximal vasopressor dosage (r = 0.65; P = .004). Preoperative big endothelin-1 levels seem to correlate with the hemodynamic alterations observed in pulmonary thromboendarterectomy and may be used to predict hemodynamic outcome after pulmonary thromboendarterectomy.

Creation of aorto-pulmonary window with pulmonary artery band is not good palliation for hypoplastic left heart syndrome.

PubMed

Hosein, Riad B M; Mehta, Chetan; Stickley, John; Mcguirk, Simon P; Jones, Timothy J; Brawn, William J; Barron, David J

2007-11-01

A small sub-group of patients with hypoplastic left heart syndrome (HLHS) have normal-sized ascending aorta and arch. An alternative to the Norwood I procedure in these patients is the creation of an aorto-pulmonary (AP) window with a distal pulmonary artery band (PAB). We reviewed our experience with this technique and compared outcomes to the Norwood procedure for HLHS. All patients treated for HLHS in a single institution between 1992 and 2005 were analysed. This identified 13 patients treated with AP window and PAB compared to 333 patients undergoing stage I Norwood procedure. An unrestrictive AP window was created and the main PA was banded. Patient records and echocardiograms were analysed. Median follow-up was 10 (IQR 0-655) days and 100% complete. There were seven early deaths (54%) in the AP window group and two conversions to Norwood circulation. This was a significantly worse outcome than for the Norwood procedure over the same period, which had an early mortality of 29% (p=0.03). Kaplan-Meier actuarial analysis demonstrated a continued survival benefit of the Norwood group at 6 months (p=0.0005). Deaths were due to either low cardiac output syndrome (n=4) or sudden unheralded arrest (n=3). This occurred despite aortic cross-clamp and circulatory arrest times being significantly lower in the AP window group compared to the Norwood group (35+/-27 vs 55+/-16 min, p<0.01 and 16+/-29 vs 55+/-20 min, p<0.01, respectively). No differences in arterial saturations or systolic blood pressure existed between the groups, but diastolic blood pressure was significantly lower in the AP window group at 27+/-10 mmHg compared to 42+/-8 mmHg in the Norwood group (p=0.01) with evidence of flow reversal in the descending aorta. Differences in diastolic blood pressure between groups were abolished after conversion to stage II. Despite favourable anatomy and shorter ischaemic times, the AP window/PAB technique has a poor outcome compared to the Norwood procedure for HLHS. Low diastolic blood pressure with reversal of descending aortic flow in diastole was a feature of the AP window/PAB circulation. We recommend the Norwood procedure for these sub-types. This may have implications for newer 'hybrid' procedures for HLHS which create a similar palliative circulation.

Fibrosis-Related Biomarkers and Risk of Total and Cause-Specific Mortality

PubMed Central

Agarwal, Isha; Glazer, Nicole L.; Barasch, Eddy; Biggs, Mary L.; Djoussé, Luc; Fitzpatrick, Annette L.; Gottdiener, John S.; Ix, Joachim H.; Kizer, Jorge R.; Rimm, Eric B.; Siscovick, David S.; Tracy, Russell P.; Zieman, Susan J.; Mukamal, Kenneth J.

2014-01-01

Fibrosis has been implicated in diverse diseases of the liver, kidney, lungs, and heart, but its importance as a risk factor for mortality remains unconfirmed. We determined the prospective associations of 2 complementary biomarkers of fibrosis, transforming growth factor-β (TGF-β) and procollagen type III N-terminal propeptide (PIIINP), with total and cause-specific mortality risks among community-living older adults in the Cardiovascular Health Study (1996–2010). We measured circulating TGF-β and PIIINP levels in plasma samples collected in 1996 and ascertained the number of deaths through 2010. Both TGF-β and PIIINP were associated with elevated risks of total and pulmonary mortality after adjustment for sociodemographic, clinical, and biochemical risk factors. For total mortality, the hazard ratios per doubling of TGF-β and PIIINP were 1.09 (95% confidence interval (CI): 1.01, 1.17; P = 0.02) and 1.14 (CI: 1.03, 1.27; P = 0.01), respectively. The corresponding hazard ratios for pulmonary mortality were 1.27 (CI: 1.01, 1.60; P = 0.04) for TGF-β and 1.52 (CI: 1.11, 2.10; P = 0.01) for PIIINP. Associations of TGF-β and PIIINP with total and pulmonary mortality were strongest among individuals with higher C-reactive protein concentrations (P for interaction < 0.05). Our findings provide some of the first large-scale prospective evidence that circulating biomarkers of fibrosis measured late in life are associated with death. PMID:24771724

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

NASA Technical Reports Server (NTRS)

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

2002-01-01

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

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.

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.

Combined usage of inhaled and intravenous milrinone in pulmonary hypertension after heart valve surgery.

PubMed

Carev, Mladen; Bulat, Cristijan; Karanović, Nenad; Lojpur, Mihajlo; Jercić, Antonio; Nenadić, Denis; Marovih, Zlatko; Husedzinović, Ino; Letica, Dalibor

2010-09-01

Secondary pulmonary hypertension is a frequent condition after heart valve surgery. It may significantly complicate the perioperative management and increase patients' morbidity and mortality. The treatment has not been yet completely defined principally because of lack of the selectivity of drugs for the pulmonary vasculature. The usage of inhaled milrinone could be the possible therapeutic option. Inodilator milrinone is commonly used intravenously for patients with pulmonary hypertension and ventricular dysfunction in cardiac surgery. The decrease in systemic vascular resistance frequently necessitates concomitant use of norepinephrine. Pulmonary vasodilators might be more effective and also devoid of potentially dangerous systemic side effects if applied by inhalation, thus acting predominantly on pulmonary circulation. There are only few reports of inhaled milrinone usage in adult post cardiac surgical patients. We reported 2 patients with severe pulmonary hypertension after valve surgery. Because of desperate clinical situation, we decided to use the combination of inhaled and intravenous milrinone. Inhaled milrinone was delivered by means of pneumatic medication nebulizer dissolved with saline in final concentration of 0.5 mg/ml. The nebulizer was attached to the inspiratory limb of the ventilator circuit, just before the Y-piece. We obtained satisfactory reduction in mean pulmonary artery pressure in both patients, and they were successfully extubated and discharged. Although it is a very small sample of patients, we conclude that the combination of inhaled and intravenous milrinone could be an effective treatment of secondary pulmonary hypertension in high-risk cardiac valve surgery patient. The exact indications for inhaled milrinone usage, optimal concentrations for this route, and the beginning and duration of treatment are yet to be determined.

Perinatal hypoxia increases susceptibility to high-altitude polycythemia and attendant pulmonary vascular dysfunction

PubMed Central

Gonzales, Marcelino; Rodriguez, Armando; Bellido, Diva; Salmon, Carlos Salinas; Ladenburger, Anne; Reardon, Lindsay; Vargas, Enrique; Moore, Lorna G.

2015-01-01

Perinatal exposures exert a profound influence on physiological function, including developmental processes vital for efficient pulmonary gas transfer throughout the lifespan. We extend the concept of developmental programming to chronic mountain sickness (CMS), a debilitating syndrome marked by polycythemia, ventilatory impairment, and pulmonary hypertension that affects ∼10% of male high-altitude residents. We hypothesized that adverse perinatal oxygenation caused abnormalities of ventilatory and/or pulmonary vascular function that increased susceptibility to CMS in adulthood. Subjects were 67 male high-altitude (3,600–4,100 m) residents aged 18–25 yr with excessive erythrocytosis (EE, Hb concentration ≥18.3 g/dl), a preclinical form of CMS, and 66 controls identified from a community-based survey (n = 981). EE subjects not only had higher Hb concentrations and erythrocyte counts, but also lower alveolar ventilation, impaired pulmonary diffusion capacity, higher systolic pulmonary artery pressure, lower pulmonary artery acceleration time, and more frequent right ventricular hypertrophy, than controls. Compared with controls, EE subjects were more often born to mothers experiencing hypertensive complications of pregnancy and hypoxia during the perinatal period, with each increasing the risk of developing EE (odds ratio = 5.25, P = 0.05 and odds ratio = 6.44, P = 0.04, respectively) after other factors known to influence EE status were taken into account. Adverse perinatal oxygenation is associated with increased susceptibility to EE accompanied by modest abnormalities of the pulmonary circulation that are independent of increased blood viscosity. The association between perinatal hypoxia and EE may be due to disrupted alveolarization and microvascular development, leading to impaired gas exchange and/or pulmonary hypertension. PMID:26092986

Perinatal hypoxia increases susceptibility to high-altitude polycythemia and attendant pulmonary vascular dysfunction.

PubMed

Julian, Colleen Glyde; Gonzales, Marcelino; Rodriguez, Armando; Bellido, Diva; Salmon, Carlos Salinas; Ladenburger, Anne; Reardon, Lindsay; Vargas, Enrique; Moore, Lorna G

2015-08-15

Perinatal exposures exert a profound influence on physiological function, including developmental processes vital for efficient pulmonary gas transfer throughout the lifespan. We extend the concept of developmental programming to chronic mountain sickness (CMS), a debilitating syndrome marked by polycythemia, ventilatory impairment, and pulmonary hypertension that affects ∼10% of male high-altitude residents. We hypothesized that adverse perinatal oxygenation caused abnormalities of ventilatory and/or pulmonary vascular function that increased susceptibility to CMS in adulthood. Subjects were 67 male high-altitude (3,600-4,100 m) residents aged 18-25 yr with excessive erythrocytosis (EE, Hb concentration ≥18.3 g/dl), a preclinical form of CMS, and 66 controls identified from a community-based survey (n = 981). EE subjects not only had higher Hb concentrations and erythrocyte counts, but also lower alveolar ventilation, impaired pulmonary diffusion capacity, higher systolic pulmonary artery pressure, lower pulmonary artery acceleration time, and more frequent right ventricular hypertrophy, than controls. Compared with controls, EE subjects were more often born to mothers experiencing hypertensive complications of pregnancy and hypoxia during the perinatal period, with each increasing the risk of developing EE (odds ratio = 5.25, P = 0.05 and odds ratio = 6.44, P = 0.04, respectively) after other factors known to influence EE status were taken into account. Adverse perinatal oxygenation is associated with increased susceptibility to EE accompanied by modest abnormalities of the pulmonary circulation that are independent of increased blood viscosity. The association between perinatal hypoxia and EE may be due to disrupted alveolarization and microvascular development, leading to impaired gas exchange and/or pulmonary hypertension. Copyright © 2015 the American Physiological Society.

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.

Cement pulmonary embolism after vertebroplasty.

PubMed

Sifuentes Giraldo, Walter Alberto; Lamúa Riazuelo, José Ramón; Gallego Rivera, José Ignacio; Vázquez Díaz, Mónica

2013-01-01

In recent years, the use of vertebral cementing techniques for vertebroplasty and kyphoplasty has spread for the treatment of pain associated with osteoporotic vertebral compression fractures. This is also associated with the increased incidence of complications related with these procedures, the most frequent being originated by leakage of cementation material. Cement can escape into the vertebral venous system and reach the pulmonary circulation through the azygous system and cava vein, producing a cement embolism. This is a frequent complication, occurring in up to 26% of patients undergoing vertebroplasty but, since most patients have no clinical or hemodynamical repercussion, this event usually goes unnoticed. However, some serious, and even fatal cases, have been reported. We report the case of a 74-year-old male patient who underwent vertebroplasty for persistent pain associated with osteoporotic L3 vertebral fracture and who developed a cement leak into the cava vein and right pulmonary artery during the procedure. Although he developed a pulmonary cement embolism, the patient remained asymptomatic and did not present complications during follow-up. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Right Ventricular Hemodynamics in Patients with Pulmonary Hypertension

NASA Astrophysics Data System (ADS)

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

2012-11-01

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

What radiologists need to know about the pulmonary-systemic flow ratio (Qp/Qs): what it is, how to calculate it, and what it is for.

PubMed

Marín Rodríguez, C; Sánchez Alegre, M L; Lancharro Zapata, Á; Alarcón Rodríguez, J

2015-01-01

Cardiac magnetic resonance imaging (cMRI) provides abundant morphological and functional information in the study of congenital heart disease. The functional information includes pulmonary output and systemic output; the ratio between these two (Qp/Qs) is the shunt fraction. After birth, in normal conditions the pulmonary output is practically identical to the systemic output, so Qp/Qs = 1. In patients with « shunts » between the systemic and pulmonary circulations, the ratio changes, and the interpretation of these findings varies in function of the location of the shunt (intracardiac or extracardiac) and of the associated structural or postsurgical changes. We review the concept of Qp/Qs; the methods to calculate it, with special emphasis on cMRI; and the meaning of the results obtained. We place special emphasis on the relevance of these findings depending on the underlying disease and the treatment the patient has undergone. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

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

Lung clearance of /sup 99m/Tc-DTPA in patients with acute lung injury and pulmonary edema

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

Coates, G.; O'Brodovich, H.; Dolovich, M.

1988-07-01

Several acute and chronic conditions that alter the integrity of the pulmonary epithelium increased the rate of absorption or clearance into the circulation of small solutes deposited in the alveoli. Technetium 99m diethylenetriamine pentaacetic acid can be deposited in the lungs as a submicronic aerosol and its rate of clearance measured with a gamma camera or simple probe. This clearance technique is currently being used to evaluate patients who have developed pulmonary edema and also to detect those patients from a high risk group who are likely to develop adult respiratory distress syndrome (ARDS). Its role in the evaluation ofmore » patients with pulmonary edema is still under active investigation. It is clear that a single measurement in patients who smoke is not useful, but repeated measurements may provide important information. The lung clearance measurement is very sensitive to changes in epithelial integrity but is not specific for ARDS. It may be most useful in combination with other predictive tests or when the clearance rate is normal. 54 references.« less

Eight Sages over Five Centuries Share Oxygen's Discovery

ERIC Educational Resources Information Center

Severinghaus, John W.

2016-01-01

During the last century, historians have discovered that between the 13th and 18th centuries, at least six sages discovered that the air we breathe contains something that we need and use. Ibn al-Nafis (1213-1288) in Cairo and Michael Servetus (1511-1553) in France accurately described the pulmonary circulation and its effect on blood color.…

75 FR 5847 - Section 5309 Bus and Bus Facilities Livability Initiative and Urban Circulator Program Grants

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-04

... Livability Initiative and Urban Circulator Program Grants AGENCY: Federal Transit Administration (FTA), DOT. ACTION: Notice to Extend Application Deadline for the Bus and Bus Facilities and Urban Circulator..., Transportation Equity Act: A Legacy for Users (SAFETEA-LU), Public Law 109-59, August 10, 2005. The Urban...

Development of the Technologies for Stabilization Treatment of the Water of the Recycling Cooling Systems at Thermal Power Plants

NASA Astrophysics Data System (ADS)

Vlasov, S. M.; Chichirova, N. D.; Chichirov, A. A.; Vlasova, A. Yu.; Filimonova, A. A.; Prosvirnina, D. V.

2018-02-01

A turbine-condensate cooling system is one of the less stable and most hard-to-control systems of maintaining optimal water chemistry. A laboratory recycling cooling water test facility, UVO-0.3, was developed for physical simulation of innovative zero-discharge water chemistry conditions and improvement of technological flowcharts of stabilization treatment of the initial and circulating water of the recycling cooling systems at thermal power plants. Experiments were conducted in the UVO-0.3 facility to investigate the processes that occur in the recycling water supply system and master new technologies of stabilization of the initial and circulating water. It is shown that, when using untreated initial water, scaling cannot be prevented even under low concentration levels. The main reason for the activation of scale depositing is the desorption of carbon dioxide that results in alkalization of the circulating water and, as a consequence, a displacement of the chemical reaction equilibrium towards the formation of slightly soluble hardness ions. Some techniques, viz., liming and alkalization of the initial water and the by-pass treatment of the circulating water, are considered. New engineering solutions have been developed for reducing the amount of scale-forming substances in the initial and circulating water. The best results were obtained by pretreating the initial water with alkalizing agents and simultaneously bypassing and treating part of the circulating water. The obtained experimental data underlie the process flowcharts of stabilization treatment of the initial and circulating TPP water that ensure scale-free and noncorrosive operation and meet the corresponding environmental requirements. Under the bypassing, the specific rates of the agents and the residual hardness are reduced compared with the conventional pretreatment.

Pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis.

PubMed

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

2017-03-22

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

Type 2 diabetes mellitus coincident with pulmonary tuberculosis is associated with heightened systemic type 1, type 17, and other proinflammatory cytokines.

PubMed

Kumar, Nathella Pavan; Sridhar, Rathinam; Banurekha, Vaithilingam V; Jawahar, Mohideen S; Fay, Michael P; Nutman, Thomas B; Babu, Subash

2013-10-01

Type 2 diabetes mellitus is a major risk factor for the development of active tuberculosis, although the biological basis underlying this susceptibility remains poorly characterized. To identify the influence of coincident diabetes mellitus on cytokine levels in pulmonary tuberculosis, we examined circulating levels of a panel of cytokines and chemokines in the plasma of individuals with tuberculosis with diabetes and compared them with those of individuals without diabetes. Tuberculosis with diabetes is characterized by elevated circulating levels of type 1 (IFN-γ, tumor necrosis factor-α, and IL-2), type 2 (IL-5), and type 17 (IL-17A) cytokines but decreased circulating levels of IL-22. This was associated with increased systemic levels of other proinflammatory cytokines (IL-1β, IL-6, and IL-18) and an antiinflammatory cytokine (IL-10) but not type 1 IFNs. Moreover, tuberculosis antigen-stimulated whole blood also showed increased levels of proinflammatory cytokines. Finally, type 1 and type 17 cytokines in plasma exhibit a significant positive correlation with hemoglobin A1C levels, indicating that impaired control of diabetes is associated with this proinflammatory milieu. Multivariate analysis revealed that the association of proinflammatory cytokines with diabetes mellitus was not influenced by age, sex, or other metabolic parameters. Our data reveal that tuberculosis with diabetes is characterized by heightened cytokine responsiveness, indicating that chronic inflammation underlying type 2 diabetes potentially contributes to increased immune pathology and poor control in tuberculosis infection.

Association of Wolbachia with heartworm disease in cats and dogs.

PubMed

Dingman, Patricia; Levy, Julie K; Kramer, Laura H; Johnson, Calvin M; Lappin, Michael R; Greiner, Ellis C; Courtney, Charles H; Tucker, Sylvia J; Morchon, Rodrigo

2010-05-28

Although the presence of adult Dirofilaria immitis in the pulmonary arteries and its associated arteritis and thromboembolic disease can explain some of the manifestations of canine and feline heartworm disease, the cause of other findings remains unclear. Cats with D. immitis antibodies but lacking adult parasites in the pulmonary arteries frequently develop histological lesions of the airways, resulting in a condition termed Heartworm-Associated Respiratory Disease. All D. immitis parasites harbor Wolbachia pipientis bacteria and D. immitis-infected animals can have circulating Wolbachia antibodies and pro-inflammatory Wolbachia antigens (WSP) deposited in tissues. Little is known about the role that Wolbachia plays in lung disease of animals naturally infected with D. immitis. The purpose of this study was to determine the contribution of Wolbachia to the pathogenesis of natural heartworm disease in cats and dogs. We hypothesized that animals having sufficient Wolbachia burden to be detected in lung tissue by immunohistochemistry and/or polymerase chain reaction (PCR) would have more severe pulmonary disease than those with bacteria below the limits of detection. We further hypothesized that animals that were immunoreactive to pro-inflammatory WSP would have more severe pulmonary lesions than those that were seronegative for WSP antibodies. Blood and lung tissue samples were collected from cats and dogs representing three different D. immitis infection statuses: heartworm-free, heartworm-exposed, heartworm-infected. There was a positive but weak correlation between the magnitude of D. immitis antibody titers and WSP titers in cats (r=0.57, p<0.001) and in dogs (r=0.39, p<0.001). Pulmonary lesions were more common in HW-infected animals than in HW-free animals. Pulmonary arteriolar occlusion was more common in HW-infected cats (57%; p=0.003) than in HW-infected dogs (17%). Although pulmonary lesions were most common in HW-infected animals, there was no clear additive effect when either Wolbachia DNA/WSP was detected in lung tissue or when circulating Wolbachia antibodies were detected. There were no significant differences in the magnitude of pulmonary lesion scores within each HW-infection status group regardless of whether Wolbachia DNA/WSP or antibodies were detected. The relationship between Wolbachia and lung pathology in heartworm-infected animals remains to be determined. The lack of clear evidence for a role of Wolbachia in heartworm disease creates a dilemma for veterinarians treating animals in D. immitis-endemic areas. Although the indiscriminant use of antibiotics should be avoided, many clinicians prescribe doxycycline based on the favorable responses observed in human filarial diseases and promising results from the first published studies of doxycycline use in D. immitis-infected dogs. (c) 2010 Elsevier B.V. All rights reserved.

Fluid dynamics in flexible tubes: An application to the study of the pulmonary circulation

NASA Technical Reports Server (NTRS)

Kuchar, N. R.

1971-01-01

Based on an analysis of unsteady, viscous flow through distensible tubes, a lumped-parameter model for the dynamics of blood flow through the pulmonary vascular bed was developed. The model is nonlinear, incorporating the variation of flow resistance with transmural pressure. Solved using a hybrid computer, the model yields information concerning the time-dependent behavior of blood pressures, flow rates, and volumes in each important class of vessels in each lobe of each lung in terms of the important physical and environmental parameters. Simulations of twenty abnormal or pathological situations of interest in environmental physiology and clinical medicine were performed. The model predictions agree well with physiological data.

Hantavirus Reservoir Hosts Associated with Peridomestic Habitats in Argentina

PubMed Central

Pini, Noemí; Bolpe, Jorge; Levis, Silvana; Mills, James; Segura, Elsa; Guthmann, Nadia; Cantoni, Gustavo; Becker, José; Fonollat, Ana; Ripoll, Carlos; Bortman, Marcelo; Benedetti, Rosendo; Sabattini, Marta; Enria, Delia

1999-01-01

Five species of sigmodontine rodents have been identified in Argentina as the putative reservoirs of six circulating hantavirus genotypes. Two species of Oligoryzomys are associated with the genotypes causing hantavirus pulmonary syndrome, Oligoryzomys flavescens for Lechiguanas and O. longicaudatus for Andes and Oran genotypes. Reports of human cases of hantavirus pulmonary syndrome prompted rodent trapping (2,299 rodents of 32 species during 27,780 trap nights) at potential exposure sites in three disease-endemic areas. Antibody reactive to Sin Nombre virus was found in six species, including the known hantavirus reservoir species. Risk for peridomestic exposure to host species that carry recognized human pathogens was high in all three major disease-endemic areas. PMID:10603213

Patent ductus arteriosus: patho-physiology, hemodynamic effects and clinical complications.

PubMed

Capozzi, Giovanbattista; Santoro, Giuseppe

2011-10-01

During fetal life, patent arterial duct diverts placental oxygenated blood from the pulmonary artery into the aorta by-passing lungs. After birth, decrease of prostacyclins and prostaglandins concentration usually causes arterial duct closure. This process may be delayed, or may even completely fail in preterm infants with arterial duct still remaining patent. If that happens, blood flow by-pass of the systemic circulation through the arterial duct results in pulmonary overflow and systemic hypoperfusion. When pulmonary flow is 50% higher than systemic flow, a hemodynamic "paradox" results, with an increase of left ventricular output without a subsequent increase of systemic output. Cardiac overload support neuro-humoral effects (activation of sympathetic nervous system and renin-angiotensin system) that finally promote heart failure. Moreover, increased pulmonary blood flow can cause vascular congestion and pulmonary edema. However, the most dangerous effect is cerebral under-perfusion due to diastolic reverse-flow and resulting in cerebral hypoxia. At last, blood flow decreases through the abdominal aorta, reducing perfusion of liver, gut and kidneys and may cause hepatic failure, renal insufficiency and necrotizing enterocolitis. Conclusions Large patent arterial duct may cause life-threatening multi-organ effects. In pre-term infant early diagnosis and timely effective treatment are cornerstones in the prevention of cerebral damage and long-term multi-organ failure.

Pulmonary vascular dysfunction in ARDS

PubMed Central

2014-01-01

Acute respiratory distress syndrome (ARDS) is characterised by diffuse alveolar damage and is frequently complicated by pulmonary hypertension (PH). Multiple factors may contribute to the development of PH in this setting. In this review, we report the results of a systematic search of the available peer-reviewed literature for papers that measured indices of pulmonary haemodynamics in patients with ARDS and reported on mortality in the period 1977 to 2010. There were marked differences between studies, with some reporting strong associations between elevated pulmonary arterial pressure or elevated pulmonary vascular resistance and mortality, whereas others found no such association. In order to discuss the potential reasons for these discrepancies, we review the physiological concepts underlying the measurement of pulmonary haemodynamics and highlight key differences between the concepts of resistance in the pulmonary and systemic circulations. We consider the factors that influence pulmonary arterial pressure, both in normal lungs and in the presence of ARDS, including the important effects of mechanical ventilation. Pulmonary arterial pressure, pulmonary vascular resistance and transpulmonary gradient (TPG) depend not alone on the intrinsic properties of the pulmonary vascular bed but are also strongly influenced by cardiac output, airway pressures and lung volumes. The great variability in management strategies within and between studies means that no unified analysis of these papers was possible. Uniquely, Bull et al. (Am J Respir Crit Care Med 182:1123–1128, 2010) have recently reported that elevated pulmonary vascular resistance (PVR) and TPG were independently associated with increased mortality in ARDS, in a large trial with protocol-defined management strategies and using lung-protective ventilation. We then considered the existing literature to determine whether the relationship between PVR/TPG and outcome might be causal. Although we could identify potential mechanisms for such a link, the existing evidence does not allow firm conclusions to be drawn. Nonetheless, abnormally elevated PVR/TPG may provide a useful index of disease severity and progression. Further studies are required to understand the role and importance of pulmonary vascular dysfunction in ARDS in the era of lung-protective ventilation. PMID:25593744

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.

Truncus arteriosus with aortic arch interruption: cardiovascular magnetic resonance findings in the unrepaired adult

PubMed Central

2010-01-01

Truncus arteriosus (TA) is a rare congenital condition defined as a single arterial vessel arising from the heart that gives origin to the systemic, pulmonary and coronary circulations. We discuss the unique case of a 28 year-old female patient with unrepaired TA and interruption of the aortic arch who underwent cardiovascular magnetic resonance (CMR). PMID:20307275

Fibromax-based nonalcoholic fatty liver disease in chronic obstructive pulmonary disease patients with obstructive sleep apnea: Methodological considerations

PubMed Central

Monneret, Denis

2017-01-01

The relationship between nonalcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA) has been well demonstrated, but remains to be evidenced in chronic obstructive pulmonary disease (COPD). Recently, Viglino et al. (Eur Respir J, 2017) attempted to determine the prevalence of liver fibrosis, steatosis and nonalcoholic steatohepatitis (NASH) in COPD patients, some of whom had OSA, basing the NAFLD diagnostic on three circulating biomarker-based liver scores: the FibroTest, SteatoTest and NashTest, from the Fibromax® panel. Among the main findings, the absence of OSA treatment emerged as independently associated with liver fibrosis and steatosis, when compared to effective treatment. However, besides the low number of treated patients, no polysomnographic respiratory data was provided, making it difficult to differentiate the impact of OSA from that of COPD in NAFLD prevalence. Furthermore, NAFLD diagnosis relied exclusively on circulating biomarker-based liver scores, without histological, imagery or other liver exploratory methods. Therefore, in this article, some methodological points are reminded and discussed, including the choice of OSA measurements, and the significance of ActiTest and AshTest scores from Fibromax® in this pathophysiological context. PMID:29225775

RADIOAUTOGRAPHIC DEMONSTRATION OF 5-HYDROXYTRYPTAMINE-3H UPTAKE BY PULMONARY ENDOTHELIAL CELLS

PubMed Central

Strum, Judy M.; Junod, Alain F.

1972-01-01

The lung is able to rapidly remove 5-hydroxytryptamme (5-HT) from the circulation by a Na+-dependent transport mechanism. In order to identify the sites of uptake, radioautographic studies were done on rat lungs which had been isolated and perfused with 5-HT-3H and 0 5 mM iproniazid, a monoamine oxidase inhibitor. In control experiments 10-4 M imipramine was added to the perfusate to inhibit the membrane transport of 5-HT At the light microscope level, silver grains were seen concentrated near capillaries and in the endothelium of large vessels From electron microscope radioautographs a semiquantitative grain count was made and 90% of the silver grains were observed over capillary endothelial cells. The grains were found over the nucleus and cytoplasm of the cell and shewed no preferential association with any particular cytoplasmic inclusion bodies, organelles, or vesicles Other cell types were unlabeled except for a few mast cells, certain vascular smooth muscle cells, and one nerve ending. This radioautographic demonstration of the cell type responsible for the rapid removal of 5-HT from the lung circulation clearly establishes the existence of a new metabolic role for pulmonary endothelial cells. PMID:5044755

Pulmonary Embolization of Fat and Bone Marrow in Cynomolgus Macaques (Macaca fascicularis)

PubMed Central

Fong, Derek L.; Murnane, Robert D.; Hotchkiss, Charlotte E.; Green, Damian J.; Hukkanen, Renee R.

2011-01-01

Fat embolization (FE), the introduction of bone marrow elements into circulation, is a known complication of bone fractures. Although FE has been described in other animal models, this study represents the first reported cases of FE and bone marrow embolism in nonhuman primates. Histopathologic findings from cynomolgus macaques (Macaca fascicularis) indicated that in all 5 cases, fat and bone marrow embolization occurred subsequent to multiple bone marrow biopsies. In the most severe case, extensive embolization was associated pulmonary damage consistent with acute respiratory distress syndrome. Fat embolism syndrome (FES) is an infrequent clinical outcome of FE and is triggered by systemic biochemical and mechanical responses to fat in circulation. Although clinical criteria diagnostic of FES were not investigated at the time of death, this severe case may represent the fulminant form of FES, which occurs within 12 h after trauma. Bone marrow biopsy as an etiology of FES has been reported only once in humans. In addition, the association of embolization with bone marrow biopsies suggests that nonhuman primates may be a useful animal model of FE. FE and FES represent important research confounders and FES should be considered as a differential diagnosis for clinical complications subsequent to skeletal trauma. PMID:21819686

Pulmonary embolization of fat and bone marrow in cynomolgus Macaques (Macaca fascicularis).

PubMed

Fong, Derek L; Murnane, Robert D; Hotchkiss, Charlotte E; Green, Damian J; Hukkanen, Renee R

2011-02-01

Fat embolization (FE), the introduction of bone marrow elements into circulation, is a known complication of bone fractures. Although FE has been described in other animal models, this study represents the first reported cases of FE and bone marrow embolism in nonhuman primates. Histopathologic findings from cynomolgus macaques (Macaca fascicularis) indicated that in all 5 cases, fat and bone marrow embolization occurred subsequent to multiple bone marrow biopsies. In the most severe case, extensive embolization was associated pulmonary damage consistent with acute respiratory distress syndrome. Fat embolism syndrome (FES) is an infrequent clinical outcome of FE and is triggered by systemic biochemical and mechanical responses to fat in circulation. Although clinical criteria diagnostic of FES were not investigated at the time of death, this severe case may represent the fulminant form of FES, which occurs within 12 h after trauma. Bone marrow biopsy as an etiology of FES has been reported only once in humans. In addition, the association of embolization with bone marrow biopsies suggests that nonhuman primates may be a useful animal model of FE. FE and FES represent important research confounders and FES should be considered as a differential diagnosis for clinical complications subsequent to skeletal trauma.

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

PubMed

Prins, Kurt W; Thenappan, Thenappan

2016-08-01

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

Achieving Benchmark Results for Neonatal Palliation of Hypoplastic Left Heart Syndrome and Related Anomalies in an Emerging Program.

PubMed

Dodge-Khatami, Ali; Chancellor, William Z; Gupta, Bhawna; Seals, Samantha R; Ebeid, Makram R; Batlivala, Sarosh P; Taylor, Mary B; Salazar, Jorge D

2015-07-01

Results of surgical management of hypoplastic left heart syndrome (HLHS) and related anomalies are often compared to published benchmark data which reflect the use of a variety of surgical and hybrid protocols. We report encouraging results achieved in an emerging program, despite a learning curve at all care levels. Rather than relying on a single preferred protocol, surgical management was based on matching surgical strategy to individual patient factors. From 2010 to 2014, a total of 47 consecutive patients with HLHS or related anomalies with ductal-dependent systemic circulation underwent initial surgical palliation, including 30 Norwood stage I, 8 hybrid stage I, and 9 salvage-to-Norwood procedures. True hybrid procedures entailed bilateral pulmonary artery banding and ductal stenting. In the salvage-to-Norwood strategy, ductal stenting was withheld in favor of continued prostaglandin infusion in anticipation of a deferred Norwood procedure. Cardiac comorbidities (obstructed pulmonary venous return, poor ventricular function, and atrioventricular valve regurgitation) and noncardiac comorbidities influenced the choice of treatment strategies and were analyzed as potential risk factors for extracorporeal membrane oxygenation (ECMO) support or in-hospital mortality. Overall hospital survival was 81% (Norwood 83.3%, hybrid 88%, "salvage" 67%; P = .4942). Extracorporeal membrane oxygenation support was used for eight (17%) patients with two survivors. For cases with obstructed pulmonary venous return (n = 10, 21%), management choices favored a hybrid or salvage strategy (P = .0026). Aortic atresia (n = 22, 47%) was treated by a Norwood or salvage-to-Norwood. No cardiac, noncardiac, or genetic comorbidities were identified as independent risk factors for ECMO or discharge mortality in a multivariable analysis. Our emerging program achieved outcomes that compare favorably to published benchmark data with respect to hospital survival. These results reflect rigorous interdisciplinary teamwork and a flexible approach to surgical palliation based on matching surgical strategy to patient factors. With major associated cardiac/noncardiac comorbidity and antegrade coronary flow, a true hybrid with ductal stenting was our preferred strategy. For high-risk situations such as aortic atresia with obstructed pulmonary venous return, the salvage hybrid-bridge-to-Norwood strategy may help achieve survival albeit with increased resource utilization. © The Author(s) 2015.

Differential roles of endothelin-1 ETA and ETB receptors and vasoactive intestinal polypeptide in regulation of the airways and the pulmonary vasculature in isolated rat lung.

PubMed

Janosi, Tibor; Peták, Ferenc; Fontao, Fabienne; Morel, Denis R; Beghetti, Maurice; Habre, Walid

2008-11-01

The available treatment strategies against pulmonary hypertension include the administration of endothelin-1 (ET-1) receptor subtype blockers (ET(A) and ET(B) antagonists); vasoactive intestinal polypeptide (VIP) has recently been suggested as a potential new therapeutic agent. We set out to investigate the ability of these agents to protect against the vasoconstriction and impairment of lung function commonly observed in patients with pulmonary hypertension. An ET(A) blocker (BQ123), ET(B) blocker (BQ788), a combination of these selective blockers (ET(A) + ET(B) blockers) or VIP (V6130) was administered into the pulmonary circulation in four groups of perfused normal rat lungs. Pulmonary vascular resistance (PVR) and forced oscillatory lung input impedance (Z(L)) were measured in all groups under baseline conditions and at 1 min intervals following ET-1 administrations. The airway resistance, inertance, tissue damping and elastance were extracted from the Z(L) spectra. While VIP, ET(A) blocker and combined ET(A) and ET(B) blockers significantly prevented the pulmonary vasoconstriction induced by ET-1, ET(B) blockade enhanced the ET-1-induced increases in PVR. In contrast, the ET(A) and ET(B) blockers markedly elevated the ET-1-induced increases in airway resistance, while VIP blunted this constrictor response. Our results suggest that VIP potently acts against the airway and pulmonary vascular constriction mediated by endothelin-1, while the ET(A) and ET(B) blockers exert a differential effect between airway resistance and PVR.

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

Improved Lung Perfusion After Left Pulmonary Artery Patch Enlargement During the Norwood Operation.

PubMed

Salehi Ravesh, Mona; Scheewe, Jens; Attmann, Tim; Al Bulushi, Abdullah; Jussli-Melchers, Marka-Jill; Jerosch-Herold, Michael; Gabbert, Dominik D; Wegner, Philip; Kramer, Hans-Heiner; Rickers, Carsten

2018-05-01

Optimal pulmonary perfusion is crucial for a well-functioning Fontan circulation in patients with hypoplastic left heart syndrome (HLHS). To obtain an adequate size of the left pulmonary artery (LPA), patch enlargement is a routine part of the hemi-Fontan procedure in our center. However, LPA patch enlargement at the time of the modified Norwood procedure may have surgical advantages. Therefore, the aim of this study was to evaluate whether anatomic and functional effects of the new approach are superior. A total of 51 consecutive HLHS patients underwent a cardiovascular magnetic resonance imaging study including assessment of LPA anatomy and lung perfusion. The LPA of 20 patients was enlarged during the modified Norwood procedure (group N) and of 31 patients during the hemi-Fontan procedure (group HF). The median indexed cross-sectional area of the LPA in group N was significantly higher than in group HF (49.5 versus 27.9 mm 2 /m 2 , p < 0.0001). The regional pulmonary perfusion as measured by first-pass, contrast-enhanced signal intensity upslope was significantly improved in group N (left side 0.67 s -1 versus 0.40 s -1 , p = 0.002; right side 0.84 s -1 versus 0.52 s -1 , p = 0.01). The total hemi-Fontan bypass and procedure times were significantly shorter in group N (both p < 0.001). These first magnetic resonance imaging data show that HLHS patients after LPA patch enlargement during the modified Norwood procedure have significantly higher LPA cross-sectional areas and show improved lung perfusion and shorter overall procedure time as compared with LPA patching during second stage (hemi-Fontan). Therefore, this promising surgical technique may improve blood flow dynamics of the Fontan circulation in the long run. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Early primary repair of tetralogy of fallot in neonates and infants less than four months of age.

