Sildenafil prevents the increase of extravascular lung water and pulmonary hypertension after meconium aspiration in newborn piglets.

Science.gov (United States)

Silvera, F E; Blasina, M F; Vaamonde, L; Tellechea, S; Godoy, C; Zabala, S; Mañana, G; Martell, M; Olivera, W

2011-08-01

Meconium aspiration syndrome causes respiratory failure after birth and in vivo monitoring of pulmonary edema is difficult. The objective of the present study was to assess hemodynamic changes and edema measured by transcardiopulmonary thermodilution in low weight newborn piglets. Additionally, the effect of early administration of sildenafil (2 mg/kg vo, 30 min after meconium aspiration) on this critical parameter was determined in the meconium aspiration syndrome model. Thirty-eight mechanically ventilated anesthetized male piglets (Sus scrofa domestica) aged 12 to 72 h (1660 ± 192 g) received diluted fresh human meconium in the airway in order to evoke pulmonary hypertension (PHT). Extravascular lung water was measured in vivo with a PiCCO monitor and ex vivo by the gravimetric method, resulting in an overestimate of 3.5 ± 2.3 mL compared to the first measurement. A significant PHT of 15 Torr above basal pressure was observed, similar to that of severely affected humans, leading to an increase in ventilatory support. The vascular permeability index increased 57%, suggesting altered alveolocapillary membrane permeability. Histology revealed tissue vessel congestion and nonspecific chemical pneumonitis. A group of animals received sildenafil, which prevented the development of PHT and lung edema, as evaluated by in vivo monitoring. In summary, the transcardiopulmonary thermodilution method is a reliable tool for monitoring critical newborn changes, offering the opportunity to experimentally explore putative therapeutics in vivo. Sildenafil could be employed to prevent PHT and edema if used in the first stages of development of the disease.

Sildenafil prevents the increase of extravascular lung water and pulmonary hypertension after meconium aspiration in newborn piglets

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F.E. Silvera

2011-08-01

Full Text Available Meconium aspiration syndrome causes respiratory failure after birth and in vivo monitoring of pulmonary edema is difficult. The objective of the present study was to assess hemodynamic changes and edema measured by transcardiopulmonary thermodilution in low weight newborn piglets. Additionally, the effect of early administration of sildenafil (2 mg/kg vo, 30 min after meconium aspiration on this critical parameter was determined in the meconium aspiration syndrome model. Thirty-eight mechanically ventilated anesthetized male piglets (Sus scrofa domestica aged 12 to 72 h (1660 ± 192 g received diluted fresh human meconium in the airway in order to evoke pulmonary hypertension (PHT. Extravascular lung water was measured in vivo with a PiCCO monitor and ex vivo by the gravimetric method, resulting in an overestimate of 3.5 ± 2.3 mL compared to the first measurement. A significant PHT of 15 Torr above basal pressure was observed, similar to that of severely affected humans, leading to an increase in ventilatory support. The vascular permeability index increased 57%, suggesting altered alveolocapillary membrane permeability. Histology revealed tissue vessel congestion and nonspecific chemical pneumonitis. A group of animals received sildenafil, which prevented the development of PHT and lung edema, as evaluated by in vivo monitoring. In summary, the transcardiopulmonary thermodilution method is a reliable tool for monitoring critical newborn changes, offering the opportunity to experimentally explore putative therapeutics in vivo. Sildenafil could be employed to prevent PHT and edema if used in the first stages of development of the disease.

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

Science.gov (United States)

2012-01-01

Introduction Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by features other than increased pulmonary vascular permeability. Pulmonary vascular permeability combined with increased extravascular lung water content has been considered a quantitative diagnostic criterion of ALI/ARDS. This prospective, multi-institutional, observational study aimed to clarify the clinical pathophysiological features of ALI/ARDS and establish its quantitative diagnostic criteria. Methods The extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI) were measured using the transpulmonary thermodilution method in 266 patients with PaO2/FiO2 ratio ≤ 300 mmHg and bilateral infiltration on chest radiography, in 23 ICUs of academic tertiary referral hospitals. Pulmonary edema was defined as EVLWI ≥ 10 ml/kg. Three experts retrospectively determined the pathophysiological features of respiratory insufficiency by considering the patients' history, clinical presentation, chest computed tomography and radiography, echocardiography, EVLWI and brain natriuretic peptide level, and the time course of all preceding findings under systemic and respiratory therapy. Results Patients were divided into the following three categories on the basis of the pathophysiological diagnostic differentiation of respiratory insufficiency: ALI/ARDS, cardiogenic edema, and pleural effusion with atelectasis, which were noted in 207 patients, 26 patients, and 33 patients, respectively. EVLWI was greater in ALI/ARDS and cardiogenic edema patients than in patients with pleural effusion with atelectasis (18.5 ± 6.8, 14.4 ± 4.0, and 8.3 ± 2.1, respectively; P edema or pleural effusion with atelectasis patients (3.2 ± 1.4, 2.0 ± 0.8, and 1.6 ± 0.5; P edema patients. A PVPI value of 2.6 to 2.85 provided a definitive diagnosis of ALI/ARDS (specificity, 0.90 to 0.95), and a value < 1.7 ruled out an ALI/ARDS diagnosis (specificity, 0.95). Conclusion

Application of positron emission tomography in the lung

International Nuclear Information System (INIS)

Valind, S.O.; Wollmer, P.E.; Rhodes, C.G.

1985-01-01

The early application of positron emission tomography in the lung was mainly concerned with the investigation of the regional volume of the vascular and extravascular compartments, using measurements of fractional blood volume and lung density. However, in addition to its passive role in the exchange of oxygen and carbon dioxide, the lung exerts a number of active, metabolic functions such as the inactivation of circulating vasoactive compounds and the synthesis and release of biologically active substances. Furthermore, many of the pulmonary disorders originate at a cellular or metabolic level, or have metabolic consequences. Many of the substrates of biochemical reactions and the biologically active compounds, or their analogs, can be labeled with positron-emitting radioisotopes without disturbing their biological or biochemical characteristics. In combination with the development of the appropriate physiological and biochemical models, the quantitative measurements possible with PET provide a unique opportunity of regionally studying the metabolic processes of the lung of man in vivo. Hence, a range of different expressions of metabolism and of lung function can be evaluated and their interdependence can be studied regionally

Time Course of Changes in Extravascular Water of the Lung After Pneumonectomy According to the Data of Transpulmonal Thermodilution

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V. V. Kuzkov

2006-01-01

Full Text Available Objective: to study the accuracy of pulmonary extravascular water (PEVW measurement by thermochromodilution (TCD and isolated thermodilution (ITD on a model of pneumonectomy and subsequent ventilator-induced lung lesion (VILL in sheep.Materials and methods: the study was conducted at the Research Laboratory of University of Tromse. The experiment included 12 sheep weighing 35.6±4.6 kg. Thoracotomy and right-sided pneumonectomy were performed in the animals under general anesthesia and controlled artificial ventilation. After measurement of the parameters of systemic hemodynamics and PEVW, the animals were divided into 2 groups: 1 1 those undergoing protective ventilation (PV, n=6 with a tidal volume (TV of 6 ml/kg and a positive end-expiratory pressure (PEEP of 2 cm H2O and 2 those with VILL (n=6 with a TV of 12 ml/kg and a PEEP of 0 cm H2O. TCD and ITD (Cold Z-021 and PiCCOplus monitors, respectively (Pulsion, Germany were used to measure volumetric parameters and PEVW. The parameters of pulmonary hemodynamics, respiratory mechanics, and blood gas composition were recorded. After euthanasia of the animals, their lungs were taken to determine the control value of PEVW by postmortem gravimetry (PG.Results: in the VILL group, significant pulmonary alveolar edema developed, which was followed by hyperthermia, elevated pulmonary pressure, and increased intrapulmonary shunting. Analysis of the data indicated a close correlation between the PEVW values obtained by TCD and ITD with PG (r=0.95 and r=0.81, respectively; p<0.01; n=12. The PG deviation was 0.57±2.05 and 2.68±3.61 ml/kg for TCD and ITD, respectively (M±2d, p<0.05.Conclusion: both used techniques have an acceptable accuracy and adequately reflect both a reduction in PEVW after pneumectomy and its increase in the presence of VILL. Volumotrauma may be the key factor that provokes the development of postpneumectomic edema of the lung. 

Oxygen-sensitive 3He-MRI in bronchiolitis obliterans after lung transplantation

International Nuclear Information System (INIS)

Gast, Klaus K.; Biedermann, Alexander; Herweling, Annette; Schreiber, Wolfgang G.; Schmiedeskamp, Joerg; Mayer, Eckhard; Heussel, Claus P.; Markstaller, Klaus; Eberle, Balthasar; Kauczor, Hans-Ulrich

2008-01-01

Oxygen-sensitive 3 He-MRI was studied for the detection of differences in intrapulmonary oxygen partial pressure (pO 2 ) between patients with normal lung transplants and those with bronchiolitis obliterans syndrome (BOS). Using software developed in-house, oxygen-sensitive 3 He-MRI datasets from patients with normal lung grafts (n = 8) and with BOS (n = 6) were evaluated quantitatively. Datasets were acquired on a 1.5-T system using a spoiled gradient echo pulse sequence. Underlying diseases were pulmonary emphysema (n 10 datasets) and fibrosis (n = 4). BOS status was verified by pulmonary function tests. Additionally, 3 He-MRI was assessed blindedly for ventilation defects. Median intrapulmonary pO 2 in patients with normal lung grafts was 146 mbar compared with 108 mbar in patients with BOS. Homogeneity of pO2 distribution was greater in normal grafts (standard deviation pO2 34 versus 43 mbar). Median oxygen decrease rate during breath hold was higher in unaffected patients (-1.75 mbar/s versus -0.38 mbar/s). Normal grafts showed fewer ventilation defects (5% versus 28%, medians). Oxygen-sensitive 3 He-MRI appears capable of demonstrating differences of intrapulmonary pO2 between normal lung grafts and grafts affected by BOS. Oxygen-sensitive 3 He-MRI may add helpful regional information to other diagnostic techniques for the assessment and follow-up of lung transplant recipients. (orig.)

Acute Respiratory Distress Syndrome in Severe Brain Injury

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Yu. A. Churlyaev

2009-01-01

Full Text Available Objective: to study the development of acute respiratory distress syndrome (ARDS in victims with isolated severe brain injury (SBI. Subject and methods. 171 studies were performed in 16 victims with SBI. Their general condition was rated as very critical. The patients were divided into three groups: 1 non-ARDS; 2 Stage 1 ARDS; and 3 Stage 2 ARDS. The indicators of Stages 1 and 2 were assessed in accordance with the classification proposed by V. V. Moroz and A. M. Golubev. Intracranial pressure (ICP, extravascular lung water index, pulmonary vascular permeability, central hemodynamics, oxygenation index, lung anastomosis, the X-ray pattern of the lung and brain (computed tomography, and its function were monitored. Results. The hemispheric cortical level of injury of the brain with function compensation of its stem was predominantly determined in the controls; subcompensation and decompensation were ascertained in the ARDS groups. According to the proposed classification, these patients developed Stages 1 and 2 ARDS. When ARDS developed, there were rises in the level of extravascular lung fluid and pulmonary vascular permeability, a reduction in the oxygenation index (it was 6—12 hours later as compared with them, increases in a lung shunt and ICP; X-ray study revealed bilateral infiltrates in the absence of heart failure in Stage 2 ARDS. The correlation was positive between ICP and extravascular lung water index, and lung vascular permeability index (r>0.4;p<0.05. Conclusion. The studies have indicated that the classification proposed by V. V. Moroz and A. M. Golubev enables an early diagnosis of ARDS. One of its causes is severe brainstem injury that results in increased extravascular fluid in the lung due to its enhanced vascular permeability. The ICP value is a determinant in the diagnosis of secondary brain injuries. Key words: acute respiratory distress syndrome, extravascu-lar lung fluid, pulmonary vascular permeability, brain injury

Interleaved quantitative BOLD: Combining extravascular R2' - and intravascular R2-measurements for estimation of deoxygenated blood volume and hemoglobin oxygen saturation.

Science.gov (United States)

Lee, Hyunyeol; Englund, Erin K; Wehrli, Felix W

2018-03-23

Quantitative BOLD (qBOLD), a non-invasive MRI method for assessment of hemodynamic and metabolic properties of the brain in the baseline state, provides spatial maps of deoxygenated blood volume fraction (DBV) and hemoglobin oxygen saturation (HbO 2 ) by means of an analytical model for the temporal evolution of free-induction-decay signals in the extravascular compartment. However, mutual coupling between DBV and HbO 2 in the signal model results in considerable estimation uncertainty precluding achievement of a unique set of solutions. To address this problem, we developed an interleaved qBOLD method (iqBOLD) that combines extravascular R 2 ' and intravascular R 2 mapping techniques so as to obtain prior knowledge for the two unknown parameters. To achieve these goals, asymmetric spin echo and velocity-selective spin-labeling (VSSL) modules were interleaved in a single pulse sequence. Prior to VSSL, arterial blood and CSF signals were suppressed to produce reliable estimates for cerebral venous blood volume fraction (CBV v ) as well as venous blood R 2 (to yield HbO 2 ). Parameter maps derived from the VSSL module were employed to initialize DBV and HbO 2 in the qBOLD processing. Numerical simulations and in vivo experiments at 3 T were performed to evaluate the performance of iqBOLD in comparison to the parent qBOLD method. Data obtained in eight healthy subjects yielded plausible values averaging 60.1 ± 3.3% for HbO 2 and 3.1 ± 0.5 and 2.0 ± 0.4% for DBV in gray and white matter, respectively. Furthermore, the results show that prior estimates of CBV v and HbO 2 from the VSSL component enhance the solution stability in the qBOLD processing, and thus suggest the feasibility of iqBOLD as a promising alternative to the conventional technique for quantifying neurometabolic parameters. Copyright © 2018. Published by Elsevier Inc.

Respiratory Biomechanics, Intrapulmonary Water, and Pulmonary Oxygenizing Function During Uncomplicated Operations under Extracorporeal Circulation

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I. A. Kozlov

2007-01-01

Full Text Available Objective: to study the time course of changes in the respiratory biomechanics, extravascular water of the lung (EVWL and its oxygenizing function and their relationship at different stages of surgical interventions under extracorporeal circulation (EC. Subjects and methods. 29 patients aged 37 to 72 years were examined during uncomplicated operations under EC. The parameters of artificial ventilation (AV and lung biomechanics were recorded in real time on a Servo-I monitoring apparatus. PaO2/FiO2, Qs/Qt, and body mass index (BMI were calculated. The EVWL index (EVWLI was determined by the transpulmonary thermodilution technique. Studies were conducted at stages: 1 after tracheal intubation and the initiation of AV; 2 before sternotomy; 3 after sternal uniting at the end of surgery. Results. Pressures in the airways and their resistance were statistically significantly unchanged. There were significant reductions in Cdyn and Cst at the end of surgery (Stage 3. The mean values of PaO2/FiO2, Qs/Qt, and EVWLI did not undergo considerable changes. There was a significant correlation between PaO2/FiO2 and Qs/Qt (r=-0.5 to -0.8; p<0.05. At Stage 1, BMI proved to be a significant predictor of the level of PaO2/FiO2 and Qs/Qt (r=-0.5 and 0.65; p<0.05. A significant moderate relationship between Qs/Qt and Cdyn was found at Stage 3 (r=-0.44; p<0.05. There were no statistically significant correlations between the parameters of respiratory biomechanics, PaO2/FiO2, Qs/Qt, and EVWLI. At the end of surgery, pulmonary oxygenizing dysfunction (POD was detected in 5 (17.2% patients with increased BMI. Alveolar mobilization with a steady-state effect was used to correct POD. Conclusion. When cardiac surgery is uncomplicated and the AV and EC protocols are carefully followed, the rate of intraoperative POD is not greater than 20%, its leading causes are obesity and, most likely, microatelectasis under AV. Key words: pulmonary oxygenizing dysfunction

Lung vital capacity and oxygen saturation in adults with cerebral palsy

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Lampe R

2014-12-01

Full Text Available Renée Lampe,1,2 Tobias Blumenstein,2 Varvara Turova,2 Ana Alves-Pinto2 1Markus Würth Stiftungsprofessur, Technical University of Munich, Munich, Germany; 2Research Unit for Cerebral Palsy and Children Neuroorthopaedics of the Buhl-Strohmaier Foundation, Orthopedic Department of the Clinic “rechts der Isar” of the Technical University of Munich, Munich, Germany Background: Individuals with infantile cerebral palsy have multiple disabilities. The most conspicuous syndrome being investigated from many aspects is motor movement disorder with a spastic gait pattern. The lung function of adults with spasticity attracts less attention in the literature. This is surprising because decreased thoracic mobility and longstanding scoliosis should have an impact on lung function. With increasing age and the level of disability, individuals become susceptible to lung infections and reflux illness, and these are accompanied by increased aspiration risk. This study examined, with different methods, to what extent adults with congenital cerebral palsy and acquired spastic paresis – following traumatic brain injury – showed restriction of lung function. It also assessed the contribution of disability level on this restriction.Methods: The oxygen saturation of 46 adults with a diagnosis of cerebral palsy was measured with an oximeter. Lung vital capacity was measured with a mobile spirometer and excursion of the thorax was clinically registered. The gross motor function levels and the presence or absence of scoliosis were determined.Results: A significantly positive correlation between lung vital capacity and chest expansion was established. Both the lung vital capacity and the thorax excursion decreased with increases in gross motor function level. Oxygen saturation remained within the normal range in all persons, in spite of reduced values of the measured lung parameters. No statistically significant dependency between lung vital capacity and oxygen

Simple method of measuring pulmonary extravascular water using heavy water

Energy Technology Data Exchange (ETDEWEB)

Basset, G; Moreau, F; Scaringella, M; Tistchenko, S; Botter, F; Marsac, J

1975-11-20

The field of application of the multiple indicators dilution method in human pathology, already used to study pulmonary edema, can be extended to cover the identification and testing of all conditions leading to increase lung water. To be really practical it must be simple, fast, sensitive, inexpensive and subject to repetition; the use of non-radioactive tracers is implied. Indocyanine Green and heavy water were chosen respectively as vascular and diffusible indicators. Original methods have been developed for the treatment and isotopic analysis of blood: mass spectrometric analysis of aqueous blood extracts after deproteinisation by zinc sulphate then rapid distillation of the supernatant under helium; infrared analysis either of acetone extracts from small blood samples (100..mu..litre) or of blood itself in a continuous measurement. The infrared technique adopted has been used on rats and on men in normal and pathological situations. The results show that the method proposed for the determination of pulmonary extravascular water meets the requirements of clinicians while respecting the patients' safety, and could be generalized to other organs.

Relationship Between Cerebral Oxygenation and Hemodynamic and Oxygen Transport Parameters in Surgery for Acquired Heart Diseases

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A. I. Lenkin

2012-01-01

Full Text Available Objective: to evaluate the relationship between cerebral oxygenation and hemodynamic and oxygen transport parameters in surgical correction of concomitant acquired heart diseases. Subjects and methods. Informed consent was received from 40 patients who required surgery because of concomitant (two or more acquired heart defects. During procedure, perioperative monitoring of oxygen transport and cerebral oxygenation was performed with the aid of PiCCO2 monitor (Pulsion Medical Systems, Germany and a Fore-Sight cerebral oximeter (CASMED, USA. Anesthesia was maintained with propofol and fen-tanyl, by monitoring the depth of anesthesia. Early postoperative intensive therapy was based on the protocol for early targeted correction of hemodynamic disorders. Oxygen transport and cerebral oxygenation parameters were estimated intraopera-tively and within 24 postoperative hours. A statistical analysis including evaluation of Spearman correlations was performed with the aid of SPSS 15.0. Results. During perfusion, there was a relationship between cerebral oximetry values and hemat-ocrit levels, and oxygen partial pressure in the venous blood. Furthermore, a negative correlation between cerebral oximetry values and blood lactate levels was found 30 minutes after initiation of extracorporeal circulation (EC. During the study, there was a positive correlation between cerebral oxygenation and values of cardiac index, central venous saturation, and oxygen delivery index. There was a negative relationship between cerebral oxygenation and extravascular lung water at the beginning of surgery and a correlation between cerebral oximetry values and oxygenation index by the end of the first 24 postoperative hours. Conclusion. The cerebral oxygenation values correlate -with the main determinants of oxygen transport during EC and after cardiac surgical procedures. Cerebral oximetry may be used in early targeted therapy for the surgical correction of acquired combined

Diode laser spectroscopy for noninvasive monitoring of oxygen in the lungs of newborn infants.

Science.gov (United States)

Svanberg, Emilie Krite; Lundin, Patrik; Larsson, Marcus; Åkeson, Jonas; Svanberg, Katarina; Svanberg, Sune; Andersson-Engels, Stefan; Fellman, Vineta

2016-04-01

Newborn infants may have pulmonary disorders with abnormal gas distribution, e.g., respiratory distress syndrome. Pulmonary radiography is the clinical routine for diagnosis. Our aim was to investigate a novel noninvasive optical technique for rapid nonradiographic bedside detection of oxygen gas in the lungs of full-term newborn infants. Laser spectroscopy was used to measure contents of oxygen gas (at 760 nm) and of water vapor (at 937 nm) in the lungs of 29 healthy newborn full-term infants (birth weight 2,900-3,900 g). The skin above the lungs was illuminated using two low-power diode lasers and diffusely emerging light was detected with a photodiode. Of the total 390 lung measurements performed, clear detection of oxygen gas was recorded in 60%, defined by a signal-to-noise ratio of >3. In all the 29 infants, oxygen was detected. Probe and detector positions for optimal pulmonary gas detection were determined. There were no differences in signal quality with respect to gender, body side or body weight. The ability to measure pulmonary oxygen content in healthy full-term neonates with this technique suggests that with further development, the method might be implemented in clinical practice for lung monitoring in neonatal intensive care.

Oxygen titration strategies in chronic neonatal lung disease.

Science.gov (United States)

Primhak, Robert

2010-09-01

The history of oxygen therapy in neonatology has been littered with error. Controversies remain in a number of areas of oxygen therapy, including targets and strategies in supplemental oxygen therapy in Chronic Neonatal Lung Disease (CNLD). This article reviews some of these controversies, and makes some recommendations based on the available evidence. In graduates of neonatal units who are left with CNLD, oxygen saturation should be kept above 93-95%, with levels below 90% being avoided as far as possible. Titration of oxygen should be done using oximetry recordings which include periods of different activities. Weaning of oxygen supplementation should only be done based on satisfactory recordings during a trial of a lower flow. There is insufficient evidence to say whether weaning for increasing hours a day or stepwise weaning to a continuous lower flow is a better method. Copyright 2010 Elsevier Ltd. All rights reserved.

Effect of oxygen breathing and perfluorocarbon emulsion treatment on air bubbles in adipose tissue during decompression sickness

DEFF Research Database (Denmark)

Randsoe, T; Hyldegaard, O

2009-01-01

Decompression sickness (DCS) after air diving has been treated with success by means of combined normobaric oxygen breathing and intravascular perfluorocarbon (PFC) emulsions causing increased survival rate and faster bubble clearance from the intravascular compartment. The beneficial PFC effect...... has been explained by the increased transport capacity of oxygen and inert gases in blood. However, previous reports have shown that extravascular bubbles in lipid tissue of rats suffering from DCS will initially grow during oxygen breathing at normobaric conditions. We hypothesize that the combined...... effect of normobaric oxygen breathing and intravascular PFC infusion could lead to either enhanced extravascular bubble growth on decompression due to the increased oxygen supply, or that PFC infusion could lead to faster bubble elimination due to the increased solubility and transport capacity in blood...

Decrease in pulmonary function and oxygenation after lung resection.

Science.gov (United States)

Brocki, Barbara Cristina; Westerdahl, Elisabeth; Langer, Daniel; Souza, Domingos S R; Andreasen, Jan Jesper

2018-01-01

Respiratory deficits are common following curative intent lung cancer surgery and may reduce the patient's ability to be physically active. We evaluated the influence of surgery on pulmonary function, respiratory muscle strength and physical performance after lung resection. Pulmonary function, respiratory muscle strength (maximal inspiratory/expiratory pressure) and 6-min walk test (6MWT) were assessed pre-operatively, 2 weeks post-operatively and 6 months post-operatively in 80 patients (age 68±9 years). Video-assisted thoracoscopic surgery was performed in 58% of cases. Two weeks post-operatively, we found a significant decline in pulmonary function (forced vital capacity -0.6±0.6 L and forced expiratory volume in 1 s -0.43±0.4 L; both p<0.0001), 6MWT (-37.6±74.8 m; p<0.0001) and oxygenation (-2.9±4.7 units; p<0.001), while maximal inspiratory and maximal expiratory pressure were unaffected. At 6 months post-operatively, pulmonary function and oxygenation remained significantly decreased (p<0.001), whereas 6MWT was recovered. We conclude that lung resection has a significant short- and long-term impact on pulmonary function and oxygenation, but not on respiratory muscle strength. Future research should focus on mechanisms negatively influencing post-operative pulmonary function other than impaired respiratory muscle strength.

Cerebral Microcirculation and Oxygen Tension in the Human Secondary Cortex

Science.gov (United States)

Linninger, A. A.; Gould, I. G.; Marinnan, T.; Hsu, C.-Y.; Chojecki, M.; Alaraj, A.

2013-01-01

The three-dimensional spatial arrangement of the cortical microcirculatory system is critical for understanding oxygen exchange between blood vessels and brain cells. A three-dimensional computer model of a 3 × 3 × 3 mm3 subsection of the human secondary cortex was constructed to quantify oxygen advection in the microcirculation, tissue oxygen perfusion, and consumption in the human cortex. This computer model accounts for all arterial, capillary and venous blood vessels of the cerebral microvascular bed as well as brain tissue occupying the extravascular space. Microvessels were assembled with optimization algorithms emulating angiogenic growth; a realistic capillary bed was built with space filling procedures. The extravascular tissue was modeled as a porous medium supplied with oxygen by advection–diffusion to match normal metabolic oxygen demand. The resulting synthetic computer generated network matches prior measured morphometrics and fractal patterns of the cortical microvasculature. This morphologically accurate, physiologically consistent, multi-scale computer network of the cerebral microcirculation predicts the oxygen exchange of cortical blood vessels with the surrounding gray matter. Oxygen tension subject to blood pressure and flow conditions were computed and validated for the blood as well as brain tissue. Oxygen gradients along arterioles, capillaries and veins agreed with in vivo trends observed recently in imaging studies within experimental tolerances and uncertainty. PMID:23842693

The unresolved issue of oxygen therapy in lung fibrosis: Some clues from a Spanish cohort

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Irene Martin-Robles

2014-01-01

Full Text Available Indication of oxygen therapy in fibrotic interstitial lung diseases is not standardized and its specific requirements are not well defined. The objective of this study was to evaluate ambulatory oxygen therapy features in lung fibrotic patients. Clinical and exploratory　data, including 6-minute walking test and pulmonary hypertension, from one hundred and seven patients with fibrotic interstitial lung disease that received ambulatory oxygen treatment were studied. In up to 40% of cases the prescription of oxygen therapy was made after performing a 6-minute walking test. Patients who required ambulatory oxygen only during exercise presented a mild to moderate reduction of the predicted % FVC (62.1 ± 19 and DLCO (49 ± 14.4 while patients who had respiratory failure at rest (mean PaO2 51.9 ± 6.7 presented a moderate reduction of %FVC (56.8 ± 15.6 but a severe decrease of %DLCO (31.67 ± 12. Pulmonary hypertension (PH was evaluated in 47.7% of patients and occurred in 60.8% of them. In conclusion, there is no pulmonary functional predictor of oxyhaemoglobin desaturation during exercise. PH is frequently associated with interstitial lung diseases, mainly when respiratory failure at rest appears. The heterogeneity of the patients and limitation of retrospective studies could be the cause of the tributes for potential benefits of oxygen treatment in interstitial lung diseases.

ExtraCorporeal Membrane Oxygenation in Newborns. Implications for Brain and Lung.

NARCIS (Netherlands)

Heyst, A.F.J. van

2004-01-01

Extracorporeal membrane oxygenation (ECMO) is a rescue treatment for newborns with severe respiratory insufficiency. In veno-arterial ECMO, venous blood is drained from the right atrium, oxygenated in an artificial lung and reinfused in the aorta. For vascular access the right internal jugular vein

Decrease in pulmonary function and oxygenation after lung resection

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Barbara Cristina Brocki

2018-01-01

Full Text Available Respiratory deficits are common following curative intent lung cancer surgery and may reduce the patient's ability to be physically active. We evaluated the influence of surgery on pulmonary function, respiratory muscle strength and physical performance after lung resection. Pulmonary function, respiratory muscle strength (maximal inspiratory/expiratory pressure and 6-min walk test (6MWT were assessed pre-operatively, 2 weeks post-operatively and 6 months post-operatively in 80 patients (age 68±9 years. Video-assisted thoracoscopic surgery was performed in 58% of cases. Two weeks post-operatively, we found a significant decline in pulmonary function (forced vital capacity −0.6±0.6 L and forced expiratory volume in 1 s −0.43±0.4 L; both p<0.0001, 6MWT (−37.6±74.8 m; p<0.0001 and oxygenation (−2.9±4.7 units; p<0.001, while maximal inspiratory and maximal expiratory pressure were unaffected. At 6 months post-operatively, pulmonary function and oxygenation remained significantly decreased (p<0.001, whereas 6MWT was recovered. We conclude that lung resection has a significant short- and long-term impact on pulmonary function and oxygenation, but not on respiratory muscle strength. Future research should focus on mechanisms negatively influencing post-operative pulmonary function other than impaired respiratory muscle strength.

Active Oxygen Metabolites and Thromboxane in Phorbol Myristate Acetate Toxicity to the Isolated, Perfused Rat Lung.

Science.gov (United States)

Carpenter, Laurie Jean

When administered intravenously or intratracheally to rats, rabbits and sheep, phorbol myristate acetate (PMA) produces changes in lung morphology and function are similar to those seen in humans with the adult respiratory distress syndrome (ARDS). Therefore, it is thought that information about the mechanism of ARDS development can be gained from experiments using PMA-treated animals. Currently, the mechanisms by which PMA causes pneumotoxicity are unknown. Results from other studies in rabbits and in isolated, perfused rabbit lungs suggest that PMA-induced lung injury is mediated by active oxygen species from neutrophils (PMN), whereas studies in sheep and rats suggest that PMN are not required for the toxic response. The role of PMN, active oxygen metabolites and thromboxane (TxA_2) in PMA-induced injury to isolated, perfused rat lungs (IPLs) was examined in this thesis. To determine whether PMN were required for PMA to produce toxicity to the IPL, lungs were perfused for 30 min with buffer containing various concentrations of PMA (in the presence or absence of PMN). When concentrations >=q57 ng/ml were added to medium devoid of added PMN, perfusion pressure and lung weight increased. When a concentration of PMA (14-28 ng/ml) that did not by itself cause lungs to accumulate fluid was added to the perfusion medium containing PMN (1 x 10 ^8), perfusion pressure increased, and lungs accumulated fluid. These results indicate that high concentrations of PMA produce lung injury which is independent of PMN, whereas injury induced by lower concentrations is PMN-dependent. To examine whether active oxygen species were involved in mediating lung injury induced by PMA and PMN, lungs were coperfused with the oxygen radical scavengers SOD and/or catalase. Coperfusion with either or both of these enzymes totally protected lungs against injury caused by PMN and PMA. These results suggest that active oxygen species (the hydroxyl radical in particular), mediate lung injury in

Prevention of reperfusion lung injury by lidocaine in isolated rat lung ventilated with higher oxygen levels.

Directory of Open Access Journals (Sweden)

Das K

2003-01-01

Full Text Available BACKGROUND: Lidocaine, an antiarrhythmic drug has been shown to be effective against post-ischaemic reperfusion injury in heart. However, its effect on pulmonary reperfusion injury has not been investigated. AIMS: We investigated the effects of lidocaine on a postischaemic reperfused rat lung model. MATERIALS AND METHODS: Lungs were isolated and perfused at constant flow with Krebs-Henseilet buffer containing 4% bovine serum albumin, and ventilated with 95% oxygen mixed with 5% CO2. Lungs were subjected to ischaemia by stopping perfusion for 60 minutes followed by reperfusion for 10 minutes. Ischaemia was induced in normothermic conditions. RESULTS: Postischaemic reperfusion caused significant (p < 0.0001 higher wet-to-dry lung weight ratio, pulmonary arterial pressure and peak airway pressure compared to control lungs. Lidocaine, at a dose of 5mg/Kg b.w. was found to significantly (p < 0.0001 attenuate the increase in the wet-to-dry lung weight ratio, pulmonary arterial pressure and peak airway pressure observed in post-ischaemic lungs. CONCLUSION: Lidocaine is effective in preventing post-ischaemic reperfusion injury in isolated, perfused rat lung.

Remodelling of Membrane Rafts Expression in Lung Cells as an Early Sign of Mechanotransduction-Signalling in Pulmonary Edema

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Paola Palestini

2011-01-01

Full Text Available Membrane rafts (MRs are clusters of lipids, organized in a “quasicrystalline” liquid-order phase, organized on the cell surface and whose pattern of molecules and physicochemical properties are distinct from those of the surrounding plasma membrane. MRs may be considered an efficient and fairly rapid cell-activated mechanism to express or mask surface receptors aimed at triggering specific response pathways. This paper reports observations concerning the role of MRs in the control of lung extravascular water that ought to be kept at minimum to assure gas diffusion, supporting the hypothesis that MRs expression is a potential mechanism of sensing minor changes in the volume of extravascular water. We present the evidence that MRs expression specifically relates to signal-transduction processes evoked by mechanical stimuli arising in the interstitial lung compartment when a small increase in extravascular volume occurs. We further hypothesize that a differential expression of MRs might also reflect the damage to precise components of the extracellular matrix caused by the perturbation in water balance and thus can trigger a molecule-oriented specific matrix remodelling.

Measurement of regional extravascular lung density and of pulmonary blood volume with positron emitting isotopes

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Larock, M.P.; Quaglia, L.; Lamotte, D.; De Landsheere, C.; Del Fiore, G.; Chevigne, M.; Peters, J.M.; Rigo, P. (Universite de Liege (Belgium))

1982-01-01

Studies of pulmonary blood volume changes with exercise can be performed after labelling of the blood pool by /sup 11/CO inhalation. Positron transaxial tomography permits the quantitative study of density distribution of the chest and of the pulmonary blood volume. This paper represents our preliminary experience with these techniques on models and control patients. We have first verified the linearity of transmission for density distribution below one. The tomographic examination first records a transmission image, then an emission image on the same section. We next normalize emission and transmission values on a region of unit density corresponding to blood: then we substract the emission from the transmission values to measure the extravascular pulmonary density. With crystal probes we record pulmonary blood volume variations before, during and after exercise. Peripheral hemodynamic variations explain the change recorded at the begining and at the end of exercise. Combination of these two techniques should help us to better study the importance of the acute changes in the ''formation'' of pulmonary oedema and its influence on regional pulmonary blood volume.

Derecruitment Test and Surfactant Therapy in Patients with Acute Lung Injury

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Alexey A. Smetkin

2012-01-01

Full Text Available Introduction. A recruitment maneuver (RM may improve gas exchange in acute lung injury (ALI. The aim of our study was to assess the predictive value of a derecruitment test in relation to RM and to evaluate the efficacy of RM combined with surfactant instillation in patients with ALI. Materials and Methods. Thirteen adult mechanically ventilated patients with ALI were enrolled into a prospective pilot study. The patients received protective ventilation and underwent RM followed by a derecruitment test. After a repeat RM, bovine surfactant (surfactant group, n=6 or vehicle only (conventional therapy group, n=7 was instilled endobronchially. We registered respiratory and hemodynamic parameters, including extravascular lung water index (EVLWI. Results. The derecruitment test decreased the oxygenation in 62% of the patients. We found no significant correlation between the responses to the RM and to the derecruitment tests. The baseline EVLWI correlated with changes in SpO2 following the derecruitment test. The surfactant did not affect gas exchange and lung mechanics but increased EVLWI at 24 and 32 hrs. Conclusions. Our study demonstrated no predictive value of the derecruitment test regarding the effects of RM. Surfactant instillation was not superior to conventional therapy and might even promote pulmonary edema in ALI.

Apneic oxygenation combined with extracorporeal arteriovenous carbon dioxide removal provides sufficient gas exchange in experimental lung injury

DEFF Research Database (Denmark)

Nielsen, Niels Dalsgaard; Kjærgaard, Benedict; Nielsen, Jakob Koefoed

In this porcine lung injury model, apneic oxygenation with arteriovenous CO2 removal provided sufficient gas exchange and stable hemodynamics, indicating that the method might have a potential in the treatment of severe ARDS.   Acknowledgements The membrane lungs were kindly provided by Novalung GmbH, Germany.......Background and aim of study We hypothesized that continuous high airway pressure without ventilatory movements (apneic oxygenation), using an open lung approach, combined with extracorporeal, pumpless, arterio-venous, carbon dioxide (CO2) removal would provide adequate gas exchange in acute lung...

Prospective longitudinal evaluation of lung function during the first year of life after extracorporeal membrane oxygenation.

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Hofhuis, Ward; Hanekamp, Manon N; Ijsselstijn, Hanneke; Nieuwhof, Eveline M; Hop, Wim C J; Tibboel, Dick; de Jongste, Johan C; Merkus, Peter J F M

2011-03-01

To collect longitudinal data on lung function in the first year of life after extracorporeal membrane oxygenation and to evaluate relationships between lung function and perinatal factors. Longitudinal data on lung function in the first year of life after extracorporeal membrane oxygenation are lacking. Prospective longitudinal cohort study. Outpatient clinic of a tertiary level pediatric hospital. The cohort consisted of 64 infants; 33 received extracorporeal membrane oxygenation for meconium aspiration syndrome, 14 for congenital diaphragmatic hernia, four for sepsis, six for persistent pulmonary hypertension of the neonate, and seven for respiratory distress syndrome of infancy. Evaluation was at 6 mos and 12 mos; 39 infants were evaluated at both time points . None. Functional residual capacity and forced expiratory flow at functional residual capacity were measured and expressed as z score. Mean (sem) functional residual capacities in z score were 0.0 (0.2) and 0.2 (0.2) at 6 mos and 12 mos, respectively. Mean (sem) forced expiratory flow was significantly below average (z score = 0) (p capacity significantly above normal: mean (sem) z score = 1.2 (0.5). Infants treated with extracorporeal membrane oxygenation have normal lung volumes and stable forced expiratory flows within normal range, although below average, within the first year of life. There is reason to believe, therefore, that extracorporeal membrane oxygenation either ameliorates the harmful effects of mechanical ventilation or somehow preserves lung function in the very ill neonate.

Oxygen therapy for interstitial lung disease: a systematic review

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Emily C. Bell

2017-02-01

Full Text Available This review aims to establish the impact of oxygen therapy on dyspnoea, health-related quality of life (HRQoL, exercise capacity and mortality in interstitial lung disease (ILD. We included studies that compared oxygen therapy to no oxygen therapy in adults with ILD. No limitations were placed on study design or intervention type. Two reviewers independently evaluated studies for inclusion, assessed risk of bias and extracted data. The primary outcome was dyspnoea. Eight studies evaluated the acute effects of oxygen (n=1509. There was no effect of oxygen therapy on modified Borg dyspnoea score at end exercise (mean difference (MD −0.06 units, 95% CI −0.24–0.13; two studies, n=27. However, effects on exercise outcomes consistently favoured oxygen therapy. One study showed reduction in dyspnoea at rest with oxygen in patients who were acutely unwell (MD visual analogue scale 30 mm versus 48 mm, p<0.05; n=10. Four studies of long-term oxygen therapy (n=2670 had high risk of bias and no inferences could be drawn. This systematic review showed no effects of oxygen therapy on dyspnoea during exercise in ILD, although exercise capacity was increased. Future trials should evaluate whether acute improvements in exercise capacity with oxygen can be translated into improved physical activity and HRQoL.

Extravascular transport in normal and tumor tissues.

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Jain, R K; Gerlowski, L E

1986-01-01

The transport characteristics of the normal and tumor tissue extravascular space provide the basis for the determination of the optimal dosage and schedule regimes of various pharmacological agents in detection and treatment of cancer. In order for the drug to reach the cellular space where most therapeutic action takes place, several transport steps must first occur: (1) tissue perfusion; (2) permeation across the capillary wall; (3) transport through interstitial space; and (4) transport across the cell membrane. Any of these steps including intracellular events such as metabolism can be the rate-limiting step to uptake of the drug, and these rate-limiting steps may be different in normal and tumor tissues. This review examines these transport limitations, first from an experimental point of view and then from a modeling point of view. Various types of experimental tumor models which have been used in animals to represent human tumors are discussed. Then, mathematical models of extravascular transport are discussed from the prespective of two approaches: compartmental and distributed. Compartmental models lump one or more sections of a tissue or body into a "compartment" to describe the time course of disposition of a substance. These models contain "effective" parameters which represent the entire compartment. Distributed models consider the structural and morphological aspects of the tissue to determine the transport properties of that tissue. These distributed models describe both the temporal and spatial distribution of a substance in tissues. Each of these modeling techniques is described in detail with applications for cancer detection and treatment in mind.

Extravascular complications following abdominal organ transplantation

International Nuclear Information System (INIS)

Low, G.; Jaremko, J.L.; Lomas, D.J.

2015-01-01

A variety of transplants have been performed in the abdomen including liver, kidney, pancreas and islet, bowel, and multivisceral transplants. Imaging plays an important role in graft surveillance particularly to exclude post-transplant complications. When complications occur, therapeutic image-guided interventions are invaluable as these may be graft-saving and even life-saving. Vascular complications following transplantation have been extensively reported in recent reviews. The focus of this review is to discuss post-transplant complications that are primarily extravascular in location. This includes biliary, urological, intestinal, malignancy, infections, and miscellaneous complications. Familiarity with the imaging appearances of these complications is helpful for radiologists as accurate diagnosis and expedient treatment has an impact on graft and patient survival

Oxygen-enhanced MRI of the lungs. Intraindividual comparison between 1.5 and 3 Tesla

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Dietrich, Olaf; Thieme, S.F.; Maxien, D.; Nikolaou, K.; Reiser, M.; Schoenberg, S.O.; Fink, C.

2011-01-01

Purpose: To assess the feasibility of oxygen-enhanced MRI of the lung at 3 Tesla and to compare signal characteristics with 1.5 Tesla. Materials and Methods: 13 volunteers underwent oxygen-enhanced lung MRI at 1.5 and 3 T with a T 1-weighted single-slice non-selective inversion-recovery single-shot half-Fourier fast-spin-echo sequence with simultaneous respiratory and cardiac triggering in coronal orientation. 40 measurements were acquired during room air breathing and subsequently during oxygen breathing (15 L/min, close-fitting face-mask). The signal-to-noise ratio (SNR) of the lung tissue was determined with a difference image method. The image quality of all acquisitions was visually assessed. The mean values of the oxygen-induced relative signal enhancement and its regional coefficient of variation were calculated and the signal enhancement was displayed as color-coded parameter maps. Oxygen-enhancement maps were visually assessed with respect to the distribution and heterogeneity of the oxygen-related signal enhancement at both field strengths. Results: The mean relative signal enhancement due to oxygen breathing was 13 % (± 5.6 %) at 1.5 T and of 9.0 % (± 8.0 %) at 3 T. The regional coefficient of variation was significantly higher at 3 T. Visual and quantitative assessment of the enhancement maps showed considerably less homogeneous distribution of the signal enhancement at 3 T. The SNR was not significantly different but showed a trend to slightly higher values (increase of about 10 %) at 3 T. Conclusion: Oxygen-enhanced pulmonary MRI is feasible at 3 Tesla. However, signal enhancement is currently more heterogeneous and slightly lower at 3 T. (orig.)

Apneic oxygenation combined with extracorporeal arteriovenous carbon dioxide removal provides sufficient gas exchange in experimental lung injury

DEFF Research Database (Denmark)

Nielsen, Niels Dalsgaard; Kjærgaard, Benedict; Koefoed-Nielsen, Jacob

2008-01-01

We hypothesized that apneic oxygenation, using an open lung approach, combined with extracorporeal CO2 removal, would provide adequate gas exchange in acute lung injury. We tested this hypothesis in nine anesthetized and mechanically ventilated pigs (85-95 kg), in which surfactant was depleted fr....../min. Thus, the method provided adequate gas exchange in this experimental model, suggesting that it might have potential as an alternative treatment modality in acute lung injury.......We hypothesized that apneic oxygenation, using an open lung approach, combined with extracorporeal CO2 removal, would provide adequate gas exchange in acute lung injury. We tested this hypothesis in nine anesthetized and mechanically ventilated pigs (85-95 kg), in which surfactant was depleted from...

Prospective longitudinal evaluation of lung function during the first year of life after extracorporeal membrane oxygenation

NARCIS (Netherlands)

Hofhuis, W.; Hanekamp, M.N.; Ijsselstijn, H.; Nieuwhof, E.M.; Hop, W.C.J.; Tibboel, D.; Jongste, J.C. de; Merkus, P.J.F.M.

2011-01-01

OBJECTIVE: To collect longitudinal data on lung function in the first year of life after extracorporeal membrane oxygenation and to evaluate relationships between lung function and perinatal factors. Longitudinal data on lung function in the first year of life after extracorporeal membrane

T1 relaxation time constants, influence of oxygen, and the oxygen transfer function of the human lung at 1.5 T—A meta-analysis

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Dietrich, Olaf, E-mail: od@dtrx.net [Josef Lissner Laboratory for Biomedical Imaging, Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Munich (Germany); Gaass, Thomas [Josef Lissner Laboratory for Biomedical Imaging, Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Munich (Germany); Comprehensive Pneumology Center, German Center for Lung Research, Munich (Germany); Reiser, Maximilian F. [Josef Lissner Laboratory for Biomedical Imaging, Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Munich (Germany)

2017-01-15

Purpose: To pool and summarize published data from magnetic resonance longitudinal relaxation measurements of the human lung at 1.5 T to provide a reliable basis of T{sub 1} relaxation time constants of healthy lung tissue both under respiration of room air and of pure oxygen. In particular, the oxygen-induced shortening of T{sub 1} was evaluated. Materials and methods: The PubMed database was comprehensively searched up to June 2016 for original publications in English containing quantitative T{sub 1} data (at least mean values and standard deviations) of the lung parenchyma of healthy subjects (minimum subject number: 3) at 1.5 T. From all included publications, T{sub 1} values of the lung of healthy subjects were extracted (inhaling room air and, if available, inhaling pure oxygen). Weighted mean values and standard deviations of all extracted data and the oxygen transfer function (OTF) were calculated. Results: 22 publications were included with a total number of 188 examined healthy subjects. 103 of these subjects (from 13 studies) were examined while breathing pure oxygen and room air; 85 subjects were examined only under room-air conditions. The weighted mean value (weighted sample standard deviation) of the room-air T{sub 1} values over all 22 studies was 1196 ms (152 ms). Based on studies with room-air and oxygen results, the mean T{sub 1} value at room-air conditions was 1172 ms (161 ms); breathing pure oxygen, the mean T{sub 1} value was reduced to 1054 ms (138 ms). This corresponds to a mean T{sub 1} reduction by 118 ms (35 ms) or 10.0 % (2.3 %) and to a mean OTF value of 1.22 (0.32) × 10{sup −3} s{sup −1}/(%O{sub 2}). Conclusion: This meta-analysis with data from 188 subjects indicates that the average T{sub 1} relaxation time constant of healthy lung tissue at 1.5 T is distributed around 1200 ms with a standard deviation of about 150 ms; breathing pure oxygen reduces this value significantly by 10 % to about 1050 ms.

Role of macrophages and oxygen radicals in IgA induced lung injury in the rat

International Nuclear Information System (INIS)

Johnson, K.J.; Ward, P.A.; Kunkel, R.G.; Wilson, B.S.

1986-01-01

Acute lung injury in the rat has been induced by the instillation of affinity-purified mouse monoclonal IgA antibody with specific reactivity to dinitrophenol (DNP) coupled to albumin. This model of lung injury requires an intact complement system but not neutrophils, and evidence suggests that pulmonary macrophages are the critical effector cell. Macrophages retrievable from the lungs of the IgA immune complex treated rats are considerably increased in number as compared to control animals which received only the antibody. In addition these cells show evidence of activation in vivo with greater spontaneous generation of the superoxide anion (O 2 - ) as well as significantly enhanced O 2 - response in the presence of a second stimulus. Inhibition studies in vivo suggest that the lung injury is mediated by oxygen radical generation by the pulmonary macrophages. Pretreatment of rats with superoxide dismutase (SOD), catalase, the iron chelator deferoxamine or the hydroxyl radical scavenger dimethyl sulfoxide (DMSO) all markedly suppressed the development of the lung injury. In summary, these studies suggest that IgA immune complex injury in the rat lung is mediated by oxygen radical formation from pulmonary macrophages

Detection of reactive oxygen species in isolated, perfused lungs by electron spin resonance spectroscopy

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Schudt Christian

2005-07-01

Full Text Available Abstract Background The sources and measurement of reactive oxygen species (ROS in intact organs are largely unresolved. This may be related to methodological problems associated with the techniques currently employed for ROS detection. Electron spin resonance (ESR with spin trapping is a specific method for ROS detection, and may address some these technical problems. Methods We have established a protocol for the measurement of intravascular ROS release from isolated buffer-perfused and ventilated rabbit and mouse lungs, combining lung perfusion with the spin probe l-hydroxy-3-carboxy-2,2,5,5-tetramethylpyrrolidine (CPH and ESR spectroscopy. We then employed this technique to characterize hypoxia-dependent ROS release, with specific attention paid to NADPH oxidase-dependent superoxide formation as a possible vasoconstrictor pathway. Results While perfusing lungs with CPH over a range of inspired oxygen concentrations (1–21 %, the rate of CP• formation exhibited an oxygen-dependence, with a minimum at 2.5 % O2. Addition of superoxide dismutase (SOD to the buffer fluid illustrated that a minor proportion of this intravascular ROS leak was attributable to superoxide. Stimulation of the lungs by injection of phorbol-12-myristate-13-acetate (PMA into the pulmonary artery caused a rapid increase in CP• formation, concomitant with pulmonary vasoconstriction. Both the PMA-induced CPH oxidation and the vasoconstrictor response were largely suppressed by SOD. When the PMA challenge was performed at different oxygen concentrations, maximum superoxide liberation and pulmonary vasoconstriction occurred at 5 % O2. Using a NADPH oxidase inhibitor and NADPH-oxidase deficient mice, we illustrated that the PMA-induced superoxide release was attributable to the stimulation of NADPH oxidases. Conclusion The perfusion of isolated lungs with CPH is suitable for detection of intravascular ROS release by ESR spectroscopy. We employed this technique to

Oxygen, the lung and the diver: friends and foes?

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van Ooij, Pieter-Jan A M; Sterk, Peter J; van Hulst, Robert A

2016-12-01

Worldwide, the number of professional and sports divers is increasing. Most of them breathe diving gases with a raised partial pressure of oxygen (P O 2 ). However, if the P O 2 is between 50 and 300 kPa (375-2250 mmHg) (hyperoxia), pathological pulmonary changes can develop, known as pulmonary oxygen toxicity (POT). Although in its acute phase, POT is reversible, it can ultimately lead to non-reversible pathological changes. Therefore, it is important to monitor these divers to prevent them from sustaining irreversible lesions.This review summarises the pulmonary pathophysiological effects when breathing oxygen with a P O 2 of 50-300 kPa (375-2250 mmHg). We describe the role and the limitations of lung function testing in monitoring the onset and development of POT, and discuss new techniques in respiratory medicine as potential markers in the early development of POT in divers. Copyright ©ERS 2016.

Long term high flow heated oxygen treatment in COPD – lung function and physical ability

DEFF Research Database (Denmark)

Weinreich, Ulla; Storgaard, Line; Hockey, Hans

2017-01-01

Introduction: Long term oxygen therapy (LTOT) improves survival in patients with COPD with resting hypoxemia. Despite this, a progressive loss of lung function and physical ability is expected in COPD. The AIRVO device delivers nasal high flow (NHF) warmed and humidified oxygen-enriched air, 20...

Extracorporeal membrane oxygenation as a bridge to lung transplantation: A single-center experience in the present era.

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Todd, Emily M; Biswas Roy, Sreeja; Hashimi, A Samad; Serrone, Rosemarie; Panchanathan, Roshan; Kang, Paul; Varsch, Katherine E; Steinbock, Barry E; Huang, Jasmine; Omar, Ashraf; Patel, Vipul; Walia, Rajat; Smith, Michael A; Bremner, Ross M

2017-11-01

Extracorporeal membrane oxygenation has been used as a bridge to lung transplantation in patients with rapid pulmonary function deterioration. The reported success of this modality and perioperative and functional outcomes are varied. We retrospectively reviewed all patients who underwent lung transplantation at our institution over 1 year (January 1, 2015, to December 31, 2015). Patients were divided into 2 groups depending on whether they required extracorporeal membrane oxygenation support as a bridge to transplant; preoperative characteristics, lung transplantation outcomes, and survival were compared between groups. Of the 93 patients, 12 (13%) received bridge to transplant, and 81 (87%) did not. Patients receiving bridge to transplant were younger, had higher lung allocation scores, had lower functional status, and were more often on mechanical ventilation at listing. Most patients who received bridge to transplant (n = 10, 83.3%) had pulmonary fibrosis. Mean pretransplant extracorporeal membrane oxygenation support was 103.6 hours in duration (range, 16-395 hours). All patients who received bridge to transplant were decannulated immediately after lung transplantation but were more likely to return to the operating room for secondary chest closure or rethoracotomy. Grade 3 primary graft dysfunction within 72 hours was similar between groups. Lung transplantation success and hospital discharge were 100% in the bridge to transplant group; however, these patients experienced longer hospital stays and higher rates of discharge to acute rehabilitation. The 1-year survival was 100% in the bridge to transplant group and 91% in the non-bridge to transplant group (log-rank, P = .24). The 1-year functional status was excellent in both groups. Extracorporeal membrane oxygenation can be used to safely bridge high-acuity patients with end-stage lung disease to lung transplantation with good 30-day, 90-day, and 1-year survival and excellent 1-year functional status

Growing experience with extracorporeal membrane oxygenation as a bridge to lung transplantation.

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Shafii, Alexis E; Mason, David P; Brown, Chase R; Vakil, Nakul; Johnston, Douglas R; McCurry, Kenneth R; Pettersson, Gosta B; Murthy, Sudish C

2012-01-01

Extracorporeal membrane oxygenation (ECMO) is rarely used as a bridge to lung transplantation (BTT) because of its associated morbidity and mortality. However, recent advancements in perfusion technology and critical care have revived interest in this application of ECMO. We retrospectively reviewed our utilization of ECMO as BTT and evaluated our early and midterm results. Nineteen patients were placed on ECMO with the intent to transplant of which 14 (74%) were successfully transplanted. Early and midterm survival of transplanted patients was 75% (1 year) and 63% (3 years), respectively, with the most favorable results observed in interstitial lung disease patients supported in the venovenous configuration. Extracorporeal membrane oxygenation-bridged transplant survival rates were equivalent to nonbridged recipients, but early morbidity and mortality are high and the failure to bridge to transplant is significant. Overall, successfully bridged patients can derive a tangible benefit, albeit with considerable consumption of resources.

Elevated Extravascular Lung Water Index (ELWI) as a Predictor of Failure of Continuous Positive Airway Pressure Via Helmet (Helmet-CPAP) in Patients With Acute Respiratory Failure After Major Surgery.

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Redondo Calvo, Francisco Javier; Bejarano Ramirez, Natalia; Uña Orejon, Rafael; Villazala Garcia, Ruben; Yuste Peña, Ana Sofia; Belda, Francisco Javier

2015-11-01

NIV is increasingly used for prevention and treatment of respiratory complications and failure. Some of them are admitted to the PACU with advanced hemodynamic monitors which allow quantification of Extravascular Lung Water (EVLW) by transpulmonary thermodilution technique (TPTD) and Pulmonary Vascular Permeability (PVP) providing information on lung edema. The objective of this study was to ascertain if EVLW Index and PVP Index may predict failure (intubation) or success (non-intubation) in patients developing acute respiratory failure (ARF) in the postoperative period following major abdominal surgery, where the first line of treatment was non-invasive continuous positive airway pressure via a helmet. Hemodynamic variables, EVLWI and PVPI were monitored with a transpulmonary thermodilution hemodynamic monitor device (PiCCO™) before and after the application of CPAP. Avoidance of intubation was observed in 66% of patients with Helmet-CPAP. In these patients after the first hour of application of CPAP, PaO2/FiO2 ratio significantly increased (303.33±65.2 vs. 141.6±14.6, P<.01). Before starting Helmet-CPAP values of EVLWI and PVPI were significantly lower in non-intubated patients (EVLWI 8.6±1.08 vs. 11.8±0.99ml/kg IBW, P<.01 and PVPI 1.7±0.56 vs. 3.0±0.88, P<.01). An optimal cut-off value for EVLWI was established at 9.5, and at 2.45 for PVPI (sensitivity of 0.7; specificity of 0.9, P<.01). In this type of patient the physiological parameters that predict the failure of Helmet-CPAP with the greatest accuracy were the value of the EVLWI and PVPI before Helmet-CPAP institution and the PaO2/FiO2 ratio and the respiratory rate after one hour of CPAP. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

The Relationship between the Plasma Triglyceride Concentration and the Severity of Acute Respiratory Distress Syndrome

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V. V. Kuzkov

2012-01-01

Full Text Available Triglycerides (TG may be involved in the pathogenesis of critical impairments. Objective: to study the relationship between the plasma concentration of TG, the outcome of the disease, and the markers of its severity in intensive care unit patients with early-stage acute respiratory distress syndrome (ARDS. Subjects and methods. The prospective study included 18 patients with acute lung injury (ALI, who needed respiratory support. For further analysis, all the patients were divided into groups with TG < 1.00 mmol/l (TGlow; n=7 and >1.00 mmol/l (TGhigh; n=11. Results. A negative correlation was found between plasma TG concentration and oxygenation index (PaO2/FiO2. In the TG^jgh group, extravas-cular lung water index was significantly higher and cardiac index was lower than those in the TGlow group. Among the deceased patients, there was a 1.03 mmol/l reduction in TG concentration by day 4 of the study whereas in the survivors, TG concentration increased by an average of 0.15 mmol/l (p=0.02. Conclusion. In the patients with ALI, the plasma concentration of TG is related to oxygenation impairments and the degree of pulmonary edema, as well as with the outcome of the disease. Key words: triglycerides, acute lung injury, extravascular lung water index, pulmonary edema.

Hypoxia-preconditioned mesenchymal stem cells ameliorate ischemia/reperfusion-induced lung injury.

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Yung-Yang Liu

Full Text Available Hypoxia preconditioning has been proven to be an effective method to enhance the therapeutic action of mesenchymal stem cells (MSCs. However, the beneficial effects of hypoxic MSCs in ischemia/reperfusion (I/R lung injury have yet to be investigated. In this study, we hypothesized that the administration of hypoxic MSCs would have a positive therapeutic impact on I/R lung injury at molecular, cellular, and functional levels.I/R lung injury was induced in isolated and perfused rat lungs. Hypoxic MSCs were administered in perfusate at a low (2.5×105 cells and high (1×106 cells dose. Rats ventilated with a low tidal volume of 6 ml/kg served as controls. Hemodynamics, lung injury indices, inflammatory responses and activation of apoptotic pathways were determined.I/R induced permeability pulmonary edema with capillary leakage and increased levels of reactive oxygen species (ROS, pro-inflammatory cytokines, adhesion molecules, cytosolic cytochrome C, and activated MAPK, NF-κB, and apoptotic pathways. The administration of a low dose of hypoxic MSCs effectively attenuated I/R pathologic lung injury score by inhibiting inflammatory responses associated with the generation of ROS and anti-apoptosis effect, however this effect was not observed with a high dose of hypoxic MSCs. Mechanistically, a low dose of hypoxic MSCs down-regulated P38 MAPK and NF-κB signaling but upregulated glutathione, prostaglandin E2, IL-10, mitochondrial cytochrome C and Bcl-2. MSCs infused at a low dose migrated into interstitial and alveolar spaces and bronchial trees, while MSCs infused at a high dose aggregated in the microcirculation and induced pulmonary embolism.Hypoxic MSCs can quickly migrate into extravascular lung tissue and adhere to other inflammatory or structure cells and attenuate I/R lung injury through anti-oxidant, anti-inflammatory and anti-apoptotic mechanisms. However, the dose of MSCs needs to be optimized to prevent pulmonary embolism and thrombosis.

[Effects of lung protective ventilation strategy combined with lung recruitment maneuver on patients with severe burn complicated with acute respiratory distress syndrome].

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Li, Xiaojian; Zhong, Xiaomin; Deng, Zhongyuan; Zhang Xuhui; Zhang, Zhi; Zhang, Tao; Tang, Wenbin; Chen, Bib; Liu, Changling; Cao, Wenjuan

2014-08-01

To investigate the effects of lung protective ventilation strategy combined with lung recruitment maneuver on ARDS complicating patients with severe burn. Clinical data of 15 severely burned patients with ARDS admitted to our burn ICU from September 2011 to September 2013 and conforming to the study criteria were analyzed. Right after the diagnosis of acute lung injury/ARDS, patients received mechanical ventilation with lung protective ventilation strategy. When the oxygenation index (OI) was below or equal to 200 mmHg (1 mmHg = 0. 133 kPa), lung recruitment maneuver was performed combining incremental positive end-expiratory pressure. When OI was above 200 mmHg, lung recruitment maneuver was stopped and ventilation with lung protective ventilation strategy was continued. When OI was above 300 mmHg, mechanical ventilation was stopped. Before combining lung recruitment maneuver, 24 h after combining lung recruitment maneuver, and at the end of combining lung recruitment maneuver, variables of blood gas analysis (pH, PaO2, and PaCO2) were obtained by blood gas analyzer, and the OI values were calculated; hemodynamic parameters including heart rate, mean arterial pressure (MAP), central venous pressure (CVP) of all patients and the cardiac output (CO), extravascular lung water index (EVLWI) of 4 patients who received pulse contour cardiac output (PiCCO) monitoring were monitored. Treatment measures and outcome of patients were recorded. Data were processed with analysis of variance of repeated measurement of a single group and LSD test. (1) Before combining lung recruitment maneuver, 24 h after combining lung recruitment maneuver, and at the end of combining lung recruitment maneuver, the levels of PaO2 and OI of patients were respectively (77 ± 8), (113 ± 5), (142 ± 6) mmHg, and (128 ± 12), (188 ± 8), (237 ± 10) mmHg. As a whole, levels of PaO2 and OI changed significantly at different time points (with F values respectively 860. 96 and 842. 09, P values below

Ventilatory control and supplemental oxygen in premature infants with apparent chronic lung disease.

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Coste, Ferdinand; Ferkol, Thomas; Hamvas, Aaron; Cleveland, Claudia; Linneman, Laura; Hoffman, Julie; Kemp, James

2015-05-01

Our goal was to evaluate changes in respiratory pattern among premature infants born at newborn intensive care unit. 37 of 49 infants (75.5%) failed the challenge, with severe or sustained falls in SpO2%. Also, 16 of 37 infants (43.2%) who failed had marked increases in the amount of periodic breathing at the time of challenge failure. An unstable respiratory pattern is unmasked with a decrease in inspired oxygen or airflow support in many premature infants. Although infants with significant chronic lung disease may also be predisposed to more periodic breathing, these data suggest that the classification of chronic lung disease of prematurity based solely on clinical requirements for supplemental oxygen or airflow do not account for multiple mechanisms that are likely contributing to the need for respiratory support. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Oxygen Therapy

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Bonnie Solmes

2000-01-01

Full Text Available LTOT is prescribed for people with chronic lung disease in whom there is a decrease in the ability of the lungs to supply enough oxygen to the body. The heart is obliged to pump faster to meet the body's oxygen requirements. This may place undue stress on the heart, resulting in palpitations, dizziness and fatigue. A low oxygen level in arterial blood is also harmful to the heart, the brain and the pulmonary blood vessels. Oxygen therapy is used to break this cycle. A person with low blood oxygen will often be able to accomplish more with less fatigue with the help of supplemental oxygen therapy. Shortness of breath is a mechanical problem resulting from the effects of chronic obstructive pulmonary disease. Oxygen therapy may or may not reduce shortness of breath, but it will help the lungs and heart to function with less stress.

Receptor for advanced glycation end products involved in lung ischemia reperfusion injury in cardiopulmonary bypass attenuated by controlled oxygen reperfusion in a canine model.

Science.gov (United States)

Rong, Jian; Ye, Sheng; Liang, Meng-ya; Chen, Guang-xian; Liu, Hai; Zhang, Jin-Xin; Wu, Zhong-kai

2013-01-01

Controlled oxygen reperfusion could protect the lung against ischemia-reperfusion injury in cardiopulmonary bypass (CPB) by downregulating high mobility group box 1 (HMGB1), a high affinity receptor of HMGB1. This study investigated the effect of controlled oxygen reperfusion on receptor for advanced glycation end products (RAGE) expression and its downstream effects on lung ischemia-reperfusion injury. Fourteen canines received CPB with 60 minutes of aortic clamping and cardioplegic arrest followed by 90 minutes of reperfusion. Animals were randomized to receive 80% FiO2 during the entire procedure (control group) or to a test group receiving a controlled oxygen reperfusion protocol. Pathologic changes in lung tissues, RAGE expression, serum interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were evaluated. The lung pathologic scores after 25 and 90 minutes of reperfusion were significantly lower in the test group compared with the control group (p RAGE expression, TNF-α, and IL-6 were downregulated by controlled oxygen treatment (p RAGE might be involved in the lung ischemia-reperfusion injury in canine model of CPB, which was downregulated by controlled oxygen reperfusion.

Pulmonary Edema: Classification, Mechanisms of Development, Diagnosis

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V. V. Moroz

2009-01-01

Full Text Available Pulmonary edema remains a topical problem of modern reanimatology. In clinical practice, there is a need for continuous monitoring of the content of extravascular water in the lung and the pulmonary vascular permeability index for the timely detection and treatment of pulmonary edema. This literature review considers the minor mechanisms of pulmonary extravas-cular water exchange in health and in different types of pulmonary edema (acute lung injury, pneumonia, sepsis, postoperative period, burns, injuries etc., as well as the most accessible current (irradiation and dilution studies permitting an estimate of the level of pulmonary extravascular water and the pulmonary vascular permeability index in clinical practice. Key words: pulmonary edema, acute lung injury, pulmonary extravascular water, pulmonary vascular permeability index.

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

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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 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 UTI group was lower than that of the UTI group. GS can effectively collaborate with UTI against ALI and/or ARDS. PMID:26261640

Measurement of brain oxygenation changes using dynamic T1-weighted imaging

DEFF Research Database (Denmark)

Haddock, Bryan; Larsson, Henrik B W; Hansen, Adam E

2013-01-01

Magnetic resonance imaging (MRI) has proven useful in evaluating oxygenation in several types of tissue and blood. This study evaluates brain tissue oxygenation changes between normoxia and hyperoxia in healthy subjects using dynamic T1 and T2*-weighted imaging sequences. The change in FiO2 induced...... by hyperoxia caused a significant decrease in T1. A model to determine changes in tissue oxygen tension from the T1-weighted MRI signal is presented based on previous findings that T1 is sensitive to oxygen tension whereas T2* is sensitive to blood saturation. The two sequences produce results with different...... regional and temporal dynamics. These differences combined with results from simulations of the T1 signal intensities, indicate an increase in extravascular oxygen tension during hyperoxia. This study concludes that T1 and T2* responses to FiO2 serve as independent biomarkers of oxygen physiology...