PubMed

Tamesberger, Melanie I; Lechner, Evelyn; Mair, Rudolf; Hofer, Anna; Sames-Dolzer, Eva; Tulzer, Gerald

2008-12-01

The ideal age for correction of tetralogy of Fallot is still under discussion. The aim of this study was to analyze morbidity and mortality in patients who underwent early primary repair of tetralogy of Fallot at the age of less than 4 months and to assess whether neonates, who needed early repair within the first 4 weeks of life, faced an increased risk. From 1995 to 2006, 90 consecutive patients with tetralogy of Fallot and pulmonary stenosis underwent early primary repair. Patient charts were analyzed retrospectively for two groups: group A, 25 neonates younger than 28 days who needed early operation owing to duct-dependent pulmonary circulation or severe hypoxemia; and group B, 65 infants younger than 4 months of age who underwent elective early repair. There was no 30-day mortality; late mortality was 2% after a median follow-up time of 4.7 years. Seven of 88 patients (8%) needed reoperation and twelve of 88 patients (14%) needed reintervention. Groups A and B did not differ significantly in terms of intensive care unit stay, days of mechanical ventilation, overall hospital stay, major or minor complications, or reoperation. Significant differences were found in a more frequent use of a transannular patch (p = 0.045) and more reinterventions (p = 0.046) in group A. Early primary repair of tetralogy of Fallot can be performed safely and effectively in infants younger than 4 months of age and even in neonates younger than 28 days with duct-dependent pulmonary circulation or severe hypoxemia.

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

PubMed

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

2016-01-01

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

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

PubMed Central

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

2016-01-01

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

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.

Computed Tomography Angiography in Patients Evaluated for Acute Pulmonary Embolism with Low Serum D-dimer Levels: A Prospective Study.

PubMed

Gimber, Lana Hirai; Travis, R Ing; Takahashi, Jayme M; Goodman, Torrey L; Yoon, Hyo-Chun

2009-01-01

Pulmonary computed tomography angiography (CTA) and the Wells criteria both have interobserver variability in the assessment of pulmonary embolism (PE). Quantitative D-dimer assay findings have been shown to have a high negative predictive value in patients with low pretest probability of PE. Evaluate roles for clinical probability and CTA in Emergency Department (ED) patients suspected of acute PE but having a low serum D-dimer level. Prospective observational study of ED patients with possible PE who underwent pulmonary CTA and had D-dimer levels

Serial Sonographic Assessment of Pulmonary Edema in Patients With Hypertensive Acute Heart Failure.

PubMed

Martindale, Jennifer L; Secko, Michael; Kilpatrick, John F; deSouza, Ian S; Paladino, Lorenzo; Aherne, Andrew; Mehta, Ninfa; Conigiliaro, Alyssa; Sinert, Richard

2018-02-01

Objective measures of clinical improvement in patients with acute heart failure (AHF) are lacking. The aim of this study was to determine whether repeated lung sonography could semiquantitatively capture changes in pulmonary edema (B-lines) in patients with hypertensive AHF early in the course of treatment. We conducted a feasibility study in a cohort of adults with acute onset of dyspnea, severe hypertension in the field or at triage (systolic blood pressure ≥ 180 mm Hg), and a presumptive diagnosis of AHF. Patients underwent repeated dyspnea and lung sonographic assessments using a 10-cm visual analog scale (VAS) and an 8-zone scanning protocol. Lung sonographic assessments were performed at the time of triage, initial VAS improvement, and disposition from the emergency department. Sonographic pulmonary edema was independently scored offline in a randomized and blinded fashion by using a scoring method that accounted for both the sum of discrete B-lines and degree of B-line fusion. Sonographic pulmonary edema scores decreased significantly from initial to final sonographic assessments (P < .001). The median percentage decrease among the 20 included patient encounters was 81% (interquartile range, 55%-91%). Although sonographic pulmonary edema scores correlated with VAS scores (ρ = 0.64; P < .001), the magnitude of the change in these scores did not correlate with each other (ρ = -0.04; P = .89). Changes in sonographic pulmonary edema can be semiquantitatively measured by serial 8-zone lung sonography using a scoring method that accounts for B-line fusion. Sonographic pulmonary edema improves in patients with hypertensive AHF during the initial hours of treatment. © 2017 by the American Institute of Ultrasound in Medicine.

Fibroblast Growth Factor Signaling Mediates Pulmonary Endothelial Glycocalyx Reconstitution

PubMed Central

Yang, Yimu; Haeger, Sarah M.; Suflita, Matthew A.; Zhang, Fuming; Dailey, Kyrie L.; Colbert, James F.; Ford, Joshay A.; Picon, Mario A.; Stearman, Robert S.; Lin, Lei; Liu, Xinyue; Han, Xiaorui; Linhardt, Robert J.

2017-01-01

The endothelial glycocalyx is a heparan sulfate (HS)–rich endovascular structure critical to endothelial function. Accordingly, endothelial glycocalyx degradation during sepsis contributes to tissue edema and organ injury. We determined the endogenous mechanisms governing pulmonary endothelial glycocalyx reconstitution, and if these reparative mechanisms are impaired during sepsis. We performed intravital microscopy of wild-type and transgenic mice to determine the rapidity of pulmonary endothelial glycocalyx reconstitution after nonseptic (heparinase-III mediated) or septic (cecal ligation and puncture mediated) endothelial glycocalyx degradation. We used mass spectrometry, surface plasmon resonance, and in vitro studies of human and mouse samples to determine the structure of HS fragments released during glycocalyx degradation and their impact on fibroblast growth factor receptor (FGFR) 1 signaling, a mediator of endothelial repair. Homeostatic pulmonary endothelial glycocalyx reconstitution occurred rapidly after nonseptic degradation and was associated with induction of the HS biosynthetic enzyme, exostosin (EXT)-1. In contrast, sepsis was characterized by loss of pulmonary EXT1 expression and delayed glycocalyx reconstitution. Rapid glycocalyx recovery after nonseptic degradation was dependent upon induction of FGFR1 expression and was augmented by FGF-promoting effects of circulating HS fragments released during glycocalyx degradation. Although sepsis-released HS fragments maintained this ability to activate FGFR1, sepsis was associated with the downstream absence of reparative pulmonary endothelial FGFR1 induction. Sepsis may cause vascular injury not only via glycocalyx degradation, but also by impairing FGFR1/EXT1–mediated glycocalyx reconstitution. PMID:28187268

Metabolism during hypodynamia

NASA Technical Reports Server (NTRS)

Federov, I. V.

1980-01-01

Physical immobilization, inaction due to space travel, a sedentary occupation, or bed confinement due to a chronic illness elicit similar alternations in the metabolism of man and animals (rat, rabbit, dog, mouse). After a preliminary period of weight loss, there is eventually weight gain due to increased lipid storage. Protein catabolism is enhanced and anabolism depressed, with elevated urinary excretion of amino acids, creatine, and ammonia. Glycogen stores are depleted and glyconeogenesis is accelerated. Polyuria develops with subsequent redistribution of body fluids in which the blood volume of the systemic circulation is decreased and that of pulmonary circulation increased. This results in depressed production of vasopressin by the posterior pituitary which further enhances urinary water and salt loss.

Patient-Specific Modeling of Hemodynamics: Supporting Surgical Planning in a Fontan Circulation Correction.

PubMed

van Bakel, Theodorus M J; Lau, Kevin D; Hirsch-Romano, Jennifer; Trimarchi, Santi; Dorfman, Adam L; Figueroa, C Alberto

2018-04-01

Computational fluid dynamics (CFD) is a modeling technique that enables calculation of the behavior of fluid flows in complex geometries. In cardiovascular medicine, CFD methods are being used to calculate patient-specific hemodynamics for a variety of applications, such as disease research, noninvasive diagnostics, medical device evaluation, and surgical planning. This paper provides a concise overview of the methods to perform patient-specific computational analyses using clinical data, followed by a case study where CFD-supported surgical planning is presented in a patient with Fontan circulation complicated by unilateral pulmonary arteriovenous malformations. In closing, the challenges for implementation and adoption of CFD modeling in clinical practice are discussed.

Ontogeny of Big endothelin-1 effects in newborn piglet pulmonary vasculature.

PubMed

Liben, S; Stewart, D J; De Marte, J; Perreault, T

1993-07-01

Endothelin-1 (ET-1), a 21-amino acid peptide produced by endothelial cells, results from the cleavage of preproendothelin, generating Big ET-1, which is then cleaved by the ET-converting enzyme (ECE) to form ET-1. Big ET-1, like ET-1, is released by endothelial cells. Big ET-1 is equipotent to ET-1 in vivo, whereas its vasoactive effects are less in vitro. It has been suggested that the effects of Big ET-1 depend on its conversion to ET-1. ET-1 has potent vasoactive effects in the newborn pig pulmonary circulation, however, the effects of Big ET-1 remain unknown. Therefore, we studied the effects of Big ET-1 in isolated perfused lungs from 1- and 7-day-old piglets using the ECE inhibitor, phosphoramidon, and the ETA receptor antagonist, BQ-123Na. The rate of conversion of Big ET-1 to ET-1 was measured using radioimmunoassay. ET-1 (10(-13) to 10(-8) M) produced an initial vasodilation, followed by a dose-dependent potent vasoconstriction (P < 0.001), which was equal at both ages. Big ET-1 (10(-11) to 10(-8) M) also produced a dose-dependent vasoconstriction (P < 0.001). The constrictor effects of Big ET-1 and ET-1 were similar in the 1-day-old, whereas in the 7-day-old, the constrictor effect of Big ET-1 was less than that of ET-1 (P < 0.017).(ABSTRACT TRUNCATED AT 250 WORDS)

What do we know about pulmonary blastoma?: review of literature and clinical case report

PubMed Central

Brodowska-Kania, Dorota; Kotwica, Ewa; Paturej, Aleksandra; Sośnicki, Witold; Patera, Janusz; Giżewska, Agnieszka; Niemczyk, Stanisław

2016-01-01

ABSTRACT Pulmonary blastoma (PB) is a rare form of lung tumour and is accountable for 0.25–0.5% of primary pulmonary malignancies. Initially pulmonary blastoma was divided into three subtypes: biphasic pulmonary blastoma (BPB) consisting of an epithelial and mesenchymal component, well differentiated fetal adenocarcinoma (WDFA) built of well differentiated epithelium and a mesenchymal component and malignant pleuropulmonary blastoma (PPB). Prognosis in this type of cancer is really poor. We present a current review of literature and a clinical case report. Treatment of PB is very difficult. Data and recommendations about the treatment of pulmonary blastoma are still available therefore we should use only observations and clinical case reports. PMID:28008207

Lung perfusion measured using magnetic resonance imaging: New tools for physiological insights into the pulmonary circulation.

PubMed

Hopkins, Susan R; Prisk, G Kim

2010-12-01

Since the lung receives the entire cardiac output, sophisticated imaging techniques are not required in order to measure total organ perfusion. However, for many years studying lung function has required physiologists to consider the lung as a single entity: in imaging terms as a single voxel. Since imaging, and in particular functional imaging, allows the acquisition of spatial information important for studying lung function, these techniques provide considerable promise and are of great interest for pulmonary physiologists. In particular, despite the challenges of low proton density and short T2* in the lung, noncontrast MRI techniques to measure pulmonary perfusion have several advantages including high reliability and the ability to make repeated measurements under a number of physiologic conditions. This brief review focuses on the application of a particular arterial spin labeling (ASL) technique, ASL-FAIRER (flow sensitive inversion recovery with an extra radiofrequency pulse), to answer physiologic questions related to pulmonary function in health and disease. The associated measurement of regional proton density to correct for gravitational-based lung deformation (the "Slinky" effect (Slinky is a registered trademark of Pauf-Slinky incorporated)) and issues related to absolute quantification are also discussed. Copyright © 2010 Wiley-Liss, Inc.

Hfe Deficiency Impairs Pulmonary Neutrophil Recruitment in Response to Inflammation

PubMed Central

Benesova, Karolina; Vujić Spasić, Maja; Schaefer, Sebastian M.; Stolte, Jens; Baehr-Ivacevic, Tomi; Waldow, Katharina; Zhou, Zhe; Klingmueller, Ursula; Benes, Vladimir; Mall, Marcus A.; Muckenthaler, Martina U.

2012-01-01

Regulation of iron homeostasis and the inflammatory response are tightly linked to protect the host from infection. Here we investigate how imbalanced systemic iron homeostasis in a murine disease model of hereditary hemochromatosis (Hfe−/− mice) affects the inflammatory responses of the lung. We induced acute pulmonary inflammation in Hfe−/− and wild-type mice by intratracheal instillation of 20 µg of lipopolysaccharide (LPS) and analyzed local and systemic inflammatory responses and iron-related parameters. We show that in Hfe−/− mice neutrophil recruitment to the bronchoalveolar space is attenuated compared to wild-type mice although circulating neutrophil numbers in the bloodstream were elevated to similar levels in Hfe−/− and wild-type mice. The underlying molecular mechanisms are likely multifactorial and include elevated systemic iron levels, alveolar macrophage iron deficiency and/or hitherto unexplored functions of Hfe in resident pulmonary cell types. As a consequence, pulmonary cytokine expression is out of balance and neutrophils fail to be recruited efficiently to the bronchoalveolar compartment, a process required to protect the host from infections. In conclusion, our findings suggest a novel role for Hfe and/or imbalanced iron homeostasis in the regulation of the inflammatory response in the lung and hereditary hemochromatosis. PMID:22745741

Novel Therapeutic Strategies for Reducing Right Heart Failure Associated Mortality in Fibrotic Lung Diseases

PubMed Central

Levy, Matthew; Oyenuga, Olusegun

2015-01-01

Fibrotic lung diseases carry a significant mortality burden worldwide. A large proportion of these deaths are due to right heart failure and pulmonary hypertension. Underlying contributory factors which appear to play a role in the mechanism of progression of right heart dysfunction include chronic hypoxia, defective calcium handling, hyperaldosteronism, pulmonary vascular alterations, cyclic strain of pressure and volume changes, elevation of circulating TGF-β, and elevated systemic NO levels. Specific therapies targeting pulmonary hypertension include calcium channel blockers, endothelin (ET-1) receptor antagonists, prostacyclin analogs, phosphodiesterase type 5 (PDE5) inhibitors, and rho-kinase (ROCK) inhibitors. Newer antifibrotic and anti-inflammatory agents may exert beneficial effects on heart failure in idiopathic pulmonary fibrosis. Furthermore, right ventricle-targeted therapies, aimed at mitigating the effects of functional right ventricular failure, include β-adrenoceptor (β-AR) blockers, angiotensin-converting enzyme (ACE) inhibitors, antioxidants, modulators of metabolism, and 5-hydroxytryptamine-2B (5-HT2B) receptor antagonists. Newer nonpharmacologic modalities for right ventricular support are increasingly being implemented. Early, effective, and individualized therapy may prevent overt right heart failure in fibrotic lung disease leading to improved outcomes and quality of life. PMID:26583148

Systemic cell-mediated reactions in vivo. Effect of the interaction of circulating antigen with sensitized lymphocytes on glomeruli and pulmonary alveoli.

PubMed Central

Bhan, A. K.; Schneeberger, E. E.; Collins, A. B.; McCluskey, R. T.

1984-01-01

The effects of systemic cell-mediated hypersensitivity reactions on glomeruli and lungs were investigated in rats. The animals were given an intravenous injection of antigen 7 days after sensitization or were given an intravenous injection of lymph node cells from sensitized syngeneic donors 1 day after antigen injection. Control animals were given an irrelevant antigen or saline. All animals received three injections of 3H-thymidine during the course of the experiments. The animals were sacrificed 2 or 3 days after antigen injection. Autoradiographs of renal and pulmonary tissue showed significantly more labeled mononuclear cells in glomeruli and pulmonary alveolar walls in the experimental groups than in the control groups. Immunofluorescence studies did not reveal antigen, rat IgG, or C3 in glomeruli. The results indicate that systemic cell-mediated reactions can lead to an accumulation of mononuclear cells in glomeruli and lungs, an effect that may contribute to tissue injury. Images Figure 1 Figure 2 Figure 3 PMID:6611090

Interactive effects of mechano- and chemo-receptor inputs on cardiorespiratory outputs in the toad.

PubMed

Wang, T; Taylor, E W; Reid, S G; Milsom, W K

2004-04-20

Arterial blood pressure (P(b)), pulmocutaneous blood flow (Q(pc)), heart rate (f(H)), and fictive ventilation (motor activity in the Vth cranial nerve, V(int)), were recorded from decerebrated, paralysed toads receiving unidirectional ventilation with experimental gas mixtures over a range of lung inflation. At the onset of spontaneous bouts of fictive ventilation, (Q(pc)) and P(b) increased immediately, often with changes in heart rate, implying central cardiorespiratory interactions. Inflation of the lungs with different gas mixtures revealed that the effect of hypercarbia on V(int) was reduced by lung inflation and that feedback from pulmonary stretch receptors may summate with central feedforward control of f(H) and (Q(pc)) in an interactive fashion. The results of bolus injections of cyanide into the carotid or the pulmonary circulations suggest there are oxygen sensitive receptors in both circuits that affect the cardiovascular system directly and respiratory activity by complex central interactions with inputs from central chemoreceptors and pulmonary stretch receptors.

Blood Biomarkers in Idiopathic Pulmonary Fibrosis.

PubMed

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

2017-06-01

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

Distribution of perfusion.

PubMed

Glenny, Robb; Robertson, H Thomas

2011-01-01

Local driving pressures and resistances within the pulmonary vascular tree determine the distribution of perfusion in the lung. Unlike other organs, these local determinants are significantly influenced by regional hydrostatic and alveolar pressures. Those effects on blood flow distribution are further magnified by the large vertical height of the human lung and the relatively low intravascular pressures in the pulmonary circulation. While the distribution of perfusion is largely due to passive determinants such as vascular geometry and hydrostatic pressures, active mechanisms such as vasoconstriction induced by local hypoxia can also redistribute blood flow. This chapter reviews the determinants of regional lung perfusion with a focus on vascular tree geometry, vertical gradients induced by gravity, the interactions between vascular and surrounding alveolar pressures, and hypoxic pulmonary vasoconstriction. While each of these determinants of perfusion distribution can be examined in isolation, the distribution of blood flow is dynamically determined and each component interacts with the others so that a change in one region of the lung influences the distribution of blood flow in other lung regions. © 2011 American Physiological Society.

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

Sotiriadis, Charalampos; Hajdu, Steven David; Degrauwe, Sophie

With the increased use of implanted venous access devices (IVADs) for continuous long-term venous access, several techniques such as percutaneous endovascular fibrin sheath removal, have been described, to maintain catheter function. Most standard techniques do not capture the stripped fibrin sheath, which is subsequently released in the pulmonary circulation and may lead to symptomatic pulmonary embolism. The presented case describes an endovascular technique which includes stripping, capture, and removal of fibrin sheath using a novel filter device. A 64-year-old woman presented with IVAD dysfunction. Stripping was performed using a co-axial snare to the filter to capture the fibrin sheath. Themore » captured fragment was subsequently removed for visual and pathological verification. No immediate complication was observed and the patient was discharged the day of the procedure.« less

Use of a Valved-Conduit for Exclusion of the Infected Portion in the Prosthetic Pulmonary Valve Endocarditis

PubMed Central

Jung, Joonho; Lee, Cheol Joo; Lim, Sang-Hyun; Choi, Ho; Park, Soo-Jin

2013-01-01

A 51-year-old male was admitted to the hospital with complaints of fever and hemoptysis. After evaluation of the fever focus, he was diagnosed with pulmonary valve infective endocarditis. Thus pulmonary valve replacement and antibiotics therapy were performed and discharged. He was brought to the emergency unit presenting with a high fever (>39℃) and general weakness 6 months after the initial operation. The echocardiography revealed prosthetic pulmonary valve endocarditis. Therefore, redo-pulmonary valve replacement using valved conduit was performed in the Rastelli fashion because of the risk of pulmonary arterial wall injury and recurrent endocarditis from the remnant inflammatory tissue. We report here on the successful surgical treatment of prosthetic pulmonary valve endocarditis with an alternative surgical method. PMID:23772409

Pulmonary function tests correlated with thoracic volumes in adolescent idiopathic scoliosis.

PubMed

Ledonio, Charles Gerald T; Rosenstein, Benjamin E; Johnston, Charles E; Regelmann, Warren E; Nuckley, David J; Polly, David W

2017-01-01

Scoliosis deformity has been linked with deleterious changes in the thoracic cavity that affect pulmonary function. The causal relationship between spinal deformity and pulmonary function has yet to be fully defined. It has been hypothesized that deformity correction improves pulmonary function by restoring both respiratory muscle efficiency and increasing the space available to the lungs. This research aims to correlate pulmonary function and thoracic volume before and after scoliosis correction. Retrospective correlational analysis between thoracic volume modeling from plain x-rays and pulmonary function tests was conducted. Adolescent idiopathic scoliosis patients enrolled in a multicenter database were sorted by pre-operative Total Lung Capacities (TLC) % predicted values from their Pulmonary Function Tests (PFT). Ten patients with the best and ten patients with the worst TLC values were included. Modeled thoracic volume and TLC values were compared before and 2 years after surgery. Scoliosis correction resulted in an increase in the thoracic volume for patients with the worst initial TLCs (11.7%) and those with the best initial TLCs (12.5%). The adolescents with the most severe pulmonary restriction prior to surgery strongly correlated with post-operative change in total lung capacity and thoracic volume (r 2  = 0.839; p < 0.001). The mean increase in thoracic volume in this group was 373.1 cm 3 (11.7%) which correlated with a 21.2% improvement in TLC. Scoliosis correction in adolescents was found to increase thoracic volume and is strongly correlated with improved TLC in cases with severe restrictive pulmonary function, but no correlation was found in cases with normal pulmonary function. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:175-182, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Diagnostic Value of Circulating CXC Chemokines in Non-small Cell Lung Cancer.

PubMed

Spaks, Artjoms; Jaunalksne, Inta; Spaka, Irina; Chudasama, Dimple; Pirtnieks, Ainis; Krievins, Dainis

2015-12-01

To evaluate the diagnostic value of circulating CXC chemokines as biomarkers for non-small cell lung cancer and compare them against a standard panel of already existing cancer biomarkers. A total of 90 individuals were enrolled in the study. We analyzed 30 patients with stage IA-IIB carcinoma of the lung who underwent pulmonary resection, 30 patients with metastatic NSCLC, and 30 healthy volunteers. The biomarkers levels were measured in plasma blood samples, by ELISA and immunoassays. The levels of circulating CXCL4, CXCL8, CXCL9, CXCL10 and CXCL11 were higher and those of circulating CXCL1 were lower in patients with early-stage NSCLC compared to metastatic NSCLC patients and controls (p<0.05). CXCL4, CXCL9 and CXCL11 were included in the panel that showed a sensitivity of 100% versus 60% for CEA, CA125 and CYFRA21-1 (p<0.001). Combination of CXCL4, CXCL9 and CXCL11 has a high diagnostic value. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Carbon Dioxide Tolerance: A Review

DTIC Science & Technology

1967-09-01

limited buffering capabilities. 3. !rrncefihdtar btif, frig. Part of the excess H4 diffuses into cells and is buffered by intracellular HCO...correspond with changes in venous pH and pulmonary 00- excretion, possibly indicating a significant role of bone CO.. stores in acclimatization to carbon...blood parameters included no change in hematocrit, re- ticulocyte counts, and white blood cell counts while scme decrease was seen in circulating

Cardio-Pulmonary Response to Shock.

DTIC Science & Technology

1983-09-30

attenuated by inhibition of Tx synthesis . These data indicate that the prostanoids exert direct and indirect acticns in moderating c function...identified as the circulating negative inotropic agent whose production is stimulated by PG synthesis during PEEP. - The large amount of prostacyclin...127 ml - in controls (p < 0.05). The importance of WBC Tx synthesis in the induction of permeability was tested by stimulating isolated WBC with the

[Pneumonia in immunosuppressed patients].

PubMed

Solyanik, O; Gaass, T; Hellbach, K; Dinkel, J

2017-01-01

Pulmonary infections are a common complication in immunosuppressed patients with a frequently fatal prognosis despite modern prophylactic therapy. An early and correct diagnosis is important for initiation of the appropriate therapy. Chest radiography is the preferred initial imaging examination but is not accurate enough for the detection of pulmonary infections in immunosuppressed patients. Pneumonia is caused by a broad spectrum of pathogens in immunocompromised patients. In addition to imaging, the clinical history and epidemiology also play an important role in the diagnostics. Using epidemiological and anamnestic information, computed tomography (CT) shows a significantly better sensitivity and specificity particularly for the diagnosis of atypical forms of pneumonia. Due to the exact imaging of the different infiltration patterns CT provides an increased sensitivity with respect to the etiological classification of pulmonary infections. This article reviews in particular the radiological findings of commonly occurring pulmonary infections in immunosuppressed patients.

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

Total heart replacement using dual intracorporeal continuous-flow pumps in a chronic bovine model: a feasibility study.

PubMed

Frazier, O H; Tuzun, Egemen; Cohn, William E; Conger, Jeffrey L; Kadipasaoglu, Kamuran A

2006-01-01

Continuous-flow pumps are small, simple, and respond physiologically to input variations, making them potentially ideal for total heart replacement. However, the physiological effects of complete pulseless flow during long-term circulatory support without a cardiac interface or with complete cardiac exclusion have not been well studied. We evaluated the feasibility of dual continuous-flow pumps as a total artificial heart (TAH) in a chronic bovine model. Both ventricles of a 6-month-old Corriente crossbred calf were excised and sewing rings attached to the reinforced atrioventricular junctions. The inlet portions of 2 Jarvik 2000 pumps were positioned through their respective sewing rings at the mid-atrial level and the pulseless atrial reservoir connected end-to-end to the pulmonary artery and aorta. Pulseless systemic and pulmonary circulations were thereby achieved. Volume status was controlled, and systemic and pulmonary resistance were managed pharmacologically to keep mean arterial pressures at 100+/-10 mmHg (systemic) and 20+/-5 mmHg (pulmonary) and both left and right atrial pressures at 15+/-5 mmHg. The left pump speed was maintained at 14,000 rpm and its output autoregulated in response to variations in right pump flow, systemic and pulmonary pressures, fluid status, and activity level. Hemodynamics, end-organ function, and neurohormonal status remained normal. These results suggest the feasibility of using dual continuous-flow pumps as a TAH.

Predictive capabilities of preoperative and postoperative pulmonary function tests in delayed repair of congenital diaphragmatic hernia.

PubMed

Tracy, T F; Bailey, P V; Sadiq, F; Noguchi, A; Silen, M L; Weber, T R

1994-02-01

To improve the survival of newborns with congenital diaphragmatic hernia (CHD), preoperative stabilization with conventional ventilatory therapy and extracorporeal membrane oxygenation (ECMO) have been used. Measurements that quantify pulmonary function may allow an accurate assessment of lethal pulmonary hypoplasia and predict outcome. Pulmonary function tests (PFTs) were obtained in 20 infants preoperatively and postoperatively; these included measurements of compliance, dynamic compliance, and tidal volume. Overall survival was 75%. Six surviving infants were initially managed with ventilator therapy alone, followed by repair (group 1). The remaining 14 patients, who were moribund at presentation or whose initial ventilator therapy failed, were placed on ECMO and received repair during bypass; nine survived (group 2), and five died (group 3). Compliance, dynamic compliance, and tidal volume obtained at initial presentation and immediately preoperatively were significantly higher for group 1 as compared with groups 2 and 3. Infants whose initial compliance was greater than 0.25 mL/cm H2O/kg and initial tidal volume was greater than 3.5 mL/kg did not require ECMO. Ultimate improvement in compliance was noted in 5 of 6 patients in group 1, 8 of 8 patients in group 2, and 5 of 5 in group 3. This improvement followed an initial decline in compliance in 9 of 14 survivors, from 15% to 76%. All six patients in group 1 had tidal volumes of more than 4 mL/kg, as did 7 of 9 patients in group 2. Only one patient among the ECMO nonsurvivors (group 3) had a postoperative tidal volume of this magnitude. These data suggest that initial PFTs may predict which infants will require ECMO.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of flow distribution in the mouse fetal circulation at late gestation by high-frequency Doppler ultrasound.

PubMed

Zhou, Yu-Qing; Cahill, Lindsay S; Wong, Michael D; Seed, Mike; Macgowan, Christopher K; Sled, John G

2014-08-15

This study used high-frequency ultrasound to evaluate the flow distribution in the mouse fetal circulation at late gestation. We studied 12 fetuses (embryonic day 17.5) from 12 pregnant CD1 mice with 40 MHz ultrasound to assess the flow in 11 vessels based on Doppler measurements of blood velocity and M-mode measurements of diameter. Specifically, the intrahepatic umbilical vein (UVIH), ductus venosus (DV), foramen ovale (FO), ascending aorta (AA), main pulmonary artery (MPA), ductus arteriosus (DA), descending thoracic aorta (DTA), common carotid artery (CCA), inferior vena cava (IVC), and right and left superior vena cavae (RSVC, LSVC) were examined, and anatomically confirmed by micro-CT. The mouse fetal circulatory system was found to be similar to that of the humans in terms of the major circuit and three shunts, but characterized by bilateral superior vena cavae and a single umbilical artery. The combined cardiac output (CCO) was 1.22 ± 0.05 ml/min, with the left ventricle (flow in AA) contributing 47.8 ± 2.3% and the right ventricle (flow in MPA) 52.2 ± 2.3%. Relative to the CCO, the flow percentages were 13.6 ± 1.0% for the UVIH, 10.4 ± 1.1% for the DV, 35.6 ± 2.4% for the DA, 41.9 ± 2.6% for the DTA, 3.8 ± 0.3% for the CCA, 29.5 ± 2.2% for the IVC, 12.7 ± 1.0% for the RSVC, and 9.9 ± 0.9% for the LSVC. The calculated flow percentage was 16.6 ± 3.4% for the pulmonary circulation and 31.2 ± 5.3% for the FO. In conclusion, the flow in mouse fetal circulation can be comprehensively evaluated with ultrasound. The baseline data of the flow distribution in normal mouse fetus serve as the reference range for future studies. Copyright © 2014 the American Physiological Society.

Genome-Wide Association Analysis of Blood Biomarkers in Chronic Obstructive Pulmonary Disease

PubMed Central

Kim, Deog Kyeom; Cho, Michael H.; Hersh, Craig P.; Lomas, David A.; Miller, Bruce E.; Kong, Xiangyang; Bakke, Per; Gulsvik, Amund; Agustí, Alvar; Wouters, Emiel; Celli, Bartolome; Coxson, Harvey; Vestbo, Jørgen; MacNee, William; Yates, Julie C.; Rennard, Stephen; Litonjua, Augusto; Qiu, Weiliang; Beaty, Terri H.; Crapo, James D.; Riley, John H.; Tal-Singer, Ruth

2012-01-01

Rationale: A genome-wide association study (GWAS) for circulating chronic obstructive pulmonary disease (COPD) biomarkers could identify genetic determinants of biomarker levels and COPD susceptibility. Objectives: To identify genetic variants of circulating protein biomarkers and novel genetic determinants of COPD. Methods: GWAS was performed for two pneumoproteins, Clara cell secretory protein (CC16) and surfactant protein D (SP-D), and five systemic inflammatory markers (C-reactive protein, fibrinogen, IL-6, IL-8, and tumor necrosis factor-α) in 1,951 subjects with COPD. For genome-wide significant single nucleotide polymorphisms (SNPs) (P < 1 × 10−8), association with COPD susceptibility was tested in 2,939 cases with COPD and 1,380 smoking control subjects. The association of candidate SNPs with mRNA expression in induced sputum was also elucidated. Measurements and Main Results: Genome-wide significant susceptibility loci affecting biomarker levels were found only for the two pneumoproteins. Two discrete loci affecting CC16, one region near the CC16 coding gene (SCGB1A1) on chromosome 11 and another locus approximately 25 Mb away from SCGB1A1, were identified, whereas multiple SNPs on chromosomes 6 and 16, in addition to SNPs near SFTPD, had genome-wide significant associations with SP-D levels. Several SNPs affecting circulating CC16 levels were significantly associated with sputum mRNA expression of SCGB1A1 (P = 0.009–0.03). Several SNPs highly associated with CC16 or SP-D levels were nominally associated with COPD in a collaborative GWAS (P = 0.001–0.049), although these COPD associations were not replicated in two additional cohorts. Conclusions: Distant genetic loci and biomarker-coding genes affect circulating levels of COPD-related pneumoproteins. A subset of these protein quantitative trait loci may influence their gene expression in the lung and/or COPD susceptibility. Clinical trial registered with www.clinicaltrials.gov (NCT 00292552). PMID:23144326

Th17 cells and IL-17 promote the skin and lung inflammation and fibrosis process in a bleomycin-induced murine model of systemic sclerosis.

PubMed

Lei, Ling; Zhao, Cheng; Qin, Fang; He, Zhi-Yi; Wang, Xu; Zhong, Xiao-Ning

2016-01-01

Systemic sclerosis (SSc) is characterised by fibrosis of the skin and internal organs, such as the lungs. Enhanced Th17 responses are associated with skin fibrosis in patients with SSc, however, whether they are associated with lung fibrosis has not been clarified. This study aimed to investigate the potential association of Th17 responses with the skin and pulmonary fibrosis as well as the potential mechanisms in a mouse bleomycin (BLM) model of SSc. BALB/c mice were injected subcutaneously with phosphate buffered saline (PBS) (control) or BLM for 28 days and the skin and pulmonary inflammation and fibrosis were characterized by histology. The percentages of circulating, skin and pulmonary infiltrating Th17 cells and the contents of collagen in mice were analysed. The levels of RORγt, IL-17A, IL-6 and TGF-β1 mRNA transcripts in the skin and lungs were determined by quantitative RTPCR and the levels of serum IL-17A, IL-6 and TGF-β1 were determined by ELISA. Furthermore, the effect of rIL-17A on the proliferation of pulmonary fibroblasts and their cytokine expression was analysed. The potential association of Th17 responses with the severity of skin and lung fibrosis was analysed. In comparison with the control mice, significantly increased skin and pulmonary inflammation and fibrosis and higher levels of hydroxyproline were detected in the BLM mice. Significantly higher frequency of circulating, skin and lung infiltrating Th17 cells and higher levels of serum, skin and lung IL-17A, TGF-β1, IL-6 and RORγt were detected in the BLM mice. The concentrations of serum IL-17A were correlated positively with the percentages of Th17 cells and the contents of skin hydroxyproline in the BLM mice. The levels of IL-17A expression were positively correlated with the skin and lung inflammatory scores as well as the skin fibrosis in the BLM mice. In addition, IL-17A significantly enhanced pulmonary fibroblast proliferation and their type I collagen, TGF-β and IL-6 expression in vitro, which were attenuated by treatment with anti-IL-17A. Our results indicate that Th17 cells participate in the pathogenesis of skin and lung fibrosis by enhancing fibroblast proliferation and cytokine production in a mouse BLM model of SSc.

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.

Bicarbonate disruption of the pulmonary endothelial barrier via activation of endogenous soluble adenylyl cyclase, isoform 10

PubMed Central

Obiako, Boniface; Calchary, Wendy; Xu, Ningyong; Kunstadt, Ryan; Richardson, Bianca; Nix, Jessica

2013-01-01

It is becoming increasingly apparent that cAMP signals within the pulmonary endothelium are highly compartmentalized, and this compartmentalization is critical to maintaining endothelial barrier integrity. Studies demonstrate that the exogenous soluble bacterial toxin, ExoY, and heterologous expression of the forskolin-stimulated soluble mammalian adenylyl cyclase (AC) chimera, sACI/II, elevate cytosolic cAMP and disrupt the pulmonary microvascular endothelial barrier. The barrier-disruptive effects of cytosolic cAMP generated by exogenous soluble ACs are in contrast to the barrier-protective effects of subplasma membrane cAMP generated by transmembrane AC, which strengthens endothelial barrier integrity. Endogenous soluble AC isoform 10 (AC10 or commonly known as sAC) lacks transmembrane domains and localizes within the cytosolic compartment. AC10 is uniquely activated by bicarbonate to generate cytosolic cAMP, yet its role in regulation of endothelial barrier integrity has not been addressed. Here we demonstrate that, within the pulmonary circulation, AC10 is expressed in pulmonary microvascular endothelial cells (PMVECs) and pulmonary artery endothelial cells (PAECs), yet expression in PAECs is lower. Furthermore, pulmonary endothelial cells selectively express bicarbonate cotransporters. While extracellular bicarbonate generates a phosphodiesterase 4-sensitive cAMP pool in PMVECs, no such cAMP response is detected in PAECs. Finally, addition of extracellular bicarbonate decreases resistance across the PMVEC monolayer and increases the filtration coefficient in the isolated perfused lung above osmolality controls. Collectively, these findings suggest that PMVECs have a bicarbonate-sensitive cytosolic cAMP pool that disrupts endothelial barrier integrity. These studies could provide an alternative mechanism for the controversial effects of bicarbonate correction of acidosis of acute respiratory distress syndrome patients. PMID:23686854

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.

[Tumor thrombus arising from the superior vena cava and extending into the right atrium in a patient with advanced testicular germ cell tumor].

PubMed

Miyake, Makito; Fujimoto, Kiyohide; Matsushita, Chie; Chihara, Yoshitomo; Tanaka, Masahiro; Hirayama, Akihide; Hirao, Yoshihiko; Uemura, Hirotsugu

2009-06-01

A 24-year-old man was referred to our hospital with a painless mass on the left side of his neck. Ultrasonography detected right testicular tumor and computerized tomography scanning revealed a left supraclavicular lymph node mass and bulky retroperitoneal lymph node mass. He initially underwent right high orchiectomy, combination chemotherapy and retroperitoneal lymph node dissection for advanced testicular non-seminomatous germ cell tumor. Six years later, late relapse was detected in the lung. After complete remission of the lung metastasis with chemotherapy, the serum alpha-fetoprotein began to increase because of superior vena caval thrombus extending into the right atrium. Emergency surgical excision was performed successfully using extracorporeal circulation to prevent pulmonary embolism and the resected specimen pathologically revealed adenocarcinoma interpreted as teratoma malignant transformation. Adjuvant chemotherapy consisting of paclitaxel, ifosfamide and nedaplatin were administered for subsequent slight elevation of serum F-human chorionic gonadotropin beta, resulting in successful normalization again. Later, he suddenly died of cerebral infarction without any evidence of recurrence 138 months after his initial presentation. We report herein an extremely uncommon case of advanced testicular germ cell tumor with development of superior vena caval thrombus extending into the right atrium.

[Retrospective study of 25 cases of pulmonary mucormycosis in acute leukaemia].

PubMed

Caillot, D; Legouge, C; Lafon, I; Ferrant, E; Pagès, P B; Plocque, A; Estivalet, L; Valot, S; Dalle, F; Abou Hanna, H; Chretien, M-L

2018-04-01

In acute leukaemia (AL), the occurrence of pulmonary mucormycosis (PM), the incidence of which is increasing, as a result of chemotherapy induced marrow aplasia, remains a life threatening complication. Analysis of clinical, biological and thoracic CT characteristics of patients with PM developing during the treatment of AL between 2000 and 2015. Day 0 (D0) was defined as the day with first CT evidence of PM. Among 1193 patients, 25 cases of PM were recorded during 2099 episodes of bone marrow aplasia. At time of diagnosis of PM, 24/25 patients had been neutropenic for a median of 12 days. None of the patients had diabetes mellitus. On initial CT (D0), the lesion was solitary in 20/25 cases and a reversed halo sign (RHS) was observed in 23/25 cases. From D1 to D7, D8 to D15 and after D15, RHS was seen in 100 %, 75 % and 27 % of cases, respectively. A tissue biopsy was positive in 17/18 cases. The detection of circulating Mucorales DNA in serum was positive in 23/24 patients and in 97/188 serum specimens between D-9 and D9. Bronchoalveolar lavage contributed to diagnosis in only 3/21 cases. The antifungal treatment was mainly based on liposomal amphotericin B combined with, or followed by, posaconazole. A pulmonary surgical resection was performed in 9/25 cases. At 3 months, 76 % of patients were alive and median overall survival was 14 months. In AL, early use of CT could improve the prognosis of PM. The presence of a RHS on CT suggests PM and is an indication for prompt antifungal treatment. Copyright © 2018 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Increased IgD milk antibody responses in a patient with Down's syndrome, pulmonary hemosiderosis and cor pulmonale.

PubMed

Galant, S; Nussbaum, E; Wittner, R; DeWeck, A L; Heiner, D C

1983-10-01

IgD antibody responses to cow's milk were investigated in a two-year-old black boy with evidence of pulmonary hemosiderosis and pulmonary hypertension. Initially a broad spectrum of immunologic responses to cow's milk were observed including IgD, IgE, and precipitin antibodies. Specific IgD antibody responses to cow's milk could be modulated in terms of challenge or elimination and correlated with the clinical course. It is possible that IgD antibodies may be important in milk-related pulmonary hemosiderosis.

The human circulating miRNome reflects multiple organ disease risks in association with short-term exposure to traffic-related air pollution.

PubMed

Krauskopf, Julian; Caiment, Florian; van Veldhoven, Karin; Chadeau-Hyam, Marc; Sinharay, Rudy; Chung, Kian Fan; Cullinan, Paul; Collins, Peter; Barratt, Benjamin; Kelly, Frank J; Vermeulen, Roel; Vineis, Paolo; de Kok, Theo M; Kleinjans, Jos C

2018-04-01

Traffic-related air pollution is a complex mixture of particulate matter (PM) and gaseous pollutants, such as nitrogen dioxide (NO2). PM exposure contributes to the pathogenesis of many diseases including several types of cancer, as well as pulmonary, cardiovascular and neurodegenerative diseases. Also exposure to NO2 has been related to increased cardiovascular mortality. In search of an early diagnostic biomarker for improved air pollution-associated health risk assessment, recent human studies have shown that certain circulating miRNAs are altered upon exposure to traffic-related air pollutants. Here, we present for the first time a global analysis of the circulating miRNA genome in an experimental cross-over study of a human population exposed to traffic-related air pollution. By utilizing next-generation sequencing technology and detailed real-time exposure measurements we identified 54 circulating miRNAs to be dose- and pollutant species-dependently associated with PM10, PM2.5, black carbon, ultrafine particles and NO2 already after 2 h of exposure. Bioinformatics analysis suggests that these circulating miRNAs actually reflect the adverse consequences of traffic pollution-induced toxicity in target tissues including the lung, heart, kidney and brain. This study shows the strong potential of circulating miRNAs as novel biomarkers for environmental health risk assessment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Pneumoperitoneum risk prognosis and correction of venous circulation disturbances in laparoscopic surgery. A pilot study.

PubMed

Emeljanov, S I; Fedenko, V V; Levite, E M; Panfilov, S A; Bobrinskaya, I G; Fedorov, A V; Matveev, N L; Evdoshenko, V V; Luosev, S V; Bokarev, V V; Musaeva, S R

1998-10-01

This study was initiated to find a method of determining the prognosis for possible changes in hemodynamic and respiratory parameters in patients with pneumoperitoneum (PP). We devised a model for a pseudopneumoperitoneum (PPP), which is created by encircling the wide pneumochamber on the entire abdomen and inflating it to a preset pressure. To verify the prognostic possibilities of the proposed model, we studied the pneumotachygraphy parameters, noninvasive and invasive monitoring parameters of PPP after induction of anaesthesia, and venous circulation disturbances, as well as the medical effect of the intermittent sequential compression device. In healthy patients, the restrictive lung syndrome did not approach the risky limit. In patients >/=60 years old, this syndrome was very close to the limit. In a number of patients with serious cardiovascular and pulmonary pathology, the pressure of >10 mmHg was considered to be intolerable. Lung compliance, which was the parameter most sensitive to the increased intraabdominal pressure, was 47 +/- 10 at baseline, and 29 +/- 4 (p > 0.05) at both PPP and real PP (14 mmHg). The PPP model is quite similar to the real PP and can be used for preoperative prognosis in laparoscopic surgery. The elevated intraabdominal pressure results in a significant disturbance of venous blood flow in the lower extremities. The use of the device for peristaltic pneumomassage of the lower limbs is effective in correcting negative changes in venous hemodynamics in laparoscopic surgery.

Bilateral vagotomy inhibits apnea and attenuates other physiological responses after blunt chest trauma.

PubMed

Gryth, Dan; Rocksén, David; Arborelius, Ulf P; Drobin, Dan; Persson, Jonas K E; Sondén, Anders; Bursell, Jenny; Olsson, Lars-Gunnar; Kjellström, B Thomas

2008-06-01

Behind armor blunt trauma (BABT) is defined as the nonpenetrating injury resulting from a ballistic impact on body armor. Some of the kinetic energy is transferred to the body, causing internal injuries and, occasionally, death. The aim of this study was to investigate if apnea and other pathophysiological effects after BABT is a vagally mediated reflex. Sixteen anesthetized pigs wearing body armor, of which five were vagotomized, were shot with a standard 7.62 mm assault rifle. These animals were compared with control animals (n = 8), shot with blank ammunition. We performed bilateral vagotomy before the shot and assessed the outcome on the apnea period, respiration, circulation, and brain function. Animals were monitored during a 2-hour period after the shot. Nonvagotomized animals had a mean apnea period of 22 (6-44) seconds. This group also showed a significant decrease in oxygen saturation compared with control animals. Furthermore, electroencephalogram-changes were more pronounced in nonvagotomized animals. In contrast, vagotomized animals were protected from apnea and showed only a minor decrease in oxygen saturation. All exposed animals showed impaired circulation, and postmortem examination revealed a pulmonary contusion. This study shows that apnea after BABT is a vagally mediated reflex that can be inhibited by bilateral vagotomy. Our results indicate that the initial apnea period is an important factor for hypoxia after BABT. Supported ventilation should begin immediately if the affected person is unconscious and suffers from apnea. It should continue until the neurologic paralysis disappears and sufficient spontaneous breathing begins.

Customizing our approach in deep vein thrombosis and pulmonary embolism treatment: overview of our clinical experience.

PubMed

Turpie, A G

1999-08-01

Until recently, the management of established deep vein thrombosis (DVT) and pulmonary embolism remained largely unchanged and unchallenged. Treatment comprised an initial intravenous bolus of unfractionated heparin (UFH), followed by dose-adjusted intravenous UFH for 5-7 days, and oral warfarin for three months. UFH is traditionally administered in hospital, and monitoring and dose adjustment remain essential features of both UFH and warfarin treatment, making therapy both costly and inconvenient. Recent clinical trials have shown that subcutaneous UFH, or low-molecular-weight heparins (LMWHs), administered subcutaneously at a weight-adjusted fixed dose, are at least as effective as standard UFH given intravenously in the treatment of DVT. The feasibility of initial treatment of DVT at home in selected patients, with associated cost-savings and improved convenience have also been demonstrated with LMWHs. Clinical trials are currently investigating the potential value of LMWHs in the treatment of pulmonary embolism and as an alternative to warfarin in secondary prevention of DVT. The role of newer anticoagulants, such as recombinant hirudin, in initial treatment of DVT, and of thrombolysis in the management of pulmonary embolism remain to be defined.

Stratospheric wind errors, initial states and forecast skill in the GLAS general circulation model

NASA Technical Reports Server (NTRS)

Tenenbaum, J.

1983-01-01

Relations between stratospheric wind errors, initial states and 500 mb skill are investigated using the GLAS general circulation model initialized with FGGE data. Erroneous stratospheric winds are seen in all current general circulation models, appearing also as weak shear above the subtropical jet and as cold polar stratospheres. In this study it is shown that the more anticyclonic large-scale flows are correlated with large forecast stratospheric winds. In addition, it is found that for North America the resulting errors are correlated with initial state jet stream accelerations while for East Asia the forecast winds are correlated with initial state jet strength. Using 500 mb skill scores over Europe at day 5 to measure forecast performance, it is found that both poor forecast skill and excessive stratospheric winds are correlated with more anticyclonic large-scale flows over North America. It is hypothesized that the resulting erroneous kinetic energy contributes to the poor forecast skill, and that the problem is caused by a failure in the modeling of the stratospheric energy cycle in current general circulation models independent of vertical resolution.

Exercise capacity before and after an 8-week multidisciplinary inpatient rehabilitation program in lung cancer patients: a pilot study.

PubMed

Spruit, Martijn A; Janssen, Paul P; Willemsen, Sonja C P; Hochstenbag, Monique M H; Wouters, Emiel F M

2006-05-01

Although lung cancer is a highly prevalent type of cancer, the effects of an inpatient multidisciplinary rehabilitation program on pulmonary function and exercise capacity have never been studied in these patients. Pulmonary function, 6-min walking distance and peak exercise capacity of 10 patients with a severely impaired pulmonary function following treatment of lung cancer were assessed in this pilot study before and after an 8-week inpatient multidisciplinary rehabilitation program. At baseline, patients had a restrictive pulmonary function and an apparent exercise intolerance (median 6-min walking distance: 63.6% predicted; median peak cycling load: 58.5% predicted). Despite the lack of change in median pulmonary function [FEV1: -0.01L, p = 0.5469], functional exercise capacity [145 m; 43.2% of the initial values, p=0.0020] and peak exercise capacity [26 W; 34.4% of the initial values, p = 0.0078] improved significantly compared to baseline. Future trials have to corroborate the present findings. Nevertheless, patients with lung cancer have a clear indication to start a comprehensive rehabilitation program following intensive treatment of their disease. In fact, based on the results of the present pilot study it appears that these patients are good candidates for pulmonary rehabilitation programs.

Protocol for a mixed-methods study of supplemental oxygen in pulmonary fibrosis.

PubMed

Belkin, Amanda; Fier, Kaitlin; Albright, Karen; Baird, Susan; Crowe, Brenda; Eres, Linda; Korn, Marjorie; Maginn, Leslie; McCormick, Mark; Root, Elisabeth D; Vierzba, Thomas; Wamboldt, Frederick S; Swigris, Jeffrey J

2014-11-01

Little is known about whether or how supplemental oxygen affects patients with pulmonary fibrosis. A mixed-methods study is described. Patients with pulmonary fibrosis, informal caregivers of pulmonary fibrosis patients and practitioners who prescribe supplemental oxygen will be interviewed to gather data on perceptions of how supplemental oxygen impacts patients. In addition, three hundred pulmonary fibrosis patients who do not use daytime supplemental oxygen will be recruited to participate in a longitudinal, pre-/post- study in which patient-reported outcome (PRO) and activity data will be collected at baseline, immediately before daytime supplemental oxygen is initiated, and then once and again 9-12 months later. Activity data will be collected using accelerometers and portable GPS data recorders. The primary outcome is change in dyspnea from before to one month after supplemental oxygen is initiated. Secondary outcomes include scores from PROs to assess cough, fatigue and quality of life as well as the activity data. In exploratory analyses, we will use longitudinal data analytic techniques to assess the trajectories of outcomes over time while controlling for potentially influential variables. Throughout the study and at its completion, results will be posted on the website for our research program (the Participation Program for Pulmonary Fibrosis or P3F) at http://www.pulmonaryfibrosisresearch.org.

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.

Is exercise good for the right ventricle? Concepts for health and disease.

PubMed

La Gerche, André; Claessen, Guido

2015-04-01

There is substantial evidence supporting the prescription of exercise training in patients with left-sided heart disease, but data on the effects of exercise are far more limited for conditions that primarily affect the right ventricle. There is evolving evidence that right ventricular (RV) function is of critical importance to circulatory function during exercise. Even in healthy individuals with normal pulmonary vascular function, the hemodynamic load on the right ventricle increases relatively more during exercise than that of the left ventricle, and this disproportionate load is far greater in patients with pulmonary hypertension. Exercise-induced increases in pulmonary artery pressures can exceed RV contractile reserve (so-called arterioventricular uncoupling), resulting in attenuated cardiac output and exercise intolerance. In this review, we explore the spectrum of RV reserve-from transient RV dysfunction observed in athletes after extreme bouts of intense endurance exercise to RV failure with minimal exertion in patients with advanced pulmonary hypertension. Recent advances and novel approaches to echocardiographic and cardiac magnetic resonance imaging have provided more accurate means of assessing the right ventricle and pulmonary circulation during exercise such that quantification of exercise reserve may provide a valuable means of assessing prognosis and response to therapies. We discuss the potential benefits and risks of exercise training in both health and disease while recognizing the need for prospective studies that assess the long-term efficacy and safety of exercise interventions in patients with pulmonary vascular and RV pathologic conditions. Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Rationale and design of a trial on the role of bosentan in Fontan patients: improvement of exercise capacity?

PubMed

Schuuring, Mark J; Vis, Jeroen C; Bouma, Berto J; van Dijk, Arie P J; van Melle, Joost P; Pieper, Petronella G; Vliegen, Hubert W; Sieswerda, Gertjan Tj; Mulder, Barbara J M

2011-07-01

The Fontan circulation is a palliative procedure performed in patients with complex congenital heart disease (CHD), making transpulmonary blood flow dependent on the systemic venous pressure. In a Fontan circulation a low pulmonary vascular resistance (PVR) is crucial, as is epitomized by the observation that a high PVR is a strong predictor of mortality. Long-term follow-up has shown that PVR may rise many years after the Fontan procedure has been performed, possibly due to micro-emboli from a dilated right atrium or from the venous system. Other mechanisms of increased PVR might be aging, obstructed airways caused by lymphatic dysfunction, lack of pulsatile pulmonary flow causing a release of endothelium-derived vasoactive molecules, and prolonged overexpression of vasoconstrictors such as endothelin-1. Mean plasma level of endothelin-1 has been shown to be significantly higher in Fontan patients compared to healthy controls. In patients with pulmonary arterial hypertension (PAH), therapy with bosentan, an endothelin-1 receptor antagonist, has demonstrated to improve exercise capacity and to reduce the elevated PVR. In addition, reduction of PVR is shown early and late after the Fontan procedure on treatment with exogenous NO, another advanced PAH therapy. However, the long term effect of reducing the PVR by bosentan treatment on exercise capacity in Fontan patients is still unknown. We designed a prospective, multicenter, randomized open label trial to study the effect of bosentan in Fontan patients. The primary endpoint will be the change in maximum exercise capacity (peak V'O2). We hypothesize that treatment with bosentan, an endothelin-1 receptor antagonist, improves maximum exercise capacity and functional capacity in adult Fontan patients. Copyright © 2011 Elsevier Inc. All rights reserved.

Prenatal Effects of Maternal Consumption of Polyphenol-Rich Foods in Late Pregnancy upon Fetal Ductus Arteriosus

PubMed Central

Zielinsky, Paulo; Busato, Stefano

2013-01-01

Fetal circulation has characteristic features, being morphologically and functionally different from extrauterine circulation. The ductus arteriosus plays a fundamental role in directing the blood flow to fetal inferior body parts. Basically, the ductus arteriosus directs 80–85% of the right ventricular output arising from the superior vena cava, coronary sinus, and a small part from the inferior vena cava to descending aorta. Its histological structure is made up predominantly by a thick muscular layer, differently from the aorta and the pulmonary artery, which increases with gestational age. The fibers have a circumferential orientation, especially at the external layers, facilitating and making effective ductal constriction. These factors may generate lumen alterations which may cause fetal and neonatal complications, such as heart failure, hydrops, neonatal pulmonary hypertension, and even death. Classically, maternal administration of indomethacin and/or other antiinflammatory drugs interfere in prostaglandins metabolism, causing ductal constriction. However, many cases of fetal ductal constriction, as well as of persistent neonatal pulmonary artery hypertension, remain without an established etiology, being referred as “idiopathic.” In recent years, a growing body of evidence has shown that herbs, fruits, nuts, and a wide diversity of substances commonly used in daily diets have definitive effects upon the metabolic pathway of inflammation, with consequent inhibition of prostaglandins synthesis. This antiinflammatory action, especially of polyphenols, when ingested during the third trimester of pregnancy, may influence the dynamics of fetal ductus arteriosus flow. The goal of this review is to present these new observations and findings, which may influence dietary orientation during pregnancy. Birth Defects Research (Part C) 99:256–274, 2013. © 2013 Wiley Periodicals, Inc. PMID:24339037

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

PubMed Central

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

2016-01-01

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

Sensitivities of Summertime Mesoscale Circulations in the Coastal Carolinas to Modifications of the Kain–Fritsch Cumulus Parameterization

EPA Science Inventory

Two mesoscale circulations, the Sandhills circulation and the sea breeze, influence the initiation of deep convection over the Sandhills and the coast in the Carolinas during the summer months. The interaction of these two circulations causes additional convection in this coastal...

Experimental Septic Shock: Models and Mechanisms

DTIC Science & Technology

1976-06-14

the renal, hepatic, and pulmonary systems with severe pathophysiological effects on the liver circulation and metabolism (7,9,11,17,18,20). The...was sustained at values between 40 and 60 nmHg. Mean plasm glucose increased for the first several hours, then progressively fell to hypoglycemic...when the state of shock is severe and when death is imminent. On the other hand, hyperglycemia con- comitantly occurring with hypoinsulinemia, termed

Biofluid mechanics of special organs and the issue of system control. Sixth International Bio-Fluid Mechanics Symposium and Workshop, March 28-30, 2008 Pasadena, California.

PubMed

Zamir, Mair; Moore, James E; Fujioka, Hideki; Gaver, Donald P

2010-03-01

In the field of fluid flow within the human body, focus has been placed on the transportation of blood in the systemic circulation since the discovery of that system; but, other fluids and fluid flow phenomena pervade the body. Some of the most fascinating fluid flow phenomena within the human body involve fluids other than blood and a service other than transport--the lymphatic and pulmonary systems are two striking examples. While transport is still involved in both cases, this is not the only service which they provide and blood is not the only fluid involved. In both systems, filtration, extraction, enrichment, and in general some "treatment" of the fluid itself is the primary function. The study of the systemic circulation has also been conventionally limited to treating the system as if it were an open-loop system governed by the laws of fluid mechanics alone, independent of physiological controls and regulations. This implies that system failures can be explained fully in terms of the laws of fluid mechanics, which of course is not the case. In this paper we examine the clinical implications of these issues and of the special biofluid mechanics issues involved in the lymphatic and pulmonary systems.

A Fatal Hantavirus Pulmonary Syndrome Misdiagnosed as Dengue: An Investigation into the First Reported Case in Rio de Janeiro State, Brazil.

PubMed

de Oliveira, Renata Carvalho; Guterres, Alexandro; Teixeira, Bernardo Rodrigues; Fernandes, Jorlan; Júnior, João Marcos Penna; de Jesus Oliveira Júnior, Reynaldo; Pereira, Liana Strecht; Júnior, João Bosco; Meneguete, Patrícia Soares; Dias, Cristina Maria Giordano; Bonvicino, Cibele Rodrigues; D'Andrea, Paulo Sérgio; de Lemos, Elba Regina Sampaio

2017-07-01

We report the results of an investigation into a fatal case of hantavirus pulmonary syndrome (HPS) in Rio de Janeiro State, Brazil, where the disease had not been reported previous to 2015. Following the notification of an HPS case, serum samples were collected from the household members and work contacts of the HPS patient and tested for antibody to hantaviruses. Seroprevalence of 22% (10/45) was indicated for hantavirus out of 45 human samples tested. Blood and tissue samples were collected from 72 rodents during fieldwork to evaluate the prevalence of hantavirus infection, by using enzyme-linked immunosorbent assay IgG, and to characterize the rodent hantavirus reservoir(s), by reverse transcription polymerase chain reaction and sequencing. Antibody prevalence was 6.9%. The circulation of a single genotype, the Juquitiba hantavirus, carried by two rodent species, black-footed pigmy rice rat ( Oligoryzomys nigripes ) and cursor grass mouse ( Akodon cursor ), was shown by analysis of the nucleotide sequences of the S segment. Juquitiba hantavirus circulates in rodents of various species, but mainly in the black-footed pigmy rice rat. HPS is a newly recognized clinical entity in Rio de Janeiro State and should be considered in patients with febrile illness and acute respiratory distress.

Design of a right ventricular mock circulation loop as a test bench for right ventricular assist devices.

PubMed

Mueller, Indra; Jansen-Park, So-Hyun; Neidlin, Michael; Steinseifer, Ulrich; Abel, Dirk; Autschbach, Rüdiger; Rossaint, Rolf; Schmitz-Rode, Thomas; Sonntag, Simon Johannes

2017-04-01

Right heart failure (RHF), e.g. due to pulmonary hypertension (PH), is a serious health issue with growing occurrence and high mortality rate. Limited efficacy of medication in advanced stages of the disease constitutes the need for mechanical circulatory support of the right ventricle (RV). An essential contribution to the process of developing right ventricular assist devices (RVADs) is the in vitro test bench, which simulates the hemodynamic behavior of the native circulatory system. To model healthy and diseased arterial-pulmonary hemodynamics in adults (mild and severe PH and RHF), a right heart mock circulation loop (MCL) was developed. Incorporating an anatomically shaped silicone RV and a silicone atrium, it not only enables investigations of hemodynamic values but also suction events or the handling of minimal invasive RVADs in an anatomical test environment. Ventricular pressure-volume loops of all simulated conditions as well as pressure and volume waveforms were recorded and compared to literature data. In an exemplary test, an RVAD was connected to the apex to further test the feasibility of studying such devices with the developed MCL. In conclusion, the hemodynamic behavior of the native system was well reproduced by the developed MCL, which is a useful basis for future RVAD tests.

Decreased levels of circulating sex hormones as a biomarker of lung cancer in male patients with solitary pulmonary nodules.

PubMed

Gu, Tao; Wen, Zongmei; Xu, Shufeng; Hua, Haixia; Zhang, Zhi; Wen, Tao; Fu, Zhanzhao; Lv, Xin

2014-06-01

An early differentiation of malignant from benign solitary pulmonary nodules (SPNs) is essential for management and prognosis of lung cancer. Here we investigated whether measurement of circulating sex hormones could be useful for an early detection of malignancy among patients with SPNs. We recruited 47 patients with malignant SPNs 45 patients with benign SPNs, and 32 healthy persons. Testosterone, estradiol, and progesterone were measured. Carcinoembryonic antigen (CEA) as well as TNF-α, IL-1 and IL-6 were also measured. We found that sex hormones were decreased significantly in patients with malignant SPNs, as compared to patients with benign SPNs and healthy controls (P<0.05). Sex hormones levels showed a trend to decline in patients with benign SPNs as compared to normal controls, but the difference was not statistically significant (P>0.05). CEA levels were only abnormally elevated in eight patients with lung adenocarcinoma. The inflammatory cytokines were remarkably higher in both patients than in normal controls. However, there was no statistical difference in these cytokines among patients. The reduced sex hormones levels seemed to be uniquely associated with lung cancer. Therefore, measurement of sex hormones may have clinical potential in the diagnosis of malignancy in patients with SPNs.

Numerical Investigation of the Middle Atlantic Bight Shelfbreak Frontal Circulation Using a High-Resolution Ocean Hindcast Model

DTIC Science & Technology

2010-05-01

circulation from December 2003 to June 2008 . The model is driven by tidal harmonics, realistic atmospheric forcing, and dynamically consistent initial and open...important element of the regional circulation (He and Wilkin 2006). We applied the method of Mellor and Yamada (1982) to compute vertical turbulent...shelfbreak ROMS hindcast ran continuously from December 2003 through January 2008 . Initial conditions were taken from the MABGOM ROMS simulation on 1

Right Cardiac Chambers Involvement by a Malignant Testicular Germ Cell Tumor: An Imaging-pathologic Correlation.

PubMed

do Nascimento, Felipe Barjud Pereira; Albieri, Lilian; Bento Dos Santos, Glaucia Aparecida; Dolhnikoff, Marisa

2016-07-01

The cardiac chamber's involvement with neoplastic embolism has been rarely reported; it is mostly associated with gastric, breast, lung, liver, and prostate cancers, and usually affects the pulmonary arteries. This paper reports a case of a 31-year-old man with a malignant testicular germ cell tumor who presented with multiple episodes of pulmonary thromboembolism and died of sudden respiratory failure 1 year after the initial diagnosis. Death was attributed to massive pulmonary embolism and pulmonary infarction associated with a neoplastic thrombus that extended from the gonadal veins to pulmonary arteries. A postmortem computerized tomographic angiography and autopsy confirmed this finding. Copyright © 2016 Elsevier Inc. All rights reserved.

Group 2 Pulmonary Hypertension: Pulmonary Venous Hypertension: Epidemiology and Pathophysiology.

PubMed

Clark, Craig B; Horn, Evelyn M

2016-08-01

Pulmonary hypertension from left heart disease (PH-LHD) is the most common form of PH, defined as mean pulmonary artery pressure ≥25 mm Hg and pulmonary artery wedge pressure ≥15 mm Hg. PH-LHD development is associated with more severe left-sided disease and its presence portends a poor prognosis, particularly once right ventricular failure develops. Treatment remains focused on the underlying LHD and despite initial enthusiasm for PH-specific therapies, most studies have been disappointing and their routine clinical use cannot be recommended. More work is urgently needed to better understand the pathophysiology underlying this disease and to develop effective therapeutic strategies. Copyright © 2016 Elsevier Inc. All rights reserved.

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) caused consecutive rightward shifts in the endothelin-1 concentration-contraction curves for all ring types, including the intact rings from endotoxemic animals. Sarafotoxin S6c failed to induce any direct constriction in rings from sham-treated or lipopolysaccharide-treated rats. However, sarafotoxin S6c induced transient vasodilation at the initial dose in rings from sham-treated rats but not lipopolysaccharide-treated rats-an effect that was attenuated by N omega-nitro-L-arginine-methylester. Acetylcholine induced an N omega-nitro-L-arginine-methylester-sensitive vasodilation that was reduced in rings from endotoxin-treated rats. Endothelin-A receptor blockade is an effective means of attenuating endothelin-1-induced contraction of isolated pulmonary artery rings, even from rats rendered endotoxemic. Endothelin-B receptors on the pulmonary artery cause vasodilation via the release of nitric oxide, and have no constrictor component. The functional effects of endothelin-B receptors on tone are lost after lipopolysaccharide treatment. The endothelium is involved in both the constrictor and dilator effects of endothelin in rat pulmonary artery, confirming a pivotal role for endothelial cells in the vascular response to sepsis.

Efficacy of vitamin D3 supplementation in reducing incidence of pulmonary tuberculosis and mortality among HIV-infected Tanzanian adults initiating antiretroviral therapy: study protocol for a randomized controlled trial.

PubMed

Sudfeld, Christopher R; Mugusi, Ferdinand; Aboud, Said; Nagu, Tumaini J; Wang, Molin; Fawzi, Wafaie W

2017-02-10

HIV-infected adults initiating antiretroviral therapy (ART) in sub-Saharan Africa continue to experience high rates of morbidity and mortality during the initial months of treatment. Observational studies in high-income and resource-limited settings indicate that HIV-infected adults with low vitamin D levels may be at increased risk of mortality, HIV disease progression, and incidence of pulmonary tuberculosis (TB). As a result, vitamin D 3 supplementation may improve survival and treatment outcomes for HIV-infected adults initiating ART. The Trial of Vitamins-4 (ToV4) is an individually randomized, double-blind, placebo-controlled trial of vitamin D 3 (cholecalciferol) supplementation conducted among 4000 HIV-infected adults with low vitamin D levels [25-hydroxyvitamin D (25(OH)D) <30 ng/mL] initiating ART in Dar es Salaam, Tanzania. The two primary aims of the trial are to determine the effect of a vitamin D 3 supplementation regimen on incidence of (1) mortality and (2) pulmonary TB as compared to a matching placebo regimen. The primary safety outcome of the study is incident hypercalcemia. The investigational vitamin D 3 regimen consists of oral supplements containing 50,000 IU vitamin D 3 taken under direct observation at randomization and once a week for 3 weeks (four doses) followed by daily oral supplements containing 2000 IU vitamin D 3 taken at home from the fourth week until trial discharge at 1 year post ART initiation. Trial participants are followed up at weekly clinic visits during the first month of ART and at monthly clinic visits thereafter until trial discharge at 1 year post ART initiation. Secondary aims of the trial are to examine the effect of the vitamin D 3 regimen on CD4 T cell reconstitution, incidence of non-TB comorbidities, body mass index (BMI), depression and anxiety, physical activity, bone health, and immunologic biomarkers. The ToV4 will provide causal evidence on the effect of vitamin D 3 supplementation on incidence of pulmonary TB and mortality among HIV-infected Tanzanian adults initiating ART. The trial will also give insight to whether vitamin D 3 supplementation trials for the prevention of pulmonary TB should be pursued in HIV-uninfected populations. ClinicalTrials.gov, NCT01798680 . Registered on 21 February 2013.

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

NASA Technical Reports Server (NTRS)

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

2002-01-01

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

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 versatility of the setup for invasive and noninvasive (i.e., MRI) measurements. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

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.

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 versatility of the setup for invasive and noninvasive (i.e., MRI) measurements. PMID:27925228

Computed Tomography Angiography in Patients Evaluated for Acute Pulmonary Embolism with Low Serum D-dimer Levels: A Prospective Study

PubMed Central

Gimber, Lana Hirai; Travis, R Ing; Takahashi, Jayme M; Goodman, Torrey L; Yoon, Hyo-Chun

2009-01-01

Context: Pulmonary computed tomography angiography (CTA) and the Wells criteria both have interobserver variability in the assessment of pulmonary embolism (PE). Quantitative D-dimer assay findings have been shown to have a high negative predictive value in patients with low pretest probability of PE. Objective: Evaluate roles for clinical probability and CTA in Emergency Department (ED) patients suspected of acute PE but having a low serum D-dimer level. Design: Prospective observational study of ED patients with possible PE who underwent pulmonary CTA and had D-dimer levels ≤1.0 μg/mL. Main Outcome: Clinical probability of PE determined by ED physicians using standard published criteria; pulmonary CTAs read by initial and study radiologists kept unaware of D-dimer results. Results: In 16 months, 744 patients underwent pulmonary CTA, with 347 study participants who had a D-dimer level ≤ 1.0 μg/mL. In one participant, CTA showed a PE that was agreed on by both the initial and study radiologists. In six participants, the initial findings were reported as positive for PE but were not interpreted as positive by the study radiologist. In none of these participants was PE diagnosed on the basis of clinical probability, of findings on ancillary studies and three-month follow-up examination, or by another radiologist, unaware of findings, acting as a tiebreaker. Conclusion: Pulmonary CTA findings positive for acute embolism should be viewed with caution, especially if the suspected PE is in a distal segmental or subsegmental artery in a patient with a serum D-dimer level of ≤1.0 μg/mL. Furthermore, the Wells criteria may be of limited additional value in this group of patients with low D-dimer levels because most will have low or intermediate clinical probability of PE. PMID:20740096

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.

Pulmonary manifestations of Q fever: analysis of 38 patients.

PubMed

Kelm, Diana J; White, Darin B; Fadel, Hind J; Ryu, Jay H; Maldonado, Fabien; Baqir, Misbah

2017-10-01

Lung involvement in both acute and chronic Q fever is not well described with only a few reported cases of pseudotumor or pulmonary fibrosis in chronic Q fever. The aim of this study was to better understand the pulmonary manifestations of Q fever. We conducted a retrospective cohort study of patients with diagnosis of Q fever at Mayo Clinic Rochester. A total of 69 patients were initially identified between 2001 and 2014. Thirty-eight patients were included in this study as 3 were pediatric patients, 20 did not meet serologic criteria for Q fever, and 8 did not have imaging available at time of initial diagnosis. Descriptive analysis was conducted using JMP software. The median age was 57 years [interquartile range (IQR) 43, 62], 84% from the Midwest, and 13% worked in an occupation involving animals. The most common presentation was fevers (61%). Respiratory symptoms, such as cough, were noted in only 4 patients (11%). Twelve patients (29%) had abnormal imaging studies attributed to Q fever. Three patients (25%) with acute Q fever had findings of consolidation, lymphadenopathy, pleural effusions, and nonspecific pulmonary nodules. Radiographic findings of chronic Q fever were seen in 9 patients (75%) and included consolidation, ground-glass opacities, pleural effusions, lymphadenopathy, pulmonary edema, and lung pseudotumor. Our results demonstrate that pulmonary manifestations are uncommon in Q fever but include cough and consolidation for acute Q fever and radiographic findings of pulmonary edema with pleural effusions, consolidation, and pseudotumor in those with chronic Q fever.

Clinical-Physiological Considerations in Patients Undergoing Staged Palliation for a Functionally Single Ventricle.

PubMed

Penny, Daniel J; Krishnamurthy, Rajesh

2016-08-01

The objectives of this review are to discuss the pathophysiology of the circulation with a functionally univentricular heart, with a focus on the unique physiologic characteristics, which provide the underpinnings for the management of these complex patients. MEDLINE and PubMed. The circulation of the patient with a functionally univentricular heart displays unique physiologic characteristics, which are quite different from those of the normal biventricular circulation. There are profound differences within the heart itself in terms of ventricular function, interventricular interactions, and myocardial architecture, which are likely to have significant implications for the efficiency of ventricular ejection and metabolism. The coupling between the systemic ventricle and the aorta also displays unique features. The 3D orientation of the Fontan anastomosis itself can profoundly impact cardiac output, although the "portal" pulmonary arterial bed is a crucial determinant of overall cardiovascular function. As a result, disease-specific approaches to improve cardiovascular function are required at all stages during the care of these complex patients.

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 also increased, while the diastolic time constant decreased. The forward compression wave energy decreased by ∼8% in controls and ∼6% in PAH patients during expiration compared to inspiration, while the wave speed remained unchanged throughout the respiratory cycle. Wave energy decreased during Valsalva manoeuvre (by ∼45%) and handgrip exercise (by ∼27%) with unaffected wave speed. Moreover, the reservoir and excess pressures decreased during Valsalva manoeuvre but remained unaltered during handgrip exercise. In conclusion, reservoir-excess pressure analysis applied to the pulmonary artery revealed distinctive differences between controls and PAH patients. Variations in the ventricular preload and afterload influence pulmonary arterial wave propagation as demonstrated by changes in wave energy during spontaneous respiration and dynamic stress tests. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Procollagen III N-terminal Propeptide and Desmosine are Released by Matrix Destruction in Pulmonary Tuberculosis

PubMed Central

Seddon, Jo; Kasprowicz, Victoria; Walker, Naomi F.; Yuen, Ho Ming; Sunpath, Henry; Tezera, Liku; Meintjes, Graeme; Wilkinson, Robert J.; Bishai, William R.; Friedland, Jon S.; Elkington, Paul T.