Modeling Approach for Oxygen Exchange in the Human Lung under Hypobaric Conditions

Science.gov (United States)

2001-06-01

Operational Medical Issues in Hypo-and Hyperbaric Conditions [les Questions medicales a caractere oprationel liees aux conditions hypobares ou hyperbares ] To...under Hypobaric Conditions DISTRIBUTION: Approved for public release, distribution unlimited This paper is part of the following report: TITLE...Approach for Oxygen Exchange in the Human Lung under Hypobaric Conditions Ing J.P.F. Lindhout*, Drs M. van de Graaff*, Ir Drs R.C. van de Graaff*, Dr

Idiopathic pulmonary fibrosis patient supported with extracorporeal membrane oxygenation for 403 days while waiting for a lung transplant: A case report

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Nao Umei, M.D.

Full Text Available According to the Extracorporeal Life Support Organization, the average duration of veno-venous extracorporeal membrane oxygenation (V-V ECMO in adults with acute respiratory failure is 10.5–13.5 days. Some patients on V-V ECMO may not recover in such a short period of time, and recently, there have been more reports of prolonged V-V ECMO. However, we do not know how long it is feasible to wait for native lung recovery or lung transplant (LTx with the use of ECMO. We describe a patient with acute exacerbation of idiopathic pulmonary fibrosis supported by ECMO for 403 days while waiting for a LTx. In this case, we kept the patient awake, and he was communicating frequently with his family. We changed the membrane oxygenator 23 times and the cannula 10 times without complication. However, we terminated the treatment on day 403 of ECMO because there was no access site for cannula insertion due to blockage by a venous thrombotic occlusion, making it impossible to continue this bridge to lung transplantation. It has become possible to maintain patients on ECMO for extended periods of time, but it is difficult to manage ECMO for more than one year without the development of a more durable lung support system. Keywords: Lung transplantation, Extracorporeal membrane oxygenation, Idiopathic pulmonary fibrosis

A CCR2 macrophage endocytic pathway mediates extravascular fibrin clearance in vivo

DEFF Research Database (Denmark)

Motley, Michael P; Madsen, Daniel H; Jürgensen, Henrik J

2016-01-01

cellular endocytosis and lysosomal targeting, revealing a novel intracellular pathway for extravascular fibrin degradation. A C-C chemokine receptor type 2 (CCR2)-positive macrophage subpopulation constituted the majority of fibrin-uptaking cells. Consequently, cellular fibrin uptake was diminished...... by elimination of CCR2-expressing cells. The CCR2-positive macrophage subtype was different from collagen-internalizing M2-like macrophages. Cellular fibrin uptake was strictly dependent on plasminogen and plasminogen activator. Surprisingly, however, fibrin endocytosis was unimpeded by the absence of the fibrin...... subsets of macrophages employing distinct molecular pathways....

Anesthetic Management of Patients Undergoing Right Lung Surgery After Left Upper Lobectomy: Selection of Tubes for One-Lung Ventilation (OLV) and Oxygenation During OLV.

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Kawagoe, Izumi; Hayashida, Masakazu; Suzuki, Kenji; Kitamura, Yoshitaka; Oh, Shiaki; Satoh, Daizoh; Inada, Eiichi

2016-08-01

To investigate anesthesia management in patients undergoing right lung surgery after a previous left upper lobectomy (LUL) that may require special precautions since angulation of the left bronchus can hamper correct placement of a left-sided double-lumen tube (DLT), and one-lung ventilation (OLV) depending solely on the left lower lobe may lead to inadequate oxygenation. A retrospective data analysis. Single university hospital. Patients underwent right lung surgery after previous LUL. None. Anesthesia management was investigated in 18 patients who underwent right lung surgery following LUL. All intubation procedures were performed under bronchoscopic guidance to prevent airway trauma. OLV could be achieved with a left-sided DLT in 12 patients, while tubes other than this were required in 6 patients, including a right-sided DLT (n = 3) and a bronchial blocker (n = 3). The presence or absence of remarkable bronchial angulation, characterized by a combination of a wide (>140°) angle between the trachea and left main bronchus and a narrow (right lung surgery after LUL. Copyright © 2016 Elsevier Inc. All rights reserved.

Towards a Biohybrid Lung: Endothelial Cells Promote Oxygen Transfer through Gas Permeable Membranes.

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Menzel, Sarah; Finocchiaro, Nicole; Donay, Christine; Thiebes, Anja Lena; Hesselmann, Felix; Arens, Jutta; Djeljadini, Suzana; Wessling, Matthias; Schmitz-Rode, Thomas; Jockenhoevel, Stefan; Cornelissen, Christian Gabriel

2017-01-01

In patients with respiratory failure, extracorporeal lung support can ensure the vital gas exchange via gas permeable membranes but its application is restricted by limited long-term stability and hemocompatibility of the gas permeable membranes, which are in contact with the blood. Endothelial cells lining these membranes promise physiological hemocompatibility and should enable prolonged application. However, the endothelial cells increase the diffusion barrier of the blood-gas interface and thus affect gas transfer. In this study, we evaluated how the endothelial cells affect the gas exchange to optimize performance while maintaining an integral cell layer. Human umbilical vein endothelial cells were seeded on gas permeable cell culture membranes and cultivated in a custom-made bioreactor. Oxygen transfer rates of blank and endothelialized membranes in endothelial culture medium were determined. Cell morphology was assessed by microscopy and immunohistochemistry. Both setups provided oxygenation of the test fluid featuring small standard deviations of the measurements. Throughout the measuring range, the endothelial cells seem to promote gas transfer to a certain extent exceeding the blank membranes gas transfer performance by up to 120%. Although the underlying principles hereof still need to be clarified, the results represent a significant step towards the development of a biohybrid lung.

Setting individualized positive end-expiratory pressure level with a positive end-expiratory pressure decrement trial after a recruitment maneuver improves oxygenation and lung mechanics during one-lung ventilation.

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Ferrando, Carlos; Mugarra, Ana; Gutierrez, Andrea; Carbonell, Jose Antonio; García, Marisa; Soro, Marina; Tusman, Gerardo; Belda, Francisco Javier

2014-03-01

We investigated whether individualized positive end-expiratory pressure (PEEP) improves oxygenation, ventilation, and lung mechanics during one-lung ventilation compared with standardized PEEP. Thirty patients undergoing thoracic surgery were randomly allocated to the study or control group. Both groups received an alveolar recruitment maneuver at the beginning and end of one-lung ventilation. After the alveolar recruitment maneuver, the control group had their lungs ventilated with a 5 cm·H2O PEEP, while the study group had their lungs ventilated with an individualized PEEP level determined by a PEEP decrement trial. Arterial blood samples, lung mechanics, and volumetric capnography were recorded at multiple timepoints throughout the procedure. The individualized PEEP values in study group were higher than the standardized PEEP values (10 ± 2 vs 5 cm·H2O; P decrement trial than with a standardized 5 cm·H2O of PEEP.

Reactive oxygen species modulator 1 (Romo1) as a novel diagnostic marker for lung cancer-related malignant effusion

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Lee, Seung Hyeun; Park, Myung Jae; Choi, Sue In; Lee, Eun Joo; Lee, Sang Yeub; In, Kwang Ho

2017-01-01

Abstract Reactive oxygen species modulator 1 (Romo1) is a novel protein that plays an important role in intracellular reactive oxygen species generation. Recently, Romo1 has been suggested to have diagnostic and prognostic potential in lung cancer. However, there is no data on the diagnostic value of Romo1 level in malignant pleural effusion. We evaluated the clinical usefulness of Romo1 in pleural fluid for the diagnosis of malignant effusion in lung cancer patients. Pleural fluid Romo1 level was measured using enzyme-linked immunosorbent assay and compared between lung cancer-associated malignant effusion (n = 53; 29 adenocarcinomas and 24 squamous cell carcinomas) and benign pleural effusions (n = 91; 31 tuberculous pleurisy, 30 parapneumonic effusion, and 30 transudate). The discriminative power of Romo1 for lung cancer-associated malignant effusion was determined using receiver operating characteristic (ROC) curve analysis and compared with those of other tumor markers. Median Romo1 level in lung cancer-associated malignant effusion was 99.3 ng/mL, which was significantly higher than that in benign pleural effusions (P effusion from benign effusions was 67.0 ng/mL with a sensitivity of 73.8% and a specificity of 84.1%. The area under the curve was 0.837 (95% confidence interval [CI]: 0.750–0.886), which was significantly better than that of cytokeratin 19 fragments (P effusion. PMID:28121949

Extravascular red blood cells and hemoglobin promote tumor growth and therapeutic resistance as endogenous danger signals.

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Yin, Tao; He, Sisi; Liu, Xiaoling; Jiang, Wei; Ye, Tinghong; Lin, Ziqiang; Sang, Yaxiong; Su, Chao; Wan, Yang; Shen, Guobo; Ma, Xuelei; Yu, Min; Guo, Fuchun; Liu, Yanyang; Li, Ling; Hu, Qiancheng; Wang, Yongsheng; Wei, Yuquan

2015-01-01

Hemorrhage is a common clinical manifestation in patients with cancer. Intratumor hemorrhage has been demonstrated to be a poor prognostic factor for cancer patients. In this study, we investigated the role of RBCs and hemoglobin (Hb) in the process of tumor progression and therapeutical response. RBCs and Hb potently promoted tumor cell proliferation and syngenic tumor growth. RBCs and Hb activated the reactive oxygen species-NF-κB pathway in both tumor cells and macrophages. RBCs and Hb also induced chemoresistance mediated, in part, by upregulating ABCB1 gene expression. Tumor growth induced by RBCs was accompanied by an inflammatory signature, increased tumor vasculature, and influx of M2 macrophages. In both the peritoneal cavity and tumor microenvironment, extravascular RBCs rapidly recruited monocyte-macrophages into the lesion sites. In addition, RBCs and Hb increased several nucleotide-binding oligomerization domain-like receptors' expression and induced IL-1β release. Our results provide novel insights into the protumor function of RBCs and Hb as endogenous danger signals, which can promote tumor cell proliferation, macrophage recruitment, and polarization. Hemorrhage may represent a useful prognostic factor for cancer patients because of its role in tumor promotion and chemoresistance. Copyright © 2014 by The American Association of Immunologists, Inc.

Lung transplantation for idiopathic pulmonary arterial hypertension on intraoperative and postoperatively prolonged extracorporeal membrane oxygenation provides optimally controlled reperfusion and excellent outcome.

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Moser, Bernhard; Jaksch, Peter; Taghavi, Shahrokh; Muraközy, Gabriella; Lang, Georg; Hager, Helmut; Krenn, Claus; Roth, Georg; Faybik, Peter; Bacher, Andreas; Aigner, Clemens; Matilla, José R; Hoetzenecker, Konrad; Hacker, Philipp; Lang, Irene; Klepetko, Walter

2018-01-01

Lung transplantation for idiopathic pulmonary arterial hypertension has the highest reported postoperative mortality of all indications. Reasons lie in the complexity of treatment of these patients and the frequent occurrence of postoperative left ventricular failure. Transplantation on intraoperative extracorporeal membrane oxygenation support instead of cardiopulmonary bypass and even more the prolongation of extracorporeal membrane oxygenation into the postoperative period helps to overcome these problems. We reviewed our experience with this concept. All patients undergoing bilateral lung transplantation for idiopathic pulmonary arterial hypertension on intraoperative extracorporeal membrane oxygenation with or without prophylactic extracorporeal membrane oxygenation prolongation into the postoperative period between January 2000 and December 2014 were retrospectively analysed. Forty-one patients entered the study. Venoarterial extracorporeal membrane oxygenation support was prolonged into the postoperative period for a median of 2.5 days (range 1-40). Ninety-day, 1-, 3- and 5-year survival rates for the patient collective were 92.7%, 90.2%, 87.4% and 87.4%, respectively. When compared with 31 patients with idiopathic pulmonary arterial hypertension transplanted in the same period of time without prolongation of extracorporeal membrane oxygenation into the postoperative period, the results compared favourably (83.9%, 77.4%, 77.4%, and 77.4%; P = 0.189). Furthermore, these results are among the best results ever reported for this particularly difficult patient population. Bilateral lung transplantation for idiopathic pulmonary arterial hypertension with intraoperative venoarterial extracorporeal membrane oxygenation support seems to provide superior outcome compared with the results reported about the use of cardiopulmonary bypass. Prophylactic prolongation of venoarterial extracorporeal membrane oxygenation into the early postoperative period provides

Measurement of lung fluid volumes and albumin exclusion in sheep

International Nuclear Information System (INIS)

Pou, N.A.; Roselli, R.J.; Parker, R.E.; Clanton, J.A.; Harris, T.R.

1989-01-01

A radioactive tracer technique was used to determine interstitial diethylenetriaminepentaacetic acid (DTPA) and albumin distribution volume in sheep lungs. 125 I- and/or 131 I-labeled albumin were injected intravenously and allowed to equilibrate for 24 h. 99m Tc-labeled DTPA and 51 Cr-labeled erythrocytes were injected and allowed to equilibrate (2 h and 15 min, respectively) before a lethal dose of thiamylal sodium. Two biopsies (1-3 g) were taken from each lung and the remaining tissue was homogenized for wet-to-dry lung weight and volume calculations. Estimates of distribution volumes from whole lung homogenized samples were statistically smaller than biopsy samples for extravascular water, interstitial 99m Tc-DTPA, and interstitial albumin. The mean fraction of the interstitium (Fe), which excludes albumin, was 0.68 +/- 0.04 for whole lung samples compared with 0.62 +/- 0.03 for biopsy samples. Hematocrit may explain the consistent difference. To make the Fe for biopsy samples match that for homogenized samples, a mean hematocrit, which was 82% of large vessel hematocrit, was required. Excluded volume fraction for exogenous sheep albumin was compared with that of exogenous human albumin in two sheep, and no difference was found at 24 h

Lung deflation and oxygen pulse in COPD: results from the NETT randomized trial.

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Come, Carolyn E; Divo, Miguel J; San José Estépar, Raúl; Sciurba, Frank C; Criner, Gerard J; Marchetti, Nathaniel; Scharf, Steven M; Mosenifar, Zab; Make, Barry J; Keller, Cesar A; Minai, Omar A; Martinez, Fernando J; Han, MeiLan K; Reilly, John J; Celli, Bartolome R; Washko, George R

2012-01-01

In COPD patients, hyperinflation impairs cardiac function. We examined whether lung deflation improves oxygen pulse, a surrogate marker of stroke volume. In 129 NETT patients with cardiopulmonary exercise testing (CPET) and arterial blood gases (ABG substudy), hyperinflation was assessed with residual volume to total lung capacity ratio (RV/TLC), and cardiac function with oxygen pulse (O(2) pulse=VO(2)/HR) at baseline and 6 months. Medical and surgical patients were divided into "deflators" and "non-deflators" based on change in RV/TLC from baseline (∆RV/TLC). We defined deflation as the ∆RV/TLC experienced by 75% of surgical patients. We examined changes in O(2) pulse at peak and similar (iso-work) exercise. Findings were validated in 718 patients who underwent CPET without ABGs. In the ABG substudy, surgical and medical deflators improved their RV/TLC and peak O(2) pulse (median ∆RV/TLC -18.0% vs. -9.3%, p=0.0003; median ∆O(2) pulse 13.6% vs. 1.8%, p=0.12). Surgical deflators also improved iso-work O(2) pulse (0.53 mL/beat, p=0.04 at 20 W). In the validation cohort, surgical deflators experienced a greater improvement in peak O(2) pulse than medical deflators (mean 18.9% vs. 1.1%). In surgical deflators improvements in O(2) pulse at rest and during unloaded pedaling (0.32 mL/beat, pdeflators were 88% more likely than non-deflators to have an improvement in O(2) pulse (OR 1.88, 95% CI 1.30-2.72, p=0.0008). In COPD, decreased hyperinflation through lung volume reduction is associated with improved O(2) pulse. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effect of different seated positions on lung volume and oxygenation in acute respiratory distress syndrome.

Science.gov (United States)

Dellamonica, J; Lerolle, N; Sargentini, C; Hubert, S; Beduneau, G; Di Marco, F; Mercat, A; Diehl, J L; Richard, J C M; Bernardin, G; Brochard, L

2013-06-01

Lung volume available for ventilation is markedly decreased during acute respiratory distress syndrome. Body positioning may contribute to increase lung volume and partial verticalization is simple to perform. This study evaluated whether verticalization had parallel effects on oxygenation and end expiratory lung volume (EELV). Prospective multicenter study in 40 mechanically ventilated patients with ALI/ARDS in five university hospital MICUs. We evaluated four 45-min successive trunk position epochs (supine slightly elevated at 15°; semi recumbent with trunk elevated at 45°; seated with trunk elevated at 60° and legs down at 45°; back to supine). Arterial blood gases, EELV measured using the nitrogen washin/washout, and static compliance were measured. Responders were defined by a PaO₂/FiO₂ increase >20 % between supine and seated position. Results are median [25th-75th percentiles]. With median PEEP = 10 cmH₂O, verticalization increased lung volume but only responders (13 patients, 32 %) had a significant increase in EELV/PBW (predicted body weight) compared to baseline. This increase persisted at least partially when patients were positioned back to supine. Responders had a lower EELV/PBW supine [14 mL/kg (13-15) vs. 18 mL/kg (15-27) (p = 0.005)] and a lower compliance [30 mL/cmH₂O (22-38) vs. 42 (30-46) (p = 0.01)] than non-responders. Strain decreased with verticalization for responders. EELV/PBW increase and PaO₂/FiO₂ increase were not correlated. Verticalization is easily achieved and improves oxygenation in approximately 32 % of the patients together with an increase in EELV. Nonetheless, effect of verticalization on EELV/PBW is not predictable by PaO₂/FiO₂ increase, its monitoring may be helpful for strain optimization.

[Extracorporeal membrane oxygenation in primary graft dysfunction in a paediatric double lung transplant: presentation of a case].

Science.gov (United States)

López-Cantero, M; Grisolía, A L; Vicente, R; Moreno, I; Ramos, F; Porta, J; Torregrosa, S

2014-04-01

Primary graft dysfunction is a leading cause of morbimortality in the immediate postoperative period of patients undergoing lung transplantation. Among the treatment options are: lung protective ventilatory strategies, nitric oxide, lung surfactant therapy, and supportive treatment with extracorporeal membrane oxygenation (ECMO) as a bridge to recovery of lung function or re-transplant. We report the case of a 9-year-old girl affected by cystic fibrosis who underwent double-lung transplantation complicated with a severe primary graft dysfunction in the immediate postoperative period and refractory to standard therapies. Due to development of multiple organ failure, it was decided to insert arteriovenous ECMO catheters (pulmonary artery-right atrium). The postoperative course was satisfactory, allowing withdrawal of ECMO on the 5th post-surgical day. Currently the patient survives free of rejection and with an excellent quality of life after 600 days of follow up. Copyright © 2012 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

The effects of colloids or crystalloids on acute respiratory distress syndrome in swine (Sus scrofa models with severe sepsis: analysis on extravascular lung water, IL-8, and VCAM-1

Directory of Open Access Journals (Sweden)

Rismala Dewi

2016-04-01

Full Text Available Background: Acute respiratory distress syndrome (ARDS is a fatal complication of severe sepsis. Due to its higher molecular weight, the use of colloids in fluid resuscitation may be associated with fewer cases of ARDS compared to crystalloids. Extravascular lung water (EVLW elevation and levels of interleukin-8 (IL-8 and vascular cell adhesion molecule-1 (VCAM-1 have been studied as indicators playing a role in the pathogenesis of ARDS. The aim of the study was to determine the effects of colloid or crystalloid on the incidence of ARDS, elevation of EVLW, and levels of IL-8 and VCAM-1, in swine models with severe sepsis.Methods: This was a randomized trial conducted at the Laboratory of Experimental Surgery, School of Veterinary Medicine, IPB, using 22 healthy swine models with a body weight of 8 to 12 kg. Subjects were randomly allocated to receive either colloid or crystalloid fluid resuscitation. After administration of endotoxin, clinical signs of ARDS, EVLW, IL-8, and VCAM-1 were monitored during sepsis, severe sepsis, and one- and three hours after fluid resuscitation. Analysis of data using the Wilcoxon test , Kolmogorov-Smirnov test, Mann-Whitney test, unpaired t test.Results: Mild ARDS was more prevalent in the colloid group, while moderate ARDS was more frequent in the crystalloid group. EVLW elevation was lower in the colloid compared to the crystalloid group. There was no significant difference in IL-8 and VCAM-1 levels between the two groups.Conclusion: The use of colloids in fluid resuscitation does not decrease the probability of ARDS events compared to crystalloids. Compared to crystalloids, colloids are associated with a lower increase in EVLWI, but not with IL-8 or VCAM-1 levels.

Prevalence and clinical significance of extravascular incidental findings in patients undergoing CT cervico-cerebral angiography

International Nuclear Information System (INIS)

Crockett, Matthew Thomas; Murphy, Blathnaid; Smith, Jennifer; Kavanagh, Eoin Carl

2015-01-01

Highlights: • CT cervico-cerebral angiography (CTCCA) is a commonly performed study for assessment of vascular pathologies of head and neck. • This study assessed the prevalence, clinical significance and management of extravascular incidental findings detected on CTCCA. • This study demonstrated the presence of clinically significant incidental findings in 14% of patients undergoing CTCCA with 8% of these findings deemed to be highly significant. 19% of patients with highly clinically significant findings did not receive appropriate follow up. • A standardised method of reporting incidental findings, such as that used in this paper is suggested to aid radiologists and referring physicians in recording and communicating these findings. - Abstract: Introduction: CT cervico-cerebral angiography (CTCCA) is now the first line diagnostic imaging modality for the majority of vascular pathologies of the head and neck with diagnostic value comparable to or better than traditional angiographic techniques. The aim of this study was to assess the prevalence, clinical significance and management of extravascular incidental findings detected on CTCCA. Materials and methods: A retrospective review of the CTCCA reports of 302 consecutive patients from 2009 to 2013 was undertaken. Extravascular incidental findings were classified, according to an adaptation of the CT colonography data and reporting system (CRADS), as EV1–EV4. EV1 = no incidental findings, EV2 = clinically insignificant incidental finding, EV3 = incidental finding of intermediate clinical significance, EV4 = highly clinically significant finding. Follow up of the electronic medical records of patients with EV3 or EV4 findings was undertaken to determine subsequent management. Results: Potentially clinically significant findings were demonstrated in 14.2% of patients with 8.6% of patients having a highly clinically significant finding. 4 incidental findings were confirmed to be malignant lesions and 5

Moscatilin Inhibits Lung Cancer Cell Motility and Invasion via Suppression of Endogenous Reactive Oxygen Species

Directory of Open Access Journals (Sweden)

Akkarawut Kowitdamrong

2013-01-01

Full Text Available Lung cancer is the leading cause of death among cancer patients worldwide, and most of them have died from metastasis. Migration and invasion are prerequisite processes associated with high metastasis potential in cancers. Moscatilin, a bibenzyl derivative isolated from the Thai orchid Dendrobium pulchellum, has been shown to have anticancer effect against numerous cancer cell lines. However, little is known regarding the effect of moscatilin on cancer cell migration and invasion. The present study demonstrates that nontoxic concentrations of moscatilin were able to inhibit human nonsmall cell lung cancer H23 cell migration and invasion. The inhibitory effect of moscatilin was associated with an attenuation of endogenous reactive oxygen species (ROS, in which hydroxyl radical (OH∙ was identified as a dominant species in the suppression of filopodia formation. Western blot analysis also revealed that moscatilin downregulated activated focal adhesion kinase (phosphorylated FAK, Tyr 397 and activated ATP-dependent tyrosine kinase (phosphorylated Akt, Ser 473, whereas their parental counterparts were not detectable changed. In conclusion, our results indicate the novel molecular basis of moscalitin-inhibiting lung cancer cell motility and invasion and demonstrate a promising antimetastatic potential of such an agent for lung cancer therapy.

CO2 clearance by membrane lungs.

Science.gov (United States)

Sun, Liqun; Kaesler, Andreas; Fernando, Piyumindri; Thompson, Alex J; Toomasian, John M; Bartlett, Robert H

2018-05-01

Commercial membrane lungs are designed to transfer a specific amount of oxygen per unit of venous blood flow. Membrane lungs are much more efficient at removing CO 2 than adding oxygen, but the range of CO 2 transfer is rarely reported. Commercial membrane lungs were studied with the goal of evaluating CO 2 removal capacity. CO 2 removal was measured in 4 commercial membrane lungs under standardized conditions. CO 2 clearance can be greater than 4 times that of oxygen at a given blood flow when the gas to blood flow ratio is elevated to 4:1 or 8:1. The CO 2 clearance was less dependent on surface area and configuration than oxygen transfer. Any ECMO system can be used for selective CO 2 removal.

Dynamic oxygen-enhanced magnetic resonance imaging of the lung in asthma—Initial experience

International Nuclear Information System (INIS)

Zhang, Wei-Juan; Niven, Robert M.; Young, Simon S.; Liu, Yu-Zhen; Parker, Geoffrey J.M.; Naish, Josephine H.

2015-01-01

Highlights: • Oxygen-enhanced MRI may have a role in the estimation of disease severity in asthma. • Heterogeneity of parameter maps reflects localized functional impairment in asthma. • OE-MRI provides non-ionising, spatial and temporal information on oxygen delivery. - Abstract: Objectives: To prospectively estimate the feasibility and reproducibility of dynamic oxygen-enhanced magnetic resonance imaging (OE-MRI) in the assessment of regional oxygen delivery, uptake and washout in asthmatic lungs. Materials and methods: The study was approved by the National Research Ethics Committee and written informed consent was obtained. Dynamic OE-MRI was performed twice at one month apart on four mild asthmatic patients (23 ± 5 years old, FEV 1 = 96 ± 3% of predicted value) and six severe asthmatic patients (41 ± 12 years old, FEV 1 = 60 ± 14% of predicted value) on a 1.5 T MR scanner using a two-dimensional T 1 -weighted inversion-recovery turbo spin echo sequence. The enhancing fraction (EF), the maximal change in the partial pressure of oxygen in lung tissue (ΔPO 2max l ) and arterial blood of the aorta (ΔPO 2max a ), and the oxygen wash-in (τ up l , τ up a ) and wash-out (τ down l , τ down a ) time constants were extracted and compared between groups using the independent-samples t-test (two-tailed). Correlations between imaging readouts and clinical measurements were assessed by Pearson's correlation analysis. Bland–Altman analysis was used to estimate the levels of agreement between the repeat scans and the intra-observer agreement in the MR imaging readouts. Results: The severe asthmatic group had significantly smaller EF (70 ± 16%) and median ΔPO 2max l (156 ± 52 mmHg) and significantly larger interquartile range of τ up l (0.84 ± 0.26 min) than the mild asthmatic group (95 ± 3%, P = 0.014; 281 ± 40 mmHg, P = 0.004; 0.20 ± 0.07 min, P = 0.001, respectively). EF, median ΔPO 2max l and τ down l and the interquartile range of τ up l

Enhancement of the acrolein-induced production of reactive oxygen species and lung injury by GADD34.

Science.gov (United States)

Sun, Yang; Ito, Sachiko; Nishio, Naomi; Tanaka, Yuriko; Chen, Nana; Liu, Lintao; Isobe, Ken-ichi

2015-01-01

Chronic obstructive pulmonary disease (COPD) is characterized by lung destruction and inflammation. As a major compound of cigarette smoke, acrolein plays a critical role in the induction of respiratory diseases. GADD34 is known as a growth arrest and DNA damage-related gene, which can be overexpressed in adverse environmental conditions. Here we investigated the effects of GADD34 on acrolein-induced lung injury. The intranasal exposure of acrolein induced the expression of GADD34, developing the pulmonary damage with inflammation and increase of reactive oxygen species (ROS). Conversely, the integrality of pulmonary structure was preserved and the generation of ROS was reduced in GADD34-knockout mice. Acrolein-induced phosphorylation of eIF2α in GADD34-knockout epithelial cells by shRNA protected cell death by reducing misfolded protein-caused oxidative stress. These data indicate that GADD34 participates in the development of acrolein-induced lung injury.

Inhibitor of neuronal nitric oxide synthase improves gas exchange in ventilator-induced lung injury after pneumonectomy

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Suborov Evgeny V

2012-06-01

Full Text Available Abstract Background Mechanical ventilation with high tidal volumes may cause ventilator-induced lung injury (VILI and enhanced generation of nitric oxide (NO. We demonstrated in sheep that pneumonectomy followed by injurious ventilation promotes pulmonary edema. We wished both to test the hypothesis that neuronal NOS (nNOS, which is distributed in airway epithelial and neuronal tissues, could be involved in the pathogenesis of VILI and we also aimed at investigating the influence of an inhibitor of nNOS on the course of VILI after pneumonectomy. Methods Anesthetized sheep underwent right pneumonectomy, mechanical ventilation with tidal volumes (VT of 6 mL/kg and FiO2 0.5, and were subsequently randomized to a protectively ventilated group (PROTV; n = 8 keeping VT and FiO2 unchanged, respiratory rate (RR 25 inflations/min and PEEP 4 cm H2O for the following 8 hrs; an injuriously ventilated group with VT of 12 mL/kg, zero end-expiratory pressure, and FiO2 and RR unchanged (INJV; n = 8 and a group, which additionally received the inhibitor of nNOS, 7-nitroindazole (NI 1.0 mg/kg/h intravenously from 2 hours after the commencement of injurious ventilation (INJV + NI; n = 8. We assessed respiratory, hemodynamic and volumetric variables, including both the extravascular lung water index (EVLWI and the pulmonary vascular permeability index (PVPI. We measured plasma nitrite/nitrate (NOx levels and examined lung biopsies for lung injury score (LIS. Results Both the injuriously ventilated groups demonstrated a 2–3-fold rise in EVLWI and PVPI, with no significant effects of NI. In the INJV group, gas exchange deteriorated in parallel with emerging respiratory acidosis, but administration of NI antagonized the derangement of oxygenation and the respiratory acidosis significantly. NOx displayed no significant changes and NI exerted no significant effect on LIS in the INJV group. Conclusion Inhibition of nNOS improved gas exchange

Inhibitor of neuronal nitric oxide synthase improves gas exchange in ventilator-induced lung injury after pneumonectomy.

Science.gov (United States)

Suborov, Evgeny V; Smetkin, Alexey A; Kondratiev, Timofey V; Valkov, Andrey Y; Kuzkov, Vsevolod V; Kirov, Mikhail Y; Bjertnaes, Lars J

2012-06-21

Mechanical ventilation with high tidal volumes may cause ventilator-induced lung injury (VILI) and enhanced generation of nitric oxide (NO). We demonstrated in sheep that pneumonectomy followed by injurious ventilation promotes pulmonary edema. We wished both to test the hypothesis that neuronal NOS (nNOS), which is distributed in airway epithelial and neuronal tissues, could be involved in the pathogenesis of VILI and we also aimed at investigating the influence of an inhibitor of nNOS on the course of VILI after pneumonectomy. Anesthetized sheep underwent right pneumonectomy, mechanical ventilation with tidal volumes (VT) of 6 mL/kg and FiO2 0.5, and were subsequently randomized to a protectively ventilated group (PROTV; n = 8) keeping VT and FiO2 unchanged, respiratory rate (RR) 25 inflations/min and PEEP 4 cm H2O for the following 8 hrs; an injuriously ventilated group with VT of 12 mL/kg, zero end-expiratory pressure, and FiO2 and RR unchanged (INJV; n = 8) and a group, which additionally received the inhibitor of nNOS, 7-nitroindazole (NI) 1.0 mg/kg/h intravenously from 2 hours after the commencement of injurious ventilation (INJV + NI; n = 8). We assessed respiratory, hemodynamic and volumetric variables, including both the extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI). We measured plasma nitrite/nitrate (NOx) levels and examined lung biopsies for lung injury score (LIS). Both the injuriously ventilated groups demonstrated a 2-3-fold rise in EVLWI and PVPI, with no significant effects of NI. In the INJV group, gas exchange deteriorated in parallel with emerging respiratory acidosis, but administration of NI antagonized the derangement of oxygenation and the respiratory acidosis significantly. NOx displayed no significant changes and NI exerted no significant effect on LIS in the INJV group. Inhibition of nNOS improved gas exchange, but did not reduce lung water extravasation following

Effects of positive end-expiratory pressure titration and recruitment maneuver on lung inflammation and hyperinflation in experimental acid aspiration-induced lung injury.

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Ambrosio, Aline M; Luo, Rubin; Fantoni, Denise T; Gutierres, Claudia; Lu, Qin; Gu, Wen-Jie; Otsuki, Denise A; Malbouisson, Luiz M S; Auler, Jose O C; Rouby, Jean-Jacques

2012-12-01

In acute lung injury positive end-expiratory pressure (PEEP) and recruitment maneuver are proposed to optimize arterial oxygenation. The aim of the study was to evaluate the impact of such a strategy on lung histological inflammation and hyperinflation in pigs with acid aspiration-induced lung injury. Forty-seven pigs were randomly allocated in seven groups: (1) controls spontaneously breathing; (2) without lung injury, PEEP 5 cm H2O; (3) without lung injury, PEEP titration; (4) without lung injury, PEEP titration + recruitment maneuver; (5) with lung injury, PEEP 5 cm H2O; (6) with lung injury, PEEP titration; and (7) with lung injury, PEEP titration + recruitment maneuver. Acute lung injury was induced by intratracheal instillation of hydrochloric acid. PEEP titration was performed by incremental and decremental PEEP from 5 to 20 cm H2O for optimizing arterial oxygenation. Three recruitment maneuvers (pressure of 40 cm H2O maintained for 20 s) were applied to the assigned groups at each PEEP level. Proportion of lung inflammation, hemorrhage, edema, and alveolar wall disruption were recorded on each histological field. Mean alveolar area was measured in the aerated lung regions. Acid aspiration increased mean alveolar area and produced alveolar wall disruption, lung edema, alveolar hemorrhage, and lung inflammation. PEEP titration significantly improved arterial oxygenation but simultaneously increased lung inflammation in juxta-diaphragmatic lung regions. Recruitment maneuver during PEEP titration did not induce additional increase in lung inflammation and alveolar hyperinflation. In a porcine model of acid aspiration-induced lung injury, PEEP titration aimed at optimizing arterial oxygenation, substantially increased lung inflammation. Recruitment maneuvers further improved arterial oxygenation without additional effects on inflammation and hyperinflation.

Radionuclide two-indicator method to determine the indices of extravascular pulmonary fluid

International Nuclear Information System (INIS)

Frenkel', V.Kh.; Morgunov, N.B.; Kamenker, S.M.; Filatova, N.P.

1982-01-01

A radionuclide two-indicator method with 131 I-human serum albumin and 169 Yb-DTRA was used for examination of 32 persons without any diseases of the circulatory and respiratory organs and 75 patients with myocardial ischemia, different stages of cardiac insufficiency. The results showed that the amount of extravascular pulmonary fluid (EPF) in patients with ischemia was much higher as compared to the controls. EPF also increased significantly with the growing of the severity of cardiac insufficiency. A conclusion has been made that the radionuclide method of the determination of EPF indices is simple and effective in studies on pulmonary water metabolisn and can be used for diagnosis of early forms of interstitial edema

A hyperoxic lung injury model in premature rabbits: the influence of different gestational ages and oxygen concentrations.

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Roberta Munhoz Manzano

Full Text Available BACKGROUND: Many animal models have been developed to study bronchopulmonary dysplasia (BPD. The preterm rabbit is a low-cost, easy-to-handle model, but it has a high mortality rate in response to the high oxygen concentrations used to induce lung injury. The aim of this study was to compare the mortality rates of two models of hyperoxia-induced lung injury in preterm rabbits. METHODS: Pregnant New Zealand white rabbits were subjected to caesarean section on gestational day 28 or 29 (full term  = 31 days. The premature rabbits in the 28-day gestation group were exposed to room air or FiO₂ ≥95%, and the rabbits in the 29-day gestation group were exposed to room air or FiO₂  = 80% for 11 days. The mean linear intercept (Lm, internal surface area (ISA, number of alveoli, septal thickness and proportion of elastic and collagen fibers were quantified. RESULTS: The survival rates in the 29-day groups were improved compared with the 28-day groups. Hyperoxia impaired the normal development of the lung, as demonstrated by an increase in the Lm, the septal thickness and the proportion of elastic fibers. Hyperoxia also decreased the ISA, the number of alveoli and the proportion of collagen fibers in the 28-day oxygen-exposed group compared with the control 28-day group. A reduced number of alveoli was found in the 29-day oxygen exposed animals compared with the control 29-day group. CONCLUSIONS: The 29-day preterm rabbits had a reduced mortality rate compared with the 28-day preterm rabbits and maintained a reduction in the alveoli number, which is comparable to BPD in humans.

Effects of a helium/oxygen mixture on individuals’ lung function and metabolic cost during submaximal exercise for participants with obstructive lung diseases

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Häussermann S

2015-09-01

Full Text Available Sabine Häussermann,1 Anja Schulze,1 Ira M Katz,2,3 Andrew R Martin,4 Christiane Herpich,1 Theresa Hunger,1 Joëlle Texereau2 1Inamed GmbH, Gauting, Germany; 2Medical R&D, Air Liquide Santé International, Centre de Recherche Paris-Saclay, Les Loges-en-Josas, France; 3Department of Mechanical Engineering, Lafayette College, Easton, PA, USA; 4Department of Mechanical Engineering, University of Alberta, Edmonton, AB, CanadaBackground: Helium/oxygen therapies have been studied as a means to reduce the symptoms of obstructive lung diseases with inconclusive results in clinical trials. To better understand this variability in results, an exploratory physiological study was performed comparing the effects of helium/oxygen mixture (78%/22% to that of medical air.Methods: The gas mixtures were administered to healthy, asthmatic, and chronic obstructive pulmonary disease (COPD participants, both moderate and severe (6 participants in each disease group, a total of 30; at rest and during submaximal cycling exercise with equivalent work rates. Measurements of ventilatory parameters, forced spirometry, and ergospirometry were obtained.Results: There was no statistical difference in ventilatory and cardiac responses to breathing helium/oxygen during submaximal exercise. For asthmatics, but not for the COPD participants, there was a statistically significant benefit in reduced metabolic cost, determined through measurement of oxygen uptake, for the same exercise work rate. However, the individual data show that there were a mixture of responders and nonresponders to helium/oxygen in all of the groups.Conclusion: The inconsistent response to helium/oxygen between individuals is perhaps the key drawback to the more effective and widespread use of helium/oxygen to increase exercise capacity and for other therapeutic applications. Keywords: helium/oxygen, inspiratory capacity, oxygen uptake, COPD, asthma, obstructive airway diseases, exercise, heliox

Scaling laws for oxygen transport across the space-filling system of respiratory membranes in the human lung

Science.gov (United States)

Hou, Chen

Space-filling fractal surfaces play a fundamental role in how organisms function at various levels and in how structure determines function at different levels. In this thesis, we develop a quantitative theory of oxygen transport to and across the surface of the highly branched, space-filling system of alveoli, the fundamental gas exchange unit (acinar airways), in the human lung. Oxygen transport in the acinar airways is by diffusion, and we treat the two steps---diffusion through the branched airways, and transfer across the alveolar membranes---as a stationary diffusion-reaction problem, taking into account that there may be steep concentration gradients between the entrance and remote alveoli (screening). We develop a renormalization treatment of this screening effect and derive an analytic formula for the oxygen current across the cumulative alveolar membrane surface, modeled as a fractal, space-filling surface. The formula predicts the current from a minimum of morphological data of the acinus and appropriate values of the transport parameters, through a number of power laws (scaling laws). We find that the lung at rest operates near the borderline between partial screening and no screening; that it switches to no screening under exercise; and that the computed currents agree with measured values within experimental uncertainties. From an analysis of the computed current as a function of membrane permeability, we find that the space-filling structure of the gas exchanger is simultaneously optimal with respect to five criteria. The exchanger (i) generates a maximum oxygen current at minimum permeability; (ii) 'wastes' a minimum of surface area; (iii) maintains a minimum residence time of oxygen in the acinar airways; (iv) has a maximum fault tolerance to loss of permeability; and (v) generates a maximum current increase when switching from rest to exercise.

Enhancement of the Acrolein-Induced Production of Reactive Oxygen Species and Lung Injury by GADD34

Science.gov (United States)

Sun, Yang; Ito, Sachiko; Nishio, Naomi; Tanaka, Yuriko; Chen, Nana; Isobe, Ken-ichi

2015-01-01

Chronic obstructive pulmonary disease (COPD) is characterized by lung destruction and inflammation. As a major compound of cigarette smoke, acrolein plays a critical role in the induction of respiratory diseases. GADD34 is known as a growth arrest and DNA damage-related gene, which can be overexpressed in adverse environmental conditions. Here we investigated the effects of GADD34 on acrolein-induced lung injury. The intranasal exposure of acrolein induced the expression of GADD34, developing the pulmonary damage with inflammation and increase of reactive oxygen species (ROS). Conversely, the integrality of pulmonary structure was preserved and the generation of ROS was reduced in GADD34-knockout mice. Acrolein-induced phosphorylation of eIF2α in GADD34-knockout epithelial cells by shRNA protected cell death by reducing misfolded protein-caused oxidative stress. These data indicate that GADD34 participates in the development of acrolein-induced lung injury. PMID:25821552

Enhancement of the Acrolein-Induced Production of Reactive Oxygen Species and Lung Injury by GADD34

Directory of Open Access Journals (Sweden)

Yang Sun

2015-01-01

Full Text Available Chronic obstructive pulmonary disease (COPD is characterized by lung destruction and inflammation. As a major compound of cigarette smoke, acrolein plays a critical role in the induction of respiratory diseases. GADD34 is known as a growth arrest and DNA damage-related gene, which can be overexpressed in adverse environmental conditions. Here we investigated the effects of GADD34 on acrolein-induced lung injury. The intranasal exposure of acrolein induced the expression of GADD34, developing the pulmonary damage with inflammation and increase of reactive oxygen species (ROS. Conversely, the integrality of pulmonary structure was preserved and the generation of ROS was reduced in GADD34-knockout mice. Acrolein-induced phosphorylation of eIF2α in GADD34-knockout epithelial cells by shRNA protected cell death by reducing misfolded protein-caused oxidative stress. These data indicate that GADD34 participates in the development of acrolein-induced lung injury.

Dynamic oxygen-enhanced magnetic resonance imaging of the lung in asthma—Initial experience

Energy Technology Data Exchange (ETDEWEB)

Zhang, Wei-Juan, E-mail: weijuan.zhang@postgrad.manchester.ac.uk [Centre for Imaging Sciences, The University of Manchester, Oxford Road, Manchester M13 9PT (United Kingdom); Biomedical Imaging Institute, The University of Manchester, Oxford Road, Manchester M13 9PT (United Kingdom); Niven, Robert M., E-mail: robert.niven@uhsm.nhs.uk [North West Lung Research Centre, University Hospital of South Manchester, Southmoor Road, Manchester M23 9LT (United Kingdom); Young, Simon S., E-mail: Simon.Young1@astrazeneca.com [Personalised Healthcare and Biomarkers, AstraZeneca R and D, Alderley Park, Macclesfield SK10 4TF (United Kingdom); Liu, Yu-Zhen, E-mail: yu-zhen.liu@astrazeneca.com [Personalised Healthcare and Biomarkers, AstraZeneca R and D, Alderley Park, Macclesfield SK10 4TF (United Kingdom); Parker, Geoffrey J.M., E-mail: Geoff.parker@manchester.ac.uk [Centre for Imaging Sciences, The University of Manchester, Oxford Road, Manchester M13 9PT (United Kingdom); Biomedical Imaging Institute, The University of Manchester, Oxford Road, Manchester M13 9PT (United Kingdom); Bioxydyn Limited, Rutherford House, Pencroft Way, Manchester M15 6SZ (United Kingdom); Naish, Josephine H., E-mail: Josephine.naish@manchester.ac.uk [Centre for Imaging Sciences, The University of Manchester, Oxford Road, Manchester M13 9PT (United Kingdom); Biomedical Imaging Institute, The University of Manchester, Oxford Road, Manchester M13 9PT (United Kingdom)

2015-02-15

Highlights: • Oxygen-enhanced MRI may have a role in the estimation of disease severity in asthma. • Heterogeneity of parameter maps reflects localized functional impairment in asthma. • OE-MRI provides non-ionising, spatial and temporal information on oxygen delivery. - Abstract: Objectives: To prospectively estimate the feasibility and reproducibility of dynamic oxygen-enhanced magnetic resonance imaging (OE-MRI) in the assessment of regional oxygen delivery, uptake and washout in asthmatic lungs. Materials and methods: The study was approved by the National Research Ethics Committee and written informed consent was obtained. Dynamic OE-MRI was performed twice at one month apart on four mild asthmatic patients (23 ± 5 years old, FEV{sub 1} = 96 ± 3% of predicted value) and six severe asthmatic patients (41 ± 12 years old, FEV{sub 1} = 60 ± 14% of predicted value) on a 1.5 T MR scanner using a two-dimensional T{sub 1}-weighted inversion-recovery turbo spin echo sequence. The enhancing fraction (EF), the maximal change in the partial pressure of oxygen in lung tissue (ΔPO{sub 2max{sub l}}) and arterial blood of the aorta (ΔPO{sub 2max{sub a}}), and the oxygen wash-in (τ{sub up{sub l}}, τ{sub up{sub a}}) and wash-out (τ{sub down{sub l}}, τ{sub down{sub a}}) time constants were extracted and compared between groups using the independent-samples t-test (two-tailed). Correlations between imaging readouts and clinical measurements were assessed by Pearson's correlation analysis. Bland–Altman analysis was used to estimate the levels of agreement between the repeat scans and the intra-observer agreement in the MR imaging readouts. Results: The severe asthmatic group had significantly smaller EF (70 ± 16%) and median ΔPO{sub 2max{sub l}} (156 ± 52 mmHg) and significantly larger interquartile range of τ{sub up{sub l}} (0.84 ± 0.26 min) than the mild asthmatic group (95 ± 3%, P = 0.014; 281 ± 40 mmHg, P = 0.004; 0.20 ± 0.07 min, P = 0

Combining "open-lung" ventilation and arteriovenous extracorporeal lung assist: influence of different tidal volumes on gas exchange in experimental lung failure.

Science.gov (United States)

Muellenbach, Ralf M; Kredel, Markus; Kuestermann, Julian; Klingelhoefer, Michael; Schuster, Frank; Wunder, Christian; Kranke, Peter; Roewer, Norbert; Brederlau, Jörg

2009-08-01

Although low-tidal ventilation may reduce mortality in acute respiratory distress syndrome (ARDS), it can also result in severe respiratory acidosis and lung derecruitment. This study tested the hypothesis that combining "open-lung" ventilation and arteriovenous extracorporeal lung assist (av-ECLA) allows for maximal tidal volume (VT) reduction without the development of decompensated respiratory acidosis and impairment of oxygenation. After induction of ARDS in eight female pigs (56.1+/-3.2 kg), lung recruitment was performed and positive end-expiratory pressure was set 3 cmH2O above the lower inflection point of the pressure-volume curve. All animals were ventilated in the pressure-controlled ventilation mode (PCV) with VTs ranging from 0-8 ml/kg. At each VT, gas exchange and hemodynamic measurements were obtained with the av-ECLA circuit clamped and declamped. With each declamping, the gas flow through the membrane lung was set to 10 l of oxygen/min. The respiratory rate was adjusted to maintain normocapnia, but limited to 40/min. After lung recruitment, oxygenation remained significantly improved although VTs were minimized to 0 ml/kg (p<0.05). PaO2 was significantly improved during PCV and av-ECLA compared with PCV alone at VTs <4 ml/kg (p<0.05). With VT <6 ml/kg, severe acidosis could only be avoided if PCV was combined with av-ECLA. Due to sufficient CO2 elimination during av-ECLA, the VTs could be reduced to 0-2 ml/kg without the risk of decompensated respiratory acidosis. It was also shown that the "open-lung" strategy chosen was associated with sustained improvements in oxygenation, even though VTs were minimized.

Nonrespiratory lung function

Energy Technology Data Exchange (ETDEWEB)

Isawa, Toyoharu [Tohoku University Research Institute for Chest Disease and Cancer, Sendai (Japan)

1994-07-01

The function of the lungs is primarily the function as a gas exchanger: the venous blood returning to the lungs is arterialized with oxygen in the lungs and the arterialized blood is sent back again to the peripheral tissues of the whole body to be utilized for metabolic oxygenation. Besides the gas exchanging function which we call ''respiratory lung function'' the lungs have functions that have little to do with gas exchange itself. We categorically call the latter function of the lungs as ''nonrespiratory lung function''. The lungs consist of the conductive airways, the gas exchanging units like the alveoli, and the interstitial space that surrounds the former two compartments. The interstitial space contains the blood and lymphatic capillaries, collagen and elastic fibers and cement substances. The conductive airways and the gas exchanging units are directly exposed to the atmosphere that contains various toxic and nontoxic gases, fume and biological or nonbiological particles. Because the conductive airways are equipped with defense mechanisms like mucociliary clearance or coughs to get rid of these toxic gases, particles or locally produced biological debris, we are usually free from being succumbed to ill effects of inhaled materials. By use of nuclear medicine techniques, we can now evaluate mucociliary clearance function, and other nonrespiratory lung functions as well in vivo.

Nonrespiratory lung function

International Nuclear Information System (INIS)

Isawa, Toyoharu

1994-01-01

The function of the lungs is primarily the function as a gas exchanger: the venous blood returning to the lungs is arterialized with oxygen in the lungs and the arterialized blood is sent back again to the peripheral tissues of the whole body to be utilized for metabolic oxygenation. Besides the gas exchanging function which we call ''respiratory lung function'' the lungs have functions that have little to do with gas exchange itself. We categorically call the latter function of the lungs as ''nonrespiratory lung function''. The lungs consist of the conductive airways, the gas exchanging units like the alveoli, and the interstitial space that surrounds the former two compartments. The interstitial space contains the blood and lymphatic capillaries, collagen and elastic fibers and cement substances. The conductive airways and the gas exchanging units are directly exposed to the atmosphere that contains various toxic and nontoxic gases, fume and biological or nonbiological particles. Because the conductive airways are equipped with defense mechanisms like mucociliary clearance or coughs to get rid of these toxic gases, particles or locally produced biological debris, we are usually free from being succumbed to ill effects of inhaled materials. By use of nuclear medicine techniques, we can now evaluate mucociliary clearance function, and other nonrespiratory lung functions as well in vivo

Unilateral lung transplantation for pulmonary fibrosis.

Science.gov (United States)

1986-05-01

Improvements in immunosuppression and surgical techniques have made unilateral lung transplantation feasible in selected patients with end-stage interstitial lung disease. We report two cases of successful unilateral lung transplantation for end-stage respiratory failure due to pulmonary fibrosis. The patients, both oxygen-dependent, had progressive disease refractory to all treatment, with an anticipated life expectancy of less than one year on the basis of the rate of progression of the disease. Both patients were discharged six weeks after transplantation and returned to normal life. They are alive and well at 26 months and 14 months after the procedure. Pulmonary-function studies have shown substantial improvement in their lung volumes and diffusing capacities. For both patients, arterial oxygen tension is now normal and there is no arterial oxygen desaturation with exercise. This experience shows that unilateral lung transplantation, for selected patients with end-stage interstitial lung disease, provides a good functional result. Moreover, it avoids the necessity for cardiac transplantation, as required by the combined heart-lung procedure, and permits the use of the donor heart for another recipient.

Does donor arterial partial pressure of oxygen affect outcomes after lung transplantation? A review of more than 12,000 lung transplants.

Science.gov (United States)

Zafar, Farhan; Khan, Muhammad S; Heinle, Jeffrey S; Adachi, Iki; McKenzie, E Dean; Schecter, Marc G; Mallory, George B; Morales, David L S

2012-04-01

In lung transplantation (LTx), the arterial partial pressure of oxygen (PaO(2)) is traditionally regarded as critical information for assessment of donor lung function. Each center sets its own thresholds; by convention, a donor PaO(2) of less than 300 mm Hg has been considered disqualifying. Limited literature exists to support such a practice. We analyzed all LTxs performed in the United States over a 9-year period to assess the effect of donor PaO(2) on graft survival. The United Network for Organ Sharing (UNOS) database was queried for LTx (January 2000-November 2009). Of 12,545 LTx performed, 12,045 (96%) had donor PaO(2) data on a fraction of inspired oxygen of 1.0, recorded at the time of procurement. Mean donor PaO(2) was 407 ± 140 mm Hg. The majority of LTxs had a donor PaO(2) greater than 300 mm Hg (9593 (80%]) whereas PaO(2) was 200 mm Hg or less in 1830 (15%) and 201 to 300 in 582 (5%) donors. Use of donors with a PaO(2) of less than 200 increased over time from 5% (45) in 2000 to 21% (295) in 2009 (P = .002). Kaplan-Meier survival analysis showed no difference in graft survival with differing donor PaO(2)s, irrespective of whether patients had a single or double LTx. A Cox multivariable analysis of 21 donor characteristics demonstrated that donor PaO(2) had no association with graft survival. Donor PaO(2) levels did not affect graft survival. The use of donors with lower PaO(2)s could substantially increase the donor pool. We are not suggesting that donor PaO(2) is not important when assessing potential lung donors but its level of importance in regard to other criteria appears less than previously believed. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

"Open lung ventilation optimizes pulmonary function during lung surgery".

Science.gov (United States)

Downs, John B; Robinson, Lary A; Steighner, Michael L; Thrush, David; Reich, Richard R; Räsänen, Jukka O

2014-12-01

We evaluated an "open lung" ventilation (OV) strategy using low tidal volumes, low respiratory rate, low FiO2, and high continuous positive airway pressure in patients undergoing major lung resections. In this phase I pilot study, twelve consecutive patients were anesthetized using conventional ventilator settings (CV) and then OV strategy during which oxygenation and lung compliance were noted. Subsequently, a lung resection was performed. Data were collected during both modes of ventilation in each patient, with each patient acting as his own control. The postoperative course was monitored for complications. Twelve patients underwent open thoracotomies for seven lobectomies and five segmentectomies. The OV strategy provided consistent one-lung anesthesia and improved static compliance (40 ± 7 versus 25 ± 4 mL/cm H2O, P = 0.002) with airway pressures similar to CV. Postresection oxygenation (SpO2/FiO2) was better during OV (433 ± 11 versus 386 ± 15, P = 0.008). All postoperative chest x-rays were free of atelectasis or infiltrates. No patient required supplemental oxygen at any time postoperatively or on discharge. The mean hospital stay was 4 ± 1 d. There were no complications or mortality. The OV strategy, previously shown to have benefits during mechanical ventilation of patients with respiratory failure, proved safe and effective in lung resection patients. Because postoperative pulmonary complications may be directly attributable to the anesthetic management, adopting an OV strategy that optimizes lung mechanics and gas exchange may help reduce postoperative problems and improve overall surgical results. A randomized trial is planned to ascertain whether this technique will reduce postoperative pulmonary complications. Copyright © 2014 Elsevier Inc. All rights reserved.

Normal overall leakiness of microvasculature for albumin in patients with chronic obstructive lung disease (COLD).

Science.gov (United States)

Henriksen, J H; Kok-Jensen, A

1984-04-01

The overall extravasation rate of albumin, TER (i.e. the fraction of the intravascular albumin mass (IVM) passing into, and during steady state returning from, the extravascular space per unit time) was determined from the disappearance of i.v. injected radioiodinated serum albumin in seven patients with severe chronic obstructive lung disease (COLD) and in seven normal controls. Arterial oxygen tension in patients with COLD was median 60 mmHg (range 47-80, normal greater than 75 mmHg), vital capacity was on the average 55% of expected normal value (median 1.80 litre, range 1.45-1.95), and forced expired volume in first sec was decreased to 21% of expected normal value (median 0.55 litre, range 0.40-0.70). Right-heart catheterization revealed pulmonary hypertension in all but one patient. TER in patients with COLD was median 6.1% IVM/h (range 3.5-10.1) as compared to that of normal controls 6.0% IVM/h (range 4.3-7.4), indicating that no significant change in microvascular leakiness to albumin could be found in patients with COLD. Thus, the results bring no support to a generally increased microvascular permeability to proteins in patients with COLD.

Vitamin D Depletion in Pregnancy Decreases Survival Time, Oxygen Saturation, Lung Weight and Body Weight in Preterm Rat Offspring.

Directory of Open Access Journals (Sweden)

Sine Lykkedegn

Full Text Available Animal studies suggest a role of vitamin D in fetal lung development although not studied in preterm animals. We tested the hypothesis that vitamin D depletion aggravates respiratory insufficiency in preterm rat offspring. Furthermore, the effects of vitamin D depletion on growth and lung surfactant were investigated. Female Sprague-Dawley rats were randomly assigned low vitamin D (VDL or control diet before mating and followed with serum 25-hydroxyvitamin D (s-25(OHD determinations. After cesarean section at gestational day 19 (E19 or day 22 (E22, placental weight, birth weight, crown-rump-length (CRL, oxygenation (SaO2 at 30 min and survival time were recorded. The pup lungs were analyzed for phospholipid levels, surfactant protein A-D mRNA and the expression of the vitamin D receptor (VDR. S-25(OHD was significantly lower in the VDL group at cesarean section (12 vs. 30nmol/L, p<0.0001. Compared to the controls, E19 VDL pups had lower birth weight (2.13 vs. 2.29g, p<0.001, lung weight (0.09 vs. 0.10g, p = 0.002, SaO2 (54% vs. 69%, p = 0.002 as well as reduced survival time (0.50 vs. 1.25h, p<0.0001. At E22, the VDL-induced pulmonary differences were leveled out, but VDL pups had lower CRL (4.0 vs. 4.5cm, p<0.0001. The phospholipid levels and the surfactant protein mRNA expression did not differ between the dietary groups. In conclusion, Vitamin D depletion led to lower oxygenation and reduced survival time in the preterm offspring, associated with reduced lung weight and birth weight. Further studies of vitamin D depletion in respiratory insufficiency in preterm neonates are warranted.

Measurement of alveolar oxygen partial pressure in the rat lung using Carr-Purcell-Meiboom-Gill spin-spin relaxation times of hyperpolarized 3He and 129Xe at 74 mT.

Science.gov (United States)

Kraayvanger, Ryan J; Bidinosti, Christopher P; Dominguez-Viqueira, William; Parra-Robles, Juan; Fox, Matthew; Lam, Wilfred W; Santyr, Giles E

2010-11-01

Regional measurement of alveolar oxygen partial pressure can be obtained from the relaxation rates of hyperpolarized noble gases, (3) He and (129) Xe, in the lungs. Recently, it has been demonstrated that measurements of alveolar oxygen partial pressure can be obtained using the spin-spin relaxation rate (R(2) ) of (3) He at low magnetic field strengths (oxygen partial pressure measurements based on Carr-Purcell-Meiboom-Gill R(2) values of hyperpolarized (3) He and (129) Xe in vitro and in vivo in the rat lung at low magnetic field strength (74 mT) are presented. In vitro spin-spin relaxivity constants for (3) He and (129) Xe were determined to be (5.2 ± 0.6) × 10(-6) Pa(-1) sec(-1) and (7.3 ± 0.4) × 10(-6) Pa(-1) s(-1) compared with spin-lattice relaxivity constants of (4.0 ± 0.4) × 10(-6) Pa(-1) s(-1) and (4.3 ± 1.3) × 10(-6) Pa(-1) s(-1), respectively. In vivo experimental measurements of alveolar oxygen partial pressure using (3) He in whole rat lung show good agreement (r(2) = 0.973) with predictions based on lung volumes and ventilation parameters. For (129) Xe, multicomponent relaxation was observed with one component exhibiting an increase in R(2) with decreasing alveolar oxygen partial pressure. Copyright © 2010 Wiley-Liss, Inc.

Late response to whole-lung irradiation alone and with whole-body hyperthermia in dogs

International Nuclear Information System (INIS)

Gillette, S.M.; Gillette, E.L.; Dawson, C.A.

1997-01-01

The late effects of whole-lung irradiation with and without whole-body hyperthermia were studied in beagle dogs. The reference doses ranged from 18 to 49.5 Gy given in 1.5-Gy fractions over 6 weeks. Whole-body hyperthermia was given in three 2-h treatments to a deep rectal temperature of 42.0 degrees C. Radiation was given simultaneously with hyperthermia on those days. Physiological and histopathological responses were evaluated. Physiological changes included decreases in cardiac output, systemic blood pressure, dynamic compliance and serotonin uptake. Early changes included an increase in extravascular water and total protein in the lavage. These changes were considered mild, were compensated for and occurred only in dogs receiving doses of 40.5 Gy or greater given in 1.5-Gy fractions over 6 weeks. Histopathological change were typical of irradiated lung and included pleural fibrosis, interstitial fibrosis, fibrotic foci, and peribronchial and perivascular fibrosis. There was no enhancement of late injury to lung by hyperthermia seen in this study. 17 refs., 3 figs., 2 tabs

Chest ultrasound and hidden lung congestion in peritoneal dialysis patients.

Science.gov (United States)

Panuccio, Vincenzo; Enia, Giuseppe; Tripepi, Rocco; Torino, Claudia; Garozzo, Maurizio; Battaglia, Giovanni Giorgio; Marcantoni, Carmelita; Infantone, Lorena; Giordano, Guido; De Giorgi, Maria Loreta; Lupia, Mario; Bruzzese, Vincenzo; Zoccali, Carmine

2012-09-01

Chest ultrasound (US) is a non-invasive well-validated technique for estimating extravascular lung water (LW) in patients with heart diseases and in end-stage renal disease. We systematically applied this technique to the whole peritoneal dialysis (PD) population of five dialysis units. We studied the cross-sectional association between LW, echocardiographic parameters, clinical [pedal oedema, New York Heart Association (NYHA) class] and bioelectrical impedance analysis (BIA) markers of volume status in 88 PD patients. Moderate to severe lung congestion was evident in 41 (46%) patients. Ejection fraction was the echocardiographic parameter with the strongest independent association with LW (r = -0.40 P = 0.002). Oedema did not associate with LW on univariate and multivariate analysis. NYHA class was slightly associated with LW (r = 0.21 P = 0.05). Among patients with severe lung congestion, only 27% had pedal oedema and the majority (57%) had no dyspnoea (NYHA Class I). Similarly, the prevalence of patients with BIA, evidence of volume excess was small (11%) and not significantly different (P = 0.79) from that observed in patients with mild or no congestion (9%). In PD patients, LW by chest US reveals moderate to severe lung congestion in a significant proportion of asymptomatic patients. Intervention studies are necessary to prove the usefulness of chest US for optimizing the control of fluid excess in PD patients.

First Danish experience with ex vivo lung perfusion of donor lungs before transplantation

DEFF Research Database (Denmark)

Henriksen, Ian Sune Iversen; Møller-Sørensen, Hasse; Møller, Christian Holdfold

2014-01-01

INTRODUCTION: The number of lung transplantations is limited by a general lack of donor organs. Ex vivo lung perfusion (EVLP) is a novel method to optimise and evaluate marginal donor lungs prior to transplantation. We describe our experiences with EVLP in Denmark during the first year after its...... otherwise considered transplantable, but failed to meet the usual criteria due to possible contusions or because they were from donors with sepsis or unable to pass the oxygenation test. RESULTS: In the study period, seven of 33 Danish lung transplantations were made possible due to EVLP. One patient died......% improved oxygenation. The median time to extubation, time in intensive care unit and the admission period were 1, 7 and 39 days, respectively. CONCLUSION: In the first year after the introduction of EVLP in Denmark, seven pairs of donor lungs that previously would have been rejected have been transplanted...

Extra-vascular type of oral intravascular papillary endothelial hyperplasia (Masson′s tumor of lower lip: A case report and review of the literature

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G S Sarode

2015-01-01

Full Text Available Intravascular papillary endothelial hyperplasia (IPEH is an unusual reactive lesion of vascular origin, which rarely occurs in the oral cavity. Pathogenetically, is it divided into true, mixed and extra-vascular types. We report a case of extra-vascular IPEH of the lower lip in 54-year-old female patient. Patient gives history of trauma 4 months back with lesion developing at the site to trauma. The lesion was 3 cm × 4 cm in size with soft to firm in consistency. Histologically, it is characterized by an exuberant papillary endothelial cell proliferation toward the lumen of an enlarged blood vessel from the area of an organizing thrombus. The lesion was surgically excised under local anesthesia. The patient was followed for 1-year with no evidence of recurrence. This paper discusses the various aspects of IPEH of the oral cavity such as pathogenesis, clinical features, histopathology treatment, and prognosis.

Lung transplantation and survival outcomes in patients with oxygen-dependent COPD with regard to their alpha-1 antitrypsin deficiency status

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Ekström M

2017-11-01

Full Text Available Magnus Ekström, Hanan Tanash Department of Respiratory Medicine and Allergology, Skåne University Hospital, Lund University, Lund, Sweden Background: Individuals with severe alpha-1 antitrypsin deficiency (AATD have an increased risk of developing COPD. However, outcomes during long-term oxygen therapy (LTOT in patients with severe AATD and hypoxemia are unknown.Patients and methods: This was a prospective, population-based, consecutive cohort study of patients on LTOT due to COPD in the period from January 1, 1987, to June 30, 2015, in the Swedish National Registry for Respiratory Failure (Swedevox. Severe AATD was identified using the Swedish AATD registry and confirmed by isoelectric focusing. Data on lung transplantation (LTx were obtained from the two lung transplantation centers in Sweden. Mortality and causes of death were assessed based on the National Causes of Death Registry and analyzed using multivariable Cox regression.Results: A total of 14,644 patients who started LTOT due to COPD were included in this study. No patient was lost to follow up. Patients with AATD were younger, included more males and more never smokers, and had fewer comorbidities. During a median follow-up of 1.6 years (interquartile range [IQR], 2.7 on LTOT, patients without severe AATD had a higher mortality, hazard ratio [HR] 1.53 (95% CI, 1.24–1.88, adjusting for age, sex, smoking status, body mass index, performance status, level of hypoxemia, and comorbidities. Cardiovascular deaths were increased. A higher proportion of AATD patients underwent LTx, 53 (19% vs 118 (1%. Survival after LTx was similar for AATD and non-AATD patients and was predicted by age.Conclusion: In oxygen-dependent COPD, patients with severe AATD have a longer survival time on LTOT, but they have a similar prognosis after lung transplantation compared with patients without AATD. Keywords: COPD, long-term oxygen therapy, lung transplantation, severe alpha-1 antitrypsin deficiency

In contrast to BOLD: signal enhancement by extravascular water protons as an alternative mechanism of endogenous fMRI signal change.

Science.gov (United States)

Figley, Chase R; Leitch, Jordan K; Stroman, Patrick W

2010-10-01

Despite the popularity and widespread application of functional magnetic resonance imaging (fMRI) in recent years, the physiological bases of signal change are not yet fully understood. Blood oxygen level-dependant (BOLD) contrast - attributed to local changes in blood flow and oxygenation, and therefore magnetic susceptibility - has become the most prevalent means of functional neuroimaging. However, at short echo times, spin-echo sequences show considerable deviations from the BOLD model, implying a second, non-BOLD component of signal change. This has been dubbed "signal enhancement by extravascular water protons" (SEEP) and is proposed to result from proton-density changes associated with cellular swelling. Given that such changes are independent of magnetic susceptibility, SEEP may offer new and improved opportunities for carrying out fMRI in regions with close proximity to air-tissue and/or bone-tissue interfaces (e.g., the prefrontal cortex and spinal cord), as well as regions close to large blood vessels, which may not be ideally suited for BOLD imaging. However, because of the interdisciplinary nature of the literature, there has yet to be a thorough synthesis, tying together the various and sometimes disparate aspects of SEEP theory. As such, we aim to provide a concise yet comprehensive overview of SEEP, including recent and compelling evidence for its validity, its current applications and its future relevance to the rapidly expanding field of functional neuroimaging. Before presenting the evidence for a non-BOLD component of endogenous functional contrast, and to enable a more critical review for the nonexpert reader, we begin by reviewing the fundamental principles underlying BOLD theory. Copyright © 2010 Elsevier Inc. All rights reserved.