2013-01-01

Background. Tuberculosis is transmitted by patients with pulmonary disease. Matrix metalloproteinases (MMPs) drive lung destruction in tuberculosis but the resulting matrix degradation products (MDPs) have not been studied. We investigate the hypothesis that MMP activity generates matrix turnover products as correlates of lung pathology. Methods. Induced sputum and plasma were collected prospectively from human immunodeficiency virus (HIV) positive and negative patients with pulmonary tuberculosis and controls. Concentrations of MDPs and MMPs were analyzed by ELISA and Luminex array in 2 patient cohorts. Results. Procollagen III N-terminal propeptide (PIIINP) was 3.8-fold higher in induced sputum of HIV-uninfected tuberculosis patients compared to controls and desmosine, released during elastin degradation, was 2.4-fold higher. PIIINP was elevated in plasma of tuberculosis patients. Plasma PIIINP correlated with induced sputum MMP-1 concentrations and radiological scores, demonstrating that circulating MDPs reflect lung destruction. In a second patient cohort of mixed HIV seroprevalence, plasma PIIINP concentration was increased 3.0-fold above controls (P < .001). Plasma matrix metalloproteinase-8 concentrations were also higher in tuberculosis patients (P = .001). Receiver operating characteristic analysis utilizing these 2 variables demonstrated an area under the curve of 0.832 (P < .001). Conclusions. In pulmonary tuberculosis, MMP-driven immunopathology generates matrix degradation products. PMID:23922364

Contribution of Progranulin to Protective Lung Immunity During Bacterial Pneumonia.

PubMed

Zou, Shan; Luo, Qin; Song, Zhixin; Zhang, Liping; Xia, Yun; Xu, Huajian; Xiang, Yu; Yin, Yibing; Cao, Ju

2017-06-01

Progranulin (PGRN) is an important immunomodulatory factor in a variety of inflammatory diseases. However, its role in pulmonary immunity against bacterial infection remains unknown. Pneumonia was induced in PGRN-deficient and normal wild-type mice using Pseudomonas aeruginosa or Staphylococcus aureus, and we assessed the effects of PGRN on survival, bacterial burden, cytokine and chemokine production, and pulmonary leukocyte recruitment after bacterial pneumonia. Patients with community-acquired pneumonia displayed elevated PGRN levels. Likewise, mice with Gram-negative and Gram-positive pneumonia had increased PGRN production in the lung and circulation. Progranulin deficiency led to increased bacterial growth and dissemination accompanied by enhanced lung injury and mortality in bacterial pneumonia, which was associated with impaired recruitment of macrophages and neutrophils in the lung. The reduced number of pulmonary macrophages and neutrophils observed in PGRN-deficient mice was related to a reduction of CCL2 and CXCL1 in the lungs after bacterial pneumonia. Importantly, therapeutic administration of PGRN improved mortality in severe bacterial pneumonia. This study supports a novel role for PGRN in pulmonary immunity and suggests that treatment with PGRN may be a viable therapy for bacterial pneumonia. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Pulmonary fat embolism after pelvic and long bone fractures in a trauma patient.

PubMed

Huang, Brady K; Monu, Johnny U V; Wandtke, John

2009-09-01

Fat embolism is a common complication of pelvic and long bone fractures. Macroscopic fat emboli in the pulmonary arteries on computed tomography have been reported postoperatively after fixation of long bone fractures for trauma, however the quantification of attenuation values of fat emboli have been infrequently reported in the literature. We present a case of pulmonary fat embolism in a 52-year-old female after acute bony trauma sustained during a motor vehicle accident. To the authors' knowledge however, pulmonary fat embolism has not been described on the initial trauma CT scan.

Maternal Dexamethasone Treatment Alters Tissue and Circulating Components of the Renin-Angiotensin System in the Pregnant Ewe and Fetus

PubMed Central

Jellyman, Juanita K.; De Blasio, Miles J.; Johnson, Emma; Giussani, Dino A.; Broughton Pipkin, Fiona; Fowden, Abigail L.

2015-01-01

Antenatal synthetic glucocorticoids promote fetal maturation in pregnant women at risk of preterm delivery and their mechanism of action may involve other endocrine systems. This study investigated the effect of maternal dexamethasone treatment, at clinically relevant doses, on components of the renin-angiotensin system (RAS) in the pregnant ewe and fetus. From 125 days of gestation (term, 145 ± 2 d), 10 ewes carrying single fetuses of mixed sex (3 female, 7 male) were injected twice im, at 10–11 pm, with dexamethasone (2 × 12 mg, n = 5) or saline (n = 5) at 24-hour intervals. At 10 hours after the second injection, maternal dexamethasone treatment increased angiotensin-converting enzyme (ACE) mRNA levels in the fetal lungs, kidneys, and heart and ACE concentration in the circulation and lungs, but not kidneys, of the fetuses. Fetal cardiac mRNA abundance of angiotensin II (AII) type 2 receptor decreased after maternal dexamethasone treatment. Between the two groups of fetuses, there were no significant differences in plasma angiotensinogen or renin concentrations; in transcript levels of renal renin, or AII type 1 or 2 receptors in the lungs and kidneys; or in pulmonary, renal or cardiac protein content of the AII receptors. In the pregnant ewes, dexamethasone administration increased pulmonary ACE and plasma angiotensinogen, and decreased plasma renin, concentrations. Some of the effects of dexamethasone treatment on the maternal and fetal RAS were associated with altered insulin and thyroid hormone activity. Changes in the local and circulating RAS induced by dexamethasone exposure in utero may contribute to the maturational and tissue-specific actions of antenatal glucocorticoid treatment. PMID:26039155

Effects of pulmonary exposure to chemically-distinct welding fumes on neuroendocrine markers of toxicity.

PubMed

Krajnak, K; Sriram, K; Johnson, C; Roberts, J R; Mercer, R; Miller, G R; Wirth, O; Antonini, J M

2017-01-01

Exposure to welding fumes may result in disorders of the pulmonary, cardiovascular, and reproductive systems. Welders are also at a greater risk of developing symptoms similar to those seen in individuals with idiopathic Parkinson's disease. In welders, there are studies that suggest that alterations in circulating prolactin concentrations may be indicative of injury to the dopamine (DA) neurons in the substantia nigra. The goal of these studies was to use an established model of welding particulate exposure to mimic the effects of welding fume inhalation on reproductive functions. Since previous investigators suggested that changes in circulating prolactin may be an early marker of DA neuron injury, movement disorders, and reproductive dysfunction, prolactin, hypothalamic tyrosine hydroxylase (TH) levels (a marker of DA synthesis), and other measures of hypothalamic-pituitary-gonadal (HPG) function were measured after repetitive instillation of welding fume particulates generated by flux core arc-hard surfacing (FCA-HS), manual metal arc-hard surfacing (MMA-HS) or gas metal arc-mild steel (GMA-MS) welding, or manganese chloride (MnCl 2 ). Exposure to welding fume particulate resulted in the accumulation of various metals in the pituitary and testes of rats, along with changes in hypothalamic TH and serum prolactin levels. Exposure to particulates with high concentrations of soluble manganese (Mn) appeared to exert the greatest influence on TH activity levels and serum prolactin concentrations. Thus, circulating prolactin levels may serve as a biomarker for welding fume/Mn-induced neurotoxicity. Other reproductive measures were collected, and these data were consistent with epidemiological findings that prolactin and testosterone may serve as biomarkers of welding particulate induced DA neuron and reproductive dysfunction.

Poor Prognosis Indicated by Venous Circulating Tumor Cell Clusters in Early-Stage Lung Cancers.

PubMed

Murlidhar, Vasudha; Reddy, Rishindra M; Fouladdel, Shamileh; Zhao, Lili; Ishikawa, Martin K; Grabauskiene, Svetlana; Zhang, Zhuo; Lin, Jules; Chang, Andrew C; Carrott, Philip; Lynch, William R; Orringer, Mark B; Kumar-Sinha, Chandan; Palanisamy, Nallasivam; Beer, David G; Wicha, Max S; Ramnath, Nithya; Azizi, Ebrahim; Nagrath, Sunitha

2017-09-15

Early detection of metastasis can be aided by circulating tumor cells (CTC), which also show potential to predict early relapse. Because of the limited CTC numbers in peripheral blood in early stages, we investigated CTCs in pulmonary vein blood accessed during surgical resection of tumors. Pulmonary vein (PV) and peripheral vein (Pe) blood specimens from patients with lung cancer were drawn during the perioperative period and assessed for CTC burden using a microfluidic device. From 108 blood samples analyzed from 36 patients, PV had significantly higher number of CTCs compared with preoperative Pe ( P < 0.0001) and intraoperative Pe ( P < 0.001) blood. CTC clusters with large number of CTCs were observed in 50% of patients, with PV often revealing larger clusters. Long-term surveillance indicated that presence of clusters in preoperative Pe blood predicted a trend toward poor prognosis. Gene expression analysis by RT-qPCR revealed enrichment of p53 signaling and extracellular matrix involvement in PV and Pe samples. Ki67 expression was detected in 62.5% of PV samples and 59.2% of Pe samples, with the majority (72.7%) of patients positive for Ki67 expression in PV having single CTCs as opposed to clusters. Gene ontology analysis revealed enrichment of cell migration and immune-related pathways in CTC clusters, suggesting survival advantage of clusters in circulation. Clusters display characteristics of therapeutic resistance, indicating the aggressive nature of these cells. Thus, CTCs isolated from early stages of lung cancer are predictive of poor prognosis and can be interrogated to determine biomarkers predictive of recurrence. Cancer Res; 77(18); 5194-206. ©2017 AACR . ©2017 American Association for Cancer Research.

Number of circulating endothelial progenitor cells and intratumoral microvessel density in non-small cell lung cancer patients: differences in angiogenic status between adenocarcinoma histologic subtypes.

PubMed

Maeda, Ryo; Ishii, Genichiro; Ito, Masami; Hishida, Tomoyuki; Yoshida, Junji; Nishimura, Mitsuyo; Haga, Hironori; Nagai, Kanji; Ochiai, Atsushi

2012-03-01

Angiogenesis plays a significant role in tumor progression. This study examined the association between the number of circulating endothelial progenitor cells (EPCs), intratumoral microvessel density (MVD) (both of which may be markers for neovascularization), and lung cancer histological types, particularly adenocarcinoma histological subtypes. A total of 83 stage I non-small cell lung cancer (NSCLC) patients underwent complete tumor resection between November 2009 and July 2010. The number of EPCs from the pulmonary artery of the resected lungs was measured by assaying CD34/vascular endothelial growth factor receptor 2 positive cells, and the MVD was assessed immunohistochemically in tumor specimens by staining for CD34. A statistically significant correlation between the number of EPCs from pulmonary artery and intratumoral MVD was found (p < 0.001). No statistically significant differences in the number of EPCs and the MVD were observed between the adenocarcinomas and the squamous cell carcinomas. Among the adenocarcinoma histological subtypes, a higher number of EPCs and MVD were found significantly more frequently in solid adenocarcinomas than in nonsolid adenocarcinomas (p < 0.001 and p = 0.011, respectively). In addition, solid adenocarcinomas showed higher levels of vascular endothelial growth factor using quantitative real-time polymerase chain reaction in the tumor tissue samples than in the nonsolid adenocarcinomas (p = 0.005). The higher number of circulating EPCs and the MVD of solid adenocarcinoma may indicate the presence of differences in the tumor angiogenic status between early-stage adenocarcinoma histological subtypes. Among adenocarcinoma patients, patients with solid adenocarcinoma may be the best candidates for antiangiogenic therapies.

Primary pulmonary malignant melanoma: a clinicopathologic study of two cases.

PubMed

Gong, Li; Liu, Xiao-Yan; Zhang, Wen-Dong; Zhu, Shao-Jun; Yao, Li; Han, Xiu-Juan; Lan, Miao; Li, Yan-Hong; Zhang, Wei

2012-09-19

Malignant melanoma involving the respiratory tract is nearly always metastatic in origin, and primary tumors are very rare. To our knowledge, about 30 cases have been reported in the English literature, one of which involved multiple brain metastases. Here, we report two cases of primary pulmonary malignant melanoma. The first case, which occurred in a 52-year-old Chinese female patient who died 4 months after the initial diagnosis, involved rapid intrapulmonary and intracranial metastases. The second patient, a 65-year-old female, underwent surgical excision, and clinical examination, histopathological characteristics, and immunohistochemical features supported the diagnosis of pulmonary malignant melanoma. No evidence for recurrence and/or metastasis has been found more than one year after the initial surgery. To establish the diagnosis of primary pulmonary malignant melanoma, any extrapulmonary origin must be excluded by detailed examination. Moreover, the tumor should be removed surgically whether it occurs as a single lesion or multiple lesions. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1480477335765055.

Direction of an initial saccade depends on radiological expertise

NASA Astrophysics Data System (ADS)

Pietrzyk, Mariusz W.; McEntee, Mark F.; Evanoff, Michael E.; Brennan, Patrick C.; Mello-Thoms, Claudia R.

2014-03-01

Purpose: To evaluate the role of radiographic details in global impression of chest x-ray images viewed by experts in thoracic and non-thoracic domains. Materials and Methods: The study was approved by IRB. Five thoracic and five non-thoracic radiologists participated in two tachistoscopic (one low pass and one with the entire frequency spectrum, each lasting 270 ms) each containing 50 PA chest radiographs with 50% prevalence of pulmonary nodule. Eye movements were monitored in order to evaluate a pre-saccade shift of visual attention, saccade latency, decision time and the time to first fixation on a pulmonary nodule. Results: Thoracic radiologists showed significantly higher pre-saccadic shift of visual attention towards pulmonary nodules once using the full frequency spectrum (p < 0.05). An initial saccade orientation made by these radiologists on full resolution images correlated at significant level with their confidence ranking of pulmonary nodules (ρ = -0.387, p < 0.001). Conclusions: Thoracic radiologists benefited from high spatial frequency appearance during a rapid presentation of chest radiograph by allocating pre-saccade attention towards pulmonary nodules. This behavior correlated with a higher number of correct decisions, followed by higher confidence in the decisions made, and briefer reaction times.

Cavopulmonary Anastomosis in a Patient With Arrhythmogenic Right Ventricular Cardiomyopathy With Severe Right Ventricular Dysfunction.

PubMed

Vaidyanathan, Swaminathan; Kothandam, Sivakumar; Kumar, Rajesh; Indrajith, Sujatha Desai; Agarwal, Ravi

2017-01-01

A 26-year-old lady presented with exertional dyspnea, palpitations, central cyanosis, and oxygen saturations of 80% in room air. Her electrocardiogram, echocardiogram, and cardiac magnetic resonance were diagnostic of arrhythmogenic right ventricular dysplasia. There was no documented ventricular arrhythmia or syncopal episodes and Holter recordings were repeatedly normal. Cardiac hemodynamics showed right to left shunt through atrial septal defect, low pulmonary blood flow, normal atrial pressures, and minimally elevated right ventricular end-diastolic pressures. Since her presenting symptoms and cyanosis were attributed to reduced pulmonary blood flow, she underwent off-pump cavopulmonary anastomosis between right superior vena cava and right pulmonary artery. As we intended to avoid the adverse effect of extracorporeal circulation on the myocardial function and pulmonary vasculature, we did not attempt to reduce the size of the atrial septal defect. Her postoperative period was uneventful; oxygen saturation improved to 89% with significant improvement in effort tolerance. At 18-month follow-up, there were no ventricular arrhythmias on surveillance. The clinical presentation of this disease may vary from serious arrhythmias warranting defibrillators and electrical ablations at one end to right ventricular pump failure warranting cardiomyoplasty or right ventricular exclusion procedures at the other end. However, when the presentation was unusual with severe cyanosis through a stretched foramen ovale leading to reduced pulmonary blood flows, Glenn shunt served as a good palliation and should be considered as one of the options in such patients.

Effect of hypoxia and hyperoxia on exercise performance in healthy individuals and in patients with pulmonary hypertension: a systematic review.

PubMed

Ulrich, Silvia; Schneider, Simon R; Bloch, Konrad E

2017-12-01

Exercise performance is determined by oxygen supply to working muscles and vital organs. In healthy individuals, exercise performance is limited in the hypoxic environment at altitude, when oxygen delivery is diminished due to the reduced alveolar and arterial oxygen partial pressures. In patients with pulmonary hypertension (PH), exercise performance is already reduced near sea level due to impairments of the pulmonary circulation and gas exchange, and, presumably, these limitations are more pronounced at altitude. In studies performed near sea level in healthy subjects, as well as in patients with PH, maximal performance during progressive ramp exercise and endurance of submaximal constant-load exercise were substantially enhanced by breathing oxygen-enriched air. Both in healthy individuals and in PH patients, these improvements were mediated by a better arterial, muscular, and cerebral oxygenation, along with a reduced sympathetic excitation, as suggested by the reduced heart rate and alveolar ventilation at submaximal isoloads, and an improved pulmonary gas exchange efficiency, especially in patients with PH. In summary, in healthy individuals and in patients with PH, alterations in the inspiratory Po 2 by exposure to hypobaric hypoxia or normobaric hyperoxia reduce or enhance exercise performance, respectively, by modifying oxygen delivery to the muscles and the brain, by effects on cardiovascular and respiratory control, and by alterations in pulmonary gas exchange. The understanding of these physiological mechanisms helps in counselling individuals planning altitude or air travel and prescribing oxygen therapy to patients with PH.

Effect of fenspiride on pulmonary function in the rat and guinea pig.

PubMed

Bee, D; Laude, E A; Emery, C J; Howard, P

1995-03-01

1. Fenspiride is an anti-inflammatory agent that may have a role in reversible obstructive airways disease. Small, but significant, improvements have been seen in airways function and arterial oxygen tension in patients with mild chronic obstructive pulmonary disease. These changes have been attributed to the anti-inflammatory properties of the drug. However, airways function can be improved by other means, e.g. improved ventilation/perfusion ratio or reduced airways resistance. The possibility that fenspiride may have actions other than anti-inflammatory was investigated in two animal species. 2. In the rat, actions on the pulmonary circulation were investigated in the isolated perfused lung, but fenspiride proved to be a poor pulmonary vasodilator, showing only a small reversal of the raised pulmonary artery pressure induced by hypoxia. 3. Ventilation was measured in the anaesthetized rat using whole-body plethysmography. Fenspiride caused no increase in ventilation or changes in arterial blood gases. However, a profound hypotensive action was observed with high doses. 4. The possibility that a decrease in airways resistance (R(aw)) might occur with fenspiride was investigated in anaesthetized guinea pigs. Capsaicin (30 mumol/l) was used to increase baseline R(aw) through bronchoconstriction. Fenspiride gave a dose-dependent partial reversal of the raised R(aw), and its administration by aerosol proved as efficacious as the intravenous route. In addition, the hypotensive side-effect found with intravenous injection was alleviated by aerosolized fenspiride.(ABSTRACT TRUNCATED AT 250 WORDS)

Post traumatic inferior vena cava thrombosis: A case report and review of literature.

PubMed

Chakroun, Amine; Nakhli, Mohamed Said; Kahloul, Mohamed; Harrathi, Mohamed Amine; Naija, Walid

2017-01-01

Post traumatic inferior vena cava (IVC) thrombosis is a rare and not well described entity with nonspecific clinical presentation. It remains a therapeutic challenge in traumatic context because of haemorrhagic risk due to anticoagulation. We report a case of IVC thrombosis in an 18 year-old man who presented with liver injury following a traffic crash. The thrombosis was incidentally diagnosed on admission by computed tomography. The patient was managed conservatively without anticoagulation initially considering the increasing haemorrhagic risk. IVC filter placing was not possible because of the unusual localization of the thrombus. Unfractionated heparin was started on the third day after CT scan control showing stability of hepatic lesions with occurrence of a pulmonary embolism. The final outcome was good. The management of post traumatic IVC thrombosis is not well described. Medical approach consists in conservative management with anticoagulation which requires the absence of active bleeding lesions. Surgical treatment is commonly based on thrombectomy under extracorporeal circulation. Interventional vascular techniques have become an important alternative approach for the treatment of many vessel lesions. Their main advantages are the relative ease and speed with which they can be performed. Post traumatic IVC thrombosis is a rare condition. Its management is not well defined. Early anticoagulation should be discussed on a case-by-case basis. Other alternatives such IVC filter or surgical thrombectomy may be used when the bleeding risk is increased. The most serious risk is pulmonary embolism. Outcome can be favorable even with non surgical approaches. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Mathematical modelling of the maternal cardiovascular system in the three stages of pregnancy.

PubMed

Corsini, Chiara; Cervi, Elena; Migliavacca, Francesco; Schievano, Silvia; Hsia, Tain-Yen; Pennati, Giancarlo

2017-09-01

In this study, a mathematical model of the female circulation during pregnancy is presented in order to investigate the hemodynamic response to the cardiovascular changes associated with each trimester of pregnancy. First, a preliminary lumped parameter model of the circulation of a non-pregnant female was developed, including the heart, the systemic circulation with a specific block for the uterine district and the pulmonary circulation. The model was first tested at rest; then heart rate and vascular resistances were individually varied to verify the correct response to parameter alterations characterising pregnancy. In order to simulate hemodynamics during pregnancy at each trimester, the main changes applied to the model consisted in reducing vascular resistances, and simultaneously increasing heart rate and ventricular wall volumes. Overall, reasonable agreement was found between model outputs and in vivo data, with the trends of the cardiac hemodynamic quantities suggesting correct response of the heart model throughout pregnancy. Results were reported for uterine hemodynamics, with flow tracings resembling typical Doppler velocity waveforms at each stage, including pulsatility indexes. Such a model may be used to explore the changes that happen during pregnancy in female with cardiovascular diseases. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Liquid Biopsy in Lung Cancer: A Perspective From Members of the Pulmonary Pathology Society.

PubMed

Sholl, Lynette M; Aisner, Dara L; Allen, Timothy Craig; Beasley, Mary Beth; Cagle, Philip T; Capelozzi, Vera L; Dacic, Sanja; Hariri, Lida P; Kerr, Keith M; Lantuejoul, Sylvie; Mino-Kenudson, Mari; Raparia, Kirtee; Rekhtman, Natasha; Roy-Chowdhuri, Sinchita; Thunnissen, Eric; Tsao, Ming; Vivero, Marina; Yatabe, Yasushi

2016-08-01

Liquid biopsy has received extensive media coverage and has been called the holy grail of cancer detection. Attempts at circulating tumor cell and genetic material capture have been progressing for several years, and recent financially and technically feasible improvements of cell capture devices, plasma isolation techniques, and highly sensitive polymerase chain reaction- and sequencing-based methods have advanced the possibility of liquid biopsy of solid tumors. Although practical use of circulating RNA-based testing has been hindered by the need to fractionate blood to enrich for RNAs, the detection of circulating tumor cells has profited from advances in cell capture technology. In fact, the US Food and Drug Administration has approved one circulating tumor cell selection platform, the CellSearch System. Although the use of liquid biopsy in a patient population with a genomically defined solid tumor may potentially be clinically useful, it currently does not supersede conventional pretreatment tissue diagnosis of lung cancer. Liquid biopsy has not been validated for lung cancer diagnosis, and its lower sensitivity could lead to significant diagnostic delay if liquid biopsy were to be used in lieu of tissue biopsy. Ultimately, notwithstanding the enthusiasm encompassing liquid biopsy, its clinical utility remains unproven.

Transcatheter Amplatzer vascular plug-embolization of a giant postnephrectomy arteriovenous fistula combined with an aneurysm of the renal pedicle by through-and-through, arteriovenous access

PubMed Central

Kayser, Ole; Schäfer, Philipp

2013-01-01

Although endovascular transcatheter embolization of arteriovenous fistulas is minimally invasive, the torrential flow prevailing within a fistula implies the risk of migration of the deployed embolization devices into the downstream venous and pulmonary circulation. We present the endovascular treatment of a giant postnephrectomy arteriovenous fistula between the right renal pedicle and the residual renal vein in a 63-year-old man. The purpose of this case report is to demonstrate that the Amplatzer vascular plug (AVP) can be safely positioned to embolize even relatively large arteriovenous fistulas (AVFs). Secondly, we illustrate that this occluder can even be introduced to the fistula via a transvenous catheter in cases where it is initially not possible to advance the deployment-catheter through a tortuous feeder artery. Migration of the vascular plug was ruled out at follow-up 4 months subsequently to the intervention. Thus, the Amplatzer vascular plug and the arteriovenous through-and-through guide wire access with subsequent transvenous deployment should be considered in similar cases. PMID:23326248

Microfluidic Investigation Reveals Distinct Roles for Actin Cytoskeleton and Myosin II Activity in Capillary Leukocyte Trafficking

PubMed Central

Gabriele, Sylvain; Benoliel, Anne-Marie; Bongrand, Pierre; Théodoly, Olivier

2009-01-01

Circulating leukocyte sequestration in pulmonary capillaries is arguably the initiating event of lung injury in acute respiratory distress syndrome. We present a microfluidic investigation of the roles of actin organization and myosin II activity during the different stages of leukocyte trafficking through narrow capillaries (entry, transit and shape relaxation) using specific drugs (latrunculin A, jasplakinolide, and blebbistatin). The deformation rate during entry reveals that cell stiffness depends strongly on F-actin organization and hardly on myosin II activity, supporting a microfilament role in leukocyte sequestration. In the transit stage, cell friction is influenced by stiffness, demonstrating that the actin network is not completely broken after a forced entry into a capillary. Conversely, membrane unfolding was independent of leukocyte stiffness. The surface area of sequestered leukocytes increased by up to 160% in the absence of myosin II activity, showing the major role of molecular motors in microvilli wrinkling and zipping. Finally, cell shape relaxation was largely independent of both actin organization and myosin II activity, whereas a deformed state was required for normal trafficking through capillary segments. PMID:19450501

Integrating bio-prosthetic valves in the Fontan operation - Novel treatment to control retrograde flow in caval veins

NASA Astrophysics Data System (ADS)

Vukicevic, Marija; Conover, Timothy; Zhou, Jian; Hsia, Tain-Yen; Figliola, Richard

2012-11-01

For a child born with only one functional heart ventricle, the sequence of palliative surgeries typically culminates in the Fontan operation. This procedure is usually successful initially, but leads to later complications, for reasons not fully understood. Examples are respiratory-dependent retrograde flows in the caval and hepatic veins, and increased pulmonary vascular resistance (PVR), hypothesized to be responsible for elevated pressure in the liver and disease of the liver and intestines. Here we study the parameters responsible for retrograde flows in the inferior vena cava (IVC) and hepatic vein (HV), and investigate two novel interventions to control retrograde flow: implanting either a Medtronic Contegra valved conduit or an Edwards lifescience pericardial aortic valve in the IVC or HV. We performed the experiments in a multi-scale, patient specific mock circuit, with normal and elevated PVR, towards the optimization of the Fontan circulation. The results show that both valves can significantly reduce retrograde flows in the veins, suggesting potential advantages in the treatment of the patients with congenital heart diseases. Fondation Leducq

Secondary Pulmonary Hypertension and Right-Sided Heart Failure at Presentation in Grave's Disease.

PubMed

Ganeshpure, Swapnil Panjabrao; Vaidya, Gaurang Nandkishor; Gattani, Vipul

2012-01-01

A young female presented with evidence of right-sided heart failure and was subsequently found to have significant pulmonary artery hypertension (PAH). Because of her normal left ventricular function and pulmonary capillary wedge pressure, the most probable site of etiology seemed to be the pulmonary vasculature. All the common possible secondary causes of PAH were ruled out, but during the investigations, she was found to have elevated thyroid function tests compatible with the diagnosis of Grave's disease. The treatment of Grave's disease, initially by medications and subsequently by radioiodine therapy, was associated with a significant reduction in the pulmonary artery systolic pressure. The purpose of this case report is to highlight one of the unusual and underdiagnosed presentations of Grave's disease.

Serial changes and prognostic implications of CT findings in combined pulmonary fibrosis and emphysema: comparison with fibrotic idiopathic interstitial pneumonias alone.

PubMed

Lee, Geewon; Kim, Ki Uk; Lee, Ji Won; Suh, Young Ju; Jeong, Yeon Joo

2017-05-01

Background Although fibrotic idiopathic interstitial pneumonias (IIPs) alone and those combined with pulmonary emphysema are naturally progressive diseases, the process of deterioration and outcomes are variable. Purpose To evaluate and compare serial changes of computed tomography (CT) abnormalities and prognostic predictive factors in fibrotic IIPs alone and those combined with pulmonary emphysema. Material and Methods A total of 148 patients with fibrotic IIPs alone (82 patients) and those combined with pulmonary emphysema (66 patients) were enrolled. Semi-quantitative CT analysis was used to assess the extents of CT characteristics which were evaluated on initial and follow-up CT images. Univariate and multivariate analyses were performed to assess the effects of clinical and CT variables on survival. Results Significant differences were noted between fibrotic scores, as determined using initial CT scans, in the fibrotic IIPs alone (21.22 ± 9.83) and those combined with pulmonary emphysema groups (14.70 ± 7.28) ( P < 0.001). At follow-up CT scans, changes in the extent of ground glass opacities (GGO) were greater ( P = 0.031) and lung cancer was more prevalent ( P = 0.001) in the fibrotic IIPs combined with pulmonary emphysema group. Multivariate Cox proportional hazards analysis showed changes in the extent of GGO (hazard ratio, 1.056) and the presence of lung cancer (hazard ratio, 4.631) were predictive factors of poor survivals. Conclusion Although patients with fibrotic IIPs alone and those combined with pulmonary emphysema have similar mortalities, lung cancer was more prevalent in patients with fibrotic IIPs combined with pulmonary emphysema. Furthermore, changes in the extent of GGO and the presence of lung cancer were independent prognostic factors of poor survivals.

Pulmonary Hypertension in Wild Type Mice and Animals with Genetic Deficit in KCa2.3 and KCa3.1 Channels

PubMed Central

Sadda, Veeranjaneyulu; Nielsen, Gorm; Hedegaard, Elise Røge; Mogensen, Susie; Köhler, Ralf; Simonsen, Ulf

2014-01-01

Objective In vascular biology, endothelial KCa2.3 and KCa3.1 channels contribute to arterial blood pressure regulation by producing membrane hyperpolarization and smooth muscle relaxation. The role of KCa2.3 and KCa3.1 channels in the pulmonary circulation is not fully established. Using mice with genetically encoded deficit of KCa2.3 and KCa3.1 channels, this study investigated the effect of loss of the channels in hypoxia-induced pulmonary hypertension. Approach and Result Male wild type and KCa3.1−/−/KCa2.3T/T(+DOX) mice were exposed to chronic hypoxia for four weeks to induce pulmonary hypertension. The degree of pulmonary hypertension was evaluated by right ventricular pressure and assessment of right ventricular hypertrophy. Segments of pulmonary arteries were mounted in a wire myograph for functional studies and morphometric studies were performed on lung sections. Chronic hypoxia induced pulmonary hypertension, right ventricular hypertrophy, increased lung weight, and increased hematocrit levels in either genotype. The KCa3.1−/−/KCa2.3T/T(+DOX) mice developed structural alterations in the heart with increased right ventricular wall thickness as well as in pulmonary vessels with increased lumen size in partially- and fully-muscularized vessels and decreased wall area, not seen in wild type mice. Exposure to chronic hypoxia up-regulated the gene expression of the KCa2.3 channel by twofold in wild type mice and increased by 2.5-fold the relaxation evoked by the KCa2.3 and KCa3.1 channel activator NS309, whereas the acetylcholine-induced relaxation - sensitive to the combination of KCa2.3 and KCa3.1 channel blockers, apamin and charybdotoxin - was reduced by 2.5-fold in chronic hypoxic mice of either genotype. Conclusion Despite the deficits of the KCa2.3 and KCa3.1 channels failed to change hypoxia-induced pulmonary hypertension, the up-regulation of KCa2.3-gene expression and increased NS309-induced relaxation in wild-type mice point to a novel mechanism to counteract pulmonary hypertension and to a potential therapeutic utility of KCa2.3/KCa3.1 activators for the treatment of pulmonary hypertension. PMID:24858807

Effect of Milrinone Infusion on Pulmonary Vasculature and Stroke Work Indices: A Single-Center Retrospective Analysis in 69 Patients Awaiting Cardiac Transplantation.

PubMed

Abramov, Dmitry; Haglund, Nicholas A; Di Salvo, Thomas G

2017-08-01

Although milrinone infusion is reported to benefit left ventricular function in chronic left heart failure, few insights exist regarding its effects on pulmonary circulation and right ventricular function. We retrospectively reviewed right heart catheterization data at baseline and during continuous infusion of milrinone in 69 patients with advanced heart failure and analyzed the effects on ventricular stroke work indices, pulmonary vascular resistance and pulmonary arterial compliance. Compared to baseline, milrinone infusion after a mean 58 ± 61 days improved mean left ventricular stroke work index (1540 ± 656 vs. 2079 ± 919 mmHg·mL/m 2 , p = 0.0007) to a much greater extent than right ventricular stroke work index (616 ± 346 vs. 654 ± 332, p = 0.053); however, patients with below median stroke work indices experienced a significant improvement in both left and right ventricular stroke work performance. Overall, milrinone reduced left and right ventricular filling pressures and pulmonary and systemic vascular resistance by approximately 20%. Despite an increase in pulmonary artery capacitance (2.3 ± 1.6 to 3.0 ± 2.0, p = 0.013) and a reduction in pulmonary vascular resistance (3.8 ± 2.3 to 3.0 ± 1.7 Wood units), milrinone did not reduce the transpulmonary gradient (13 ± 7 vs. 12 ± 6 mmHg, p = 0.252), the pulmonary artery pulse pressure (25 ± 10 vs. 24 ± 10, p = 0.64) or the pulmonary artery diastolic to pulmonary capillary wedge gradient (2.0 ± 6.5 vs. 2.4 ± 6.0, p = 0.353). Milrinone improved left ventricular stroke work indices to a greater extent than right ventricular stroke work indices and had beneficial effects on right ventricular net input impedance, predominantly via augmentation of left ventricular stroke volume and passive unloading of the pulmonary circuit. Patients who had the worst biventricular performance benefited the most from chronic milrinone infusion.

Study of Cardiac Arrest Caused by Acute Pulmonary Thromboembolism and Thrombolytic Resuscitation in a Porcine Model

PubMed Central

Zhao, Lian-Xing; Li, Chun-Sheng; Yang, Jun; Tong, Nan; Xiao, Hong-Li; An, Le

2016-01-01

Background: The success rate of resuscitation in cardiac arrest (CA) caused by pulmonary thromboembolism (PTE) is low. Furthermore, there are no large animal models that simulate clinical CA. The aim of this study was to establish a porcine CA model caused by PTE and to investigate the pathophysiology of CA and postresuscitation. Methods: This model was induced in castrated male pigs (30 ± 2 kg; n = 21) by injecting thrombi (10–15 ml) via the left external jugular vein. Computed tomographic pulmonary angiography (CTPA) was performed at baseline, CA, and return of spontaneous circulation (ROSC). After CTPA during CA, cardiopulmonary resuscitation (CPR) with thrombolysis (recombinant tissue plasminogen activator 50 mg) was initiated. Hemodynamic, respiratory, and blood gas data were monitored. Cardiac troponins T, cardiac troponin I, creatine kinase-MB, myoglobin, and brain natriuretic peptide (BNP) were measured by enzyme-linked immunosorbent assay. Data were compared between baseline and CA with paired-sample t-test and compared among different time points for survival animals with repeated measures analysis of variance. Results: Seventeen animals achieved CA after emboli injection, while four achieved CA after 5–8 ml more thrombi. Nine animals survived 6 h after CPR. CTPA showed obstruction of the pulmonary arteries. Mean aortic pressure data showed occurrence of CA caused by PTE (Z = −2.803, P = 0.002). The maximal rate of mean increase of left ventricular pressure (dp/dtmax) was statistically decreased (t = 6.315, P = 0.000, variation coefficient = 0.25), and end-tidal carbon dioxide partial pressure (PetCO2) decreased to the lowest value (t = 27.240, P = 0.000). After ROSC (n = 9), heart rate (HR) and mean right ventricular pressure (MRVP) remained different versus baseline until 2 h after ROSC (HR, P = 0.036; MRVP, P = 0.027). Myoglobin was statistically increased from CA to 1 h after ROSC (P = 0.036, 0.026, 0.009, respectively), and BNP was increased from 2 h to 6 h after ROSC (P = 0.012, 0.014, 0.039, respectively). Conclusions: We established a porcine model of CA caused by PTE. The dp/dtmax and PetCO2 may be important for the occurrence of CA, while MRVP may be more important in postresuscitation. PMID:27364794

Further observations on mesenteric vasoconstriction, survival and the clotting defect after endotoxin administration

PubMed Central

Cohen, M. M.; Greenway, C. V.; Innes, I. R.; Lister, G. E.; Murthy, V. S.; Scott, G. D.

1973-01-01

1. The initial response after endotoxin administration (3 mg/kg) in cats involved pulmonary vasoconstriction. This was not seen when endotoxin was given by slow infusion and it could be prevented after a bolus injection of endotoxin by pretreatment of the cats with aspirin (10 mg/kg). Intense mesenteric vasoconstriction occurred in all the cats. 2. The mesenteric vasoconstriction was a specific response of the mesenteric blood vessels. At the time the mesenteric bed constricted, the renal bed dilated, the hepatic arterial bed remained unchanged and the smooth muscle of the intestinal wall relaxed. 3. Arterial blood from cats with a fully developed mesenteric vasoconstriction after endotoxin administration was perfused through a normal intestine. No immediate vasoconstriction developed but the perfused intestine constricted slowly over 60 minutes. This suggests that mesenteric constriction was not due to circulating vasoconstrictor factors or the intestinal innervation, but involved a slow local mechanism within the intestine. It could not be prevented or reversed by a variety of pharmacological agents. 4. These observations suggest that endotoxin caused a unique type of mesenteric vasoconstriction in cats by a local mechanism which took up to 60 min to develop, was sufficiently potent to reduce mesenteric flow to <30% control, and was maintained until death of the cats. Blood from these animals did not clot when placed in a glass tube. 5. The mesenteric constriction and the clotting defect could be prevented by repeated administration of aminophylline and dextran solution before and after a bolus intravenous injection of endotoxin. Arterial pressure and mesenteric flow were maintained for at least 10 h in these experiments. Inadequate treatment intensified rather than reduced the intestinal mucosal damage. 6. Cats were treated with aspirin, endotoxin and the optimal regimen for prevention of the mesenteric constriction and allowed to recover from the anaesthetic agent. In this series, 63% survived indefinitely compared to 25% after aspirin and endotoxin treatment and 0% after endotoxin alone. 7. The possible mechanisms of action of aspirin and aminophylline-dextran solution are discussed. Our failure to obtain 100% survival is probably due to pulmonary damage which develops 10-24 h after endotoxin administration. This delayed pulmonary action of endotoxin is not prevented by aspirin treatment and it seems unlikely that aspirin will be of any value in the treatment of the pulmonary lesion in man. PMID:4788202

Sarcoidosis-associated pulmonary hypertension.

PubMed

Cordova, Francis C; D'Alonzo, Gilbert

2013-09-01

Pulmonary hypertension is a serious complication of sarcoidosis. This review discusses clinical characteristics of patients with sarcoid-associated pulmonary hypertension (SAPH) and pitfalls in the diagnosis, and highlights potential therapies. SAPH is common in patients with advanced disease, but it can occur in patients with minimal disease burden. Risk factors for SAPH include restrictive lung physiology, hypoxemia, advanced Scadding chest X-ray stage, and low carbon monoxide diffusion capacity. Echocardiogram is a good initial screening tool in the diagnosis of pulmonary hypertension, but right heart catheterization is necessary to confirm the diagnosis. Treatment with pulmonary vasodilators, including endothelin antagonists, can lead to improvements in pulmonary hemodynamics in some patients but may not improve their exercise capacity. Forced vital capacity is an important predictor of exercise performance in patients with SAPH. Clinical observations and response to specific therapies for pulmonary hypertension suggest the presence of different SAPH phenotypes. Patients who complain of persistent dyspnea should be screened for the presence of pulmonary hypertension. The prognosis of SAPH is poor and it is prudent to consider referral of these patients for lung transplantation. In some patients with SAPH, treatment with anti-inflammatory agents and pulmonary vasodilators can lower pulmonary arterial pressures, improve dyspnea and functionality, and enhance overall quality of life.

A pig model of acute right ventricular afterload increase by hypoxic pulmonary vasoconstriction.

PubMed

Knai, Kathrine; Skjaervold, Nils Kristian

2017-01-03

The aim of this study was to construct a non-invasive model for acute right ventricular afterload increase by hypoxic pulmonary vasoconstriction. Intact animal models are vital to improving our understanding of the pathophysiology of acute right ventricular failure. Acute right ventricular failure is caused by increased afterload of the right ventricle by chronic or acute pulmonary hypertension combined with regionally or globally reduced right ventricular contractile capacity. Previous models are hampered by their invasiveness; this is unfortunate as the pulmonary circulation is a low-pressure system that needs to be studied in closed chest animals. Hypoxic pulmonary vasoconstriction is a mechanism that causes vasoconstriction in alveolar vessels in response to alveolar hypoxia. In this study we explored the use of hypoxic pulmonary vasoconstriction as a means to increase the pressure load on the right ventricle. Pulmonary hypertension was induced by lowering the FiO 2 to levels below the physiological range in eight anesthetized and mechanically ventilated pigs. The pigs were monitored with blood pressure measurements and blood gases. The mean pulmonary artery pressures (mPAP) of the animals increased from 18.3 (4.2) to 28.4 (4.6) mmHg and the pulmonary vascular resistance (PVR) from 254 (76) dyns/cm 5 to 504 (191) dyns/cm 5 , with a lowering of FiO 2 from 0.30 to 0.15 (0.024). The animals' individual baseline mPAPs varied substantially as did their response to hypoxia. The reduced FiO 2 level yielded an overall lowering in oxygen offer, but the global oxygen consumption was unaltered. We showed in this study that the mPAP and the PVR could be raised by approximately 100% in the study animals by lowering the FiO 2 from 0.30 to 0.15 (0.024). We therefore present a novel method for minimally invasive (closed chest) right ventricular afterload manipulations intended for future studies of acute right ventricular failure. The method should in theory be reversible, although this was not studied in this work.

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.

Atrial isomerism: a surgical experience.

PubMed

Sinzobahamvya, N; Arenz, C; Brecher, A M; Urban, A E

1999-06-01

Most publications on atrial isomerism are autopsy or case reports. The authors review 41 consecutive children operated on from 1980 through to 1996 with emphasis on associated cardiac anomalies, surgical procedures and outcome. Left atrial isomerism was present in 23 patients. Interruption of the inferior vena cava (56%), atrio-ventricular septal defect (47%), common atrium (38%) and cor triatriatum sinistrum (30%) were the most common diagnoses. Biventricular repair was achieved in 17 children and total cavo-pulmonary connection in two. Three underwent staged palliation: modified Blalock-Taussig shunt for two and bidirectional Glenn anastomosis for one. The remainder received a cardiac pacemaker. One patient died early after repair. Two underwent reoperation to correct a regurgitant left atrio-ventricular valve: one of these, in another hospital, had peroperative death. Three died later. Actuarial survival rate after repair and total cavo-pulmonary connection that was stabilized after 2 years was 84%. In the 18 children with right atrial isomerism, pulmonary atresia or stenosis predominated (89%) with discordant ventriculo-arterial connection (72%), atrio-ventricular septal defect (72%), 'single' ventricle (55%) and extracardiac total anomalous pulmonary venous drainage (50%). Biventricular repair was achieved in two patients and complete Fontan circulation in eight. The other eight underwent various staged palliative procedures and correction of extracardiac total anomalous pulmonary venous drainage. Five patients died postoperatively: two in our unit after modified Blalock-Taussig shunt and total cavo-pulmonary connection, three in other hospitals after repair (n = 1) and Fontan (n = 2). Five died later. One was lost for review. Survival after repair and Fontan stabilized after 6 months at 49%. In conclusion, the cardiovascular malformations associated with left atrial isomerism can often be successfully corrected. Those accompanying right atrial isomerism usually preclude a biventricular repair, require staged palliation and carry a poor prognosis.

Pulmonary function in space

NASA Technical Reports Server (NTRS)

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

1997-01-01

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

Library Specifications for a New Circulation System for Concordia University Libraries.

ERIC Educational Resources Information Center

Tallon, James

This study of library requirements for a new circulation system is organized into three sections: (1) items required for initial implementation in July 1982; (2) items relating to notice generation and activity statistics, with implementation expected by fall 1982; and (3) items provided in the system as initially implemented, with additional…

[The rehabilitative treatment of the patients presenting with chronic obstructive pulmonary disease including the application of the manual handling methods].

PubMed

Ayrapetova, N S; Eremushkin, M A; Antonovich, I V; Kuznetsov, O F; Samorukov, A E; Budylin, S P; Tarasova, L Yu; Derevnina, N A

The objective of the present study was to identify the peculiar features and advantages of different methods for the mechanical impact on the thoracic tissues of the patients presenting with chronic obstructive pulmonary disease (COPD) and to develop specific indications for their clinical applications. This randomized prospective comparative study included 137 patients with COPD. In accordance with the currently accepted classification (GOLD, 2013), all the patients had COPD of medium severity. The smoldering inflammatory process was diagnosed in 75 (54.7%) patients, grade I and II respiratory insufficiency in 80 (58.4%) and 57 (41.6%) patients, respectively. The external respiration function was evaluated by means of pneumotachometry techniques during the forced expiratory maneuver and by spirometry. The pulmonary hemodynamics and myocardial contractility of the right ventricle were studied with the use of rheopulmonography and central hemodynamics by tetrapolar thoracic rheography. The routine inflammatory and immune tests were employed. Investigations of the systemic circulation have demonstrated the prevalence of its hyperkinetic type (54,0%) over the hypokinetic and eukinetic ones (23,3% and 22,7% respectively). All the patients were divided into three group identical in terms of clinical and functional characteristics. The patients comprising group 1 (n=46) were prescribed the rehabilitative treatment in the form of classical chest massage, those of group 2 (n=47) were treated by means of intense massage of asymmetric chest zones, and the patients included in group 3 (n=44) underwent manual therapy. It was shown that intense massage produced the most pronounced beneficial effect. Classical massage also resulted in the reduction of the inflammatory manifestations but its effectiveness was significantly lower than that of the intense treatment (р<0,05-0,02). Manual therapy failed to cause any appreciable changes in the character and severity of the inflammatory process (р>0,5). The intense massage of asymmetric chest zones proved to provide the most efficient tool for the anti-inflammatory treatment of the patients presenting with chronic obstructive pulmonary disease in comparison with other known methods for the mechanical impact on the thoracic tissues. However, the application of this technique is limited in the patients with the hypokinetic type of systemic circulation and pulmonary hypertension. The most important advantage of chest massage by the conventional method is the possibility of its application for the treatment of the patients suffering from severe forms of COPD associated with pulmonary and systemic cardiohemodynamic disturbances with alveolar hypoxia. Manual therapy can be recommended in the first place to the patients with COPD in remission and the accompanying functional blockade of the vertebral segments.

Neonatal Cardio-pulmonary Arrest: Emergency Catheterization of Umbilical Vein

PubMed Central

Paes, Bosco A.; Blatz, Susan; Kraftcheck, D.J.

1990-01-01

In an emergency, the physician responsible for neonatal care must be skilled in umbilical catheterization. Several drugs can be given through an endotracheal tube, but some require intravenous administration. The umbilical vein is a better route of administration than peripheral veins because it is easily located and can be entered readily. It allows immediate access to the central circulation, enhancing drug distribution. The authors outline the procedure in a step-by-step description. This pictorial article can be used as a handy reference by physicians needing to administer fluids and drugs during cardio-pulmonary arrest in neonates. Imagesp1136-ap1136-bp1136-cp1136-dp1137-ap1137-bp1137-cp1137-dp1137-ep1138-ap1138-bp1138-cp1138-dp1139-ap1139-bp1139-cp1139-dp1140-ap1140-bp1140-cp1140-d PMID:21233982

The patent ductus arteriosus in term infants, children, and adults.

PubMed

Schneider, Douglas J

2012-04-01

During fetal life, the ductus arteriosus is a normal and essential structure that connects the pulmonary artery to the distal aortic arch, permitting right ventricular ejection into the aorta. After birth, with commencement of pulmonary blood flow and a 2-ventricle circulation, a variety of physiological and biochemical signals normally result in complete closure of the ductus. Persistent patency of the ductus arteriosus may impair systemic cardiac output and result in deleterious effects on the cardiovascular system and lungs. Although surgery is still the treatment of choice for most premature infants with patent ductus arteriosus (PDA), transcatheter techniques have largely supplanted surgery for closure of PDA in children and adults. This article is a review of the PDA in term infants, children, and adults, with focus on the clinical manifestations and management. Copyright © 2012 Elsevier Inc. All rights reserved.

Cavitary Pulmonary Sporotrichosis: Case Report and Literature Review.

PubMed

Rojas, Florencia D; Fernández, Mariana S; Lucchelli, Juan Manuel; Lombardi, Dora; Malet, José; Vetrisano, María Eugenia; Cattana, María Emilia; Sosa, María de Los Ángeles; Giusiano, Gustavo

2017-12-01

A case of cavitary pulmonary sporotrichosis without mucocutaneous involvement caused by Sporothrix schenckii is reported in a sexagenarian woman with a long smoking history. The patient was hospitalized for septic shock with multiorgan failure from a respiratory focus. The diagnosis was delayed due to the fungal etiological agent was not initially considered in the differential diagnosis. A good clinical and radiological evolution was obtained with the antifungal therapy. Occasional cases of primary pulmonary sporotrichosis have been reported in the literature. Due to its low incidence, this is a less-known and underestimated clinical form. Both clinical suspicion and microbiological studies are needed to reach pulmonary sporotrichosis diagnosis.

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.

Increased systemic vascular resistance in neonates with pulmonary hypertension.

PubMed

Milstein, J M; Goetzman, B W; Riemenschneider, T A; Wennberg, R P

1979-11-01

The time necessary for aortic diastolic pressure to decrease to 50 percent of an initially selected value after dissipation of the dicrotic notch (T 1/2) was determined in newborn infants with and without pulmonary hypertension. The mean T 1/2 was 671 +/- 167 msec in seven infants with clinical evidence of pulmonary hypertension and documented right to left ductus arteriosus shunting; 849 +/- 243 msec in nine infants with clinical evidence of pulmonary hypertension but no documented right to left ductus arteriosus shunting; and 457 +/- 66 msec in eight infants with hyaline membrane disease and no clinical evidence of pulmonary hypertension or a patent ductus arteriosus. The mean T 1/2 values in the former two groups were significantly different from that in the group with no pulmonary hypertension (P less than 0.01). An evaluation of factors affecting T 1/2 leads to the conclusion that the patients with pulmonary hypertension had increased systemic vascular resistance as well. This finding has important diagnostic, etiologic and therapeutic implications.

Dictionary learning-based CT detection of pulmonary nodules

NASA Astrophysics Data System (ADS)

Wu, Panpan; Xia, Kewen; Zhang, Yanbo; Qian, Xiaohua; Wang, Ge; Yu, Hengyong

2016-10-01

Segmentation of lung features is one of the most important steps for computer-aided detection (CAD) of pulmonary nodules with computed tomography (CT). However, irregular shapes, complicated anatomical background and poor pulmonary nodule contrast make CAD a very challenging problem. Here, we propose a novel scheme for feature extraction and classification of pulmonary nodules through dictionary learning from training CT images, which does not require accurately segmented pulmonary nodules. Specifically, two classification-oriented dictionaries and one background dictionary are learnt to solve a two-category problem. In terms of the classification-oriented dictionaries, we calculate sparse coefficient matrices to extract intrinsic features for pulmonary nodule classification. The support vector machine (SVM) classifier is then designed to optimize the performance. Our proposed methodology is evaluated with the lung image database consortium and image database resource initiative (LIDC-IDRI) database, and the results demonstrate that the proposed strategy is promising.

Small pulmonary nodules in baseline and incidence screening rounds of low-dose CT lung cancer screening

PubMed Central

Walter, Joan E.; Oudkerk, Matthijs

2017-01-01

Currently, lung cancer screening by low-dose computed tomography (LDCT) is widely recommended for high-risk individuals by US guidelines, but there still is an ongoing debate concerning respective recommendations for European countries. Nevertheless, the available data regarding pulmonary nodules released by lung cancer screening studies could improve future screening guidelines, as well as the clinical practice of incidentally detected pulmonary nodules on routine CT scans. Most lung cancer screening trials present results for baseline and incidence screening rounds separately, clustering pulmonary nodules initially found at baseline screening and newly detected pulmonary nodules after baseline screening together. This approach does not appreciate possible differences among pulmonary nodules detected at baseline and firstly detected at incidence screening rounds and is heavily influenced by methodological differences of the respective screening trials. This review intends to create a basis for assessing non-calcified pulmonary nodules detected during LDCT lung cancer screening in a more clinical relevant manner. The aim is to present data of non-calcified pulmonary baseline nodules and new non-calcified pulmonary incident nodules without clustering them together, thereby also simplifying translation to the clinical practice of incidentally detected pulmonary nodules. Small pulmonary nodules newly detected at incidence screening rounds of LDCT lung cancer screening may possess a greater lung cancer probability than pulmonary baseline nodules at a smaller size, which is essential for the development of new guidelines. PMID:28331823

Secondary Pulmonary Hypertension and Right-Sided Heart Failure at Presentation in Grave's Disease

PubMed Central

Ganeshpure, Swapnil Panjabrao; Vaidya, Gaurang Nandkishor; Gattani, Vipul

2012-01-01

A young female presented with evidence of right-sided heart failure and was subsequently found to have significant pulmonary artery hypertension (PAH). Because of her normal left ventricular function and pulmonary capillary wedge pressure, the most probable site of etiology seemed to be the pulmonary vasculature. All the common possible secondary causes of PAH were ruled out, but during the investigations, she was found to have elevated thyroid function tests compatible with the diagnosis of Grave's disease. The treatment of Grave's disease, initially by medications and subsequently by radioiodine therapy, was associated with a significant reduction in the pulmonary artery systolic pressure. The purpose of this case report is to highlight one of the unusual and underdiagnosed presentations of Grave's disease. PMID:23198182

Pulmonary accumulation of polymorphonuclear leukocytes in the adult respiratory distress syndrome

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

Powe, J.E.; Short, A.; Sibbald, W.J.

1982-11-01

The polymorphonuclear leukocyte (PMN) plays an integral role in the development of permeability pulmonary edema associated with the adult respiratory distress syndrome (ARDS). This report describes 3 patients with ARDS secondary to systemic sepsis who demonstrated an abnormal diffuse accumulation of Indium (/sup 111/In)-labeled PMNs in their lungs, without concomitant clinical or laboratory evidence of a primary chest infection. In one patient, the accumulation of the pulmonary activity during an initial pass suggested that this observation was related to diffuse leukoaggregation within the pulmonary microvasculature. A 4th patient with ARDS was on high-dose corticosteroids at the time of a similarmore » study, and showed no pulmonary accumulation of PMNs, suggesting a possible reason for the reported beneficial effect of corticosteroids in human ARDS.« less

Exercise training improves peak oxygen consumption and haemodynamics in patients with severe pulmonary arterial hypertension and inoperable chronic thrombo-embolic pulmonary hypertension: a prospective, randomized, controlled trial

PubMed Central

Ehlken, Nicola; Lichtblau, Mona; Klose, Hans; Weidenhammer, Johannes; Fischer, Christine; Nechwatal, Robert; Uiker, Sören; Halank, Michael; Olsson, Karen; Seeger, Werner; Gall, Henning; Rosenkranz, Stephan; Wilkens, Heinrike; Mertens, Dirk; Seyfarth, Hans-Jürgen; Opitz, Christian; Ulrich, Silvia; Egenlauf, Benjamin; Grünig, Ekkehard

2016-01-01

Abstract Aims The impact of exercise training on the right heart and pulmonary circulation has not yet been invasively assessed in patients with pulmonary hypertension (PH) and right heart failure. This prospective randomized controlled study investigates the effects of exercise training on peak VO2/kg, haemodynamics, and further clinically relevant parameters in PH patients. Methods and results Eighty-seven patients with pulmonary arterial hypertension and inoperable chronic thrombo-embolic PH (54% female, 56 ± 15 years, 84% World Health Organization functional class III/IV, 53% combination therapy) on stable disease-targeted medication were randomly assigned to a control and training group. Medication remained unchanged during the study period. Non-invasive assessments and right heart catheterization at rest and during exercise were performed at baseline and after 15 weeks. Primary endpoint was the change in peak VO2/kg. Secondary endpoints included changes in haemodynamics. For missing data, multiple imputation and responder analyses were performed. The study results showed a significant improvement of peak VO2/kg in the training group (difference from baseline to 15 weeks: training +3.1 ± 2.7 mL/min/kg equals +24.3% vs. control −0.2 ± 2.3 mL/min/kg equals +0.9%, P < 0.001). Cardiac index (CI) at rest and during exercise, mean pulmonary arterial pressure, pulmonary vascular resistance, 6 min walking distance, quality of life, and exercise capacity significantly improved by exercise training. Conclusion Low-dose exercise training at 4–7 days/week significantly improved peak VO2/kg, haemodynamics, and further clinically relevant parameters. The improvements of CI at rest and during exercise indicate that exercise training may improve the right ventricular function. Further, large multicentre trials are necessary to confirm these results. PMID:26231884

Effect of inhaled nitric oxide on pulmonary hemodynamics after acute lung injury in dogs

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

Romand, J.A.; Pinsky, M.R.; Firestone, L.

Increased pulmonary vascular resistance (PVR) and mismatch in ventilation-to-perfusion ratio characterize acute lung injury (ALI). Pulmonary arterial pressure (Ppa) decreases when nitric oxide (NO) is inhaled during hypoxic pulmonary vasoconstriction (HPV); thus NO inhalation may reduce PVR and improve gas exchange in ALI. The authors studied the hemodynamic and gas exchange effects of NO inhalation during HPV and then ALI in eight anesthetized open-chest mechanically ventilated dogs. Right atrial pressure, Ppa, and left ventricular and arterial pressures were measured, and cardiac output was estimated by an aortic flow probe. Shunt and dead space were also estimated. The effect of 5-minmore » exposures to 0, 17, 28, 47, and 0 ppm inhaled NO was recorded during hyperoxia, hypoxia, and oleic acid-induced ALI. During ALI, partial [beta]-adrenergic blockage (propanolol, 0.15 mg/kg iv) was induced and 74 ppm NO was inhaled. Nitrosylhemoglobin (NO-Hb) and methemoglobin (MetHb) levels were measured. During hyperoxia, NO inhalation had no measurable effects. Hypoxia increased Ppa and calculated PVR, both of which decreased with 17 ppm NO. ALI decreased arterial Po[sub 2] and increased airway pressure, shunt, and dead space ventilation. Ppa and PVR were greater during ALI than during hyperoxia. NO inhalation had no measurable effect during ALI before or after [beta]-adrenergic blockage. MetHb remained low, and NO-Hb was unmeasurable. Bolus infusion of nitroglycerin (15 [mu]g) induced an immediate decrease in Ppa and PVR during ALI. Short-term NO inhalation does not affect PVR or gas exchange in dogs with oleic acid-induced ALI, nor does it increase NO-Hb or MetHb. In contrast, NO can diminish hypoxia-induced elevations in pulmonary vascular tone. These data suggest that NO inhalation selectively dilates the pulmonary circulation and specifically reduces HPV but not oleic acid-induced increases in pulmonary vasomotor tone. 28 refs., 3 figs., 2 tabs.« less

Endogenous circulating sympatholytic factor in orthostatic intolerance

NASA Technical Reports Server (NTRS)

Shapiro, R. E.; Winters, B.; Hales, M.; Barnett, T.; Schwinn, D. A.; Flavahan, N.; Berkowitz, D. E.

2000-01-01

Sympathotonic orthostatic hypotension (SOH) is an idiopathic syndrome characterized by tachycardia, hypotension, elevated plasma norepinephrine, and symptoms of orthostatic intolerance provoked by assumption of an upright posture. We studied a woman with severe progressive SOH with blood pressure unresponsive to the pressor effects of alpha(1)-adrenergic receptor (AR) agonists. We tested the hypothesis that a circulating factor in this patient interferes with vascular adrenergic neurotransmission. Preincubation of porcine pulmonary artery vessel rings with patient plasma produced a dose-dependent inhibition of vasoconstriction to phenylephrine in vitro, abolished vasoconstriction to direct electrical stimulation, and had no effect on nonadrenergic vasoconstrictive stimuli (endothelin-1), PGF-2alpha (or KCl). Preincubation of vessels with control plasma was devoid of these effects. SOH plasma inhibited the binding of an alpha(1)-selective antagonist radioligand ([(125)I]HEAT) to membrane fractions derived from porcine pulmonary artery vessel rings, rat liver, and cell lines selectively overexpressing human ARs of the alpha(1B) subtype but not other AR subtypes (alpha(1A) and alpha(1D)). We conclude that a factor in SOH plasma can selectively and irreversibly inhibit adrenergic ligand binding to alpha(1B) ARs. We propose that this factor contributes to a novel pathogenesis for SOH in this patient. This patient's syndrome represents a new disease entity, and her plasma may provide a unique tool for probing the selective functions of alpha(1)-ARs.

Skill acquisition and retention in automated external defibrillator (AED) use and CPR by lay responders: a prospective study.

PubMed

Woollard, Malcolm; Whitfeild, Richard; Smith, Anna; Colquhoun, Michael; Newcombe, Robert G; Vetteer, Norman; Chamberlain, Douglas

2004-01-01

This prospective study evaluated the acquisition and retention of skills in cardio-pulmonary resuscitation (CPR) and the use of the automated external defibrillator (AED) by lay volunteers involved in the Department of Health, England National Defibrillator Programme. One hundred and twelve trainees were tested immediately before and after and initial 4-h class; 76 were similarly reassessed at refresher training 6 months later. A standardised test scenario that required assessment of the casualty, CPR and the use of on AED was evaluated using recording manikin data and video recordings. Before training only 44% of subjects delivered a shock. Afterwards, all did so and the average delay to first shock was reduced by 57 s. All trainees placed the defibrillator electrodes in an "acceptable" position after training, but very few did so in the recommended "ideal" position. After refresher training 80% of subjects used the correct sequence for CPR and shock delivery, yet a third failed to perform adequate safety checks before all shocks. The trainees self-assessed AED competence score was 86 (scale 0-100) after the initial class and their confidence that they would act in a real emergency was rated at a similar level. Initial training improved performance of all CPR skills, although all except compression rate had deteriorated after 6 months. The proportion of subjects able to correctly perform most CPR skill was higher following refresher training that after the initial class. Although this course was judged to be effective in teaching delivery of counter-shocks, the need was identified for more emphasis on positioning of electrodes, pre-shock safety checks, airway opening, ventilation volume, checking for signs of a circulation, hand positioning, and depth and rate of chest compressions.

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

PubMed

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

2017-06-20

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

[Pulmonary non invasive infection by Scedosporium apiospermum].

PubMed

Cruz, Rodrigo; Barros, Manuel; Reyes, Mirtha

2015-08-01

We reported a case of non-invasive pulmonary infection by Scedosporium apiospermum in 67 years old female with bronchiectasis and caverns secondary to tuberculosis. Diagnosis was made with lung CT and bronchial lavage cultures. The patient was initially treated with itraconazole for six weeks without success and then voriconazole for 16 weeks, with good clinical response.

Introduction to Pulmonary Fibrosis

MedlinePlus

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Cytokine–Ion Channel Interactions in Pulmonary Inflammation

PubMed Central

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

2018-01-01

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

Estimating the effect of lung collapse and pulmonary shunt on gas exchange during breath-hold diving: the Scholander and Kooyman legacy.

PubMed

Fahlman, A; Hooker, S K; Olszowka, A; Bostrom, B L; Jones, D R

2009-01-01

We developed a mathematical model to investigate the effect of lung compression and collapse (pulmonary shunt) on the uptake and removal of O(2), CO(2) and N(2) in blood and tissue of breath-hold diving mammals. We investigated the consequences of pressure (diving depth) and respiratory volume on pulmonary shunt and gas exchange as pressure compressed the alveoli. The model showed good agreement with previous studies of measured arterial O(2) tensions (Pa(O)(2)) from freely diving Weddell seals and measured arterial and venous N(2) tensions from captive elephant seals compressed in a hyperbaric chamber. Pulmonary compression resulted in a rapid spike in Pa(O)(2) and arterial CO(2) tension, followed by cyclical variation with a periodicity determined by Q(tot). The model showed that changes in diving lung volume are an efficient behavioural means to adjust the extent of gas exchange with depth. Differing models of lung compression and collapse depth caused major differences in blood and tissue N(2) estimates. Our integrated modelling approach contradicted predictions from simple models, and emphasised the complex nature of physiological interactions between circulation, lung compression and gas exchange. Overall, our work suggests the need for caution in interpretation of previous model results based on assumed collapse depths and all-or-nothing lung collapse models.

One and a half ventricular repair as an alternative for hypoplastic right ventricle.

PubMed

Maluf, Miguel Angel; Carvalho, Antonio Carlos; Carvalho, Werther Brunow

2010-01-01

Patients with complex congenital heart disease, characterized by right ventricle hypoplasia, had a palliative surgical option with one and a half ventricular repair. From July 2001 to March 2009, nine patients (mean age 5.2 years, range 3 to 9 years) with hypoplastic right ventricle, underwent correction with one and a half ventricle technique. Preoperative diagnoses included: pulmonary atresia with intact ventricular septum, in six and Ebstein's anomaly, in three cases. Six patients had bidirectional cavo-pulmonary shunt (Glenn operation) previously. The surgical approach was performed with cardiopulmonary bypass to correct intracardiac defects: atrial septal defect closure (nine cases); right ventricle outlet tract reconstruction with porcine pulmonary prosthesis (seven cases); tricuspid valvuloplasty (three cases). There was one (11.1%) hospital death. All the patients left the hospital in good clinical conditions. One patient presented pulmonary stenosis at distal prosthesis anastomosis and needed surgical correction. There was one (12.5%) late deaths after reoperation. At mean follow-up of 39.8 months (range 16 months to 8.4 years) seven patients are alive in functional class I (NYHA). Surgical treatment of congenital cardiac anomalies in the presence of a hypoplastic right ventricle by means of one and a half ventricle repair has the advantages of reducing the surgical risk of biventricular repair compared to the Fontan circulation; it maintains a low right atrium pressure, a pulsatile pulmonary blood flow and improves the systemic oxygen saturation with short and medium-term promising results. Longer follow-up is needed to prove the efficacy of such a repair in the long term.

[Pneumocystis jiroveci infection in immunocompetent patients with pulmonary disorders, in Portugal].

PubMed

Matos, Olga; Costa, Marina Célia; Correia, Isabel; Monteiro, Paula; Vieira, Jorge Roldão; Soares, Jorge; Bonnet, Marina; Esteves, Francisco; Antunes, Francisco

2006-01-01

The use of molecular tools with a great capacity to detect and differentiate strains of Pneumocystis has resulted: in the identification of low numbers of P. jiroveci organisms in clinically silent, colonized, immunocompromised patients and in immunocompetent persons. Considering this information, the aim of this study was to determine the prevalence of P. jiroveci carriers (subclinical infections) in Portuguese patients with pulmonary disorders and in healthy individuals. A total of 45 pulmonary specimens were collected from 45 immunocompetent adults with pulmonary disorders, and 37 oral washings from 37 healthy adults, between March 2001 and February 2004. All samples were analysed by indirect immunofluorescence with monoclonal antibodies and by amplification of the LSU mtrRNA by nested PCR. The results obtained in this study indicate that: 1) P. jiroveci is frequently detected (24.4%) in patients with pulmonary disorders in Portugal; 2) this population might play a role in circulation and transmission of P. jiroveci organisms in the community; 3) patients receiving corticosteroids are more likely to have detectable P. jiroveci in lungs (18%) than patients who are not receiving this immunosuppressor (12%); 4) P. jiroveci is infrequently detected in healthy adults. This may be due to very low numbers of latent organisms present in the lungs of healthy adults, difficulty in detecting few organisms, or due to the type of samples used. Screening of these individuals and notification of the results to their physician might be important: for further follow-up and whether or not prophylaxis or treatment should be prescribed; and for the clarification of the epidemiology of P. jiroveci asymptomatic infections.

Quantitative intravital two-photon excitation microscopy reveals absence of pulmonary vaso-occlusion in unchallenged Sickle Cell Disease mice

PubMed Central

Bennewitz, Margaret F; Watkins, Simon C; Sundd, Prithu

2014-01-01

Sickle cell disease (SCD) is a genetic disorder that leads to red blood cell (RBC) sickling, hemolysis and the upregulation of adhesion molecules on sickle RBCs. Chronic hemolysis in SCD results in a hyper-inflammatory state characterized by activation of circulating leukocytes, platelets and endothelial cells even in the absence of a crisis. A crisis in SCD is often triggered by an inflammatory stimulus and can lead to the acute chest syndrome (ACS), which is a type of lung injury and a leading cause of mortality among SCD patients. Although it is believed that pulmonary vaso-occlusion could be the phenomenon contributing to the development of ACS, the role of vaso-occlusion in ACS remains elusive. Intravital imaging of the cremaster microcirculation in SCD mice has been instrumental in establishing the role of neutrophil-RBC-endothelium interactions in systemic vaso-occlusion; however, such studies, although warranted, have never been done in the pulmonary microcirculation of SCD mice. Here, we show that two-photon excitation fluorescence microscopy can be used to perform quantitative analysis of neutrophil and RBC trafficking in the pulmonary microcirculation of SCD mice. We provide the experimental approach that enables microscopic observations under physiological conditions and use it to show that RBC and neutrophil trafficking is comparable in SCD and control mice in the absence of an inflammatory stimulus. The intravital imaging scheme proposed in this study can be useful in elucidating the cellular and molecular mechanism of pulmonary vaso-occlusion in SCD mice following an inflammatory stimulus. PMID:25995970

Reduced contribution of endothelin to the regulation of systemic and pulmonary vascular tone in severe familial hypercholesterolaemia

PubMed Central

Bender, Shawn B; de Beer, Vincent J; Tharp, Darla L; van Deel, Elza D; Bowles, Douglas K; Duncker, Dirk J; Laughlin, M Harold; Merkus, Daphne

2014-01-01

Vascular dysfunction has been associated with familial hypercholesterolaemia (FH), a severe form of hyperlipidaemia. We recently demonstrated that swine with FH exhibit reduced exercise-induced systemic, but not pulmonary, vasodilatation involving reduced nitric oxide (NO) bioavailability. Since NO normally limits endothelin (ET) action, we examined the hypothesis that reduced systemic vasodilatation during exercise in FH swine results from increased ET-mediated vasoconstriction. Systemic and pulmonary vascular responses to exercise were examined in chronically instrumented normal and FH swine in the absence and presence of the ETA/B receptor antagonist tezosentan. Intrinsic reactivity to ET was further assessed in skeletal muscle arterioles. FH swine exhibited ∼9-fold elevation in total plasma cholesterol versus normal swine. Similar to our recent findings, systemic, not pulmonary, vasodilatation during exercise was reduced in FH swine. Blockade of ET receptors caused marked systemic vasodilatation at rest and during exercise in normal swine that was significantly reduced in FH swine. The reduced role of ET in FH swine in vivo was not the result of decreased arteriolar ET responsiveness, as responsiveness was increased in isolated arterioles. Smooth muscle ET receptor protein content was unaltered by FH. However, circulating plasma ET levels were reduced in FH swine. ET receptor antagonism caused pulmonary vasodilatation at rest and during exercise in normal, but not FH, swine. Therefore, contrary to our hypothesis, FH swine exhibit a generalised reduction in the role of ET in regulating vascular tone in vivo probably resulting from reduced ET production. This may represent a unique vascular consequence of severe familial hypercholesterolaemia. PMID:24421352

[Experts consensus on the management of the right heart function in critically ill patients].

PubMed

Wang, X T; Liu, D W; Zhang, H M; Long, Y; Guan, X D; Qiu, H B; Yu, K J; Yan, J; Zhao, H; Tang, Y Q; Ding, X; Ma, X C; Du, W; Kang, Y; Tang, B; Ai, Y H; He, H W; Chen, D C; Chen, H; Chai, W Z; Zhou, X; Cui, N; Wang, H; Rui, X; Hu, Z J; Li, J G; Xu, Y; Yang, Y; Ouyan, B; Lin, H Y; Li, Y M; Wan, X Y; Yang, R L; Qin, Y Z; Chao, Y G; Xie, Z Y; Sun, R H; He, Z Y; Wang, D F; Huang, Q Q; Jiang, D P; Cao, X Y; Yu, R G; Wang, X; Chen, X K; Wu, J F; Zhang, L N; Yin, M G; Liu, L X; Li, S W; Chen, Z J; Luo, Z

2017-12-01

To establish the experts consensus on the right heart function management in critically ill patients. The panel of consensus was composed of 30 experts in critical care medicine who are all members of Critical Hemodynamic Therapy Collaboration Group (CHTC Group). Each statement was assessed based on the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) principle. Then the Delphi method was adopted by 52 experts to reassess all the statements. (1) Right heart function is prone to be affected in critically illness, which will result in a auto-exaggerated vicious cycle. (2) Right heart function management is a key step of the hemodynamic therapy in critically ill patients. (3) Fluid resuscitation means the process of fluid therapy through rapid adjustment of intravascular volume aiming to improve tissue perfusion. Reversed fluid resuscitation means reducing volume. (4) The right ventricle afterload should be taken into consideration when using stroke volume variation (SVV) or pulse pressure variation (PPV) to assess fluid responsiveness.(5)Volume overload alone could lead to septal displacement and damage the diastolic function of the left ventricle. (6) The Starling curve of the right ventricle is not the same as the one applied to the left ventricle,the judgement of the different states for the right ventricle is the key of volume management. (7) The alteration of right heart function has its own characteristics, volume assessment and adjustment is an important part of the treatment of right ventricular dysfunction (8) Right ventricular enlargement is the prerequisite for increased cardiac output during reversed fluid resuscitation; Nonetheless, right heart enlargement does not mandate reversed fluid resuscitation.(9)Increased pulmonary vascular resistance induced by a variety of factors could affect right heart function by obstructing the blood flow. (10) When pulmonary hypertension was detected in clinical scenario, the differentiation of critical care-related pulmonary hypertension should be a priority. (11) Attention should be paid to the change of right heart function before and after implementation of mechanical ventilation and adjustment of ventilator parameter. (12) The pulmonary arterial pressure should be monitored timingly when dealing with critical care-related pulmonary hypertension accompanied with circulatory failure.(13) The elevation of pulmonary aterial pressure should be taken into account in critical patients with acute right heart dysfunction. (14) Prone position ventilation is an important measure to reduce pulmonary vascular resistance when treating acute respiratory distress syndrome patients accompanied with acute cor pulmonale. (15) Attention should be paid to right ventricle-pulmonary artery coupling during the management of right heart function. (16) Right ventricular diastolic function is more prone to be affected in critically ill patients, the application of critical ultrasound is more conducive to quantitative assessment of right ventricular diastolic function. (17) As one of the parameters to assess the filling pressure of right heart, central venous pressure can be used to assess right heart diastolic function. (18). The early and prominent manifestation of non-focal cardiac tamponade is right ventricular diastolic involvement, the elevated right atrial pressure should be noticed. (19) The effect of increased intrathoracic pressure on right heart diastolic function should be valued. (20) Ttricuspid annular plane systolic excursion (TAPSE) is an important parameter that reflects right ventricular systolic function, and it is recommended as a general indicator of critically ill patient. (21) Circulation management with right heart protection as the core strategy is the key point of the treatment of acute respiratory distress syndrome. (22) Right heart function involvement after cardiac surgery is very common and should be highly valued. (23) Right ventricular dysfunction should not be considered as a routine excuse for maintaining higher central venous pressure. (24) When left ventricular dilation, attention should be paid to the effect of left ventricle on right ventricular diastolic function. (25) The impact of left ventricular function should be excluded when the contractility of the right ventricle is decreased. (26) When the right heart load increases acutely, the shunt between the left and right heart should be monitored. (27) Attention should be paid to the increase of central venous pressure caused by right ventricular dysfunction and its influence on microcirculation blood flow. (28) When the vasoactive drugs was used to reduce the pressure of pulmonary circulation, different effects on pulmonary and systemic circulation should be evaluated. (29) Right atrial pressure is an important factor affecting venous return. Attention should be paid to the influence of the pressure composition of the right atrium on the venous return. (30) Attention should be paid to the role of the right ventricle in the acute pulmonary edema. (31) Monitoring the difference between the mean systemic filling pressure and the right atrial pressure is helpful to determine whether the infusion increases the venous return. (32) Venous return resistance is often considered to be a insignificant factor that affects venous return, but attention should be paid to the effect of the specific pathophysiological status, such as intrathoracic hypertension, intra-abdominal hypertension and so on. Consensus can promote right heart function management in critically ill patients, optimize hemodynamic therapy, and even affect prognosis.