Evaluation of N-acetylcysteine and methylprednisolone as therapies for oxygen and acrolein-induced lung damage

Energy Technology Data Exchange (ETDEWEB)

Critchley, J.A.J.H. (Univ. of Edinburgh (England)); Beeley, J.M.; Clark, R.J.; Buchanan, J.D. (Royal Naval Hospital Hoslar, Gosport (England)); Summerfield, M.; Bell, S. (Admiralty Research Establishment, Alverstoke (England)); Spurlock, M.S.; Edginton, J.A.G. (Chemical Defence Establishment, Porton Down (England))

1990-04-01

Reactive oxidizing species are implicated in the etiology of a range of inhalational pulmonary injuries. Consequently, various free radical scavengers have been tested as potential prophylactic agents. The sulfydryl compound, N-acetylcysteine (NAC) is the only such compound clinically available for use in realistic dosages, and it is well established as an effective antidote for the hepatic and renal toxicity of paracetamol. Another approach in pulmonary injury prophylaxis is methylprednisolone therapy. The authors evaluated NAC and methylprednisolone in two rats models of inhalation injury: 40-hr exposure to >97% oxygen at 1.1 bar and 15-min exposure to acrolein vapor (210 ppm). The increases in lung wet/dry weight ratios, seen with both oxygen and acrolein toxicity were reduced with both treatments. However, with oxygen, NAC therapy was associated with considerably increased mortality and histological changes. Furthermore, IP NAC administration resulted in large volumes of ascitic fluid. With acrolein, IV, NAC had no significant effect on mortality or pulmonary histological damage. Methylprednisolone had no beneficial effects on either the mortality or histological damage observed in either toxicity model. They caution against the ad hoc use of NAC in the management of inhalational pulmonary injury.

A brief clinical case of monitoring of oxygenator performance and patient-machine interdependency during prolonged veno-venous extracorporeal membrane oxygenation.

Science.gov (United States)

Belliato, Mirko; Degani, Antonella; Buffa, Antonino; Sciutti, Fabio; Pagani, Michele; Pellegrini, Carlo; Iotti, Giorgio Antonio

2017-10-01

Monitoring veno-venous extracorporeal membrane oxygenation (vvECMO) during 76 days of continuous support in a 42-years old patient with end-stage pulmonary disease, listed for double-lung transplantation. Applying a new monitor (Landing ® , Eurosets, Medolla, Italy) and describing how measured and calculated parameters can be used to understand the variable interdependency between artificial membrane lung (ML) and patient native lung (NL). During vvECMO, in order to understand how the respiratory function is shared between ML and NL, ideally we should obtain data about oxygen transfer and CO 2 removal, both by ML and NL. Measurements for NL can be made on the mechanical ventilator. Measurements for ML are typically made from gas analysis on blood samples drawn from the ECMO system before and after the oxygenator, and therefore are non-continuous. Differently, the Landing monitor provides a continuous measurement of the oxygen transfer from the ML, combined with hemoglobin level, saturation of drained blood and saturation of reinfused blood. Moreover, the Landing monitor provides hemodynamics data about circulation through the ECMO system, with blood flow, pre-oxygenator pressure and post-oxygenator pressure. Of note, measurements include the drain negative pressure, whose monitoring may be particularly useful to prevent hemolysis. Real-time monitoring of vvECMO provides data helpful to understand the complex picture of a patient with severely damaged lungs on one side and an artificial lung on the other side. Data from vvECMO monitoring may help to adapt the settings of both mechanical ventilator and vvECMO. Data about oxygen transfer by the oxygenator are important to evaluate the performance of the device and may help to avoid unnecessary replacements, thus reducing risks and costs.

The Pathway for Oxygen: Tutorial Modelling on Oxygen Transport from Air to Mitochondrion: The Pathway for Oxygen.

Science.gov (United States)

Bassingthwaighte, James B; Raymond, Gary M; Dash, Ranjan K; Beard, Daniel A; Nolan, Margaret

2016-01-01

The 'Pathway for Oxygen' is captured in a set of models describing quantitative relationships between fluxes and driving forces for the flux of oxygen from the external air source to the mitochondrial sink at cytochrome oxidase. The intervening processes involve convection, membrane permeation, diffusion of free and heme-bound O2 and enzymatic reactions. While this system's basic elements are simple: ventilation, alveolar gas exchange with blood, circulation of the blood, perfusion of an organ, uptake by tissue, and consumption by chemical reaction, integration of these pieces quickly becomes complex. This complexity led us to construct a tutorial on the ideas and principles; these first PathwayO2 models are simple but quantitative and cover: (1) a 'one-alveolus lung' with airway resistance, lung volume compliance, (2) bidirectional transport of solute gasses like O2 and CO2, (3) gas exchange between alveolar air and lung capillary blood, (4) gas solubility in blood, and circulation of blood through the capillary syncytium and back to the lung, and (5) blood-tissue gas exchange in capillaries. These open-source models are at Physiome.org and provide background for the many respiratory models there.

Clearance of 99mTc-labeled albumin from lungs in anesthetized guinea pigs

International Nuclear Information System (INIS)

Connelly, J.C.; Peterson, B.T.

1993-01-01

Gamma imaging was used to measure the rate of clearance of aerosolized 99m Tc-human serum albumin (HSA) from the lungs of control guinea pigs and guinea pigs that received increased lung inflation or lung injury. Anesthetized guinea pigs were ventilated for 6 min with an aerosol of HSA and the radioactivity in the chest was monitored for 2 h with a gamma camera to determine whether the clearance rate would be a reliable assessment of lung epithelial permeability. Increased lung volumes were effected by application of 5 or 7 cm H 2 O positive end-expired pressure (5-PEEP and 7-PEEP, respectively). Lung injury was induced either by intravenous oleic acid (OA, 27-73 μl/kg) or inhalation of nitrogen dioxide (NO 2 , 80-100 ppm) for 2 h. Postmortem extravascular lung water volume (EVLW) provided an assessment of the degree of lung injury. Tracer clearance rates in animals receiving 5 or 7 cm H 2 O PEEP were not significantly different from controls (K = 0.15 ± 0.05 and 0.24 ± 0.10 vs 0.12 ± 0.03%/min, respectively, p > .05). Animals exposed to NO 2 had faster tracer clearance rates (K = 0.33 ± 0.21%/min, p 2 -exposed guinea pigs correlated well with injury as assessed by EVLW (r = .93, p 2 O PEEP (K = 0.58 ± 0.41%/min, EVLW = 8.1 ± 0.8 mL/g dry lung tissue, p < .05), but there was no correlation between these parameters in this injury model. It is concluded that imaging of the disappearance of radiolabeled HSA in the guinea pig can be a useful index of lung epithelial permeability, but this technique is limited to certain models of lung injury. 33 refs

A hybrid multibreath wash-in wash-out lung function quantification scheme in human subjects using hyperpolarized 3 He MRI for simultaneous assessment of specific ventilation, alveolar oxygen tension, oxygen uptake, and air trapping.

Science.gov (United States)

Hamedani, Hooman; Kadlecek, Stephen; Xin, Yi; Siddiqui, Sarmad; Gatens, Heather; Naji, Joseph; Ishii, Masaru; Cereda, Maurizio; Rossman, Milton; Rizi, Rahim

2017-08-01

To present a method for simultaneous acquisition of alveolar oxygen tension (P A O 2 ), specific ventilation (SV), and apparent diffusion coefficient (ADC) of hyperpolarized (HP) gas in the human lung, allowing reinterpretation of the P A O 2 and SV maps to produce a map of oxygen uptake (R). An imaging scheme was designed with a series of identical normoxic HP gas wash-in breaths to measure ADC, SV, P A O 2 , and R in less than 2 min. Signal dynamics were fit to an iterative recursive model that regionally solved for these parameters. This measurement was successfully performed in 12 subjects classified in three healthy, smoker, and chronic obstructive pulmonary disease (COPD) cohorts. The overall whole lung ADC, SV, P A O 2 , and R in healthy, smoker, and COPD subjects was 0.20 ± 0.03 cm 2 /s, 0.39 ± 0.06,113 ± 2 Torr, and 1.55 ± 0.35 Torr/s, respectively, in healthy subjects; 0.21 ± 0.03 cm 2 /s, 0.33 ± 0.06, 115.9 ± 4 Torr, and 0.97 ± 0.2 Torr/s, respectively, in smokers; and 0.25 ± 0.06 cm 2 /s, 0.23 ± 0.08, 114.8 ± 6.0Torr, and 0.94 ± 0.12 Torr/s, respectively, in subjects with COPD. Hetrogeneity of SV, P A O 2 , and R were indicators of both smoking-related changes and disease, and the severity of the disease correlated with the degree of this heterogeneity. Subjects with symptoms showed reduced oxygen uptake and specific ventilation. High-resolution, nearly coregistered and quantitative measures of lung function and structure were obtained with less than 1 L of HP gas. This hybrid multibreath technique produced measures of lung function that revealed clear differences among the cohorts and subjects and were confirmed by correlations with global lung measurements. Magn Reson Med 78:611-624, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Efficacy and safety of lung recruitment in pediatric patients with acute lung injury.

Science.gov (United States)

Boriosi, Juan P; Sapru, Anil; Hanson, James H; Asselin, Jeanette; Gildengorin, Ginny; Newman, Vivienne; Sabato, Katie; Flori, Heidi R

2011-07-01

To assess the safety and efficacy of a recruitment maneuver, the Open Lung Tool, in pediatric patients with acute lung injury and acute respiratory distress syndrome. Prospective cohort study using a repeated-measures design. Pediatric intensive care unit at an urban tertiary children's hospital. Twenty-one ventilated pediatric patients with acute lung injury. Recruitment maneuver using incremental positive end-expiratory pressure. The ratio of partial pressure of arterial oxygen over fraction of inspired oxygen (Pao2/Fio2 ratio) increased 53% immediately after the recruitment maneuver. The median Pao2/Fio2 ratio increased from 111 (interquartile range, 73-266) prerecruitment maneuver to 170 (interquartile range, 102-341) immediately postrecruitment maneuver (p interquartile range, 116-257) 4 hrs postrecruitment maneuver (p interquartile range, 127-236) 12 hrs postrecruitment maneuver (p interquartile range, 44-60) prerecruitment maneuver compared with 48 torr (interquartile range, 43-50) immediately postrecruitment maneuver (p = .69), 45 torr (interquartile range, 41-50) at 4 hrs postrecruitment maneuver (p interquartile range, 38-51) at 12 hrs postrecruitment maneuver. Recruitment maneuvers were well tolerated except for significant increase in Paco2 in three patients. There were no serious adverse events related to the recruitment maneuver. Using the modified open lung tool recruitment maneuver, pediatric patients with acute lung injury may safely achieve improved oxygenation and ventilation with these benefits potentially lasting up to 12 hrs postrecruitment maneuver.

Deconvoluting lung evolution: from phenotypes to gene regulatory networks

DEFF Research Database (Denmark)

Torday, J.S.; Rehan, V.K.; Hicks, J.W.

2007-01-01

other. Pathways of lung evolution are similar between crocodiles and birds but a low compliance of mammalian lung may have driven the development of the diaphragm to permit lung inflation during inspiration. To meet the high oxygen demands of flight, bird lungs have evolved separate gas exchange...... independent of ventilation as well as a unique mechanism for adjusting metabolic rate. Some of the most ancient oxygen-sensing molecules, i.e., hypoxia-inducible factor-1alpha and erythropoietin, are up-regulated during mammalian lung development and growth under apparently normoxic conditions, suggesting...

Topography of pulmonary structure and function in man using positron emission tomography (PET) with special reference to methodology and normal physiology

International Nuclear Information System (INIS)

Brundin, L.H.

1992-01-01

Positron emission tomography (PET) allows regional quantification of specific tracer compounds to be made within a tomographic slice of the body. The present thesis which is methodological and descriptive, centers on in vivo measurements of regional lung compartments (gas, red cells, plasma and extravascular tissue) and ventilation and blood flow in normal subjects. A method of measuring regional lung hematocrit (rH) was developed and rH was found to be found to be 90% of the peripheral hematocrit in normal subjects. No significant regional variations within the lung fields were found in normal subjects or in patients with anemia or pneumonia, which enables the pulmonary whole blood volume to be regionally quantified using a single vascular tracer. This allowed a deeper examination of the interrelationship between the different lung compartments and their variation in the gravity dependent axis and during hyperinflation. Smokers were found to have higher extravascular density than non-smokers. By combining measurement of ventilation and . V A / . Q, methods were developed to 1. correct the measured . V A / . Q for incomplete equilibrium of 13 N within the alveolar space. 2. calculate regional pulmonary perfusion. By further combining these measurements with measurements of vascular and extravascular lung volumes 1. relationship between ventilation and vascular and extravascular volumes were explored and found to be consistent with the theory that ventilation is determined by the elastic properties of lung tissue and 2. relationships between blood flow and blood volume (transit times) were investigated. We conclude that blood volume plays a significant role in the matching of ventilation and perfusion and that blood flow is fairly well matched by blood volumes, thus reducing the gravitational impact on capillary transit time and hematocrit ratio which might be of rheological importance. (au)

Fractional-Order Control of a Nonlinear Time-Delay System: Case Study in Oxygen Regulation in the Heart-Lung Machine

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S. J. Sadati

2012-01-01

Full Text Available A fractional-order controller will be proposed to regulate the inlet oxygen into the heart-lung machine. An analytical approach will be explained to satisfy some requirements together with practical implementation of some restrictions for the first time. Primarily a nonlinear single-input single-output (SISO time-delay model which was obtained previously in the literature is introduced for the oxygen generation process in the heart-lung machine system and we will complete it by adding some new states to control it. Thereafter, the system is linearized using the state feedback linearization approach to find a third-order time-delay dynamics. Consequently classical PID and fractional order controllers are gained to assess the quality of the proposed technique. A set of optimal parameters of those controllers are achieved through the genetic algorithm optimization procedure through minimizing a cost function. Our design method focuses on minimizing some famous performance criterions such as IAE, ISE, and ITSE. In the genetic algorithm, the controller parameters are chosen as a random population. The best relevant values are achieved by reducing the cost function. A time-domain simulation signifies the performance of controller with respect to a traditional optimized PID controller.

Vitamin D Depletion in Pregnancy Decreases Survival Time, Oxygen Saturation, Lung Weight and Body Weight in Preterm Rat Offspring

DEFF Research Database (Denmark)

Lykkedegn, Sine; Sorensen, Grith Lykke; Beck-Nielsen, Signe Sparre

2016-01-01

Animal studies suggest a role of vitamin D in fetal lung development although not studied in preterm animals. We tested the hypothesis that vitamin D depletion aggravates respiratory insufficiency in preterm rat offspring. Furthermore, the effects of vitamin D depletion on growth and lung...... surfactant were investigated. Female Sprague-Dawley rats were randomly assigned low vitamin D (VDL) or control diet before mating and followed with serum 25-hydroxyvitamin D (s-25(OH)D) determinations. After cesarean section at gestational day 19 (E19) or day 22 (E22), placental weight, birth weight, crown......-rump-length (CRL), oxygenation (SaO2) at 30 min and survival time were recorded. The pup lungs were analyzed for phospholipid levels, surfactant protein A-D mRNA and the expression of the vitamin D receptor (VDR). S-25(OH)D was significantly lower in the VDL group at cesarean section (12 vs. 30nmol/L, p

Mitochondrial Targeted Endonuclease III DNA Repair Enzyme Protects against Ventilator Induced Lung Injury in Mice

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Masahiro Hashizume

2014-08-01

Full Text Available The mitochondrial targeted DNA repair enzyme, 8-oxoguanine DNA glycosylase 1, was previously reported to protect against mitochondrial DNA (mtDNA damage and ventilator induced lung injury (VILI. In the present study we determined whether mitochondrial targeted endonuclease III (EndoIII which cleaves oxidized pyrimidines rather than purines from damaged DNA would also protect the lung. Minimal injury from 1 h ventilation at 40 cmH2O peak inflation pressure (PIP was reversed by EndoIII pretreatment. Moderate lung injury due to ventilation for 2 h at 40 cmH2O PIP produced a 25-fold increase in total extravascular albumin space, a 60% increase in W/D weight ratio, and marked increases in MIP-2 and IL-6. Oxidative mtDNA damage and decreases in the total tissue glutathione (GSH and the GSH/GSSH ratio also occurred. All of these indices of injury were attenuated by mitochondrial targeted EndoIII. Massive lung injury caused by 2 h ventilation at 50 cmH2O PIP was not attenuated by EndoIII pretreatment, but all untreated mice died prior to completing the two hour ventilation protocol, whereas all EndoIII-treated mice lived for the duration of ventilation. Thus, mitochondrial targeted DNA repair enzymes were protective against mild and moderate lung damage and they enhanced survival in the most severely injured group.

Inhibition of acid-induced lung injury by hyperosmolar sucrose in rats.

Science.gov (United States)

Safdar, Zeenat; Yiming, Maimiti; Grunig, Gabriele; Bhattacharya, Jahar

2005-10-15

Acid aspiration causes acute lung injury (ALI). Recently, we showed that a brief intravascular infusion of hyperosmolar sucrose, given concurrently with airway acid instillation, effectively blocks the ensuing ALI. The objective of the present study was to determine the extent to which intravascular infusion of hyperosmolar sucrose might protect against acid-induced ALI when given either before or after acid instillation. Our studies were conducted in anesthetized rats and in isolated, blood-perfused rat lungs. We instilled HCl through the airway, and we quantified lung injury in terms of the extravascular lung water (EVLW) content, filtration coefficient (Kfc), and cell counts and protein concentration in the bronchoalveolar lavage. We infused hyperosmolar sucrose via the femoral vein. In anesthetized rats, airway HCl instillation induced ALI as indicated by a 52% increase of EVLW and a threefold increase in Kfc. However, a 15-min intravenous infusion of hyperosmolar sucrose given up to 1 h before or 30 min after acid instillation markedly blunted the increases in EVLW, as well as the increases in cell count, and in protein concentration in the bronchoalveolar lavage. Hyperosmolar pretreatment also blocked the acid-induced increase of Kfc. Studies in isolated perfused lungs indicated that the protective effect of hyperosmolar sucrose was leukocyte independent. We conclude that a brief period of vascular hyperosmolarity protects against acid-induced ALI when the infusion is administered shortly before, or shortly after, acid instillation in the airway. The potential applicability of hyperosmolar sucrose in therapy for ALI requires consideration.

Influence of substrate composition on vitro oxygen consumption of ...

African Journals Online (AJOL)

The endogenous oxygen consumption of lung, liver and spleen slices is only slightly increased by glucose in an SRP medium compared with its effect on heart and kidney slices. Individual substrates which induced a highly significant increase in oxygen uptake of lung tissue were succinate, acetate, pyruvate and glucose, ...

Ex vivo lung perfusion with adenosine A2A receptor agonist allows prolonged cold preservation of lungs donated after cardiac death.

Science.gov (United States)

Wagner, Cynthia E; Pope, Nicolas H; Charles, Eric J; Huerter, Mary E; Sharma, Ashish K; Salmon, Morgan D; Carter, Benjamin T; Stoler, Mark H; Lau, Christine L; Laubach, Victor E; Kron, Irving L

2016-02-01

Ex vivo lung perfusion has been successful in the assessment of marginal donor lungs, including donation after cardiac death (DCD) donor lungs. Ex vivo lung perfusion also represents a unique platform for targeted drug delivery. We sought to determine whether ischemia-reperfusion injury would be decreased after transplantation of DCD donor lungs subjected to prolonged cold preservation and treated with an adenosine A2A receptor agonist during ex vivo lung perfusion. Porcine DCD donor lungs were preserved at 4°C for 12 hours and underwent ex vivo lung perfusion for 4 hours. Left lungs were then transplanted and reperfused for 4 hours. Three groups (n = 4/group) were randomized according to treatment with the adenosine A2A receptor agonist ATL-1223 or the dimethyl sulfoxide vehicle: Infusion of dimethyl sulfoxide during ex vivo lung perfusion and reperfusion (DMSO), infusion of ATL-1223 during ex vivo lung perfusion and dimethyl sulfoxide during reperfusion (ATL-E), and infusion of ATL-1223 during ex vivo lung perfusion and reperfusion (ATL-E/R). Final Pao2/Fio2 ratios (arterial oxygen partial pressure/fraction of inspired oxygen) were determined from samples obtained from the left superior and inferior pulmonary veins. Final Pao2/Fio2 ratios in the ATL-E/R group (430.1 ± 26.4 mm Hg) were similar to final Pao2/Fio2 ratios in the ATL-E group (413.6 ± 18.8 mm Hg), but both treated groups had significantly higher final Pao2/Fio2 ratios compared with the dimethyl sulfoxide group (84.8 ± 17.7 mm Hg). Low oxygenation gradients during ex vivo lung perfusion did not preclude superior oxygenation capacity during reperfusion. After prolonged cold preservation, treatment of DCD donor lungs with an adenosine A2A receptor agonist during ex vivo lung perfusion enabled Pao2/Fio2 ratios greater than 400 mm Hg after transplantation in a preclinical porcine model. Pulmonary function during ex vivo lung perfusion was not predictive of outcomes after transplantation. Copyright �

Oxidative Stress and Lung Ischemia-Reperfusion Injury

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Renata Salatti Ferrari

2015-01-01

Full Text Available Ischemia-reperfusion (IR injury is directly related to the formation of reactive oxygen species (ROS, endothelial cell injury, increased vascular permeability, and the activation of neutrophils and platelets, cytokines, and the complement system. Several studies have confirmed the destructiveness of the toxic oxygen metabolites produced and their role in the pathophysiology of different processes, such as oxygen poisoning, inflammation, and ischemic injury. Due to the different degrees of tissue damage resulting from the process of ischemia and subsequent reperfusion, several studies in animal models have focused on the prevention of IR injury and methods of lung protection. Lung IR injury has clinical relevance in the setting of lung transplantation and cardiopulmonary bypass, for which the consequences of IR injury may be devastating in critically ill patients.

Pyrrolidine dithiocarbamate administered during ex-vivo lung perfusion promotes rehabilitation of injured donor rat lungs obtained after prolonged warm ischemia.

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Cyril Francioli

Full Text Available Damaged lung grafts obtained after circulatory death (DCD lungs and warm ischemia may be at high risk of reperfusion injury after transplantation. Such lungs could be pharmacologically reconditioned using ex-vivo lung perfusion (EVLP. Since acute inflammation related to the activation of nuclear factor kappaB (NF-κB is instrumental in lung reperfusion injury, we hypothesized that DCD lungs might be treated during EVLP by pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB. Rat lungs exposed to 1h warm ischemia and 2 h cold ischemia were subjected to EVLP during 4h, in absence (CTRL group, N = 6 or in presence of PDTC (2.5g/L, PDTC group, N = 6. Static pulmonary compliance (SPC, peak airway pressure (PAWP, pulmonary vascular resistance (PVR, and oxygenation capacity were determined during EVLP. After EVLP, we measured the weight gain of the heart-lung block (edema, and the concentration of LDH (cell damage, proteins (permeability edema and of the cytokines IL-6, TNF-α and CINC-1 in bronchoalveolar lavage (BAL, and we evaluated NF-κB activation by the degree of phosphorylation and degradation of its inhibitor IκBα in lung tissue. In CTRL, we found significant NF-κB activation, lung edema, and a massive release of LDH, proteins and cytokines. SPC significantly decreased, PAWP and PVR increased, while oxygenation tended to decrease. Treatment with PDTC during EVLP inhibited NF-κB activation, did not influence LDH release, but markedly reduced lung edema and protein concentration in BAL, suppressed TNFα and IL-6 release, and abrogated the changes in SPC, PAWP and PVR, with unchanged oxygenation. In conclusion, suppression of innate immune activation during EVLP using the NF-κB inhibitor PDTC promotes significant improvement of damaged rat DCD lungs. Future studies will determine if such rehabilitated lungs are suitable for in vivo transplantation.

Increased permeability-oedema and atelectasis in pulmonary dysfunction after trauma and surgery: a prospective cohort study

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Groeneveld AB Johan

2007-07-01

Full Text Available Abstract Background Trauma and surgery may be complicated by pulmonary dysfunction, acute lung injury (ALI and acute respiratory distress syndrome (ARDS, but the mechanisms are incompletely understood. Methods We evaluated lung capillary protein permeability non-invasively with help of the 67Ga-transferrin pulmonary leak index (PLI technique and extravascular lung water (EVLW by the transpulmonary thermal-dye dilution technique in consecutive, mechanically ventilated patients in the intensive care unit within 24 h of direct, blunt thoracic trauma (n = 5, 2 with ARDS, and within 12 h of indirect trauma by transhiatal oesophagectomy (n = 8, abdominal surgery for cancer (n = 6 and bone surgery (n = 4. We studied transfusion history, haemodynamics, oxygenation and mechanics of the lungs. The lung injury score (LIS, 0–4 was calculated. Plain radiography was also done to judge densities and atelectasis. Results The PLI and EVLW were elevated above normal in 61 and 30% of patients, respectively, and the PLI directly related to the number of red cell concentrates given (rs = 0.69, P s = 0.55, P = 0.007. Thoracic trauma patients had a worse oxygenation requiring higher airway pressures and thus higher LIS than the other patient groups, unrelated to PLI and EVLW but attributable to a higher cardiac output and thereby venous admixture. Finally, patients with radiographic signs of atelectasis had more impaired oxygenation and more densities than those without. Conclusion The oxygenation defect and radiographic densities in mechanically ventilated patients with pulmonary dysfunction and ALI/ARDS after trauma and surgery are likely caused by atelectasis rather than by increased permeability-oedema related to red cell transfusion.

Influence of vascular network design on gas transfer in lung assist device technology.

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Bassett, Erik K; Hoganson, David M; Lo, Justin H; Penson, Elliot J N; Vacanti, Joseph P

2011-01-01

Blood oxygenators are vital for the critically ill, but their use is limited to the hospital setting. A portable blood oxygenator or a lung assist device for ambulatory or long-term use would greatly benefit patients with chronic lung disease. In this work, a biomimetic blood oxygenator system was developed which consisted of a microfluidic vascular network covered by a gas permeable silicone membrane. This system was used to determine the influence of key microfluidic parameters-channel size, oxygen exposure length, and blood shear rate-on blood oxygenation and carbon dioxide removal. Total gas transfer increased linearly with flow rate, independent of channel size and oxygen exposure length. On average, CO(2) transfer was 4.3 times higher than oxygen transfer. Blood oxygen saturation was also found to depend on the flow rate per channel but in an inverse manner; oxygenation decreased and approached an asymptote as the flow rate per channel increased. These relationships can be used to optimize future biomimetic vascular networks for specific lung applications: gas transfer for carbon dioxide removal in patients with chronic obstructive pulmonary disease or oxygenation for premature infants requiring complete lung replacement therapy.

Ischemia and reperfusion of the lung tissues induced increase of lung permeability and lung edema is attenuated by dimethylthiourea (PP69).

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Chen, K H; Chao, D; Liu, C F; Chen, C F; Wang, D

2010-04-01

This study sought to determine whether oxygen radical scavengers of dimethylthiourea (DMTU), superoxide dismutase (SOD), or catalase (CAT) pretreatment attenuated ischemia-reperfusion (I/R)-induced lung injury. After isolation from a Sprague-Dawley rat, the lungs were perfused through the pulmonary artery cannula with rat whole blood diluted 1:1 with a physiological salt solution. An acute lung injury was induced by 10 minutes of hypoxia with 5% CO2-95% N2 followed by 65 minutes of ischemia and then 65 minutes of reperfusion. I/R significantly increased microvascular permeability as measured by the capillary filtration coefficient (Kfc), lung weight-to-body weight ratio (LW/BW), and protein concentration in bronchoalveolar lavage fluid (PCBAL). DMTU pretreatment significantly attenuated the acute lung injury. The capillary filtration coefficient (P<.01), LW/BW (P<.01) and PCBAL (P<.05) were significantly lower among the DMTU-treated rats than hosts pretreated with SOD or CAT. The possible mechanisms of the protective effect of DMTU in I/R-induced lung injury may relate to the permeability of the agent allowing it to scavenge intracellular hydroxyl radicals. However, whether superoxide dismutase or catalase antioxidants showed protective effects possibly due to their impermeability of the cell membrane not allowing scavenging of intracellular oxygen radicals. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Comparative analysis of parameters of oxygenation, ventilation and acid-base status during intraoperative application of conventional and protective lung ventilation

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Videnović N.

2015-01-01

Full Text Available The aim of this study was to perform a comparative analysis applied conventional (traditional and protective mechanical lung ventilation in clinical conditions with regard to intraoperative parameters changes of oxygenation, ventilation and acid-base status. This was a prospective study that included 240 patients. All patients underwent the same elective surgery (classic cholecystectomy. Patients were divided into two groups of 120 patients, A and B. In group A during the operation had received conventional lung ventilation with tidal volume of 10-15 ml/kg body weight, respiratory rate 12/min. and a PEEP zero. In group B was applied protective lung ventilation with a tidal volume of 6-8 ml/kg body weight, respiratory rate 12/min. and a PEEP of 7 mbar. Monitoring of oxygenation included the monitoring SaO2 and PaO2. Monitoring of ventilation included the determination of the value of tidal volume and minute volume ventilation, peak inspiratory pressure (Ppeak, medium pressure in the airway (Paw.mean, PEEP, PaCO2 and EtCO2. Monitoring of acid-base status was performed via determination of the pH values of arterial blood. Monitoring was carried out in four intervals: T1 - 5-10 minutes after the establishment of the airway, T2 - after opening peritoneum, T3 - after removal of the gallbladder, T4 - after the closure of the abdominal wall. All monitoring results are presented as mean. The statistical significance of differences in mean values was tested by t - test mean values in the case of two independent samples. As a statistical significance test taken as standard values p <0.01 and p <0.001. Comparative analysis of the value of SaO2, PaO2, Ppeak did not reach statistical significance. Statistical significance there is in the analysis of values of tidal volume and Paw.mean (p <0.001. Analysis of PaCO2 and pH of arterial blood showed no statistical significance in the first interval measurements but did interval T2-T4 (p <0.001. Based on the

The heart as an extravascular target of endothelin-1 in ...

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Exposure to particulate matter air pollution has been causally linked to cardiovascular disease in humans. Several broad and overlapping hypotheses describing the biological mechanisms by which particulate matter exposure leads to cardiovascular disease and cardiac dysfunction have been explored, though linkage with specific factors or genes remains limited. Given evidence pointing to autocrine/paracrine signaling systems as modulators of cardiac dysfunction, the present review highlights the emerging role of endothelins as mediators of cardiac dysfunction following particulate matter exposure. Endothelin-1 is a small multifunctional protein expressed in the pulmonary and cardiovascular system, known for its ability to constrict blood vessels. Although endothelin-1 can also directly and indirectly (via secondary signaling events) modulate cardiac contractility, heart rate, and rhythm, research on the role of endothelins in the context of air pollution has tended to focus on the vascular effects. The plausibility of endothelin as a mechanism underlying particulate matter-induced cardiac dysfunction is further supported by the therapeutic utility of certain endothelin receptor antagonists. Extravascular effects of endothelin on the heart could better explain one mechanism by which particulate matter exposure may lead to cardiac dysfunction. We propose and support the novel hypothesis that autocrine/paracrine signaling systems, such as endothelins, mediate cardiac

Transmission of arterial oxygen partial pressure oscillations to the cerebral microcirculation in a porcine model of acute lung injury caused by cyclic recruitment and derecruitment.

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Klein, K U; Boehme, S; Hartmann, E K; Szczyrba, M; Heylen, L; Liu, T; David, M; Werner, C; Markstaller, K; Engelhard, K

2013-02-01

Cyclic recruitment and derecruitment (R/D) play a key role in the pathomechanism of acute lung injury (ALI) leading to respiration-dependent oscillations of arterial partial pressure of oxygen (Pa(O(2))). These Pa(O(2)) oscillations could also be forwarded to the cerebral microcirculation. In 12 pigs, partial pressure of oxygen was measured in the thoracic aorta (Pa(O(2))) and subcortical cerebral tissue (Pbr(O(2))). Cerebral cortical haemoglobin oxygen saturation (Sbr(O(2))), cerebral blood flow (CBF), and peripheral haemoglobin saturation (Sp(O(2))) were assessed by spectroscopy and laser Doppler flowmetry. Measurements at different fractions of inspired oxygen (F(I(O(2)))) were performed at baseline and during cyclic R/D. frequency domain analysis, the Mann-Whitney test, linear models to test the influence of Pa(O(2)) and systolic arterial pressure (SAP) oscillations on cerebral measurements. Parameters [mean (SD)] remained stable during baseline. Pa(O(2)) oscillations [10.6 (8) kPa, phase(reference)], systemic arterial pressure (SAP) oscillations [20 (9) mm Hg, phase(Pa(O(2))-SAP) -33 (72)°], and Sp(O(2))oscillations [1.9 (1.7)%, phase(Pa(O(2))-Sp(O(2))) 264 (72)°] were detected during lung R/D at 1.0. Pa(O(2)) oscillations decreased [2.7 (3.5) kPa, P=0.0008] and Sp(O(2)) oscillations increased [6.8 (3.9)%, P=0.0014] at F(I(O(2))) 0.3. In the brain, synchronized Pbr(O(2)) oscillations [0.6 (0.4) kPa, phase(Pa(O(2))-Pbr(O(2))) 90 (39)°], Sbr(O(2)) oscillations [4.1 (1.5)%, phase(Pa(O(2))-Sbr(O(2))) 182 (54)°], and CBF oscillations [198 (176) AU, phase(Pa(O(2))-CBF) 201 (63)°] occurred that were dependent on Pa(O(2)) and SAP oscillations. Pa(O(2)) oscillations caused by cyclic R/D are transmitted to the cerebral microcirculation in a porcine model of ALI. These cyclic oxygen alterations could play a role in the crosstalk of acute lung and brain injury.

First Danish experience with ex vivo lung perfusion of donor lungs before transplantation.

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Henriksen, Ian Sune Iversen; Møller-Sørensen, Hasse; Møller, Christian Holdfold; Zemtsovski, Mikhail; Nilsson, Jens Christian; Seidelin, Casper Tobias; Perch, Michael; Iversen, Martin; Steinbrüchel, Daniel

2014-03-01

The number of lung transplantations is limited by a general lack of donor organs. Ex vivo lung perfusion (EVLP) is a novel method to optimise and evaluate marginal donor lungs prior to transplantation. We describe our experiences with EVLP in Denmark during the first year after its introduction. The study was conducted by prospective registration of donor offers and lung transplantations in Denmark from 1 May 2012 to 30 April 2013. Donor lungs without any contraindications were transplanted in the traditional manner. Taken for EVLP were donor lungs that were otherwise considered transplantable, but failed to meet the usual criteria due to possible contusions or because they were from donors with sepsis or unable to pass the oxygenation test. In the study period, seven of 33 Danish lung transplantations were made possible due to EVLP. One patient died of non-EVLP-related causes, but all other recipients were alive with normal graft function at the end of our registration period. All lungs showed an improved PaO2/FiO2 ratio from a median 23.1 kPa (8.8-38.9) within the donor to 58.8 kPa (34.9-76.5) (FiO2 = 1.0) after EVLP, which corresponds to a 155% improved oxygenation. The median time to extubation, time in intensive care unit and the admission period were 1, 7 and 39 days, respectively. In the first year after the introduction of EVLP in Denmark, seven pairs of donor lungs that previously would have been rejected have been transplanted as a result of their improved function. EVLP seems to be a safe way to increase the use of marginal donor lungs. no funding was granted for the present paper. not relevant.

Interstitial lung disease: Diagnostic approach

OpenAIRE

Kaushik Saha

2014-01-01

Interstitial lung disease (ILD) is a final common pathway of a broad heterogeneous group of parenchymal lung disorders. It is characterized by progressive fibrosis of the lung leading to restriction and diminished oxygen transfer. Clinically, the presenting symptoms of ILD are non-specific (cough and progressive dyspnea on exertion) and are often attributed to other diseases, thus delaying diagnosis and timely therapy. Clues from the medical history along with the clinical context and radiolo...

Discrepancy between severity of lung impairment and seniority on the lung transplantation list.

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Travaline, J M; Cordova, F C; Furukawa, S; Criner, G J

2004-12-01

Organ allocation for lung transplantation, based mainly on accrued time on a waiting list, may not be an equitable system of organ allocation. To provide an objective view of the current practice concerning lung allocation, and timing for transplantation, we examined illness severity and list seniority in patients on a lung transplantation waiting list. Adult patients awaiting lung transplantation underwent testing for mean pulmonary artery pressure (mPpa), maximum oxygen consumption (VO2 max), 6-minute walk distance (6MWD), forced expiratory volume in 1 second, mean partial pressure of carbon dioxide, partial pressure of oxygen/fractional concentration of inspired oxygen, and diffusing capacity of the lung for carbon monoxide. Relationships between physiological variables and waiting list rankings were then determined. Thirty-four patients were tested and there was no correlation between time spent waiting on the list and mPpa (r=0.01; P=.94), VO2 max percentage predicted (r=0.07; P=.71), or 6MWD (r=0.15; P=.42). Many patients with functional impairments as indicated by low maximum VO2 or by short 6MWD are scheduled to receive their transplant after patients with levels that indicate a lower degree of risk. When compared with a hypothetical reranking based on mean Ppa, 24 of the 34 patients (71%) on our current waiting list were found to be 5 positions higher or lower than this new risk-based ranking. Sixteen patients (47%) were 10 or more positions away from their hypothetical severity-based ranking, and 9 (26%) were at least 15 positions out of place. Sixteen of the 34 patients were ranked lower than they would be based on a severity of illness using the pulmonary artery pressure alone, 17 were ranked higher than "should be" based on pulmonary artery mean, and only 1 patient (ranked in position 15) was appropriately positioned based on seniority and severity of disease based on PA mean. Rank order for lung transplantation has no relationship with illness

Comparison of lung protective ventilation strategies in a rabbit model of acute lung injury.

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Rotta, A T; Gunnarsson, B; Fuhrman, B P; Hernan, L J; Steinhorn, D M

2001-11-01

To determine the impact of different protective and nonprotective mechanical ventilation strategies on the degree of pulmonary inflammation, oxidative damage, and hemodynamic stability in a saline lavage model of acute lung injury. A prospective, randomized, controlled, in vivo animal laboratory study. Animal research facility of a health sciences university. Forty-six New Zealand White rabbits. Mature rabbits were instrumented with a tracheostomy and vascular catheters. Lavage-injured rabbits were randomized to receive conventional ventilation with either a) low peak end-expiratory pressure (PEEP; tidal volume of 10 mL/kg, PEEP of 2 cm H2O); b) high PEEP (tidal volume of 10 mL/kg, PEEP of 10 cm H2O); c) low tidal volume with PEEP above Pflex (open lung strategy, tidal volume of 6 mL/kg, PEEP set 2 cm H2O > Pflex); or d) high-frequency oscillatory ventilation. Animals were ventilated for 4 hrs. Lung lavage fluid and tissue samples were obtained immediately after animals were killed. Lung lavage fluid was assayed for measurements of total protein, elastase activity, tumor necrosis factor-alpha, and malondialdehyde. Lung tissue homogenates were assayed for measurements of myeloperoxidase activity and malondialdehyde. The need for inotropic support was recorded. Animals that received a lung protective strategy (open lung or high-frequency oscillatory ventilation) exhibited more favorable oxygenation and lung mechanics compared with the low PEEP and high PEEP groups. Animals ventilated by a lung protective strategy also showed attenuation of inflammation (reduced tracheal fluid protein, tracheal fluid elastase, tracheal fluid tumor necrosis factor-alpha, and pulmonary leukostasis). Animals treated with high-frequency oscillatory ventilation had attenuated oxidative injury to the lung and greater hemodynamic stability compared with the other experimental groups. Both lung protective strategies were associated with improved oxygenation, attenuated inflammation, and

First Danish experience with ex vivo lung perfusion of donor lungs before transplantation

DEFF Research Database (Denmark)

Henriksen, Ian Sune Iversen; Møller-Sørensen, Hasse; Møller, Christian Holdfold

2014-01-01

INTRODUCTION: The number of lung transplantations is limited by a general lack of donor organs. Ex vivo lung perfusion (EVLP) is a novel method to optimise and evaluate marginal donor lungs prior to transplantation. We describe our experiences with EVLP in Denmark during the first year after its...... introduction. MATERIAL AND METHODS: The study was conducted by prospective registration of donor offers and lung transplantations in Denmark from 1 May 2012 to 30 April 2013. Donor lungs without any contraindications were transplanted in the traditional manner. Taken for EVLP were donor lungs that were...... otherwise considered transplantable, but failed to meet the usual criteria due to possible contusions or because they were from donors with sepsis or unable to pass the oxygenation test. RESULTS: In the study period, seven of 33 Danish lung transplantations were made possible due to EVLP. One patient died...

Alveolar and serum concentrations of imipenem in two lung transplant recipients supported with extracorporeal membrane oxygenation.

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Welsch, C; Augustin, P; Allyn, J; Massias, L; Montravers, P; Allou, N

2015-02-01

Venovenous extracorporeal membrane oxygenation (ECMO) is increasingly used in patients with respiratory failure who fail conventional treatment. Postoperative pneumonia is the most common infection after lung transplantation (40%). Imipenem is frequently used for empirical treatment of nosocomial pneumonia in the intensive care unit. Nevertheless, few data are available on the impact of ECMO on pharmacokinetics, and no data on imipenem dosing during ECMO. Currently, no guidelines exist for antibiotic dosing during ECMO support. We report the cases of 2 patients supported with venovenous ECMO for refractory acute respiratory distress syndrome following single lung transplantation for pulmonary fibrosis, treated empirically with 1 g of imipenem intravenously every 6 h. Enterobacter cloacae was isolated from the respiratory sample of Patient 1 and Klebsiella pneumoniae was isolated from the respiratory sample of Patient 2. Minimum inhibitory concentrations of the 2 isolated strains were 0.125 and 0.25 mg/L, respectively. Both patients were still alive on day 28. This is the first report, to our knowledge, of imipenem concentrations in lung transplantation patients supported with ECMO. This study confirms high variability in imipenem trough concentrations in patients on ECMO and with preserved renal function. An elevated dosing regimen (4 g/24 h) is more likely to optimize drug exposure, and therapeutic drug monitoring is recommended, where available. Population pharmacokinetic studies are indicated to develop evidence-based dosing guidelines for ECMO patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Methylene Blue in Ventilator-Induced Lung Injury after Pneumonectomy: an Experimental Study

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Ye. V Suborov

2007-01-01

Full Text Available Objective: to study the expediency and efficiency of using methylene blue (MB on a model of pneumectomy (PE and subsequent ventilator-induced lung injury (VILI in sheep. Materials and methods. The study was conducted at the Research Laboratory of University of Tromse. The experiment included 23 sheep weighing 41.0±4.9 kg. Thoracotomy and right-sided pneumonectomy were performed in the animals under general anesthesia and controlled artificial ventilation. After measurement of the parameters of systemic hemodynamics and extravascular water of the lung (EVWL, the animals were divided into 3 groups: 1 a control group (CG, n=7 with a tidal volume (TV of 6 ml/kg and an end-expiratory positive pressure (PEEP of 2 cm H2O; 2 a VILI group (n=9 with a TV of 12 ml/kg and a PEEP of 0 cm H2O; 3 a group of MB (n=7 that was given in parallel with a damaging ventilation mode. The thermodilution technique (using a Cold Z-021 monitor, (Pulsion, Germany was employed to measure volumetric parameters and EVWL. The parameters of pulmonary hemodynamics, respiratory mechanics, and blood gas composition were recorded. Results: After its reduction at PE, EVWL index increased during damaging ventilation in the VILI and MB groups. In addition, there was an increase in pulmonary artery wedge pressure after PE in the MB and VILI groups. In the latter group, arterial hypoxemia was observed at the end of the experiment. Along with this, after PE pulmonary compliance decreased and airway pressure elevated in the VILI and MB groups. Conclusion: In the presented model of VILI, MB does not prevent the development of postp-neumectomic edema of the lung. Key words: thermochromodilution, acute lung injury, pneumectomy, ventilator-induced lung injury, postpneumectomic edema of the lung, methylene blue.

Positive end expiratory pressure during one-lung ventilation: Selecting ideal patients and ventilator settings with the aim of improving arterial oxygenation

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Hoftman Nir

2011-01-01

Full Text Available The efficacy of positive end-expiratory pressure (PEEP in treating intraoperative hypoxemia during one-lung ventilation (OLV remains in question given conflicting results of prior studies. This study aims to (1 evaluate the efficacy of PEEP during OLV, (2 assess the utility of preoperative predictors of response to PEEP, and (3 explore optimal intraoperative settings that would maximize the effects of PEEP on oxygenation. Forty-one thoracic surgery patients from a single tertiary care university center were prospectively enrolled in this observational study. After induction of general anesthesia, a double-lumen endotracheal tube was fiberoptically positioned and OLV initiated. Intraoperatively, PEEP = 5 and 10 cmH 2 O were sequentially applied to the ventilated lung during OLV. Arterial oxygenation, cardiovascular performance parameters, and proposed perioperative variables that could predict or enhance response to PEEP were analysed. T-test and c2 tests were utilized for continuous and categorical variables, respectively. Multivariate analyses were carried out using a classification tree model of binary recursive partitioning. PEEP improved arterial oxygenation by ≥20% in 29% of patients (n = 12 and failed to do so in 71% (n = 29; however, no cardiovascular impact was noted. Among the proposed clinical predictors, only intraoperative tidal volume per kilogram differed significantly between responders to PEEP and non-responders (mean 6.6 vs. 5.7 ml/kg, P = 0.013; no preoperative variable predicted response to PEEP. A multivariate analysis did not yield a clinically significant model for predicting PEEP responsiveness. PEEP improved oxygenation in a subset of patients; larger, although still protective tidal volumes favored a positive response to PEEP. No preoperative variables, however, could be identified as reliable predictors for PEEP responders.

Urokinase Plasminogen Activator Receptor-Deficient Mice Demonstrate Reduced Hyperoxia-Induced Lung Injury

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van Zoelen, Marieke A. D.; Florquin, Sandrine; de Beer, Regina; Pater, Jennie M.; Verstege, Marleen I.; Meijers, Joost C. M.; van der Poll, Tom

2009-01-01

Patients with respiratory failure often require supplemental oxygen therapy and mechanical ventilation. Although both supportive measures are necessary to guarantee adequate oxygen uptake, they can also cause or worsen lung inflammation and injury. Hyperoxia-induced lung injury is characterized by

Whole lung lavage with intermittent double lung ventilation. A modified technique for managing pulmonary alveolar proteinosis

International Nuclear Information System (INIS)

Ahmed, Raees; Iqbal, Mobeen; Kashef, Sayed H.; Almomatten, Mohammed I.

2005-01-01

Whole lung lavage is still the most effective treatment for pulmonary alveolar proteinosis. We report a 21-year-old male diagnosed with pulmonary alveolar proteinosis by open lung biopsy and who underwent whole lung lavage with a modified technique. He showed significant improvement in clinical and functional parameters. The technique of intermittent double lung ventilation during lavage procedure keeps the oxygen saturation in acceptable limits in patients at risk for severe hypoxemia and allows the procedure to be completed in a single setting. (author)

Oxygen-enhanced magnetic resonance ventilation imaging of lung

International Nuclear Information System (INIS)

Ohno, Yoshiharu; Chen Qun; Hatabu, Hiroto

2001-01-01

The oxygen-enhanced magnetic resonance (MR) ventilation imaging is a new technique, and the full extent of its physiological significance has not been elucidated. This review article includes background on (1) respiratory physiology; (2) mechanism and optimization of oxygen-enhanced MR imaging technique; (3) recent applications in animal and human models; and (4) merits and demerits of the technique in comparison with hyperpolarized noble gas MR ventilation imaging. Application of oxygen-enhanced MR ventilation imaging to patients with pulmonary diseases has been very limited. However, we believe that further basic studies, as well as clinical applications of this new technique will define the real significance of oxygen-enhanced MR ventilation imaging in the future of pulmonary functional imaging and its usefulness for diagnostic radiology

A Case of Pulmonary Tumor Thrombotic Microangiopathy Diagnosed by Transbronchial Lung Biopsy and Treated with Chemotherapy and Long-Term Oxygen and Anticoagulation Therapies

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Atsushi Kitamura

2013-01-01

Full Text Available A 41-year-old woman, who underwent breast resection for cancer of the right breast and adjuvant chemotherapy 2 years ago, was admitted to our hospital due to shortness of breath upon exertion. High-resolution computed tomography of the chest showed small nodular opacities in the peribronchiolar area in both lungs, as well as mediastinal and hilar lymphadenopathy. A transbronchial lung biopsy revealed breast cancer metastasis and pulmonary tumor thrombotic microangiopathy (PTTM. Treatment of PTTM is rarely reported due to the difficulty of antemortem diagnosis; however, the patient was effectively treated with chemotherapy and oxygen and anticoagulation therapies for 3 months.

Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue.

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Sakadzić, Sava; Roussakis, Emmanuel; Yaseen, Mohammad A; Mandeville, Emiri T; Srinivasan, Vivek J; Arai, Ken; Ruvinskaya, Svetlana; Devor, Anna; Lo, Eng H; Vinogradov, Sergei A; Boas, David A

2010-09-01

Measurements of oxygen partial pressure (pO(2)) with high temporal and spatial resolution in three dimensions is crucial for understanding oxygen delivery and consumption in normal and diseased brain. Among existing pO(2) measurement methods, phosphorescence quenching is optimally suited for the task. However, previous attempts to couple phosphorescence with two-photon laser scanning microscopy have faced substantial difficulties because of extremely low two-photon absorption cross-sections of conventional phosphorescent probes. Here we report to our knowledge the first practical in vivo two-photon high-resolution pO(2) measurements in small rodents' cortical microvasculature and tissue, made possible by combining an optimized imaging system with a two-photon-enhanced phosphorescent nanoprobe. The method features a measurement depth of up to 250 microm, sub-second temporal resolution and requires low probe concentration. The properties of the probe allowed for direct high-resolution measurement of cortical extravascular (tissue) pO(2), opening many possibilities for functional metabolic brain studies.

Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue

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Sakadžić, Sava; Roussakis, Emmanuel; Yaseen, Mohammad A.; Mandeville, Emiri T.; Srinivasan, Vivek J.; Arai, Ken; Ruvinskaya, Svetlana; Devor, Anna; Lo, Eng H.; Vinogradov, Sergei A.; Boas, David A.

2010-01-01

The ability to measure oxygen partial pressure (pO2) with high temporal and spatial resolution in three dimensions is crucial for understanding oxygen delivery and consumption in normal and diseased brain. Among existing pO2 measurement methods, phosphorescence quenching is optimally suited for the task. However, previous attempts to couple phosphorescence with two-photon laser scanning microscopy have faced substantial difficulties because of extremely low two-photon absorption cross-sections of conventional phosphorescent probes. Here, we report the first practical in vivo two-photon high-resolution pO2 measurements in small rodents’ cortical microvasculature and tissue, made possible by combining an optimized imaging system with a two-photon-enhanced phosphorescent nanoprobe. The method features a measurement depth of up to 250 µm, sub-second temporal resolution and requires low probe concentration. Most importantly, the properties of the probe allowed for the first direct high-resolution measurement of cortical extravascular (tissue) pO2, opening numerous possibilities for functional metabolic brain studies. PMID:20693997

The experimental study of oxygen contrast MR ventilation imaging

International Nuclear Information System (INIS)

Yang Jian; Guo Youmin; Wu Xiaoming; Xi Nong; Wang Jianguo; Zhu Li; Lei Xiaoyan; Xie Enyi

2003-01-01

Objective: To study the feasibility and basic technology of the oxygen contrast MR ventilation imaging in lung. Methods: Six canine lungs were scanned by using inversion recovery pulse sequence with turbo spin echo acquisition before and after inhalation of the 100% oxygen as T 1 contrast agent, and the T 1 values were measured. The contrast-to-noise ratio (CNR) for each inversion recovery time was compared and the relationship between arterial blood oxygen pressure (PaO 2 ) and T 1 relaxation rate was observed. Subtraction technique was employed in the postprocessing of pre- and post-oxygen conditions. Results: Molecular oxygen could shorten the pulmonary T 1 value (average 13.37%, t=2.683, P 1 value of pre- and post-oxygen conditions. The relaxtivity of T 1 resulted in excellent linear correlation (r 2 =0.9974) with PaO 2 . Through the subtraction of pre- and post-oxygen image, the oxygen contrast MR ventilation -image was obtained. Conclusion: The oxygen contrast MR ventilation imaging has the feasibility and clinical potential for the assessment of regional pulmonary function

Bilateral versus single lung transplant for idiopathic pulmonary fibrosis.

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Lehmann, Sven; Uhlemann, Madlen; Leontyev, Sergey; Seeburger, Joerg; Garbade, Jens; Merk, Denis R; Bittner, Hartmuth B; Mohr, Friedrich W

2014-10-01

It is unknown if uni- or bilateral lung transplant is best for treatment of usual idiopathic pulmonary fibrosis. We reviewed our single-center experience comparing both treatments. Between 2002 and 2011, one hundred thirty-eight patients at our institution underwent a lung transplant. Of these, 58 patients presented with idiopathic pulmonary fibrosis (56.9%) and were the focus of this study. Thirty-nine patients received a single lung transplant and 19 patients a bilateral sequential lung transplant. The mean patient age was 54 ± 10 years, and 69% were male. The intraoperative course was uneventful, save for 7 patients who needed extracorporeal membrane oxygenation support. Three patients had respiratory failure before the lung transplant that required mechanical ventilation and was supported by extracorporeal membrane oxygenation. Elevated pulmonary artery pressure > 40 mm Hg was identified as an independent predictor of early mortality by uni- and multivariate analysis (P = .01; OR 9.7). Using a Cox regression analysis, postoperative extracorporeal membrane oxyge-nation therapy (P = .01; OR 10.2) and the need for > 10 red blood cell concentrate during the first 72 hours after lung transplant (P = .01; OR 5.6) were independent predictors of long-term survival. Actuarial survival at 1 and 5 years was 65.6% and 55.3%, with no significant between-group differences (70.6% and 54.3%). Lung transplant is a safe and curative treatment for idiopathic pulmonary fibrosis. According to our results, unilateral lung transplant for idiopathic pulmonary fibrosis is an alternative to bilateral lung transplant and may affect the allocation process.

Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo

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Kawamura, Tomohiro; Wakabayashi, Nobunao; Shigemura, Norihisa; Huang, Chien-Sheng; Masutani, Kosuke; Tanaka, Yugo; Noda, Kentaro; Peng, Ximei; Takahashi, Toru; Billiar, Timothy R.; Okumura, Meinoshin; Toyoda, Yoshiya; Kensler, Thomas W.

2013-01-01

Hyperoxic lung injury is a major concern in critically ill patients who receive high concentrations of oxygen to treat lung diseases. Successful abrogation of hyperoxic lung injury would have a huge impact on respiratory and critical care medicine. Hydrogen can be administered as a therapeutic medical gas. We recently demonstrated that inhaled hydrogen reduced transplant-induced lung injury and induced heme oxygenase (HO)-1. To determine whether hydrogen could reduce hyperoxic lung injury and investigate the underlying mechanisms, we randomly assigned rats to four experimental groups and administered the following gas mixtures for 60 h: 98% oxygen (hyperoxia), 2% nitrogen; 98% oxygen (hyperoxia), 2% hydrogen; 98% balanced air (normoxia), 2% nitrogen; and 98% balanced air (normoxia), 2% hydrogen. We examined lung function by blood gas analysis, extent of lung injury, and expression of HO-1. We also investigated the role of NF-E2-related factor (Nrf) 2, which regulates HO-1 expression, by examining the expression of Nrf2-dependent genes and the ability of hydrogen to reduce hyperoxic lung injury in Nrf2-deficient mice. Hydrogen treatment during exposure to hyperoxia significantly improved blood oxygenation, reduced inflammatory events, and induced HO-1 expression. Hydrogen did not mitigate hyperoxic lung injury or induce HO-1 in Nrf2-deficient mice. These findings indicate that hydrogen gas can ameliorate hyperoxic lung injury through induction of Nrf2-dependent genes, such as HO-1. The findings suggest a potentially novel and applicable solution to hyperoxic lung injury and provide new insight into the molecular mechanisms and actions of hydrogen. PMID:23475767

Glutamine Attenuates Acute Lung Injury Caused by Acid Aspiration

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Chih-Cheng Lai

2014-08-01

Full Text Available Inadequate ventilator settings may cause overwhelming inflammatory responses associated with ventilator-induced lung injury (VILI in patients with acute respiratory distress syndrome (ARDS. Here, we examined potential benefits of glutamine (GLN on a two-hit model for VILI after acid aspiration-induced lung injury in rats. Rats were intratracheally challenged with hydrochloric acid as a first hit to induce lung inflammation, then randomly received intravenous GLN or lactated Ringer’s solution (vehicle control thirty min before different ventilator strategies. Rats were then randomized to receive mechanical ventilation as a second hit with a high tidal volume (TV of 15 mL/kg and zero positive end-expiratory pressure (PEEP or a low TV of 6 mL/kg with PEEP of 5 cm H2O. We evaluated lung oxygenation, inflammation, mechanics, and histology. After ventilator use for 4 h, high TV resulted in greater lung injury physiologic and biologic indices. Compared with vehicle treated rats, GLN administration attenuated lung injury, with improved oxygenation and static compliance, and decreased respiratory elastance, lung edema, extended lung destruction (lung injury scores and lung histology, neutrophil recruitment in the lung, and cytokine production. Thus, GLN administration improved the physiologic and biologic profiles of this experimental model of VILI based on the two-hit theory.

Maintaining Oxygenation Successfully with High Flow Nasal Cannula during Diagnostic Bronchoscopy on a Postoperative Lung Transplant Patient in the Intensive Care

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Sara Diab

2014-01-01

Full Text Available Bronchoscopy is an important diagnostic and therapeutic intervention for a variety of patients displaying pulmonary pathology. The heterogeneity of the patients undergoing bronchoscopy affords a challenge for providing minimal and safe respiratory support during anesthesia. Currently, options are intubation and general anesthesia versus frequently inadequate sedation or local anaesthesia with low flow oxygen through nasal prongs or mouthpiece. The advent of high flow nasal cannula allows the clinician to have a “middle man” that allows high flow oxygen delivery as well as a degree of respiratory support, which in some cases has been noted to be between 3 and 4 cm of continuous positive airway pressure-like effect. There are minimal data analyzing the use of high flow nasal cannula during anesthesia for bronchoscopy. We present a case report of orthotropic lung transplant recipient undergoing diagnostic bronchoscopy whilst being supported with high flow nasal oxygen in the intensive care unit.

Lung morphometry, collagen and elastin content: changes after hyperoxic exposure in preterm rabbits

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Renata Suman Mascaretti

2009-11-01

Full Text Available INTRODUCTION: Elastic and collagen fiber deposition increases throughout normal lung development, and this fiber network significantly changes when development of the lung is disturbed. In preterm rats and lambs, prolonged hyperoxic exposure is associated with impaired alveolization and causes significant changes in the deposition and structure of elastic fibers. OBJECTIVES: To evaluate the effects of hyperoxic exposure on elastic and collagen fiber deposition in the lung interstitial matrix and in alveolarization in preterm rabbits. METHODS: After c-section, 28-day preterm New-Zealand-White rabbits were randomized into 2 study groups, according to the oxygen exposure, namely: Room air (oxygen = 21% or Oxygen (oxygen > 95%. The animals were killed on day 11 and their lungs were analyzed for the alveolar size (Lm, the internal surface area (ISA, the alveoli number, and the density and distribution of collagen and elastic fibers. RESULTS: An increase in the Lm and a decrease in the alveoli number were observed among rabbits that were exposed to hyperoxia with no differences regarding the ISA. No difference in the density of elastic fibers was observed after oxygen exposure, however there were fewer collagen fibers and an evident disorganization of fiber deposition. DISCUSSION: This model reproduces anatomo-pathological injuries representing the arrest of normal alveolar development and lung architecture disorganization by just a prolonged exposition to oxygen. CONCLUSIONS: In the preterm rabbit, prolonged oxygen exposure impaired alveolization and also lowered the proportion of collagen fibers, with an evident fiber network disorganization.

Measurements of regional lung water with 0-15 labeled water and CO-15 labeled carboxyhemoglobin

International Nuclear Information System (INIS)

Helmeke, H.J.; Schober, O.; Lehr, L.; Junker, D.; Meyer, G.J.; Fitschen, J.; Bossaller, C.; Hundeshagen, H.

1982-01-01

Determination of regional vascular lung water is only practicable by external imaging since it is the only method which allows analysis of many regions. 0-15 was produced by our medical cyclotron (MC-35) via the N-14(d,n)0-15 reaction and processed to H 2 O-15 as the diffusible and to CO-15-hemiglobin autologous erythrocytes - as the intravascular tracer. The activity over both lungs applied as a bolus into the right atrium (5-10 mCi/1 sec) was followed by a positron camera (4200; Cycl. Corp.). Data acquisition and analysis was done in a pdp 11-55 computer system. Mean transit times were computed by the 'height over area' and the 'ratio of moments' method. The extravascular lung water per unit of plasma volume (ELW/Vp) was calculated according to Fazio et al. (1976).The lungs were divided into six zones. 47 investigations in 27 patients were caried out (controls, patients with heart failure, and critically ill with respiratory distress). As expected critically ill patients (ELW/Vp = 0.39+-0.19/0.66+-0.21) demonstrated a higher ELW/Vp than those suffering from myocardial insufficiency (ELW/V = 0.30+-0.13) or controls (ELW/Vp = 0.22+-0.11). Various factors involved in the measurement of lung water are mentioned. Because of methodological considerations and the worse discrimination concerning of the 'ratio of moments' method we prefer the 'height over area' analysis in the determination of transit times. The scintigraphic estimation of the so defind regional lung water is possible as the discrimination of groups is; the follow up or quantification of regional lung water of a patient in clinical routine work seems to be not yet established under the demonstrated conditions. (Author)

Study of perioperative extravascular lung water and intrathoracic blood volume in patients undergoing CABG surgery with or without cardiopulmonary bypass

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Samia Ragab El Azab

2014-10-01

Discussion and Conclusion: The clinical advantage of off-pump CABG surgery over standard extracorporeal circulation in regard to lung water content was not found in our study. In conclusion, the presumed superiority of off pump surgery for coronary artery bypass grafting could not be confirmed in our group of patients.

Successful Semi-Ambulatory Veno-Arterial Extracorporeal Membrane Oxygenation Bridge to Heart-Lung Transplantation in a Very Small Child.

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Wong, J Y W; Buchholz, H; Ryerson, L; Conradi, A; Adatia, I; Dyck, J; Rebeyka, I; Lien, D; Mullen, J

2015-08-01

Lung transplantation (LTx) may be denied for children on extracorporeal membrane oxygenation (ECMO) due to high risk of cerebral hemorrhage. Rarely has successful LTx been reported in children over 10 years of age receiving awake or ambulatory veno-venous ECMO. LTx following support with ambulatory veno-arterial ECMO (VA ECMO) in children has never been reported to our knowledge. We present the case of a 4-year-old, 12-kg child with heritable pulmonary artery hypertension and refractory right ventricular failure. She was successfully bridged to heart-lung transplantation (HLTx) using ambulatory VA ECMO. Initial resuscitation with standard VA ECMO was converted to an ambulatory circuit using Berlin heart cannulae. She was extubated and ambulating around her bed while on VA ECMO for 40 days. She received an HLTx from an oversized marginal lung donor. Despite a cardiac arrest and Grade 3 primary graft dysfunction, she made a full recovery without neurological deficits. She achieved 104% force expiratory volume in 1 s 33 months post-HLTx. Ambulatory VA ECMO may be a useful strategy to bridge very young children to LTx or HLTx. Patient tailored ECMO cannulation, minimization of hemorrhage, and thrombosis risks while on ECMO contributed to a successful HLTx in our patient. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Contemporary Outcomes of Extracorporeal Membrane Oxygenation Used as Bridge to Lung Transplantation.

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Hakim, Ali H; Ahmad, Usman; McCurry, Kenneth R; Johnston, Douglas R; Pettersson, Gosta B; Budev, Marie; Murthy, Sudish; Blackstone, Eugene H; Tong, Michael Z

2018-07-01

Extracorporeal membrane oxygenation (ECMO), when used as bridge to lung transplantation, (BTT) identifies high-risk candidates. Recent advances in cannula design and patient selection fosters "awake ambulatory ECMO" as a viable option for critically ill candidates in an attempt to retard deconditioning while awaiting allografts. From 2012 to 2015, 30 patients underwent ECMO as BTT. Candidacy for ECMO was determined before listing for transplant. A dual-lumen single cannula was used first in 13 of 30 patients (43%). Of the remaining 30 patients, 6 (20%) were supported with venoarterial ECMO and 11 (37%) with venovenous ECMO, with double-site cannulation in 11 (37%), and 6 of 11 converted to a dual-lumen single cannula. All ECMO patients were managed in a dedicated heart/lung failure intensive care unit, and early aggressive physical therapy, ambulation, and spontaneous breathing trials were emphasized. BTT was successful in 26 patients (87%). In the 19 patients with dual-lumen single cannula, 5 (26%) were successfully ambulated, and 6 (32%) achieved spontaneous ventilation. Median (25th, 75th percentile) lengths of stay in the intensive care unit and hospital were 33 days (20, 46 days) and 56 days (28, 78 days), respectively, and were 20 and 31 days, respectively, in patients successfully ambulated (intensive care unit: p = 0.5; hospital: p = 0.4). Among all patients who received a transplant, 30-day, 1-year, and 3-year survival were 92%, 85%, and 80%, respectively. Among patients undergoing primary transplants, 3-year survival was 91%. ECMO as BTT has led to encouraging perioperative outcomes and early survival. Careful patient selection and early use of ECMO seems to allow for preservation of vitality while these critically ill candidates await donor organs, which may improve outcomes. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Contribution of Neutrophils to Acute Lung Injury

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Grommes, Jochen; Soehnlein, Oliver

2010-01-01

Treatment of acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), remain unsolved problems of intensive care medicine. ALI/ARDS are characterized by lung edema due to increased permeability of the alveolar-capillary barrier and subsequent impairment of arterial oxygenation. Lung edema, endothelial and epithelial injury are accompanied by an influx of neutrophils into the interstitium and broncheoalveolar space. Hence, activation and recruitment of neut...

iNKT Cell Emigration out of the Lung Vasculature Requires Neutrophils and Monocyte-Derived Dendritic Cells in Inflammation

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Ajitha Thanabalasuriar

2016-09-01

Full Text Available iNKT cells are a subset of innate T cells that recognize glycolipids presented on CD1d molecules and protect against bacterial infections, including S. pneumoniae. Using lung intravital imaging, we examined the behavior and mechanism of pulmonary iNKT cell activation in response to the specific iNKT cell ligand α-galactosylceramide or S. pneumoniae infection. In untreated mice, the major fraction of iNKT cells resided in the vasculature, but a small critical population resided in the extravascular space in proximity to monocyte-derived DCs. Administration of either α-GalCer or S. pneumoniae induced CD1d-dependent rapid recruitment of neutrophils out of the vasculature. The neutrophils guided iNKT cells from the lung vasculature via CCL17. Depletion of monocyte-derived DCs abrogated both the neutrophil and subsequent iNKT cell extravasation. Moreover, impairing iNKT cell recruitment by blocking CCL17 increased susceptibility to S. pneumoniae infection, suggesting a critical role for the influx of iNKT cells in host defense.

Extracorporeal Membrane Oxygenation for End-Stage Interstitial Lung Disease With Secondary Pulmonary Hypertension at Rest and Exercise: Insights From Simulation Modeling.