Primary pulmonary NK/T-cell lymphoma: A case report and literature review.

PubMed

Qiu, Yajuan; Hou, Junna; Hao, Dexun; Zhang, Dandan

2018-06-01

Extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is an aggressive disease with poor prognosis. The lung is a relatively rare site of involvement. The current study presents a case of primary pulmonary ENKTL with fever and dyspnea, mimicking pneumonia and initially treated with empirical antibiotics. The patient demonstrated rapid deterioration and died shortly following diagnosis. To the best of our knowledge, large-scale investigations referring to primary pulmonary ENKTL are not available. As a result, the exact incidence and clinical features of primary pulmonary ENKTL are unknown. In the current report, a literature review is presented to discuss the clinical characteristics, diagnosis, treatment, and prognosis factors of this malignant disease.

Enhancing Insights into Pulmonary Vascular Disease through a Precision Medicine Approach. A Joint NHLBI-Cardiovascular Medical Research and Education Fund Workshop Report.

PubMed

Newman, John H; Rich, Stuart; Abman, Steven H; Alexander, John H; Barnard, John; Beck, Gerald J; Benza, Raymond L; Bull, Todd M; Chan, Stephen Y; Chun, Hyung J; Doogan, Declan; Dupuis, Jocelyn; Erzurum, Serpil C; Frantz, Robert P; Geraci, Mark; Gillies, Hunter; Gladwin, Mark; Gray, Michael P; Hemnes, Anna R; Herbst, Roy S; Hernandez, Adrian F; Hill, Nicholas S; Horn, Evelyn M; Hunter, Kendall; Jing, Zhi-Cheng; Johns, Roger; Kaul, Sanjay; Kawut, Steven M; Lahm, Tim; Leopold, Jane A; Lewis, Greg D; Mathai, Stephen C; McLaughlin, Vallerie V; Michelakis, Evangelos D; Nathan, Steven D; Nichols, William; Page, Grier; Rabinovitch, Marlene; Rich, Jonathan; Rischard, Franz; Rounds, Sharon; Shah, Sanjiv J; Tapson, Victor F; Lowy, Naomi; Stockbridge, Norman; Weinmann, Gail; Xiao, Lei

2017-06-15

The Division of Lung Diseases of the NHLBI and the Cardiovascular Medical Education and Research Fund held a workshop to discuss how to leverage the anticipated scientific output from the recently launched "Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics" (PVDOMICS) program to develop newer approaches to pulmonary vascular disease. PVDOMICS is a collaborative, protocol-driven network to analyze all patient populations with pulmonary hypertension to define novel pulmonary vascular disease (PVD) phenotypes. Stakeholders, including basic, translational, and clinical investigators; clinicians; patient advocacy organizations; regulatory agencies; and pharmaceutical industry experts, joined to discuss the application of precision medicine to PVD clinical trials. Recommendations were generated for discussion of research priorities in line with NHLBI Strategic Vision Goals that include: (1) A national effort, involving all the stakeholders, should seek to coordinate biosamples and biodata from all funded programs to a web-based repository so that information can be shared and correlated with other research projects. Example programs sponsored by NHLBI include PVDOMICS, Pulmonary Hypertension Breakthrough Initiative, the National Biological Sample and Data Repository for PAH, and the National Precision Medicine Initiative. (2) A task force to develop a master clinical trials protocol for PVD to apply precision medicine principles to future clinical trials. Specific features include: (a) adoption of smaller clinical trials that incorporate biomarker-guided enrichment strategies, using adaptive and innovative statistical designs; and (b) development of newer endpoints that reflect well-defined and clinically meaningful changes. (3) Development of updated and systematic variables in imaging, hemodynamic, cellular, genomic, and metabolic tests that will help precisely identify individual and shared features of PVD and serve as the basis of novel phenotypes for therapeutic interventions.

Toxicodynamics of rigid polystyrene microparticles on pulmonary gas exchange in mice: Implications for microemboli-based drug delivery systems

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

Kutscher, H.L.; Gao, D.; Li, S.

The toxicodynamic relationship between the number and size of pulmonary microemboli resulting from uniformly sized, rigid polystyrene microparticles (MPs) administered intravenously and their potential effects on pulmonary gas exchange were investigated. CD-1 male mice (6–8 weeks) were intravenously administered 10, 25 and 45 μm diameter MPs. Oxygen hemoglobin saturation in the blood (SpO{sub 2}) was measured non-invasively using a pulse oximeter while varying inhaled oxygen concentration (F{sub I}O{sub 2}). The resulting data were fit to a physiologically based non-linear mathematical model that estimates 2 parameters: ventilation–perfusion ratio (V{sub A}/Q) and shunt (percentage of deoxygenated blood returning to systemic circulation). Themore » number of MPs administered prior to a statistically significant reduction in normalized V{sub A}/Q was dependent on particle size. MP doses that resulted in a significant reduction in normalized V{sub A}/Q one day post-treatment were 4000, 40,000 and 550,000 MPs/g for 45, 25 and 10 μm MPs, respectively. The model estimated V{sub A}/Q and shunt returned to baseline levels 7 days post-treatment. Measuring SpO{sub 2} alone was not sufficient to observe changes in gas exchange; however, when combined with model-derived V{sub A}/Q and shunt early reversible toxicity from pulmonary microemboli was detected suggesting that the model and physical measurements are both required for assessing toxicity. Moreover, it appears that the MP load required to alter gas exchange in a mouse prior to lethality is significantly higher than the anticipated required MP dose for effective drug delivery. Overall, the current results indicate that the microemboli-based approach for targeted pulmonary drug delivery is potentially safe and should be further explored. -- Highlights: ► Murine pulmonary gas exchange after microembolization was non-invasively studied. ► A physiologically based model quantified impairment of pulmonary gas exchange. ► Number and size of microemboli determine severity of impaired gas exchange. ► Pulmonary gas exchange returns to baseline within 7 days.« less

Experimental investigation of the effects of inserting a bovine venous valve in the inferior vena cava of Fontan circulation

NASA Astrophysics Data System (ADS)

Santhanakrishnan, Arvind; Johnson, Jacob; Kotz, Monica; Tang, Elaine; Khiabani, Reza; Yoganathan, Ajit; Maher, Kevin

2012-11-01

The Fontan procedure is a palliative surgery performed on patients with single ventricle (SV) congenital heart defects. The SV is used for systemic circulation and the venous return from the inferior vena cava (IVC) and superior vena cava (SVC) is routed to the pulmonary arteries (PA), resulting in a total cavopulmonary connection (TCPC). Hepatic venous hypertension is commonly manifested in the Fontan circulation, leading to long-term complications including liver congestion and cirrhosis. Respiratory intrathoracic pressure changes affect the venous return from the IVC to the PA. Using a physical model of an idealized TCPC, we examine placement of a unidirectional bovine venous valve within the IVC as a method of alleviating hepatic venous hypertension. A piston pump is used to provide pulsatility in the internal flow through the TCPC, while intrathoracic pressure fluctuations are imposed on the external walls of the model using a pair of linear actuators. When implanted in the extrathoracic position, the hepatic venous pressure is lowered from baseline condition. The effects of changing caval flow distribution and intrathoracic pressure on TCPC hemodynamics will be examined.

Control of respiration-driven retrograde flow in the subdiaphragmatic venous return of the Fontan circulation

PubMed Central

Vukicevic, M; Conover, T; Jaeggli, M; Zhou, J; Pennati, G; Hsia, TY; Figliola, RS

2014-01-01

Respiration influences the subdiaphragmatic venous return in the total cavopulmonary connection (TCPC) of the Fontan circulation whereby both the inferior vena cava (IVC) and hepatic vein flows can experience retrograde motion. Controlling retrograde flows could improve patient outcomes. Using a patient-specific model within a Fontan mock circulatory system with respiration, we inserted a valve into the IVC to examine its effects on local hemodynamics while varying retrograde volumes by changing vascular impedances. A bovine valved conduit reduced IVC retrograde flow to within 3% of antegrade flow in all cases. The valve closed only under conditions supporting retrograde flow and its effects on local hemodynamics increased with larger retrograde volume. Liver and TCPC pressures improved only while the valve leaflets were closed while cycle-averaged pressures improved only slightly (italic>1 mm Hg). Increased pulmonary vascular resistance raised mean circulation pressures but the valve functioned and cardiac output improved and stabilized. Power loss across the TCPC improved by 12–15% (pbold>0.05) with a valve. The effectiveness of valve therapy is dependent on patient vascular impedance. PMID:24814833

An improved method for detecting circulating microRNAs with S-Poly(T) Plus real-time PCR

PubMed Central

Niu, Yanqin; Zhang, Limin; Qiu, Huiling; Wu, Yike; Wang, Zhiwei; Zai, Yujia; Liu, Lin; Qu, Junle; Kang, Kang; Gou, Deming

2015-01-01

We herein describe a simple, sensitive and specific method for analysis of circulating microRNAs (miRNA), termed S-Poly(T) Plus real-time PCR assay. This new method is based on our previously developed S-Poly(T) method, in which a unique S-Poly(T) primer is used during reverse-transcription to increase sensitivity and specificity. Further increased sensitivity and simplicity of S-Poly(T) Plus, in comparison with the S-Poly(T) method, were achieved by a single-step, multiple-stage reaction, where RNAs were polyadenylated and reverse-transcribed at the same time. The sensitivity of circulating miRNA detection was further improved by a modified method of total RNA isolation from serum/plasma, S/P miRsol, in which glycogen was used to increase the RNA yield. We validated our methods by quantifying miRNA expression profiles in the sera of the patients with pulmonary arterial hypertension associated with congenital heart disease. In conclusion, we developed a simple, sensitive, and specific method for detecting circulating miRNAs that allows the measurement of 266 miRNAs from 100 μl of serum or plasma. This method presents a promising tool for basic miRNA research and clinical diagnosis of human diseases based on miRNA biomarkers. PMID:26459910

Improved pulmonary function in working divers breathing nitrox at shallow depths

NASA Technical Reports Server (NTRS)

Fitzpatrick, Daniel T.; Conkin, Johnny

2003-01-01

INTRODUCTION: There is limited data about the long-term pulmonary effects of nitrox use in divers at shallow depths. This study examined changes in pulmonary function in a cohort of working divers breathing a 46% oxygen enriched mixture while diving at depths less than 12 m. METHODS: A total of 43 working divers from the Neutral Buoyancy Laboratory (NBL), NASA-Johnson Space Center completed a questionnaire providing information on diving history prior to NBL employment, diving history outside the NBL since employment, and smoking history. Cumulative dive hours were obtained from the NBL dive-time database. Medical records were reviewed to obtain the diver's height, weight, and pulmonary function measurements from initial pre-dive, first year and third year annual medical examinations. RESULTS: The initial forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were greater than predicted, 104% and 102%, respectively. After 3 yr of diving at the NBL, both the FVC and FEV1 showed a significant (p < 0.01) increase of 6.3% and 5.5%, respectively. There were no significant changes in peak expiratory flow (PEF), forced mid-expiratory flow rate (FEF(25-75%)), and forced expiratory flow rates at 25%, 50%, and 75% of FVC expired (FEF25%, FEF50%, FEF75%). Cumulative NBL dive hours was the only contributing variable found to be significantly associated with both FVC and FEV1 at 1 and 3 yr. CONCLUSIONS: NBL divers initially belong to a select group with larger than predicted lung volumes. Regular diving with nitrox at shallow depths over a 3-yr period did not impair pulmonary function. Improvements in FVC and FEV1 were primarily due to a training effect.

EM algorithm applied for estimating non-stationary region boundaries using electrical impedance tomography

NASA Astrophysics Data System (ADS)

Khambampati, A. K.; Rashid, A.; Kim, B. S.; Liu, Dong; Kim, S.; Kim, K. Y.

2010-04-01

EIT has been used for the dynamic estimation of organ boundaries. One specific application in this context is the estimation of lung boundaries during pulmonary circulation. This would help track the size and shape of lungs of the patients suffering from diseases like pulmonary edema and acute respiratory failure (ARF). The dynamic boundary estimation of the lungs can also be utilized to set and control the air volume and pressure delivered to the patients during artificial ventilation. In this paper, the expectation-maximization (EM) algorithm is used as an inverse algorithm to estimate the non-stationary lung boundary. The uncertainties caused in Kalman-type filters due to inaccurate selection of model parameters are overcome using EM algorithm. Numerical experiments using chest shaped geometry are carried out with proposed method and the performance is compared with extended Kalman filter (EKF). Results show superior performance of EM in estimation of the lung boundary.

The Risks of Scuba Diving: A Focus on Decompression Illness

PubMed Central

2014-01-01

Decompression Illness includes both Decompression Sickness (DCS) and Pulmonary Overinflation Syndrome (POIS), subsets of diving-related injury related to scuba diving. DCS is a condition in which gas bubbles that form while diving do not have adequate time to be resorbed or “off-gassed,” resulting in entrapment in specific regions of the body. POIS is due to an overly rapid ascent to the surface resulting in the rupture of alveoli and subsequent extravasation of air bubbles into tissue planes or even the cerebral circulation. Divers must always be cognizant of dive time and depth, and be trained in the management of decompression. A slow and controlled ascent, plus proper control of buoyancy can reduce the dangerous consequences of pulmonary barotrauma. The incidence of adverse effects can be diminished with safe practices, allowing for the full enjoyment of this adventurous aquatic sport. PMID:25478296

Tricuspid valve dysplasia with severe tricuspid regurgitation: fetal pulmonary artery size predicts lung viability in the presence of small lung volumes.

PubMed

Nathan, A T; Marino, B S; Dominguez, T; Tabbutt, S; Nicolson, S; Donaghue, D D; Spray, T L; Rychik, J

2010-01-01

Congenital tricuspid valve disease (Ebstein's anomaly, tricuspid valve dysplasia) with severe tricuspid regurgitation and cardiomegaly is associated with poor prognosis. Fetal echocardiography can accurately measure right atrial enlargement, which is associated with a poor prognosis in the fetus with tricuspid valve disease. Fetal lung volumetric assessments have been used in an attempt to predict viability of fetuses using ultrasonogram and prenatal MRI. We describe a fetus with tricuspid dysplasia, severe tricuspid regurgitation, right atrial enlargement and markedly reduced lung volumes. The early gestational onset of cardiomegaly with bilateral lung compression raised the possibility of severe lung hypoplasia with decreased broncho-alveolar development. Use of fetal echocardiography with measurement of pulmonary artery size combined with prenatal MRI scanning of lung volumes resulted in an improved understanding of this anomaly and directed the management strategy towards a successful Fontan circulation. 2010 S. Karger AG, Basel.

Just another abdominal pain? Psoas abscess-like metastasis in large cell lung cancer with adrenal insufficiency

PubMed Central

Bernardino, Vera; Val-Flores, Luis Silva; Lopes Dias, João; Bento, Luís

2015-01-01

The authors report the case of a 69-year-old man with chronic obstructive pulmonary disease and previous pulmonary tuberculosis, who presented to the emergency department with abdominal and low back pain, anorexia and weight loss, rapidly evolving into shock. An initial CT scan revealed pulmonary condensation with associated cavitation and an iliopsoas mass suggestive of a psoas abscess. He was admitted in an intensive care unit unit; after a careful examination and laboratory assessment, the aetiology was yet undisclosed. MRI showed multiple retroperitoneal lymphadenopathies, bulky nodular adrenal lesions and bilateral iliac lytic lesions. Hypocortisolism was detected and treated with steroids. A CT-guided biopsy to the psoas mass and lytic lesions identified infiltration of non-small lung carcinoma. The patient died within days. Psoas metastases and adrenal insufficiency as initial manifestations of malignancy are rare and can be misdiagnosed, particularly in the absence of a known primary tumour. PMID:26063108

A Study to Determine the Evolution of Advances in Medical Technology Expected in the Next 25 Years and Possible Impacts on Coast Guard Operations and Support Programs.

DTIC Science & Technology

1980-05-01

abnormalities in pressure tracings of the systemic, the central venous or pulmonary arterial circulation. At some sites (especially the Latter-Day Saints...accurate measurement of central venous pressure has been by direct venous cannulation. However, a group of Swiss doctors has extended the principle of... venous stop flow pressure to develop a noninvasive method of measuring central venous pressure. The method consists of venous auscultation at the thoracic

Detection and Prevention of G-Induced Regional Atelectasis, Edema, and Hypoperfusion.

DTIC Science & Technology

1975-12-01

Venous admixture in the pulmonary circulation of anesthetized dogs. J Appl Physiol 15:418 (1960). 13. Fowler, W. S., E. R. Cornish, Jr., and S. S...rebreathing method. J Clin Invest 38: 2073-2086 (1959). 18. Mead, J., and C. Collier. Relation of volume history of lungs to respiratory mechanics in... catheterization room for fluoroscopic studies, if these are required. A footrest (Fig. 1, point h), guided by stainless-steel tracks at the base of the table, is

Cadherin-11 Regulation of Fibrosis through Modulation of Epithelial-to-Mesenchymal Transition: Implications for Pulmonary Fibrosis in Scleroderma

DTIC Science & Technology

2015-10-01

first tested on a sera from healthy patients (n=20), systemic lupus erythematosus patients (n=29) and systemic sclerosis patients (n=20). Patients...with lupus and systemic sclerosis both had an increase in circulating soluble cadherin-11 levels that was statistically significant over levels seen...level. These data suggest that cadherin-11 levels are increased in patients with systemic sclerosis and lupus . These data use a small set of samples

Cadherin-11 Regulation of Fibrosis through Modulation of Epithelial-to-Mesenchymal Transition: Implications for Pulmonary Fibrosis in Scleroderma

DTIC Science & Technology

2016-05-01

first tested on a sera from healthy patients (n=20), systemic lupus erythematosus patients (n=29) and systemic sclerosis patients (n=20). Patients...with lupus and systemic sclerosis both had an increase in circulating soluble cadherin-11 levels that was statistically significant over levels seen...level. These data suggest that cadherin-11 levels are increased in patients with systemic sclerosis and lupus . These data use a small set of samples

[A case of pulmonary embolism and a case of ileus as complications after laparoscopic radical prostatectomy].

PubMed

Fujita, Akiko; Yamazaki, Yasuo; Yamashita, Tomomitsu; Ibuki, Takae; Hosokawa, Toyoshi; Tanaka, Yoshifumi

2003-01-01

In recent years, the use of laparoscopic techniques for surgical operations has been increasing, because this procedure is less invasive and is excellent in regard to patient's quality of life. Normally, complications are rare in laparoscopic surgery. However, we experienced a case of pulmonary embolism and one case of ileus as complications after laparoscopic radical prostatectomy. Especially, in this type of operation, the danger of complications is increased due to the severe head down and lithotomy position, which is employed to ensure a good view during operation. In this particular case, the long duration of operation may have been another related risk factor. There were no risk factors for pulmonary embolism such as those encountered when a patient is aged, obese, or bed ridden for a long time. However, an intermittent air massage must be applied to the lower legs to prevent thrombus due to poor blood circulation of the lower extremities below the knee during the surgery. It is also necessary to change the posture of the patient frequently after the operation. In addition, the administration of low molecular weight heparin may also be effective.

Serum insulin-like growth factor-1 (IGF-1) during CF pulmonary exacerbation: trends and biomarker correlations.

PubMed

Gifford, A H; Nymon, A B; Ashare, A

2014-04-01

Cystic fibrosis (CF) is characterized by low circulating levels of insulin-like growth factor-1 (IGF-1), a hormone produced by the liver that governs anabolism and influences immune cell function. Because treatment of CF pulmonary exacerbation (CFPE) often improves body weight and lung function, we questioned whether serum IGF-1 trends were emblematic of these responses. Initially, we compared serum levels between healthy adults with CF and controls of similar age. We then measured serum IGF-1 throughout the CFPE cycle. We also investigated correlations among IGF-1 and other serum biomarkers during CFPE. Anthopometric, spirometric, and demographic data were collected. Serum IGF-1 concentrations were measured by ELISA. CF subjects in their usual state of health had lower serum IGF-1 levels than controls. Serum IGF-1 concentrations fell significantly from baseline at the beginning of CFPE. Treatment with intravenous antibiotics was associated with significant improvement in serum IGF-1 levels, body mass index (BMI), and percent-predicted forced expiratory volume in 1 sec (FEV1 %). At early and late CFPE, serum IGF-1 was directly correlated with FEV1 %, serum iron, hemoglobin concentration, and transferrin saturation (TSAT) and indirectly correlated with alpha-1-antitrypsin. This study not only supports the paradigm that CF is characterized by IGF-1 deficiency but also that trends in lung function, nutritional status, and serum IGF-1 are related. Improvements in all three parameters after antibiotics for CFPE likely highlight the connection between lung function and nutritional status in CF. Close correlations among IGF-1 and iron-related hematologic parameters suggest that IGF-1 may participate in CF iron homeostasis, another process that is known to be influenced by CFPE. © 2013 Wiley Periodicals, Inc.

Stretching the stress boundary: Linking air pollution health effects to a neurohormonal stress response.

PubMed

Kodavanti, Urmila P

2016-12-01

Inhaled pollutants produce effects in virtually all organ systems in our body and have been linked to chronic diseases including hypertension, atherosclerosis, Alzheimer's and diabetes. A neurohormonal stress response (referred to here as a systemic response produced by activation of the sympathetic nervous system and hypothalamus-pituitary-adrenal (HPA)-axis) has been implicated in a variety of psychological and physical stresses, which involves immune and metabolic homeostatic mechanisms affecting all organs in the body. In this review, we provide new evidence for the involvement of this well-characterized neurohormonal stress response in mediating systemic and pulmonary effects of a prototypic air pollutant - ozone. A plethora of systemic metabolic and immune effects are induced in animals exposed to inhaled pollutants, which could result from increased circulating stress hormones. The release of adrenal-derived stress hormones in response to ozone exposure not only mediates systemic immune and metabolic responses, but by doing so, also modulates pulmonary injury and inflammation. With recurring pollutant exposures, these effects can contribute to multi-organ chronic conditions associated with air pollution. This review will cover, 1) the potential mechanisms by which air pollutants can initiate the relay of signals from respiratory tract to brain through trigeminal and vagus nerves, and activate stress responsive regions including hypothalamus; and 2) the contribution of sympathetic and HPA-axis activation in mediating systemic homeostatic metabolic and immune effects of ozone in various organs. The potential contribution of chronic environmental stress in cardiovascular, neurological, reproductive and metabolic diseases, and the knowledge gaps are also discussed. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu. Published by Elsevier B.V.

Removal of 5-hydroxytryptamine in the pulmonary circulation of rat isolated lungs

PubMed Central

Alabaster, Valerie A.; Bakhle, Y. S.

1970-01-01

1. Rat isolated lungs perfused via the pulmonary artery with Krebs solution removed 92% of the 5-hydroxytryptamine (5-HT) infused through it. This degree of removal was independent of concentration in the range from 5 to 100 g/ml. 2. The removal of 5-HT by the lungs was inhibited by amitriptyline and desmethylimipramine (10-6-10-5M). 3. The monoamine oxidase inhibitors, mebanazine and iproniazid (10-6-10-5M), inhibited the initial removal slightly, but their main effect was to preserve the 5-HT taken up and this 5-HT slowly reappeared in the effluent from the lungs. Tranylcypromine (5 × 10-7-10-6M) showed a combination of amitriptyline-like and mebanazine-like effects on the 5-HT removal in rat lung. 4. Experiments with 3H-5-HT showed that although under normal conditions only 10% of the radioactivity appeared in the lung effluent as 5-HT within the first 5 min, the rest of radioactivity administered could be recovered in the effluent over 50 min as a metabolite, probably 5-hydroxyindoleacetic acid. 5. The following amines were without effect on the removal of 5-HT by rat lungs: noradrenaline (6 × 10-7M), normetanephrine (5 × 10-6M), metaraminol (10-6M), reserpine (10-6-10-5M) and phenoxybenzamine (10-5M). 6. We conclude that the removal of 5-HT by rat lungs involves a process of uptake and metabolism rather than one of uptake and storage, but this process is not the catecholamine Uptake2. The cells involved in this process might be either capillary endothelial cells or septal cells. PMID:5497795

Reversible pulmonary hypertension in Whipple disease: a case report with clinicopathological implications, and literature review.

PubMed

Lyle, Pamela L; Weber, Robert D; Bogarin, Javier; Kircher, Tobias

2009-01-01

Whipple disease is a rare multisystemic disorder of infectious aetiology caused by Tropheryma whipplei. Pulmonary hypertension is a rare association for which the underlying pathophysiological mechanism is unclear. Our patient was a 54-year-old man with a 1-year history of progressive polyarticular arthritis, and worsening respiratory and gastrointestinal symptoms. Pulmonary artery catheterisation demonstrated moderate-to-severe pulmonary hypertension. Duodenal biopsies, with electron microscopy, were diagnostic of Whipple disease. Involvement by Whipple disease was also evident in the stomach, bone marrow and pulmonary pleura. A 2-week course of intravenous ceftriaxone was initiated and this was followed by a 1-year course of trimethoprim/sulfamethoxazole (160/800), once daily. Nine months into antibiotic treatment, a repeat echocardiogram showed normalisation of the size and function of the cardiac chambers, including the right atrium and right ventricle. There was complete resolution of the severe tricuspid insufficiency and pulmonary hypertension. Whipple disease is not generally considered as a possible cause of pulmonary hypertension but such awareness is important given that it may be potentially reversible with antibiotic therapy.

Reversible pulmonary hypertension in Whipple disease: a case report with clinicopathological implications, and literature review

PubMed Central

Lyle, Pamela L; Weber, Robert D; Bogarin, Javier; Kircher, Tobias

2009-01-01

Whipple disease is a rare multisystemic disorder of infectious aetiology caused by Tropheryma whipplei. Pulmonary hypertension is a rare association for which the underlying pathophysiological mechanism is unclear. Our patient was a 54-year-old man with a 1-year history of progressive polyarticular arthritis, and worsening respiratory and gastrointestinal symptoms. Pulmonary artery catheterisation demonstrated moderate-to-severe pulmonary hypertension. Duodenal biopsies, with electron microscopy, were diagnostic of Whipple disease. Involvement by Whipple disease was also evident in the stomach, bone marrow and pulmonary pleura. A 2-week course of intravenous ceftriaxone was initiated and this was followed by a 1-year course of trimethoprim/sulfamethoxazole (160/800), once daily. Nine months into antibiotic treatment, a repeat echocardiogram showed normalisation of the size and function of the cardiac chambers, including the right atrium and right ventricle. There was complete resolution of the severe tricuspid insufficiency and pulmonary hypertension. Whipple disease is not generally considered as a possible cause of pulmonary hypertension but such awareness is important given that it may be potentially reversible with antibiotic therapy. PMID:21686934

Pulmonary manifestations in systemic lupus erythematosus: pleural involvement, acute pneumonitis, chronic interstitial lung disease and diffuse alveolar hemorrhage.

PubMed

Aguilera-Pickens, Georgina; Abud-Mendoza, Carlos

2018-05-14

Systemic lupus erythematosus is the diffuse autoimmune connective tissue disease that most frequently involves pulmonary involvement, affecting 20% of 90% of the patients. The percentage varies depending on the defining criteria (symptoms, pulmonary tests or histopathological studies). At least once during the disease course, 50% of those affected have pleural and/or pulmonary manifestations, which are associated with higher morbidity and mortality. Pulmonary involvement has no correlation with lupus activity biomarkers, and it is necessary to rule out infectious processes in the initial approach. Bacterial infection is most frequently the cause of lung involvement in lupus and is one of the most important causes of death. Pulmonary involvement is considered to be primary when it is associated with disease activity, and secondary when other causes participate. Drugs have been reported to be associated with pulmonary damage, including interstitial disease. The incidence of malignant lung diseases is increased in systemic lupus erythematosus. Treatment depends on the type and severity of pulmonary involvement. Copyright © 2018 Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. Publicado por Elsevier España, S.L.U. All rights reserved.

Prenatal effects of maternal consumption of polyphenol-rich foods in late pregnancy upon fetal ductus arteriosus.

PubMed

Zielinsky, Paulo; Busato, Stefano

2013-12-01

Fetal circulation has characteristic features, being morphologically and functionally different from extrauterine circulation. The ductus arteriosus plays a fundamental role in directing the blood flow to fetal inferior body parts. Basically, the ductus arteriosus directs 80-85% of the right ventricular output arising from the superior vena cava, coronary sinus, and a small part from the inferior vena cava to descending aorta. Its histological structure is made up predominantly by a thick muscular layer, differently from the aorta and the pulmonary artery, which increases with gestational age. The fibers have a circumferential orientation, especially at the external layers, facilitating and making effective ductal constriction. These factors may generate lumen alterations which may cause fetal and neonatal complications, such as heart failure, hydrops, neonatal pulmonary hypertension, and even death. Classically, maternal administration of indomethacin and/or other antiinflammatory drugs interfere in prostaglandins metabolism, causing ductal constriction. However, many cases of fetal ductal constriction, as well as of persistent neonatal pulmonary artery hypertension, remain without an established etiology, being referred as "idiopathic." In recent years, a growing body of evidence has shown that herbs, fruits, nuts, and a wide diversity of substances commonly used in daily diets have definitive effects upon the metabolic pathway of inflammation, with consequent inhibition of prostaglandins synthesis. This antiinflammatory action, especially of polyphenols, when ingested during the third trimester of pregnancy, may influence the dynamics of fetal ductus arteriosus flow. The goal of this review is to present these new observations and findings, which may influence dietary orientation during pregnancy. Copyright © 2013 Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution-NonCommercialNoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is noncommercial and no modifi-cations or adaptations are made.

Coenzyme Q1 redox metabolism during passage through the rat pulmonary circulation and the effect of hyperoxia

PubMed Central

Audi, Said H.; Merker, Marilyn P.; Krenz, Gary S.; Ahuja, Taniya; Roerig, David L.; Bongard, Robert D.

2008-01-01

The objective was to evaluate the pulmonary disposition of the ubiquinone homolog coenzyme Q1 (CoQ1) on passage through lungs of normoxic (exposed to room air) and hyperoxic (exposed to 85% O2 for 48 h) rats. CoQ1 or its hydroquinone (CoQ1H2) was infused into the arterial inflow of isolated, perfused lungs, and the venous efflux rates of CoQ1H2 and CoQ1 were measured. CoQ1H2 appeared in the venous effluent when CoQ1 was infused, and CoQ1 appeared when CoQ1H2 was infused. In normoxic lungs, CoQ1H2 efflux rates when CoQ1 was infused decreased by 58 and 33% in the presence of rotenone (mitochondrial complex I inhibitor) and dicumarol [NAD(P)H-quinone oxidoreductase 1 (NQO1) inhibitor], respectively. Inhibitor studies also revealed that lung CoQ1H2 oxidation was via mitochondrial complex III. In hyperoxic lungs, CoQ1H2 efflux rates when CoQ1 was infused decreased by 23% compared with normoxic lungs. Based on inhibitor effects and a kinetic model, the effect of hyperoxia could be attributed predominantly to 47% decrease in the capacity of complex I-mediated CoQ1 reduction, with no change in the other redox processes. Complex I activity in lung homogenates was also lower for hyperoxic than for normoxic lungs. These studies reveal that lung complexes I and III and NQO1 play a dominant role in determining the vascular concentration and redox status of CoQ1 during passage through the pulmonary circulation, and that exposure to hyperoxia decreases the overall capacity of the lung to reduce CoQ1 to CoQ1H2 due to a depression in complex I activity. PMID:18703762

Coenzyme Q1 redox metabolism during passage through the rat pulmonary circulation and the effect of hyperoxia.

PubMed

Audi, Said H; Merker, Marilyn P; Krenz, Gary S; Ahuja, Taniya; Roerig, David L; Bongard, Robert D

2008-10-01

The objective was to evaluate the pulmonary disposition of the ubiquinone homolog coenzyme Q(1) (CoQ(1)) on passage through lungs of normoxic (exposed to room air) and hyperoxic (exposed to 85% O(2) for 48 h) rats. CoQ(1) or its hydroquinone (CoQ(1)H(2)) was infused into the arterial inflow of isolated, perfused lungs, and the venous efflux rates of CoQ(1)H(2) and CoQ(1) were measured. CoQ(1)H(2) appeared in the venous effluent when CoQ(1) was infused, and CoQ(1) appeared when CoQ(1)H(2) was infused. In normoxic lungs, CoQ(1)H(2) efflux rates when CoQ(1) was infused decreased by 58 and 33% in the presence of rotenone (mitochondrial complex I inhibitor) and dicumarol [NAD(P)H-quinone oxidoreductase 1 (NQO1) inhibitor], respectively. Inhibitor studies also revealed that lung CoQ(1)H(2) oxidation was via mitochondrial complex III. In hyperoxic lungs, CoQ(1)H(2) efflux rates when CoQ(1) was infused decreased by 23% compared with normoxic lungs. Based on inhibitor effects and a kinetic model, the effect of hyperoxia could be attributed predominantly to 47% decrease in the capacity of complex I-mediated CoQ(1) reduction, with no change in the other redox processes. Complex I activity in lung homogenates was also lower for hyperoxic than for normoxic lungs. These studies reveal that lung complexes I and III and NQO1 play a dominant role in determining the vascular concentration and redox status of CoQ(1) during passage through the pulmonary circulation, and that exposure to hyperoxia decreases the overall capacity of the lung to reduce CoQ(1) to CoQ(1)H(2) due to a depression in complex I activity.

Proposal for Prevention or Alleviation of Protein/Lymph-Losing Enteropathy (PLE/LLE) After Fontan Circulation Treatment of Univentricular Hearts: Restoration of Lymph Balance With a "Lymphatic Right-to-Left Shunt."

PubMed

James, H; Witte, M H; Bernas, M; Barber, B

2016-09-01

In Fontan circulations created for univentricular hearts, systemic venous return is diverted to the lungs before returning to the heart. The Total Cavopulmonary Connection (TCPC) is often the preferred surgical procedure whereby a 4-way anastomosis is created with inflow from the superior vena cava (SVC) and inferior vena cava (IVC) and outflow to the right and left branches of the pulmonary artery. In this arrangement, the systemic venous pressure must be elevated sufficiently to perfuse the lungs passively without the normal boost of the right ventricle. Hence, unlike surgical corrections for other congenital heart conditions, the systemic venous pressures in a Fontan circuit must be elevated to make the circulation work. It is proposed here that the incidence of PLE/LLE is directly related to elevated venous and lymphatic pressures, which cause leakage of proteins/lymph into the gastrointestinal tract (GIT) and expulsion from the body. It is commonly held that elevated venous pressures are relatively better tolerated in the upper body, but much less so in the heptatosplanchnic circulation and the lower body. It is also well established that elevated venous pressure increases lymph formation, most of which is produced in the hepatosplanchnic region (liver and intestine). It is further argued here that the increase in lymph filling pressure arising from the higher lymph flow, in association with the backpressure exerted by elevated venous pressure at the main drainage point into the venous system, results in a substantial increase in pressure in the thoracic duct. This pressure is transmitted back to the intestinal lymphatics, causing dilatation with lacteal rupture and protein or bulk lymph leakage into the intestine. We propose in this paper a new approach, based on experimental evidence, to prevent and/or alleviate this condition by draining or redirecting the thoracic duct (or, alternatively, a more localized intestinal lymphatic vessel) into one of the pulmonary veins or the left atrium, which are typically at near-normal pressure in a Fontan circulation. This “lymphatic-venous right-to-left” shunt maneuver would significantly reduce the venous backpressure on the lymphatics as well as improve lymph circulation, resulting in a decrease in the intestinal lymphatic pressure and thereby prevent or alleviate protein/lymph loss, i.e. lymph balance would be restored. Moreover, the greatly facilitated lymphatic flow would encourage further capillary filtration to relieve excessive venous pressure in the hepatosplanchnic region and protect the liver and kidneys. This paper is intended as a discussion document for elicitation of comments on the soundness and viability of this proposal as well as on technical challenges and steps to explore and advance it.