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Chicotka, Scott; Burkhoff, Daniel; Dickstein, Marc L; Bacchetta, Matthew

Interstitial lung disease (ILD) represents a collection of lung disorders with a lethal trajectory with few therapeutic options with the exception of lung transplantation. Various extracorporeal membrane oxygenation (ECMO) configurations have been used for bridge to transplant (BTT), yet no optimal configuration has been clearly demonstrated. Using a cardiopulmonary simulation, we assessed different ECMO configurations for patients with end-stage ILD to assess the physiologic deficits and help guide the development of new long-term pulmonary support devices. A cardiopulmonary ECMO simulation was created, and changes in hemodynamics and blood gases were compared for different inflow and outflow anatomic locations and for different sweep gas and blood pump flow rates. The system simulated the physiologic response of patients with severe ILD at rest and during exercise with central ECMO, peripheral ECMO, and with no ECMO. The output parameters were total cardiac output (CO), mixed venous oxygen (O2) saturation, arterial pH, and O2 delivery (DO2)/O2 utilization (VO2) at different levels of exercise. The model described the physiologic state of progressive ILD and showed the relative effects of using various ECMO configurations to support them. It elucidated the optimal device configurations and required physiologic pump performance and provided insight into the physiologic demands of exercise in ILD patients. The simulation program was able to model the pathophysiologic state of progressive ILD with PH and demonstrate how mechanical support devices can be implemented to improve cardiopulmonary function at rest and during exercise. The information generated from simulation can be used to optimize ECMO configuration selection for BTT patients and provide design guidance for new devices to better meet the physiologic demands of exercise associated with normal activities of daily living.

Oxygen diffusion and oxygen effect in tumor tissue

International Nuclear Information System (INIS)

Eissa, H.M.; Hehn, G.

1979-06-01

The diffusion of oxygen in tumor cords of bronchus carcinoma of the lung have been studied with refined computer methods for solving the diffusion equation in axis symmetric tumor structures. In this tumor configuration we may find three different regions consisting of euoxic cells, hypoxic tumor cells and necrotic parts. In the case of oxygen supply from a capillary inside a cylinder of tumor tissue with radius 200 μm or in a tumor cord of radius 300 μm with oxygen supply by capillaries outside, we get a relation of well oxygenated cells to hypoxic cells approximately as 1:8 or as 1:1.1 respectively. Of course most of the tumor cords observed in histological slices have smaller diameters, so that an average of approximately 20% hypoxic cells can be assumed. Based on the work of Ardenne, the diffusion of oxygen and glucose in a tumor of type DS-carcinosarcom has been investigated in both intact tumor and tumor treated with ionizing radiation. We can show that a strong reoxygenation effect takes place in that the well supplied regions may increase in some tumor configurations up to a factor of four by volume. The biological consequences of the oxygen pressure determined in tumor cells are discussed in detail. The investigation of oxygen diffusion in the intercapillary tumor region should give a quantitative physical basis for considering the oxygen effect with the aim to explain the advantages of neutron therapy against conventional radiotherapy. (orig./MG) [de

Apoptotic action of peroxisome proliferator-activated receptor-gamma activation in human non small-cell lung cancer is mediated via proline oxidase-induced reactive oxygen species formation.

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Kim, Ki Young; Ahn, Jin Hee; Cheon, Hyae Gyeong

2007-09-01

Peroxisome proliferator-activated receptor (PPAR)-gamma ligands have been shown to inhibit human lung cancers by inducing apoptosis and differentiation. In the present study, we elucidated the apoptotic mechanism of PPARgamma activation in human lung cancers by using a novel PPARgamma agonist, 1-(trans-methylimino-N-oxy)-6-(2-morpholinoethoxy)-3-phenyl-(1H-indene-2-carboxylic acid ethyl ester (KR-62980), and rosiglitazone. PPARgamma activation selectively inhibited cell viability of non-small-cell lung cancer with little effect on small-cell lung cancer and normal lung cells. The cell death induced by PPARgamma activation presented apoptotic features of oligonucleosomal DNA fragmentation in A549 human non-small-cell lung cancer cell line. Reactive oxygen species (ROS) production was accompanied by increased expression of proline oxidase (POX), a redox enzyme expressed in mitochondria, upon incubation with the agonists. POX RNA interference treatment blocked PPARgamma-induced ROS formation and cytotoxicity, suggesting that POX plays a functional role in apoptosis through ROS formation. The apoptotic effects by the agonists were antagonized by bisphenol A diglycidyl ether, a PPARgamma antagonist, and by knockdown of PPARgamma expression, indicating the involvement of PPARgamma in these actions. The results of the present study suggest that PPARgamma activation induces apoptotic cell death in non-small-cell lung carcinoma mainly through ROS formation via POX induction.

Variable tidal volumes improve lung protective ventilation strategies in experimental lung injury.

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Spieth, Peter M; Carvalho, Alysson R; Pelosi, Paolo; Hoehn, Catharina; Meissner, Christoph; Kasper, Michael; Hübler, Matthias; von Neindorff, Matthias; Dassow, Constanze; Barrenschee, Martina; Uhlig, Stefan; Koch, Thea; de Abreu, Marcelo Gama

2009-04-15

Noisy ventilation with variable Vt may improve respiratory function in acute lung injury. To determine the impact of noisy ventilation on respiratory function and its biological effects on lung parenchyma compared with conventional protective mechanical ventilation strategies. In a porcine surfactant depletion model of lung injury, we randomly combined noisy ventilation with the ARDS Network protocol or the open lung approach (n = 9 per group). Respiratory mechanics, gas exchange, and distribution of pulmonary blood flow were measured at intervals over a 6-hour period. Postmortem, lung tissue was analyzed to determine histological damage, mechanical stress, and inflammation. We found that, at comparable minute ventilation, noisy ventilation (1) improved arterial oxygenation and reduced mean inspiratory peak airway pressure and elastance of the respiratory system compared with the ARDS Network protocol and the open lung approach, (2) redistributed pulmonary blood flow to caudal zones compared with the ARDS Network protocol and to peripheral ones compared with the open lung approach, (3) reduced histological damage in comparison to both protective ventilation strategies, and (4) did not increase lung inflammation or mechanical stress. Noisy ventilation with variable Vt and fixed respiratory frequency improves respiratory function and reduces histological damage compared with standard protective ventilation strategies.

Epithelial–mesenchymal transition during oncogenic transformation induced by hexavalent chromium involves reactive oxygen species-dependent mechanism in lung epithelial cells

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Ding, Song-Ze, E-mail: dingsongze@hotmail.com [Department of Internal Medicine, Henan Provincial People’s Hospital, Zhengzhou University, Wei-Wu Road, Zhengzhou, Henan 450000 (China); Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Yang, Yu-Xiu; Li, Xiu-Ling [Department of Internal Medicine, Henan Provincial People’s Hospital, Zhengzhou University, Wei-Wu Road, Zhengzhou, Henan 450000 (China); Michelli-Rivera, Audrey [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Han, Shuang-Yin [Department of Internal Medicine, Henan Provincial People’s Hospital, Zhengzhou University, Wei-Wu Road, Zhengzhou, Henan 450000 (China); Wang, Lei; Pratheeshkumar, Poyil; Wang, Xin; Lu, Jian; Yin, Yuan-Qin; Budhraja, Amit; Hitron, Andrew J. [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States)

2013-05-15

Hexavalent chromium [Cr(VI)] is an important human carcinogen associated with pulmonary diseases and lung cancer. Exposure to Cr(VI) induces DNA damage, cell morphological change and malignant transformation in human lung epithelial cells. Despite extensive studies, the molecular mechanisms remain elusive, it is also not known if Cr(VI)-induced transformation might accompany with invasive properties to facilitate metastasis. We aimed to study Cr(VI)-induced epithelial–mesenchymal transition (EMT) and invasion during oncogenic transformation in lung epithelial cells. The results showed that Cr(VI) at low doses represses E-cadherin mRNA and protein expression, enhances mesenchymal marker vimentin expression and transforms the epithelial cell into fibroblastoid morphology. Cr(VI) also increases cell invasion and promotes colony formation. Further studies indicated that Cr(VI) uses multiple mechanisms to repress E-cadherin expression, including activation of E-cadherin repressors such as Slug, ZEB1, KLF8 and enhancement the binding of HDAC1 in E-cadherin gene promoter, but DNA methylation is not responsible for the loss of E-cadherin. Catalase reduces Cr(VI)-induced E-cadherin and vimentin protein expression, attenuates cell invasion in matrigel and colony formation on soft agar. These results demonstrate that exposure to a common human carcinogen, Cr(VI), induces EMT and invasion during oncogenic transformation in lung epithelial cells and implicate in cancer metastasis and prevention. - Graphical abstract: Epithelial–mesenchymal transition during oncogenic transformation induced by hexavalent chromium involves reactive oxygen species-dependent mechanisms in lung epithelial cells. - Highlights: • We study if Cr(VI) might induce EMT and invasion in epithelial cells. • Cr(VI) induces EMT by altering E-cadherin and vimentin expression. • It also increases cell invasion and promotes oncogenic transformation. • Catalase reduces Cr(VI)-induced EMT, invasion and

Effects of pleural effusion drainage on oxygenation, respiratory mechanics, and hemodynamics in mechanically ventilated patients.

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Razazi, Keyvan; Thille, Arnaud W; Carteaux, Guillaume; Beji, Olfa; Brun-Buisson, Christian; Brochard, Laurent; Mekontso Dessap, Armand

2014-09-01

In mechanically ventilated patients, the effect of draining pleural effusion on oxygenation is controversial. We investigated the effect of large pleural effusion drainage on oxygenation, respiratory function (including lung volumes), and hemodynamics in mechanically ventilated patients after ultrasound-guided drainage. Arterial blood gases, respiratory mechanics (airway, pleural and transpulmonary pressures, end-expiratory lung volume, respiratory system compliance and resistance), and hemodynamics (blood pressure, heart rate, and cardiac output) were recorded before and at 3 and 24 hours (H24) after pleural drainage. The respiratory settings were kept identical during the study period. The mean volume of effusion drained was 1,579 ± 684 ml at H24. Uncomplicated pneumothorax occurred in two patients. Respiratory mechanics significantly improved after drainage, with a decrease in plateau pressure and a large increase in end-expiratory transpulmonary pressure. Respiratory system compliance, end-expiratory lung volume, and PaO2/FiO2 ratio all improved. Hemodynamics were not influenced by drainage. Improvement in the PaO2/FiO2 ratio from baseline to H24 was positively correlated with the increase in end-expiratory lung volume during the same time frame (r = 0.52, P = 0.033), but not with drained volume. A high value of pleural pressure or a highly negative transpulmonary pressure at baseline predicted limited lung expansion following effusion drainage. A lesser improvement in oxygenation occurred in patients with ARDS. Drainage of large (≥500 ml) pleural effusion in mechanically ventilated patients improves oxygenation and end-expiratory lung volume. Oxygenation improvement correlated with an increase in lung volume and a decrease in transpulmonary pressure, but was less so in patients with ARDS.

Prevention of ischemia-reperfusion lung injury during static cold preservation by supplementation of standard preservation solution with HEMO2life® in pig lung transplantation model.

Science.gov (United States)

Glorion, M; Polard, V; Favereau, F; Hauet, T; Zal, F; Fadel, E; Sage, E

2017-10-25

We describe the results of adding a new biological agent HEMO 2 life ® to a standard preservation solution for hypothermic static lung preservation aiming to improve early functional parameters after lung transplantation. HEMO 2 life ® is a natural oxygen carrier extracted from Arenicola marina with high oxygen affinity developed as an additive to standard organ preservation solutions. Standard preservation solution (Perfadex ® ) was compared with Perfadex ® associated with HEMO 2 life ® and with sham animals after 24 h of hypothermic preservation followed by lung transplantation. During five hours of lung reperfusion, functional parameters and biomarkers expression in serum and in bronchoalveolar lavage fluid (BALF) were measured. After five hours of reperfusion, HEMO 2 life ® group led to significant improvement in functional parameters: reduction of graft vascular resistance (p preservation improves early graft function after prolonged cold ischemia in lung transplantation.

Oxidative lung injury correlates with one-lung ventilation time during pulmonary lobectomy: a study of exhaled breath condensate and blood.

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García-de-la-Asunción, José; García-del-Olmo, Eva; Perez-Griera, Jaume; Martí, Francisco; Galan, Genaro; Morcillo, Alfonso; Wins, Richard; Guijarro, Ricardo; Arnau, Antonio; Sarriá, Benjamín; García-Raimundo, Miguel; Belda, Javier

2015-09-01

During lung lobectomy, the operated lung is collapsed and hypoperfused; oxygen deprivation is accompanied by reactive hypoxic pulmonary vasoconstriction. After lung lobectomy, ischaemia present in the collapsed state is followed by expansion-reperfusion and lung injury attributed to the production of reactive oxygen species. The primary objective of this study was to investigate the time course of several markers of oxidative stress simultaneously in exhaled breath condensate and blood and to determine the relationship between oxidative stress and one-lung ventilation time in patients undergoing lung lobectomy. This single-centre, observational, prospective study included 28 patients with non-small-cell lung cancer who underwent lung lobectomy. We measured the levels of hydrogen peroxide, 8-iso-PGF2α, nitrites plus nitrates and pH in exhaled breath condensate (n = 25). The levels of 8-iso-PGF2α and nitrites plus nitrates were also measured in blood (n = 28). Blood samples and exhaled breath condensate samples were collected from all patients at five time points: preoperatively; during one-lung ventilation, immediately before resuming two-lung ventilation; immediately after resuming two-lung ventilation; 60 min after resuming two-lung ventilation and 180 min after resuming two-lung ventilation. Both exhaled breath condensate and blood exhibited significant and simultaneous increases in oxidative-stress markers immediately before two-lung ventilation was resumed. However, all these values underwent larger increases immediately after resuming two-lung ventilation. In both exhaled breath condensate and blood, marker levels significantly and directly correlated with the duration of one-lung ventilation immediately before resuming two-lung ventilation and immediately after resuming two-lung ventilation. Although pH significantly decreased in exhaled breath condensate immediately after resuming two-lung ventilation, these pH values were inversely correlated with the

Incomplete Memories: The Natural Suppression of Tissue-Resident Memory CD8 T Cells in the Lung

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Katie L. Reagin

2018-01-01

Full Text Available The yearly, cyclic impact of viruses like influenza on human health and the economy is due to the high rates of mutation of traditional antibody targets, which negate any preexisting humoral immunity. However, the seasonality of influenza infections can equally be attributed to an absent or defective memory CD8 T cell response since the epitopes recognized by these cells are derived from essential virus proteins that mutate infrequently. Experiments in mouse models show that protection from heterologous influenza infection is temporally limited and conferred by a population of tissue-resident memory (TRM cells residing in the lung and lung airways. TRM are elicited by a diverse set of pathogens penetrating mucosal barriers and broadly identified by extravascular staining and expression of the activation and adhesion molecules CD69 and CD103. Interestingly, lung TRM fail to express these molecules, which could limit tissue retention, resulting in airway expulsion or death with concomitant loss of heterologous protection. Here, we make the case that respiratory infections uniquely evoke a form of natural immunosuppression whereby specific cytokines and cell–cell interactions negatively impact memory cell programming and differentiation. Respiratory memory is not only short-lived but most of the memory cells in the lung parenchyma may not be bona fide TRM. Given the quantity of microbes humans inhale over a lifetime, limiting cellular residence could be a mechanism employed by the respiratory tract to preserve organismal vitality. Therefore, successful efforts to improve respiratory immunity must carefully and selectively breach these inherent tissue barriers.

Oxygen in the critically ill: friend or foe?

Science.gov (United States)

Damiani, Elisa; Donati, Abele; Girardis, Massimo

2018-04-01

To examine the potential harmful effects of hyperoxia and summarize the results of most recent clinical studies evaluating oxygen therapy in critically ill patients. Excessive oxygen supplementation may have detrimental pulmonary and systemic effects because of enhanced oxidative stress and inflammation. Hyperoxia-induced lung injury includes altered surfactant protein composition, reduced mucociliary clearance and histological damage, resulting in atelectasis, reduced lung compliance and increased risk of infections. Hyperoxemia causes vasoconstriction, reduction in coronary blood flow and cardiac output and may alter microvascular perfusion. Observational studies showed a close relationship between hyperoxemia and increased mortality in several subsets of critically ill patients. In absence of hypoxemia, the routine use of oxygen therapy in patients with myocardial infarction, stroke, traumatic brain injury, cardiac arrest and sepsis, showed no benefit but rather it seems to be harmful. In patients admitted to intensive care unit, a conservative oxygen therapy aimed to maintain arterial oxygenation within physiological range has been proved to be well tolerated and may improve outcome. Liberal O2 use and unnecessary hyperoxia may be detrimental in critically ill patients. The current evidence supports the use of a conservative strategy in O2 therapy to avoid patient exposure to unnecessary hyperoxemia.

Studies on the correlation between pre-and post-operative perfusion scintigraphy and differential spirometry in operated lungs

International Nuclear Information System (INIS)

Kaseda, Shizuka; Ikeda, Takaaki; Sakai, Tadaaki; Tomaru, Hiroko; Ishihara, Tsuneo; Kikuchi, Keiichi.

1982-01-01

For the purpose of clarifying the relationship between the percentage of perfusion and that of vital capacity or oxygen uptake on the affected lung, perfusion scintigraphy using sup(99m)Tc-MAA and differential spirometry were performed in twenty patients including sixteen patients with lung cancer. Both examinations were performed before and after the operation. The results are as follows: (1) There is a significant correlation between the percentage of perfusion and that of vital capacity or oxygen uptake of the affected lung before and after the operation. (2) The estimation of the percentage of vital capacity or oxygen uptake of the affected lung is possible by combining the spirometry and sup(99m)Tc-MAA pulmonary scintigraphy. (author)

Oxygen, the lung and the diver: friends and foes?

NARCIS (Netherlands)

van Ooij, Pieter-Jan A. M.; Sterk, Peter J.; van Hulst, Robert A.

2016-01-01

Worldwide, the number of professional and sports divers is increasing. Most of them breathe diving gases with a raised partial pressure of oxygen (PO2). However, if the PO2 is between 50 and 300 kPa (375-2250 mmHg) (hyperoxia), pathological pulmonary changes can develop, known as pulmonary oxygen

Comparison of lung preservation solutions in human lungs using an ex vivo lung perfusion experimental model

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Israel L. Medeiros

2012-09-01

Full Text Available OBJECTIVE: Experimental studies on lung preservation have always been performed using animal models. We present ex vivo lung perfusion as a new model for the study of lung preservation. Using human lungs instead of animal models may bring the results of experimental studies closer to what could be expected in clinical practice. METHOD: Brain-dead donors whose lungs had been declined by transplantation teams were used. The cases were randomized into two groups. In Group 1, Perfadex®was used for pulmonary preservation, and in Group 2, LPDnac, a solution manufactured in Brazil, was used. An ex vivo lung perfusion system was used, and the lungs were ventilated and perfused after 10 hours of cold ischemia. The extent of ischemic-reperfusion injury was measured using functional and histological parameters. RESULTS: After reperfusion, the mean oxygenation capacity was 405.3 mmHg in Group 1 and 406.0 mmHg in Group 2 (p = 0.98. The mean pulmonary vascular resistance values were 697.6 and 378.3 dyn·s·cm-5, respectively (p =0.035. The mean pulmonary compliance was 46.8 cm H20 in Group 1 and 49.3 ml/cm H20 in Group 2 (p =0.816. The mean wet/dry weight ratios were 2.06 and 2.02, respectively (p=0.87. The mean Lung Injury Scores for the biopsy performed after reperfusion were 4.37 and 4.37 in Groups 1 and 2, respectively (p = 1.0, and the apoptotic cell counts were 118.75/mm² and 137.50/mm², respectively (p=0.71. CONCLUSION: The locally produced preservation solution proved to be as good as Perfadex®. The clinical use of LPDnac may reduce costs in our centers. Therefore, it is important to develop new models to study lung preservation.

National review of use of extracorporeal membrane oxygenation as respiratory support in thoracic surgery excluding lung transplantation.

Science.gov (United States)

Rinieri, Philippe; Peillon, Christophe; Bessou, Jean-Paul; Veber, Benoît; Falcoz, Pierre-Emmanuel; Melki, Jean; Baste, Jean-Marc

2015-01-01

Extracorporeal membrane oxygenation (ECMO) for respiratory support is increasingly used in intensive care units (ICU), but rarely during thoracic surgical procedures outside the transplantation setting. ECMO can be an alternative to cardiopulmonary bypass for major trachea-bronchial surgery and single-lung procedures without in-field ventilation. Our aim was to evaluate the intraoperative use of ECMO as respiratory support in thoracic surgery: benefits, indications and complications. This was a multicentre retrospective study (questionnaire) of use of ECMO as respiratory support during the thoracic surgical procedure. Lung transplantation and lung resection for tumour invading the great vessels and/or the left atrium were excluded, because they concern respiratory and circulatory support. From March 2009 to September 2012, 17 of the 34 centres in France applied ECMO within veno-venous (VV) (n=20) or veno-arterial (VA) (n=16) indications in 36 patients. Ten VA ECMO were performed with peripheral cannulation and 6 with central cannulation; all VV ECMO were achieved through peripheral cannulation. Group 1 (total respiratory support) was composed of 28 patients without mechanical ventilation, involving 23 tracheo-bronchial and 5 single-lung procedures. Group 2 (partial respiratory support) was made up of 5 patients with respiratory insufficiency. Group 3 was made up of 3 patients who underwent thoracic surgery in a setting of acute respiratory distress syndrome (ARDS) with preoperative ECMO. Mortality at 30 days in Groups 1, 2 and 3 was 7, 40 and 67%, respectively (P<0.05). In Group 1, ECMO was weaned intraoperatively or within 24 h in 75% of patients. In Group 2, ECMO was weaned in ICU over several days. In Group 1, 2 patients with VA support were converted to VV support for chronic respiratory indications. Bleeding was the major complication with 17% of patients requiring return to theatre for haemostasis. There were two cannulation-related complications (6%). VV or

Hypoxia, innate immunity and infection in the lung.

LENUS (Irish Health Repository)

Schaible, Bettina

2012-02-01

The mucosal surface of the lung is the key interface between the external atmosphere and the bloodstream. Normally, this well oxygenated tissue is maintained in state of sterility by a number of innate immune processes. These include a physical and dynamic mucus barrier, the production of microbiocidal peptides and the expression of specific pattern recognition receptors on alveolar epithelial cells and resident macrophages and dendritic cells which recognise microbial structures and initiate innate immune responses which promote the clearance of potentially infectious agents. In a range of diseases, the mucosal surface of the lung experiences decreased oxygen tension leading to localised areas of prominent hypoxia which can impact upon innate immune and subsequent infectious and inflammatory processes. Under these conditions, the lung is generally more susceptible to infection and subsequent inflammation. In the current review, we will discuss recent data pertaining to the role of hypoxia in regulating both host and pathogen in the lung during pulmonary disease and how this contributes to innate immunity, infection and inflammation.

Sevoflurane posttreatment prevents oxidative and inflammatory injury in ventilator-induced lung injury.

Directory of Open Access Journals (Sweden)

Julie Wagner

Full Text Available Mechanical ventilation is a life-saving clinical treatment but it can induce or aggravate lung injury. New therapeutic strategies, aimed at reducing the negative effects of mechanical ventilation such as excessive production of reactive oxygen species, release of pro-inflammatory cytokines, and transmigration as well as activation of neutrophil cells, are needed to improve the clinical outcome of ventilated patients. Though the inhaled anesthetic sevoflurane is known to exert organ-protective effects, little is known about the potential of sevoflurane therapy in ventilator-induced lung injury. This study focused on the effects of delayed sevoflurane application in mechanically ventilated C57BL/6N mice. Lung function, lung injury, oxidative stress, and inflammatory parameters were analyzed and compared between non-ventilated and ventilated groups with or without sevoflurane anesthesia. Mechanical ventilation led to a substantial induction of lung injury, reactive oxygen species production, pro-inflammatory cytokine release, and neutrophil influx. In contrast, sevoflurane posttreatment time dependently reduced histological signs of lung injury. Most interestingly, increased production of reactive oxygen species was clearly inhibited in all sevoflurane posttreatment groups. Likewise, the release of the pro-inflammatory cytokines interleukin-1β and MIP-1β and neutrophil transmigration were completely prevented by sevoflurane independent of the onset of sevoflurane administration. In conclusion, sevoflurane posttreatment time dependently limits lung injury, and oxidative and pro-inflammatory responses are clearly prevented by sevoflurane irrespective of the onset of posttreatment. These findings underline the therapeutic potential of sevoflurane treatment in ventilator-induced lung injury.

Enhanced Heme Function and Mitochondrial Respiration Promote the Progression of Lung Cancer Cells

Science.gov (United States)

Alam, Md Maksudul; Shah, Ajit; Cao, Thai M.; Sullivan, Laura A.; Brekken, Rolf; Zhang, Li

2013-01-01

Lung cancer is the leading cause of cancer-related mortality, and about 85% of the cases are non-small-cell lung cancer (NSCLC). Importantly, recent advance in cancer research suggests that altering cancer cell bioenergetics can provide an effective way to target such advanced cancer cells that have acquired mutations in multiple cellular regulators. This study aims to identify bioenergetic alterations in lung cancer cells by directly measuring and comparing key metabolic activities in a pair of cell lines representing normal and NSCLC cells developed from the same patient. We found that the rates of oxygen consumption and heme biosynthesis were intensified in NSCLC cells. Additionally, the NSCLC cells exhibited substantially increased levels in an array of proteins promoting heme synthesis, uptake and function. These proteins include the rate-limiting heme biosynthetic enzyme ALAS, transporter proteins HRG1 and HCP1 that are involved in heme uptake, and various types of oxygen-utilizing hemoproteins such as cytoglobin and cytochromes. Several types of human tumor xenografts also displayed increased levels of such proteins. Furthermore, we found that lowering heme biosynthesis and uptake, like lowering mitochondrial respiration, effectively reduced oxygen consumption, cancer cell proliferation, migration and colony formation. In contrast, lowering heme degradation does not have an effect on lung cancer cells. These results show that increased heme flux and function are a key feature of NSCLC cells. Further, increased generation and supply of heme and oxygen-utilizing hemoproteins in cancer cells will lead to intensified oxygen consumption and cellular energy production by mitochondrial respiration, which would fuel cancer cell proliferation and progression. The results show that inhibiting heme and respiratory function can effectively arrest the progression of lung cancer cells. Hence, understanding heme function can positively impact on research in lung cancer

Nonintrusive gas monitoring in neonatal lungs using diode laser spectroscopy: feasibility study.

Science.gov (United States)

Lewander, Märta; Bruzelius, Anders; Svanberg, Sune; Svanberg, Katarina; Fellman, Vineta

2011-12-01

A feasibility study on noninvasive, real-time monitoring of gases in lungs of preterm infants is reported, where a laser-spectroscopic technique using diode lasers tuned to oxygen and water vapor absorption lines was employed on realistic tissue phantoms. Our work suggests that the technique could provide a new possibility for surveillance of the lung function of preterm infants, in particular the oxygenation, which is of prime importance in this patient group.

Open lung approach vs acute respiratory distress syndrome network ventilation in experimental acute lung injury.

Science.gov (United States)

Spieth, P M; Güldner, A; Carvalho, A R; Kasper, M; Pelosi, P; Uhlig, S; Koch, T; Gama de Abreu, M

2011-09-01

Setting and strategies of mechanical ventilation with positive end-expiratory pressure (PEEP) in acute lung injury (ALI) remains controversial. This study compares the effects between lung-protective mechanical ventilation according to the Acute Respiratory Distress Syndrome Network recommendations (ARDSnet) and the open lung approach (OLA) on pulmonary function and inflammatory response. Eighteen juvenile pigs were anaesthetized, mechanically ventilated, and instrumented. ALI was induced by surfactant washout. Animals were randomly assigned to mechanical ventilation according to the ARDSnet protocol or the OLA (n=9 per group). Gas exchange, haemodynamics, pulmonary blood flow (PBF) distribution, and respiratory mechanics were measured at intervals and the lungs were removed after 6 h of mechanical ventilation for further analysis. PEEP and mean airway pressure were higher in the OLA than in the ARDSnet group [15 cmH(2)O, range 14-18 cmH(2)O, compared with 12 cmH(2)O; 20.5 (sd 2.3) compared with 18 (1.4) cmH(2)O by the end of the experiment, respectively], and OLA was associated with improved oxygenation compared with the ARDSnet group after 6 h. OLA showed more alveolar overdistension, especially in gravitationally non-dependent regions, while the ARDSnet group was associated with more intra-alveolar haemorrhage. Inflammatory mediators and markers of lung parenchymal stress did not differ significantly between groups. The PBF shifted from ventral to dorsal during OLA compared with ARDSnet protocol [-0.02 (-0.09 to -0.01) compared with -0.08 (-0.12 to -0.06), dorsal-ventral gradients after 6 h, respectively]. According to the OLA, mechanical ventilation improved oxygenation and redistributed pulmonary perfusion when compared with the ARDSnet protocol, without differences in lung inflammatory response.

Laboratory testing of extravascular body fluids in Croatia: a survey of the Working group for extravascular body fluids of the Croatian Society of Medical Biochemistry and Laboratory Medicine.

Science.gov (United States)

Kopcinovic, Lara Milevoj; Vogrinc, Zeljka; Kocijan, Irena; Culej, Jelena; Aralica, Merica; Jokic, Anja; Antoncic, Dragana; Bozovic, Marija

2016-10-15

We hypothesized that extravascular body fluid (EBF) analysis in Croatia is not harmonized and aimed to investigate preanalytical, analytical and postanalytical procedures used in EBF analysis in order to identify key aspects that should be addressed in future harmonization attempts. An anonymous online survey created to explore laboratory testing of EBF was sent to secondary, tertiary and private health care Medical Biochemistry Laboratories (MBLs) in Croatia. Statements were designed to address preanalytical, analytical and postanalytical procedures of cerebrospinal, pleural, peritoneal (ascites), pericardial, seminal, synovial, amniotic fluid and sweat. Participants were asked to declare the strength of agreement with proposed statements using a Likert scale. Mean scores for corresponding separate statements divided according to health care setting were calculated and compared. The survey response rate was 0.64 (58 / 90). None of the participating private MBLs declared to analyse EBF. We report a mean score of 3.45 obtained for all statements evaluated. Deviations from desirable procedures were demonstrated in all EBF testing phases. Minor differences in procedures used for EBF analysis comparing secondary and tertiary health care MBLs were found. The lowest scores were obtained for statements regarding quality control procedures in EBF analysis, participation in proficiency testing programmes and provision of interpretative comments on EBF's test reports. Although good laboratory EBF practice is present in Croatia, procedures for EBF analysis should be further harmonized to improve the quality of EBF testing and patient safety.

A numerical two layer model for blood oxygenation in lungs

International Nuclear Information System (INIS)

Aminatai, A.

2001-01-01

In the modelling of the simultaneous transport of O 2 and CO 2 in the pulmonary circulation described in our earlier studies, the blood has been treated as a homogeneous layer of haemoglobin solution. Since the size of the erythrocyte is not negligible in comparison with that of the capillary, the blood can no longer be considered as a homogeneous fluid and hence, It is worthwhile to consider the blood flow as a two-phase flow consisting of cells and plasma. In the present study, the heterogeneous nature of blood has been proposed by considering the axial train model for the flow [whitmore (1967)], in order to analyze the effect of cell free plasma layer on the process of blood oxygenation in pulmonary capillaries. The proposed model consists of a core of suspended erythrocytes surrounded by a cell free plasma layer near the wall. The coupled system of convective diffusion equaions together with the physiologically relevant boundary, entrance and interface conditions is solved numerically by a four-point semi-implicit scheme to gether with a fixed point iterative technique. The distance traversed by the blood before getting fully oxygenated is computed. It is shown that the core haematocrit and the thickness of the cell depleted layer affect the oxygenation process significantly. It is found that (i) oxygen takes longest and carbondioxide is the fastest to attain equilibraton, (ii) the blood is completely oxygenated within one-fifth part of its transit and (iii) the rate of oxygenation is smaller in case of homogeneous model than that in heterogenous model in the capillary. Finally, the effect of various physiological parameters on the rate of oxygenation has been examined

Static inflation attenuates ischemia/reperfusion injury in an isolated rat lung in situ.

Science.gov (United States)

Kao, Shang Jyh; Wang, David; Yeh, Diana Yu-Wung; Hsu, Kang; Hsu, Yung Hsiang; Chen, Hsing I

2004-08-01

Ischemia (I)/reperfusion (R) lung injury is an important clinical issue in lung transplantation. In the present study, we observed the effects of lung static inflation, different perfusates, and ventilatory gas with nitrogen or oxygen on the I/R-induced pulmonary damage. A total of 96 male Sprague-Dawley rats were used. The lung was isolated in situ. In an isolated lung, the capillary filtration coefficient (Kfc), lung weight gain (LWG), lung weight (LW)/body weight (BW) ratio, and protein concentration in BAL fluid (PCBAL) were measured or calculated to evaluate the degree of lung injury. Histologic examinations with hematoxylin-eosin staining were performed. I/R caused lung injury, as reflected by increases in Kfc, LWG, LW/BW, and PCBAL. The histopathologic picture revealed the presence of hyaline membrane formation and the infiltration of inflammatory cells. These values were significantly attenuated by static lung inflation. The I/R lung damage appeared to be less in the lung perfused with whole blood than in the lung perfused with an isotonic solution. Therapy with ventilatory air (ie, nitrogen or oxygen) did not alter the I/R lung damage. The data suggest that lung inflation is protective to I/R injury, irrespective of the type of ventilatory air used for treatment. The preservation of the lung for transplantation is better kept at a static inflation state and perfused with whole blood instead of an isotonic physiologic solution.

Characteristic patterns in the fibrotic lung. Comparing idiopathic pulmonary fibrosis with chronic lung allograft dysfunction.

Science.gov (United States)

Fernandez, Isis E; Heinzelmann, Katharina; Verleden, Stijn; Eickelberg, Oliver

2015-03-01

Tissue fibrosis, a major cause of death worldwide, leads to significant organ dysfunction in any organ of the human body. In the lung, fibrosis critically impairs gas exchange, tissue oxygenation, and immune function. Idiopathic pulmonary fibrosis (IPF) is the most detrimental and lethal fibrotic disease of the lung, with an estimated median survival of 50% after 3-5 years. Lung transplantation currently remains the only therapeutic alternative for IPF and other end-stage pulmonary disorders. Posttransplant lung function, however, is compromised by short- and long-term complications, most importantly chronic lung allograft dysfunction (CLAD). CLAD affects up to 50% of all transplanted lungs after 5 years, and is characterized by small airway obstruction with pronounced epithelial injury, aberrant wound healing, and subepithelial and interstitial fibrosis. Intriguingly, the mechanisms leading to the fibrotic processes in the engrafted lung exhibit striking similarities to those in IPF; therefore, antifibrotic therapies may contribute to increased graft function and survival in CLAD. In this review, we focus on these common fibrosis-related mechanisms in IPF and CLAD, comparing and contrasting clinical phenotypes, the mechanisms of fibrogenesis, and biomarkers to monitor, predict, or prognosticate disease status.

Lysophosphatidic acid generation by pulmonary NKT cell ENPP-2/autotaxin exacerbates hyperoxic lung injury.

Science.gov (United States)

Nowak-Machen, Martina; Lange, Martin; Exley, Mark; Wu, Sherry; Usheva, Anny; Robson, Simon C

2015-12-01

Hyperoxia is still broadly used in clinical practice in order to assure organ oxygenation in critically ill patients, albeit known toxic effects. In this present study, we hypothesize that lysophosphatidic acid (LPA) mediates NKT cell activation in a mouse model of hyperoxic lung injury. In vitro, pulmonary NKT cells were exposed to hyperoxia for 72 h, and the induction of the ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP-2) was examined and production of lysophosphatidic acid (LPA) was measured. In vivo, animals were exposed to 100 % oxygen for 72 h and lungs and serum were harvested. Pulmonary NKT cells were then incubated with the LPA antagonist Brp-LPA. Animals received BrP-LPA prior to oxygen exposure. Autotaxin (ATX, ENPP-2) was significantly up-regulated on pulmonary NKT cells after hyperoxia (p NKT cells. LPA levels were significantly reduced by incubating NKT cells with LPA-BrP during oxygen exposure (p NKT cell numbers in vivo. BrP-LPA injection significantly improved survival as well as significantly decreased lung injury and lowered pulmonary NKT cell numbers. We conclude that NKT cell-induced hyperoxic lung injury is mediated by pro-inflammatory LPA generation, at least in part, secondary to ENPP-2 up-regulation on pulmonary NKT cells. Being a potent LPA antagonist, BrP-LPA prevents hyperoxia-induced lung injury in vitro and in vivo.

Morphological respiratory diffusion capacity of the lungs of ball pythons (Python regius).

Science.gov (United States)

Starck, J Matthias; Aupperle, Heike; Kiefer, Ingmar; Weimer, Isabel; Krautwald-Junghanns, Maria-Elisabeth; Pees, Michael

2012-08-01

This study aims at a functional and morphological characterization of the lung of a boid snake. In particular, we were interested to see if the python's lungs are designed with excess capacity as compared to resting and working oxygen demands. Therefore, the morphological respiratory diffusion capacity of ball pythons (Python regius) was examined following a stereological, hierarchically nested approach. The volume of the respiratory exchange tissue was determined using computed tomography. Tissue compartments were quantified using stereological methods on light microscopic images. The tissue diffusion barrier for oxygen transport was characterized and measured using transmission electron micrographs. We found a significant negative correlation between body mass and the volume of respiratory tissue; the lungs of larger snakes had relatively less respiratory tissue. Therefore, mass-specific respiratory tissue was calculated to exclude effects of body mass. The volume of the lung that contains parenchyma was 11.9±5.0mm(3)g(-1). The volume fraction, i.e., the actual pulmonary exchange tissue per lung parenchyma, was 63.22±7.3%; the total respiratory surface was, on average, 0.214±0.129m(2); it was significantly negatively correlated to body mass, with larger snakes having proportionally smaller respiratory surfaces. For the air-blood barrier, a harmonic mean of 0.78±0.05μm was found, with the epithelial layer representing the thickest part of the barrier. Based on these findings, a median diffusion capacity of the tissue barrier ( [Formula: see text] ) of 0.69±0.38ml O(2)min(-1)mmHg(-1) was calculated. Based on published values for blood oxygen concentration, a total oxygen uptake capacity of 61.16mlO(2)min(-1)kg(-1) can be assumed. This value exceeds the maximum demand for oxygen in ball pythons by a factor of 12. We conclude that healthy individuals of P. regius possess a considerable spare capacity for tissue oxygen exchange. Copyright © 2012 Elsevier Gmb

Contrast-enhanced MRI of the lung

International Nuclear Information System (INIS)

Kauczor, Hans-Ulrich; Kreitner, Karl-Friedrich

2000-01-01

The lung has long been neglected by MR imaging. This is due to unique intrinsic difficulties: (1) signal loss due to cardiac pulsation and respiration; (2) susceptibility artifacts caused by multiple air-tissue interfaces; (3) low proton density. There are many MR strategies to overcome these problems. They consist of breath-hold imaging, respiratory and cardiac gating procedures, use of short repetition and echo times, increase of the relaxivity of existing spins by administration of intravenous contrast agents, and enrichment of spin density by hyperpolarized noble gases or oxygen. Improvements in scanner performance and frequent use of contrast media have increased the interest in MR imaging and MR angiography of the lung. They can be used on a routine basis for the following indications: characterization of pulmonary nodules, staging of bronchogenic carcinoma, in particular assessment of chest wall invasion; evaluation of inflammatory activity in interstitial lung disease; acute pulmonary embolism, chronic thromboembolic pulmonary hypertension, vascular involvement in malignant disease; vascular abnormalities. Future perspectives include perfusion imaging using extracellular or intravascular (blood pool) contrast agents and ventilation imaging using inhalation of hyperpolarized noble gases, of paramagnetic oxygen or of aerosolized contrast agents. These techniques represent new approaches to functional lung imaging. The combination of visualization of morphology and functional assessment of ventilation and perfusion is unequalled by any other technique

Aerosolized prostacyclin for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS)

DEFF Research Database (Denmark)

Afshari, Arash; Brok, Jesper; Møller, Ann

2010-01-01

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are critical conditions that are associated with high mortality and morbidity. Aerosolized prostacyclin has been used to improve oxygenation despite the limited evidence available so far.......Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are critical conditions that are associated with high mortality and morbidity. Aerosolized prostacyclin has been used to improve oxygenation despite the limited evidence available so far....

Pulmonary fibrosis in youth treated with radioiodine for juvenile thyroid cancer and lung metastases after Chernobyl

International Nuclear Information System (INIS)

Hebestreit, Helge; Burkhardt, Antje; Biko, Johannes; Reiners, Christoph; Drozd, Valentina; Demidchik, Yuri; Trusen, Andreas; Beer, Meinrad

2011-01-01

The objective of this project was to systematically determine the prevalence and consequences of pulmonary fibrosis in youth with thyroid carcinoma and lung metastases from Belarus who were treated with radioiodine ( 131 I). A total of 69 patients treated for juvenile thyroid carcinoma and lung metastasis with 131 I were assessed. A group of 29 patients without lung metastases and prior 131 I treatment served as controls. The assessments included a CT scan of the lungs, extensive pulmonary function testing and an incremental cycle test to volitional fatigue with measurements of oxygen uptake (V. O 2 ), oxygen saturation and alveolar-arterial difference in oxygen partial pressure (ΔaaO 2 ). Five patients with lung metastases showed advanced pulmonary fibrosis on CT scans and also had poorer lung functions compared with the 62 patients with none or minor signs of fibrosis and the 29 controls. Furthermore, these five patients showed lower peak V.O 2 , lower oxygen saturation at peak exercise and higher exercise ΔaaO 2 . They were younger at the time of cancer diagnosis and had received chemotherapy more frequently than youth with pulmonary metastases who did not develop fibrosis. One of the five patients subsequently died from pulmonary fibrosis. Following the Chernobyl catastrophe, about 7% of children treated with radioiodine for thyroid carcinoma and lung metastases displayed pulmonary fibrosis which was associated with functional impairments. Based on the characteristics of affected individuals, the number of radioiodine courses may have to be limited, especially in young children, and chemotherapy should be avoided. (orig.)

A theoretical model for the effects of reduced hemoglobin-oxygen affinity on tumor oxygenation

International Nuclear Information System (INIS)

Kavanagh, Brian D.; Secomb, Timothy W.; Hsu, Richard; Lin, P.-S.; Venitz, Jurgen; Dewhirst, Mark W.

2002-01-01

Purpose: To develop a theoretical model for oxygen delivery to tumors, and to use the model to simulate the effects of changing the affinity of hemoglobin for oxygen on tumor oxygenation. Methods and Materials: Hemoglobin affinity is expressed in terms of P 50 , the partial pressure of oxygen (Po 2 ) at half saturation. Effects of changing P 50 on arterial Po 2 are predicted using an effective vessel approach to describe diffusive oxygen transport in the lungs, assuming fixed systemic oxygen demand and fixed blood flow rate. The decline in oxygen content of blood as it flows through normal tissue before entering the tumor region is assumed fixed. The hypoxic fraction of the tumor region is predicted using a three-dimensional simulation of diffusion from a network of vessels whose geometry is derived from observations of tumor microvasculature in the rat. Results: In air-breathing rats, predicted hypoxic fraction decreases with moderate increases in P 50 , but increases with further increases of P 50 , in agreement with previous experimental results. In rats breathing hyperoxic gases, and in humans breathing either normoxic or hyperoxic gases, increased P 50 is predicted to improve tumor oxygenation. Conclusions: The results support the administration of synthetic agents to increase P 50 during radiation treatment of tumors

Perfusion lung scintigraphy in primary pulmonary hypertension

International Nuclear Information System (INIS)

Ogawa, Y.; Hayashida, K.; Uehara, T.; Shimonagata, T.; Nishimura, T.; Osaka Univ., Suita

1993-01-01

15 cases of primary pulmonary hypertension were classified into two groups by patterns of perfusion lung scintigraphy. Perfusion scintigrams showed multiple, small, ill-defined defects (mottled + ve) pattern in eight cases, and the remaining seven cases had a normal (mottled - ve) pattern. The mean pulmonary arterial pressure in patients with a mottled pattern (54 ± 10 mmHg) was higher than in those with a normal pattern (42 ± 9 mmHg, p < 0.05). There were no significant differences between the two groups in right ventricular ejection fraction, partial pressures of oxygen in the arterial blood or alveolo-arterial oxygen difference. All the patients with a mottled pattern died within 2 years following the lung scintigraphy. There was a significant difference in the survival curves between the two groups. (author)

Manual of extravascular minimally invasive interventional procedures of the liver and biliary tract

International Nuclear Information System (INIS)

Miranda Mena, Shirley

2011-01-01

The use of interventional radiology and image-guided surgery has increased. Interventional radiologists are involved in patient treatment, well as in the diagnosis of the disease carrying his knowledge to the tumor treatment and procedures more invasive. Large amount of didactic material there are available, but the country lacks a manual to standardize interventional radiological techniques carried out. Also, those that could be instituted and adapted effectively in the management of hepatobiliary pathology of the Sistema de Salud Publica in Costa Rica, that covers the main procedures and adopt guidelines in a standardized way. A manual of procedures minimally invasive radiologic extravascular of the liver and biliary tract, is presented with broad bibliographic support that directs, standardizes and is adaptable to the needs and own resources of Costa Rica. Interventional radiology has been a non surgical alternative of a low index of complications, useful for the management of some health problems, avoids surgery and certainly lower costs. An alternative to surgical treatment of many conditions is offered, thereby reducing complications (morbidity) and can eliminate the need for hospitalization, in some cases. The development of new materials has allowed the most common working tools of the medical field are improved and become increasingly more efficient in the diagnosis and treatment of diseases, improving the training of radiologists in the interventional field. (author) [es

Development of pulmonary vascular response to oxygen

International Nuclear Information System (INIS)

Morin, F.C. III; Egan, E.A.; Ferguson, W.; Lundgren, C.E.

1988-01-01

The ability of the pulmonary circulation of the fetal lamb to respond to a rise in oxygen tension was studied from 94 to 146 days of gestation. The unanesthetized ewe breathed room air at normal atmospheric pressure, followed by 100% oxygen at three atmospheres absolute pressure in a hyperbaric chamber. In eleven near-term lambs, fetal arterial oxygen tension (Pa O 2 ) increased from 25 to 55 Torr, which increased the proportion or right ventricular output distributed to the fetal lungs from 8 to 59%. In five very immature lambs fetal Pa O 2 increased from 27 to 174 Torr, but the proportion of right ventricular output distributed to the lung did not change. In five of the near-term lambs, pulmonary blood flow was measured. For each measurement of the distribution of blood flow, approximately 8 x 10 5 spheres of 15-μm diameter, labeled with either 153 Gd, 113 Sn, 103 Ru, 95 Nb, or 46 Sc were injected. It increased from 34 to 298 ml · kg fetal wt -1 · min -1 , an 8.8-fold increase. The authors conclude that the pulmonary circulation of the fetal lamb does not respond to an increase in oxygen tension before 101 days of gestation; however, near term an increase in oxygen tension alone can induce the entire increase in pulmonary blood flow that normally occurs after the onset of breathing at birth

Dissolution and reactive oxygen species generation of inhaled cemented tungsten carbide particles in artificial human lung fluids

International Nuclear Information System (INIS)

Stefaniak, A B; Leonard, S S; Hoover, M D; Virji, M A; Day, G A

2009-01-01

Inhalation of both cobalt (Co) and tungsten carbide (WC) particles is associated with development of hard metal lung disease (HMD) via generation of reactive oxygen species (ROS), whereas Co alone is sufficient to cause asthma via solubilization and hapten formation. We characterized bulk and aerodynamically size-separated W, WC, Co, spray dryer (pre-sintered), and chamfer grinder (post-sintered) powders. ROS generation was measured in the murine RAW 264.7 cell line using electron spin resonance. When dose was normalized to surface area, hydroxyl radical generation was independent of particle size, which suggests that particle surface chemistry may be an important exposure factor. Chamfer grinder particles generated the highest levels of ROS, consistent with the hypothesis that intimate contact of metals is important for ROS generation. In artificial extracellular lung fluid, alkylbenzyldimethylammonium chloride (ABDC), added to prevent mold growth during experiments, did not influence dissolution of Co (44.0±5.2 vs. 48.3±6.4%); however, dissolution was higher (p<0.05) in the absence of phosphate (62.0±5.4 vs. 48.3±6.4%). In artificial macrophage phagolysosomal fluid, dissolution of Co (36.2±10.4%) does not appear to be influenced (p=0.30) by the absence of glycine (29.8±2.1%), phosphate (39.6±8.6%), or ABDC (44.0±10.5%). These results aid in assessing and understanding Co and W inhalation dosimetry.

Oxygen supplementation for critically ill patients

DEFF Research Database (Denmark)

Barbateskovic, M; Schjørring, O L; Jakobsen, J C

2018-01-01

. The objective of this systematic review is to critically assess the evidence of randomised clinical trials on the effects of higher versus lower inspiratory oxygen fractions or targets of arterial oxygenation in critically ill adult patients. METHODS: We will search for randomised clinical trials in major......BACKGROUND: In critically ill patients, hypoxaemia is a common clinical manifestation of inadequate gas exchange in the lungs. Supplemental oxygen is therefore given to all critically ill patients. This can result in hyperoxaemia, and some observational studies have identified harms with hyperoxia...... in international guidelines despite lack of robust evidence of its effectiveness. To our knowledge, no systematic review of randomised clinical trials has investigated the effects of oxygen supplementation in critically ill patients. This systematic review will provide reliable evidence to better inform future...

Oxygen Supplementation to Stabilize Preterm Infants in the Fetal to Neonatal Transition: No Satisfactory Answer.

Science.gov (United States)

Torres-Cuevas, Isabel; Cernada, Maria; Nuñez, Antonio; Escobar, Javier; Kuligowski, Julia; Chafer-Pericas, Consuelo; Vento, Maximo

2016-01-01

Fetal life elapses in a relatively low oxygen environment. Immediately after birth with the initiation of breathing, the lung expands and oxygen availability to tissue rises by twofold, generating a physiologic oxidative stress. However, both lung anatomy and function and the antioxidant defense system do not mature until late in gestation, and therefore, very preterm infants often need respiratory support and oxygen supplementation in the delivery room to achieve postnatal stabilization. Notably, interventions in the first minutes of life can have long-lasting consequences. Recent trials have aimed to assess what initial inspiratory fraction of oxygen and what oxygen targets during this transitional period are best for extremely preterm infants based on the available nomogram. However, oxygen saturation nomogram informs only of term and late preterm infants but not on extremely preterm infants. Therefore, the solution to this conundrum may still have to wait before a satisfactory answer is available.

Quantitative aspects of oxygen and carbon dioxide exchange ...

African Journals Online (AJOL)

Quantitative aspects of oxygen and carbon dioxide exchange through the ... ceratophthalmus (Crustacea: Decapoda) during rest and exercise in water and ... intersects zero time on the x-axis, indicating rapid gas exchange at the lung surface.

Effects of whole-body gamma irradiation on oxygen transport by rat erythrocytes

International Nuclear Information System (INIS)

Thiriot, Christian; Kergonou, J.F.; Rocquet, Guy; Allary, Michel; Saint-Blancard, Jacques

1982-01-01

In this work, we studied the influence of whole-body gamma irradiation (8 Gy) upon oxygen transport by erythrocytes, through the erythrocyte count and related parameters, and through the factors affecting the oxygen affinity of hemoglobin. The oxygen affinity of hemoglobin is increased from day D + 5 after irradiation, and a severe erythropenia develops from day D + 8. These modifications probably result in tissue hypoxia via diminished oxygen transport from lungs to tissues, and decreased oxygen release from oxyhemoglobin in tissues

Closed-loop mechanical ventilation for lung injury: a novel physiological-feedback mode following the principles of the open lung concept.

Science.gov (United States)

Schwaiberger, David; Pickerodt, Philipp A; Pomprapa, Anake; Tjarks, Onno; Kork, Felix; Boemke, Willehad; Francis, Roland C E; Leonhardt, Steffen; Lachmann, Burkhard

2018-06-01

Adherence to low tidal volume (V T ) ventilation and selected positive end-expiratory pressures are low during mechanical ventilation for treatment of the acute respiratory distress syndrome. Using a pig model of severe lung injury, we tested the feasibility and physiological responses to a novel fully closed-loop mechanical ventilation algorithm based on the "open lung" concept. Lung injury was induced by surfactant washout in pigs (n = 8). Animals were ventilated following the principles of the "open lung approach" (OLA) using a fully closed-loop physiological feedback algorithm for mechanical ventilation. Standard gas exchange, respiratory- and hemodynamic parameters were measured. Electrical impedance tomography was used to quantify regional ventilation distribution during mechanical ventilation. Automatized mechanical ventilation provided strict adherence to low V T -ventilation for 6 h in severely lung injured pigs. Using the "open lung" approach, tidal volume delivery required low lung distending pressures, increased recruitment and ventilation of dorsal lung regions and improved arterial blood oxygenation. Physiological feedback closed-loop mechanical ventilation according to the principles of the open lung concept is feasible and provides low tidal volume ventilation without human intervention. Of importance, the "open lung approach"-ventilation improved gas exchange and reduced lung driving pressures by opening atelectasis and shifting of ventilation to dorsal lung regions.

Hyperbaric oxygen sensitizes anoxic Pseudomonas aeruginosa biofilm to ciprofloxacin

DEFF Research Database (Denmark)

Kolpen, Mette; Lerche, Christian J; Kragh, Kasper Nørskov

2017-01-01

Chronic Pseudomonas aeruginosa lung infection is characterized by the presence of endobronchial antibiotic-tolerant biofilm subject to strong oxygen (O2) depletion due to the activity of surrounding polymorphonuclear leukocytes. The exact mechanisms affecting the antibiotic susceptibility...... metabolism activity and the endogenous formation of reactive O2 radicals (ROS). In this study we aimed to apply hyperbaric oxygen treatment (HBOT) in order to sensitize anoxic P. aeruginosa agarose-biofilms established to mimic situations with intense O2 consumption by the host response in the cystic...... fibrosis (CF) lung. Application of HBOT resulted in enhanced bactericidal activity of ciprofloxacin at clinically relevant durations and was accompanied by indications of restored aerobic respiration, involvement of endogenous lethal oxidative stress and increased bacterial growth. The findings highlight...

Processing of membranes for oxygenation using the Bellhouse-effect

Directory of Open Access Journals (Sweden)

Neußer C.

2015-09-01

Full Text Available State-of-the-art lung support systems are limited to short time application because of a lack of long term hemocompatibility and protein absorption on the membrane surfaces. In a highly interdisciplinary project at RWTH Aachen University a biohybrid lung assist system with endothelialised gas exchange flat membranes is developed to improve long term compatibility of oxygenators. To increase the gas exchange performance of flat membranes hollows are imprinted in the membrane surfaces. This approach is based on the research of B. J. Bell-house et al. [1], who discovered this effect, now known as Bellhouse-effect, around 1960. In this paper a processes to manufacture membrane assemblies for oxygenation with imprinted hollows on the flat membrane surfaces is reviewed.

Neurogenic Pulmonary Edema (A Case Report

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Funda Gümüş

2012-08-01

Full Text Available Neurogenic pulmonary edema is a life threatening complication of severe central nervous system injury. The most common cause of neurogenic pulmonary edema is subarachnoid hemorrhage followed by head trauma and epilepsy. The rare causes are cervical spine trauma, multiplesclerosis, cerebellar hemorrhage and intracranial tumors. Neurogenic pulmonary edema is characterized by an increase in extravascular lung water in patients who have sustained a sudden change in neurologic condition. The exact pathophysiology is unclear but it probably involves an adrenergic response to the central nervous system injury which leads to increased catecholamine, pulmonary hydrostatic pressure and increased lung capillary permeability. The presenting symptoms are nonspecific and often include dyspnea, tachypnea, tachycardia, hypoxemia, pinkfroty secretion, bilateral pulmonary infiltrates and crackles. These symptoms start within minutes or hours and resolves 48-72 hours that typically for neurogenic pulmonary edema. Basic principles of treatment, surgical decompression, reduce intracranial pressure, controlled ventilation with suplemental oxygen, positive end expiratory pressure and diuresis. We report a case with neurogenic pulmonary edema that occured after head trauma. (Journal of the Turkish Society Intensive Care 2012; 10: 59-62

The nitric oxide prodrug JS-K is effective against non-small-cell lung cancer cells in vitro and in vivo: involvement of reactive oxygen species.

Science.gov (United States)

Maciag, Anna E; Chakrapani, Harinath; Saavedra, Joseph E; Morris, Nicole L; Holland, Ryan J; Kosak, Ken M; Shami, Paul J; Anderson, Lucy M; Keefer, Larry K

2011-02-01

Non-small-cell lung cancer is among the most common and deadly forms of human malignancies. Early detection is unusual, and there are no curative therapies in most cases. Diazeniumdiolate-based nitric oxide (NO)-releasing prodrugs are a growing class of promising NO-based therapeutics. Here, we show that O(2)-(2,4-dinitrophenyl)-1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K) is a potent cytotoxic agent against a subset of human non-small-cell lung cancer cell lines both in vitro and as xenografts in mice. JS-K treatment led to 75% reduction in the growth of H1703 lung adenocarcinoma cells in vivo. Differences in sensitivity to JS-K in different lung cancer cell lines seem to be related to their endogenous levels of reactive oxygen species (ROS)/reactive nitrogen species (RNS). Other related factors, levels of peroxiredoxin 1 (PRX1) and 8-oxo-deoxyguanosine glycosylase (OGG1), also correlated with drug sensitivity. Treatment of the lung adenocarcinoma cells with JS-K resulted in oxidative/nitrosative stress in cells with high basal levels of ROS/RNS, which, combined with the arylating properties of the compound, was reflected in glutathione depletion and alteration in cellular redox potential, mitochondrial membrane permeabilization, and cytochrome c release. Inactivation of manganese superoxide dismutase by nitration was associated with increased superoxide and significant DNA damage. Apoptosis followed these events. Taken together, the data suggest that diazeniumdiolate-based NO-releasing prodrugs may have application as a personalized therapy for lung cancers characterized by high levels of ROS/RNS. PRX1 and OGG1 proteins, which can be easily measured, could function as biomarkers for identifying tumors sensitive to the therapy.

Tangeretin sensitises human lung cancer cells to TRAIL- induced ...

African Journals Online (AJOL)

Keywords: Apoptosis, Death receptors, Lung cancer, Tangeretin, Reactive oxygen ... strategies that specifically target molecules .... concentrations were determined using a Bio-Rad ..... suppresses invasion of colon and pancreatic cancer.

Oxygen supplementation to stabilize preterm infants in the fetal to neonatal transition: no satisfactory answer.

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Isabel eTorres-Cuevas

2016-04-01

Full Text Available Fetal life elapses in a relatively low oxygen environment. Immediately after birth with the initiation of breathing the lung expands and oxygen availability to tissue rises by twofold generating a physiologic oxidative stress. However, both lung anatomy and function and the antioxidant defense system do not mature until late in gestation and therefore very preterm infants often need respiratory support and oxygen supplementation in the delivery room to achieve postnatal stabilization. Notably, interventions in the first minutes of life can have long-lasting consequences. Recent trials have aimed to assess what initial inspiratory fraction of oxygen and what oxygen targets during this transitional period are best for extremely preterm infants based on the available nomogram. However, oxygen saturation nomogram informs only of term and late preterm infants but not on extremely preterm infants. Therefore, the solution to this conundrum may still have to wait before a satisfactory answer is available.

Response of rat lung tissue to short-term hyperoxia: a proteomic approach.

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Spelten, Oliver; Wetsch, Wolfgang A; Wrettos, Georg; Kalenka, Armin; Hinkelbein, Jochen

2013-11-01

An inspiratory oxygen fraction of 1.0 is often required to avoid hypoxia both in many pre- and in-hospital situations. On the other hand, hyperoxia may lead to deleterious consequences (cell growth inhibition, inflammation, and apoptosis) for numerous tissues including the lung. Whereas clinical effects of hyperoxic lung injury are well known, its impact on the expression of lung proteins has not yet been evaluated sufficiently. The aim of this study was to analyze time-dependent alterations of protein expression in rat lung tissue after short-term normobaric hyperoxia (NH). After approval of the local ethics committee for animal research, N = 36 Wistar rats were randomized into six different groups: three groups with NH with exposure to 100 % oxygen for 3 h and three groups with normobaric normoxia (NN) with exposure to room air (21 % oxygen). After the end of the experiments, lungs were removed immediately (NH0 and NN0), after 3 days (NH3 and NN3) and after 7 days (NH7 and NN7). Lung lysates were analyzed by two-dimensional gel electrophoresis (2D-GE) followed by peptide mass fingerprinting using mass spectrometry. Statistical analysis was performed with Delta 2D (DECODON GmbH, Greifswald, Germany; ANOVA, Bonferroni correction, p pO2 was significantly higher in NH-groups compared to NN-groups (581 ± 28 vs. 98 ± 12 mmHg; p < 0.01), all other physiological parameters did not differ. Expression of 14 proteins were significantly altered: two proteins were up-regulated and 12 proteins were down-regulated. Even though NH was comparatively short termed, significant alterations in lung protein expression could be demonstrated up to 7 days after hyperoxia. The identified proteins indicate an association with cell growth inhibition, regulation of apoptosis, and approval of structural cell integrity.

A novel method for right one-lung ventilation modeling in rabbits.

Science.gov (United States)

Xu, Ze-Ping; Gu, Lian-Bing; Bian, Qing-Ming; Li, Peng-Yi; Wang, Li-Jun; Chen, Xiao-Xiang; Zhang, Jing-Yuan

2016-08-01

There is no standard method by which to establish a right one-lung ventilation (OLV) model in rabbits. In the present study, a novel method is proposed to compare with two other methods. After 0.5 h of baseline two-lung ventilation (TLV), 40 rabbits were randomly divided into sham group (TLV for 3 h as a contrast) and three right-OLV groups (right OLV for 3 h with different methods): Deep intubation group, clamp group and blocker group (deeply intubate the self-made bronchial blocker into the left main bronchus, the novel method). These three methods were compared using a number of variables: Circulation by heart rate (HR), mean arterial pressure (MAP); oxygenation by arterial blood gas analysis; airway pressure; lung injury by histopathology; and time, blood loss, success rate of modeling. Following OLV, compared with the sham group, arterial partial pressure of oxygen and arterial hemoglobin oxygen saturation decreased, peak pressure increased and lung injury scores were higher in three OLV groups at 3 h of OLV. All these indexes showed no differences between the three OLV groups. During right-OLV modeling, less time was spent in the blocker group (6±2 min), compared with the other two OLV groups (13±4 min in deep intubation group, Pright-OLV model in rabbits.

Oxygen Exposure Resulting in Arterial Oxygen Tensions Above the Protocol Goal Was Associated With Worse Clinical Outcomes in Acute Respiratory Distress Syndrome.

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Aggarwal, Neil R; Brower, Roy G; Hager, David N; Thompson, B Taylor; Netzer, Giora; Shanholtz, Carl; Lagakos, Adrian; Checkley, William

2018-04-01

High fractions of inspired oxygen may augment lung damage to exacerbate lung injury in patients with acute respiratory distress syndrome. Participants enrolled in Acute Respiratory Distress Syndrome Network trials had a goal partial pressure of oxygen in arterial blood range of 55-80 mm Hg, yet the effect of oxygen exposure above this arterial oxygen tension range on clinical outcomes is unknown. We sought to determine if oxygen exposure that resulted in a partial pressure of oxygen in arterial blood above goal (> 80 mm Hg) was associated with worse outcomes in patients with acute respiratory distress syndrome. Longitudinal analysis of data collected in these trials. Ten clinical trials conducted at Acute Respiratory Distress Syndrome Network hospitals between 1996 and 2013. Critically ill patients with acute respiratory distress syndrome. None. We defined above goal oxygen exposure as the difference between the fraction of inspired oxygen and 0.5 whenever the fraction of inspired oxygen was above 0.5 and when the partial pressure of oxygen in arterial blood was above 80 mm Hg. We then summed above goal oxygen exposures in the first five days to calculate a cumulative above goal oxygen exposure. We determined the effect of a cumulative 5-day above goal oxygen exposure on mortality prior to discharge home at 90 days. Among 2,994 participants (mean age, 51.3 yr; 54% male) with a study-entry partial pressure of oxygen in arterial blood/fraction of inspired oxygen that met acute respiratory distress syndrome criteria, average cumulative above goal oxygen exposure was 0.24 fraction of inspired oxygen-days (interquartile range, 0-0.38). Participants with above goal oxygen exposure were more likely to die (adjusted interquartile range odds ratio, 1.20; 95% CI, 1.11-1.31) and have lower ventilator-free days (adjusted interquartile range mean difference of -0.83; 95% CI, -1.18 to -0.48) and lower hospital-free days (adjusted interquartile range mean difference of -1.38; 95

Neutrophil extracellular traps are pathogenic in primary graft dysfunction after lung transplantation.

Science.gov (United States)

Sayah, David M; Mallavia, Beñat; Liu, Fengchun; Ortiz-Muñoz, Guadalupe; Caudrillier, Axelle; DerHovanessian, Ariss; Ross, David J; Lynch, Joseph P; Saggar, Rajan; Ardehali, Abbas; Ware, Lorraine B; Christie, Jason D; Belperio, John A; Looney, Mark R

2015-02-15

Primary graft dysfunction (PGD) causes early mortality after lung transplantation and may contribute to late graft failure. No effective treatments exist. The pathogenesis of PGD is unclear, although both neutrophils and activated platelets have been implicated. We hypothesized that neutrophil extracellular traps (NETs) contribute to lung injury in PGD in a platelet-dependent manner. To study NETs in experimental models of PGD and in lung transplant patients. Two experimental murine PGD models were studied: hilar clamp and orthotopic lung transplantation after prolonged cold ischemia (OLT-PCI). NETs were assessed by immunofluorescence microscopy and ELISA. Platelet activation was inhibited with aspirin, and NETs were disrupted with DNaseI. NETs were also measured in bronchoalveolar lavage fluid and plasma from lung transplant patients with and without PGD. NETs were increased after either hilar clamp or OLT-PCI compared with surgical control subjects. Activation and intrapulmonary accumulation of platelets were increased in OLT-PCI, and platelet inhibition reduced NETs and lung injury, and improved oxygenation. Disruption of NETs by intrabronchial administration of DNaseI also reduced lung injury and improved oxygenation. In bronchoalveolar lavage fluid from human lung transplant recipients, NETs were more abundant in patients with PGD. NETs accumulate in the lung in both experimental and clinical PGD. In experimental PGD, NET formation is platelet-dependent, and disruption of NETs with DNaseI reduces lung injury. These data are the first description of a pathogenic role for NETs in solid organ transplantation and suggest that NETs are a promising therapeutic target in PGD.

Role of metal-induced reactive oxygen species generation in lung ...

Indian Academy of Sciences (India)

Unknown

Inhalation of residual oil fly ash (ROFA) increases pulmonary morbidity in exposed workers. We examined the ... vated levels of ambient air pollutants is associated with increased .... study to assess the role that ROS play in the lung disease.

Severe hypoxemia during veno-venous extracorporeal membrane oxygenation: exploring the limits of extracorporeal respiratory support

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Liane Brescovici Nunes

2014-03-01

Full Text Available OBJECTIVE: Veno-venous extracorporeal oxygenation for respiratory support has emerged as a rescue alternative for patients with hypoxemia. However, in some patients with more severe lung injury, extracorporeal support fails to restore arterial oxygenation. Based on four clinical vignettes, the aims of this article were to describe the pathophysiology of this concerning problem and to discuss possibilities for hypoxemia resolution. METHODS: Considering the main reasons and rationale for hypoxemia during veno-venous extracorporeal membrane oxygenation, some possible bedside solutions must be considered: 1 optimization of extracorporeal membrane oxygenation blood flow; 2 identification of recirculation and cannula repositioning if necessary; 3 optimization of residual lung function and consideration of blood transfusion; 4 diagnosis of oxygenator dysfunction and consideration of its replacement; and finally 5 optimization of the ratio of extracorporeal membrane oxygenation blood flow to cardiac output, based on the reduction of cardiac output. CONCLUSION: Therefore, based on the pathophysiology of hypoxemia during veno-venous extracorporeal oxygenation support, we propose a stepwise approach to help guide specific interventions.

Lung scan abnormalities in asthma and their correlation with lung function

International Nuclear Information System (INIS)

Vernon, P.; Burton, G.H.; Seed, W.A.; Charing Cross Hospital, London

1986-01-01

We have used asthma as a model of airways disease to test how well an automated, quantitative method of analysis of lung scans correlates with physiological measurements of disturbed lung function and gas exchange. We studies 25 asthmatics (age 16-73) of widely differing severity (forced expiratory volume in 1-s FEV 1 22%-123% of predicted value), who had airways tests, arterial blood gas analysis, and krypton-technetium lung scans within a short time of each other. In all patients with airways obstruction and in some with normal function during remission, scans showed the typical appearances of multiple defects of ventilation and perfusion. The severity of ventilation defects was assessed from the posterior view of the krypton scan compared to an age- and sex-matched normal range to yield an underventilation score. This correlated closely with the severity of airways obstruction as measured by forced expiratory manouevres. Ventilation and perfusion defects were usually imperfectly matched; the severity of this was computed using a subtraction method applied to the counts on the posterior krypton and technetium scans. The degree of mismatch was inversely related to the arterial partial pressure of oxygen (r=-0.86). The results suggest that computer scan analysis can provide usual functional information about the lung in airways disease. (orig.)

Hydrogen alleviates hyperoxic acute lung injury related endoplasmic reticulum stress in rats through upregulation of SIRT1.

Science.gov (United States)

Sun, Qiang; Han, Wenjie; Hu, Huijun; Fan, Danfeng; Li, Yanbo; Zhang, Yu; Lv, Yan; Li, Mingxin; Pan, Shuyi

2017-06-01

Hyperoxic acute lung injury (HALI) is a major clinical problem for patients undergoing supplemental oxygen therapy. Currently in clinical settings there exist no effective means of prevention or treatment methods. Our previous study found that: hydrogen could reduce HALI, as well as oxidative stress. This research will further explore the mechanism underlying the protective effect of hydrogen on oxygen toxicity. Rats were randomly assigned into three experimental groups and were exposed in a oxygen chamber for 60 continuous hours: 100% balanced air (control); 100% oxygen (HALI); 100% oxygen with hydrogen treatment (HALI + HRS). We examined lung function by wet to dry ratio of lung, lung pleural effusion and cell apoptosis. We also detected endoplasmic reticulum stress (ERS) by examining the expression of CHOP, GRP78 and XBP1. We further investigated the role of Sirtuin 1 (SIRT1) in HALI, which contributes to cellular regulation including ERS, by examining its expression after hydrogen treatment with SIRT1 inhibitor. Hydrogen could significantly reduce HALI by reducing lung edema and apoptosis, inhibiting the elevating of ERS and increased SIRT1 expression. By inhibition of SIRT1 expression, the effect of hydrogen on prevention of HALI is significantly weakened, the inhibition of the ERS was also reversed. Our findings indicate that hydrogen could reduce HALI related ERS and the mechanism of hydrogen may be associated with upregulation of SIRT1, this study reveals the molecular mechanisms underlying the protective effect of hydrogen, which provides a new theoretical basis for clinical application of hydrogen.

The Nitric Oxide Prodrug JS-K Is Effective against Non–Small-Cell Lung Cancer Cells In Vitro and In Vivo: Involvement of Reactive Oxygen SpeciesS⃞

Science.gov (United States)

Chakrapani, Harinath; Saavedra, Joseph E.; Morris, Nicole L.; Holland, Ryan J.; Kosak, Ken M.; Shami, Paul J.; Anderson, Lucy M.; Keefer, Larry K.

2011-01-01

Non–small-cell lung cancer is among the most common and deadly forms of human malignancies. Early detection is unusual, and there are no curative therapies in most cases. Diazeniumdiolate-based nitric oxide (NO)-releasing prodrugs are a growing class of promising NO-based therapeutics. Here, we show that O2-(2,4-dinitrophenyl)-1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K) is a potent cytotoxic agent against a subset of human non–small-cell lung cancer cell lines both in vitro and as xenografts in mice. JS-K treatment led to 75% reduction in the growth of H1703 lung adenocarcinoma cells in vivo. Differences in sensitivity to JS-K in different lung cancer cell lines seem to be related to their endogenous levels of reactive oxygen species (ROS)/reactive nitrogen species (RNS). Other related factors, levels of peroxiredoxin 1 (PRX1) and 8-oxo-deoxyguanosine glycosylase (OGG1), also correlated with drug sensitivity. Treatment of the lung adenocarcinoma cells with JS-K resulted in oxidative/nitrosative stress in cells with high basal levels of ROS/RNS, which, combined with the arylating properties of the compound, was reflected in glutathione depletion and alteration in cellular redox potential, mitochondrial membrane permeabilization, and cytochrome c release. Inactivation of manganese superoxide dismutase by nitration was associated with increased superoxide and significant DNA damage. Apoptosis followed these events. Taken together, the data suggest that diazeniumdiolate-based NO-releasing prodrugs may have application as a personalized therapy for lung cancers characterized by high levels of ROS/RNS. PRX1 and OGG1 proteins, which can be easily measured, could function as biomarkers for identifying tumors sensitive to the therapy. PMID:20962031

Bacterial sinusitis can be a focus for initial lung colonisation and chronic lung infection in patients with cystic fibrosis

DEFF Research Database (Denmark)

Aanæs, Kasper

2013-01-01

(Pseudomonas aeruginosa, Achromobacter xylosoxidans, Burkholderia cepacia complex). The environment in the sinuses is in many ways similar to that of the lower respiratory tract, e.g. low oxygen concentration in secretions. Sinus bacteria are more difficult to eradicate than in the lungs, thus, having good...

The change of longitudinal relaxation rate in oxygen enhanced pulmonary MRI depends on age and BMI but not diffusing capacity of carbon monoxide in healthy never-smokers.

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Simon Sven Ivan Kindvall

Full Text Available Oxygen enhanced pulmonary MRI is a promising modality for functional lung studies and has been applied to a wide range of pulmonary conditions. The purpose of this study was to characterize the oxygen enhancement effect in the lungs of healthy, never-smokers, in light of a previously established relationship between oxygen enhancement and diffusing capacity of carbon monoxide in the lung (DL,CO in patients with lung disease.In 30 healthy never-smoking volunteers, an inversion recovery with gradient echo read-out (Snapshot-FLASH was used to quantify the difference in longitudinal relaxation rate, while breathing air and 100% oxygen, ΔR1, at 1.5 Tesla. Measurements were performed under multiple tidal inspiration breath-holds.In single parameter linear models, ΔR1 exhibit a significant correlation with age (p = 0.003 and BMI (p = 0.0004, but not DL,CO (p = 0.33. Stepwise linear regression of ΔR1 yields an optimized model including an age-BMI interaction term.In this healthy, never-smoking cohort, age and BMI are both predictors of the change in MRI longitudinal relaxation rate when breathing oxygen. However, DL,CO does not show a significant correlation with the oxygen enhancement. This is possibly because oxygen transfer in the lung is not diffusion limited at rest in healthy individuals. This work stresses the importance of using a physiological model to understand results from oxygen enhanced MRI.

Mechanical ventilation in patients subjected to extracorporeal membrane oxygenation (ECMO).

Science.gov (United States)

López Sanchez, M

2017-11-01

Mechanical ventilation (MV) is a crucial element in the management of acute respiratory distress syndrome (ARDS), because there is high level evidence that a low tidal volume of 6ml/kg (protective ventilation) improves survival. In these patients with refractory respiratory insufficiency, venovenous extracorporeal membrane oxygenation (ECMO) can be used. This salvage technique improves oxygenation, promotes CO 2 clearance, and facilitates protective and ultraprotective MV, potentially minimizing ventilation-induced lung injury. Although numerous trials have investigated different ventilation strategies in patients with ARDS, consensus is lacking on the optimal MV settings during venovenous ECMO. Although the concept of "lung rest" was introduced years ago, there are no evidence-based guidelines on its use in application to MV in patients supported by ECMO. How MV in ECMO patients can promote lung recovery and weaning from ventilation is not clear. The purpose of this review is to describe the ventilation strategies used during venovenous ECMO in clinical practice. Copyright © 2017 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

[The oxygen consumption of ostrich embryos during incubation].

Science.gov (United States)

Reiner, G; Dzapo, V

1995-02-01

This work deals with the oxygen consumption of ostrich chicks during incubation. Brood eggs were incubated in a hermetic isolated acrylic-glass cylinder. Reduction of oxygen content in the air surrounding the egg was measured using an oxygen-sensitive electrode. A sigmoid curve could be drawn during incubation, with the steepest phase being around day 26. Maximum oxygen consumption was reached on day 36. It was slightly decreased until day 39, when the embryo switches to lung circulation, followed again by an increase until hatching. Average oxygen consumptions for the whole brood interval were calculated to 63.6 liters. Oxygen volumes consumed on day 36 result in a demand about to 240 liters of fresh air per egg and day. Oxygen consumption of the embryos on day 36 was significantly positive correlated with their vitality. Numb or less vital embryos could be clearly differentiated from others. The higher a chick's oxygen consumption, the earlier and shorter its hatching. Possible applications of the method in regard to the evaluation of incubation parameters or chicken constitution are discussed.

Satellite in transit metastases in rapidly fatal conjunctival melanoma: implications for angiotropism and extravascular migratory metastasis (description of a murine model for conjunctival melanoma).

Science.gov (United States)

Barnhill, Raymond L; Lemaitre, Stéphanie; Lévy-Gabrielle, Christine; Rodrigues, Manuel; Desjardins, Laurence; Dendale, Rémi; Vincent-Salomon, Anne; Roman-Roman, Sergio; Lugassy, Claire; Cassoux, Nathalie

2016-02-01

Little information is currently available concerning loco-regional metastases such as satellite and in transit metastases and their natural history in conjunctival melanoma as compared to cutaneous melanoma. Angiotropism, a marker of extravascular migration of melanoma cells along vascular channels, often appears responsible for microscopic satellite, satellite and in transit metastases development in cutaneous melanoma. In addition, diffuse tissue microscopic satellites are correlated with widespread melanoma dissemination and death. Herein we report rapid conjunctival melanoma progression and a fatal outcome in four of five patients following recurrence as satellite in transit metastases. Five patients aged 31, 60, 63, 56, and 67 years developed primary conjunctival melanoma, histologically characterised by tumour thicknesses of 4, 4, 1.1, 3, and 2 mm. Two or more conjunctival melanomas manifested ulceration, significant mitotic rates, necrosis, angiotropism, and intralesional transformation. The conjunctival melanoma recurred in a matter of months as one or more discrete satellite in transit lesions in the vicinity of the primary melanoma. Histological examination revealed well-defined micronodules containing atypical melanocytes in the subepithelial connective tissue stroma. All lesions were extravascular and most appeared angiotropic. Four of five patients subsequently developed parotid or other loco-regional nodal disease and rapidly ensuing widespread metastases and death. The time course from diagnosis to the demise of the patients averaged about 13 (range 7-20) months. Our findings suggest that satellite in transit metastases constitute an important new risk marker for possible rapid metastatic disease progression and death in patients with conjunctival melanoma. This finding appears to take on even greater significance if such lesions develop rapidly, i.e., in a matter of weeks or months following diagnosis of primary conjunctival melanoma, and if the

Contribution of neutrophils to acute lung injury.

Science.gov (United States)

Grommes, Jochen; Soehnlein, Oliver

2011-01-01

Treatment of acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), remain unsolved problems of intensive care medicine. ALI/ARDS are characterized by lung edema due to increased permeability of the alveolar-capillary barrier and subsequent impairment of arterial oxygenation. Lung edema, endothelial and epithelial injury are accompanied by an influx of neutrophils into the interstitium and broncheoalveolar space. Hence, activation and recruitment of neutrophils are regarded to play a key role in progression of ALI/ARDS. Neutrophils are the first cells to be recruited to the site of inflammation and have a potent antimicrobial armour that includes oxidants, proteinases and cationic peptides. Under pathological circumstances, however, unregulated release of these microbicidal compounds into the extracellular space paradoxically can damage host tissues. This review focuses on the mechanisms of neutrophil recruitment into the lung and on the contribution of neutrophils to tissue damage in ALI.

The effect of hyperbaric oxygen treatment on aspiration pneumonia.

Science.gov (United States)

Sahin, Sevtap Hekimoglu; Kanter, Mehmet; Ayvaz, Suleyman; Colak, Alkin; Aksu, Burhan; Guzel, Ahmet; Basaran, Umit Nusret; Erboga, Mustafa; Ozcan, Ali

2011-08-01

We have studied whether hyperbaric oxygen (HBO) prevents different pulmonary aspiration materials-induced lung injury in rats. The experiments were designed in 60 Sprague-Dawley rats, ranging in weight from 250 to 300 g, randomly allotted into one of six groups (n = 10): saline control, Biosorb Energy Plus (BIO), hydrochloric acid (HCl), saline + HBO treated, BIO + HBO treated, and HCl + HBO treated. Saline, BIO, HCl were injected into the lungs in a volume of 2 ml/kg. A total of seven HBO sessions were performed at 2,4 atm 100% oxygen for 90 min at 6-h intervals. Seven days later, rats were sacrificed, and both lungs in all groups were examined biochemically and histopathologically. Our findings show that HBO inhibits the inflammatory response reducing significantly (P fibrosis, granuloma, and necrosis formation in different pulmonary aspiration models. Pulmonar aspiration significantly increased the tissue HP content, malondialdehyde (MDA) levels and decreased (P < 0.05) the antioxidant enzyme (SOD, GSH-Px) activities. HBO treatment significantly (P < 0.05) decreased the elevated tissue HP content, and MDA levels and prevented inhibition of SOD, and GSH-Px (P < 0.05) enzymes in the tissues. Furthermore, there is a significant reduction in the activity of inducible nitric oxide synthase, TUNEL and arise in the expression of surfactant protein D in lung tissue of different pulmonary aspiration models with HBO therapy. It was concluded that HBO treatment might be beneficial in lung injury, therefore, shows potential for clinical use.

Adult venovenous extracorporeal membrane oxygenation for severe respiratory failure: Current status and future perspectives.

Science.gov (United States)

Sen, Ayan; Callisen, Hannelisa E; Alwardt, Cory M; Larson, Joel S; Lowell, Amelia A; Libricz, Stacy L; Tarwade, Pritee; Patel, Bhavesh M; Ramakrishna, Harish

2016-01-01

Extracorporeal membrane oxygenation (ECMO) for severe acute respiratory failure was proposed more than 40 years ago. Despite the publication of the ARDSNet study and adoption of lung protective ventilation, the mortality for acute respiratory failure due to acute respiratory distress syndrome has continued to remain high. This technology has evolved over the past couple of decades and has been noted to be safe and successful, especially during the worldwide H1N1 influenza pandemic with good survival rates. The primary indications for ECMO in acute respiratory failure include severe refractory hypoxemic and hypercarbic respiratory failure in spite of maximum lung protective ventilatory support. Various triage criteria have been described and published. Contraindications exist when application of ECMO may be futile or technically impossible. Knowledge and appreciation of the circuit, cannulae, and the physiology of gas exchange with ECMO are necessary to ensure lung rest, efficiency of oxygenation, and ventilation as well as troubleshooting problems. Anticoagulation is a major concern with ECMO, and the evidence is evolving with respect to diagnostic testing and use of anticoagulants. Clinical management of the patient includes comprehensive critical care addressing sedation and neurologic issues, ensuring lung recruitment, diuresis, early enteral nutrition, treatment and surveillance of infections, and multisystem organ support. Newer technology that delinks oxygenation and ventilation by extracorporeal carbon dioxide removal may lead to ultra-lung protective ventilation, avoidance of endotracheal intubation in some situations, and ambulatory therapies as a bridge to lung transplantation. Risks, complications, and long-term outcomes and resources need to be considered and weighed in before widespread application. Ethical challenges are a reality and a multidisciplinary approach that should be adopted for every case in consideration.

Effects of Early Continuous Venovenous Hemofiltration on E-Selectin, Hemodynamic Stability, and Ventilatory Function in Patients with Septic-Shock-Induced Acute Respiratory Distress Syndrome

Directory of Open Access Journals (Sweden)

Jian-biao Meng

2016-01-01

Full Text Available Objective. To investigate the effects of 72-hour early-initiated continuous venovenous hemofiltration (ECVVH treatment in patients with septic-shock-induced acute respiratory distress syndrome (ARDS (not acute kidney injury, AKI with regard to serum E-selectin and measurements of lung function and hemodynamic stability. Methods. This prospective nonblinded single institutional randomized study involved 51 patients who were randomly assigned to receive or not receive ECVVH, an ECVVH group (n=24 and a non-ECVVH group (n=27. Besides standard therapies, patients in ECVVH group underwent CVVH for 72 h. Results. At 0 and 24 h after initiation of treatment, arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2 ratio, extravascular lung water index (EVLWI, and E-selectin level were not significantly different between groups (all P>0.05. Compared to non-ECVVH group, PaO2/FiO2 is significantly higher and EVLWI and E-selectin level are significantly lower in ECVVH group (all P<0.05 at 48 h and 72 h after initiation of treatment. The lengths of mechanical ventilation and stay in intensive care unit (ICU were shorter in ECVVH group (all P<0.05, but there was no difference in 28-day mortality between two groups. Conclusions. In patients with septic-shock-induced ARDS (not AKI, treatment with ECVVH in addition to standard therapies improves endothelial function, lung function, and hemodynamic stability and reduces the lengths of mechanical ventilation and stay in ICU.

Continuous distending pressure effects on variables contributing to oxygenation in healthy and ARDS model pigs during HFOV

Science.gov (United States)

Laviola, Marianna; Hajny, Ondrej; Roubik, Karel

2014-10-01

High frequency oscillatory ventilation (HFOV) is an alternative mode of mechanical ventilation. HFOV has been shown to provide adequate ventilation and oxygenation in acute respiratory distress syndrome (ARDS) patients and may represent an effective lung-protective ventilation in patients where conventional ventilation is failing. The aim of this study is to evaluate effects of continuous distending pressure (CDP) on variables that contribute to the oxygenation in healthy and ARDS lung model pigs. Methods. In order to simulate a lung disease, lung injury was induced by lavage with normal saline with detergent in three pigs. HFOV ventilation was applied before and after the lung lavage. CDP was stepwise increased by 2 cmH2O, until the maximum CDP (before the lung lavage 32 cmH2O and after the lung lavage 42 cmH2O) and then it was stepwise decreased by 2 cmH2O to the initial value. In this paper we analyzed the following parameters acquired during our experiments: partial pressure of oxygen in arterial blood (PaO2), cardiac output (CO) and mixed venous blood oxygen saturation (SvO2). In order to find how both PaO2 and CO affected SvO2 during the increase of CDP before and after lavage, a nonlinear regression fitting of the response in SvO2 on the predictors (PaO2 and CO) was implemented. Results. Before the lavage, with increasing of CDP, PaO2 remained constant, CO strongly decreased and SvO2 slightly decreased. After the lavage, with increasing of CDP, PaO2 strongly increased, CO decreased and SvO2 increased. So, development of SvO2 followed the PaO2 and CO trends. Changes in PaO2 and CO occur at decisive CDP step and it was much higher after the lung lavage compared to the healthy lungs. The implemented nonlinear model gives a good goodness of fitting in all three pigs. The values of PaO2 and CO estimated coefficients changed at the same decisive step of CDP identified by the trends. Also the algorithm identified a CDP step much higher after the lung lavage

Initial mechanical ventilator settings and lung protective ventilation in the ED.

Science.gov (United States)

Wilcox, Susan R; Richards, Jeremy B; Fisher, Daniel F; Sankoff, Jeffrey; Seigel, Todd A

2016-08-01

Mechanical ventilation with low tidal volumes has been shown to improve outcomes for patients both with and without acute respiratory distress syndrome. This study aims to characterize mechanically ventilated patients in the emergency department (ED), describe the initial ED ventilator settings, and assess for associations between lung protective ventilation strategies in the ED and outcomes. This was a multicenter, prospective, observational study of mechanical ventilation at 3 academic EDs. We defined lung protective ventilation as a tidal volume of less than or equal to 8 mL/kg of predicted body weight and compared outcomes for patients ventilated with lung protective vs non-lung protective ventilation, including inhospital mortality, ventilator days, intensive care unit length of stay, and hospital length of stay. Data from 433 patients were analyzed. Altered mental status without respiratory pathology was the most common reason for intubation, followed by trauma and respiratory failure. Two hundred sixty-one patients (60.3%) received lung protective ventilation, but most patients were ventilated with a low positive end-expiratory pressure, high fraction of inspired oxygen strategy. Patients were ventilated in the ED for a mean of 5 hours and 7 minutes but had few ventilator adjustments. Outcomes were not significantly different between patients receiving lung protective vs non-lung protective ventilation. Nearly 40% of ED patients were ventilated with non-lung protective ventilation as well as with low positive end-expiratory pressure and high fraction of inspired oxygen. Despite a mean ED ventilation time of more than 5 hours, few patients had adjustments made to their ventilators. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats

Energy Technology Data Exchange (ETDEWEB)

Bakkal, B.H. [Department of Radiation Oncology, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Gultekin, F.A. [Department of General Surgery, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Guven, B. [Department of Biochemistry, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Turkcu, U.O. [Mugla School of Health Sciences, Mugla Sitki Kocman University, Mugla (Turkey); Bektas, S. [Department of Pathology, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Can, M. [Department of Biochemistry, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey)

2013-09-27

Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg). Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage.

Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats

International Nuclear Information System (INIS)

Bakkal, B.H.; Gultekin, F.A.; Guven, B.; Turkcu, U.O.; Bektas, S.; Can, M.

2013-01-01

Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg). Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage

Roentgenoradionuclide study of the liver lymphatic system (the development of the method and criteria for the evaluation of extravascular plasma flow)

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Tatochenko, K V; Morgunov, N B; Uskov, I A [Pervyj Moskovskij Meditsinskij Inst. (USSR)

1984-05-01

An attempt was made to develop an instrumental method for the evaluation of the extravascular plasma flow (lymph flow) of the liver. Ultrasonography of the liver does not give an opportunity to differentiate between different states including those accompanied by the excess lymph discharge into the liver. The results of intraparenchymal lymphography of the liver were analysed in patients with and without biliary and portal hypertension. 11 criteria have been singled out that make it possible to judge an elevated production of the lymph in the liver. A method of ''radioangiolymphography'' of the liver based on the administration of diffusing and nondiffusing radiopharmaceuticals in the afferent vessels of the liver was worked out. Variation in the parameters of the radionuclide circulation seems to reflect significantly extrahepatic circulation in the liver and holds great promise for the use in hepatology.

Roentgenoradionuclide study of the liver lymphatic system (the development of the method and criteria for the evaluation of extravascular plasma flow)

International Nuclear Information System (INIS)

Tatochenko, K.V.; Morgunov, N.B.; Uskov, I.A.

1984-01-01

An attempt was made to develop an instrumental method for the evaluation of the extravascular plasma flow (lymph flow) of the liver. Ultrasonography of the liver does not give an opportunity to differentiate between different states including those accompanied by the excess lymph discharge into the liver. The results of intraparenchymal lymphography of the liver were analysed in patients with and without biliary and portal hypertension. 11 criteria have been singled out that make it possible to judge an elevated production of the lymph in the liver. A method of ''radioangiolymphography'' of the liver based on the administration of diffusing and nondiffusing radiopharmaceuticals in the afferent vessels of the liver was worked out. Variation in the parameters of the radionuclide circulation seems to reflect significantly extrahepatic circulation in the liver and holds great promise for the use in hepatology

Pulmonary Oxidative Stress, Inflammation and Cancer: Respirable Particulate Matter, Fibrous Dusts and Ozone as Major Causes of Lung Carcinogenesis through Reactive Oxygen Species Mechanisms

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Spyridon Loridas

2013-08-01

Full Text Available Reactive oxygen or nitrogen species (ROS, RNS and oxidative stress in the respiratory system increase the production of mediators of pulmonary inflammation and initiate or promote mechanisms of carcinogenesis. The lungs are exposed daily to oxidants generated either endogenously or exogenously (air pollutants, cigarette smoke, etc.. Cells in aerobic organisms are protected against oxidative damage by enzymatic and non-enzymatic antioxidant systems. Recent epidemiologic investigations have shown associations between increased incidence of respiratory diseases and lung cancer from exposure to low levels of various forms of respirable fibers and particulate matter (PM, at occupational or urban air polluting environments. Lung cancer increases substantially for tobacco smokers due to the synergistic effects in the generation of ROS, leading to oxidative stress and inflammation with high DNA damage potential. Physical and chemical characteristics of particles (size, transition metal content, speciation, stable free radicals, etc. play an important role in oxidative stress. In turn, oxidative stress initiates the synthesis of mediators of pulmonary inflammation in lung epithelial cells and initiation of carcinogenic mechanisms. Inhalable quartz, metal powders, mineral asbestos fibers, ozone, soot from gasoline and diesel engines, tobacco smoke and PM from ambient air pollution (PM10 and PM2.5 are involved in various oxidative stress mechanisms. Pulmonary cancer initiation and promotion has been linked to a series of biochemical pathways of oxidative stress, DNA oxidative damage, macrophage stimulation, telomere shortening, modulation of gene expression and activation of transcription factors with important role in carcinogenesis. In this review we are presenting the role of ROS and oxidative stress in the production of mediators of pulmonary inflammation and mechanisms of carcinogenesis.

Development of pulmonary oxygen toxicity in rats after hyperoxic exposure

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Siermontowski Piotr

2014-06-01

Full Text Available The aim of the study was to examine the effects of hyperbaric oxygen on lung aeration on an animal experimental model and compare the obtained results with the anticipated scope of damage to pulmonary parenchyma in humans under the same exposure conditions. The research was carried out on Black Hood rats that were kept in a hyperbaric chamber designed for animals in an atmosphere of pure oxygen and at overpressures of 0.15, 0.2, 0.3, 0.4, and 0.5 MPa for 1, 2 or 4 h. After sacrificing the animals, histopathological specimens were obtained encompassing cross-sections of entire lungs, which were subjected to qualitative and quantitative examination with the use of the 121-point Haug grid. A statistically significant decrease in pulmonary parenchyma was observed as a result of an increasing oxygen partial pressure as well as with prolonged exposure time. The intensification of changes observed was much higher than expected on the basis of calculations performed with the use of tables.

Lung volumes, pulmonary ventilation, and hypoxia following rapid decompression to 60,000 ft (18,288 m).

Science.gov (United States)

Connolly, Desmond M; D'Oyly, Timothy J; McGown, Amanda S; Lee, Vivienne M

2013-06-01

Rapid decompressions (RD) to 60,000 ft (18,288 m) were undertaken by six subjects to provide evidence of satisfactory performance of a contemporary, partial pressure assembly life support system for the purposes of flight clearance. A total of 12 3-s RDs were conducted with subjects breathing 56% oxygen (balance nitrogen) at the base (simulated cabin) altitude of 22,500 ft (6858 m), switching to 100% oxygen under 72 mmHg (9.6 kPa) of positive pressure at the final (simulated aircraft) altitude. Respiratory pressures, flows, and gas compositions were monitored continuously throughout. All RDs were completed safely, but one subject experienced significant hypoxia during the minute at final altitude, associated with severe hemoglobin desaturation to a low of 53%. Accurate data on subjects' lung volumes were obtained and individual responses post-RD were reviewed in relation to patterns of pulmonary ventilation. The occurrence of severe hypoxia is explained by hypoventilation in conjunction with unusually large lung volumes (total lung capacity 10.18 L). Subjects' lung volumes and patterns of pulmonary ventilation are critical, but idiosyncratic, determinants of alveolar oxygenation and severity of hypoxia following RD to 60,000 ft (18,288 m). At such extreme altitudes even vaporization of water condensate in the oxygen mask may compromise oxygen delivery. An altitude ceiling of 60,000 ft (18,288 m) is the likely threshold for reliable protection using partial pressure assemblies and aircrew should be instructed to take two deep 'clearing' breaths immediately following RD at such extreme pressure breathing altitudes.

Feasibility assessment of using oxygen-enhanced magnetic resonance imaging for evaluating the effect of pharmacological treatment in COPD

International Nuclear Information System (INIS)

Morgan, Alexandra R.; Parker, Geoff J.M.; Roberts, Caleb; Buonaccorsi, Giovanni A.; Maguire, Niall C.; Hubbard Cristinacce, Penny L.; Singh, Dave; Vestbo, Jørgen; Bjermer, Leif; Jögi, Jonas; Taib, Ziad; Sarv, Janeli; Bruijnzeel, Piet L.B.; Olsson, Lars E.; Bondesson, Eva; Nihlén, Ulf; McGrath, Deirdre M.; Young, Simon S.

2014-01-01

Highlights: • We investigate physiologic response to standard COPD treatment regimes using OE-MRI. • We assess the potential role of OE-MRI in future drug development studies. • In COPD, OE-MRI parameters showed response to single-dose formoterol. • OE-MRI parameters showed response to 8-week formoterol/budesonide treatment. • OE-MRI measurements are feasible in a small-scale multi-center trial setting. - Abstract: Objectives: Oxygen-enhanced MRI (OE-MRI) biomarkers have potential value in assessment of COPD, but need further evaluation before treatment-induced changes can be interpreted. The objective was to evaluate how OE-MRI parameters of regional ventilation and oxygen uptake respond to standard pharmacological interventions in COPD, and how the response compares to that of gold standard pulmonary function tests. Materials and methods: COPD patients (n = 40), mean FEV 1 58% predicted normal, received single-dose inhaled formoterol 9 μg, or placebo, followed by 8 weeks treatment bid with a combination of budesonide and formoterol Turbuhaler ® 320/9 μg or formoterol Turbuhaler ® . OE-MRI biomarkers were obtained, as well as X-ray computed tomography (CT) biomarkers and pulmonary function tests, in a two-center study. An ANCOVA statistical model was used to assess effect size of intervention measurable in OE-MRI parameters of lung function. Results: OE-MRI data were successfully acquired at both study sites. 8-week treatment with budesonide/formoterol significantly decreased lung wash-out time by 31% (p < 0.01), decreased the change in lung oxygen level upon breathing pure oxygen by 13% (p < 0.05) and increased oxygen extraction from the lung by 58% (p < 0.01). Single-dose formoterol increased both lung wash-out time (+47%, p < 0.05) and lung oxygenation time (+47%, p < 0.05). FEV 1 was improved by single-dose formoterol (+12%, p < 0.001) and 8 weeks of budesonide/formoterol (+ 18%, p < 0.001), consistent with published studies. Conclusions: In COPD

Feasibility assessment of using oxygen-enhanced magnetic resonance imaging for evaluating the effect of pharmacological treatment in COPD

Energy Technology Data Exchange (ETDEWEB)

Morgan, Alexandra R., E-mail: alex.morgan@bioxydyn.com [Bioxydyn Ltd, Manchester (United Kingdom); Centre for Imaging Sciences and Biomedical Imaging Institute, Manchester Academic Health Sciences Centre, University of Manchester, Manchester (United Kingdom); Parker, Geoff J.M.; Roberts, Caleb [Bioxydyn Ltd, Manchester (United Kingdom); Centre for Imaging Sciences and Biomedical Imaging Institute, Manchester Academic Health Sciences Centre, University of Manchester, Manchester (United Kingdom); Buonaccorsi, Giovanni A.; Maguire, Niall C. [Bioxydyn Ltd, Manchester (United Kingdom); Hubbard Cristinacce, Penny L. [Centre for Imaging Sciences and Biomedical Imaging Institute, Manchester Academic Health Sciences Centre, University of Manchester, Manchester (United Kingdom); Singh, Dave; Vestbo, Jørgen [University of Manchester, Medicines Evaluation Unit, Manchester Academic Health Sciences Centre, University Hospital of South Manchester, Manchester (United Kingdom); Bjermer, Leif [Department of Respiratory Medicine and Allergology, Skåne University Hospital, Lund (Sweden); Jögi, Jonas [Department of Clinical Physiology, Skåne University Hospital and Lund University, Lund (Sweden); Taib, Ziad; Sarv, Janeli; Bruijnzeel, Piet L.B.; Olsson, Lars E.; Bondesson, Eva [AstraZeneca R and D, Mölndal (Sweden); Nihlén, Ulf [Department of Respiratory Medicine and Allergology, Skåne University Hospital, Lund (Sweden); AstraZeneca R and D, Mölndal (Sweden); McGrath, Deirdre M. [Centre for Imaging Sciences and Biomedical Imaging Institute, Manchester Academic Health Sciences Centre, University of Manchester, Manchester (United Kingdom); Young, Simon S. [AstraZeneca R and D, Alderley Park (United Kingdom); and others

2014-11-15

Highlights: • We investigate physiologic response to standard COPD treatment regimes using OE-MRI. • We assess the potential role of OE-MRI in future drug development studies. • In COPD, OE-MRI parameters showed response to single-dose formoterol. • OE-MRI parameters showed response to 8-week formoterol/budesonide treatment. • OE-MRI measurements are feasible in a small-scale multi-center trial setting. - Abstract: Objectives: Oxygen-enhanced MRI (OE-MRI) biomarkers have potential value in assessment of COPD, but need further evaluation before treatment-induced changes can be interpreted. The objective was to evaluate how OE-MRI parameters of regional ventilation and oxygen uptake respond to standard pharmacological interventions in COPD, and how the response compares to that of gold standard pulmonary function tests. Materials and methods: COPD patients (n = 40), mean FEV{sub 1} 58% predicted normal, received single-dose inhaled formoterol 9 μg, or placebo, followed by 8 weeks treatment bid with a combination of budesonide and formoterol Turbuhaler{sup ®} 320/9 μg or formoterol Turbuhaler{sup ®}. OE-MRI biomarkers were obtained, as well as X-ray computed tomography (CT) biomarkers and pulmonary function tests, in a two-center study. An ANCOVA statistical model was used to assess effect size of intervention measurable in OE-MRI parameters of lung function. Results: OE-MRI data were successfully acquired at both study sites. 8-week treatment with budesonide/formoterol significantly decreased lung wash-out time by 31% (p < 0.01), decreased the change in lung oxygen level upon breathing pure oxygen by 13% (p < 0.05) and increased oxygen extraction from the lung by 58% (p < 0.01). Single-dose formoterol increased both lung wash-out time (+47%, p < 0.05) and lung oxygenation time (+47%, p < 0.05). FEV{sub 1} was improved by single-dose formoterol (+12%, p < 0.001) and 8 weeks of budesonide/formoterol (+ 18%, p < 0.001), consistent with published studies

The Oxygen Dissociation Curve of Hemoglobin: Bridging the Gap between Biochemistry and Physiology

Science.gov (United States)

Gómez-Cambronero, Julian

2001-06-01

Cooperativity is a very difficult concept for biochemistry students in the health sciences. An analogy between breaking salt bonds and tearing apart a block of four stamps has been proposed for hemoglobin (Hb). However, since tearing is equated to binding of molecules, two intrinsically contradictory terms, students still have difficulty. I apply the pictorial analogy to the releasing of oxygen instead of the binding, thus bridging biochemistry (cooperativity) with physiology (oxygen dissociation). I embark on an imaginary journey from the lungs (saturation at 100 mmHg) to the oxygen-starved tissues. The stamps represent fully loaded Hb. By making two cuts the first "oxygen" is released. For the second, only one cut is needed. With one final cut, the last two stamps are separated. This means that less energy is needed to unload oxygen: just small drops in partial pressure do the trick in the right place (tissues) but not in the wrong one (lungs). In doing this, I use the three main models of learning: association, discovery and mentoring. Additionally, by guiding students to discover the truth by themselves, I can use hemoglobin as a wonderful excuse to apply the "Socratic method" in the classroom.

Comparison of portable oxygen concentrators in a simulated airplane environment.

Science.gov (United States)

Fischer, Rainald; Wanka, Eva R; Einhaeupl, Franziska; Voll, Klaus; Schiffl, Helmut; Lang, Susanne M; Gruss, Martin; Ferrari, Uta

2013-01-01

Portable oxygen concentrators (POC) are highly desirable for patients with lung disease traveling by airplane, as these devices allow theoretically much higher travel times if additional batteries can be used. However, it is unclear whether POCs produce enough oxygen in airplanes at cruising altitude, even if complying with aviation regulations. We evaluated five frequently used POCs (XPO2 (Invacare, USA), Freestyle (AirSep C., USA), Evergo (Philipps Healthcare, Germany), Inogen One (Inogen, USA), Eclipse 3 (Sequal, USA)) at an altitude of 2650 m (as simulated airplane environment) in 11 patients with chronic obstructive lung disease (COPD) and compared theses POCs with the standard oxygen system (WS120, EMS Ltd., Germany) used by Lufthansa. Oxygen was delivered by each POC for 30 min to each patient at rest, blood gases were then drawn from the arterialized ear lobe. All POCs were able to deliver enough oxygen to increase the PaO(2) of our subjects by at least 1.40 kPa (10 mmHg). However, to achieve this increase, the two most lightweight POCs (Freestyle and Invacare XPO2) had to be run at their maximum level. This causes a significant reduction of battery life. The three other POCs (EverGo, Inogen One, Eclipse 3) and the WS120 were able to increase the PaO(2) by more than 2.55 kPa (20 mmHg), which provides extra safety for patients with more severe basal hypoxemia. When choosing the right oxygen system for air travel in patients in COPD, not only weight, but also battery life and maximum possible oxygen output must be considered carefully. Copyright © 2012 Elsevier Ltd. All rights reserved.

Morphological Pulmonary Diffusion Capacity for Oxygen of Burmese Pythons (Python molurus): a Comparison of Animals in Healthy Condition and with Different Pulmonary Infections.

Science.gov (United States)

Starck, J M; Weimer, I; Aupperle, H; Müller, K; Marschang, R E; Kiefer, I; Pees, M

2015-11-01

A qualitative and quantitative morphological study of the pulmonary exchange capacity of healthy and diseased Burmese pythons (Python molurus) was carried out in order to test the hypothesis that the high morphological excess capacity for oxygen exchange in the lungs of these snakes is one of the reasons why pathological processes extend throughout the lung parenchyma and impair major parts of the lungs before clinical signs of respiratory disease become apparent. Twenty-four Burmese pythons (12 healthy and 12 diseased) were included in the study. A stereology-based approach was used to quantify the lung parenchyma using computed tomography. Light microscopy was used to quantify tissue compartments and the respiratory exchange surface, and transmission electron microscopy was used to measure the thickness of the diffusion barrier. The morphological diffusion capacity for oxygen of the lungs and the anatomical diffusion factor were calculated. The calculated anatomical diffusion capacity was compared with published values for oxygen consumption of healthy snakes, and the degree to which the exchange capacity can be obstructed before normal physiological function is impaired was estimated. Heterogeneous pulmonary infections result in graded morphological transformations of pulmonary parenchyma involving lymphocyte migration into the connective tissue and thickening of the septal connective tissue, increasing thickness of the diffusion barrier and increasing transformation of the pulmonary epithelium into a columnar pseudostratified or stratified epithelium. The transformed epithelium developed by hyperplasia of ciliated cells arising from the tip of the faveolar septa and by hyperplasia of type II pneumocytes. These results support the idea that the lungs have a remarkable overcapacity for oxygen consumption and that the development of pulmonary disease continuously reduces the capacity for oxygen consumption. However, due to the overcapacity of the lungs, this

Hydroxysafflor yellow A suppress oleic acid-induced acute lung injury via protein kinase A

International Nuclear Information System (INIS)

Wang, Chaoyun; Huang, Qingxian; Wang, Chunhua; Zhu, Xiaoxi; Duan, Yunfeng; Yuan, Shuai; Bai, Xianyong

2013-01-01

Inflammation response and oxidative stress play important roles in acute lung injury (ALI). Activation of the cAMP/protein kinase A (PKA) signaling pathway may attenuate ALI by suppressing immune responses and inhibiting the generation of reactive oxygen species (ROS). Hydroxysafflor yellow A (HSYA) is a natural flavonoid compound that reduces oxidative stress and inflammatory cytokine-mediated damage. In this study, we examined whether HSYA could protect the lungs from oleic acid (OA)-induced injury, which was used to mimic ALI, and determined the role of the cAMP/PKA signaling pathway in this process. Arterial oxygen tension (PaO 2 ), carbon dioxide tension, pH, and the PaO 2 /fraction of inspired oxygen ratio in the blood were detected using a blood gas analyzer. We measured wet/dry lung weight ratio and evaluated tissue morphology. The protein and inflammatory cytokine levels in the bronchoalveolar lavage fluid and serum were determined using enzyme-linked immunoassay. The activities of superoxide dismutase, glutathione peroxidase, PKA, and nicotinamide adenine dinucleotide phosphate oxidase, and the concentrations of cAMP and malondialdehyde in the lung tissue were detected using assay kits. Bcl-2, Bax, caspase 3, and p22 phox levels in the lung tissue were analyzed using Western blotting. OA increased the inflammatory cytokine and ROS levels and caused lung dysfunction by decreasing cAMP synthesis, inhibiting PKA activity, stimulating caspase 3, and reducing the Bcl-2/Bax ratio. H-89 increased these effects. HSYA significantly increased the activities of antioxidant enzymes, inhibited the inflammatory response via cAMP/PKA pathway activation, and attenuated OA-induced lung injury. Our results show that the cAMP/PKA signaling pathway is required for the protective effect of HSYA against ALI. - Highlights: • Oleic acid (OA) cause acute lung injury (ALI) via inhibiting cAMP/PKA signal pathway. • Blocking protein kinase A (PKA) activation may enhance Cytokine

A Short Period of Ventilation without Perfusion Seems to Reduce Atelectasis without Harming the Lungs during Ex Vivo Lung Perfusion

Directory of Open Access Journals (Sweden)

Sandra Lindstedt

2013-01-01

Full Text Available To evaluate the lung function of donors after circulatory deaths (DCDs, ex vivo lung perfusion (EVLP has been shown to be a valuable method. We present modified EVLP where lung atelectasis is removed, while the lung perfusion is temporarily shut down. Twelve pigs were randomized into two groups: modified EVLP and conventional EVLP. When the lungs had reached 37°C in the EVLP circuit, lung perfusion was temporarily shut down in the modified EVLP group, and positive end-expiratory pressure (PEEP was increased to 10 cm H2O for 10 minutes. In the conventional EVLP group, PEEP was increased to 10 cm H2O for 10 minutes with unchanged lung perfusion. In the modified EVLP group, the arterial oxygen partial pressure (PaO2 was 18.5 ± 7.0 kPa before and 64.5 ± 6.0 kPa after the maneuver (P<0.001. In the conventional EVLP group, the PaO2 was 16.8 ± 3.1 kPa and 46.8 ± 2.7 kPa after the maneuver (P<0.01; P<0.01. In the modified EVLP group, the pulmonary graft weight was unchanged, while in the conventional EVLP group, the pulmonary graft weight was significantly increased. Modified EVLP with normoventilation of the lungs without ongoing lung perfusion for 10 minutes may eliminate atelectasis almost completely without harming the lungs.

Adult venovenous extracorporeal membrane oxygenation for severe respiratory failure: Current status and future perspectives

Directory of Open Access Journals (Sweden)

Ayan Sen

2016-01-01

Full Text Available Extracorporeal membrane oxygenation (ECMO for severe acute respiratory failure was proposed more than 40 years ago. Despite the publication of the ARDSNet study and adoption of lung protective ventilation, the mortality for acute respiratory failure due to acute respiratory distress syndrome has continued to remain high. This technology has evolved over the past couple of decades and has been noted to be safe and successful, especially during the worldwide H1N1 influenza pandemic with good survival rates. The primary indications for ECMO in acute respiratory failure include severe refractory hypoxemic and hypercarbic respiratory failure in spite of maximum lung protective ventilatory support. Various triage criteria have been described and published. Contraindications exist when application of ECMO may be futile or technically impossible. Knowledge and appreciation of the circuit, cannulae, and the physiology of gas exchange with ECMO are necessary to ensure lung rest, efficiency of oxygenation, and ventilation as well as troubleshooting problems. Anticoagulation is a major concern with ECMO, and the evidence is evolving with respect to diagnostic testing and use of anticoagulants. Clinical management of the patient includes comprehensive critical care addressing sedation and neurologic issues, ensuring lung recruitment, diuresis, early enteral nutrition, treatment and surveillance of infections, and multisystem organ support. Newer technology that delinks oxygenation and ventilation by extracorporeal carbon dioxide removal may lead to ultra-lung protective ventilation, avoidance of endotracheal intubation in some situations, and ambulatory therapies as a bridge to lung transplantation. Risks, complications, and long-term outcomes and resources need to be considered and weighed in before widespread application. Ethical challenges are a reality and a multidisciplinary approach that should be adopted for every case in consideration.

[Treatment of acute respiratory distress syndrome using pressure and volume controlled ventilation with lung protective strategy].

Science.gov (United States)

Ge, Ying; Wan, Yong; Wang, Da-qing; Su, Xiao-lin; Li, Jun-ying; Chen, Jing

2004-07-01

To investigate the significance and effect of pressure controlled ventilation (PCV) as well as volume controlled ventilation (VCV) by lung protective strategy on respiratory mechanics, blood gas analysis and hemodynamics in patients with acute respiratory distress syndrome (ARDS). Fifty patients with ARDS were randomly divided into PCV and VCV groups with permissive hypercapnia and open lung strategy. Changes in respiratory mechanics, blood gas analysis and hemodynamics were compared between two groups. Peak inspiration pressure (PIP) in PCV group was significantly lower than that in VCV group, while mean pressure of airway (MPaw) was significantly higher than that in VCV after 24 hours mechanical ventilation. After 24 hours mechanical ventilation, there were higher central venous pressure (CVP) and slower heart rate (HR) in two groups, CVP was significantly higher in VCV compared with PCV, and PCV group had slower HR than VCV group, the two groups had no differences in mean blood pressure (MBP) at various intervals. All patients showed no ventilator-induced lung injury. Arterial blood oxygenations were obviously improved in two groups after 24 hours mechanical ventilation, PCV group had better partial pressure of oxygen in artery (PaO2) than VCV group. Both PCV and VCV can improve arterial blood oxygenations, prevent ventilator-induced lung injury, and have less disturbance in hemodynamic parameters. PCV with lung protective ventilatory strategy should be early use for patients with ARDS.

Penguin lungs and air sacs: implications for baroprotection, oxygen stores and buoyancy.

Science.gov (United States)

Ponganis, P J; St Leger, J; Scadeng, M

2015-03-01

The anatomy and volume of the penguin respiratory system contribute significantly to pulmonary baroprotection, the body O2 store, buoyancy and hence the overall diving physiology of penguins. Therefore, three-dimensional reconstructions from computerized tomographic (CT) scans of live penguins were utilized to measure lung volumes, air sac volumes, tracheobronchial volumes and total body volumes at different inflation pressures in three species with different dive capacities [Adélie (Pygoscelis adeliae), king (Aptenodytes patagonicus) and emperor (A. forsteri) penguins]. Lung volumes scaled to body mass according to published avian allometrics. Air sac volumes at 30 cm H2O (2.94 kPa) inflation pressure, the assumed maximum volume possible prior to deep dives, were two to three times allometric air sac predictions and also two to three times previously determined end-of-dive total air volumes. Although it is unknown whether penguins inhale to such high volumes prior to dives, these values were supported by (a) body density/buoyancy calculations, (b) prior air volume measurements in free-diving ducks and (c) previous suggestions that penguins may exhale air prior to the final portions of deep dives. Based upon air capillary volumes, parabronchial volumes and tracheobronchial volumes estimated from the measured lung/airway volumes and the only available morphometry study of a penguin lung, the presumed maximum air sac volumes resulted in air sac volume to air capillary/parabronchial/tracheobronchial volume ratios that were not large enough to prevent barotrauma to the non-collapsing, rigid air capillaries during the deepest dives of all three species, and during many routine dives of king and emperor penguins. We conclude that volume reduction of airways and lung air spaces, via compression, constriction or blood engorgement, must occur to provide pulmonary baroprotection at depth. It is also possible that relative air capillary and parabronchial volumes are

ROS Mediates Radiation-Induced Differentiation in Human Lung Fibroblast

International Nuclear Information System (INIS)

Park, Sa Rah; Ahn, Ji Yeon; Kim, Mi Hyeung; Lim, Min Jin; Yun, Yeon Sook; Song, Jie Young

2009-01-01

One of the most common tumors worldwide is lung cancer and the number of patients with lung cancer received radiotherapy is increasing rapidly. Although radiotherapy may have lots of advantages, it can also induce serious adverse effects such as acute radiation pneumonitis and pulmonary fibrosis. Pulmonary fibrosis is characterized by excessive production of smooth muscle actin-alpha (a-SMA) and accumulation of extracellular matrix (ECM) such as collagen and fibronectin. There has been a great amount of research about fibrosis but the exact mechanism causing the reaction is not elucidated especially in radiation-induced fibrosis. Until now it has been known that several factors such as transforming growth factor (TGF-b), tumor necrosis factor (TNF), IL-6, platelet-derived growth factor (PDGF) and reactive oxygen species are related to fibrosis. It is also reported that reactive oxygen species (ROS) can be induced by radiation and can act as a second messenger in various signaling pathways. Therefore we focused on the role of ROS in radiation induced fibrosis. Here, we suggest that irradiation generate ROS mainly through NOX4, result in differentiation of lung fibroblast into myofibroblast

Fetal lung volume in congenital diaphragmatic hernia: association of prenatal MR imaging findings with postnatal chronic lung disease.

Science.gov (United States)

Debus, Angelika; Hagelstein, Claudia; Kilian, A Kristina; Weiss, Christel; Schönberg, Stefan O; Schaible, Thomas; Neff, K Wolfgang; Büsing, Karen A

2013-03-01

To assess whether chronic lung disease (CLD) in surviving infants with congenital diaphragmatic hernia (CDH) is associated with lung hypoplasia on the basis of the results of antenatal observed-to-expected fetal lung volume (FLV) ratio measurement at magnetic resonance (MR) imaging. The study received approval from the institutional review board, with waiver of informed consent for this retrospective review from patients who had previously given informed consent for prospective studies. The ratio of observed to expected FLV at MR imaging was calculated in 172 fetuses with CDH. At postpartum day 28, the need for supplemental oxygen implicated the diagnosis of CLD. At day 56, patients with CLD were assigned to one of three groups-those with mild, moderate, or severe CLD-according to their demand for oxygen. Logistic regression analysis was used to assess the prognostic value of the individual observed-to-expected FLV ratio for association with postnatal development of CLD. Children with CLD were found to have significantly smaller observed-to-expected FLV ratios at MR imaging than infants without CLD (P CLD revealed significant differences in observed-to-expected FLV ratio between patients with mild CLD and those with moderate (P = .012) or severe (P = .007) CLD. For an observed-to-expected FLV ratio of 5%, 99% of patients with CDH developed CLD, compared with less than 5% of fetuses with an observed-to-expected FLV ratio of 50%. Perinatally, development and grade of CLD were further influenced by the need for extracorporeal membrane oxygenation (ECMO) (P CLD in surviving infants with CDH is associated with the prenatally determined observed-to-expected FLV ratio. Early neonatal therapeutic decisions can additionally be based on this ratio. Perinatally, ECMO requirement and gestational age at delivery are useful in further improving the estimated probability of CLD.

Pulmonary interstitial glycogenosis in the setting of lung growth abnormality: radiographic and pathologic correlation

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Castillo, Monette; Vade, Aruna; Lim-Dunham, Jennifer Eden [Loyola University Health System, Department of Radiology, Maywood, IL (United States); Masuda, Emi [Henry Ford Hospital, Department of Radiology, Detroit, MI (United States); Massarani-Wafai, Rasan [Loyola University Health System, Department of Pathology, Maywood, IL (United States)

2010-09-15

Pulmonary interstitial glycogenosis (PIG) is a rare pediatric interstitial lung disease. We report a case of a term boy presenting with tachypnea at birth requiring supplemental oxygen. Chest radiographs followed by high-resolution CT (HRCT) demonstrated hyperinflation and diffuse interstitial markings interspersed with multiple cystic spaces. An open lung biopsy demonstrated a minor component of PIG superimposed upon poor alveolarization. PIG in the setting of lung growth abnormality might be more common than previously described. Additionally, radiographic findings associated with most pediatric interstitial lung diseases are nonspecific, and histopathologic correlation is essential for diagnosis. (orig.)

Chronic lung disease in newborns.

Science.gov (United States)

Sankar, M Jeeva; Agarwal, Ramesh; Deorari, Ashok K; Paul, Vinod K

2008-04-01

Chronic lung disease (CLD) or bronchopulmonary dysplasia (BPD) occurs in preterm infants who require respiratory support in the first few days of birth. Apart from prematurity, oxygen therapy and assisted ventilation, factors like intrauterine/postnatal infections, patent ductus arteriosus, and genetic polymorphisms also contribute to its pathogenesis. The severe form of BPD with extensive inflammatory changes is rarely seen nowadays; instead, a milder form characterized by decreased alveolar septation due to arrest in lung development is more common. A multitude of strategies, mainly pharmacological and ventilatory, have been employed for prevention and treatment of BPD. Unfortunately, most of them have not been proved to be beneficial. A comprehensive protocol for management of BPD based on the current evidence is discussed here.

Thallium pulmonary scintigraphy. Relationship to pulmonary fluid volumes during left atrial hypertension and the acute release of pressure

International Nuclear Information System (INIS)

Slutsky, R.A.

1984-01-01

To evaluate the relationship between thallium-201 lung activity and pulmonary fluid volumes, we compared thallium pulmonary scintigrams with measures of intravascular (PBV), extravascular (EVLW) and total lung water (TLW) during gradual left atrial (LA) hypertension and then serially after the acute release of pressure. The study group was composed of nine mongrel dogs who were each studied at seven levels of elevated LA pressure, and then every 15 minutes for 2 hours after the acute release of pressure. During LA pressure (congestion phase) elevation, lung counts (normalized for myocardial activity), correlated best with TLW (r . .91), rather than PBV (r . .84) or EVLW (r . .81). After the release of pressure (recovery phase), lung counts correlated well with EVLW (r . .92) and TLW (r . .82), but not with PBV (r . .28). Postmortem lung counts from 197 separate lung sections correlated well with the corresponding wet weight/dry weight ratio from that section (r . .81). Thus, we conclude that changes in pulmonary thallium emissions during cardiogenic pulmonary edema relate to corresponding changes in pulmonary fluid volumes. During congestion, the confounding effects of nonlinear increases in EVLW and PBV make thallium emissions more a marker of TLW than either the intravascular or extravascular pulmonary fluid compartment. After pressure release, PBV immediately returns to normal, at which time EVLW and pulmonary emissions correlate closely. These latter data, more applicable to postexercise stress thallium data, lend support to the hypothesis that elevated pulmonary emissions during postexercise thallium scintigrams reflect elevations in EVLW that develop during exercise

Mild hypothermia increases pulmonary anti-inflammatory response during protective mechanical ventilation in a piglet model of acute lung injury.

Science.gov (United States)

Cruces, Pablo; Erranz, Benjamín; Donoso, Alejandro; Carvajal, Cristóbal; Salomón, Tatiana; Torres, María Fernanda; Díaz, Franco

2013-11-01

The effects of mild hypothermia (HT) on acute lung injury (ALI) are unknown in species with metabolic rate similar to that of humans, receiving protective mechanical ventilation (MV). We hypothesized that mild hypothermia would attenuate pulmonary and systemic inflammatory responses in piglets with ALI managed with a protective MV. Acute lung injury (ALI) was induced with surfactant deactivation in 38 piglets. The animals were then ventilated with low tidal volume, moderate positive end-expiratory pressure (PEEP), and permissive hypercapnia throughout the experiment. Subjects were randomized to HT (33.5°C) or normothermia (37°C) groups over 4 h. Plasma and tissue cytokines, tissue apoptosis, lung mechanics, pulmonary vascular permeability, hemodynamic, and coagulation were evaluated. Lung interleukin-10 concentrations were higher in subjects that underwent HT after ALI induction than in those that maintained normothermia. No difference was found in other systemic and tissue cytokines. HT did not induce lung or kidney tissue apoptosis or influence lung mechanics or markers of pulmonary vascular permeability. Heart rate, cardiac output, oxygen uptake, and delivery were significantly lower in subjects that underwent HT, but no difference in arterial lactate, central venous oxygen saturation, and coagulation test was observed. Mild hypothermia induced a local anti-inflammatory response in the lungs, without affecting lung function or coagulation, in this piglet model of ALI. The HT group had lower cardiac output without signs of global dysoxia, suggesting an adaptation to the decrease in oxygen uptake and delivery. Studies are needed to determine the therapeutic role of HT in ALI. © 2013 John Wiley & Sons Ltd.

Cell–cell signaling drives the evolution of complex traits: introduction—lung evo-devo

Science.gov (United States)

Torday, John S.; Rehan, V. K.

2009-01-01

Physiology integrates biology with the environment through cell–cell interactions at multiple levels. The evolution of the respiratory system has been “deconvoluted” (Torday and Rehan in Am J Respir Cell Mol Biol 31:8–12, 2004) through Gene Regulatory Networks (GRNs) applied to cell–cell communication for all aspects of lung biology development, homeostasis, regeneration, and aging. Using this approach, we have predicted the phenotypic consequences of failed signaling for lung development, homeostasis, and regeneration based on evolutionary principles. This cell–cell communication model predicts other aspects of vertebrate physiology as adaptational responses. For example, the oxygen-induced differentiation of alveolar myocytes into alveolar adipocytes was critical for the evolution of the lung in land dwelling animals adapting to fluctuating Phanarezoic oxygen levels over the past 500 million years. Adipocytes prevent lung injury due to oxygen radicals and facilitate the rise of endothermy. In addition, they produce the class I cytokine leptin, which augments pulmonary surfactant activity and alveolar surface area, increasing selection pressure for both respiratory oxygenation and metabolic demand initially constrained by high-systemic vascular pressure, but subsequently compensated by the evolution of the adrenomedullary beta-adrenergic receptor mechanism. Conserted positive selection for the lung and adrenals created further selection pressure for the heart, which becomes progressively more complex phylogenetically in tandem with the lung. Developmentally, increasing heart complexity and size impinges precociously on the gut mesoderm to induce the liver. That evolutionary-developmental interaction is significant because the liver provides regulated sources of glucose and glycogen to the evolving physiologic system, which is necessary for the evolution of the neocortex. Evolution of neocortical control furthers integration of physiologic systems. Such

Black Lung Program: Further Improvements Can Be Made in Claims Adjudication

Science.gov (United States)

1990-03-21

Law Judges SS Social Security Administration S I ction Miners sometimes develop black lung disease ( neumoconiosis or a chronic respiratory condition res...the identifica- tion and measurement of impairments involving the lung’s efficiency in exchanging oxygen and carbon dioxide. When these test results...and carbon dioxide. When these test results, judged by criteria established by the Secretary of Labor, demonstrate the miner’s inability to perform

Combined effects of sivelestat and resveratrol on severe acute pancreatitis-associated lung injury in rats.

Science.gov (United States)

Wang, Houhong; Wang, Shuai; Tang, Amao; Gong, Huihui; Ma, Panpan; Chen, Li

2014-08-01

Despite extensive research and clinical efforts made in the management of acute pancre-atitis during the past few decades, to date no effective cure is available and the mortality from severe acute pancre-atitis remains high. Given that lung is the primary cause of early death in acute pancreatitis patients, novel therapeutic approaches aiming to prevent lung injury have become a subject of intensive investigation. In a previous study, we demonstrated that sivelestat, a specific inhibitor of neutrophil elastase, is effective in protecting against lung failure in rats with taurocholate-induced acute pancreatitis. As part of the analyses extended from that study, the present study aimed to evaluate the role of sivelestat and/or resveratrol in the protection against acute pancreatitis-associated lung injury. The extended analyses demonstrated the following: (1) sodium taurocholate induced apparent lung injury and dysfunction manifested by histological anomalies, including vacuolization and apoptosis of the cells in the lung, as well as biochemical aberrations in the blood (an increase in amylase concentration and a decrease in partial arterial oxygen pressure) and increases in activities of reactive oxygen species, interleukin 6, myeloperoxidase, neutrophil elastase, lung edema, bronchotracho alveolar lavage protein concentration, and bronchotracho alveolar lavage cell infiltration in the lung; and (2) in lung tissues, either sivelestat or resveratrol treatment effectively attenuated the taurocholate-induced abnormalities in all parameters analyzed except for serum amylase concentration. In addition, combined treatment with both sivelestat and resveratrol demonstrated additive protective effects on pancreatitis-associated lung injury compared with single treatment.

Noninvasive monitoring of gas in the lungs and intestines of newborn infants using diode lasers: feasibility study.

Science.gov (United States)

Lundin, Patrik; Svanberg, Emilie Krite; Cocola, Lorenzo; Lewander Xu, Märta; Somesfalean, Gabriel; Andersson-Engels, Stefan; Jahr, John; Fellman, Vineta; Svanberg, Katarina; Svanberg, Sune

2013-12-01

Preterm newborn infants have a high morbidity rate. The most frequently affected organs where free gas is involved are the lungs and intestines. In respiratory distress syndrome, both hyperexpanded and atelectatic (collapsed) areas occur, and in necrotizing enterocolitis, intramural gas may appear in the intestine. Today, these conditions are diagnosed with x-ray radiography. A bed-side, rapid, nonintrusive, and gas-specific technique for in vivo gas sensing would improve diagnosis. We report the use of noninvasive laser spectroscopy, for the first time, to assess gas content in the lungs and intestines of three full-term infants. Water vapor and oxygen were studied with two low-power diode lasers, illuminating the skin and detecting light a few centimeters away. Water vapor was easily detected in the intestines and was also observed in the lungs. The relatively thick chest walls of the infants prevented detection of the weaker oxygen signal in this study. However, results from a previous phantom study, together with scaling of the results presented here to the typical chest-wall thickness of preterm infants, suggest that oxygen also should be detectable in their lungs.

Fitness to Fly Testing in Patients with Congenital Heart and Lung Disease.

Science.gov (United States)

Spoorenberg, Mandy E; van den Oord, Marieke H A H; Meeuwsen, Ted; Takken, Tim

2016-01-01

During commercial air travel passengers are exposed to a low ambient cabin pressure, comparable to altitudes of 5000 to 8000 ft (1524 to 2438 m). In healthy passengers this causes a fall in partial pressure of oxygen, which results in relative hypoxemia, usually without symptoms. Patients with congenital heart or lung disease may experience more severe hypoxemia during air travel. This systematic review provides an overview of the current literature focusing on whether it is safe for patients with congenital heart or lung disease to fly. The Pubmed database was searched and all studies carried out at an (simulated) altitude of 5000-8000 ft (1524-2438 m) for a short time period (several hours) and related to patients with congenital heart or lung disease were reviewed. Included were 11 studies. These studies examined patients with cystic fibrosis, neonatal (chronic) lung disease and congenital (a)cyanotic heart disease during a hypoxic challenge test, in a hypobaric chamber, during commercial air travel, or in the mountains. Peripheral/arterial saturation, blood gases, lung function, and/or the occurrence of symptoms were listed. Based on the current literature, it can be concluded that air travel is safe for most patients. However, those at risk of hypoxia can benefit from supplemental in-flight oxygen. Therefore, patients with congenital heart and lung disease should be evaluated carefully prior to air travel to select the patients at risk for hypoxia using the current studies and guidelines.

B-lines with Lung Ultrasound: The Optimal Scan Technique at Rest and During Stress.

Science.gov (United States)

Scali, Maria Chiara; Zagatina, Angela; Simova, Iana; Zhuravskaya, Nadezhda; Ciampi, Quirino; Paterni, Marco; Marzilli, Mario; Carpeggiani, Clara; Picano, Eugenio

2017-11-01

Various lung ultrasound (LUS) scanning modalities have been proposed for the detection of B-lines, also referred to as ultrasound lung comets, which are an important indication of extravascular lung water at rest and after exercise stress echo (ESE). The aim of our study was to assess the lung water spatial distribution (comet map) at rest and after ESE. We performed LUS at rest and immediately after semi-supine ESE in 135 patients (45 women, 90 men; age 62 ± 12 y, resting left ventricular ejection fraction = 41 ± 13%) with known or suspected heart failure or coronary artery disease. B-lines were measured by scanning 28 intercostal spaces (ISs) on the antero-lateral chest, 2nd-5th IS, along with the midaxillary (MA), anterior axillary (AA), mid-clavicular (MC) and parasternal (PS) lines. Complete 28-region, 16-region (3rd and 4th IS), 8-region (3rd IS), 4-region (3rd IS, only AA and MA) and 1-region (left 3rd IS, MA) scans were analyzed. In each space, the B-lines were counted from 0 = black lung to 10 = white lung. Interpretable images were obtained in all spaces (feasibility = 100 %). B-lines (>0 in at least 1 space) were present at ESE in 93 patients (69%) and absent in 42. More B-lines were found in the 3rd IS and along AA and MA lines. The B-line cumulative distribution was symmetric at rest (right/left = 1.10) and asymmetric with left lung predominance during stress (right/left = 0.67). The correlation of per-patient B-line number between 28-S and 16-S (R 2  = 0.9478), 8-S (R 2  = 0.9478) and 4-S scan (R 2  = 0.9146) was excellent, but only good with 1-S (R 2  = 0.8101). The average imaging and online analysis time were 5 s per space. In conclusion, during ESE, the comet map of lung water accumulation follows a predictable spatial pattern with wet spots preferentially aligned with the third IS and along the AA and MA lines. The time-saving 4-region scan is especially convenient during stress, simply dismissing dry regions and

Use of Lung Opening Maneuver in Patients with Acute Respiratory Failure After Cardiosurgical Operations

Directory of Open Access Journals (Sweden)

A. A. Yeremenko

2006-01-01

Full Text Available Postoperative respiratory failure is a most common complication and a main cause of postoperative death. The lung opening maneuver is a most effective method of respiratory therapy for this syndrome.Objective. To evaluate the impact of recruiting maneuver on gas exchange parameters, the biomechanical properties of the lung, and hemodynamic parameters. To determine whether the lung opening maneuver can be fully performed in patients undergoing cardiac surgery.Materials and methods. The study covered 19 patients aged 53 to 70 years who had postoperative failure. The indication for the recruiting maneuver was a decrease in the oxygenation index below 250 mm Hg during assisted ventilation (AV with FiO2>0.5, an inspiratory-expira-tory phase ratio of 1:1 to 3:1, and a positive end-expiratory pressure of 5—10 cm H2O.Results. A decrease in the oxygenation index to 139±36 mm Hg was observed before the recruiting maneuver was applied. Cd;n. averaged 41.1±8.4 ml/cm H2O. After use of the recruiting maneuver, there were increases in the oxygenation index up to 371±121 mm Hg and in Cd;n. up to 64.3±10 ml/cm H2O in all the patients. When the recruiting maneuver was employed, 14 patients were observed to have elevated blood pressures corrected with a vasopressor. One patient developed pneumothorax that was drained in proper time.Conclusion. The application of the lung opening maneuver leads to a considerable improvement of gas exchange parameters and lung mechanical properties.

Chrysophanol-induced cell death (necrosis) in human lung cancer A549 cells is mediated through increasing reactive oxygen species and decreasing the level of mitochondrial membrane potential.