Effects of body position on the carbon monoxide diffusing capacity in patients with chronic heart failure: relation to hemodynamic changes.

PubMed

Faggiano, P; D'Aloia, A; Simoni, P; Gualeni, A; Foglio, K; Ambrosino, N; Giordano, A

1998-01-01

Pulmonary diffusion has been found to be reduced in patients with congestive heart failure. The effects of postural changes on the diffusing capacity had been evaluated in healthy subjects, but not in patients with heart failure. The aim of this study was to evaluate the posture-induced changes in diffusing capacity in patients with chronic heart failure and their relation to the hemodynamic profile. The pulmonary carbon monoxide diffusing capacity (DLCO) was measured in the supine position, with 20 degrees passive head elevation, and in the sitting position, both postures maintained for 10 min, in a group of 32 male patients with mild to moderate chronic heart failure due to left ventricular systolic dysfunction (ejection fraction <35%). On a separate day, in the absence of any changes in clinical status and therapy, the hemodynamic parameters were measured by right-heart catheterization. The sequence of postures was assigned randomly. The mean values of DLCO were slightly reduced and did not differ in the two positions (20.3 +/- 5.7 vs. 19.4 +/- 5.6 ml/min/mm Hg, 77 +/- 23 vs. 75 +/- 20% of predicted, respectively). The patients were then subdivided according to changes in DLCO from the supine to the sitting position: DLCO increased (+23%) in 9 patients (28%, group 1), decreased (-17.5%) in 17 patients (53%, group 2), and remained within the coefficient of reproducibility ( +/- 5 %) in 6 patients (group 3). As compared with group 2, group 1 patients showed a significant increase in mean pulmonary artery pressure (+7 vs. -15%, p < 0.01) and pulmonary capillary wedge pressure (+8 vs. -22%, p < 0.005) from the supine to the sitting position, while the cardiac index showed a smaller - but not significant - decrease in group 1 (-5 vs. -12%). The percent changes in DLCO significantly correlated with changes in pulmonary capillary wedge (r = 0.54, p < 0.0005) and mean pulmonary artery (r = 0.47, p < 0.005) pressures. In chronic heart failure postural changes may induce different responses in diffusing capacity. To a greater extent than in healthy subjects, the most common response is a decrease in DLCO in the sitting as compared with the supine position. The DLCO changes correlate with variations in pulmonary circulation pressure, probably due to changes in pulmonary vascular recruitment and pulmonary capillary blood volume.

[Cryoballon isolation of the pulmonary veins in atrial fibrillation: mid-term results after the first 55 patients].

PubMed

Tóth, Zsuzsanna; Nagy-Baló, Edina; Kertész, Attila; Clemens, Marcell; Herczku, Csaba; Tint, Diana; Kun, Csaba; Edes, István; Csanádi, Zoltán

2010-01-31

Several transcatheter techniques based on radiofrequency energy were elaborated for the treatment of atrial fibrillation through the last decade. Recently, similar success rates with a better safety profile concerning life threatening complications were reported with the novel methode of cryoballon isolation of the pulmonary veins. This paper summarizes our initial experience with cryoballon ablation after the first 55 patients. [corrected] Symptomatic patients refractory to aniarrhythmic medication mostly with paroxysmal atrial fibrillation without significant structural heart disease were enrolled. Cannulation and isolation of all pulmonary veins were attempted using a 28 mm double-wall cryoballon inflated at the ostium of the vein and abolishing eletrical activity of atrial tissue around its perimeter by freezing to -70 C. Intravenous heparin during and oral anticoagulant after the procedure was administered. Conventional ECGs, Holter ECGs and transtelephonic ECG recordings were used through 6 months follow-up for rhythm monitoring. In 55 patients enrolled (18 female; age: 56 + or - 33,64 years) 165 out ot 192 (86%) pulmonary veins were successfully isolated. All pulmonary veins were isolated in 37 patients (67%). Procedure time was 155.67 + or - 100.66 min, while fluoroscopy time was 34.04 + or - 31.89 min. In 34 patients with 6 months follow-up 24 (70%) either remained free of arrhythmia (17 patients) or had a significant decrease in arrhythmia burden (7 patients). Based on our initial experience, cryoballon isolation of pulmonary veins appears to be a more simple procedure with similar efficacy to radiofrequency ablation in the treatment of atrial fibrillation.

The Infection Returns: A Case of Pulmonary Sporotrichosis Relapse after Chemotherapy

PubMed Central

2018-01-01

Background Pulmonary sporotrichosis is a rare disease caused by a dimorphic fungus, Sporothrix schenckii. It is rarely found in association with malignancy. We present a case of pulmonary sporotrichosis recurrence after chemotherapy. Case Presentation A 44-year-old man, treated for pulmonary sporotrichosis in the past, presented with dysphagia and was found to have squamous cell carcinoma of the esophagus. After undergoing chemotherapy, extensive cavitary lesions were observed on thoracic computed tomography scan. A bronchoalveolar lavage revealed the presence of Sporothrix schenckii sensu lato. Despite treatment with itraconazole, he eventually required a left pneumonectomy for progressive destructive cavitary lesions involving the left lung. Conclusion This case highlights the importance of considering past fungal infections, albeit cured, in patients initiating immunosuppressive therapy. PMID:29559998

CD4 T Cell Epitope Specificity and Cytokine Potential Are Preserved as Cells Transition from the Lung Vasculature to Lung Tissue following Influenza Virus Infection.

PubMed

DiPiazza, Anthony; Laniewski, Nathan; Rattan, Ajitanuj; Topham, David J; Miller, Jim; Sant, Andrea J

2018-07-01

Pulmonary CD4 T cells are critical in respiratory virus control, both by delivering direct effector function and through coordinating responses of other immune cells. Recent studies have shown that following influenza virus infection, virus-specific CD4 T cells are partitioned between pulmonary vasculature and lung tissue. However, very little is known about the peptide specificity or functional differences of CD4 T cells within these two compartments. Using a mouse model of influenza virus infection in conjunction with intravascular labeling in vivo , the cell surface phenotype, epitope specificity, and functional potential of the endogenous polyclonal CD4 T cell response was examined by tracking nine independent CD4 T cell epitope specificities. These studies revealed that tissue-localized CD4 cells were globally distinct from vascular cells in expression of markers associated with transendothelial migration, residency, and micropositioning. Despite these differences, there was little evidence for remodeling of the viral epitope specificity or cytokine potential as cells transition from vasculature to the highly inflamed lung tissue. Our studies also distinguished cells in the pulmonary vasculature from peripheral circulating CD4 T cells, providing support for the concept that the pulmonary vasculature does not simply reflect circulating cells that are trapped within the narrow confines of capillary vessels but rather is enriched in transitional cells primed in the draining lymph node that have specialized potential to enter the lung tissue. IMPORTANCE CD4 T cells convey a multitude of functions in immunity to influenza, including those delivered in the lymph node and others conveyed by CD4 T cells that leave the lymph node, enter the blood, and extravasate into the lung tissue. Here, we show that the transition of recently primed CD4 cells detected in the lung vasculature undergo profound changes in expression of markers associated with tissue localization as they establish residence in the lung. However, this transition does not edit CD4 T cell epitope specificity or the cytokine potential of the CD4 T cells. Thus, CD4 T cells that enter the infected lung can convey diverse functions and have a sufficiently broad viral antigen specificity to detect the complex array of infected cells within the infected tissue, offering the potential for more effective protective function. Copyright © 2018 American Society for Microbiology.

Severe Tuberculosis in Humans Correlates Best with Neutrophil Abundance and Lymphocyte Deficiency and Does Not Correlate with Antigen-Specific CD4 T-Cell Response

PubMed Central

Panteleev, Alexander V.; Nikitina, Irina Yu; Burmistrova, Irina A.; Kosmiadi, George A.; Radaeva, Tatyana V.; Amansahedov, Rasul B.; Sadikov, Pavel V.; Serdyuk, Yana V.; Larionova, Elena E.; Bagdasarian, Tatef R.; Chernousova, Larisa N.; Ganusov, Vitaly V.; Lyadova, Irina V.

2017-01-01

It is generally thought that Mycobacterium tuberculosis (Mtb)-specific CD4+ Th1 cells producing IFN-γ are essential for protection against tuberculosis (TB). In some studies, protection has recently been associated with polyfunctional subpopulation of Mtb-specific Th1 cells, i.e., with cells able to simultaneously secrete several type 1 cytokines. However, the role for Mtb-specific Th1 cells and their polyfunctional subpopulations during established TB disease is not fully defined. Pulmonary TB is characterized by a great variability of disease manifestations. To address the role for Mtb-specific Th1 responses during TB, we investigated how Th1 and other immune cells correlated with particular TB manifestations, such as the degree of pulmonary destruction, TB extent, the level of bacteria excretion, clinical disease severity, clinical TB forms, and “Timika X-ray score,” an integrative parameter of pulmonary TB pathology. In comparison with healthy Mtb-exposed controls, TB patients (TBP) did not exhibit deficiency in Mtb-specific cytokine-producing CD4+ cells circulating in the blood and differed by a polyfunctional profile of these cells, which was biased toward the accumulation of bifunctional TNF-α+IFN-γ+IL-2− lymphocytes. Importantly, however, severity of different TB manifestations was not associated with Mtb-specific cytokine-producing cells or their polyfunctional profile. In contrast, several TB manifestations were strongly correlated with leukocyte numbers, the percent or the absolute number of lymphocytes, segmented or band neutrophils. In multiple alternative statistical analyses, band neutrophils appeared as the strongest positive correlate of pulmonary destruction, bacteria excretion, and “Timika X-ray score.” In contrast, clinical TB severity was primarily and inversely correlated with the number of lymphocytes in the blood. The results suggest that: (i) different TB manifestations may be driven by distinct mechanisms; (ii) quantitative parameters and polyfunctional profile of circulating Mtb-specific CD4+ cells play a minor role in determining TB severity; and (iii) general shifts in production/removal of granulocytic and lymphocytic lineages represent an important factor of TB pathogenesis. Mechanisms leading to these shifts and their specific role during TB are yet to be determined but are likely to involve changes in human hematopoietic system. PMID:28871253

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

Lee, Deok Hee; Hwang, Jae Cheol; Lim, Soo Mee

Purpose: To describe the findings of pleural and pulmonary staining of the inferior phrenic artery, which can be confused with tumor staining during transarterial chemoembolization (TACE) of hepatoma.Methods: Fifteen patients who showed pleural and pulmonary staining without relationship to hepatic masses at inferior phrenic arteriography were enrolled. The staining was noted at initial TACE (n = 8), at successive TACE (n = 5), and after hepatic surgery (n = 2). The angiographic pattern, the presence of pleural change on computed tomography (CT), and clinical history were evaluated.Results: Draining pulmonary veins were seen in all cases. The lower margin of themore » staining corresponded to the lower margin of the pleura in 10 patients. CT showed pleural and/or pulmonary abnormalities in all cases. After embolization of the inferior phrenic artery, the accumulation of iodized oil in the lung was noted.Conclusion: Understanding the CT and angiographic findings of pleural and pulmonary staining during TACE may help differentiate benign staining from tumor staining.« less

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.

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.

[Factors linked to delayed diagnosis of tuberculosis in Conakry (Guinea)].

PubMed

Camara, A; Diallo, A; Camara, L M; Fielding, K; Sow, O Y; Chaperon, J

2006-03-01

Untreated smear-positive pulmonary tuberculosis constitutes a reservoir of infection which is highly contagious. The present study was conducted in Conakry, Guinea, to determine the different options which are available when seeking treatment or care, and to ascertain the average delay in diagnosis of pulmonary tuberculosis and the main factors linked to the delay in diagnosis after the initial onset of symptoms. Through a cross-sectional study, 113 consecutive patients with smear-positive pulmonary tuberculosis were interviewed through the use of a questionnaire. The median total delay from the onset of symptoms of pulmonary tuberculosis until the diagnosis was 11 weeks. This delay period exceeded 4 weeks for 90 of the patients (80%). The average delay linked to the conventional health care system was double that of the one at the fault of the patient (6 weeks versus 3 weeks, respectively). 54% of the patients had initially resorted to non-conventional care. To shorten this mean delay period, it is necessary to both strengthen the professional abilities and skills which train for one to better to detect tuberculosis and to sensitize the population to the subject matter and information on the illness and its symptoms.

Mechanics of cryopreserved aortic and pulmonary homografts.

PubMed

Vesely, I; Casarotto, D C; Gerosa, G

2000-01-01

The surgical placement of pulmonary valve grafts into the aortic position (the Ross procedure) has been performed for three decades. Cryopreserved pulmonary valves have had mixed clinical results, however. The objectives of this study were to compare the mechanics of cryopreserved human aortic and pulmonary valve cusps and roots to determine if the pulmonary root can withstand the greater pressures of the aortic position. Six aortic and six pulmonary valve roots were obtained from the Oxford Valve Bank. They were harvested during cardiac transplantation from hearts explanted for dilated cardiomyopathy (mean patient age 68 years). The whole roots were initially stored frozen at -186 degrees C, then shipped packed on dry ice. After complete thawing, the roots were pressurized whole; test strips were then cut from the valve cusps, roots and sinuses and tested for stress/strain, stress relaxation, and ultimate failure strength. The pulmonary roots were more distensible (30% versus 20% strain to lock-up) and less compliant when loaded to aortic pressures. The pulmonary valve cusp and root tissue also showed greater extensibility and greater stiffness (lower compliance) when subjected to the same loads. We conclude that mechanical differences between aortic and pulmonary valve tissues are minimal. The pulmonary root should withstand the forces imposed on it when placed in the aortic position. However, if implanted whole, the pulmonary root will distend about 30% more than the aortic root when subjected to aortic pressures. These geometric changes may affect valve function in the long term and should be appreciated when implanting a pulmonary valve graft.

High Prevalence of Pulmonary Hypertension Complicates the Care of Infants with Omphalocele.

PubMed

Hutson, Shandee; Baerg, Joanne; Deming, Douglas; St Peter, Shawn D; Hopper, Andrew; Goff, Donna A

2017-01-01

Omphalocele is one of the most common abdominal wall defects. Many newborn infants born with omphalocele present with significant respiratory distress at birth, requiring mechanical ventilatory support, and have clinical evidence of pulmonary hypertension. Little information exists on the prevalence of and risk factors associated with pulmonary hypertension in this cohort of infants. To describe the prevalence of and risk factors associated with pulmonary hypertension among infants with omphalocele. This is a multicenter retrospective chart review of demographic data and clinical characteristics of infants with omphalocele admitted to the neonatal intensive care units of Loma Linda University Children's Hospital and Children's Mercy Hospital between 1994 and 2011. Echocardiogram images were reviewed for pulmonary hypertension, and statistical analyses were performed to identify risk factors associated with the presence of pulmonary hypertension. Pulmonary hypertension was diagnosed in 32/56 (57%) infants with omphalocele. Compared to infants without pulmonary hypertension, infants with pulmonary hypertension were more likely to have a liver-containing defect (16/32 [50%] vs. 5/24 [21%], p = 0.03), require intubation at birth (18/32 [56%] vs. 6/24 [17%], p = 0.03), and die during initial hospitalization (12/32 [38%] vs. 2/24 [8%], p = 0.01). The majority of infants with omphalocele have evidence of pulmonary hypertension which is associated with increased mortality. Echocardiograms to screen for pulmonary hypertension should be obtained at ≥2 days of life in infants with omphalocele, especially in those with liver within the omphalocele sac and/or in those infants who require intubation at birth to screen for pulmonary hypertension. © 2017 S. Karger AG, Basel.

Right Ventricular Perfusion: Physiology and Clinical Implications.

PubMed

Crystal, George J; Pagel, Paul S

2018-01-01

Regulation of blood flow to the right ventricle differs significantly from that to the left ventricle. The right ventricle develops a lower systolic pressure than the left ventricle, resulting in reduced extravascular compressive forces and myocardial oxygen demand. Right ventricular perfusion has eight major characteristics that distinguish it from left ventricular perfusion: (1) appreciable perfusion throughout the entire cardiac cycle; (2) reduced myocardial oxygen uptake, blood flow, and oxygen extraction; (3) an oxygen extraction reserve that can be recruited to at least partially offset a reduction in coronary blood flow; (4) less effective pressure-flow autoregulation; (5) the ability to downregulate its metabolic demand during coronary hypoperfusion and thereby maintain contractile function and energy stores; (6) a transmurally uniform reduction in myocardial perfusion in the presence of a hemodynamically significant epicardial coronary stenosis; (7) extensive collateral connections from the left coronary circulation; and (8) possible retrograde perfusion from the right ventricular cavity through the Thebesian veins. These differences promote the maintenance of right ventricular oxygen supply-demand balance and provide relative resistance to ischemia-induced contractile dysfunction and infarction, but they may be compromised during acute or chronic increases in right ventricle afterload resulting from pulmonary arterial hypertension. Contractile function of the thin-walled right ventricle is exquisitely sensitive to afterload. Acute increases in pulmonary arterial pressure reduce right ventricular stroke volume and, if sufficiently large and prolonged, result in right ventricular failure. Right ventricular ischemia plays a prominent role in these effects. The risk of right ventricular ischemia is also heightened during chronic elevations in right ventricular afterload because microvascular growth fails to match myocyte hypertrophy and because microvascular dysfunction is present. The right coronary circulation is more sensitive than the left to α-adrenergic-mediated constriction, which may contribute to its greater propensity for coronary vasospasm. This characteristic of the right coronary circulation may increase its vulnerability to coronary vasoconstriction and impaired right ventricular perfusion during administration of α-adrenergic receptor agonists.

CD16-positive circulating monocytes and fibrotic manifestations of systemic sclerosis.

PubMed

Lescoat, Alain; Lecureur, Valérie; Roussel, Mikael; Sunnaram, Béatrice Ly; Ballerie, Alice; Coiffier, Guillaume; Jouneau, Stéphane; Fardel, Olivier; Fest, Thierry; Jégo, Patrick

2017-07-01

The objective of this study is to assess the association of clinical manifestations of systemic sclerosis (SSc) with the absolute count of circulating blood monocyte subpopulations according to their membrane expression of CD16. Forty-eight consecutive patients fulfilling the 2013 ACR/EULAR classification criteria for SSc were included in this cross-sectional study. CD16+ monocyte absolute count was defined by flow cytometry and confronted to the clinical characteristics of SSc patients. Twenty-three healthy donors (HD) were randomly selected for comparison. SSc patients had an increased number of total circulating blood monocytes compared to HD (p < 0.001). The CD16- subpopulation absolute count was increased in SSc patients compared to HD (p < 0.001) but was similar in limited SSc (lSSc) and diffuse SSc (dSSc). On the contrary, the CD16+ population absolute count was increased in dSSc compared to both HD and lSSc patients (dSSc 0.071 Giga/L (±0.034) vs HD 0.039 Giga/L (±0.030), p < 0.01, and dSSc 0.071 Giga/L (±0.034) vs lSSc 0.048 Giga/L (±0.024), p < 0.05). The CD16+ monocyte subpopulation absolute count was significantly correlated with the severity of skin fibrosis evaluated by the modified Rodnan skin score (p < 0.001). The CD16+ monocyte subpopulation was also associated with pulmonary fibrosis (p < 0.05), with the severity of the restrictive ventilatory defect evaluated by total lung capacity (p < 0.05) and with the pulmonary function impairment reflected by diffusing capacity of the lungs for carbon monoxyde measures (p < 0.01). These results suggest that CD16+ monocytes are associated with the main fibrotic manifestations of SSc and their role in the pathogenesis of fibrosis in this autoimmune disorder should therefore be further considered.

Brain versus lung: hierarchy of feedback loops in single-ventricle patients with superior cavopulmonary connection.

PubMed

Fogel, Mark A; Durning, Suzanne; Wernovsky, Gil; Pollock, Avrum N; Gaynor, J William; Nicolson, Susan

2004-09-14

CO2 vasodilates and O2 vasoconstricts the cerebral vascular bed; the opposite is true in the lungs. When the brain and lungs are connected exclusively in series, which feedback loop predominates is unknown. The circulation of the superior cavopulmonary connection (SCPC) provides a unique physiology to answer this question. To determine cerebral and pulmonary blood flow and to establish the hierarchy of cerebral and pulmonary feedback mechanisms, 12 intubated, ventilated, single-ventricle patients in SCPC physiology (age 2.2+/-0.5 years) underwent magnetic resonance imaging velocity mapping of their jugular veins and aorta in room air, hypercarbia, and 100% O2. Flows in these vessels and arterial blood gases were measured. With 22+/-6 torr CO2 (Pco2) increased from 40 to 63 mm Hg, P<0.01), flow to the brain and lungs increased (1.5 to 2.7 L/min per m2, P=0.0003), Po2 improved (48 to 60 mm Hg, P=0.0004), and cardiac index increased (4.3 to 5.4 L/min per m2, P=0.0003). The increased cardiac index accounted for the increased cerebral and pulmonary blood flow (R=0.73, P=0.02) and cerebral O2 transport increased by 80% (P=0.0005) while preserving body O2 delivery. Hyperoxia did not change cerebral and pulmonary blood flow; Po2 increased 94% (P=0.01). The cerebral CO2 feedback loop predominates over the pulmonary one when they directly compete with each other. CO2 has a major impact on flow distribution whereas O2 has little impact. Increased CO2 improves cerebral oxygenation in SCPC patients. This may provide a clue in determining neurological sequelae in SC physiology and may influence timing of Fontan completion.

Effect of Treatment of Cystic Fibrosis Pulmonary Exacerbations on Systemic Inflammation

PubMed Central

Thompson, Valeria; Chmiel, James F.; Montgomery, Gregory S.; Nasr, Samya Z.; Perkett, Elizabeth; Saavedra, Milene T.; Slovis, Bonnie; Anthony, Margaret M.; Emmett, Peggy; Heltshe, Sonya L.

2015-01-01

Rationale: In cystic fibrosis (CF), pulmonary exacerbations present an opportunity to define the effect of antibiotic therapy on systemic measures of inflammation. Objectives: Investigate whether plasma inflammatory proteins demonstrate and predict a clinical response to antibiotic therapy and determine which proteins are associated with measures of clinical improvement. Methods: In this multicenter study, a panel of 15 plasma proteins was measured at the onset and end of treatment for pulmonary exacerbation and at a clinically stable visit in patients with CF who were 10 years of age or older. Measurements and Main Results: Significant reductions in 10 plasma proteins were observed in 103 patients who had paired blood collections during antibiotic treatment for pulmonary exacerbations. Plasma C-reactive protein, serum amyloid A, calprotectin, and neutrophil elastase antiprotease complexes correlated most strongly with clinical measures at exacerbation onset. Reductions in C-reactive protein, serum amyloid A, IL-1ra, and haptoglobin were most associated with improvements in lung function with antibiotic therapy. Having higher IL-6, IL-8, and α1-antitrypsin (α1AT) levels at exacerbation onset were associated with an increased risk of being a nonresponder (i.e., failing to recover to baseline FEV1). Baseline IL-8, neutrophil elastase antiprotease complexes, and α1AT along with changes in several plasma proteins with antibiotic treatment, in combination with FEV1 at exacerbation onset, were predictive of being a treatment responder. Conclusions: Circulating inflammatory proteins demonstrate and predict a response to treatment of CF pulmonary exacerbations. A systemic biomarker panel could speed up drug discovery, leading to a quicker, more efficient drug development process for the CF community. PMID:25714657

Increased virulence of Cunninghamella bertholletiae in experimental pulmonary mucormycosis: correlation with circulating molecular biomarkers, sporangiospore germination and hyphal metabolism.

PubMed

Petraitis, Vidmantas; Petraitiene, Ruta; Antachopoulos, Charalampos; Hughes, Johanna E; Cotton, Margaret P; Kasai, Miki; Harrington, Susan; Gamaletsou, Maria N; Bacher, John D; Kontoyiannis, Dimitrios P; Roilides, Emmanuel; Walsh, Thomas J

2013-01-01

Members of the order Mucorales are emerging invasive molds that cause infections in immunocompromised patients. However, little is known about the relation between different species of Mucorales and their virulence in invasive pulmonary mucormycosis. Based upon our earlier epidemiological studies, we hypothesized that Cunninghamella bertholletiae would demonstrate increased virulence. Therefore, we studied the relative virulence of C. bertholletiae (CB), Rhizopus oryzae (RO), R. microsporus (RM), and Mucor circinelloides (MC) in experimental invasive pulmonary mucormycosis in persistently neutropenic rabbits in relation to the fungi in vitro sporangiospore germination rate and hyphal metabolic activity. Rabbits infected with CB demonstrated (1) higher lung weights in comparison to RM (P ≤ 0.05), RO and MC (P ≤ 0.001), (2) pulmonary infarcts in comparison to RO and MC (P ≤ 0.001), (3) tissue fungal burden (CFU/g) vs. MC (P ≤ 0.001), and (4) the lowest survival of 0% (0/18), in comparison to 16% (3/18, P ≤ 0.01) of RM, 81% (21/26) of RO, and 83% (15/18) of MC-infected rabbits (P ≤ 0.001). Serum PCR concentration-time-curve showed the greatest amplitude for CB. Virulence correlated directly with sporangiospore germination rate at 4 h among species, i.e., CB (67-85%) > RM (14-56%) > RO (4-30%) > MC (0%), and hyphal metabolic activity, i.e., CB (1.22-1.51) > MC (0.54-0.64) = RM (0.38-0.41) = RO (0.37-0.59). C. bertholletiae was significantly more virulent in experimental invasive pulmonary mucormycosis than R. microsporus, R. oryzae, and M. circinelloides. In vivo virulence correlated with species-dependent differences of in vitro germination rate and hyphal metabolic activity.

Galectin-3 Is Associated with Restrictive Lung Disease and Interstitial Lung Abnormalities.

PubMed

Ho, Jennifer E; Gao, Wei; Levy, Daniel; Santhanakrishnan, Rajalakshmi; Araki, Tetsuro; Rosas, Ivan O; Hatabu, Hiroto; Latourelle, Jeanne C; Nishino, Mizuki; Dupuis, Josée; Washko, George R; O'Connor, George T; Hunninghake, Gary M

2016-07-01

Galectin-3 (Gal-3) has been implicated in the development of pulmonary fibrosis in experimental studies, and Gal-3 levels have been found to be elevated in small studies of human pulmonary fibrosis. We sought to study whether circulating Gal-3 concentrations are elevated early in the course of pulmonary fibrosis. We examined 2,596 Framingham Heart Study participants (mean age, 57 yr; 54% women; 14% current smokers) who underwent Gal-3 assessment using plasma samples and pulmonary function testing between 1995 and 1998. Of this sample, 1,148 underwent subsequent volumetric chest computed tomography. Higher Gal-3 concentrations were associated with lower lung volumes (1.4% decrease in percentage of predicted FEV1 per 1 SD increase in log Gal-3; 95% confidence interval [CI], 0.8-2.0%; P < 0.001; 1.2% decrease in percentage of predicted FVC; 95% CI, 0.6-1.8%; P < 0.001) and decreased diffusing capacity of the lung for carbon monoxide (2.1% decrease; 95% CI, 1.3-2.9%; P < 0.001). These associations remained significant after multivariable adjustment (P ≤ 0.008 for all). Compared with the lowest quartile, participants in the highest Gal-3 quartile were more than twice as likely to have interstitial lung abnormalities visualized by computed tomography (multivariable-adjusted odds ratio, 2.67; 95% CI, 1.49-4.76; P < 0.001). Elevated Gal-3 concentrations are associated with interstitial lung abnormalities coupled with a restrictive pattern, including decreased lung volumes and altered gas exchange. These findings suggest a potential role for Gal-3 in early stages of pulmonary fibrosis.

Galectin-3 Is Associated with Restrictive Lung Disease and Interstitial Lung Abnormalities

PubMed Central

Gao, Wei; Levy, Daniel; Santhanakrishnan, Rajalakshmi; Araki, Tetsuro; Rosas, Ivan O.; Hatabu, Hiroto; Latourelle, Jeanne C.; Nishino, Mizuki; Dupuis, Josée; Washko, George R.; O’Connor, George T.; Hunninghake, Gary M.

2016-01-01

Rationale: Galectin-3 (Gal-3) has been implicated in the development of pulmonary fibrosis in experimental studies, and Gal-3 levels have been found to be elevated in small studies of human pulmonary fibrosis. Objectives: We sought to study whether circulating Gal-3 concentrations are elevated early in the course of pulmonary fibrosis. Methods: We examined 2,596 Framingham Heart Study participants (mean age, 57 yr; 54% women; 14% current smokers) who underwent Gal-3 assessment using plasma samples and pulmonary function testing between 1995 and 1998. Of this sample, 1,148 underwent subsequent volumetric chest computed tomography. Measurements and Main Results: Higher Gal-3 concentrations were associated with lower lung volumes (1.4% decrease in percentage of predicted FEV1 per 1 SD increase in log Gal-3; 95% confidence interval [CI], 0.8–2.0%; P < 0.001; 1.2% decrease in percentage of predicted FVC; 95% CI, 0.6–1.8%; P < 0.001) and decreased diffusing capacity of the lung for carbon monoxide (2.1% decrease; 95% CI, 1.3–2.9%; P < 0.001). These associations remained significant after multivariable adjustment (P ≤ 0.008 for all). Compared with the lowest quartile, participants in the highest Gal-3 quartile were more than twice as likely to have interstitial lung abnormalities visualized by computed tomography (multivariable-adjusted odds ratio, 2.67; 95% CI, 1.49–4.76; P < 0.001). Conclusions: Elevated Gal-3 concentrations are associated with interstitial lung abnormalities coupled with a restrictive pattern, including decreased lung volumes and altered gas exchange. These findings suggest a potential role for Gal-3 in early stages of pulmonary fibrosis. PMID:26771117

Immunity against influenza A(H1N1) infections is determined by age at the time of initial strain circulation.

PubMed

Delabre, R M; Salez, N; Lapidus, N; Lemaitre, M; Leruez-Ville, M; de Lamballerie, X; Carrat, F

2017-01-01

We explored age-dependent patterns in haemagglutination inhibition (HI) titre to seasonal [1956 A(H1N1), 1977 A(H1N1), 2007 A(H1N1)] and pandemic [A(H1N1)pdm09] influenza strains using serological data collected from an adult French influenza cohort. Subjects were recruited by their general practitioners from 2008 to 2009 and followed until 2010. We explored age-related differences between strain-specific HI titres using 1053 serological samples collected over the study period from 398 unvaccinated subjects. HI titres against the tested seasonal and pandemic strains were determined using the HI technique. Geometric mean titres (GMTs) were estimated using regression models for interval-censored data. Generalized additive mixed models were fit to log-transformed HI estimates to study the relationship between HI titre and age (age at inclusion and/or age at initial strain circulation). GMT against one strain was consistently highest in the birth cohort exposed to that strain during childhood, with peak titres observed in subjects aged 7-8 years at the time of initial strain circulation. Our results complete previous findings on influenza A(H3N2) strains and identify a strain-dependent relationship between HI titre and age at initial strain circulation.

Perioperative circulating tumor cells in surgical patients with non-small cell lung cancer: does surgical manipulation dislodge cancer cells thus allowing them to pass into the peripheral blood?

PubMed

Sawabata, Noriyoshi; Funaki, Soichiro; Hyakutake, Takeru; Shintani, Yasushi; Fujiwara, Ayako; Okumura, Meinoshin

2016-12-01

We herein evaluated the status of circulating tumor cells (CTC) dislodged from the tumor during surgery in patients who underwent pulmonary resection for non-small cell lung cancer (NSCLC) to assess the clinical implications. Tumor cells in the peripheral arterial blood before surgery (Before) and immediately after lung resection (After) and in the blood from the pulmonary vein of the resected lung were detected using a size selective method. The clinicopathological characteristics and the prognosis were then analyzed according to the CTC status: no tumor cells detected (N), single tumor cell or total number less than 4 cells (S), and existence of clustered cells (C). According to the CTC status, the patients were classified into the following three groups: Before-C and After-C, Group I (n = 6); Before-S or N and After-C, Group II (n = 9); and Before-S or N and After-S or N, Group III (n = 8). Group III showed a high rate of p-stage IA, smaller tumor size, lower CEA level, lower SUVmax level, and a higher relapse-free survival rate than the other groups. CTCs were detected in patients after undergoing lung resection, some of which may have been dislodged by the surgical procedure. The presence of clustered CTCs after the operation indicated an unfavorable outcome.

Cerebral oxygen saturation and peripheral perfusion in the extremely premature infant with intraventricular and/or pulmonary haemorrhage early in life.

PubMed

Beausoleil, Thierry P; Janaillac, Marie; Barrington, Keith J; Lapointe, Anie; Dehaes, Mathieu

2018-04-25

Extremely preterm infants are at higher risk of pulmonary (PH) and intraventricular (IVH) haemorrhage during the transitioning physiology due to immature cardiovascular system. Monitoring of haemodynamics can detect early abnormal circulation that may lead to these complications. We described time-frequency relationships between near infrared spectroscopy (NIRS) cerebral regional haemoglobin oxygen saturation (CrSO 2 ) and preductal peripheral perfusion index (PI), capillary oxygen saturation (SpO 2 ) and heart rate (HR) in extremely preterm infants in the first 72 h of life. Patients were sub-grouped in infants with PH and/or IVH (N H  = 8) and healthy controls (N C  = 11). Data were decomposed in wavelets allowing the analysis of localized variations of power. This approach allowed to quantify the percentage of time of significant cross-correlation, semblance, gain (transfer function) and coherence between signals. Ultra-low frequencies (<0.28 mHz) were analyzed as slow and prolonged periods of impaired circulation are considered more detrimental than transient fluctuations. Cross-correlation between CrSO 2 and oximetry (PI, SpO 2 and HR) as well as in-phase semblance and gain between CrSO 2 and HR were significantly lower while anti-phase semblance between CrSO 2 and HR was significantly higher in PH-IVH infants compared to controls. These differences may reflect haemodynamic instability associated with cerebrovascular autoregulation and hemorrhagic complications observed during the transitioning physiology.

CXCL14 is a candidate biomarker for Hedgehog signalling in idiopathic pulmonary fibrosis.

PubMed

Jia, Guiquan; Chandriani, Sanjay; Abbas, Alexander R; DePianto, Daryle J; N'Diaye, Elsa N; Yaylaoglu, Murat B; Moore, Heather M; Peng, Ivan; DeVoss, Jason; Collard, Harold R; Wolters, Paul J; Egen, Jackson G; Arron, Joseph R

2017-09-01

Idiopathic pulmonary fibrosis (IPF) is associated with aberrant expression of developmental pathways, including Hedgehog (Hh). As Hh signalling contributes to multiple pro-fibrotic processes, Hh inhibition may represent a therapeutic option for IPF. However, no non-invasive biomarkers are available to monitor lung Hh activity. We assessed gene and protein expression in IPF and control lung biopsies, mouse lung, fibroblasts stimulated in vitro with sonic hedgehog (SHh), and plasma in IPF patients versus controls, and cancer patients before and after treatment with vismodegib, a Hh inhibitor. Lung tissue from IPF patients exhibited significantly greater expression of Hh-related genes versus controls. The gene most significantly upregulated in both IPF lung biopsies and fibroblasts stimulated in vitro with SHh was CXCL14 , which encodes a soluble secreted chemokine whose expression is inhibited in vitro by the addition of vismodegib. CXCL14 expression was induced by SHh overexpression in mouse lung. Circulating CXCL14 protein levels were significantly higher in plasma from IPF patients than controls. In cancer patients, circulating CXCL14 levels were significantly reduced upon vismodegib treatment. CXCL14 is a systemic biomarker that could be used to identify IPF patients with increased Hh pathway activity and monitor the pharmacodynamic effects of Hh antagonist therapy in IPF. Post-results, NCT00968981. 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/.

Heterotaxy syndrome with severe pulmonary hypertension in an adult.

PubMed

Brandenburg, Vincent M; Krueger, Stefan; Haage, Patrick; Mertens, Peter; Riehl, Jochen

2002-05-01

Heterotaxy syndrome is a rare clinical entity in adults, characterized by situs ambiguus, congenital heart defects, and splenic malformations. We report the case of an adult with heterotaxy syndrome (including situs ambiguus, bilateral superior vena cava, hypoplastic right-sided spleen and portosystemic shunts) presenting with dyspnea due to severe pulmonary hypertension. Vasodilatory therapy was initiated, leading to marked reduction of clinical symptoms. This case exhibits 2 particular and partially novel features: primary diagnosis of heterotaxy syndrome may be delayed until adulthood, and heterotaxy syndrome may be associated with pulmonary hypertension, possibly on the basis of longstanding portosystemic shunts.

Pharmacology of milrinone in neonates with persistent pulmonary hypertension of the newborn and suboptimal response to inhaled nitric oxide.