Science.gov (United States)

Ni, Chien-Hang; Yu, Chun-Shu; Lu, Hsu-Feng; Yang, Jai-Sing; Huang, Hui-Ying; Chen, Po-Yuan; Wu, Shin-Hwar; Ip, Siu-Wan; Chiang, Su-Yin; Lin, Jaung-Geng; Chung, Jing-Gung

2014-05-01

Chrysophanol (1,8-dihydroxy-3-methylanthraquinone) is one of the anthraquinone compounds, and it has been shown to induce cell death in different types of cancer cells. The effects of chrysophanol on human lung cancer cell death have not been well studied. The purpose of this study is to examine chrysophanol-induced cytotoxic effects and also to investigate such influences that involved apoptosis or necrosis in A549 human lung cancer cells in vitro. Our results indicated that chrysophanol decreased the viable A549 cells in a dose- and time-dependent manner. Chrysophanol also promoted the release of reactive oxygen species (ROS) and Ca(2+) and decreased the levels of mitochondria membrane potential (ΔΨm ) and adenosine triphosphate in A549 cells. Furthermore, chrysophanol triggered DNA damage by using Comet assay and DAPI staining. Importantly, chrysophanol only stimulated the cytocheome c release, but it did not activate other apoptosis-associated protein levels including caspase-3, caspase-8, Apaf-1, and AIF. In conclusion, human lung cancer A549 cells treated with chrysophanol exhibited a cellular pattern associated with necrotic cell death and not apoptosis in vitro. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 740-749, 2014. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

[Alveolar ventilation and recruitment under lung protective ventilation].

Science.gov (United States)

Putensen, Christian; Muders, Thomas; Kreyer, Stefan; Wrigge, Hermann

2008-11-01

Goal of mechanical ventilation is to improve gas exchange and reduce work of breathing without contributing to further lung injury. Besides providing adequate EELV and thereby arterial oxygenation PEEP in addition to a reduction in tidal volume is required to prevent cyclic alveolar collapse and tidal recruitment and hence protective mechanical ventilation. Currently, there is no consensus if and if yes at which price alveolar recruitment with high airway pressures should be intended ("open up the lung"), or if it is more important to reduce the mechanical stress and strain to the lungs as much as possible ("keep the lung closed"). Potential of alveolar recruitment differs from patient to patient but also between lung regions. Potential for recruitment depends probably more on regional lung mechanics - especially on lung elastance - than on the underlying disease. Based on available data neither high PEEP nor other methods used for alveolar recruitment could demonstrate a survival benefit in patients with ARDS. These results may support an individualized titration of PEEP or other manoeuvres used for recruitment taking into consideration the regional effects. Bedside imaging techniques allowing titration of PEEP or other manoeuvres to prevent end-expiratory alveolar collapse (tidal recruitment) and inspiratory overinflation may be a promising development.

Cardiogenic Shock and Lung Injury as a Complication of Defibrillation

Directory of Open Access Journals (Sweden)

Hasan Serdar Kıhtır

2017-12-01

Full Text Available Local burns, embolism, and arrhythmia are the most common side effects observed after electrical shock treatments. However, systolic function may be rarely affected and pulmonary edema may develop. The cases of pulmonary edema after electrical shock treatments have been reported since 1960s and the proposed mechanism is the inadequacy of the left atrium cuff and ventricle. It was learned that a 7-year-old-girl without any known disease except vesicoureteral reflux had a ventricular fibrillation during general anesthesia induction and defibrillation at 2 joule/kg was attempted. It was also learned that the procedure was delayed and the patient was diagnosed with a long QT (QTc: 0.47 ms and had respiratory distress and circulatory disturbances after four hours. Pulmonary edema and heart failure was determined, and due to hipoxemia (SpO2 <88% not getting any better with non-invasive ventilation, the patient was intubated and followed with mechanical ventilation. A thermodilution catheter was inserted into the femoral artery and a low cardiac index (CI: 1.58 L/min/m2, elevated extravascular lung water index (EVLWI: 18 mL/kg and high pulmonary vascular permeability index (PVPI: 7.6 were determined. The patient was treated by mechanical ventilation and vasoactive/inotropic management and discharged at the fifth day of hospitalization without any sequela. Having high EVLWI with high PVPI suggest that the pulmonary edema mechanism may also be caused by alveolocapillary membrane damage, which is not accompanied by heart failure alone. This case is presented to show that it is the first child in the literature and that the results of transpulmonary thermodilution can also give information about lung function as well as cardiac function.

Lung function and postural changes during pregnancy.

Science.gov (United States)

Nørregaard, O; Schultz, P; Ostergaard, A; Dahl, R

1989-11-01

The aim of this study was to determine the effects of postural changes on lung function in pregnant women during the first, second, third trimester and post partum. A significant decrease in FRC, PEF and FEV1 was observed as a result of the postural changes. Arterial oxygenation, MVV and DLCO remained largely the same.

Transpulmonary pressures and lung mechanics with glossopharyngeal insufflation and exsufflation beyond normal lung volumes in competitive breath-hold divers.

Science.gov (United States)

Loring, Stephen H; O'Donnell, Carl R; Butler, James P; Lindholm, Peter; Jacobson, Francine; Ferrigno, Massimo

2007-03-01

Throughout life, most mammals breathe between maximal and minimal lung volumes determined by respiratory mechanics and muscle strength. In contrast, competitive breath-hold divers exceed these limits when they employ glossopharyngeal insufflation (GI) before a dive to increase lung gas volume (providing additional oxygen and intrapulmonary gas to prevent dangerous chest compression at depths recently greater than 100 m) and glossopharyngeal exsufflation (GE) during descent to draw air from compressed lungs into the pharynx for middle ear pressure equalization. To explore the mechanical effects of these maneuvers on the respiratory system, we measured lung volumes by helium dilution with spirometry and computed tomography and estimated transpulmonary pressures using an esophageal balloon after GI and GE in four competitive breath-hold divers. Maximal lung volume was increased after GI by 0.13-2.84 liters, resulting in volumes 1.5-7.9 SD above predicted values. The amount of gas in the lungs after GI increased by 0.59-4.16 liters, largely due to elevated intrapulmonary pressures of 52-109 cmH(2)O. The transpulmonary pressures increased after GI to values ranging from 43 to 80 cmH(2)O, 1.6-2.9 times the expected values at total lung capacity. After GE, lung volumes were reduced by 0.09-0.44 liters, and the corresponding transpulmonary pressures decreased to -15 to -31 cmH(2)O, suggesting closure of intrapulmonary airways. We conclude that the lungs of some healthy individuals are able to withstand repeated inflation to transpulmonary pressures far greater than those to which they would normally be exposed.

Computational design and in vitro characterization of an integrated maglev pump-oxygenator.

Science.gov (United States)

Zhang, Juntao; Taskin, M Ertan; Koert, Andrew; Zhang, Tao; Gellman, Barry; Dasse, Kurt A; Gilbert, Richard J; Griffith, Bartley P; Wu, Zhongjun J

2009-10-01

For the need for respiratory support for patients with acute or chronic lung diseases to be addressed, a novel integrated maglev pump-oxygenator (IMPO) is being developed as a respiratory assist device. IMPO was conceptualized to combine a magnetically levitated pump/rotor with uniquely configured hollow fiber membranes to create an assembly-free, ultracompact system. IMPO is a self-contained blood pump and oxygenator assembly to enable rapid deployment for patients requiring respiratory support or circulatory support. In this study, computational fluid dynamics (CFD) and computer-aided design were conducted to design and optimize the hemodynamics, gas transfer, and hemocompatibility performances of this novel device. In parallel, in vitro experiments including hydrodynamic, gas transfer, and hemolysis measurements were conducted to evaluate the performance of IMPO. Computational results from CFD analysis were compared with experimental data collected from in vitro evaluation of the IMPO. The CFD simulation demonstrated a well-behaved and streamlined flow field in the main components of this device. The results of hydrodynamic performance, oxygen transfer, and hemolysis predicted by computational simulation, along with the in vitro experimental data, indicate that this pump-lung device can provide the total respiratory need of an adult with lung failure, with a low hemolysis rate at the targeted operating condition. These detailed CFD designs and analyses can provide valuable guidance for further optimization of this IMPO for long-term use.

Bulk manufacture of concentrated oxygen gas-filled microparticles for intravenous oxygen delivery.

Science.gov (United States)

Kheir, John N; Polizzotti, Brian D; Thomson, Lindsay M; O'Connell, Daniel W; Black, Katherine J; Lee, Robert W; Wilking, James N; Graham, Adam C; Bell, David C; McGowan, Francis X

2013-08-01

Self-assembling, concentrated, lipid-based oxygen microparticles (LOMs) have been developed to administer oxygen gas when injected intravenously, preventing organ injury and death from systemic hypoxemia in animal models. Distinct from blood substitutes, LOMs are a one-way oxygen carrier designed to rescue patients who experience life-threatening hypoxemia, as caused by airway obstruction or severe lung injury. Here, we describe methods to manufacture large quantities of LOMs using an in-line, recycling, high-shear homogenizer, which can create up to 4 liters of microparticle emulsion in 10 minutes, with particles containing a median diameter of 0.93 microns and 60 volume% of gas phase. Using this process, we screen 30 combinations of commonly used excipients for their ability to form stable LOMs. LOMs composed of DSPC and cholesterol in a 1:1 molar ratio are stable for a 100 day observation period, and the number of particles exceeding 10 microns in diameter does not increase over time. When mixed with blood in vitro, LOMs fully oxygenate blood within 3.95 seconds of contact, and do not cause hemolysis or complement activation. LOMs can be manufactured in bulk by high shear homogenization, and appear to have a stability and size profile which merit further testing. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pulmonary uptake of thallium-201 in patients with congenital heart disease; Comparison between total anomalous pulmonary venous connection and tetralogy of Fallot

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Kohata, Tohru; Ono, Yasuo; Iwatani, Hajime; Fukushima, Hideki; Kamiya, Tetsuro; Yagihara, Toshikatsu; Nishimura, Tsunehiko; Takamiya, Makoto (National Cardiovascular Center, Suita, Osaka (Japan))

1992-01-01

To evaluate the pulmonary extravascular space in patients with congenital heart disease, lung uptake of Tl-201 was quantitatively studied. Patients' diseases consisted of total anomalous pulmonary venous connection (TAPVC)--supracardiac (I), paracardiac (II) and infracardiac (III) types--, tetralogy of Fallot (T/F), ventricular septal defect (VSD), and patent ductus arteriosus (PDA). Tl-201 imaging was performed before operation and in the early and late stages after operation. Twenty-five other patients with arrhythemias or a history of Kawasaki disease without perfusion defects served as controls. Lung uptake of Tl-201 was analyzed with a computer using the anterior image of the chest, and the averge count ratio of the right lung (P) to the left ventricular wall (LV) was calculated. P/LV values were compared between the patients before and after operation, and differences in anatomical types in TAPVC were also evaluated. In TAPVC, P/LV values decreased gradually after operation, but were significantly higher than those of controls even in the late stage. In the late stage after operation, type I TAPVC had significantly higher P/LV values than those of type-II. In T/F, the P/LV values were significantly higher after operation, even in the late stage, than before operation. In the VSD or PDA group, the P/LV value returned to normal after operation and was significantly lower than that before operation. In conclusion, TAPVC patients was considered to have a larger pulmonary extravascular space even in the late stage after operation, suggesting a sign of pulmonary congestion due to intrapulmonary vascular damage in utero. In T/F, scanty pulmonary vascular beds before operation were perfused with increased pulmonary blood flow after operation. Therefore, postoperative increases in pulmonary blood flow may be responsible for the increased pulmonary extravascular space. (N.K.).

Aspiration lung disorders in bovines: a case report and review.

Science.gov (United States)

Shakespeare, Anthony S

2012-11-01

Lung aspiration disorders in bovines are invariably diagnosed as infectious aspiration pneumonias. There is a distinct differentiation between aspiration pneumonia and aspiration pneumonitis in humans that can be applied to bovines. The nature and quantity of the aspirate can result in differing pathogeneses which can require differing therapeutic approaches. Whilst blood gases were important in detecting and prognosticating lung problems, changes in barometric pressure with altitude have to be considered when interpreting partial pressures of oxygen. Anatomical differences in the lungs of bovines can explain why this species is more prone to certain pneumonic problems. Pulmonary physiotherapy is important in treating lung disorders in humans and should be considered as an adjunct therapy in bovine respiratory conditions. A case work-up was used to highlight some of the points discussed in this article.

Prolonged Extracorporeal Membrane Oxygenation Support for Acute Respiratory Distress Syndrome

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Wen-Je Ko

2006-01-01

Full Text Available When all conventional treatments for respiratory failure in patients with acute respiratory distress syndrome (ARDS have failed, extracorporeal membrane oxygenation (ECMO can provide a chance of survival in these desperately ill patients. A 49-year-old male patient developed septic shock and progressive ARDS after liver abscess drainage. Venovenous ECMO was given due to refractory respiratory failure on postoperative day 6. Initially, two heparin-binding hollow-fiber microporous membrane oxygenators in parallel were used in the ECMO circuit. Twenty-two oxygenators were changed in the first 22 days of ECMO support because of plasma leak in the oxygenators. Each oxygenator had an average life of 48 hours. Thereafter, a single silicone membrane oxygenator was used in the ECMO circuit, which did not require change during the remaining 596 hours of ECMO. The patient's tidal volume was only 90 mL in the nadir and less than 300 mL for 26 days during the ECMO course. The patient required ECMO support for 48 days and survived despite complications, including septic shock, ARDS, acute renal failure, drug-induced leukopenia, and multiple internal bleeding. This patient received an unusually long duration of ECMO support. However, he survived, recovered well, and was in New York Heart Association functional class I-II, with a forced expiratory volume in 1 second of 81% of the predicted level 18 months later. In conclusion, ECMO can provide a chance of survival for patients with refractory ARDS. The reversibility of lung function is possible in ARDS patients regardless of the severity of lung dysfunction at the time of treatment.

Extended high-frequency partial liquid ventilation in lung injury: gas exchange, injury quantification, and vapor loss.

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Doctor, Allan; Al-Khadra, Eman; Tan, Puay; Watson, Kenneth F; Diesen, Diana L; Workman, Lisa J; Thompson, John E; Rose, Charles E; Arnold, John H

2003-09-01

High-frequency oscillatory ventilation with perflubron (PFB) reportedly improves pulmonary mechanics and gas exchange and attenuates lung injury. We explored PFB evaporative loss kinetics, intrapulmonary PFB distribution, and dosing strategies during 15 h of high-frequency oscillation (HFO)-partial liquid ventilation (PLV). After saline lavage lung injury, 15 swine were rescued with high-frequency oscillatory ventilation (n = 5), or in addition received 10 ml/kg PFB delivered to dependent lung [n = 5, PLV-compartmented (PLV(C))] or 10 ml/kg distributed uniformly within the lung [n = 5, PLV(U)]. In the PLV(C) group, PFB vapor loss was replaced. ANOVA revealed an unsustained improvement in oxygenation index in the PLV(U) group (P = 0.04); the reduction in oxygenation index correlated with PFB losses. Although tissue myeloperoxidase activity was reduced globally by HFO-PLV (P PFB distribution optimized gas exchange during HFO-PLV; additionally, monitoring PFB evaporative loss appears necessary to stabilize intrapulmonary PFB volume.

Lung damage and pulmonary uptake of serotonin in intact dogs

International Nuclear Information System (INIS)

Dawson, C.A.; Christensen, C.W.; Rickaby, D.A.; Linehan, J.H.; Johnston, M.R.

1985-01-01

The authors examined the influence of glass bead embolization and oleic acid, dextran, and imipramine infusion on the pulmonary uptake of trace doses of [ 3 H]serotonin and the extravascular volume accessible to [ 14 C]antipyrine in anesthetized dogs. Embolization and imipramine decreased serotonin uptake by 53 and 61%, respectively, but no change was observed with oleic acid or dextran infusion. The extravascular volume accessible to the antipyrine was reduced by 77% after embolization and increased by 177 and approximately 44% after oleic acid and dextran infusion, respectively. The results suggest that when the perfused endothelial surface is sufficiently reduced, as with embolization, the uptake of trace doses of serotonin will be depressed. In addition, decreases in serotonin uptake in response to imipramine in this study and in response to certain endothelial toxins in other studies suggest that serotonin uptake can reveal certain kinds of changes in endothelial function. However, the lack of a response to oleic acid-induced damage in the present study suggests that serotonin uptake is not sensitive to all forms of endothelial damage

Edaravone Decreases Paraquat Toxicity in A549 Cells and Lung Isolated Mitochondria

OpenAIRE

Shokrzadeh, Mohammad; Shaki, Fatemeh; Mohammadi, Ebrahim; Rezagholizadeh, Neda; Ebrahimi, Fatemeh

2014-01-01

Edaravone, an antioxidant and radical scavenger, showed protective effects against oxidative stress-like condition. Paraquat (PQ) is toxic herbicide considerable evidence suggests that oxidative stress and mitochondrial dysfunction contribute to PQ toxicity. In this study, protective effect of edaravone against PQ induced toxicity and reactive oxygen species (ROS) generation in A549 cells and lung isolated mitochondria were evaluated. A549 cells and lung isolated mitochondria were divided int...

Oxygen Toxicity and Special Operations Forces Diving: Hidden and Dangerous

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Thijs T. Wingelaar

2017-07-01

Full Text Available In Special Operations Forces (SOF closed-circuit rebreathers with 100% oxygen are commonly utilized for covert diving operations. Exposure to high partial pressures of oxygen (PO2 could cause damage to the central nervous system (CNS and pulmonary system. Longer exposure time and higher PO2 leads to faster development of more serious pathology. Exposure to a PO2 above 1.4 ATA can cause CNS toxicity, leading to a wide range of neurologic complaints including convulsions. Pulmonary oxygen toxicity develops over time when exposed to a PO2 above 0.5 ATA and can lead to inflammation and fibrosis of lung tissue. Oxygen can also be toxic for the ocular system and may have systemic effects on the inflammatory system. Moreover, some of the effects of oxygen toxicity are irreversible. This paper describes the pathophysiology, epidemiology, signs and symptoms, risk factors and prediction models of oxygen toxicity, and their limitations on SOF diving.

[Expression of various matrix metalloproteinases in mice with hyperoxia-induced acute lung injury].

Science.gov (United States)

Zhang, Xiang-feng; Ding, Shao-fang; Gao, Yuan-ming; Liang, Ying; Foda, Hussein D

2006-08-01

To investigate the role of matrix metalloproteinases (MMPs) and extracellular matrix metalloproteinase inducer (EMMPRIN) in the pathogenesis of acute lung injury induced by hyperoxia. Fifty four mice were exposed in sealed cages to >98% oxygen (for 24-72 hours), and another 18 mice to room air. The severity of lung injury was assessed, and the expression of mRNA and protein of MMP-2, MMP-9 and EMMPRIN in lung tissue, after exposure for 24, 48 and 72 hours of hyperoxia were studied by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Hyperoxia caused acute lung injury; this was accompanied by increased expression of an upregulation of MMP-2, MMP-9 and EMMPRIN mRNA and protein in lung tissues. Hyperoxia causes acute lung injury in mice; increases in MMP-2, MMP-9 and EMMPRIN may play an important role in the development of hyperoxia induced lung injury in mice.

The use of deuterium in medicine

International Nuclear Information System (INIS)

Roth, E.; Sutton, J.; Marsac, J.

1981-03-01

Whenever a corporal function experiences a disturbance reflected either by changes in metabolic activity or modifications of the importance of pools of certain molecules the possibility exists of making use of isotopes in diagnosis. This paper discusses the use of deuterium to measure total body water and extravascular water in the lungs, and gives examples of clinical applications

Relationship of pleural effusions to increased permeability pulmonary edema in anesthetized sheep.

OpenAIRE

Wiener-Kronish, J P; Broaddus, V C; Albertine, K H; Gropper, M A; Matthay, M A; Staub, N C

1988-01-01

We studied anesthetized sheep to determine the relationship between increased permeability pulmonary edema and the development and mechanism of pleural effusion formation. In 12 sheep with intact, closed thoraces, we studied the time course of pleural liquid formation after 0.12 ml/kg i.v. oleic acid. After 1 h, there were no pleural effusions, even though extravascular lung water increased 50% to 6.0 +/- 0.7 g/g dry lung. By 3 h pleural effusions had formed, they reached a maximum at 5 h (48...

Effects of ventilation strategy on distribution of lung inflammatory cell activity

Science.gov (United States)

2013-01-01

Introduction Leukocyte infiltration is central to the development of acute lung injury, but it is not known how mechanical ventilation strategy alters the distribution or activation of inflammatory cells. We explored how protective (vs. injurious) ventilation alters the magnitude and distribution of lung leukocyte activation following systemic endotoxin administration. Methods Anesthetized sheep received intravenous endotoxin (10 ng/kg/min) followed by 2 h of either injurious or protective mechanical ventilation (n = 6 per group). We used positron emission tomography to obtain images of regional perfusion and shunting with infused 13N[nitrogen]-saline and images of neutrophilic inflammation with 18F-fluorodeoxyglucose (18F-FDG). The Sokoloff model was used to quantify 18F-FDG uptake (Ki), as well as its components: the phosphorylation rate (k3, a surrogate of hexokinase activity) and the distribution volume of 18F-FDG (Fe) as a fraction of lung volume (Ki = Fe × k3). Regional gas fractions (fgas) were assessed by examining transmission scans. Results Before endotoxin administration, protective (vs. injurious) ventilation was associated with a higher ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen (PaO2/FiO2) (351 ± 117 vs. 255 ± 74 mmHg; P ventilation, which also increased the shunt fraction in dependent lung. Protective ventilation resulted in less nonaerated lung (20-fold; P protective (vs. injurious) ventilation, especially in dependent lung regions (0.0075 ± 0.0043/min vs. 0.0157 ± 0.0072/min; P ventilation and accounted for most of the between-group difference in Ki. Dependent regions of the protective ventilation group exhibited lower k3 values per neutrophil than those in the injurious ventilation group (P = 0.01). In contrast, Fe was not affected by ventilation strategy (P = 0.52). Lung neutrophil counts were not different between groups, even when regional inflation was accounted for. Conclusions During systemic

Aspiration lung disorders in bovines: A case report and review

Directory of Open Access Journals (Sweden)

Anthony S. Shakespeare

2012-04-01

Full Text Available Lung aspiration disorders in bovines are invariably diagnosed as infectious aspiration pneumonias. There is a distinct differentiation between aspiration pneumonia and aspiration pneumonitis in humans that can be applied to bovines. The nature and quantity of the aspirate can result in differing pathogeneses which can require differing therapeutic approaches. Whilst blood gases were important in detecting and prognosticating lung problems, changes in barometric pressure with altitude have to be considered when interpreting partial pressures of oxygen. Anatomical differences in the lungs of bovines can explain why this species is more prone to certain pneumonic problems. Pulmonary physiotherapy is important in treating lung disorders in humans and should be considered as an adjunct therapy in bovine respiratory conditions. A case work-up was used to highlight some of the points discussed in this article.

Aspiration lung disorders in bovines: A case report and review

Directory of Open Access Journals (Sweden)

Anthony S. Shakespeare

2012-11-01

Full Text Available Lung aspiration disorders in bovines are invariably diagnosed as infectious aspiration pneumonias. There is a distinct differentiation between aspiration pneumonia and aspiration pneumonitis in humans that can be applied to bovines. The nature and quantity of the aspirate can result in differing pathogeneses which can require differing therapeutic approaches. Whilst blood gases were important in detecting and prognosticating lung problems, changes in barometric pressure with altitude have to be considered when interpreting partial pressures of oxygen. Anatomical differences in the lungs of bovines can explain why this species is more prone to certain pneumonic problems. Pulmonary physiotherapy is important in treating lung disorders in humans and should be considered as an adjunct therapy in bovine respiratory conditions. A case work-up was used to highlight some of the points discussed in this article.

Four-Hour Dives with Exercise While Breathing Oxygen Partial Pressure of 1.3 ATM

National Research Council Canada - National Science Library

Shykoff, B

2006-01-01

.... Still, because the increased ventilatory demands and blood flow to the lungs during underwater exercise may cause pulmonary injury or may increase oxygen-induced injury over those ventilatory demands...

Effects of a preemptive alveolar recruitment strategy on arterial oxygenation during one-lung ventilation with different tidal volumes in patients with normal pulmonary function test.

Science.gov (United States)

Jung, Jong Dal; Kim, Sang Hun; Yu, Byung Sik; Kim, Hye Ji

2014-08-01

Hypoxemia during one-lung ventilation (OLV) remains a major concern. The present study compared the effect of alveolar recruitment strategy (ARS) on arterial oxygenation during OLV at varying tidal volumes (Vt) with or without positive end-expiratory pressure (PEEP). In total, 120 patients undergoing wedge resection by video assisted thoracostomy were randomized into four groups comprising 30 patients each: those administered a 10 ml/kg tidal volume with or without preemptive ARS (Group H and Group H-ARS, respectively) and those administered a 6 ml/kg tidal volume and a 8 cmH2O PEEP with or without preemptive ARS (Group L and Group L-ARS, respectively). ARS was performed using pressure-controlled ventilation with a 40 cmH2O plateau airway pressure and a 15 cmH2O PEEP for at least 10 breaths until OLV began. Preemptive ARS significantly improved the PaO2/FiO2 ratio compared to the groups that did not receive ARS (P volume combined with 8 cmH2O PEEP after preemptive ARS may reduce the risk of pulmonary injury caused by high tidal volume during one-lung ventilation in patients with normal pulmonary function.

Cardiopulmonary function and oxygen delivery during total liquid ventilation.

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Tsagogiorgas, Charalambos; Alb, Markus; Herrmann, Peter; Quintel, Michael; Meinhardt, Juergen P

2011-10-01

Total liquid ventilation (TLV) with perfluorocarbons has shown to improve cardiopulmonary function in the injured and immature lung; however there remains controversy over the normal lung. Hemodynamic effects of TLV in the normal lung currently remain undetermined. This study compared changes in cardiopulmonary and circulatory function caused by either liquid or gas tidal volume ventilation. In a prospective, controlled study, 12 non-injured anesthetized, adult New Zealand rabbits were primarily conventionally gas-ventilated (CGV). After instrumentation for continuous recording of arterial (AP), central venous (CVP), left artrial (LAP), pulmonary arterial pressures (PAP), and cardiac output (CO) animals were randomized into (1) CGV group and (2) TLV group. In the TLV group partial liquid ventilation was initiated with instillation of perfluoroctylbromide (12 ml/kg). After 15 min, TLV was established for 3 hr applying a volume-controlled, pressure-limited, time-cycled ventilation mode using a double-piston configured TLV. Controls (CGV) remained gas-ventilated throughout the experiment. During TLV, heart rate, CO, PAP, MAP, CVP, and LAP as well as derived hemodynamic variables, arterial and mixed venous blood gases, oxygen delivery, PVR, and SVR did not differ significantly compared to CGV. Liquid tidal volumes suitable for long-term TLV in non-injured rabbits do not significantly impair CO, blood pressure, and oxygen dynamics when compared to CGV. Copyright © 2011 Wiley-Liss, Inc.

Effects of vertical positioning on gas exchange and lung volumes in acute respiratory distress syndrome.

Science.gov (United States)

Richard, Jean-Christophe M; Maggiore, Salvatore Maurizio; Mancebo, Jordi; Lemaire, François; Jonson, Bjorn; Brochard, Laurent

2006-10-01

Supine position may contribute to the loss of aerated lung volume in patients with acute respiratory distress syndrome (ARDS). We hypothesized that verticalization increases lung volume and improves gas exchange by reducing the pressure surrounding lung bases. Prospective observational physiological study in a medical ICU. In 16 patients with ARDS we measured arterial blood gases, pressure-volume curves of the respiratory system recorded from positive-end expiratory pressure (PEEP), and changes in lung volume in supine and vertical positions (trunk elevated at 45 degrees and legs down at 45 degrees ). Vertical positioning increased PaO(2) significantly from 94+/-33 to 142+/-49 mmHg, with an increase higher than 40% in 11 responders. The volume at 20 cmH(2)O measured on the PV curve from PEEP increased using the vertical position only in responders (233+/-146 vs. -8+/-9 1ml in nonresponders); this change was correlated to oxygenation change (rho=0.55). End-expiratory lung volume variation from supine to vertical and 1 h later back to supine, measured in 12 patients showed a significant increase during the 1-h upright period in responders (n=7) but not in nonresponders (n=5; 215+/-220 vs. 10+/-22 ml), suggesting a time-dependent recruitment. Vertical positioning is a simple technique that may improve oxygenation and lung recruitment in ARDS patients.

Postoperative inspiratory muscle training in addition to breathing exercises and early mobilization improves oxygenation in high-risk patients after lung cancer surgery: a randomized controlled trial.

Science.gov (United States)

Brocki, Barbara Cristina; Andreasen, Jan Jesper; Langer, Daniel; Souza, Domingos Savio R; Westerdahl, Elisabeth

2016-05-01

The aim was to investigate whether 2 weeks of inspiratory muscle training (IMT) could preserve respiratory muscle strength in high-risk patients referred for pulmonary resection on the suspicion of or confirmed lung cancer. Secondarily, we investigated the effect of the intervention on the incidence of postoperative pulmonary complications. The study was a single-centre, parallel-group, randomized trial with assessor blinding and intention-to-treat analysis. The intervention group (IG, n = 34) underwent 2 weeks of postoperative IMT twice daily with 2 × 30 breaths on a target intensity of 30% of maximal inspiratory pressure, in addition to standard postoperative physiotherapy. Standard physiotherapy in the control group (CG, n = 34) consisted of breathing exercises, coughing techniques and early mobilization. We measured respiratory muscle strength (maximal inspiratory/expiratory pressure, MIP/MEP), functional performance (6-min walk test), spirometry and peripheral oxygen saturation (SpO2), assessed the day before surgery and again 3-5 days and 2 weeks postoperatively. Postoperative pulmonary complications were evaluated 2 weeks after surgery. The mean age was 70 ± 8 years and 57.5% were males. Thoracotomy was performed in 48.5% (n = 33) of cases. No effect of the intervention was found regarding MIP, MEP, lung volumes or functional performance at any time point. The overall incidence of pneumonia was 13% (n = 9), with no significant difference between groups [IG 6% (n = 2), CG 21% (n = 7), P = 0.14]. An improved SpO2 was found in the IG on the third and fourth postoperative days (Day 3: IG 93.8 ± 3.4 vs CG 91.9 ± 4.1%, P = 0.058; Day 4: IG 93.5 ± 3.5 vs CG 91 ± 3.9%, P = 0.02). We found no association between surgical procedure (thoracotomy versus thoracoscopy) and respiratory muscle strength, which was recovered in both groups 2 weeks after surgery. Two weeks of additional postoperative IMT, compared with standard physiotherapy alone, did not preserve

Clinical management and outcomes of patients with Hermansky-Pudlak syndrome pulmonary fibrosis evaluated for lung transplantation.

Science.gov (United States)

El-Chemaly, Souheil; O'Brien, Kevin J; Nathan, Steven D; Weinhouse, Gerald L; Goldberg, Hilary J; Connors, Jean M; Cui, Ye; Astor, Todd L; Camp, Philip C; Rosas, Ivan O; Lemma, Merte; Speransky, Vladislav; Merideth, Melissa A; Gahl, William A; Gochuico, Bernadette R

2018-01-01

Pulmonary fibrosis is a progressive, fatal manifestation of Hermansky-Pudlak syndrome (HPS). Some patients with advanced HPS pulmonary fibrosis undergo lung transplantation despite their disease-associated bleeding tendency; others die while awaiting donor organs. The objective of this study is to determine the clinical management and outcomes of a cohort with advanced HPS pulmonary fibrosis who were evaluated for lung transplantation. Six patients with HPS-1 pulmonary fibrosis were evaluated at the National Institutes of Health Clinical Center and one of two regional lung transplant centers. Their median age was 41.5 years pre-transplant. Three of six patients died without receiving a lung transplant. One of these was referred with end-stage pulmonary fibrosis and died before a donor organ became available, and donor organs were not identified for two other patients sensitized from prior blood product transfusions. Three of six patients received bilateral lung transplants; they did not have a history of excessive bleeding. One patient received peri-operative desmopressin, one was transfused with intra-operative platelets, and one received extracorporeal membrane oxygenation and intra-operative prothrombin complex concentrate, platelet transfusion, and desmopressin. One transplant recipient experienced acute rejection that responded to pulsed steroids. No evidence of chronic lung allograft dysfunction or recurrence of HPS pulmonary fibrosis was detected up to 6 years post-transplant in these three lung transplant recipients. In conclusion, lung transplantation and extracorporeal membrane oxygenation are viable options for patients with HPS pulmonary fibrosis. Alloimmunization in HPS patients is an important and potentially preventable barrier to lung transplantation; interventions to limit alloimmunization should be implemented in HPS patients at risk of pulmonary fibrosis to optimize their candidacy for future lung transplants.

Inhaled Nitric Oxide for the Prevention of Impaired Arterial Oxygenation during Myocardial Revascularization with Extracorporeal Circulation

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I. A. Kozlov

2011-01-01

Full Text Available Objective: to study the efficacy of inhaled nitric oxide used intraoperatively to prevent lung oxygenating dysfunction in patients with coronary heart disease after myocardial revascularization under extracorporeal circulation (EC. Subjects and methods. Thirty-two patients aged 55.0±2.0 years were examined. The inclusion criteria were the standard course of surgical intervention (the absence of hemorrhage, acute cardiovascular insufficiency, perioperative myocardial infarction, etc., a pulmonary artery wedge pressure of less than 15 – mm Hg throughout the study, and the baseline arterial partial oxygen tension/inspired mixture oxygen fraction (PaO2/FiO2 ratio of at least 350 mm Hg. There was a control group (n=21; Group 1 that used no special measures to prevent and/or to correct lung oxygenating dysfunction and Group 2 (n=11 that received inhaled nitric oxide. Ihe administration of inhaled nitric oxide at a concentration of 10 ppm was initiated after water anesthesia, stopped during EC, and resumed in the postperfusion period. Results. At the end, PaO2/FiO2 and intrapulmonary shunt fraction did not differ between the groups (p>0.05. Before EC, the patients receiving inhaled nitric oxide had a lower intrapulmonary blood shunting (8.9±0.7 and 11.7±1.0%; p<0.05. There were no intergroup differences in the values of PaO2/FiO2 at this stage. In the earliest postperfusion period, PaO2/FiO2 was higher in Group 2 than that in Group 1. At the end of operations, Groups 1 and 2 had a PaO2/FiO2 of 336.0±16.8 and 409.0±24.3 mm Hg, respectively (p<0.05 and an intrapulmonary shunt fraction of 14.5±1.0 and 10.4±1.0% (p<0.05. At the end of surgery, the rate of a reduction in PaO2/FiO2 to the level below 350 mm Hg was 52.4±11.1% in Group 1 and 18.2±11.6% in Group 2 (p<0.05. Six hours after surgery, PaO2/FiO2 values less than 300 mm Hg were diagnosed in 61.9±10.5% of Group 1 patients and in 27.3±13.4% of Group 2 ones (p<0.05. Conclusion. The

Mast cells and exosomes in hyperoxia-induced neonatal lung disease.

Science.gov (United States)

Veerappan, A; Thompson, M; Savage, A R; Silverman, M L; Chan, W S; Sung, B; Summers, B; Montelione, K C; Benedict, P; Groh, B; Vicencio, A G; Peinado, H; Worgall, S; Silver, R B

2016-06-01

Chronic lung disease of prematurity (CLD) is a frequent sequela of premature birth and oxygen toxicity is a major associated risk factor. Impaired alveolarization, scarring, and inflammation are hallmarks of CLD. Mast cell hyperplasia is a feature of CLD but the role of mast cells in its pathogenesis is unknown. We hypothesized that mast cell hyperplasia is a consequence of neonatal hyperoxia and contributes to CLD. Additionally, mast cell products may have diagnostic and prognostic value in preterm infants predisposed to CLD. To model CLD, neonatal wild-type and mast cell-deficient mice were placed in an O2 chamber delivering hyperoxic gas mixture [inspired O2 fraction (FiO2 ) of 0.8] (HO) for 2 wk and then returned to room air (RA) for an additional 3 wk. Age-matched controls were kept in RA (FiO2 of 0.21). Lungs from HO mice had increased numbers of mast cells, alveolar simplification and enlargement, and increased lung compliance. Mast cell deficiency proved protective by preserving air space integrity and lung compliance. The mast cell mediators β-hexosaminidase (β-hex), histamine, and elastase increased in the bronchoalveolar lavage fluid of HO wild-type mice. Tracheal aspirate fluids (TAs) from oxygenated and mechanically ventilated preterm infants were analyzed for mast cell products. In TAs from infants with confirmed cases of CLD, β-hex was elevated over time and correlated with FiO2 Mast cell exosomes were also present in the TAs. Collectively, these data show that mast cells play a significant role in hyperoxia-induced lung injury and their products could serve as potential biomarkers in evolving CLD. Copyright © 2016 the American Physiological Society.

Visualization of neonatal lung injury associated with mechanical ventilation using x-ray dark-field radiography

Science.gov (United States)

Yaroshenko, Andre; Pritzke, Tina; Koschlig, Markus; Kamgari, Nona; Willer, Konstantin; Gromann, Lukas; Auweter, Sigrid; Hellbach, Katharina; Reiser, Maximilian; Eickelberg, Oliver; Pfeiffer, Franz; Hilgendorff, Anne

2016-04-01

Mechanical ventilation (MV) and supplementation of oxygen-enriched gas, often needed in postnatal resuscitation procedures, are known to be main risk factors for impaired pulmonary development in the preterm and term neonates. Unfortunately, current imaging modalities lack in sensitivity for the detection of early stage lung injury. The present study reports a new imaging approach for diagnosis and staging of early lung injury induced by MV and hyperoxia in neonatal mice. The imaging method is based on the Talbot-Lau x-ray grating interferometry that makes it possible to quantify the x-ray small-angle scattering on the air-tissue interfaces. This so-called dark-field signal revealed increasing loss of x-ray small-angle scattering when comparing images of neonatal mice undergoing hyperoxia and MV-O2 with animals kept at room air. The changes in the dark field correlated well with histologic findings and provided superior differentiation than conventional x-ray imaging and lung function testing. The results suggest that x-ray dark-field radiography is a sensitive tool for assessing structural changes in the developing lung. In the future, with further technical developments x-ray dark-field imaging could be an important tool for earlier diagnosis and sensitive monitoring of lung injury in neonates requiring postnatal oxygen or ventilator therapy.

The pharmaco-kinetics of angiographic contrast media with special reference to the extravascular spaces. Fundamental studies on dogs for the characterization of angiographic media. Pt. 1

International Nuclear Information System (INIS)

Lagemann, K.

1975-01-01

The pharmaco-kinetics of angiographic contrast media in the extra-vascular space, which are largely unknown, were investigated experimentally in dogs. As part of a basic study, using radio-active contrast media, it was possible to determine the concentration and rate of elimination in practically all organs and tissues. Measurements were carried out first after prolonged infusion of contrast under conditions of balanced flow, and secondly six hours after the end of the infusion. It was therefore possible to determine the inflow and loss of contrast medium in various organs, or organs systems. The most commonly used angiographic contrast media in Germany were investigated. Their kinetic behaviour is largely identical, their pattern of distribution and elimination depended principally on the organ or tissue. (orig.) [de

Occurrence of hypermutable Pseudomonas aeruginosa in cystic fibrosis patients is associated with the oxidative stress caused by chronic lung inflammation

DEFF Research Database (Denmark)

Ciofu, Oana; Riis, Bente; Pressler, Tacjana

2005-01-01

Oxidative stress caused by chronic lung inflammation in patients with cystic fibrosis (CF) and chronic lung infection with Pseudomonas aeruginosa is characterized by the reactive oxygen species (ROS) liberated by polymorphonuclear leukocytes (PMNs). We formulated the hypothesis that oxidation...

Edaravone prevents lung injury induced by hepatic ischemia-reperfusion.

Science.gov (United States)

Uchiyama, Munehito; Tojo, Kentaro; Yazawa, Takuya; Ota, Shuhei; Goto, Takahisa; Kurahashi, Kiyoyasu

2015-04-01

Lung injury is a major clinical concern after hepatic ischemia-reperfusion (I/R), due to the production of reactive oxygen species in the reperfused liver. We investigated the efficacy of edaravone, a potent free-radical scavenger, for attenuating lung injury after hepatic I/R. Adult male Sprague-Dawley rats were assigned to sham + normal saline (NS), I/R + NS, or I/R + edaravone group. Rats in the I/R groups were subjected to 90 min of partial hepatic I/R. Five minutes before reperfusion, 3 mg/kg edaravone was administered to the I/R + edaravone group. After 6 h of reperfusion, we evaluated lung histopathology and wet-to-dry ratio. We also measured malondialdehyde (MDA), an indicator of oxidative stress, in the liver and the lung, as well as cytokine messenger RNA expressions in the reperfused liver and plasma cytokine concentrations. Histopathology revealed lung damages after 6 h reperfusion of partial ischemic liver. Moreover, a significant increase in lung wet-to-dry ratio was observed. MDA concentration increased in the reperfused liver, but not in the lungs. Edaravone administration attenuated the lung injury and the increase of MDA in the reperfused liver. Edaravone also suppressed the reperfusion-induced increase of interleukin-6 messenger RNA expressions in the liver and plasma interleukin-6 concentrations. Edaravone administration before reperfusion of the ischemic liver attenuates oxidative stress in the reperfused liver and the subsequent lung injury. Edaravone may be beneficial for preventing lung injury induced by hepatic I/R. Copyright © 2015 Elsevier Inc. All rights reserved.

Carboxyhemoglobin half-life during hyperbaric oxygen in a patient with lung dysfunction: a case report.

Science.gov (United States)

Weaver, Lindell K; Deru, Kayla

2017-01-01

The carboxyhemoglobin half-life (COHb t1/2) during hyperbaric oxygen (HBO₂) is often quoted as 23 minutes, derived from the average of two adult male volunteers breathing HBO₂ at 3 atmospheres absolute (ATA). However, the mean COHb t1/2 of 12 male volunteer smokers was 26.3 minutes at 1.58 ATA and in 12 non-intubated carbon monoxide (CO) poisoned patients treated at 3 ATA, was 43 minutes. An 81-year old male, poisoned by an improperly ventilated natural gas heater, was intubated for coma, then treated with HBO₂. His PaO₂/FiO₂ = 283 from aspiration. His initial COHb was 34.4%, and 18 minutes before HBO₂, 5.9%. After a compression interval of 17 minutes, the COHb measured after 22 minutes at 3 ATA was 3.3%. By exponential decay, his COHb t1/2 before HBO₂ was 95 minutes. We estimate the range for COHb t1/2 during compression as 62-81 minutes and for the 3-ATA interval, 58 to 49 minutes, respectively. The mid-point estimate of COHb t1/2 at 3 ATA was 53 minutes. The COHb t1/2 we calculated is greater than previously reported, but longer in our patient possibly because of concomitant respiratory failure, lung dysfunction, and mechanical ventilation. The often-cited COHb t1/2 of 23 minutes, likely underestimates the actual COHb t1/2 in CO-poisoned patients, especially those with cardiopulmonary dysfunction.

Lung function studies in diagnostics and follow-up of pulmonary sarcoidosis

International Nuclear Information System (INIS)

Braadvik, I.

1994-06-01

In 66 patients the relationship between lung volumes and lung mechanics in pulmonary sarcoidosis was investigated. Lung volumes, static lung mechanics, lung resistance, dynamic lung mechanics and arterial blood gases at rest and during exercise were obtained. Fifteen functionally compromised patients received steroids during one year. They were re-investigated during the treatment and at a follow-up after an average of 7 years. In another 41 patients with newly diagnosed sarcoidosis, the kinetics of the lung clearance of 99m Tc-DTPA measured over 180 minutes was explored, and compared to kinetics in healthy smokers. The relationship between lung clearance and lung volumes, lung mechanics, arterial blood gases and disease activity assessed with serum angiotensin-converting enzyme and 67 Ga scintigraphy was studied. Reducing lung volumes and compliance, increased resistance and arterial oxygen tension were common. Vital capacity (VC), and changes of VC at follow-up, corresponded to the slope of the static elastic pressure/volume curve, and to the variation of it. Other static lung volumes reflected rather the position of the curve along the volume axis. Reduced VC also reflected obstruction. Forced expiratory volume in one second revealed to equal extent lung stiffness and obstruction. Lung mechanics showed abnormalities not always evident from spirometry.In 50% of the patients lung clearance of 99m Tc-DTPA disclosed an abnormally fast mono-exponential clearance or a bi-exponential clearance, which however differed from that in smokers. Lung clearance more readily detected abnormal function than did spirometry. Clearance did nor correlate with other investigations. 67 Ga lung activity was higher in patients with a pathologic lung clearance

Correction of Pulmonary Oxygenizing Dysfunction in the Early Activation of Cardiosurgical Patients

Directory of Open Access Journals (Sweden)

I. A. Kozlov

2009-01-01

Full Text Available Objective: to justify a comprehensive approach to preventing and correcting pulmonary oxygenizing dysfunction requiring prolonged artificial ventilation in patients operated on under extracorporeal circulation for coronary heart disease. Subjects and methods. One hundred and twenty-three patients aged 55±0.6 years were examined. The study excluded patients with a complicated course of operations (perioperative myocardial infarction, acute cardiovascular insufficiency, hemorrhage, and long extracorporeal circulation. Stimulating spirometry was initiated 2 days before surgery. An alveolar opening maneuver was performed using a continuous dynamic thoracopulmonary compliance monitoring. The parameters of lung oxygenizing function and biomechanics were analyzed. Results. In 78% of the patients, preoperative inspiratory lung capacity was 5—30% lower than the age-related normal values. After extracorporeal circulation, pulmonary oxygenizing dysfunction was diagnosed in 40.9% of cases; at the same time PaO2/FiO2 was associated with an intrapulmonary shunt fraction (Qs/St (r=-0.53; p=0.002 and Qs/Qt was related to static thoracopulmonary compliance (Cst (r=-0.39; p=0.03. Preoperative stimulating spirometry provided a considerable increase in intraoperative PaO2/FiO2 values (p<0.05; improved Cst and decreased Qs/Qt. After extracorporeal circulation, the incidence of pulmonary oxygenizing dysfunction was decreased by more than twice (p<0.05. Patients with relative arterial hypoxemia showed a noticeable relationship to the magnitudes of a reduction in Cst and a rise in Qs/Qt (r=0.72; p=0.008, which served as the basis for applying the alveolar opening maneuver. This type of lung support corrected arterial hypoxemia in 67% of cases. Conclusion. In car-diosurgical patients with coronary heart disease, effective prophylaxis and correction of relative arterial hypoxemia caused by the interrelated impairments of pulmonary biomechanical properties and

Evaluation of lung function changes before and after surfactant application during artificial ventilation in newborn rats with congenital diaphragmatic hernia

NARCIS (Netherlands)

E.C. Scheffers; H. IJsselstijn (Hanneke); R. Tenbrinck (Robert); B.F. Lachmann (Burkhard); J.C. de Jongste (Johan); J.C. Molenaar; D. Tibboel (Dick)

1994-01-01

textabstractPatients with congenital diaphragmatic hernia (CDH) have unilateral or bilateral hypoplasia of the lungs including delayed maturation of the terminal air sacs. Because these lungs are highly susceptible to barotrauma and oxygen toxicity, even in full-term newborns, continued research

Normobaric pulmonary oxygen toxicity : experimental studies on the mechanism of the protective role of endotoxin and the role of surfactant.

NARCIS (Netherlands)

J. Klein (Jan)

1991-01-01

textabstractAdministration of above-ambient oxygen tensions, necessary for treatment of severe hypoxemia caused by respiratory failure or acute lung injury, is potentially toxic for the lungs. This thesis is based on six articles dealing with this topic: one review article and five articles

Radioaerosol lung imaging - history and pharmaceuticals

International Nuclear Information System (INIS)

Isawa, Toyoharu

1994-01-01

The first use of a radioactive tracer to study lung function was made by Knipping and others in 1955. They used radioactive 133 Xe (xenon) gas as an inhalation agent in a patient with lung cancer and found that distal to a tumor no radioactivity was detected indicating no ventilation although chest x-rays appeared as if there was active ventilation. Subsequently with advance in technology a number of radioactive gases such as 81m Kr (krypton) and cyclotron produced 15 O 2 (oxygen), 11 C (carbon) and 13 N 2 (nitrogen) became available to assess regional lung function. The advantages of these gases are manifold, but their utility is mostly limited due to high cost. An alternative to the use of radioactive gases to study regional ventilation is the use of particulate radioactive aerosol. Radioaerosol inhalation lung imaging technique was developed in 1965 almost simultaneously by Taplin and others and Pircher and others just 2 years following Taplin's invention of 131 I-MAA for perfusion lung imaging. Their main aim was to use 131 I-human serum albumin (HSA), and 99m Tc-HSA, 131 I-rose bengal, 197 Hg-chlormerodrin and colloidal 198 Au as agents for radioaerosol generation, and Taplin himself preferred 198 Au colloids for serial studies from economical reasons. Already in 1965, however, Taplin said that the best agent would be 99m Tc-HSA. Pircher used 131 I-HSA aerosol. Taplin already noted at that time that the inhaled aerosol was removed from the lungs mainly by ciliary action and that it was not absorbed either from the lungs or the intestine. Anyway it is noteworthy that the idea of radioaerosol inhalation lung imaging was proposed soon after the advent of perfusion lung imaging. Besides 131 I-HSA and colloidal 198 Au, the following agents have been or are currently being used. The superiority of 99m TC over other radioisotopes used in the past is beyond dispute

Influence of Substrate Composition on vitro Oxygen Consumption of ...

African Journals Online (AJOL)

1974-09-11

Sep 11, 1974 ... and it activates the angiotensin sys- tem by converting angiotensin I to angiotensin n.l3 It also participates in the de 110\\10 synthesis of fatty acids," pro- teins" and of phospholipids (surfactant)." The oxygen consumed by the lung is used not only for its own basal metabolic needs but for additional metabolic.

Cyclic PaO2 oscillations assessed in the renal microcirculation: correlation with tidal volume in a porcine model of lung lavage.

Science.gov (United States)

Thomas, Rainer; Möllmann, Christian; Ziebart, Alexander; Liu, Tanghua; David, Matthias; Hartmann, Erik K

2017-07-11

Oscillations of the arterial partial pressure of oxygen induced by varying shunt fractions occur during cyclic alveolar recruitment within the injured lung. Recently, these were proposed as a pathomechanism that may be relevant for remote organ injury following acute respiratory distress syndrome. This study examines the transmission of oxygen oscillations to the renal tissue and their tidal volume dependency. Lung injury was induced by repetitive bronchoalveolar lavage in eight anaesthetized pigs. Cyclic alveolar recruitment was provoked by high tidal volume ventilation. Oscillations of the arterial partial pressure of oxygen were measured in real-time in the macrocirculation by multi-frequency phase fluorimetry and in the renal microcirculation by combined white-light spectrometry and laser-Doppler flowmetry during tidal volume down-titration. Significant respiratory-dependent oxygen oscillations were detected in the macrocirculation and transmitted to the renal microcirculation in a substantial extent. The amplitudes of these oscillations significantly correlate to the applied tidal volume and are minimized during down-titration. In a porcine model oscillations of the arterial partial pressure of oxygen are induced by cyclic alveolar recruitment and transmitted to the renal microcirculation in a tidal volume-dependent fashion. They might play a role in organ crosstalk and remote organ damage following lung injury.

A 3D-Printed Oxygen Control Insert for a 24-Well Plate.

Directory of Open Access Journals (Sweden)

Martin D Brennan

Full Text Available 3D printing has emerged as a method for directly printing complete microfluidic devices, although printing materials have been limited to oxygen-impermeable materials. We demonstrate the addition of gas permeable PDMS (Polydimethylsiloxane membranes to 3D-printed microfluidic devices as a means to enable oxygen control cell culture studies. The incorporation of a 3D-printed device and gas-permeable membranes was demonstrated on a 24-well oxygen control device for standard multiwell plates. The direct printing allows integrated distribution channels and device geometries not possible with traditional planar lithography. With this device, four different oxygen conditions were able to be controlled, and six wells were maintained under each oxygen condition. We demonstrate enhanced transcription of the gene VEGFA (vascular endothelial growth factor A with decreasing oxygen levels in human lung adenocarcinoma cells. This is the first 3D-printed device incorporating gas permeable membranes to facilitate oxygen control in cell culture.

OPTICAL IMAGING OF LIPOPOLYSACCHARIDE-INDUCED OXIDATIVE STRESS IN ACUTE LUNG INJURY FROM HYPEROXIA AND SEPSIS

Directory of Open Access Journals (Sweden)

REYHANEH SEPEHR

2013-07-01

Full Text Available Reactive oxygen species (ROS have been implicated in the pathogenesis of many acute and chronic pulmonary disorders such as acute lung injury (ALI in adults and bronchopulmonary dysplasia (BPD in premature infants. Bacterial infection and oxygen toxicity, which result in pulmonary vascular endothelial injury, contribute to impaired vascular growth and alveolar simplification seen in the lungs of premature infants with BPD. Hyperoxia induces ALI, reduces cell proliferation, causes DNA damage and promotes cell death by causing mitochondrial dysfunction. The objective of this study was to use an optical imaging technique to evaluate the variations in fluorescence intensities of the auto-fluorescent mitochondrial metabolic coenzymes, NADH and FAD in four different groups of rats. The ratio of these fluorescence signals (NADH/FAD, referred to as NADH redox ratio (NADH RR has been used as an indicator of tissue metabolism in injuries. Here, we investigated whether the changes in metabolic state can be used as a marker of oxidative stress caused by hyperoxia and bacterial lipopolysaccharide (LPS exposure in neonatal rat lungs. We examined the tissue redox states of lungs from four groups of rat pups: normoxic (21% O2 pups, hyperoxic (90% O2 pups, pups treated with LPS (normoxic + LPS, and pups treated with LPS and hyperoxia (hyperoxic + LPS. Our results show that hyperoxia oxidized the respiratory chain as reflected by a ~ 31% decrease in lung tissue NADH RR as compared to that for normoxic lungs. LPS treatment alone or with hyperoxia had no significant effect on lung tissue NADH RR as compared to that for normoxic or hyperoxic lungs, respectively. Thus, NADH RR serves as a quantitative marker of oxidative stress level in lung injury caused by two clinically important conditions: hyperoxia and LPS exposure.

Formation of reactive oxygen species in rat epithelial cells upon ...

Indian Academy of Sciences (India)

In our study, we investigated the influence of fly ash on the promotion of early inflammatory reactions like the formation of reactive oxygen species (ROS) in rat lung epithelial cells (RLE-6TN). Furthermore, we determined the formation of nitric oxide (NO). The cells show a clear dose-response relationship concerning the ...

The effect of CSF-1 administration on lung maturation in a mouse model of neonatal hyperoxia exposure.

Science.gov (United States)

Jones, Christina V; Alikhan, Maliha A; O'Reilly, Megan; Sozo, Foula; Williams, Timothy M; Harding, Richard; Jenkin, Graham; Ricardo, Sharon D

2014-09-06

Lung immaturity due to preterm birth is a significant complication affecting neonatal health. Despite the detrimental effects of supplemental oxygen on alveolar formation, it remains an important treatment for infants with respiratory distress. Macrophages are traditionally associated with the propagation of inflammatory insults, however increased appreciation of their diversity has revealed essential functions in development and regeneration. Macrophage regulatory cytokine Colony-Stimulating Factor-1 (CSF-1) was investigated in a model of neonatal hyperoxia exposure, with the aim of promoting macrophages associated with alveologenesis to protect/rescue lung development and function. Neonatal mice were exposed to normoxia (21% oxygen) or hyperoxia (Hyp; 65% oxygen); and administered CSF-1 (0.5 μg/g, daily × 5) or vehicle (PBS) in two treatment regimes; 1) after hyperoxia from postnatal day (P)7-11, or 2) concurrently with five days of hyperoxia from P1-5. Lung structure, function and macrophages were assessed using alveolar morphometry, barometric whole-body plethysmography and flow cytometry. Seven days of hyperoxia resulted in an 18% decrease in body weight and perturbation of lung structure and function. In regime 1, growth restriction persisted in the Hyp + PBS and Hyp + CSF-1 groups, although perturbations in respiratory function were resolved by P35. CSF-1 increased CSF-1R+/F4/80+ macrophage number by 34% at P11 compared to Hyp + PBS, but was not associated with growth or lung structural rescue. In regime 2, five days of hyperoxia did not cause initial growth restriction in the Hyp + PBS and Hyp + CSF-1 groups, although body weight was decreased at P35 with CSF-1. CSF-1 was not associated with increased macrophages, or with functional perturbation in the adult. Overall, CSF-1 did not rescue the growth and lung defects associated with hyperoxia in this model; however, an increase in CSF-1R+ macrophages was not associated with an

[USE OF PROTECTIVE LUNG VENTILATION REGIMEN IN CARDIAC SURGERY PATIENTS.

Science.gov (United States)

Pshenichniy, T A; Akselrod, B A; Titova, I V; Trekova, N A; Khrustaleva, M V

2017-09-01

In cardiac surgery, protective lung ventilation and/or preventive brdnchoscopy (PB) are able to decrease lung injury effects of cardiopulmonary bypass (CPB) and mechanical ventilation. define lung complication risks, evaluate the effect ofprotective lung ventilation (PLV) on lung functioning, and investigate the feasibility ofpreventive PB in higher pulmonary risk (PR) patients. 66 patients participated in prospective randomized research. Allocation was based on PR and intraoperative mechanical ventilation type. PLV includedfollowing parameters: PCK PIP - up to 20 cm H20, Vt - 6 ml/ kg of PBW, PEEP - 5-10 cm H20, IE ratio - 1:1.5-1:1, EtCO2 - 35-42 mm Hg, FiO2 - 45-60%, lung ventilation during CPB, alveolar recruitment. Four groups were formed: A - higher PR plus PLV- B - higher PR plus conventional LV (CLV), C - lower PR plus PLV- D - lower PR plus CLV PIP PEEP dynamic compliance, p/f ratio and intrapulmonary shunt (Qs/Qt) were recorded. Seventeen patients of group A underwent PB. Advanced dynamic compliance, higher p/f ratio and lower Qs/Qt were seen in group A, in comparison with group B (pProtective lung ventilation improves lung biomechanics and oxygenating function in higher risk patients and decreases intrapulmonary shunt fraction in higher and lower risk patients. Addictive preventive bronchoscopy can be successfully used in higher risk patients.

Lung function measurement in awake young children

DEFF Research Database (Denmark)

Bisgaard, H; Klug, B

1995-01-01

) and transcutaneous measurements of oxygen tension (Ptc,O2) were compared with concomitant measurements of specific airway resistance (sRaw) and forced expiratory volume in one second (FEV1) by whole body plethysmography and spirometry, respectively, during methacholine challenge in 21 young children aged 4-6 yrs...... to methacholine in young children aged 4-6 yrs. This implies that ZIOS, Rint and Ptc,O2 provide convenient indices of changes in lung function. Their combined use will be useful for monitoring airway diseases of young children.......The aim of the study was to evaluate methods applicable in a clinical setting for monitoring of changes in lung function in awake young children. Impedance measurements by the impulse oscillation technique (ZIOS), respiratory resistance measurements by the interrupter technique (Rint...

Nitric oxide and carbon monoxide diffusing capacity after a 1-h oxygen dive to 9 m of sea water

NARCIS (Netherlands)

van Ooij, P. J. A. M.; van Hulst, R. A.; Houtkooper, A.; Sterk, P. J.

2014-01-01

To prevent extensive pulmonary lesions in submerged oxygen divers lung function like the forced vital capacity (FVC) or the diffusing capacity for carbon monoxide (DL,co) are used to monitor pulmonary oxygen toxicity (POT). As the diffusing capacity for nitric oxide (DL,no) measures more accurately

Lung microvascular transport properties measured by multiple indicator dilution methods in patients with adult respiratory distress syndrome. A comparison between patients reversing respiratory failure and those failing to reverse

International Nuclear Information System (INIS)

Harris, T.R.; Bernard, G.R.; Brigham, K.L.; Higgins, S.B.; Rinaldo, J.E.; Borovetz, H.S.; Sibbald, W.J.; Kariman, K.; Sprung, C.L.

1990-01-01

We conducted indicator dilution studies on the lungs of patients in the early phases of adult respiratory distress syndrome (ARDS) to test the hypothesis that capillary permeability was increased in patients with respiratory failure. Indicator dilution studies were performed using 51Cr-erythrocytes, 125I-albumin, 14C-urea, and 3H-water as tracers. The injectate was infused as a bolus into a central venous line. Peripheral arterial blood was collected and counted for radioactivity. Mathematical analysis of the indicator curves yielded cardiac output, measures of the product of capillary permeability and surface area for urea (PS and D1/2S), the intravascular lung volume (Vv), and the extravascular lung water volume (Ve). Permeability was separated from surface area by normalizing PS and D1/2S to Vv. Patients could be divided into 16 in whom blood gas determinations and radiologic criteria for ARDS were reversed and 23 in whom they were not. We examined indicator dilution and other measures of lung function in the two groups to determine whether significant differences in microvascular function existed. PS and PS/Vv were significantly higher in the nonreversal patients. Ve was above normal, but not different between groups. Linear regression analysis showed significant correlations for all of the following in the nonreversal group: Ve and all measures of permeability, pulmonary vascular resistance (PVR), and the inverse of permeability-surface area measures and AaDO2 and PVR. Only measures of Ve and PS correlated in the reversal group. These results support the hypothesis that capillary permeability is increased in patients with early ARDS and continuing respiratory failure

Effect of one-lung ventilation on end-tidal carbon dioxide during cardiopulmonary resuscitation in a pig model of cardiac arrest.

Science.gov (United States)

Ryu, Dong Hyun; Jung, Yong Hun; Jeung, Kyung Woon; Lee, Byung Kook; Jeong, Young Won; Yun, Jong Geun; Lee, Dong Hun; Lee, Sung Min; Heo, Tag; Min, Yong Il

2018-01-01

Unrecognized endobronchial intubation frequently occurs after emergency intubation. However, no study has evaluated the effect of one-lung ventilation on end-tidal carbon dioxide (ETCO2) during cardiopulmonary resuscitation (CPR). We compared the hemodynamic parameters, blood gases, and ETCO2 during one-lung ventilation with those during conventional two-lung ventilation in a pig model of CPR, to determine the effect of the former on ETCO2. A randomized crossover study was conducted in 12 pigs intubated with double-lumen endobronchial tube to achieve lung separation. During CPR, the animals underwent three 5-min ventilation trials based on a randomized crossover design: left-lung, right-lung, or two-lung ventilation. Arterial blood gases were measured at the end of each ventilation trial. Ventilation was provided using the same tidal volume throughout the ventilation trials. Comparison using generalized linear mixed model revealed no significant group effects with respect to aortic pressure, coronary perfusion pressure, and carotid blood flow; however, significant group effect in terms of ETCO2 was found (P < 0.001). In the post hoc analyses, ETCO2 was lower during the right-lung ventilation than during the two-lung (P = 0.006) or left-lung ventilation (P < 0.001). However, no difference in ETCO2 was detected between the left-lung and two-lung ventilations. The partial pressure of arterial carbon dioxide (PaCO2), partial pressure of arterial oxygen (PaO2), and oxygen saturation (SaO2) differed among the three types of ventilation (P = 0.003, P = 0.001, and P = 0.001, respectively). The post hoc analyses revealed a higher PaCO2, lower PaO2, and lower SaO2 during right-lung ventilation than during two-lung or left-lung ventilation. However, the levels of these blood gases did not differ between the left-lung and two-lung ventilations. In a pig model of CPR, ETCO2 was significantly lower during right-lung ventilation than during two-lung ventilation. However

Mucoid conversion of Pseudomonas aeruginosa by hydrogen peroxide: a mechanism for virulence activation in the cystic fibrosis lung

DEFF Research Database (Denmark)

Mathee, Kalai; Ciofu, Oana; Sternberg, Claus

1999-01-01

leukocytes (PMNs), which release free oxygen radicals such as H(2)O(2) The mucoid phenotype among the strains infecting CF patients indicates overproduction of a linear polysaccharide called alginate. To mimic the inflammatory environment of the CF lung, P. aeruginosa PAO1, a typical non-mucoid strain....... These findings indicate that gene activation in bacteria by toxic oxygen radicals, similar to that found in plants and mammalian cells, may serve as a defence mechanism for the bacteria. This suggests that mucoid conversion is a response to oxygen radical exposure and that this response is a mechanism of defence...... by the bacteria. This is the first report to show that PMNs and their oxygen radicals can cause this phenotypic and genotypic change which is so typical of the intractable form of P. aeruginosa in the CF lung. These findings may provide a basis for the development of anti-oxidant and anti-inflammatory therapy...

Lung Ultrasound for Diagnosing Pneumothorax in the Critically Ill Neonate.

Science.gov (United States)

Raimondi, Francesco; Rodriguez Fanjul, Javier; Aversa, Salvatore; Chirico, Gaetano; Yousef, Nadya; De Luca, Daniele; Corsini, Iuri; Dani, Carlo; Grappone, Lidia; Orfeo, Luigi; Migliaro, Fiorella; Vallone, Gianfranco; Capasso, Letizia

2016-08-01

To evaluate the accuracy of lung ultrasound for the diagnosis of pneumothorax in the sudden decompensating patient. In an international, prospective study, sudden decompensation was defined as a prolonged significant desaturation (oxygen saturation pneumothorax was detected in 26 (62%). Lung ultrasound accuracy in diagnosing pneumothorax was as follows: sensitivity 100%, specificity 100%, positive predictive value 100%, and negative predictive value 100%. Clinical evaluation of pneumothorax showed sensitivity 84%, specificity 56%, positive predictive value 76%, and negative predictive value 69%. After sudden decompensation, a lung ultrasound scan was performed in an average time of 5.3 ± 5.6 minutes vs 19 ± 11.7 minutes required for a chest radiography. Emergency drainage was performed after an ultrasound scan but before radiography in 9 cases. Lung ultrasound shows high accuracy in detecting pneumothorax in the critical infant, outperforming clinical evaluation and reducing time to imaging diagnosis and drainage. Copyright © 2016 Elsevier Inc. All rights reserved.

Cost and effectiveness of lung lobectomy by video-assisted thoracic surgery for lung cancer.

Science.gov (United States)

Mafé, Juan J; Planelles, Beatriz; Asensio, Santos; Cerezal, Jorge; Inda, María-Del-Mar; Lacueva, Javier; Esteban, Maria-Dolores; Hernández, Luis; Martín, Concepción; Baschwitz, Benno; Peiró, Ana M

2017-08-01

Video-assisted thoracic surgery (VATS) emerged as a minimally invasive surgery for diseases in the field of thoracic surgery. We herein reviewed our experience on thoracoscopic lobectomy for early lung cancer and evaluated Health System use. A cost-effectiveness study was performed comparing VATS vs. open thoracic surgery (OPEN) for lung cancer patients. Demographic data, tumor localization, dynamic pulmonary function tests [forced vital capacity (FVC), forced expiratory volume in one second (FEV1), diffusion capacity (DLCO) and maximal oxygen uptake (VO2max)], surgical approach, postoperative details, and complications were recorded and analyzed. One hundred seventeen patients underwent lung resection by VATS (n=42, 36%; age: 63±9 years old, 57% males) or OPEN (n=75, 64%; age: 61±11 years old, 73% males). Pulmonary function tests decreased just after surgery with a parallel increasing tendency during first 12 months. VATS group tended to recover FEV1 and FVC quicker with significantly less clinical and post-surgical complications (31% vs. 53%, P=0.015). Costs including surgery and associated hospital stay, complications and costs in the 12 months after surgery were significantly lower for VATS (P<0.05). The VATS approach surgery allowed earlier recovery at a lower cost than OPEN with a better cost-effectiveness profile.

Pilot study of a new device to titrate oxygen flow in hypoxic patients on long-term oxygen therapy.

Science.gov (United States)

Cirio, Serena; Nava, Stefano

2011-04-01

The O(2) Flow Regulator (Dima, Bologna, Italy) is a new automated oxygen regulator that titrates the oxygen flow based on a pulse-oximetry signal to maintain a target S(pO(2)). We tested the device's safety and efficacy. We enrolled 18 subjects with chronic lung disease, exercise-induced desaturation, and on long-term oxygen therapy, in a randomized crossover study with 2 constant-work-load 15-min cycling exercise tests, starting with the patient's previously prescribed usual oxygen flow. In one test the oxygen flow was titrated manually by the respiratory therapist, and in the other test the oxygen flow was titrated by the O(2) Flow Regulator, to maintain an S(pO(2)) of 94%. We measured S(pO(2)) throughout each test, the time spent by the respiratory therapist to set the device or to manually regulate the oxygen flow, and the total number of respiratory-therapist titration interventions during the trial. There were no differences in symptoms or heart rate between the exercise tests. Compared to the respiratory-therapist-controlled tests, during the O(2) Flow Regulator tests S(pO(2)) was significantly higher (95 ± 2% vs 93 ± 3%, P = .04), significantly less time was spent below the target S(pO(2)) (171 ± 187 s vs 340 ± 220 s, P less respiratory therapist time (5.6 ± 3.7 min vs 2.0 ± 0.1 min, P = .005). The O(2) Flow Regulator may be a safe and effective alternative to manual oxygen titration during exercise in hypoxic patients. It provided stable S(pO(2)) and avoided desaturations in our subjects.

A comparison of conventional surfactant treatment and partial liquid ventilation on the lung volume of injured ventilated small lungs

International Nuclear Information System (INIS)

Proquitté, Hans; Hartenstein, Sebastian; Wauer, Roland R; Schmalisch, Gerd; Koelsch, Uwe; Rüdiger, Mario

2013-01-01

As an alternative to surfactant therapy (ST), partial liquid ventilation (PLV) with perfluorocarbons (PFC) has been considered as a treatment for acute lung injury (ALI) in newborns. The instilled PFC is much heavier than the instilled surfactant and the aim of this study was to investigate whether PLV, compared to ST, increases the end-expiratory volume of the lung (V L ). Fifteen newborn piglets (age <12 h, mean weight 678 g) underwent saline lung lavage to achieve a surfactant depletion. Thereafter animals were randomized to PLV (n = 8), receiving PFC PF5080 (3M, Germany) at 30 mL kg −1 , and ST (n = 7) receiving 120 mg Curosurf®. Blood gases, hemodynamics and static compliance were measured initially (baseline), immediately after ALI, and after 240 min mechanical ventilation with either technique. Subsequently all piglets were killed; the lungs were removed in toto and frozen in liquid N 2 . After freeze-drying the lungs were cut into lung cubes (LCs) with edge lengths of 0.7 cm, to calculate V L . All LCs were weighed and the density of the dried lung tissue was calculated. No statistically significant differences between treatment groups PLV and ST (means ± SD) were noted in body weight (676 ± 16 g versus 679 ± 17 g; P = 0.974) or lung dry weight (1.64 ± 0.29 g versus 1.79 ± 0.48 g; P = 0.48). Oxygenation index and ventilatory efficacy index did not differ significantly between both groups at any time. V L (34.28 ± 6.13 mL versus 26.22 ± 8.1 mL; P < 0.05) and the density of the dried lung tissue (48.07 ± 5.02 mg mL −1 versus 69.07 ± 5.30 mg mL −1 ; P < 0.001), however, differed significantly between the PLV and ST groups. A 4 h PLV treatment of injured ventilated small lungs increased V L by 30% and decreased lung density by 31% compared to ST treatment, indicating greater lung distension after PLV compared to ST. (paper)

Avaliação e recondicionamento pulmonar ex vivo Ex vivo lung evaluation and reconditioning

Directory of Open Access Journals (Sweden)

Paulo Manuel Pêgo-Fernandes

2010-12-01

lungs are perfused ex vivo with Steen Solution, an extra-cellular solution with high colloid osmotic pressure. A membrane oxygenator connected to the circuit receives gas from a mixture of nitrogen and carbon dioxide and maintains a normal mixed venous blood gas level in the perfusate. The lungs are gradually rewarmed, reperfused and ventilated. They are evaluated through analyses of oxygenation capacity, pulmonary vascular resistance (PVR, lung compliance (LC. RESULTS: The arterial oxygen pressure (with inspired oxygen fractions of 100% increased from a mean of 193.3 mmHg in the organ donor at the referring hospital to a mean of 495.3 mmHg during the ex vivo evaluation. After 1 hour of EVLP, mean PVR was 737.3 dynes/sec/cm5, and mean LC was 42.2 ml/cmH2O. CONCLUSIONS: The ex vivo evaluation model can improve oxygenation capacity of "marginal" lungs rejected for transplantation. It has a great potential to increase lung donor availability and, possibly, to reduce the waiting time on the list.

Pulmonary hypertension due to unclassified interstitial lung disease in a Pembroke Welsh corgi.

Science.gov (United States)

Morita, Tomoya; Nakamura, Kensuke; Tatsuyuki, Osuga; Kobayashi, Atsushi; Ichii, Osamu; Yabuki, Akira; Takiguchi, Mitsuyoshi

2018-04-23

A 12 year-old intact male Pembroke Welsh corgi weighing 10.8 kg was presented for evaluation of a 3-month history of dyspnea, and a 1-week history of exercise intolerance and anorexia. Severe hypoxemia (PaO 2 56 mmHg), diffuse lung alveolar infiltration, and severe pulmonary hypertension (tricuspid regurgitation pressure gradient was 81 mmHg) were identified. A tentative diagnosis of severe PH due to lung disease or pulmonary thromboembolism was made and treated intensively. After 5 days of hospitalization, the dog died despite oxygen supplementation and anticoagulant therapy. This dog was diagnosed as unclassified interstitial lung disease based on histopathological findings.

Influence of long-term drinking alcohol on the cytokines in the rats with endogenous and exogenous lung injury.

Science.gov (United States)

Liu, Y D; Liu, W; Liu, Z

2013-02-01

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are syndromes of acute respiratory failure. Exploration of the impacts of long-term drinking alcohol on the cytokines of rats with endogenous and exogenous lung injuries. Through giving the model rats long-term drinking alcohol or water, we acquired the changes of the cytokines in the serum and bronchoalveolar lavage fluid (BALF) of these rats with lung injuries due to different incentives. The partial pressure of oxygen in rats with lung damage after long-term drinking alcohol were significantly lower than those drinking water group (p exogenous lung injury were higher than those of rats with endogenous lung injury (p endogenous lung injury were higher than those with exogenous lung injury (p exogenous lung injury. The expression of TNF-α, IL-6 and IL-10 are different according to the different ways that lead to the acute lung injury.

Mechanical ventilation drives pneumococcal pneumonia into lung injury and sepsis in mice: protection by adrenomedullin.

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Müller-Redetzky, Holger C; Will, Daniel; Hellwig, Katharina; Kummer, Wolfgang; Tschernig, Thomas; Pfeil, Uwe; Paddenberg, Renate; Menger, Michael D; Kershaw, Olivia; Gruber, Achim D; Weissmann, Norbert; Hippenstiel, Stefan; Suttorp, Norbert; Witzenrath, Martin

2014-04-14

Ventilator-induced lung injury (VILI) contributes to morbidity and mortality in acute respiratory distress syndrome (ARDS). Particularly pre-injured lungs are susceptible to VILI despite protective ventilation. In a previous study, the endogenous peptide adrenomedullin (AM) protected murine lungs from VILI. We hypothesized that mechanical ventilation (MV) contributes to lung injury and sepsis in pneumonia, and that AM may reduce lung injury and multiple organ failure in ventilated mice with pneumococcal pneumonia. We analyzed in mice the impact of MV in established pneumonia on lung injury, inflammation, bacterial burden, hemodynamics and extrapulmonary organ injury, and assessed the therapeutic potential of AM by starting treatment at intubation. In pneumococcal pneumonia, MV increased lung permeability, and worsened lung mechanics and oxygenation failure. MV dramatically increased lung and blood cytokines but not lung leukocyte counts in pneumonia. MV induced systemic leukocytopenia and liver, gut and kidney injury in mice with pneumonia. Lung and blood bacterial burden was not affected by MV pneumonia and MV increased lung AM expression, whereas receptor activity modifying protein (RAMP) 1-3 expression was increased in pneumonia and reduced by MV. Infusion of AM protected against MV-induced lung injury (66% reduction of pulmonary permeability p protect against development of lung injury, sepsis and extrapulmonary organ injury in mechanically ventilated individuals with severe pneumonia.

Flow-controlled expiration: a novel ventilation mode to attenuate experimental porcine lung injury.

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Goebel, U; Haberstroh, J; Foerster, K; Dassow, C; Priebe, H-J; Guttmann, J; Schumann, S

2014-09-01

Whereas the effects of various inspiratory ventilatory modifications in lung injury have extensively been studied, those of expiratory ventilatory modifications are less well known. We hypothesized that the newly developed flow-controlled expiration (FLEX) mode provides a means of attenuating experimental lung injury. Experimental acute respiratory distress syndrome was induced by i.v. injection of oleic acid in 15 anaesthetized and mechanically ventilated pigs. After established lung injury ([Formula: see text]ratio ventilation (VCV) or a treatment group receiving VCV with additional FLEX (VCV+FLEX). At predefined times, lung mechanics and oxygenation were assessed. At the end of the experiment, the pigs were killed, and bronchoalveolar fluid and lung biopsies were taken. Expression of inflammatory cytokines was analysed in lung tissue and bronchoalveolar fluid. Lung injury score was determined on the basis of stained tissue samples. Compared with the control group (VCV; n=8), the VCV+FLEX group (n=7) demonstrated greater dynamic lung compliance and required less PEEP at comparable [Formula: see text] (both Pprotective ventilation. © The Author [2014]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Pharmacologic Interventions to Improve Splanchnic Oxygenation During Ventilation with Positive End-Expiratory Pressure

NARCIS (Netherlands)

Fournell, A.; Scheeren, T. W. L.; Picker, O.; Schwarte, L. A.; Wolf, M; Bucher, HU; Rudin, M; VanHuffel, S; Wolf, U; Bruley, DF; Harrison, DK

2012-01-01

Mechanical ventilation with positive end-expiratory pressure (PEEP) is an indispensable tool in the management of respiratory failure to preserve or improve lung function and systemic oxygenation. However, PEEP per se may also, as has been shown in experimental animals, impair regional

Human umbilical cord-derived mesenchymal stem cells protect from hyperoxic lung injury by ameliorating aberrant elastin remodeling in the lung of O2-exposed newborn rat.

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Hou, Chen; Peng, Danyi; Gao, Li; Tian, Daiyin; Dai, Jihong; Luo, Zhengxiu; Liu, Enmei; Chen, Hong; Zou, Lin; Fu, Zhou

2018-01-08

The incidence and mortality rates of bronchopulmonary dysplasia (BPD) remain very high. Therefore, novel therapies are imminently needed to improve the outcome of this disease. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) show promising therapeutic effects on oxygen-induced model of BPD. In our experiment, UC-MSCs were intratracheally delivered into the newborn rats exposed to hyperoxia, a well-established BPD model. This study demonstrated that UC-MSCs reduce elastin expression stimulated by 90% O 2 in human lung fibroblasts-a (HLF-a), and inhibit HLF-a transdifferentiation into myofibroblasts. In addition, the therapeutic effects of UC-MSCs in neonatal rats with BPD, UC-MSCs could inhibit lung elastase activity and reduce aberrant elastin expression and deposition in the lung of BPD rats. Overall, this study suggested that UC-MSCs could ameliorate aberrant elastin expression in the lung of hyperoxia-induced BPD model which may be associated with suppressing increased TGFβ1 activation. Copyright © 2017. Published by Elsevier Inc.

Evaluation of Lung Function in Liver Transplant Candidates.

Science.gov (United States)

Roque, L; Sankarankutty, A K; Silva, O C; Mente, E D

2018-04-01

A wide variety of pulmonary conditions are found in cirrhotic patients and may compromise the pleura, diaphragm, parenchyma, and pulmonary vasculature, influencing the results of liver transplantation. To evaluate the pulmonary function (lung capacities, volumes, and gasometric study) of patients with liver cirrhosis awaiting liver transplantation. Cirrhotic patients, subdivided into 3 groups stratified by liver disease severity using the Child-Pugh-Turcotte score, were compared with a control group of healthy volunteers. In spirometry, the parameters evaluated were total lung capacity, forced volume in the first second, and the relationship between forced volume in the first minute and forced vital capacity. Blood gas analysis was performed. In the control group, arterial oxygenation was evaluated by peripheral oxygen saturation by pulse oximetry. Of the 55 patients (75% men, 51 ± 12.77 years), 11 were Child A (73% men, 52 ± 14.01 years), 23 were Child B (75% men, 51 ± 12.77 years), and 21 were Child C (95% men, 50 ± 12.09 years). The control group had 20 individuals (50% men, 47 ± 8.15 years). Pulmonary capacities and volumes by the parameters evaluated were within the normal range. Arterial blood gas analysis detected no hypoxemia, but a tendency to low partial gas pressure was noted. In this population of cirrhotic patients the parameters of spirometry were normal in relation to the lung capacities and volumes in the different groups. No hypoxemia was detected, but a tendency to hypocapnia in the blood gas was noted. Copyright © 2018. Published by Elsevier Inc.

Disruption of the Hepcidin/Ferroportin Regulatory System Causes Pulmonary Iron Overload and Restrictive Lung Disease

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Joana Neves

2017-06-01

Full Text Available Emerging evidence suggests that pulmonary iron accumulation is implicated in a spectrum of chronic lung diseases. However, the mechanism(s involved in pulmonary iron deposition and its role in the in vivo pathogenesis of lung diseases remains unknown. Here we show that a point mutation in the murine ferroportin gene, which causes hereditary hemochromatosis type 4 (Slc40a1C326S, increases iron levels in alveolar macrophages, epithelial cells lining the conducting airways and lung parenchyma, and in vascular smooth muscle cells. Pulmonary iron overload is associated with oxidative stress, restrictive lung disease with decreased total lung capacity and reduced blood oxygen saturation in homozygous Slc40a1C326S/C326S mice compared to wild-type controls. These findings implicate iron in lung pathology, which is so far not considered a classical iron-related disorder.

Hyperbaric oxygen sensitizes anoxic Pseudomonas aeruginosa biofilm to ciprofloxacin

DEFF Research Database (Denmark)

Kolpen, Mette; Lerche, Christian J; Kragh, Kasper Nørskov

2017-01-01

fibrosis (CF) lung. Application of HBOT resulted in enhanced bactericidal activity of ciprofloxacin at clinically relevant durations and was accompanied by indications of restored aerobic respiration, involvement of endogenous lethal oxidative stress and increased bacterial growth. The findings highlight...... that oxygenation by HBOT improves the bactericidal activity of ciprofloxacin on P. aeruginosa biofilm and suggest that bacterial biofilms is sensitized to antibiotics by supplying hyperbaric O2....

Intersections of lung progenitor cells, lung disease and lung cancer.

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Kim, Carla F

2017-06-30

The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials. Copyright ©ERS 2017.

Intersections of lung progenitor cells, lung disease and lung cancer

Directory of Open Access Journals (Sweden)

Carla F. Kim

2017-06-01

Full Text Available The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials.

Histogram based analysis of lung perfusion of children after congenital diaphragmatic hernia repair.

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Kassner, Nora; Weis, Meike; Zahn, Katrin; Schaible, Thomas; Schoenberg, Stefan O; Schad, Lothar R; Zöllner, Frank G

2018-05-01

To investigate a histogram based approach to characterize the distribution of perfusion in the whole left and right lung by descriptive statistics and to show how histograms could be used to visually explore perfusion defects in two year old children after Congenital Diaphragmatic Hernia (CDH) repair. 28 children (age of 24.2±1.7months; all left sided hernia; 9 after extracorporeal membrane oxygenation therapy) underwent quantitative DCE-MRI of the lung. Segmentations of left and right lung were manually drawn to mask the calculated pulmonary blood flow maps and then to derive histograms for each lung side. Individual and group wise analysis of histograms of left and right lung was performed. Ipsilateral and contralateral lung show significant difference in shape and descriptive statistics derived from the histogram (Wilcoxon signed-rank test, phistogram derived parameters. Histogram analysis can be a valuable tool to characterize and visualize whole lung perfusion of children after CDH repair. It allows for several possibilities to analyze the data, either describing the perfusion differences between the right and left lung but also to explore and visualize localized perfusion patterns in the 3D lung volume. Subgroup analysis will be possible given sufficient sample sizes. Copyright © 2017 Elsevier Inc. All rights reserved.

Postnatal follow-up of the oxygenation index, arterial to alveolar oxygen tension ratio and alveolar arterial oxygen tension difference values in neonates with the respiratory distress syndrome treated with conventional ventilatory support.

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Atanasov, A; Despotova-Toleva, L

1997-01-01

Recent development of sophisticated intensive care technique for use in newborn infants with the respiratory distress syndrome (RDS) has resulted in changes in the therapeutic strategies and moved the problem of neonatal survival into the realm of new therapeutic realities. At present, the mechanical ventilation methods form an integral part of the intensive care strategy of infants with RDS. They have come to the forefront of infant care because of their successful use in ventilatory support and children survival where other therapeutic modalities have failed. The present prospective observational longitudinal study was designed to assess the real-time convenience, reliability and accuracy of the changes in the oxygenation index (OI), arterial-to-alveolar oxygen tension ratio (a/A PO2) and alveolar-arterial oxygen gradient (A-a)DO2 in ventilator-dependent neonates with RDS, to analyze their feasibility and potential information yield in oxygen inhalation therapy as well as their prognostic implications and predictive value. Twenty neonates with RDS, heralded by respiratory failure which necessitated the initiation of oxygen inhalation therapy and ventilatory support within 24 hours of birth, were enrolled in the study. Ten of the infants survived and the remaining ten died. OI, (a/A PO2) and (A-a)DO2 were followed up sequentially and thoroughly analyzed as the primary outcome measures of the study. The indices were calculated on the basis of the complete monitoring of the ventilatory equipment parameters and acid-base status carried out on an hourly basis. Our results show that: 1. The combination of three indexes (OI, (a/A)PO2 and (A-a)DO2 we propose is a useful discriminating predictor of neonatal lung maturity reflecting arterial blood gas status in ventilator-dependent neonates with RDS. 2. The indices detect the efficacy of the modern conventional ventilatory support with real-time convenience and reliable accuracy forming the cornerstone of clinical decision

Spontaneous breathing during lung-protective ventilation in an experimental acute lung injury model: high transpulmonary pressure associated with strong spontaneous breathing effort may worsen lung injury.

Science.gov (United States)

Yoshida, Takeshi; Uchiyama, Akinori; Matsuura, Nariaki; Mashimo, Takashi; Fujino, Yuji

2012-05-01

We investigated whether potentially injurious transpulmonary pressure could be generated by strong spontaneous breathing and exacerbate lung injury even when plateau pressure is limited to ventilation, each combined with weak or strong spontaneous breathing effort. Inspiratory pressure for low tidal volume ventilation was set at 10 cm H2O and tidal volume at 6 mL/kg. For moderate tidal volume ventilation, the values were 20 cm H2O and 7-9 mL/kg. The groups were: low tidal volume ventilation+spontaneous breathingweak, low tidal volume ventilation+spontaneous breathingstrong, moderate tidal volume ventilation+spontaneous breathingweak, and moderate tidal volume ventilation+spontaneous breathingstrong. Each group had the same settings for positive end-expiratory pressure of 8 cm H2O. Respiratory variables were measured every 60 mins. Distribution of lung aeration and alveolar collapse were histologically evaluated. Low tidal volume ventilation+spontaneous breathingstrong showed the most favorable oxygenation and compliance of respiratory system, and the best lung aeration. By contrast, in moderate tidal volume ventilation+spontaneous breathingstrong, the greatest atelectasis with numerous neutrophils was observed. While we applied settings to maintain plateau pressure at ventilation+spontaneous breathingstrong, transpulmonary pressure rose >33 cm H2O. Both minute ventilation and respiratory rate were higher in the strong spontaneous breathing groups. Even when plateau pressure is limited to mechanical ventilation, transpulmonary pressure and tidal volume should be strictly controlled to prevent further lung injury.

Predictive role of arterial carboxyhemoglobin concentrations in ovine burn and smoke inhalation-induced lung injury.

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Lange, Matthias; Cox, Robert A; Enkhbaatar, Perenlei; Whorton, Elbert B; Nakano, Yoshimitsu; Hamahata, Atsumori; Jonkam, Collette; Esechie, Aimalohi; von Borzyskowski, Sanna; Traber, Lillian D; Traber, Daniel L

2011-05-01

Inhalation injury frequently occurs in burn patients and contributes to the morbidity and mortality of these injuries. Arterial carboxyhemoglobin has been proposed as an indicator of the severity of inhalation injury; however, the interrelation between arterial carboxyhemoglobin and histological alterations has not yet been investigated. Chronically instrumented sheep were subjected to a third degree burn of 40% of the total body surface area and inhalation of 48 breaths of cotton smoke. Carboxyhemoglobin was measured immediately after injury and correlated to clinical parameters of pulmonary function as well as histopathology scores from lung tissue harvested 24 hours after the injury. The injury was associated with a significant decline in pulmonary oxygenation and increases in pulmonary shunting, lung lymph flow, wet/dry weight ratio, congestion score, edema score, inflammation score, and airway obstruction scores. Carboxyhemoglobin was negatively correlated to pulmonary oxygenation and positively correlated to pulmonary shunting, lung lymph flow, and lung wet/dry weight ratio. No significant correlations could be detected between carboxyhemoglobin and histopathology scores and airway obstruction scores. Arterial carboxyhemoglobin in sheep with combined burn and inhalation injury are correlated with the degree of pulmonary failure and edema formation, but not with certain histological alterations including airway obstruction scores.

Determinants of oxygen and carbon dioxide transfer during extracorporeal membrane oxygenation in an experimental model of multiple organ dysfunction syndrome.

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Park, Marcelo; Costa, Eduardo Leite Vieira; Maciel, Alexandre Toledo; Silva, Débora Prudêncio E; Friedrich, Natalia; Barbosa, Edzangela Vasconcelos Santos; Hirota, Adriana Sayuri; Schettino, Guilherme; Azevedo, Luciano Cesar Pontes

2013-01-01

Extracorporeal membrane oxygenation (ECMO) has gained renewed interest in the treatment of respiratory failure since the advent of the modern polymethylpentene membranes. Limited information exists, however, on the performance of these membranes in terms of gas transfers during multiple organ failure (MOF). We investigated determinants of oxygen and carbon dioxide transfer as well as biochemical alterations after the circulation of blood through the circuit in a pig model under ECMO support before and after induction of MOF. A predefined sequence of blood and sweep flows was tested before and after the induction of MOF with fecal peritonitis and saline lavage lung injury. In the multivariate analysis, oxygen transfer had a positive association with blood flow (slope = 66, Pmembrane PaCO(2) (slope = -0.96, P = 0.001) and SatO(2) (slope = -1.7, Ptransfer had a positive association with blood flow (slope = 17, Pmembrane PaCO(2) (slope = 1.2, Ptransfers were significantly determined by blood flow. Oxygen transfer was modulated by the pre-membrane SatO(2) and CO(2), while carbon dioxide transfer was affected by the gas flow, pre-membrane CO(2) and hemoglobin.

Polysomnography for the management of oxygen supplementation therapy in infants with chronic lung disease of prematurity.

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Kulkarni, Gaurav; de Waal, Koert; Grahame, Sally; Collison, Adam; Roddick, Laurence; Hilton, Jodi; Gulliver, Tanya; Whitehead, Bruce; Mattes, Joerg

2018-04-25

Some infants with bronchopulmonary dysplasia (BPD) may require oxygen supplementation at home but a role for overnight polysomnography (PSG) in the management of home oxygen therapy has been rarely described. Forty-one infants with BPD born at less than 30 weeks gestational age were discharged with continuous home oxygen supplementation therapy between 2010 and 2013. PSG data were recorded on oxygen supplementation versus room air at median post conceptual age of 2 months (range 1-5.5 months) (first PSG after discharge to home). Those infants who continued oxygen supplementation therapy at home had at least one more PSG before oxygen therapy was discontinued (last PSG). We also collected PSG data in 10 healthy term infants (median age 3.5 months; range 2-4 months). In infants with BPD in room air, increased numbers of central apnoeas, hypopnoeas and SaO 2 desaturations were the predominant PSG features with a median apnoea-hypopnoea index (AHI) of 16.8 events per hour (range 0-155). On oxygen supplementation therapy, median AHI dramatically improved (2.2, range 0-22; p < 0.001) and was not different from control infants (2.0, range 0-3.9; p = 0.31). AHI on room air at the last PSG when home oxygen was ceased was 4.1 per hour (range 0-13.8) slightly higher than in healthy infants. Central sleep disordered breathing in infants with BPD dramatically normalises with low flow nasal cannula home oxygen therapy and improves with age. Mild central sleep disordered breathing remains detectable, although much improved, when compared to healthy infants at the time when the decision to cease home oxygen therapy was made by the physician.

The matching of ventilation and perfusion in the lung of the Tegu lizard, Tupinambis nigropunctatus.

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Hlastala, M P; Standaert, T A; Pierson, D J; Luchtel, D L

1985-06-01

Ventilation-perfusion (VA/Q) distribution was evaluated in the Tegu lizard, Tupinambis nigropunctatus, using the multiple inert gas elimination technique (MIGET) in order to define the limitations to gas exchange in the large chambered unicameral lung. The lizards (0.52-1.1 kg) were anesthetized with halothane and ventilated. Body temperature was maintained at 35 degrees C. Arterial and sinus venosus PO2 averaged 79.4 +/- 5.9 and 47.3 +/- 6.4 torr while breathing air and 232.1 +/- 31 and 64.8 +/- 11.5 torr while breathing oxygen. VA/Q distributions were broad and right-to-left shunt averaged 21% while breathing air and 27% while breathing oxygen. Gas exchange was significantly impaired due to the presence of both shunt and VA/Q heterogeneity. The walls of the lung enclose a large axial air chamber. Microscopic examination revealed approximately three generations of septa which subdivided the wall into tubular-shaped gas-exchange chambers. Wall thickness averages 2.8 mm at the anterior end of the lung, 2.1 mm in the middle portion of the lung and 1.4 mm at the posterior end. The thickness of the blood-air barrier (epithelial-basal lamina-endothelial cell layer) ranged from 0.35 to 0.90 micron. Although this barrier is slightly thicker than in the mammalian lung (0.1-0.5 micron), it is unlikely to be a source of diffusion limitation in gas exchange at rest.

Enhancement of the Acrolein-Induced Production of Reactive Oxygen Species and Lung Injury by GADD34

OpenAIRE

Sun, Yang; Ito, Sachiko; Nishio, Naomi; Tanaka, Yuriko; Chen, Nana; Liu, Lintao; Isobe, Ken-ichi

2015-01-01

Chronic obstructive pulmonary disease (COPD) is characterized by lung destruction and inflammation. As a major compound of cigarette smoke, acrolein plays a critical role in the induction of respiratory diseases. GADD34 is known as a growth arrest and DNA damage-related gene, which can be overexpressed in adverse environmental conditions. Here we investigated the effects of GADD34 on acrolein-induced lung injury. The intranasal exposure of acrolein induced the expression of GADD34, developing...

Heart and Lungs Protection Technique for Cardiac Surgery with Cardiopulmonary Bypass

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Vladimir Pichugin

2014-12-01

Full Text Available Introduction: Cardioplegic cardiac arrest with subsequent ischemic-reperfusion injuries can lead to the development of inflammation of the myocardium, leucocyte activation, and release of cardiac enzymes. Flow reduction to the bronchial arteries, causing low-flow lung ischemia, leads to the development of a pulmonary regional inflammatory response. Hypoventilation during cardiopulmonary bypass (CPB is responsible for development of microatelectasis, hydrostatic pulmonary edema, poor compliance, and a higher incidence of infection. Based on these facts, prevention methods of these complications were developed. The aim of this study was to evaluate constant coronary perfusion (CCP and the “beating heart” in combination with pulmonary artery perfusion (PAP and “ventilated lungs” technique for heart and lung protection in cardiac surgery with CPB.Methods. After ethical approval and written informed consent, 80 patients undergoing cardiac surgery with normothermic CPB were randomized in three groups. In the first group (22 patients, the crystalloid cardioplegia without lung ventilation/perfusion techniques were used. In the second group (30 patients, the CCP and “beating heart” without lung ventilation/perfusion techniques were used. In the third group (28 patients, the CCP with PAP and lung ventilation techniques were used. Clinical, functional parameters, myocardial damage markers (CK MB level, oxygenation index, and lung compliance were investigated.Results. There were higher rates of spontaneous cardiac recovery and lower doses of inotrops in the second and third groups. Myocardial contractility function was better preserved in the second and third groups. The post-operative levels of CK-MB were lower than in control group.  Three hours after surgery CK-MB levels in the second and third  groups were lower by 38.1% and 33.3%, respectively. Eight hours after surgery, CK-MB levels were lower in the second and third groups by 45.9% and

Evaluation of oxygenation status during fractionated radiotherapy in human nonsmall cell lung cancers using [F-18]fluoromisonidazole positron emission tomography

International Nuclear Information System (INIS)

Wui-Jin, Koh; Bergman, Kenneth S.; Rasey, Janet S.; Peterson, Lanell M.; Evans, Margaret L.; Graham, Michael M.; Grierson, John R.; Lindsley, Karen L.; Lewellen, Thomas K.; Krohn, Kenneth A.; Griffin, Thomas W.

1995-01-01

Purpose: Recent clinical investigations have shown a strong correlation between pretreatment tumor hypoxia and poor response to radiotherapy. These observations raise questions about standard assumptions of tumor reoxygenation during radiotherapy, which has been poorly studied in human cancers. Positron emission tomography (PET) imaging of [F-18]fluoromisonidazole (FMISO) uptake allows noninvasive assessment of tumor hypoxia, and is amenable for repeated studies during fractionated radiotherapy to systematically evaluate changes in tumor oxygenation. Methods and Materials: Seven patients with locally advanced nonsmall cell lung cancers underwent sequential [F-18]FMISO PET imaging while receiving primary radiotherapy. Computed tomograms were used to calculate tumor volumes, define tumor extent for PET image analysis, and assist in PET image registration between serial studies. Fractional hypoxic volume (FHV) was calculated for each study as the percentage of pixels within the analyzed imaged tumor volume with a tumor:blood [F-18]FMISO ratio ≥ 1.4 by 120 min after injection. Serial FHVs were compared for each patient. Results: Pretreatment FHVs ranged from 20-84% (median 58%). Subsequent FHVs varied from 8-79% (median 29%) at midtreatment, and ranged from 3-65% (median 22%) by the end of radiotherapy. One patient had essentially no detectable residual tumor hypoxia by the end of radiation, while two others showed no apparent decrease in serial FHVs. There was no correlation between tumor size and pretreatment FHV. Conclusions: Although there is a general tendency toward improved oxygenation in human tumors during fractionated radiotherapy, these changes are unpredictable and may be insufficient in extent and timing to overcome the negative effects of existing pretreatment hypoxia. Selection of patients for clinical trials addressing radioresistant hypoxic cancers can be appropriately achieved through single pretreatment evaluations of tumor hypoxia

PEGylated anticancer-carbon nanotubes complex targeting mitochondria of lung cancer cells

Science.gov (United States)

Kim, Sang-Woo; Lee, Yeon Kyung; Lee, Jong Yeon; Hong, Jeong Hee; Khang, Dongwoo

2017-11-01

Although activating apoptosis in cancer cells by targeting the mitochondria is an effective strategy for cancer therapy, insufficient targeting of the mitochondria in cancer cells restricts the availability in clinical treatment. Here, we report on a polyethylene glycol-coated carbon nanotube (CNT)-ABT737 nanodrug that improves the mitochondrial targeting of lung cancer cells. The polyethylene glycol-coated CNT-ABT737 nanodrug internalized into the early endosomes via macropinocytosis and clathrin-mediated endocytosis in advance of early endosomal escape and delivered into the mitochondria. Cytosol release of the nanodrug led to apoptosis of lung cancer cells by abruption of the mitochondrial membrane potential, inducing Bcl-2-mediated apoptosis and generating intracellular reactive oxygen species. As such, this study provides an effective strategy for increasing the anti-lung cancer efficacy by increasing mitochondria accumulation rate of cytosol released anticancer nanodrugs.

A bench evaluation of fraction of oxygen in air delivery and tidal volume accuracy in home care ventilators available for hospital use

Science.gov (United States)

Baboi, Loredana; Subtil, Fabien

2016-01-01

Background Turbine-powered ventilators are not only designed for long-term ventilation at home but also for hospital use. It is important to verify their capabilities in delivering fraction of oxygen in air (FIO2) and tidal volume (VT). Methods We assessed the FIO2 accuracy and the VT delivery in four home care ventilators (HCV) on the bench. The four HCV were Astral 150, Elisée 150, Monnal T50 and Trilogy 200 HCV, which were connected to a lung model (ASL 5000). For assessing FIO2 accuracy, lung model was set to mimic an obstructive lung and HCV were set in volume controlled mode (VC). They supplied with air, 3 or 15 L/min oxygen and FIO2 was measured by using a ventilator tester (Citrex H4TM). For the VT accuracy, the lung model was set in a way to mimic three adult configurations (normal, obstructive, or restrictive respiratory disorder) and one pediatric configuration. Each HCV was set in VC. Two VT (300 and 500 mL) in adult lung configuration and one 50 mL VT in pediatric lung configuration, at two positive end expiratory pressures 5 and 10 cmH2O, were tested. VT accuracy was measured as volume error (the relative difference between set and measured VT). Statistical analysis was performed by suing one-factor ANOVA with a Bonferroni correction for multiple tests. Results For Astral 150, Elisée 150, Monnal T50 and Trilogy 200, FIO2 averaged 99.2%, 93.7%, 86.3%, and 62.1%, respectively, at 15 L/min oxygen supplementation rate (P<0.001). Volume error was 0.5%±0%, −38%±0%, −9%±0%, −29%±0% and −36%±0% for pediatric lung condition (P<0.001). In adult lung configurations, Monnal T50 systematically over delivered VT and Trilogy 150 was sensitive to lung configuration when VT was set to 300 mL at either positive end-expiratory pressure (PEEP). Conclusions HCV are different in terms of FIO2 efficiency and VT delivery. PMID:28149559

Very low tidal volume ventilation with associated hypercapnia--effects on lung injury in a model for acute respiratory distress syndrome.

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Hans Fuchs

Full Text Available BACKGROUND: Ventilation using low tidal volumes with permission of hypercapnia is recommended to protect the lung in acute respiratory distress syndrome. However, the most lung protective tidal volume in association with hypercapnia is unknown. The aim of this study was to assess the effects of different tidal volumes with associated hypercapnia on lung injury and gas exchange in a model for acute respiratory distress syndrome. METHODOLOGY/PRINCIPAL FINDINGS: In this randomized controlled experiment sixty-four surfactant-depleted rabbits were exposed to 6 hours of mechanical ventilation with the following targets: Group 1: tidal volume = 8-10 ml/kg/PaCO(2 = 40 mm Hg; Group 2: tidal volume = 4-5 ml/kg/PaCO(2 = 80 mm Hg; Group 3: tidal volume = 3-4 ml/kg/PaCO(2 = 120 mm Hg; Group 4: tidal volume = 2-3 ml/kg/PaCO(2 = 160 mm Hg. Decreased wet-dry weight ratios of the lungs, lower histological lung injury scores and higher PaO(2 were found in all low tidal volume/hypercapnia groups (group 2, 3, 4 as compared to the group with conventional tidal volume/normocapnia (group 1. The reduction of the tidal volume below 4-5 ml/kg did not enhance lung protection. However, oxygenation and lung protection were maintained at extremely low tidal volumes in association with very severe hypercapnia and no adverse hemodynamic effects were observed with this strategy. CONCLUSION: Ventilation with low tidal volumes and associated hypercapnia was lung protective. A tidal volume below 4-5 ml/kg/PaCO(2 80 mm Hg with concomitant more severe hypercapnic acidosis did not increase lung protection in this surfactant deficiency model. However, even at extremely low tidal volumes in association with severe hypercapnia lung protection and oxygenation were maintained.

Reinforcement of the bactericidal effect of ciprofloxacin on Pseudomonas aeruginosa biofilm by hyperbaric oxygen treatment

DEFF Research Database (Denmark)

Kolpen, Mette; Mousavi, Nabi; Sams, Thomas

2016-01-01

Chronic Pseudomonas aeruginosa lung infection is the most severe complication in cystic fibrosis patients. It is characterised by antibiotic-tolerant biofilms in the endobronchial mucus with zones of oxygen (O2) depletion mainly due to polymorphonuclear leucocyte activity. Whilst the exact mechan...

Lung collapse among aquatic reptiles and amphibians during long-term diving.

Science.gov (United States)

Ultsch, Gordon R; Brainerd, Elizabeth L; Jackson, Donald C

2004-09-01

Numerous aquatic reptiles and amphibians that typically breathe both air and water can remain fully aerobic in normoxic (aerated) water by taking up oxygen from the water via extrapulmonary avenues. Nevertheless, if air access is available, these animals do breathe air, however infrequently. We suggest that such air breathing does not serve an immediate gas exchange function under these conditions, nor is it necessarily related to buoyancy requirements, but serves to keep lungs inflated that would otherwise collapse during prolonged submergence. We also suggest that lung deflation is routine in hibernating aquatic reptiles and amphibians in the northern portions of their ranges, where ice cover prevents surfacing for extended periods.

Single-dose relative biological effectiveness and toxicity studies under conditions of hypothermia and hyperbaric oxygen

International Nuclear Information System (INIS)

Hering, E.R.; Blekkenhorst, G.; Harrison, G.G.; Morrell, D.; Korrubel, J.; Gregory, A.; Phillips, J.; Manca, V.; Sealy, R.; Cape Town Univ.

1986-01-01

An approach to using hyperbaric oxygen with radiation in a clinical situation has been described in the preceding paper in this issue. To ascertain whether there might be a change in the relative biological effectiveness of radiation on normal mammalian tissue treated under conditions of hypothermia and hyperbaric oxygen, the acute reaction to radiation of pig skin was studied. A single dose enhancement ratio at the erythema reaction level of 1.4+-0.08 was obtained when compared with irradiation at normal body temperature in air. The authors studied also a series of antioxidant enzymes in rat liver and lung after exposure to hypothermia and hyperbaric oxygen. Enzyme changes were such as to combat oxygen toxicity which might develop as a result of the pre-treatment. (author)

Transcriptome Analysis of the Preterm Rabbit Lung after Seven Days of Hyperoxic Exposure.

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Thomas Salaets

Full Text Available The neonatal management of preterm born infants often results in damage to the developing lung and subsequent morbidity, referred to as bronchopulmonary dysplasia (BPD. Animal models may help in understanding the molecular processes involved in this condition and define therapeutic targets. Our goal was to identify molecular pathways using the earlier described preterm rabbit model of hyperoxia induced lung-injury. Transcriptome analysis by mRNA-sequencing was performed on lungs from preterm rabbit pups born at day 28 of gestation (term: 31 days and kept in hyperoxia (95% O2 for 7 days. Controls were preterm pups kept in normoxia. Transcriptomic data were analyzed using Array Studio and Ingenuity Pathway Analysis (IPA, in order to identify the central molecules responsible for the observed transcriptional changes. We detected 2217 significantly dysregulated transcripts following hyperoxia, of which 90% could be identified. Major pathophysiological dysregulations were found in inflammation, lung development, vascular development and reactive oxygen species (ROS metabolism. To conclude, amongst the many dysregulated transcripts, major changes were found in the inflammatory, oxidative stress and lung developmental pathways. This information may be used for the generation of new treatment hypotheses for hyperoxia-induced lung injury and BPD.

Mangosenone F, A Furanoxanthone from Garciana mangostana, Induces Reactive Oxygen Species-Mediated Apoptosis in Lung Cancer Cells and Decreases Xenograft Tumor Growth.

Science.gov (United States)

Seo, Kyung Hye; Ryu, Hyung Won; Park, Mi Jin; Park, Ki Hun; Kim, Jin Hyo; Lee, Mi-Ja; Kang, Hyeon Jung; Kim, Sun Lim; Lee, Jin Hwan; Seo, Woo Duck

2015-11-01

Mangosenone F (MSF), a natural xanthone, was isolated form Carcinia mangotana, and a few studies have reported its glycosidase inhibitor effect. In this study we investigated the anti lung cancer effect of MSF both in vitro and in vivo. MSF inhibited cancer cell cytotoxicity and induced and induced apoptosis via reactive oxygen species (ROS) generation in NCI-H460. MSF treatment also showed in pronounced release of apoptogenic cytochrome c from the mitochondria to the cytosol, downregulation of Bcl-2 and Bcl-xL, and upregulation of Bax, suggesting that caspase-mediated pathways were involved in MSF-induced apoptosis. ROS activation of the mitogen-activated protein kinase signaling pathway was shown to play a predominant role in the apoptosis mechanism of MSF. Compared with cisplatin treatment, MSF treatment showed significantly increased inhibition of the growth of NCI-H460 cells xenografted in nude mice. Together, these results indicate the potential of MSF as a candidate natural anticancer drug by promoting ROS production. Copyright © 2015 John Wiley & Sons, Ltd.

Data-driven classification of ventilated lung tissues using electrical impedance tomography

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Gómez-Laberge, Camille; Hogan, Matthew J; Elke, Gunnar; Weiler, Norbert; Frerichs, Inéz; Adler, Andy

2011-01-01

Current methods for identifying ventilated lung regions utilizing electrical impedance tomography images rely on dividing the image into arbitrary regions of interest (ROI), manually delineating ROI, or forming ROI with pixels whose signal properties surpass an arbitrary threshold. In this paper, we propose a novel application of a data-driven classification method to identify ventilated lung ROI based on forming k clusters from pixels with correlated signals. A standard first-order model for lung mechanics is then applied to determine which ROI correspond to ventilated lung tissue. We applied the method in an experimental study of 16 mechanically ventilated swine in the supine position, which underwent changes in positive end-expiratory pressure (PEEP) and fraction of inspired oxygen (F I O 2 ). In each stage of the experimental protocol, the method performed best with k = 4 and consistently identified 3 lung tissue ROI and 1 boundary tissue ROI in 15 of the 16 subjects. When testing for changes from baseline in lung position, tidal volume, and respiratory system compliance, we found that PEEP displaced the ventilated lung region dorsally by 2 cm, decreased tidal volume by 1.3%, and increased the respiratory system compliance time constant by 0.3 s. F I O 2 decreased tidal volume by 0.7%. All effects were tested at p < 0.05 with n = 16. These findings suggest that the proposed ROI detection method is robust and sensitive to ventilation dynamics in the experimental setting

Nasal Cannula Apneic Oxygenation Prevents Desaturation During Endotracheal Intubation: An Integrative Literature Review

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Bill R. Christian

2018-02-01

Full Text Available Patients requiring emergency airway management may be at greater risk of acute hypoxemic events because of underlying lung pathology, high metabolic demands, insufficient respiratory drive, obesity, or the inability to protect their airway against aspiration. Emergency tracheal intubation is often required before complete information needed to assess the risk of procedural hypoxia is acquired (i.e., arterial blood gas level, hemoglobin value, or chest radiograph. During pre-oxygenation, administering high-flow nasal oxygen in addition to a non-rebreather face mask can significantly boost the effective inspired oxygen. Similarly, with the apnea created by rapid sequence intubation (RSI procedures, the same high-flow nasal cannula can help maintain or increase oxygen saturation during efforts to secure the tube (oral intubation. Thus, the use of nasal oxygen during pre-oxygenation and continued during apnea can prevent hypoxia before and during intubation, extending safe apnea time, and improve first-pass success attempts. We conducted a literature review of nasal-cannula apneic oxygenation during intubation, focusing on two components: oxygen saturation during intubation, and oxygen desaturation time. We performed an electronic literature search from 1980 to November 2017, using PubMed, Elsevier, ScienceDirect, and EBSCO. We identified 14 studies that pointed toward the benefits of using nasal cannula during emergency intubation.

Increasing the inspiratory time and I:E ratio during mechanical ventilation aggravates ventilator-induced lung injury in mice.

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Müller-Redetzky, Holger C; Felten, Matthias; Hellwig, Katharina; Wienhold, Sandra-Maria; Naujoks, Jan; Opitz, Bastian; Kershaw, Olivia; Gruber, Achim D; Suttorp, Norbert; Witzenrath, Martin

2015-01-28

Lung-protective ventilation reduced acute respiratory distress syndrome (ARDS) mortality. To minimize ventilator-induced lung injury (VILI), tidal volume is limited, high plateau pressures are avoided, and positive end-expiratory pressure (PEEP) is applied. However, the impact of specific ventilatory patterns on VILI is not well defined. Increasing inspiratory time and thereby the inspiratory/expiratory ratio (I:E ratio) may improve oxygenation, but may also be harmful as the absolute stress and strain over time increase. We thus hypothesized that increasing inspiratory time and I:E ratio aggravates VILI. VILI was induced in mice by high tidal-volume ventilation (HVT 34 ml/kg). Low tidal-volume ventilation (LVT 9 ml/kg) was used in control groups. PEEP was set to 2 cm H2O, FiO2 was 0.5 in all groups. HVT and LVT mice were ventilated with either I:E of 1:2 (LVT 1:2, HVT 1:2) or 1:1 (LVT 1:1, HVT 1:1) for 4 hours or until an alternative end point, defined as mean arterial blood pressure below 40 mm Hg. Dynamic hyperinflation due to the increased I:E ratio was excluded in a separate group of animals. Survival, lung compliance, oxygenation, pulmonary permeability, markers of pulmonary and systemic inflammation (leukocyte differentiation in lung and blood, analyses of pulmonary interleukin-6, interleukin-1β, keratinocyte-derived chemokine, monocyte chemoattractant protein-1), and histopathologic pulmonary changes were analyzed. LVT 1:2 or LVT 1:1 did not result in VILI, and all individuals survived the ventilation period. HVT 1:2 decreased lung compliance, increased pulmonary neutrophils and cytokine expression, and evoked marked histologic signs of lung injury. All animals survived. HVT 1:1 caused further significant worsening of oxygenation, compliance and increased pulmonary proinflammatory cytokine expression, and pulmonary and blood neutrophils. In the HVT 1:1 group, significant mortality during mechanical ventilation was observed. According to the "baby lung

Nicotinamide exacerbates hypoxemia in ventilator-induced lung injury independent of neutrophil infiltration.

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Heather D Jones

Full Text Available Ventilator-induced lung injury is a form of acute lung injury that develops in critically ill patients on mechanical ventilation and has a high degree of mortality. Nicotinamide phosphoribosyltransferase is an enzyme that is highly upregulated in ventilator-induced lung injury and exacerbates the injury when given exogenously. Nicotinamide (vitamin B3 directly inhibits downstream pathways activated by Nicotinamide phosphoribosyltransferase and is protective in other models of acute lung injury.We administered nicotinamide i.p. to mice undergoing mechanical ventilation with high tidal volumes to study the effects of nicotinamide on ventilator-induced lung injury. Measures of injury included oxygen saturations and bronchoalveolar lavage neutrophil counts, protein, and cytokine levels. We also measured expression of nicotinamide phosophoribosyltransferase, and its downstream effectors Sirt1 and Cebpa, Cebpb, Cebpe. We assessed the effect of nicotinamide on the production of nitric oxide during ventilator-induced lung injury. We also studied the effects of ventilator-induced lung injury in mice deficient in C/EBPε.Nicotinamide treatment significantly inhibited neutrophil infiltration into the lungs during ventilator-induced lung injury, but did not affect protein leakage or cytokine production. Surprisingly, mice treated with nicotinamide developed significantly worse hypoxemia during mechanical ventilation. This effect was not linked to increases in nitric oxide production or alterations in expression of Nicotinamide phosphoribosyl transferase, Sirt1, or Cebpa and Cebpb. Cebpe mRNA levels were decreased with either nicotinamide treatment or mechanical ventilation, but mice lacking C/EBPε developed the same degree of hypoxemia and ventilator-induced lung injury as wild-type mice.Nicotinamide treatment during VILI inhibits neutrophil infiltration of the lungs consistent with a strong anti-inflammatory effect, but paradoxically also leads to the

Mechanical ventilation during extracorporeal membrane oxygenation.

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Schmidt, Matthieu; Pellegrino, Vincent; Combes, Alain; Scheinkestel, Carlos; Cooper, D Jamie; Hodgson, Carol

2014-01-21

The timing of extracorporeal membrane oxygenation (ECMO) initiation and its outcome in the management of respiratory and cardiac failure have received considerable attention, but very little attention has been given to mechanical ventilation during ECMO. Mechanical ventilation settings in non-ECMO studies have been shown to have an effect on survival and may also have contributed to a treatment effect in ECMO trials. Protective lung ventilation strategies established for non-ECMO-supported respiratory failure patients may not be optimal for more severe forms of respiratory failure requiring ECMO support. The influence of positive end-expiratory pressure on the reduction of the left ventricular compliance may be a matter of concern for patients receiving ECMO support for cardiac failure. The objectives of this review were to describe potential mechanisms for lung injury during ECMO for respiratory or cardiac failure, to assess the possible benefits from the use of ultra-protective lung ventilation strategies and to review published guidelines and expert opinions available on mechanical ventilation-specific management of patients requiring ECMO, including mode and ventilator settings. Articles were identified through a detailed search of PubMed, Ovid, Cochrane databases and Google Scholar. Additional references were retrieved from the selected studies. Growing evidence suggests that mechanical ventilation settings are important in ECMO patients to minimize further lung damage and improve outcomes. An ultra-protective ventilation strategy may be optimal for mechanical ventilation during ECMO for respiratory failure. The effects of airway pressure on right and left ventricular afterload should be considered during venoarterial ECMO support of cardiac failure. Future studies are needed to better understand the potential impact of invasive mechanical ventilation modes and settings on outcomes.

Propofol attenuates oxidant-induced acute lung injury in an isolated perfused rabbit-lung model.

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Yumoto, Masato; Nishida, Osamu; Nakamura, Fujio; Katsuya, Hirotada

2005-01-01

Reactive oxygen species have been strongly implicated in the pathogenesis of acute lung injury (ALI). Some animal studies suggest that free radical scavengers inhibit the onset of oxidant-induced ALI. Propofol (2,6-diisopropylphenol) is chemically similar to phenol-based free radical scavengers such as the endogenous antioxidant vitamin E. Both in vivo and in vitro studies have suggested that propofol has antioxidant potential. We hypothesized that propofol may attenuate ALI by acting as a free-radical scavenger. We investigated the effects of propofol on oxidant-induced ALI induced by purine and xanthine oxidase (XO), in isolated perfused rabbit lung, in two series of experiments. In series 1, we examined the relationship between the severity of ALI and the presence of hydrogen peroxide (H2O2). In series 2, we evaluated the effects of propofol on attenuating ALI and the dose dependence of these effects. The lungs were perfused for 90 min, and we evaluated the effects on the severity of ALI by monitoring the pulmonary capillary filtration coefficient (Kfc), pulmonary arterial pressure (Ppa), and the pulmonary capillary hydrostatic pressure (Ppc). In series 1, treatment with catalase (an H2O2 scavenger) prior to the addition of purine and XO resulted in complete prevention of ALI, suggesting that H2O2 may be involved closely in the pathogenesis of ALI. In series 2, pretreatment with propofol at concentrations in excess of 0.5 mM significantly inhibited the increases in the Kfc values, and that in excess of 0.75 mM significantly inhibited the increase in the Ppa values. Propofol attenuates oxidant-induced ALI in an isolated perfused rabbit lung model, probably due to its antioxidant action.

Micro-fibers shape effects on gas exchange in Total Artificial Lung

KAUST Repository

Qamar, Adnan; Guglani, Aditya; Samtaney, Ravi

2014-01-01

Flow and oxygen transport dynamics of a pulsatile flow past an array of square and circular cross section micro-fiber is numerically investigated in the present work. The study is motivated to optimize the design of an Total Artificial Lung (TAL) under clinical trials. Effects of three non-dimensional parameters: Reynolds number, non-dimensional amplitude of free stream velocity and Keulegan Carpenter number on oxygen transport and total drag (resistance) of both the fibers are studied. Range of parameters investigated corresponds to operating range of TAL. For most of the cases investigated, results show enhanced oxygen transport for square fiber but higher resistance when compare with the circular fiber case under almost all flow conditions. For both fibers, oxygen transfer rate are enhanced at higher Reynolds number, higher velocity amplitude and lower KC values. Overall drag is found to decrease with increasing Reynolds number and decreasing amplitude and is not significantly effected by Keulegan Carpenter number. © 2014 IEEE.

Micro-fibers shape effects on gas exchange in Total Artificial Lung

KAUST Repository

Qamar, Adnan

2014-02-01

Flow and oxygen transport dynamics of a pulsatile flow past an array of square and circular cross section micro-fiber is numerically investigated in the present work. The study is motivated to optimize the design of an Total Artificial Lung (TAL) under clinical trials. Effects of three non-dimensional parameters: Reynolds number, non-dimensional amplitude of free stream velocity and Keulegan Carpenter number on oxygen transport and total drag (resistance) of both the fibers are studied. Range of parameters investigated corresponds to operating range of TAL. For most of the cases investigated, results show enhanced oxygen transport for square fiber but higher resistance when compare with the circular fiber case under almost all flow conditions. For both fibers, oxygen transfer rate are enhanced at higher Reynolds number, higher velocity amplitude and lower KC values. Overall drag is found to decrease with increasing Reynolds number and decreasing amplitude and is not significantly effected by Keulegan Carpenter number. © 2014 IEEE.

Continuous positive airway pressure (CPAP after lung resection: a randomized clinical trial

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Ligia dos Santos Roceto

Full Text Available CONTEXT AND OBJECTIVE: Noninvasive mechanical ventilation during the postoperative period (PO following lung resection can restore residual functional capacity, improve oxygenation and spare the inspiratory muscles. The objective of this study was to assess the efficacy of continuous positive airway pressure (CPAP associated with physiotherapy, compared with physiotherapy alone after lung resection. DESIGN AND SETTING: Open randomized clinical trial conducted in the clinical hospital of Universidade Estadual de Campinas. METHOD: Sessions were held in the immediate postoperative period (POi and on the first and second postoperative days (PO1 and PO2, and the patients were reassessed on the discharge day. CPAP was applied for two hours and the pressure adjustment was set between 7 and 8.5 cmH2O. The oxygenation index (OI, Borg scale, pain scale and presence of thoracic drains and air losses were evaluated. RESULTS : There was a significant increase in the OI in the CPAP group in the POi compared to the Chest Physiotherapy (CP group, P = 0.024. In the CP group the OI was significantly lower on PO1 (P = 0,042, than CPAP group. The air losses were significantly greater in the CPAP group in the POi and on PO1 (P = 0.001, P = 0.028, but there was no significant difference between the groups on PO2 and PO3. There was a statistically significant difference between the groups regarding the Borg scale in the POi (P < 0.001, but there were no statistically significant differences between the groups regarding the pain score. CONCLUSION: CPAP after lung resection is safe and improves oxygenation, without increasing the air losses through the drains. CLINICAL TRIAL REGISTRATION: NCT01285648

Response of the oxygen uptake efficiency slope to orthotopic heart transplantation: lack of correlation with changes in central hemodynamic parameters and resting lung function.

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Van Laethem, Christophe; Goethals, Marc; Verstreken, Sofie; Walravens, Maarten; Wellens, Francis; De Proft, Margot; Bartunek, Jozef; Vanderheyden, Marc

2007-09-01

Recently, a new linear measure of ventilatory response to exercise, the oxygen uptake efficiency slope (OUES), was proposed in the evaluation of heart failure patients. No data are available on the response of the OUES after orthotopic heart transplantation (HTx). Thirty patients who underwent HTx between 1999 and 2003 were included in the study. Data from maximal cardiopulmonary exercise test, resting pulmonary function and hemodynamic assessment were collected before the transplant at time of screening and 1 year after HTx. During the first year after HTx, OUES and normalized OUES for body weight (OUES/kg) increased significantly from 15.6 +/- 4.9 to 19.7 +/- 4.8 (p volumes or capacities and measures of central hemodynamic function after HTx. OUES improved significantly after HTx, but, similar to other exercise parameters, remained considerably impaired. The changes in OUES were highly correlated with the improvements in other exercise variables, but did not correlate with marked improvements in central hemodynamics or resting lung function.

Comparisons of different mean airway pressure settings during high-frequency oscillation in inflammatory response to oleic acid-induced lung injury in rabbits

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Koichi Ono

2009-03-01

Full Text Available Koichi Ono1, Tomonobu Koizumi2, Rikimaru Nakagawa1, Sumiko Yoshikawa2, Tetsutarou Otagiri11Department of Anesthesiology and Resuscitation; 2First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, JapanPurpose: The present study was designed to examine effects of different mean airway pressure (MAP settings during high-frequency oscillation (HFO on oxygenation and inflammatory responses to acute lung injury (ALI in rabbits.Methods: Anesthetized rabbits were mechanically ventilated with a conventional mechanical ventilation (CMV mode (tidal volume 6 ml/kg, inspired oxygen fraction [FIo2] of 1.0, respiratory rate [RR] of 30/min, positive end-expiratory pressure [PEEP] of 5 cmH2O. ALI was induced by intravenous administration of oleic acid (0.08 ml/kg and the animals were randomly allocated to the following three experimental groups; animals (n = 6 ventilated using the same mode of CMV, or animals ventilated with standard MAP (MAP 10 cmH2O, n = 7, and high MAP (15 cmH2O, n = 6 settings of HFO (Hz 15. The MAP settings were calculated by the inflation limb of the pressure-volume curve during CMV.Results: HFO with a high MAP setting significantly improved the deteriorated oxygenation during oleic acid-induced ALI and reduced wet/dry ratios, neutrophil counts and interleukin-8 concentration in bronchoalveolar lavage fluid, compared to those parameters in CMV and standard MAP-HFO.Conclusions: These findings suggest that only high MAP setting during HFO could contribute to decreased lung inflammation as well as improved oxygenation during the development of ALI.Keywords: lung protective ventilation, open lung ventilation, IL-8, neutrophil

Gill and lung ventilation responses to steady-state aquatic hypoxia and hyperoxia in the bullfrog tadpole.

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West, N H; Burggren, W W

1982-02-01

Gill ventilation frequency (fG), the pressure amplitude (PBC) and stroke volume (VS) of buccal ventilation cycles, the frequency of air breaths (fL), water flow over the gills (VW), gill oxygen uptake (MGO2), oxygen utilization (U), and heart frequency (fH) have been measured in unanaesthetized, air breathing Rana catesbeiana tadpoles (stage XVI-XIX). The animals were unrestrained except for ECG leads or cannulae, and were able to surface voluntarily for air breathing. They were subjected to aquatic normoxia, hyperoxia and three levels of aquatic hypoxia, and their respiratory responses recorded in the steady state. The experiments were performed at 20 +/- 0.5 degrees C. In hyperoxia there was an absence of air breathing, and fG, PBC and VW fell from the normoxic values, while U increased, resulting in no significant change in MGO2. Animals in normoxia showed a very low fL which increased in progressively more hypoxic states. VW increased from the normoxic value in mild hypoxia (PO2 = 96 +/- 2 mm Hg), but fell, associated with a reduction in PBC, in moderate (PO2 = 41 +/- 1 mm Hg) and severe (PO2 = 21 +/- 3 mm Hg) hypoxia in the presence of lung ventilation. Gill MGO2 was not significantly different from the normoxic value in mild hypoxia but fell in moderate hypoxia, while in severe hypoxia oxygen was lost to the ventilating water from the blood perfusing the gills. There was no significant change in fH from the normoxic value in either hypoxia or hyperoxia. These data indicate, that in the bimodally breathing bullfrog tadpole, aquatic PO2 exerts a strong control over both gill and lung ventilation. Furthermore, there is an interaction between gill and lung ventilation such that the onset of a high frequency of lung ventilation in moderate and severe hypoxia promotes a suppression of gill ventilation cycles.

The environmental carcinogen 3-nitrobenzanthrone and its main metabolite 3-aminobenzanthrone enhance formation of reactive oxygen intermediates in human A549 lung epithelial cells

International Nuclear Information System (INIS)

Hansen, Tanja; Seidel, Albrecht; Borlak, Juergen

2007-01-01

The environmental contaminant 3-nitrobenzanthrone (3-NBA) is highly mutagenic and a suspected human carcinogen. We aimed to evaluate whether 3-NBA is able to deregulate critical steps in cell cycle control and apoptosis in human lung epithelial A549 cells. Increased intracellular Ca 2+ and caspase activities were detected upon 3-NBA exposure. As shown by cell cycle analysis, an increased number of S-phase cells was observed after 24 h of treatment with 3-NBA. Furthermore, 3-NBA was shown to inhibit cell proliferation when added to subconfluent cell cultures. The main metabolite of 3-NBA, 3-ABA, induced statistically significant increases in tail moment as judged by alkaline comet assay. The potential of 3-NBA and 3-ABA to enhance the production of reactive oxygen species (ROS) was demonstrated by flow cytometry using 2',7'-dichlorofluorescein-diacetate (DCFH-DA). The enzyme inhibitors allopurinol, dicumarol, resveratrol and SKF525A were used to assess the impact of metabolic conversion on 3-NBA-mediated ROS production. Resveratrol decreased dichlorofluorescein (DCF) fluorescence by 50%, suggesting a role for CYP1A1 in 3-NBA-mediated ROS production. Mitochondrial ROS production was significantly attenuated (20% reduction) by addition of rotenone (complex I inhibition) and thenoyltrifluoroacetone (TTFA, complex II inhibition). Taken together, the results of the present study provide evidence for a genotoxic potential of 3-ABA in human epithelial lung cells. Moreover, both compounds lead to increased intracellular ROS and create an environment favorable to DNA damage and the promotion of cancer

Unusual case of a vanishing bronchus of the left allograft in a lung transplant recipient

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Don Hayes

2013-01-01

Full Text Available We present an interesting case of a complete vanishing of the left main bronchus in a lung transplant recipient who had a successful outcome due to acute respiratory support with venovenous extracorporeal membrane oxygenation in order to perform airway dilation.

Physiologic Evaluation of Ventilation Perfusion Mismatch and Respiratory Mechanics at Different Positive End-expiratory Pressure in Patients Undergoing Protective One-lung Ventilation.

Science.gov (United States)

Spadaro, Savino; Grasso, Salvatore; Karbing, Dan Stieper; Fogagnolo, Alberto; Contoli, Marco; Bollini, Giacomo; Ragazzi, Riccardo; Cinnella, Gilda; Verri, Marco; Cavallesco, Narciso Giorgio; Rees, Stephen Edward; Volta, Carlo Alberto

2018-03-01

Arterial oxygenation is often impaired during one-lung ventilation, due to both pulmonary shunt and atelectasis. The use of low tidal volume (VT) (5 ml/kg predicted body weight) in the context of a lung-protective approach exacerbates atelectasis. This study sought to determine the combined physiologic effects of positive end-expiratory pressure and low VT during one-lung ventilation. Data from 41 patients studied during general anesthesia for thoracic surgery were collected and analyzed. Shunt fraction, high V/Q and respiratory mechanics were measured at positive end-expiratory pressure 0 cm H2O during bilateral lung ventilation and one-lung ventilation and, subsequently, during one-lung ventilation at 5 or 10 cm H2O of positive end-expiratory pressure. Shunt fraction and high V/Q were measured using variation of inspired oxygen fraction and measurement of respiratory gas concentration and arterial blood gas. The level of positive end-expiratory pressure was applied in random order and maintained for 15 min before measurements. During one-lung ventilation, increasing positive end-expiratory pressure from 0 cm H2O to 5 cm H2O and 10 cm H2O resulted in a shunt fraction decrease of 5% (0 to 11) and 11% (5 to 16), respectively (P ventilation, high positive end-expiratory pressure levels improve pulmonary function without increasing high V/Q and reduce driving pressure.

Prone position for the prevention of lung infection.

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Beuret, P

2002-04-01

Pulmonary infection is frequent in brain injured patients. It has been identified as an independent predictor of unfavorable neurological outcome, calling for attempts of prevention. We recently evaluated intermittent prone positioning for the prevention of ventilator-associated pneumonia (VAP) in comatose brain injured patients, in a randomized study. 25 patients were included in the prone position (PP) group: they were positioned on prone four hours once daily until they could get up to sit in an armchair; 26 patients were included in the supine position (SP) group. The main characteristics of the patients from the two groups were similar at randomization. The primary end-point was the incidence of lung worsening, defined by an increase in the Lung Injury Score by at least one point since the time of randomization. The incidence of lung worsening was lower in the PP group (12%) than in the SP group (50%) (p=0.003). The incidence of VAP was 38.4% in the SP group and 20% in the PP group (p=0.14). There was no serious complication attributable to prone positioning. In conclusion, the beneficial effect of prone positioning for prevention of lung infection in brain injured patients is not well established. However, in those patients, prone positioning is able to avoid the worsening of pulmonary function, especially in oxygenation.

The Effect of Compartmental Asymmetry on the Monitoring of Pulmonary Mechanics and Lung Volumes.

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Keenan, Joseph C; Cortes-Puentes, Gustavo A; Adams, Alexander B; Dries, David J; Marini, John J

2016-11-01

Esophageal pressure measurement for computation of transpulmonary pressure (P tp ) has begun to be incorporated into clinical use for evaluating forces across the lungs. Gaps exist in our understanding of how esophageal pressure (and therefore P tp ), a value measured at a single site, responds when respiratory system compartments are asymmetrically affected by whole-lung atelectasis or unilateral injury as well as changes in chest wall compliance. We reasoned that P tp would track with aerated volume changes as estimated by functional residual capacity (FRC) and tidal volume. We examined this hypothesis in the setting of asymmetric lungs and changes in intra-abdominal pressure. This study was conducted in the animal laboratory of a university-affiliated hospital. Models of unilateral atelectasis and unilateral and bilateral lung injury exposed to intra-abdominal hypertension (IAH) in 10 deeply sedated mechanically ventilated swine. Atelectasis was created by balloon occlusion of the left main bronchus. Unilateral lung injury was induced by saline lavage of isolated right lung. Diffuse lung injury was induced by saline lavage of both lungs. The peritoneum was insufflated with air to create a model of pressure-regulated IAH. We measured esophageal pressures, airway pressures, FRC by gas dilution, and oxygenation. FRC was reduced by IAH in normal lungs (P volume in the setting of thoracic asymmetry and changes in intra-abdominal pressure. However, used alone, it cannot distinguish the relative contributions of air-space distention and recruitment of lung units. Copyright © 2016 by Daedalus Enterprises.

Activation of rho is involved in the mechanism of hydrogen-peroxide-induced lung edema in isolated perfused rabbit lung.

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Chiba, Y; Ishii, Y; Kitamura, S; Sugiyama, Y

2001-09-01

Acute lung injury is attributed primarily to increased vascular permeability caused by reactive oxygen species derived from neutrophils, such as hydrogen peroxide (H2O2). Increased permeability is accompanied by the contraction and cytoskeleton reorganization of endothelial cells, resulting in intercellular gap formation. The Rho family of Ras-like GTPases is implicated in the regulation of the cytoskeleton and cell contraction. We examined the role of Rho in H2O2-induced pulmonary edema with the use of isolated perfused rabbit lungs. To our knowledge, this is the first study to examine the role of Rho in increased vascular permeability induced by H2O2 in perfused lungs. Vascular permeability was evaluated on the basis of the capillary filtration coefficient (Kfc, ml/min/cm H2O/100 g). We found that H2O2 (300 microM) increased lung weight, Kfc, and pulmonary capillary pressure. These effects of H2O2 were abolished by treatment with Y-27632 (50 microM), an inhibitor of the Rho effector p160 ROCK. In contrast, the muscular relaxant papaverine inhibited the H2O2-induced rise in pulmonary capillary pressure, but did not suppress the increases in lung weight and Kfc. These findings indicate that H2O2 causes pulmonary edema by elevating hydrostatic pressure and increasing vascular permeability. Y-27632 inhibited the formation of pulmonary edema by blocking both of these H2O2-induced effects. Our results suggest that Rho-related pathways have a part in the mechanism of H2O2-induced pulmonary edema. Copyright 2001 Academic Press.