PubMed

McNamara, Patrick J; Shivananda, Sandesh P; Sahni, Mohit; Freeman, David; Taddio, Anna

2013-01-01

Persistent pulmonary hypertension of the newborn is a common problem with significant morbidity and mortality. Inhaled nitric oxide is the standard care, but up to 40% of neonates are nonresponders. Milrinone is a phosphodiesterase III inhibitor which increases the bioavailability of cyclic adenosine monophosphate and has been shown to improve pulmonary hemodynamics in animal experimental models. The primary objective was to investigate the pharmacological profile of milrinone in persistent pulmonary hypertension of the newborn. Secondary objectives were to delineate short-term outcomes and safety profile. An open label study of milrinone in neonates with persistent pulmonary hypertension of the newborn was conducted. Patients received an intravenous loading dose of milrinone (50 μg/kg) over 60 mins followed by a maintenance infusion (0.33-0.99 μg/kg/min) for 24-72 hrs. Physiologic indices of cardiorespiratory stability and details of cointerventions were recorded. Serial blood milrinone levels were collected after the bolus, following initiation of the maintenance infusion to determine steady state levels, and following discontinuation of the drug to determine clearance. Echocardiography was performed before and after (1, 12 hrs) milrinone initiation. Milrinone. Eleven neonates with a diagnosis of persistent pulmonary hypertension of the newborn who met eligibility criteria were studied. The median (SD) gestational age and weight at birth were 39.2 ± 1.3 wks and 3481 ± 603 g. The mean (± sd) half-life, total body clearance, volume of distribution, and steady state concentration of milrinone were 4.1 ± 1.1 hrs, 0.11 ± 0.01 L/kg/hr, 0.56 ± 0.19 L/kg, and 290.9 ± 77.7 ng/mL. The initiation of milrinone led to an improvement in PaO2 (p = 0.002) and a sustained reduction in FIO2 (p < 0.001), oxygenation index (p < 0.001), mean airway pressure (p = 0.03), and inhaled nitric oxide dose (p < 0.001). Although a transient reduction in systolic arterial pressure (p < 0.001) was seen following the bolus, there was overall improvement in base deficit (p = 0.01) and plasma lactate (p = 0.04) with a trend towards lower inotrope score. Serial echocardiography revealed lower pulmonary artery pressure, improved right and left ventricular output, and reduced bidirectional or right-left shunting (p < 0.05) after milrinone treatment. The pharmacokinetics of milrinone in persistent pulmonary hypertension of the newborn is consistent with published data. The administration of intravenous milrinone led to better oxygenation and improvements in pulmonary and systemic hemodynamics in patients with suboptimal response to inhaled nitric oxide. These data support the need for a randomized controlled trial in neonates.

Exposure to high concentrations of inspired oxygen does not worsen lung injury after cardiac arrest.

PubMed

Elmer, Jonathan; Wang, Bo; Melhem, Samer; Pullalarevu, Raghavesh; Pullalarevu, Raghevesh; Vaghasia, Nishit; Buddineni, Jaya; Rosario, Bedda L; Doshi, Ankur A; Callaway, Clifton W; Dezfulian, Cameron

2015-03-10

Post-cardiac arrest patients are often exposed to 100% oxygen during cardiopulmonary resuscitation and the early post-arrest period. It is unclear whether this contributes to development of pulmonary dysfunction or other patient outcomes. We performed a retrospective cohort study including post-arrest patients who survived and were mechanically ventilated at least 24 hours after return of spontaneous circulation. Our primary exposure of interest was inspired oxygen, which we operationalized by calculating the area under the curve of the fraction of inspired oxygen (FiO₂AUC) for each patient over 24 hours. We collected baseline demographic, cardiovascular, pulmonary and cardiac arrest-specific covariates. Our main outcomes were change in the respiratory subscale of the Sequential Organ Failure Assessment score (SOFA-R) and change in dynamic pulmonary compliance from baseline to 48 hours. Secondary outcomes were survival to hospital discharge and Cerebral Performance Category at discharge. We included 170 patients. The first partial pressure of arterial oxygen (PaO₂):FiO₂ ratio was 241 ± 137, and 85% of patients had pulmonary failure and 55% had cardiovascular failure at presentation. Higher FiO₂AUC was not associated with change in SOFA-R score or dynamic pulmonary compliance from baseline to 48 hours. However, higher FiO₂AUC was associated with decreased survival to hospital discharge and worse neurological outcomes. This was driven by a 50% decrease in survival in the highest quartile of FiO₂AUC compared to other quartiles (odds ratio for survival in the highest quartile compared to the lowest three quartiles 0.32 (95% confidence interval 0.13 to 0.79), P = 0.003). Higher exposure to inhaled oxygen in the first 24 hours after cardiac arrest was not associated with deterioration in gas exchange or pulmonary compliance after cardiac arrest, but was associated with decreased survival and worse neurological outcomes.

Pulmonary exposure to carbonaceous nanomaterials and sperm quality.

PubMed

Skovmand, Astrid; Jacobsen Lauvås, Anna; Christensen, Preben; Vogel, Ulla; Sørig Hougaard, Karin; Goericke-Pesch, Sandra

2018-01-31

Semen quality parameters are potentially affected by nanomaterials in several ways: Inhaled nanosized particles are potent inducers of pulmonary inflammation, leading to the release of inflammatory mediators. Small amounts of particles may translocate from the lungs into the lung capillaries, enter the systemic circulation and ultimately reach the testes. Both the inflammatory response and the particles may induce oxidative stress which can directly affect spermatogenesis. Furthermore, spermatogenesis may be indirectly affected by changes in the hormonal milieu as systemic inflammation is a potential modulator of endocrine function. The aim of this study was to investigate the effects of pulmonary exposure to carbonaceous nanomaterials on sperm quality parameters in an experimental mouse model. Effects on sperm quality after pulmonary inflammation induced by carbonaceous nanomaterials were investigated by intratracheally instilling sexually mature male NMRI mice with four different carbonaceous nanomaterials dispersed in nanopure water: graphene oxide (18 μg/mouse/i.t.), Flammruss 101, Printex 90 and SRM1650b (0.1 mg/mouse/i.t. each) weekly for seven consecutive weeks. Pulmonary inflammation was determined by differential cell count in bronchoalveolar lavage fluid. Epididymal sperm concentration and motility were measured by computer-assisted sperm analysis. Epididymal sperm viability and morphological abnormalities were assessed manually using Hoechst 33,342/PI flourescent and Spermac staining, respectively. Epididymal sperm were assessed with regard to sperm DNA integrity (damage). Daily sperm production was measured in the testis, and testosterone levels were measured in blood plasma by ELISA. Neutrophil numbers in the bronchoalveolar fluid showed sustained inflammatory response in the nanoparticle-exposed groups one week after the last instillation. No significant changes in epididymal sperm parameters, daily sperm production or plasma testosterone levels were found. Despite the sustained pulmonary inflammatory response, an eight week exposure to graphene oxide, Flammruss 101, Printex 90 and the diesel particle SRM1650b in the present study did not appear to affect semen parameters, daily sperm production or testosterone concentration in male NMRI mice.

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 Inc. All rights reserved.

Inhaled carbon monoxide does not cause pulmonary vasodilation in the late-gestation fetal lamb.

PubMed

Grover, T R; Rairigh, R L; Zenge, J P; Abman, S H; Kinsella, J P

2000-04-01

As observed with nitric oxide (NO), carbon monoxide (CO) binds and may activate soluble guanylate cyclase and increase cGMP levels in smooth muscle cells in vitro. Because inhaled NO (I(NO)) causes potent and sustained pulmonary vasodilation, we hypothesized that inhaled CO (I(CO)) may have similar effects on the perinatal lung. To determine whether I(CO) can lower pulmonary vascular resistance (PVR) during the perinatal period, we studied the effects of I(CO) on late-gestation fetal lambs. Catheters were placed in the main pulmonary artery, left pulmonary artery (LPA), aorta, and left atrium to measure pressure. An ultrasonic flow transducer was placed on the LPA to measure blood flow to the left lung. After baseline measurements, fetal lambs were mechanically ventilated with a hypoxic gas mixture (inspired O(2) fraction < 0.10) to maintain a constant fetal arterial PO(2). After 60 min (baseline), the lambs were treated with I(CO) [5-2,500 parts/million (ppm)]. Comparisons were made with I(NO) (5 and 20 ppm) and combined I(NO) (5 ppm) and I(CO) (100 and 2,500 ppm). We found that I(CO) did not alter left lung blood flow or PVR at any of the study doses. In contrast, low-dose I(NO) decreased PVR by 47% (P < 0.005). The combination of I(NO) and I(CO) did not enhance the vasodilator response to I(NO). To determine whether endogenous CO contributes to vascular tone in the fetal lung, zinc protoporphyrin IX, an inhibitor of heme oxygenase, was infused into the LPA in three lambs. Zinc protoporphyrin IX had no effect on baseline PVR, aortic pressure, or the pressure gradient across the ductus arteriosus. We conclude that I(CO) does not cause vasodilation in the near-term ovine transitional circulation, and endogenous CO does not contribute significantly to baseline pulmonary vascular tone or ductus arteriosus tone in the late-gestation ovine fetus.

Endothelial nitric oxide synthase in hypoxic newborn porcine pulmonary vessels

PubMed Central

Hislop, A; Springall, D; Oliveira, H; Pollock, J; Polak, J; Haworth, S

1997-01-01

AIMS—To determine if the failure of neonatal pulmonary arteries to dilate is due to a lack of nitric oxide synthase (NOS).
METHODS—A monoclonal antibody to endothelial NOS was used to demonstrate the distribution and density of NOS in the developing porcine lung after a period in hypobaric hypoxia. Newborn piglets were made hypertensive by exposure to hypobaric hypoxia (50.8 kPa) from < 5 minutes of age to 2.5 days of age, 3-6 days of age or 14-17 days of age. A semiquantitative scoring system was used to assess the distribution of endothelial NOS by light microscopy.
RESULTS—NOS was present in the arteries in all hypoxic animals. However, hypoxia from birth caused a reduction in NOS compared with those lungs normal at birth and those normal at 3 days. Hypoxia from 3-6 days led to a high density of NOS compared with normal lungs at 6 days. Hypoxia from 14-17 days had little effect on the amount of NOS. On recovery in room air after exposure to hypoxia from birth there was a transient increase in endothelial NOS after three days of recovery, mirroring that seen at three days in normal animals.
CONCLUSIONS—Suppression of NOS production in the first few days of life may contribute to pulmonary hypertension in neonates.

 Keywords: pulmonary circulation; nitric oxide synthase; hypoxia; endothelium; piglets PMID:9279177

Pulmonary artery haemorrhage in newborn calves following bluetongue virus serotype 8 experimental infections of pregnant heifers.

PubMed

Martinelle, Ludovic; Dal Pozzo, Fabiana; Sarradin, Pierre; De Leeuw, Ilse; De Clercq, Kris; Thys, Christine; Thiry, Etienne; Saegerman, Claude

2013-12-27

The emergence of bluetongue disease (BT) among livestock in Europe in 2006 raised many questions including the occurrence and epidemiological significance of foetal infections in cattle. To clarify these aspects, vaccinated and unvaccinated pregnant heifers were sequentially infected twice in an isolation facility (biosafety level 3) with a northern European outbreak strain of Bluetongue virus serotype 8 (BTV-8). The study was terminated 2 months after calving with necropsy of the dams and their offspring. The cattle were monitored throughout the study by clinical scoring and for the presence of circulating neutralising antibodies, and after calving for the presence of infectious virus and viral RNA in blood and milk. Four calves, one born from a vaccinated dam and three from non-vaccinated ones, that were infected at 120 days of gestation had obvious haemorrhage of the pulmonary artery at necropsy. Although haemorrhage of the pulmonary artery is highly characteristic of BT, viral RNA was not detected in any of these calves. Furthermore, although none of the calves born from heifers infected prior to mid-gestation had teratogenic BTV typical brain lesions, some had lesions at birth suggestive of in utero BTV infection. Despite the lack of viral RNA detection, the presence of haemorrhage of the pulmonary artery deserves to be reported as a new observation in the context of the multiple investigations having as main subject the BTV placental crossing in cattle. Copyright © 2013 Elsevier B.V. All rights reserved.

An autopsy case of non-traumatic fat embolism syndrome.

PubMed

Sakashita, Mai; Sakashita, Shingo; Sakata, Akiko; Uesugi, Noriko; Ishige, Kazunori; Hyodo, Ichinosuke; Noguchi, Masayuki

2017-09-01

Fat embolism syndrome (FES) occurs after long bone fractures and the symptoms appear 24-72 h after the initial trauma. Fat emboli can affect both the pulmonary and systemic circulation. Apart from the most common type of FES that originates from bone fracture, non-traumatic FES has been also reported. We have experienced an autopsy case of non-traumatic FES. An 81-year-old man with hepatocellular carcinoma associated with alcoholic liver cirrhosis suddenly lost consciousness before transcatheter arterial chemoembolization treatment for his disease and died 5 h after the episode. At autopsy, numerous fat droplets were detected in the alveolar capillaries of the lung and glomerular capillaries of the kidney. Lipid analysis of lung autopsy specimens by thin-layer chromatography showed that the emboli were composed mainly of tristearin. Free fatty acids (FFA) has been considered to be the main component of fat emboli and can be a cause of acute respiratory distress syndrome (ARDS). However, in the present case, the lung specimen contained tristearin and ARDS did not occur. This is the first report of non-traumatic FES in which lipid analysis of human autopsy specimens has been conducted. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Neural crest contribution to the cardiovascular system.

PubMed

Brown, Christopher B; Baldwin, H Scott

2006-01-01

Normal cardiovascular development requires complex remodeling of the outflow tract and pharyngeal arch arteries to create the separate pulmonic and systemic circulations. During remodeling, the outflow tract is septated to form the ascending aorta and the pulmonary trunk. The initially symmetrical pharyngeal arch arteries are remodeled to form the aortic arch, subclavian and carotid arteries. Remodeling is mediated by a population of neural crest cells arising between the mid-otic placode and somite four called the cardiac neural crest. Cardiac neural crest cells form smooth muscle and pericytes in the great arteries, and the neurons of cardiac innervation. In addition to the physical contribution of smooth muscle to the cardiovascular system, cardiac neural crest cells also provide signals required for the maintenance and differentiation of the other cell layers in the pharyngeal apparatus. Reciprocal signaling between the cardiac neural crest cells and cardiogenic mesoderm of the secondary heart field is required for elaboration of the conotruncus and disruption in this signaling results in primary myocardial dysfunction. Cardiovascular defects attributed to the cardiac neural crest cells may reflect either cell autonomous defects in the neural crest or defects in signaling between the neural crest and adjacent cell layers.

Adiponectin as a routine clinical biomarker.

PubMed

Kishida, Ken; Funahashi, Tohru; Shimomura, Iichiro

2014-01-01

Adiponectin is a protein synthesized and secreted predominantly by adipocytes into the peripheral blood. However, circulating adiponectin level is inversely related with body weight, especially visceral fat accumulation. The mechanism of this paradoxical relation remains obscure. Low circulating adiponectin concentrations (hypoadiponectinemia; <4 μg/mL) are associated with a variety of diseases, including dysmetabolism (type 2 diabetes, insulin resistance, hypertension, dyslipidemia, metabolic syndrome, hyperuricemia), atherosclerosis (coronary artery disease, stroke, peripheral artery disease), sleep apnea, non-alcoholic fatty liver disease, gastritis and gastro-esophageal reflux disease, inflammatory bowel diseases, pancreatitis, osteoporosis, and cancer (endometrial cancer, postmenopausal breast cancer, leukemia, colon cancer, gastric cancer, prostate cancer). On the other hand, hyperadiponectinemia is associated with cardiac, renal and pulmonary diseases. This review article focuses on the significance of adiponectin as a clinical biomarker of obesity-related diseases. Routine measurement of adiponectin in patients with lifestyle-related diseases is highly recommended. Copyright © 2013 Elsevier Ltd. All rights reserved.

A "live" biopsy in a small-cell lung cancer patient by detection of circulating tumor cells.

PubMed

Bevilacqua, Simona; Gallo, Marianna; Franco, Renato; Rossi, Antonio; De Luca, Antonella; Rocco, Gaetano; Botti, Gerardo; Gridelli, Cesare; Normanno, Nicola

2009-07-01

A 71-year-old patient with a pulmonary lesion was diagnosed with a low-grade neuroendocrine tumor following examination of a fine needle aspiration biopsy. Analysis of a peripheral blood sample with the CellSearch system revealed the presence of putative circulating tumor cells (CTC) that were positive for EpCAM and cytokeratin (CK) expression. Since EpCAM is not usually expressed in neuroendocrine tumors, we performed a biopsy of liver metastases. Morphological and immunophenotypical characterization revealed that the patient had an EpCAM and CK positive small-cell lung cancer (SCLC). By using the CellSearch apparatus, EpCAM/CK positive CTC were detected in peripheral blood samples from 3 out of 4 additional SCLC patients. This study is the first to demonstrate that CTC can be identified in SCLC patients by using the CellSearch system.

Effects and mechanisms of action of sildenafil citrate in human chorionic arteries

PubMed Central

Maharaj, Chrisen H; O'Toole, Daniel; Lynch, Tadhg; Carney, John; Jarman, James; Higgins, Brendan D; Morrison, John J; Laffey, John G

2009-01-01

Objectives Sildenafil citrate, a specific phosphodiesterase-5 inhibitor, is increasingly used for pulmonary hypertension in pregnancy. Sildenafil is also emerging as a potential candidate for the treatment of intra-uterine growth retardation and for premature labor. Its effects in the feto-placental circulation are not known. Our objectives were to determine whether phosphodiesterase-5 is present in the human feto-placental circulation, and to characterize the effects and mechanisms of action of sildenafil citrate in this circulation. Study Design Ex vivo human chorionic plate arterial rings were used in all experiments. The presence of phosphodiesterase-5 in the feto-placental circulation was determined by western blotting and immunohistochemical staining. In a subsequent series of pharmacologic studies, the effects of sildenafil citrate in pre-constricted chorionic plate arterial rings were determined. Additional studies examined the role of cGMP and nitric oxide in mediating the effects of sildenafil. Results Phosphodiesterase-5 mRNA and protein was demonstrated in human chorionic plate arteries. Immunohistochemistry demonstrated phosphodiesterase-5 within the arterial muscle layer. Sildenafil citrate produced dose dependent vasodilatation at concentrations at and greater than 10 nM. Both the direct cGMP inhibitor methylene blue and the cGMP-dependent protein kinase inhibitor Rp-8-Br-PET-cGMPS significantly attenuated the vasodilation produced by sildenafil citrate. Inhibition of NO production with L-NAME did not attenuate the vasodilator effects of sildenafil. In contrast, sildenafil citrate significantly enhanced the vasodilation produced by the NO donor sodium nitroprusside. Conclusion Phosphodiesterase-5 is present in the feto-placental circulation. Sildenafil citrate vasodilates the feto-placental circulation via a cGMP dependent mechanism involving increased responsiveness to NO. PMID:19389232

Rapid-onset plasma leakage of extracorporeal oxygenation membranes possibly due to hyperbilirubinemia.

PubMed

Kida, Yoshiko; Ohshimo, Shinichiro; Kyo, Michihito; Tanabe, Yuko; Suzuki, Kei; Hosokawa, Koji; Shime, Nobuaki

2018-06-02

Extracorporeal membrane oxygenation (ECMO) is an emerging tool for supporting cardiopulmonary function in patients with cardiorespiratory failure or arrest. The oxygenator of the ECMO circuit requires effective oxygenation and removal of carbon dioxide from the blood. Major problems that can occur with the oxygenator include plasma leakage, one of the late-onset serious complications necessitating device replacement. However, the rapid onset of plasma leakage is rare. We present a 1-year-old boy with acute respiratory failure due to Pneumocystis and Aspergillus pneumonia. He presented with tachypnea, tachycardia, and hypoxemia despite the ventilatory support, and was therefore placed on venoarterial ECMO with a drainage catheter from the right internal jugular vein (12 Fr) and a return catheter to the right internal carotid artery (10 Fr). Extracorporeal circulation was initiated at a blood flow of 1 L/min (145 mL/kg/min) and a sweep gas flow of 1 L/min with FiO 2 of 0.7. Although he was successfully weaned from the venoarterial ECMO on day 15 with an improvement of cardiopulmonary function, he was later placed on venoarterial ECMO again because of the progression of pulmonary hypertension. Laboratory tests showed increased concentrations of hepatic enzymes and hyperbilirubinemia (total bilirubin 31.6 mg/dL). Six hours after starting ECMO circulation, plasma leakage from the oxygenator occurred. Although we replaced the oxygenator with a new one, the replacement showed plasma leakage after 6 h. Disassembly of the oxygenator revealed congestion from bilirubin in the membrane fibers. We described a case of repeated, rapid-onset plasma leakage after implementation of ECMO. Hyperbilirubinemia was likely associated with the plasma leakage of this patient.

Ethnic Variation in Inflammatory Profile in Tuberculosis

PubMed Central

Coussens, Anna K.; Wilkinson, Robert J.; Nikolayevskyy, Vladyslav; Elkington, Paul T.; Hanifa, Yasmeen; Islam, Kamrul; Timms, Peter M.; Bothamley, Graham H.; Claxton, Alleyna P.; Packe, Geoffrey E.; Darmalingam, Mathina; Davidson, Robert N.; Milburn, Heather J.; Baker, Lucy V.; Barker, Richard D.; Drobniewski, Francis A.; Mein, Charles A.; Bhaw-Rosun, Leena; Nuamah, Rosamond A.; Griffiths, Christopher J.; Martineau, Adrian R.

2013-01-01

Distinct phylogenetic lineages of Mycobacterium tuberculosis (MTB) cause disease in patients of particular genetic ancestry, and elicit different patterns of cytokine and chemokine secretion when cultured with human macrophages in vitro. Circulating and antigen-stimulated concentrations of these inflammatory mediators might therefore be expected to vary significantly between tuberculosis patients of different ethnic origin. Studies to characterise such variation, and to determine whether it relates to host or bacillary factors, have not been conducted. We therefore compared circulating and antigen-stimulated concentrations of 43 inflammatory mediators and 14 haematological parameters (inflammatory profile) in 45 pulmonary tuberculosis patients of African ancestry vs. 83 patients of Eurasian ancestry in London, UK, and investigated the influence of bacillary and host genotype on these profiles. Despite having similar demographic and clinical characteristics, patients of differing ancestry exhibited distinct inflammatory profiles at presentation: those of African ancestry had lower neutrophil counts, lower serum concentrations of CCL2, CCL11 and vitamin D binding protein (DBP) but higher serum CCL5 concentrations and higher antigen-stimulated IL-1 receptor antagonist and IL-12 secretion. These differences associated with ethnic variation in host DBP genotype, but not with ethnic variation in MTB strain. Ethnic differences in inflammatory profile became more marked following initiation of antimicrobial therapy, and immunological correlates of speed of elimination of MTB from the sputum differed between patients of African vs. Eurasian ancestry. Our study demonstrates a hitherto unappreciated degree of ethnic heterogeneity in inflammatory profile in tuberculosis patients that associates primarily with ethnic variation in host, rather than bacillary, genotype. Candidate immunodiagnostics and immunological biomarkers of response to antimicrobial therapy should be derived and validated in tuberculosis patients of different ethnic origin. PMID:23853590

A moderate elevation of circulating levels of IGF-I does not alter ErbB2 induced mammary tumorigenesis

PubMed Central

2011-01-01

Background Epidemiological evidence suggests that moderately elevated levels of circulating insulin-like growth factor-I (IGF-I) are associated with increased risk of breast cancer in women. How circulating IGF-I may promote breast cancer incidence is unknown, however, increased IGF-I signaling is linked to trastuzumab resistance in ErbB2 positive breast cancer. Few models have directly examined the effect of moderately high levels of circulating IGF-I on breast cancer initiation and progression. The purpose of this study was to assess the ability of circulating IGF-I to independently initiate mammary tumorigenesis and/or accelerate the progression of ErbB2 mediated mammary tumor growth. Methods We crossed heterozygous TTR-IGF-I mice with heterozygous MMTV-ErbB2 mice to generate 4 different genotypes: TTR-IGF-I/MMTV-ErbB2 (bigenic), TTR-IGF-I only, MMTV-ErbB2 only, and wild type (wt). Virgin females were palpated twice a week and harvested when tumors reached 1000 mm3. For study of normal development, blood and tissue were harvested at 4, 6 and 9 weeks of age in TTR-IGF-I and wt mice. Results TTR-IGF-I and TTR-IGF-I/ErbB2 bigenic mice showed a moderate 35% increase in circulating total IGF-I compared to ErbB2 and wt control mice. Elevation of circulating IGF-I had no effect upon pubertal mammary gland development. The transgenic increase in IGF-I alone wasn't sufficient to initiate mammary tumorigenesis. Elevated circulating IGF-I had no effect upon ErbB2-induced mammary tumorigenesis or metastasis, with median time to tumor formation being 30 wks and 33 wks in TTR-IGF-I/ErbB2 bigenic and ErbB2 mice respectively (p = 0.65). Levels of IGF-I in lysates from ErbB2/TTR-IGF-I tumors compared to ErbB2 was elevated in a similar manner to the circulating IGF-I, however, there was no effect on the rate of tumor growth (p = 0.23). There were no morphological differences in tumor type (solid adenocarcinomas) between bigenic and ErbB2 mammary glands. Conclusion Using the first transgenic animal model to elevate circulating levels of IGF-I to those comparable to women at increased risk of breast cancer, we showed that moderately high levels of systemic IGF-I have no effect on pubertal mammary gland development, initiating mammary tumorigenesis or promoting ErbB2 driven mammary carcinogenesis. Our work suggests that ErbB2-induced mammary tumorigenesis is independent of the normal variation in circulating levels of IGF-I. PMID:21867536

Pulmonary alveolar microlithiasis: an interesting case report with systematic review of Indian literature.

PubMed

Ganesan, Nidhya; Ambroise, Marie Moses; Ramdas, Anita; Kisku, King Herald; Singh, Kulwant; Varghese, Renu G' Boy

2015-06-01

Pulmonary alveolar microlithiasis is a rare disease characterized by intra-alveolar presence of microliths. This study reports an interesting case of pulmonary alveolar microlithiasis and provides a systematic review of cases reported from India. A 23-year-old female presented with a history of cough, wheeze, chest pain, and episodic wheeze for five months. Pulmonary function tests demonstrated an obstructive pattern, and chest Xray showed fine micronodular opacities predominantly involving the middle and lower zones of both lungs. Transbronchial lung biopsy revealed the diagnosis. She responded well to inhaled steroid therapy. A systematic review of literature was performed and identified 73 cases of pulmonary alveolar microlithiasis reported from India. The mean (SD) age of the patients was 28.8 (14.9) years, with an almost equal male:female ratio. Many patients were asymptomatic at presentation. Breathlessness and cough were the most common symptoms, and the disease progressed into respiratory failure associated with cor pulmonale. About one-third of the cases were initially misdiagnosed and treated as pulmonary tuberculosis. Extra-pulmonary manifestations and comorbidities were also evident in our series. This systematic review helps to determine epidemiological and clinical characteristics of pulmonary alveolar microlithiasis. Further research is needed to elucidate the etiopathogenesis, diagnosis, and therapeutic options, which are beneficial in developing and identifying cost-effective treatment for pulmonary alveolar microlithiasis.

The Evolving Classification of Pulmonary Hypertension.

PubMed

Foshat, Michelle; Boroumand, Nahal

2017-05-01

- An explosion of information on pulmonary hypertension has occurred during the past few decades. The perception of this disease has shifted from purely clinical to incorporate new knowledge of the underlying pathology. This transfer has occurred in light of advancements in pathophysiology, histology, and molecular medical diagnostics. - To update readers about the evolving understanding of the etiology and pathogenesis of pulmonary hypertension and to demonstrate how pathology has shaped the current classification. - Information presented at the 5 World Symposia on pulmonary hypertension held since 1973, with the last meeting occurring in 2013, was used in this review. - Pulmonary hypertension represents a heterogeneous group of disorders that are differentiated based on differences in clinical, hemodynamic, and histopathologic features. Early concepts of pulmonary hypertension were largely influenced by pharmacotherapy, hemodynamic function, and clinical presentation of the disease. The initial nomenclature for pulmonary hypertension segregated the clinical classifications from pathologic subtypes. Major restructuring of this disease classification occurred between the first and second symposia, which was the first to unite clinical and pathologic information in the categorization scheme. Additional changes were introduced in subsequent meetings, particularly between the third and fourth World Symposia meetings, when additional pathophysiologic information was gained. Discoveries in molecular diagnostics significantly progressed the understanding of idiopathic pulmonary arterial hypertension. Continued advancements in imaging modalities, mechanistic pathogenicity, and molecular biomarkers will enable physicians to define pulmonary hypertension phenotypes based on the pathobiology and allow for treatment customization.

Relapsed hepatoblastoma confined to the lung is effectively treated with pulmonary metastasectomy.

PubMed

Shi, Yan; Geller, James I; Ma, Irene T; Chavan, Rishikesh S; Masand, Prakash M; Towbin, Alexander J; Chintagumpala, Murali; Nuchtern, Jed G; Tiao, Greg M; Thompson, Patrick A; Vasudevan, Sanjeev A

2016-04-01

In children diagnosed with hepatoblastoma (HB), the lungs are the most common site of metastasis at both initial presentation and relapse. Previous studies have encouraged pulmonary metastasectomy to achieve a disease-free state after resection of the primary hepatic lesion. However, there is no consensus about how to manage recurrent pulmonary metastasis. A retrospective, multi-institutional review was performed from 2005 to 2014 to identify HB patients ≤18years of age who had disease recurrence associated with pulmonary metastases alone. Ten patients between the ages of 8 and 33months were identified. Pulmonary metastatic recurrence was detected by measuring alpha-fetoprotein (AFP) levels and/or with CT scans of the chest. All patients subsequently underwent pulmonary metastasectomy without post-operative complications. At last follow-up, 8 patients were alive and had normal AFP levels. The 8 survivors had a median follow-up from therapy completion of 18.5months. Two patients who presented with extrapulmonary recurrence subsequently died of treatment refractory disease. This review supports surgical resection as a safe and, in the context of multimodal therapy, efficacious approach to manage HB patients who present with isolated pulmonary relapse. Copyright © 2016 Elsevier Inc. All rights reserved.

Dental technician pneumoconiosis mimicking pulmonary tuberculosis: a case report.

PubMed

Tan, Han Loong; Faisal, Mohamed; Soo, Chun Ian; Ban, Andrea Y L; Manap, Roslina Abdul; Hassan, Tidi M

2016-09-07

Dental laboratory technicians are at risk of developing occupational respiratory diseases due to exposure to various potentially toxic substances in their working environment. Since 1939, few cases of silicosis among dental technician have been reported. We illustrate a 38 year-old female, who worked in a dental laboratory for 20 years, initially treated as pulmonary tuberculosis and chronic necrotising aspergillosis without much improvement. Computed tomography guided lung biopsy and bronchoscopic transbronchial lung biopsy were performed. Lung tissue biopsies showed presence of refractile dental materials within the areas of histiocyte proliferation. The diagnosis of dental technician pneumoconiosis was obtained and our patient underwent pulmonary rehabilitation. This case highlights the importance of obtaining a detailed occupational history in tuberculosis endemic area, as pulmonary tuberculosis is a great mimicker of other respiratory diseases.

Protective effect of pulmonary hypertension against right-sided tamponade in pericardial effusion.

PubMed

Khan, M Usman; Khouzam, Rami N

2015-01-01

Patients with pericardial effusion are susceptible to cardiac tamponade. A compressing circumferential pericardial effusion typically results in an equalization of intracardiac and pericardial pressure during diastole and a progressive collapse of the right atrium and ventricle. Pulmonary hypertension that increases the afterload of the right ventricle may result in elevated pressures initially in the right ventricle and subsequently in the right atrium. This may lead to right ventricular hypertrophy and a pathologic structural and functional remodeling of both right heart chambers. Conversely, elevated pressures within the right heart chambers caused by longstanding pulmonary hypertension may resist and protect against tamponade of these chambers in the setting of a coexisting pericardial effusion. In such cases, a sudden reduction in pulmonary arterial pressures may result in tamponade of the right heart chambers.

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

Spanwise Spacing Effects on the Initial Structure and Decay of Axial Vortices

NASA Technical Reports Server (NTRS)

Wendt, B. J.; Reichert, B. A.

1996-01-01

The initial structure and axial decay of an array of streamwise vortices embedded in a turbulent pipe boundary layer is experimentally investigated. The vortices are shed in counter-rotating fashion from an array of equally-spaced symmetric airfoil vortex generators. Vortex structure is quantified in terms of crossplane circulation and peak streamwise vorticity. Flow conditions are subsonic and incompressible. The focus of this study is on the effect of the initial spacing between the parent vortex generators. Arrays with vortex generators spaced at 15 and 30 degrees apart are considered. When the spacing between vortex generators is decreased the circulation and peak vorticity of the shed vortices increases. Analysis indicates this strengthening results from regions of fluid acceleration in the vicinity of the vortex generator array. Decreased spacing between the constituent vortices also produces increased rates of circulation and peak vorticity decay.

Initiation of the Immune Response by Extracellular Hsp72: Chaperokine Activity of Hsp72

PubMed Central

Asea, Alexzander

2007-01-01

Heat shock proteins exert their beneficial effects via basically two modes of action depending on their relative location within the host. Intracellular heat shock proteins found within cells serve a cytoprotective role by chaperoning naïve, misfolded and/or denatured proteins in response to stressful stimuli by a process known as the stress response. However, stressful stimuli also induce the release of intracellular heat shock proteins into the extracellular milieu and circulation. The extracellular heat shock protein proteins serve a cytostimulatory role by initiating immune responses designed to fend off microbial infection and destroy neoplastic transformed cells. This review will briefly cover recent advances into elucidating the mechanism(s) by which stress induces the release of heat shock proteins into the circulation, how it initiates immune responses and suggest the possible biological significance of circulating Hsp to the host. PMID:17502920

Initiation of the Immune Response by Extracellular Hsp72: Chaperokine Activity of Hsp72.

PubMed

Asea, Alexzander

2006-08-01

Heat shock proteins exert their beneficial effects via basically two modes of action depending on their relative location within the host. Intracellular heat shock proteins found within cells serve a cytoprotective role by chaperoning naïve, misfolded and/or denatured proteins in response to stressful stimuli by a process known as the stress response. However, stressful stimuli also induce the release of intracellular heat shock proteins into the extracellular milieu and circulation. The extracellular heat shock protein proteins serve a cytostimulatory role by initiating immune responses designed to fend off microbial infection and destroy neoplastic transformed cells. This review will briefly cover recent advances into elucidating the mechanism(s) by which stress induces the release of heat shock proteins into the circulation, how it initiates immune responses and suggest the possible biological significance of circulating Hsp to the host.

The rationale for liquid biopsy in colorectal cancer: a focus on circulating tumor cells.

PubMed

Gazzaniga, Paola; Raimondi, Cristina; Nicolazzo, Chiara; Carletti, Raffaella; di Gioia, Cira; Gradilone, Angela; Cortesi, Enrico

2015-01-01

Capturing circulating tumor cells (CTCs) and/or circulating tumor DNA from blood, which represents a precious source of biological material derived from both primary and metastatic tumors, has been named a 'liquid biopsy'. While the circulating tumor DNA might be more representative of the bulk of the metastatic tumor, CTCs are thought to reflect more of the metastases-initiating cells. Consequently, a liquid biopsy made of tumor cells and tumor DNA that is able to track cancer evolution, as a fingerprint of the patient's individual tumor, and is easy to perform at every stage of the disease course, sounds attractive. This article mainly focuses on the applications of CTCs to track tumor dynamics in real time using colorectal cancer as a model system. The analysis of viable CTCs at DNA, RNA and protein levels, as well as their expansion in vitro, may allow deep investigation of the features of metastases-initiating cells.

Dynamic Risk Stratification of Patient Long-Term Outcome After Pulmonary Endarterectomy: Results From the United Kingdom National Cohort

PubMed Central

Cannon, John E.; Su, Li; Kiely, David G.; Page, Kathleen; Toshner, Mark; Swietlik, Emilia; Treacy, Carmen; Ponnaberanam, Anie; Condliffe, Robin; Sheares, Karen; Taboada, Dolores; Dunning, John; Tsui, Steven; Ng, Choo; Gopalan, Deepa; Screaton, Nicholas; Elliot, Charlie; Gibbs, Simon; Howard, Luke; Corris, Paul; Lordan, James; Johnson, Martin; Peacock, Andrew; MacKenzie-Ross, Robert; Schreiber, Benji; Coghlan, Gerry; Dimopoulos, Kostas; Wort, Stephen J.; Gaine, Sean; Moledina, Shahin; Jenkins, David P.; Pepke-Zaba, Joanna

2018-01-01

Background Chronic thromboembolic pulmonary hypertension results from incomplete resolution of pulmonary emboli. Pulmonary endarterectomy (PEA) is potentially curative, but residual pulmonary hypertension following surgery is common and its impact on long-term outcome is poorly understood. We wanted to identify factors correlated with poor long-term outcome after surgery and specifically define clinically relevant residual pulmonary hypertension post-PEA. Methods and Results Eight hundred eighty consecutive patients (mean age, 57 years) underwent PEA for chronic thromboembolic pulmonary hypertension. Patients routinely underwent detailed reassessment with right heart catheterization and noninvasive testing at 3 to 6 months and annually thereafter with discharge if they were clinically stable at 3 to 5 years and did not require pulmonary vasodilator therapy. Cox regressions were used for survival (time-to-event) analyses. Overall survival was 86%, 84%, 79%, and 72% at 1, 3, 5, and 10 years for the whole cohort and 91% and 90% at 1 and 3 years for the recent half of the cohort. The majority of patient deaths after the perioperative period were not attributable to right ventricular failure (chronic thromboembolic pulmonary hypertension). At reassessment, a mean pulmonary artery pressure of ≥30 mm Hg correlated with the initiation of pulmonary vasodilator therapy post-PEA. A mean pulmonary artery pressure of ≥38 mm Hg and pulmonary vascular resistance ≥425 dynes·s–1·cm–5 at reassessment correlated with worse long-term survival. Conclusions Our data confirm excellent long-term survival and maintenance of good functional status post-PEA. Hemodynamic assessment 3 to 6 months and 12 months post-PEA allows stratification of patients at higher risk of dying of chronic thromboembolic pulmonary hypertension and identifies a level of residual pulmonary hypertension that may guide the long-term management of patients postsurgery. PMID:27052413