Functional imaging of the lung using a gaseous contrast agent: {sup 3}Helium-magnetic resonance imaging; Funktionelle Bildgebung der Lunge mit gasfoermigem Kontrastmittel: {sup 3}Helium-Magnetresonanztomographie

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Gast, K.K.; Heussel, C.P. [Klinik mit Poliklinik fuer Radiologie, Klinikum der Johannes Gutenberg-Univ., Mainz (Germany); Schreiber, W.G. [AG Medizinische Physik, Klinik mit Poliklinik fuer Radiologie, Klinikum der Johannes Gutenberg-Univ., Mainz (Germany); Kauczor, H.U. [Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany)

2005-05-01

Current imaging methods of the lung concentrate on morphology as well as on the depiction of the pulmonary parenchyma. The need of an advanced and more subtle imaging technology compared to conventional radiography is met by computed topograhy as the method of choice. Nevertheless, computed tomography yields very limited functional information. This is to be derived from arterial blood gas analysis, spirometry and body plethysmography. These methods, however, lack the scope for regional allocation of any pathology. Magnetic resonance imaging of the lung has been advanced by the use of hyperpolarised {sup 3}Helium as an inhaled gaseous contrast agent. The inhalation of the gas provides functional data by distribution, diffusion and relaxation of its hyperpolarised state. Because anatomical landmarks of the lung can be visualised as well, functional information can be linked with regional information. Furthermore, the method provides high spatial and temporal resolution and lacks the potential side-effects of ionising radiation. Four different modalities have been established: 1. Spin density imaging studies the distribution of gas, normally after a single inhalation of contrast gas in inspiratory breath hold. 2. Dynamic cine imaging studies the distribution of gas with respect to regional time constants of pulmonary gas inflow. 3. Diffusion weighted imaging can exhibit the presence and severity of pulmonary airspace enlargement, as in pulmonary emphysema. 4. Oxygen sensitive imaging displays intrapulmonary oxygen partial pressure and its distribution. Currently, the method is limited by comparably high costs and limited availability. As there have been recent developments which might bring this modality closer to clinical use, this review article will comprise the methodology as well as the current state of the art and standard of knowledge of magnetic resonance imaging of the lung using hyperpolarised {sup 3}Helium. (orig.)

Asphyxiation death caused by oxygen-depleting cargo on a ship.

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Sundal, Marjana Kjetland; Lilleng, Peer Kaare; Barane, Hans; Morild, Inge; Vevelstad, Merete

2017-10-01

The extreme danger associated with entering enclosed spaces loaded with oxygen-depleting organic cargo in ships and tanks is obviously underestimated, both among crew and management. We present a case report to highlight this occupational hazard and to increase the knowledge about the imperative precautions, in order to prevent future accidents. An experienced customs officer was found lifeless at the bottom of the unattended cargo hold on a ship loaded with woodchips. The oxygen content in the cargo atmosphere was below 2%, which is incompatible with life. Forensic autopsy revealed injuries related to the fall, and there were no positive toxicological findings in blood, lung or urine. Management and workers must be taught about the extreme rapidity of developing unconsciousness and asphyxiant death when entering enclosed spaces loaded with oxygen-depleting cargo. Even a single inhalation can result in unconsciousness and death. Dozens of annual deaths and severe injuries can easily be prevented if simple precautions are followed. Copyright © 2017 Elsevier B.V. All rights reserved.

Reservoir Cannulas for Pediatric Oxygen Therapy: A Proof-of-Concept Study

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Grace Wu

2016-01-01

Full Text Available Hypoxemia is a complication of pneumonia—the leading infectious cause of death in children worldwide. Treatment generally requires oxygen-enriched air, but access in low-resource settings is expensive and unreliable. We explored use of reservoir cannulas (RCs, which yield oxygen savings in adults but have not been examined in children. Toddler, small child, and adolescent breathing profiles were simulated with artificial lung and airway models. An oxygen concentrator provided flow rates of 0 to 5 L/min via a standard nasal cannula (NC or RC, and delivered oxygen fraction (FdO2 was measured. The oxygen savings ratio (SR and absolute flow savings (AFS were calculated, comparing NC and RC. We demonstrated proof-of-concept that pendant RCs could conserve oxygen during pediatric therapy. SR mean and standard deviation were 1.1±0.2 to 1.4±0.4, 1.1±0.1 to 1.7±0.3, and 1.3±0.1 to 2.4±0.3 for toddler, small child, and adolescent models, respectively. Maximum AFS observed were 0.3±0.3, 0.2±0.1, and 1.4±0.3 L/min for the same models. RCs have the potential to reduce oxygen consumption during treatment of hypoxemia in children; however, further evaluation of products is needed, followed by clinical analysis in patients.

Reservoir Cannulas for Pediatric Oxygen Therapy: A Proof-of-Concept Study

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Wu, Grace; DiBlasi, Robert M.; Saxon, Eugene; Austin, Glenn; Ginsburg, Amy Sarah

2016-01-01

Hypoxemia is a complication of pneumonia—the leading infectious cause of death in children worldwide. Treatment generally requires oxygen-enriched air, but access in low-resource settings is expensive and unreliable. We explored use of reservoir cannulas (RCs), which yield oxygen savings in adults but have not been examined in children. Toddler, small child, and adolescent breathing profiles were simulated with artificial lung and airway models. An oxygen concentrator provided flow rates of 0 to 5 L/min via a standard nasal cannula (NC) or RC, and delivered oxygen fraction (FdO2) was measured. The oxygen savings ratio (SR) and absolute flow savings (AFS) were calculated, comparing NC and RC. We demonstrated proof-of-concept that pendant RCs could conserve oxygen during pediatric therapy. SR mean and standard deviation were 1.1 ± 0.2 to 1.4 ± 0.4, 1.1 ± 0.1 to 1.7 ± 0.3, and 1.3 ± 0.1 to 2.4 ± 0.3 for toddler, small child, and adolescent models, respectively. Maximum AFS observed were 0.3 ± 0.3, 0.2 ± 0.1, and 1.4 ± 0.3 L/min for the same models. RCs have the potential to reduce oxygen consumption during treatment of hypoxemia in children; however, further evaluation of products is needed, followed by clinical analysis in patients. PMID:27999601

A novel mechanical lung model of pulmonary diseases to assist with teaching and training

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Shaw Geoffrey M

2006-08-01

Full Text Available Abstract Background A design concept of low-cost, simple, fully mechanical model of a mechanically ventilated, passively breathing lung is developed. An example model is built to simulate a patient under mechanical ventilation with accurate volumes and compliances, while connected directly to a ventilator. Methods The lung is modelled with multiple units, represented by rubber bellows, with adjustable weights placed on bellows to simulate compartments of different superimposed pressure and compliance, as well as different levels of lung disease, such as Acute Respiratory Distress Syndrome (ARDS. The model was directly connected to a ventilator and the resulting pressure volume curves recorded. Results The model effectively captures the fundamental lung dynamics for a variety of conditions, and showed the effects of different ventilator settings. It was particularly effective at showing the impact of Positive End Expiratory Pressure (PEEP therapy on lung recruitment to improve oxygenation, a particulary difficult dynamic to capture. Conclusion Application of PEEP therapy is difficult to teach and demonstrate clearly. Therefore, the model provide opportunity to train, teach, and aid further understanding of lung mechanics and the treatment of lung diseases in critical care, such as ARDS and asthma. Finally, the model's pure mechanical nature and accurate lung volumes mean that all results are both clearly visible and thus intuitively simple to grasp.

Alda-1 Protects Against Acrolein-Induced Acute Lung Injury and Endothelial Barrier Dysfunction.

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Lu, Qing; Mundy, Miles; Chambers, Eboni; Lange, Thilo; Newton, Julie; Borgas, Diana; Yao, Hongwei; Choudhary, Gaurav; Basak, Rajshekhar; Oldham, Mahogany; Rounds, Sharon

2017-12-01

Inhalation of acrolein, a highly reactive aldehyde, causes lung edema. The underlying mechanism is poorly understood and there is no effective treatment. In this study, we demonstrated that acrolein not only dose-dependently induced lung edema but also promoted LPS-induced acute lung injury. Importantly, acrolein-induced lung injury was prevented and rescued by Alda-1, an activator of mitochondrial aldehyde dehydrogenase 2. Acrolein also dose-dependently increased monolayer permeability, disrupted adherens junctions and focal adhesion complexes, and caused intercellular gap formation in primary cultured lung microvascular endothelial cells (LMVECs). These effects were attenuated by Alda-1 and the antioxidant N-acetylcysteine, but not by the NADPH inhibitor apocynin. Furthermore, acrolein inhibited AMP-activated protein kinase (AMPK) and increased mitochondrial reactive oxygen species levels in LMVECs-effects that were associated with impaired mitochondrial respiration. AMPK total protein levels were also reduced in lung tissue of mice and LMVECs exposed to acrolein. Activation of AMPK with 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside blunted an acrolein-induced increase in endothelial monolayer permeability, but not mitochondrial oxidative stress or inhibition of mitochondrial respiration. Our results suggest that acrolein-induced mitochondrial dysfunction may not contribute to endothelial barrier dysfunction. We speculate that detoxification of acrolein by Alda-1 and activation of AMPK may be novel approaches to prevent and treat acrolein-associated acute lung injury, which may occur after smoke inhalation.

Arteriovenous extracorporeal lung assist allows for maximization of oscillatory frequencies: a large-animal model of respiratory distress

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Kranke Peter

2008-11-01

Full Text Available Abstract Background Although the minimization of the applied tidal volume (VT during high-frequency oscillatory ventilation (HFOV reduces the risk of alveolar shear stress, it can also result in insufficient CO2-elimination with severe respiratory acidosis. We hypothesized that in a model of acute respiratory distress (ARDS the application of high oscillatory frequencies requires the combination of HFOV with arteriovenous extracorporeal lung assist (av-ECLA in order to maintain or reestablish normocapnia. Methods After induction of ARDS in eight female pigs (56.5 ± 4.4 kg, a recruitment manoeuvre was performed and intratracheal mean airway pressure (mPaw was adjusted 3 cmH2O above the lower inflection point (Plow of the pressure-volume curve. All animals were ventilated with oscillatory frequencies ranging from 3–15 Hz. The pressure amplitude was fixed at 60 cmH2O. At each frequency gas exchange and hemodynamic measurements were obtained with a clamped and de-clamped av-ECLA. Whenever the av-ECLA was de-clamped, the oxygen sweep gas flow through the membrane lung was adjusted aiming at normocapnia. Results Lung recruitment and adjustment of the mPaw above Plow resulted in a significant improvement of oxygenation (p Conclusion In this animal model of ARDS, maximization of oscillatory frequencies with subsequent minimization of VT leads to hypercapnia that can only be reversed by adding av-ECLA. When combined with a recruitment strategy, these high frequencies do not impair oxygenation

Silicon Micropore-Based Parallel Plate Membrane Oxygenator.

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Dharia, Ajay; Abada, Emily; Feinberg, Benjamin; Yeager, Torin; Moses, Willieford; Park, Jaehyun; Blaha, Charles; Wright, Nathan; Padilla, Benjamin; Roy, Shuvo

2018-02-01

Extracorporeal membrane oxygenation (ECMO) is a life support system that circulates the blood through an oxygenating system to temporarily (days to months) support heart or lung function during cardiopulmonary failure until organ recovery or replacement. Currently, the need for high levels of systemic anticoagulation and the risk for bleeding are main drawbacks of ECMO that can be addressed with a redesigned ECMO system. Our lab has developed an approach using microelectromechanical systems (MEMS) fabrication techniques to create novel gas exchange membranes consisting of a rigid silicon micropore membrane (SμM) support structure bonded to a thin film of gas-permeable polydimethylsiloxane (PDMS). This study details the fabrication process to create silicon membranes with highly uniform micropores that have a high level of pattern fidelity. The oxygen transport across these membranes was tested in a simple water-based bench-top set-up as well in a porcine in vivo model. It was determined that the mass transfer coefficient for the system using SµM-PDMS membranes was 3.03 ± 0.42 mL O 2 min -1 m -2 cm Hg -1 with pure water and 1.71 ± 1.03 mL O 2 min -1 m -2 cm Hg -1 with blood. An analytic model to predict gas transport was developed using data from the bench-top experiments and validated with in vivo testing. This was a proof of concept study showing adequate oxygen transport across a parallel plate SµM-PDMS membrane when used as a membrane oxygenator. This work establishes the tools and the equipoise to develop future generations of silicon micropore membrane oxygenators. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Extracorporeal gas exchange with the DeltaStream rotary blood pump in experimental lung injury.

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Dembinski, Rolf; Kopp, Rüdger; Henzler, Dietrich; Hochhausen, Nadine; Oslender, Nicole; Max, Martin; Rossaint, Rolf; Kuhlen, Ralf

2003-06-01

In most severe cases of the acute respiratory distress syndrome, veno-venous extracorporeal membrane oxygenation (ECMO) can be used to facilitate gas exchange. However, the clinical use is limited due to the size and the concomitant risk of severe adverse events of conventionally-used centrifugal blood pumps with high extracorporeal blood volumes. The DeltaStream blood pump is a small-sized rotary blood pump that may reduce extracorporeal blood volume, foreign surfaces, contact activation of the coagulation system, and blood trauma. The aim of the present study was to test the safety and efficacy of the DeltaStream pump for ECMO in animals with normal lung function and experimental acute lung injury (ALI). Therefore, veno-venous ECMO was performed for 6 hours in mechanically ventilated pigs with normal lung function (n=6) and with ALI induced by repeated lung lavage (n=6) with a blood flow of 30% of the cardiac output. Gas flow with a FiO2 of 1.0 was set to equal blood flow. With a mean activated clotting time of 121 +/- 22 s, no circulatory impairment or thrombus formation was revealed during ECMO. Furthermore, free plasma Hb did not increase. In controls, hemodynamics and gas exchange remained unchanged. In animals with ALI, hemodynamics remained stable and gas transfer across the extracorporeal oxygenators was optimal, but only in 2 animals was a marked increase in PaO2 observed. CO2 removal was efficacious in all animals. We concluded that the DeltaStream blood pump may be used for veno-venous ECMO without major blood damage or hemodynamic impairment.

Standardisation of oxygen exposure in the development of mouse models for bronchopulmonary dysplasia

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Claudio Nardiello

2017-02-01

Full Text Available Progress in developing new therapies for bronchopulmonary dysplasia (BPD is sometimes complicated by the lack of a standardised animal model. Our objective was to develop a robust hyperoxia-based mouse model of BPD that recapitulated the pathological perturbations to lung structure noted in infants with BPD. Newborn mouse pups were exposed to a varying fraction of oxygen in the inspired air (FiO2 and a varying window of hyperoxia exposure, after which lung structure was assessed by design-based stereology with systemic uniform random sampling. The efficacy of a candidate therapeutic intervention using parenteral nutrition was evaluated to demonstrate the utility of the standardised BPD model for drug discovery. An FiO2 of 0.85 for the first 14 days of life decreased total alveoli number and concomitantly increased alveolar septal wall thickness, which are two key histopathological characteristics of BPD. A reduction in FiO2 to 0.60 or 0.40 also caused a decrease in the total alveoli number, but the septal wall thickness was not impacted. Neither a decreasing oxygen gradient (from FiO2 0.85 to 0.21 over the first 14 days of life nor an oscillation in FiO2 (between 0.85 and 0.40 on a 24 h:24 h cycle had an appreciable impact on lung development. The risk of missing beneficial effects of therapeutic interventions at FiO2 0.85, using parenteral nutrition as an intervention in the model, was also noted, highlighting the utility of lower FiO2 in selected studies, and underscoring the need to tailor the model employed to the experimental intervention. Thus, a state-of-the-art BPD animal model that recapitulates the two histopathological hallmark perturbations to lung architecture associated with BPD is described. The model presented here, where injurious stimuli have been systematically evaluated, provides a most promising approach for the development of new strategies to drive postnatal lung maturation in affected infants.

Oxygen and oxidative stress in the perinatal period

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Isabel Torres-Cuevas

2017-08-01

Full Text Available Fetal life evolves in a hypoxic environment. Changes in the oxygen content in utero caused by conditions such as pre-eclampsia or type I diabetes or by oxygen supplementation to the mother lead to increased free radical production and correlate with perinatal outcomes.In the fetal-to-neonatal transition asphyxia is characterized by intermittent periods of hypoxia ischemia that may evolve to hypoxic ischemic encephalopathy associated with neurocognitive, motor, and neurosensorial impairment. Free radicals generated upon reoxygenation may notably increase brain damage. Hence, clinical trials have shown that the use of 100% oxygen given with positive pressure in the airways of the newborn infant during resuscitation causes more oxidative stress than using air, and increases mortality.Preterm infants are endowed with an immature lung and antioxidant system. Clinical stabilization of preterm infants after birth frequently requires positive pressure ventilation with a gas admixture that contains oxygen to achieve a normal heart rate and arterial oxygen saturation. In randomized controlled trials the use high oxygen concentrations (90% to 100% has caused more oxidative stress and clinical complications that the use of lower oxygen concentrations (30–60%. A correlation between the amount of oxygen received during resuscitation and the level of biomarkers of oxidative stress and clinical outcomes was established. Thus, based on clinical outcomes and analytical results of oxidative stress biomarkers relevant changes were introduced in the resuscitation policies. However, it should be underscored that analysis of oxidative stress biomarkers in biofluids has only been used in experimental and clinical research but not in clinical routine. The complexity of the technical procedures, lack of automation, and cost of these determinations have hindered the routine use of biomarkers in the clinical setting. Overcoming these technical and economical difficulties

Interaction of the pathogenic mold Aspergillus fumigatus with lung epithelial cells

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Nir eOsherov

2012-09-01

Full Text Available Aspergillus fumigatus is an opportunistic environmental mold that can cause severe allergic responses in atopic individuals and poses a life-threatening risk for severely immunocompromised patients. Infection is caused by inhalation of fungal spores (conidia into the lungs. The initial point of contact between the fungus and the host is a monolayer of lung epithelial cells. Understanding how these cells react to fungal contact is crucial to elucidating the pathobiology of Aspergillus-related disease states. The experimental systems, both in vitro and in vivo, used to study these interactions, are described. Distinction is made between bronchial and alveolar epithelial cells. The experimental findings suggest that lung epithelial cells are more than just innocent bystanders or a purely physical barrier against infection. They can be better described as an active extension of our innate immune system, operating as a surveillance mechanism that can specifically identify fungal spores and activate an offensive response to block infection. This response includes the internalization of adherent conidia and the release of cytokines, antimicrobial peptides and reactive oxygen species. In the case of allergy, lung epithelial cells can dampen an over-reactive immune response by releasing anti-inflammatory compounds such as kinurenine. This review summarizes our current knowledge regarding the interaction of A. fumigatus with lung epithelial cells. A better understanding of the interactions between A. fumigatus and lung epithelial cells has therapeutic implications, as stimulation or inhibition of the epithelial response may alter disease outcome.

Nontypeable Haemophilus influenzae induces sustained lung oxidative stress and protease expression.

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Paul T King

Full Text Available Nontypeable Haemophilus influenzae (NTHi is a prevalent bacterium found in a variety of chronic respiratory diseases. The role of this bacterium in the pathogenesis of lung inflammation is not well defined. In this study we examined the effect of NTHi on two important lung inflammatory processes 1, oxidative stress and 2, protease expression. Bronchoalveolar macrophages were obtained from 121 human subjects, blood neutrophils from 15 subjects, and human-lung fibroblast and epithelial cell lines from 16 subjects. Cells were stimulated with NTHi to measure the effect on reactive oxygen species (ROS production and extracellular trap formation. We also measured the production of the oxidant, 3-nitrotyrosine (3-NT in the lungs of mice infected with this bacterium. NTHi induced widespread production of 3-NT in mouse lungs. This bacterium induced significantly increased ROS production in human fibroblasts, epithelial cells, macrophages and neutrophils; with the highest levels in the phagocytic cells. In human macrophages NTHi caused a sustained, extracellular production of ROS that increased over time. The production of ROS was associated with the formation of macrophage extracellular trap-like structures which co-expressed the protease metalloproteinase-12. The formation of the macrophage extracellular trap-like structures was markedly inhibited by the addition of DNase. In this study we have demonstrated that NTHi induces lung oxidative stress with macrophage extracellular trap formation and associated protease expression. DNase inhibited the formation of extracellular traps.

Pulmonary microRNA profiling: implications in upper lobe predominant lung disease

OpenAIRE

Armstrong, David A.; Nymon, Amanda B.; Ringelberg, Carol S.; Lesseur, Corina; Hazlett, Haley F.; Howard, Louisa; Marsit, Carmen J.; Ashare, Alix

2017-01-01

Background Numerous pulmonary diseases manifest with upper lobe predominance including cystic fibrosis, smoking-related chronic obstructive pulmonary disease, and tuberculosis. Zonal hypoxia, characteristic of these pulmonary maladies, and oxygen stress in general is known to exert profound effects on various important aspects of cell biology. Lung macrophages are major participants in the pulmonary innate immune response and regional differences in macrophage responsiveness to hypoxia may co...

The role of reactive oxygen species (ROS) production on diallyl disulfide (DADS) induced apoptosis and cell cycle arrest in human A549 lung carcinoma cells

International Nuclear Information System (INIS)

Wu Xinjiang; Kassie, Fekadu; Mersch-Sundermann, Volker

2005-01-01

Diallyl disulfide (DADS), an oil soluble constituent of garlic (Allium sativum), has been reported to cause antimutagentic and anticarcinogenic effects in vitro and in vivo by modulating phases I and II enzyme activities. In recent years, several studies suggested that the chemopreventive effects of DADS can also be attributed to induction of cell cycle arrest and apoptosis in cancer cells. In the present study, we reported that DADS-induced cell cycle arrest at G2/M and apoptosis in human A549 lung cancer cells in a time- and dose-dependent manner. Additionally, a significant increase of intracellular reactive oxygen species (ROS) was induced in A549 cells less than 0.5 h after DADS treatment, indicating that ROS may be an early event in DADS-modulated apoptosis. Treatment of A549 cells with N-acetyl cysteine (NAC) completely abrogated DADS-induced cell cycle arrest and apoptosis. The result indicated that oxidative stress modulates cell proliferation and cell death induced by DADS

The role of reactive oxygen species (ROS) production on diallyl disulfide (DADS) induced apoptosis and cell cycle arrest in human A549 lung carcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Wu Xinjiang [Institute of Indoor and Environmental Toxicology, Faculty of Medicine, Justus-Liebig-University of Giessen, Aulweg 123, D-35385 Giessen (Germany); Kassie, Fekadu [Institute of Indoor and Environmental Toxicology, Faculty of Medicine, Justus-Liebig-University of Giessen, Aulweg 123, D-35385 Giessen (Germany); Mersch-Sundermann, Volker [Institute of Indoor and Environmental Toxicology, Faculty of Medicine, Justus-Liebig-University of Giessen, Aulweg 123, D-35385 Giessen (Germany)]. E-mail: Volker.mersch-sundermann@uniklinikum-giessen.de

2005-11-11

Diallyl disulfide (DADS), an oil soluble constituent of garlic (Allium sativum), has been reported to cause antimutagentic and anticarcinogenic effects in vitro and in vivo by modulating phases I and II enzyme activities. In recent years, several studies suggested that the chemopreventive effects of DADS can also be attributed to induction of cell cycle arrest and apoptosis in cancer cells. In the present study, we reported that DADS-induced cell cycle arrest at G2/M and apoptosis in human A549 lung cancer cells in a time- and dose-dependent manner. Additionally, a significant increase of intracellular reactive oxygen species (ROS) was induced in A549 cells less than 0.5 h after DADS treatment, indicating that ROS may be an early event in DADS-modulated apoptosis. Treatment of A549 cells with N-acetyl cysteine (NAC) completely abrogated DADS-induced cell cycle arrest and apoptosis. The result indicated that oxidative stress modulates cell proliferation and cell death induced by DADS.

Lung cancer

International Nuclear Information System (INIS)

Aisner, J.

1985-01-01

This book contains 13 chapters. Some of the chapter titles are: The Pathology of Lung Cancer; Radiotherapy for Non-Small-Cell Cancer of the Lung; Chemotherapy for Non-Small-Cell Lung Cancer; Immunotherapy in the Management of Lung Cancer; Preoperative Staging and Surgery for Non-Small-Cell Lung Cancer; and Prognostic Factors in Lung Cancer

Intravenous immunoglobulin prevents murine antibody-mediated acute lung injury at the level of neutrophil reactive oxygen species (ROS production.

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John W Semple

Full Text Available Transfusion-related acute lung injury (TRALI is a leading cause of transfusion-associated mortality that can occur with any type of transfusion and is thought to be primarily due to donor antibodies activating pulmonary neutrophils in recipients. Recently, a large prospective case controlled clinical study of cardiac surgery patients demonstrated that despite implementation of male donors, a high incidence of TRALI still occurred and suggested a need for additional interventions in susceptible patient populations. To examine if intravenous immunoglobulin (IVIg may be effective, a murine model of antibody-mediated acute lung injury that approximates human TRALI was examined. When BALB/c mice were injected with the anti-major histocompatibility complex class I antibody 34-1-2s, mild shock (reduced rectal temperature and respiratory distress (dyspnea were observed and pre-treatment of the mice with 2 g/kg IVIg completely prevented these symptoms. To determine IVIg's usefulness to affect severe lung damage, SCID mice, previously shown to be hypersensitive to 34-1-2s were used. SCID mice treated with 34-1-2s underwent severe shock, lung damage (increased wet/dry ratios and 40% mortality within 2 hours. Treatment with 2 g/kg IVIg 18 hours before 34-1-2s administration completely protected the mice from all adverse events. Treatment with IVIg after symptoms began also reduced lung damage and mortality. While the prophylactic IVIg administration did not affect 34-1-2s-induced pulmonary neutrophil accumulation, bone marrow-derived neutrophils from the IVIg-treated mice displayed no spontaneous ROS production nor could they be stimulated in vitro with fMLP or 34-1-2s. These results suggest that IVIg prevents murine antibody-mediated acute lung injury at the level of neutrophil ROS production and thus, alleviating tissue damage.

Surfactant treatment before first breath for respiratory distress syndrome in preterm lambs: comparison of a peptide-containing synthetic lung surfactant with porcine-derived surfactant

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van Zyl JM

2013-08-01

Full Text Available Johann M van Zyl,1 Johan Smith2 1Division of Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa; 2Department of Paediatrics and Child Health, Tygerberg Children's Hospital, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa Background: In a recent study utilizing a saline-lavaged adult rabbit model, we described a significant improvement in systemic oxygenation and pulmonary shunt after the instillation of a novel synthetic peptide-containing surfactant, Synsurf. Respiratory distress syndrome in the preterm lamb more closely resembles that of the human infant, as their blood gas, pH values, and lung mechanics deteriorate dramatically from birth despite ventilator support. Moreover, premature lambs have lungs which are mechanically unstable, with the advantage of being able to measure multiple variables over extended periods. Our objective in this study was to investigate if Synsurf leads to improved systemic oxygenation, lung mechanics, and histology in comparison to the commercially available porcine-derived lung surfactant Curosurf® when administered before first breath in a preterm lamb model. Materials and methods: A Cesarean section was performed under general anesthesia on 18 time-dated pregnant Dohne Merino ewes at 129–130 days gestation. The premature lambs were delivered and ventilated with an expiratory tidal volume of 6–8 mL/kg for the first 30 minutes and thereafter at 8–10 mL/kg. In a randomized controlled trial, the two surfactants tested were Synsurf and Curosurf®, both at a dose of 100 mg/kg phospholipids (1,2-dipalmitoyl-L-α-phosphatidylcholine; 90% in Synsurf, 40% in Curosurf®. A control group of animals was treated with normal saline. Measurements of physiological variables, blood gases, and lung mechanics were made before and after surfactant and saline replacement and at 15, 30, 45, 60, 90, 120, 180

Perioperative lung protective ventilation in obese patients.

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Fernandez-Bustamante, Ana; Hashimoto, Soshi; Serpa Neto, Ary; Moine, Pierre; Vidal Melo, Marcos F; Repine, John E

2015-05-06

The perioperative use and relevance of protective ventilation in surgical patients is being increasingly recognized. Obesity poses particular challenges to adequate mechanical ventilation in addition to surgical constraints, primarily by restricted lung mechanics due to excessive adiposity, frequent respiratory comorbidities (i.e. sleep apnea, asthma), and concerns of postoperative respiratory depression and other pulmonary complications. The number of surgical patients with obesity is increasing, and facing these challenges is common in the operating rooms and critical care units worldwide. In this review we summarize the existing literature which supports the following recommendations for the perioperative ventilation in obese patients: (1) the use of protective ventilation with low tidal volumes (approximately 8 mL/kg, calculated based on predicted -not actual- body weight) to avoid volutrauma; (2) a focus on lung recruitment by utilizing PEEP (8-15 cmH2O) in addition to recruitment maneuvers during the intraoperative period, as well as incentivized deep breathing and noninvasive ventilation early in the postoperative period, to avoid atelectasis, hypoxemia and atelectrauma; and (3) a judicious oxygen use (ideally less than 0.8) to avoid hypoxemia but also possible reabsorption atelectasis. Obesity poses an additional challenge for achieving adequate protective ventilation during one-lung ventilation, but different lung isolation techniques have been adequately performed in obese patients by experienced providers. Postoperative efforts should be directed to avoid hypoventilation, atelectasis and hypoxemia. Further studies are needed to better define optimum protective ventilation strategies and analyze their impact on the perioperative outcomes of surgical patients with obesity.

Telomere elongation protects heart and lung tissue cells from fatal damage in rats exposed to severe hypoxia.

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Wang, Yaping; Zhao, Zhen; Zhu, Zhiyong; Li, Pingying; Li, Xiaolin; Xue, Xiaohong; Duo, Jie; Ma, Yingcai

2018-02-17

The effects of acute hypoxia at high altitude on the telomere length of the cells in the heart and lung tissues remain unclear. This study aimed to investigate the change in telomere length of rat heart and lung tissue cells in response to acute exposure to severe hypoxia and its role in hypoxia-induced damage to heart and lung tissues. Forty male Wistar rats (6-week old) were randomized into control group (n = 10) and hypoxia group (n = 30). Rats in control group were kept at an altitude of 1500 m, while rats in hypoxia group were exposed to simulated hypoxia with an altitude of 5000 m in a low-pressure oxygen chamber for 1, 3, and 7 days (n = 10). The left ventricular and right middle lobe tissues of each rat were collected for measurement of telomere length and reactive oxygen species (ROS) content, and the mRNA and protein levels of telomerase reverse transcriptase (TERT), hypoxia-inducible factor1α (HIF-1α), and hypoxia-inducible factor1α (HIF-2α). Increased exposure to hypoxia damaged rat heart and lung tissue cells and increased ROS production and telomere length. The mRNA and protein levels of TERT and HIF-1α were significantly higher in rats exposed to hypoxia and increased with prolonged exposure; mRNA and protein levels of HIF-2α increased only in rats exposed to hypoxia for 7 days. TERT was positively correlated with telomere length and the levels of HIF-1α but not HIF-2α. Acute exposure to severe hypoxia causes damage to heart and lung tissues due to the production of ROS but promotes telomere length and adaptive response by upregulating TERT and HIF-1α, which protect heart and lung tissue cells from fatal damage.

Cytotoxic effects of air freshener biocides in lung epithelial cells.

Science.gov (United States)

Kwon, Jung-Taek; Lee, Mimi; Seo, Gun-Baek; Kim, Hyun-Mi; Shim, Ilseob; Lee, Doo-Hee; Kim, Taksoo; Seo, Jung Kwan; Kim, Pilje; Choi, Kyunghee

2013-09-01

This study evaluated the cytotoxicity of mixtures of citral (CTR) and either benzisothiazolinone (BIT, Mix-CTR-BIT) or triclosan (TCS, Mix-CTR-TCS) in human A549 lung epithelial cells. We investigated the effects of various mix ratios of these common air freshener ingredients on cell viability, cell proliferation, reactive oxygen species (ROS) generation, and DNA damage. Mix-CTR-BIT and Mix-CTR-TCS significantly decreased the viability of lung epithelial cells and inhibited cell growth in a dose-dependent manner. In addition, both mixtures increased ROS generation, compared to that observed in control cells. In particular, cell viability, growth, and morphology were affected upon increase in the proportion of BIT or TCS in the mixture. However, comet analysis showed that treatment of cells with Mix-CTR-BIT or Mix-CTR-TCS did not increase DNA damage. Taken together, these data suggested that increasing the content of biocides in air fresheners might induce cytotoxicity, and that screening these compounds using lung epithelial cells may contribute to hazard assessment.

The Preterm Lung and Airway: Past, Present, and Future

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Richard J. Martin

2013-08-01

Full Text Available The tremendous advancement that has occurred in neonatal intensive care over the last 40–50 years can be largely attributed to greater understanding of developmental pathobiology in the newborn lung. Nonetheless, this improved survival from respiratory distress syndrome has been associated with continuing longer-term morbidity in the form of bronchopulmonary dysplasia (BPD. As a result, neonatal lung injury is a renewed focus of scientific interest. The onset of such an injury may begin in the delivery room, and this has generated interest in minimizing oxygen therapy and aggressive ventilatory support during the transition from fetal to neonatal lung. Fortunately, antenatal steroid therapy and selective use of surfactant therapy are now widely practiced, although fine tuning of this therapy for selected populations is ongoing. Newer therapeutic approaches address many aspects of BPD, including the pro-inflammatory component that characterizes this disorder. Finally, there is a greater need to understand the epidemiology and pathogenesis of the longer-term respiratory morbidity, most notably asthma, that persists in the preterm survivors of neonatal intensive care.

Flavin-containing monooxygenase S-oxygenation of a series of thioureas and thiones

International Nuclear Information System (INIS)

Henderson, Marilyn C.; Siddens, Lisbeth K.; Krueger, Sharon K.; Stevens, J. Fred; Kedzie, Karen; Fang, Wenkui K.; Heidelbaugh, Todd; Nguyen, Phong; Chow, Ken; Garst, Michael; Gil, Daniel; Williams, David E.

2014-01-01

Mammalian flavin-containing monooxygenase (FMO) is active towards many drugs with a heteroatom having the properties of a soft nucleophile. Thiocarbamides and thiones are S-oxygenated to the sulfenic acid which can either react with glutathione and initiate a redox-cycle or be oxygenated a second time to the unstable sulfinic acid. In this study, we utilized LC–MS/MS to demonstrate that the oxygenation by hFMO of the thioureas under test terminated at the sulfenic acid. With thiones, hFMO catalyzed the second reaction and the sulfinic acid rapidly lost sulfite to form the corresponding imidazole. Thioureas are often pulmonary toxicants in mammals and, as previously reported by our laboratory, are excellent substrates for hFMO2. This isoform is expressed at high levels in the lung of most mammals, including non-human primates. Genotyping to date indicates that individuals of African (up to 49%) or Hispanic (2–7%) ancestry have at least one allele for functional hFMO2 in lung, but not Caucasians nor Asians. In this study the major metabolite formed by hFMO2 with thioureas from Allergan, Inc. was the sulfenic acid that reacted with glutathione. The majority of thiones were poor substrates for hFMO3, the major form in adult human liver. However, hFMO1, the major isoform expressed in infant and neonatal liver and adult kidney and intestine, readily S-oxygenated thiones under test, with K m s ranging from 7 to 160 μM and turnover numbers of 30–40 min −1 . The product formed was identified by LC–MS/MS as the imidazole. The activities of the mouse and human FMO1 and FMO3 orthologs were in good agreement with the exception of some thiones for which activity was much greater with hFMO1 than mFMO1

Flavin-containing monooxygenase S-oxygenation of a series of thioureas and thiones

Energy Technology Data Exchange (ETDEWEB)

Henderson, Marilyn C.; Siddens, Lisbeth K. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331-7301 (United States); Krueger, Sharon K. [The Linus Pauling Institute, Oregon State University, Corvallis, OR 97331-7301 (United States); Stevens, J. Fred [The Linus Pauling Institute, Oregon State University, Corvallis, OR 97331-7301 (United States); College of Pharmacy, Oregon State University, Corvallis, OR 97331-7301 (United States); Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331-7301 (United States); Kedzie, Karen [Department of Biological Sciences, Allergan, Inc., Irvine, CA 92623-9534 (United States); Fang, Wenkui K.; Heidelbaugh, Todd; Nguyen, Phong; Chow, Ken; Garst, Michael [Department of Chemical Sciences, Allergan, Inc., Irvine, CA 92623-9534 (United States); Gil, Daniel [Department of Biological Sciences, Allergan, Inc., Irvine, CA 92623-9534 (United States); Williams, David E., E-mail: david.williams@oregonstate.edu [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331-7301 (United States); The Linus Pauling Institute, Oregon State University, Corvallis, OR 97331-7301 (United States); Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331-7301 (United States)

2014-07-15

Mammalian flavin-containing monooxygenase (FMO) is active towards many drugs with a heteroatom having the properties of a soft nucleophile. Thiocarbamides and thiones are S-oxygenated to the sulfenic acid which can either react with glutathione and initiate a redox-cycle or be oxygenated a second time to the unstable sulfinic acid. In this study, we utilized LC–MS/MS to demonstrate that the oxygenation by hFMO of the thioureas under test terminated at the sulfenic acid. With thiones, hFMO catalyzed the second reaction and the sulfinic acid rapidly lost sulfite to form the corresponding imidazole. Thioureas are often pulmonary toxicants in mammals and, as previously reported by our laboratory, are excellent substrates for hFMO2. This isoform is expressed at high levels in the lung of most mammals, including non-human primates. Genotyping to date indicates that individuals of African (up to 49%) or Hispanic (2–7%) ancestry have at least one allele for functional hFMO2 in lung, but not Caucasians nor Asians. In this study the major metabolite formed by hFMO2 with thioureas from Allergan, Inc. was the sulfenic acid that reacted with glutathione. The majority of thiones were poor substrates for hFMO3, the major form in adult human liver. However, hFMO1, the major isoform expressed in infant and neonatal liver and adult kidney and intestine, readily S-oxygenated thiones under test, with K{sub m}s ranging from 7 to 160 μM and turnover numbers of 30–40 min{sup −1}. The product formed was identified by LC–MS/MS as the imidazole. The activities of the mouse and human FMO1 and FMO3 orthologs were in good agreement with the exception of some thiones for which activity was much greater with hFMO1 than mFMO1.

Do dental procedures affect lung function and arterial oxygen saturation in asthmatic patients?

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Magdy Mahmoud Emara

2013-04-01

Conclusion: Asthmatic patients may be at a higher risk of developing oxygen desaturation after dental procedures regardless of their type with and without local anesthesia and a decrease in PEF after dental procedures with local anesthesia.

Unintended inhalation of nitric oxide by contamination of compressed air: physiologic effects and interference with intended nitric oxide inhalation in acute lung injury.

Science.gov (United States)

Benzing, A; Loop, T; Mols, G; Geiger, K

1999-10-01

Compressed air from a hospital's central gas supply may contain nitric oxide as a result of air pollution. Inhaled nitric oxide may increase arterial oxygen tension and decrease pulmonary vascular resistance in patients with acute lung injury and acute respiratory distress syndrome. Therefore, the authors wanted to determine whether unintentional nitric oxide inhalation by contamination of compressed air influences arterial oxygen tension and pulmonary vascular resistance and interferes with the therapeutic use of nitric oxide. Nitric oxide concentrations in the compressed air of a university hospital were measured continuously by chemiluminescence during two periods (4 and 2 weeks). The effects of unintended nitric oxide inhalation on arterial oxygen tension (n = 15) and on pulmonary vascular resistance (n = 9) were measured in patients with acute lung injury and acute respiratory distress syndrome by changing the source of compressed air of the ventilator from the hospital's central gas supply to a nitric oxide-free gas tank containing compressed air. In five of these patients, the effects of an additional inhalation of 5 ppm nitric oxide were evaluated. During working days, compressed air of the hospital's central gas supply contained clinically effective nitric oxide concentrations (> 80 parts per billion) during 40% of the time. Change to gas tank-supplied nitric oxide-free compressed air decreased the arterial oxygen tension by 10% and increased pulmonary vascular resistance by 13%. The addition of 5 ppm nitric oxide had a minimal effect on arterial oxygen tension and pulmonary vascular resistance when added to hospital-supplied compressed air but improved both when added to tank-supplied compressed air. Unintended inhalation of nitric oxide increases arterial oxygen tension and decreases pulmonary vascular resistance in patients with acute lung injury and acute respiratory distress syndrome. The unintended nitric oxide inhalation interferes with the

Central extracorporeal membrane oxygenation requiring pulmonary arterial venting after near-drowning.

Science.gov (United States)

Kimura, Mitsutoshi; Kinoshita, Osamu; Fujimoto, Yoshifumi; Murakami, Arata; Shindo, Takahiro; Kashiwa, Koichi; Ono, Minoru

2014-02-01

Extracorporeal membrane oxygenation (ECMO) is an effective respiratory and circulatory support in patients in refractory cardiogenic shock or cardiac arrest. Peripheral ECMO sometimes requires left heart drainage; however, few reports state that pulmonary arterial (PA) venting is required during ECMO support. We present a case of a 14-year-old boy who required PA venting during ECMO support after resuscitation from near-drowning in freshwater. A biventricular assist device with an oxygenator implantation was intended on day 1; however, we were unable to proceed because of increasing of pulmonary vascular resistance from the acute lung injury. Central ECMO with PA venting was then performed. On day 13, central ECMO was converted to biventricular assist device with an oxygenator, which was removed on day 16. This case suggests that PA venting during ECMO support may be necessary in some cases of respiratory and circulatory failure with high pulmonary vascular resistance after near-drowning.

High Glucose Promotes Tumor Invasion and Increases Metastasis-Associated Protein Expression in Human Lung Epithelial Cells by Upregulating Heme Oxygenase-1 via Reactive Oxygen Species or the TGF-β1/PI3K/Akt Signaling Pathway

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Xiaowen Kang

2015-02-01

Full Text Available Background: Growing evidence indicates that heme oxygenase-1 (HO-1 is up-regulated in malignancies and subsequently alters tumor aggressiveness and various cancer-related factors, such as high glucose (HG levels. HO-1 expression can be induced when glucose concentrations are above 25 mM; however, the role of HO-1 in lung cancer patients with diabetes remains unknown. Therefore, in this study we investigated the promotion of tumor cell invasion and the expression of metastasis-associated proteins by inducing the up-regulation of HO-1 expression by HG treatment in A549 human lung epithelial cells. Methods: The expression of HO-1and metastasis-associated protein expression was explored by western blot analysis. HO-1 enzymatic activity, reactive oxygen species (ROS production and TGF-β1 production were examined by ELISA. Invasiveness was analyzed using a Transwell chamber. Results: HG treatment of A549 cells induced an increase in HO-1 expression, which was mediated by the HG-induced generation of reactive oxygen species (ROS and transforming growth factor-β1 (TGF-β1 in a concentration- and time-dependent manner. Following the increase in HO-1 expression, the enzymatic activity of HO-1 also increased in HG-treated cells. Pretreatment with N-acetyl-L-cysteine (NAC or with phosphatidylinositol 3-kinase (PI3K/Akt inhibitors attenuated the HG-induced increase in HO-1 expression. HG treatment of A549 cells enhanced the invasion potential of these cells, as shown with a Transwell assay, and increased metastasis-associated protein expression. However, HO-1 siRNA transfection significantly decreased these capabilities. Conclusion: this study is the first to demonstrate that HG treatment of A549 human lung epithelial cells promotes tumor cell invasion and increases metastasis-associated protein expression by up-regulating HO-1 expression via ROS or the TGF-β1/PI3K/Akt signaling pathway.

Interplay between the lung microbiome and lung cancer.

Science.gov (United States)

Mao, Qixing; Jiang, Feng; Yin, Rong; Wang, Jie; Xia, Wenjie; Dong, Gaochao; Ma, Weidong; Yang, Yao; Xu, Lin; Hu, Jianzhong

2018-02-28

The human microbiome confers benefits or disease susceptibility to the human body through multiple pathways. Disruption of the symbiotic balance of the human microbiome is commonly found in systematic diseases such as diabetes, obesity, and chronic gastric diseases. Emerging evidence has suggested that dysbiosis of the microbiota may also play vital roles in carcinogenesis at multiple levels, e.g., by affecting metabolic, inflammatory, or immune pathways. Although the impact of the gut microbiome on the digestive cancer has been widely explored, few studies have investigated the interplay between the microbiome and lung cancer. Some recent studies have shown that certain microbes and microbiota dysbiosis are correlated with development of lung cancer. In this mini-review, we briefly summarize current research findings describing the relationship between the lung microbiome and lung cancer. We further discuss the potential mechanisms through which the lung microbiome may play a role in lung carcinogenesis and impact lung cancer treatment. A better knowledge of the interplay between the lung microbiome and lung cancer may promote the development of innovative strategies for early prevention and personalized treatment in lung cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

DNA damage in lung after oral exposure to diesel exhaust particles in Big Blue (R) rats

DEFF Research Database (Denmark)

Müller, Anne Kirstine; Farombi, E.O.; Møller, P.

2004-01-01

Several chemical mutagens and carcinogens, including polycyclic aromatic hydrocarbons (PAHs) and nitrated PAHs, are adsorbed to the surface of diesel exhaust particles (DEP). DEP can induce formation of reactive oxygen species and cause oxidative DNA damage as well as bulky carcinogen DNA adducts....... Lung tissue is a target organ for DEP induced cancer following inhalation. Recent studies have provided evidence that the lung is also a target organ for DNA damage and cancer after oral exposure to other complex mixtures of PAHs. The genotoxic effect of oral administration of DEP was investigated...

Mitochondrial Complex IV Subunit 4 Isoform 2 Is Essential for Acute Pulmonary Oxygen Sensing.

Science.gov (United States)

Sommer, Natascha; Hüttemann, Maik; Pak, Oleg; Scheibe, Susan; Knoepp, Fenja; Sinkler, Christopher; Malczyk, Monika; Gierhardt, Mareike; Esfandiary, Azadeh; Kraut, Simone; Jonas, Felix; Veith, Christine; Aras, Siddhesh; Sydykov, Akylbek; Alebrahimdehkordi, Nasim; Giehl, Klaudia; Hecker, Matthias; Brandes, Ralf P; Seeger, Werner; Grimminger, Friedrich; Ghofrani, Hossein A; Schermuly, Ralph T; Grossman, Lawrence I; Weissmann, Norbert

2017-08-04

Acute pulmonary oxygen sensing is essential to avoid life-threatening hypoxemia via hypoxic pulmonary vasoconstriction (HPV) which matches perfusion to ventilation. Hypoxia-induced mitochondrial superoxide release has been suggested as a critical step in the signaling pathway underlying HPV. However, the identity of the primary oxygen sensor and the mechanism of superoxide release in acute hypoxia, as well as its relevance for chronic pulmonary oxygen sensing, remain unresolved. To investigate the role of the pulmonary-specific isoform 2 of subunit 4 of the mitochondrial complex IV (Cox4i2) and the subsequent mediators superoxide and hydrogen peroxide for pulmonary oxygen sensing and signaling. Isolated ventilated and perfused lungs from Cox4i2 -/- mice lacked acute HPV. In parallel, pulmonary arterial smooth muscle cells (PASMCs) from Cox4i2 -/- mice showed no hypoxia-induced increase of intracellular calcium. Hypoxia-induced superoxide release which was detected by electron spin resonance spectroscopy in wild-type PASMCs was absent in Cox4i2 -/- PASMCs and was dependent on cysteine residues of Cox4i2. HPV could be inhibited by mitochondrial superoxide inhibitors proving the functional relevance of superoxide release for HPV. Mitochondrial hyperpolarization, which can promote mitochondrial superoxide release, was detected during acute hypoxia in wild-type but not Cox4i2 -/- PASMCs. Downstream signaling determined by patch-clamp measurements showed decreased hypoxia-induced cellular membrane depolarization in Cox4i2 -/- PASMCs compared with wild-type PASMCs, which could be normalized by the application of hydrogen peroxide. In contrast, chronic hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling were not or only slightly affected by Cox4i2 deficiency, respectively. Cox4i2 is essential for acute but not chronic pulmonary oxygen sensing by triggering mitochondrial hyperpolarization and release of mitochondrial superoxide which, after conversion

Combined diffusion-weighted, blood oxygen level-dependent, and dynamic contrast-enhanced MRI for characterization and differentiation of renal cell carcinoma.

Science.gov (United States)

Notohamiprodjo, Mike; Staehler, Michael; Steiner, Nicole; Schwab, Felix; Sourbron, Steven P; Michaely, Henrik J; Helck, Andreas D; Reiser, Maximilian F; Nikolaou, Konstantin

2013-06-01

To investigate a multiparametric magnetic resonance imaging (MRI) approach comprising diffusion-weighted imaging (DWI), blood oxygen-dependent (BOLD), and dynamic contrast-enhanced (DCE) MRI for characterization and differentiation of primary renal cell carcinoma (RCC). Fourteen patients with clear-cell carcinoma and four patients with papillary RCC were examined with DWI, BOLD MRI, and DCE MRI at 1.5T. The apparent diffusion coefficient (ADC) was calculated with a monoexponential decay. The spin-dephasing rate R2* was derived from parametric R2* maps. DCE-MRI was analyzed using a two-compartment exchange model allowing separation of perfusion (plasma flow [FP] and plasma volume [VP]), permeability (permeability surface area product [PS]), and extravascular extracellular volume (VE). Statistical analysis was performed with Wilcoxon signed-rank test, Pearson's correlation coefficient, and receiver operating characteristic curve analysis. Clear-cell RCC showed higher ADC and lower R2* compared to papillary subtypes, but differences were not significant. FP of clear-cell subtypes was significantly higher than in papillary RCC. Perfusion parameters showed moderate but significant inverse correlation with R2*. VE showed moderate inverse correlation with ADC. Fp and Vp showed best sensitivity for histological differentiation. Multiparametric MRI comprising DWI, BOLD, and DCE MRI is feasible for assessment of primary RCC. BOLD moderately correlates to DCE MRI-derived perfusion. ADC shows moderate correlation to the extracellular volume, but does not correlate to tumor oxygenation or perfusion. In this preliminary study DCE-MRI appeared superior to BOLD and DWI for histological differentiation. Copyright © 2013 AUR. Published by Elsevier Inc. All rights reserved.

RC-3095, a Selective Gastrin-Releasing Peptide Receptor Antagonist, Does Not Protect the Lungs in an Experimental Model of Lung Ischemia-Reperfusion Injury

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Vera L. Oliveira-Freitas

2015-01-01

Full Text Available RC-3095, a selective GRPR antagonist, has been shown to have anti-inflammatory properties in different models of inflammation. However, its protective effect on lungs submitted to lung ischemia-reperfusion injury has not been addressed before. Then, we administrated RC-3095 intravenously before and after lung reperfusion using an animal model of lung ischemia-reperfusion injury (LIRI by clamping the pulmonary hilum. Twenty Wistar rats were subjected to an experimental model in four groups: SHAM, ischemia-reperfusion (IR, RC-Pre, and RC-Post. The final mean arterial pressure significantly decreased in IR and RC-Pre compared to their values before reperfusion (P<0.001. The RC-Post group showed significant decrease of partial pressure of arterial oxygen at the end of the observation when compared to baseline (P=0.005. Caspase-9 activity was significantly higher in the RC-Post as compared to the other groups (P<0.013. No significant differences were observed in eNOS activity among the groups. The groups RC-Pre and RC-Post did not show any significant decrease in IL-1β (P=0.159 and TNF-α (P=0.260, as compared to IR. The histological score showed no significant differences among the groups. In conclusion, RC-3095 does not demonstrate a protective effect in our LIRI model. Additionally, its use after reperfusion seems to potentiate cell damage, stimulating apoptosis.

Assessment of lung ventilation by MR imaging: current status and future perspectives

International Nuclear Information System (INIS)

Kauczor, Hans-Ulrich; Hanke, Alexander; Beek, Edwin J.R. van

2002-01-01

The aim of this paper is to review the present status of novel MRI techniques as a new important instrument for functional ventilation imaging. The current status and future perspectives in research and clinical applications are summarized. Morphological lung imaging is based on chest radiography and computed tomography, whereas scintigraphy is used for ventilation imaging. During recent years, MRI has emerged as a new means for functional imaging of ventilation. Aerosolized contrast agents and oxygen are used in proton imaging, whereas non-proton imaging relies on fluorine compounds, such as sulfur hexafluoride and perfluorcarbons, or on hyperpolarized noble gases, such as helium-3 or xenon-129. All the gases are administered as inhaled ''contrast agents'' for imaging of the airways and airspaces. In general, straightforward images demonstrate the homogeneity of ventilation in a breath-hold and allow for determination of ventilated lung. The different properties of the different compounds enable the measurement of additional functional parameters. They comprise airspace size, regional oxygen partial pressure, and analysis of ventilation distribution, ventilation/perfusion ratios, and gas exchange, including oxygen uptake. Novel MRI techniques provide the potential for functional imaging of ventilation. The next steps include definition of the value and the potential of the different contrast mechanisms as well as determination of the significance of the functional information with regard to physiological research and patient management in chronic obstructive pulmonary disease and others. (orig.)

Zaria Universal Oxygenator Holder phase I

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Sunday Adoga Edaigbini

2014-01-01

Full Text Available Introduction: The conduct of cardiopulmonary bypass surgery requires the use of equipment and devices like the oxygenator. The oxygenator comes in different makes and each manufacturer customizes the carrier or ′holder′ of this device specific to their design. Aim: This paper presents an innovation designed to overcome the need to purchase a different holder for every oxygenator thereby cutting the cost. Materials and Methods: A sheet of iron measuring 1.9 cm (width × 0.1 cm (thickness was used to design the holder circular main frame. Another sheet measuring 2 cm (width × 0.6 cm (thickness × 24 cm (length was used to construct a V-shaped handle with the arms of the V attached to the main frame 7 cm apart. At the narrow base of the handle is a latch requiring two 13-gauge screws to attach the holder to the heart-lung machine. Within the circumference of the main frame are four T-shaped side arms which grip the oxygenator; located at 2, 5, 7 and 11 O′clock positions. The stem of the T consist of a 0.6 cm (thickness × 13 cm (length rod drilled through the main frame. The cross of the T consists of variable lengths of the same sheet as the mainframe attached to the stem by a screw mechanism. At the base of the T, is attached a circular handle (4 cm in diameter made of 0.4 cm iron rod. Result: An oxygenator holder which weighs 1.75 kg with a total length of 54 cm (the diameter of the mainframe is 30 cm. Its advantages include (i affordability, (ii materials are locally accessible, (iii versatility (iv reproducibility. The disadvantages include, (i it requires some time to fit, (ii caution is required in fitting the oxygenator to avoid breakage, (iii a spanner is required to lock the latch. Conclusion: The concept of a universal holder is pertinent, especially in resource poor environments to avoid purchasing a new holder whenever the usual oxygenator common to the centre is unavailable. This device is amenable to further modifications to

Lung physiology and how aerosol deposits in the lungs

International Nuclear Information System (INIS)

Isawa, Toyoharu

1994-01-01

Weibel's morphologic data has been referred to not only for predicting aerosol deposition in the lungs but also lung physiology. During breathing the volume of air passes all through the mouth, the larynx, the trachea and the conductive airways into the alveolar space. When the airflow is not laminar and disturbed at the bifurcation or the irregular airway surface, eddies and turbulence occur there to result in deposition of aerosol by impaction or sedimentation. At high flow rates, there are more chances for turbulence to occur at these sites. Because the cross-section and volume of the subsequent airways increase, the flow rate decreases. It is worthwhile to remember that the pressure drop and resistance do not necessarily follow Poiseuille's law even in the large airways, and that with the turbulent flow the density of a gas plays an important role. If Poiseuille's law is applied, the resistance becomes sixteenfold when the radius of the airway segment is halved. When we breathe quietly, the flow in the trachea and the intermediate conductive airways is laminar and in very small conductive airways including the terminal bronchioles the airflow becomes so slow in velocity that the axial diffusion becomes more prominent, especially distal to the terminal bronchioles the cross-sectional area increases so much that molecular diffusion becomes more important. For gas transfer to occur, molecules of oxygen should pass through the surfactant layer, the alveolar epithelium, the basement membrane, the endothelium of the capillaries, and the plasma to get to the red blood cell to combine with hemoglobin

Induction of reactive oxygen species-stimulated distinctive autophagy by chelerythrine in non-small cell lung cancer cells.

Science.gov (United States)

Tang, Zheng-Hai; Cao, Wen-Xiang; Wang, Zhao-Yu; Lu, Jia-Hong; Liu, Bo; Chen, Xiuping; Lu, Jin-Jian

2017-08-01

Chelerythrine (CHE), a natural benzo[c]phenanthridine alkaloid, shows anti-cancer effect through a number of mechanisms. Herein, the effect and mechanism of the CHE-induced autophagy, a type II programmed cell death, in non-small cell lung cancer (NSCLC) cells were studied for the first time. CHE induced cell viability decrease, colony formation inhibition, and apoptosis in a concentration-dependent manner in NSCLC A549 and NCI-H1299 cells. In addition, CHE triggered the expression of phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II). The CHE-induced expression of LC3-II was further increased in the combination treatment with chloroquine (CQ), an autophagy inhibitor, and large amounts of red-puncta were observed in the CHE-treated A549 cells with stable expression of mRFP-EGFP-LC3, indicating that CHE induces autophagy flux. Silence of beclin 1 reversed the CHE-induced expression of LC3-II. Inhibition of autophagy remarkably reversed the CHE-induced cell viability decrease and apoptosis in NCI-H1299 cells but not in A549 cells. Furthermore, CHE triggered reactive oxygen species (ROS) generation in both cell lines. A decreased level of ROS through pretreatment with N-acetyl-L-cysteine reversed the CHE-induced cell viability decrease, apoptosis, and autophagy. Taken together, CHE induced distinctive autophagy in A549 (accompanied autophagy) and NCI-H1299 (pro-death autophagy) cells and a decreased level of ROS reversed the effect of CHE in NSCLC cells in terms of cell viability, apoptosis, and autophagy. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

[Peroxynitrite effect on the haemoglobin oxygen affinity in vitro in presence of different partial pressure of carbon dioxide].

Science.gov (United States)

Stepuro, T L; Zinchuk, V V

2011-08-01

Peroxynitrite (ONOO-) besides its toxic possesses regulatory action that includes the modulation of oxygen binding properties of blood. The aim of this work was to estimate ONOO- effect on the haemoglobin oxygen affinity (HOA) in vitro in presence of different partial pressure of carbon dioxide (CO2). The ONOO- presence in venous blood in conditions of hypercapnia induced oxyhaemoglobin dissociation curve shift leftward while in hypocapnic conditions the result of a different character was obtained. The revealed effect of ONOO- is realized, possibly, through various modifications ofhaemoglobin whose formation is dependent on the CO2 pressure. The ONOO- influences the HOA in different manner that can be important in regulation of blood oxygenation in lungs and maintenance of oxygen consumption in tissues.

Physiological closed-loop control in intelligent oxygen therapy: A review.

Science.gov (United States)

Sanchez-Morillo, Daniel; Olaby, Osama; Fernandez-Granero, Miguel Angel; Leon-Jimenez, Antonio

2017-07-01

Oxygen therapy has become a standard care for the treatment of patients with chronic obstructive pulmonary disease and other hypoxemic chronic lung diseases. In current systems, manually continuous adjustment of O 2 flow rate is a time-consuming task, often unsuccessful, that requires experienced staff. The primary aim of this systematic review is to collate and report on the principles, algorithms and accuracy of autonomous physiological close-loop controlled oxygen devices as well to present recommendations for future research and studies in this area. A literature search was performed on medical database MEDLINE, engineering database IEEE-Xplore and wide-raging scientific databases Scopus and Web of Science. A narrative synthesis of the results was carried out. A summary of the findings of this review suggests that when compared to the conventional manual practice, the closed-loop controllers maintain higher saturation levels, spend less time below the target saturation, and save oxygen resources. Nonetheless, despite of their potential, autonomous oxygen therapy devices are scarce in real clinical applications. Robustness of control algorithms, fail-safe mechanisms, limited reliability of sensors, usability issues and the need for standardized evaluating methods of assessing risks can be among the reasons for this lack of matureness and need to be addressed before the wide spreading of a new generation of automatic oxygen devices. Copyright © 2017 Elsevier B.V. All rights reserved.

Oxygen and oxidative stress in the perinatal period.

Science.gov (United States)

Torres-Cuevas, Isabel; Parra-Llorca, Anna; Sánchez-Illana, Angel; Nuñez-Ramiro, Antonio; Kuligowski, Julia; Cháfer-Pericás, Consuelo; Cernada, María; Escobar, Justo; Vento, Máximo

2017-08-01

Fetal life evolves in a hypoxic environment. Changes in the oxygen content in utero caused by conditions such as pre-eclampsia or type I diabetes or by oxygen supplementation to the mother lead to increased free radical production and correlate with perinatal outcomes. In the fetal-to-neonatal transition asphyxia is characterized by intermittent periods of hypoxia ischemia that may evolve to hypoxic ischemic encephalopathy associated with neurocognitive, motor, and neurosensorial impairment. Free radicals generated upon reoxygenation may notably increase brain damage. Hence, clinical trials have shown that the use of 100% oxygen given with positive pressure in the airways of the newborn infant during resuscitation causes more oxidative stress than using air, and increases mortality. Preterm infants are endowed with an immature lung and antioxidant system. Clinical stabilization of preterm infants after birth frequently requires positive pressure ventilation with a gas admixture that contains oxygen to achieve a normal heart rate and arterial oxygen saturation. In randomized controlled trials the use high oxygen concentrations (90% to 100%) has caused more oxidative stress and clinical complications that the use of lower oxygen concentrations (30-60%). A correlation between the amount of oxygen received during resuscitation and the level of biomarkers of oxidative stress and clinical outcomes was established. Thus, based on clinical outcomes and analytical results of oxidative stress biomarkers relevant changes were introduced in the resuscitation policies. However, it should be underscored that analysis of oxidative stress biomarkers in biofluids has only been used in experimental and clinical research but not in clinical routine. The complexity of the technical procedures, lack of automation, and cost of these determinations have hindered the routine use of biomarkers in the clinical setting. Overcoming these technical and economical difficulties constitutes a

Effect of protective lung ventilation strategy combined with lung recruitment maneuver in patients with acute respiratory distress syndrome (ARDS

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Sheng Yu

2017-01-01

Full Text Available Objective: To evaluate the efficacy and safety of protective lung ventilation strategy combined with lung recruitment maneuver (RM in the treatment patients with acute respiratory distress syndrome (ARDS.Methods: Totally 74 patients with ARDS admitted to the Department of Intensive Care Unit, Changshu Second People's Hospital in Jiangsu Province between September 2010 and June 2013 were selected and randomly divided into lung recruitment group and non-lung recruitment group, and the initial ventilation solution for both groups was synchronized intermittent mandatory ventilation (SIMV. For RM, SIMV mode (pressure control and pressure support was adopted. Positive end expiratory pressure (PEEP was increased by 5 cm H2O every time and maintained for 40-50 s before entering the next increasing period, and the peak airway pressure was kept below 45 cm H2O. After PEEP reached the maximum value, it was gradually reduced by 5 cm H2O every time and finally maintained at 15 cm H2O for 10 min.Results: A total of 74 patients with mean age of (49.0±18.6 years old were enrolled, 36 patients were enrolled in lung recruitment maneuver (RM group and 38 patients were enrolled into non-lung recruitment maneuver (non-RM group. 44 were male and accounted for 59.5% of all the patients. For the indicators such as PEEP, pressure support (PS, plateau airway pressure (Pplat, peak airway pressure (Ppeak, vital capacity (VC and fraction of inspired oxygen (FiO2, no statistical differences in the indicators were found between the RM group and non-RM group on D1, D3 and D7 (P>0.05, except that only FiO2 of RM group on D7 was significantly lower than that of non-RM group (47.2±10.0 vs. (52.2±10.5, P0.05. 28-day mortality, ICU mortality and in-hospital mortality were 25% vs. 28.9%, 25% vs. 26.3% and 36.1% vs. 39.5% respectively between RM group and non-RM group (all P>0.05.Conclusion: Protective lung ventilation strategy combined with lung recruitment maneuver can improve

Dying for Oxygen: Roles of Hypoxia Inducible Factor 2a and 3a during lung development

NARCIS (Netherlands)

Y. Huang (Yadi)

2012-01-01

textabstractCongenital lung lesions comprise a broad spectrum of rare but clinically significant developmental abnormalities, including congenital cystic adenomatoid malformation, bronchopulmonary sequestrations, congenital lobar emphysema, and bronchogenic cysts, which are commonly surgically

Humidification of Blow-By Oxygen During Recovery of Postoperative Pediatric Patients: One Unit's Journey.

Science.gov (United States)

Donahue, Suzanne; DiBlasi, Robert M; Thomas, Karen

2018-02-02

To examine the practice of nebulizer cool mist blow-by oxygen administered to spontaneously breathing postanesthesia care unit (PACU) pediatric patients during Phase one recovery. Existing evidence was evaluated. Informal benchmarking documented practices in peer organizations. An in vitro study was then conducted to simulate clinical practice and determine depth and amount of airway humidity delivery with blow-by oxygen. Informal benchmarking information was obtained by telephone interview. Using a three-dimensional printed simulation model of the head connected to a breathing lung simulator, depth and amount of moisture delivery in the respiratory tree were measured. Evidence specific to PACU administration of cool mist blow-by oxygen was limited. Informal benchmarking revealed that routine cool mist oxygenated blow-by administration was not widely practiced. The laboratory experiment revealed minimal moisture reaching the mid-tracheal area of the simulated airway model. Routine use of oxygenated cool mist in spontaneously breathing pediatric PACU patients is not supported. Copyright © 2017 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

Pulmonary lesion induced by low and high positive end-expiratory pressure levels during protective ventilation in experimental acute lung injury.

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Pássaro, Caroline P; Silva, Pedro L; Rzezinski, Andréia F; Abrantes, Simone; Santiago, Viviane R; Nardelli, Liliane; Santos, Raquel S; Barbosa, Carolina M L; Morales, Marcelo M; Zin, Walter A; Amato, Marcelo B P; Capelozzi, Vera L; Pelosi, Paolo; Rocco, Patricia R M

2009-03-01

To investigate the effects of low and high levels of positive end-expiratory pressure (PEEP), without recruitment maneuvers, during lung protective ventilation in an experimental model of acute lung injury (ALI). Prospective, randomized, and controlled experimental study. University research laboratory. Wistar rats were randomly assigned to control (C) [saline (0.1 mL), intraperitoneally] and ALI [paraquat (15 mg/kg), intraperitoneally] groups. After 24 hours, each group was further randomized into four groups (six rats each) at different PEEP levels = 1.5, 3, 4.5, or 6 cm H2O and ventilated with a constant tidal volume (6 mL/kg) and open thorax. Lung mechanics [static elastance (Est, L) and viscoelastic pressure (DeltaP2, L)] and arterial blood gases were measured before (Pre) and at the end of 1-hour mechanical ventilation (Post). Pulmonary histology (light and electron microscopy) and type III procollagen (PCIII) messenger RNA (mRNA) expression were measured after 1 hour of mechanical ventilation. In ALI group, low and high PEEP levels induced a greater percentage of increase in Est, L (44% and 50%) and DeltaP2, L (56% and 36%) in Post values related to Pre. Low PEEP yielded alveolar collapse whereas high PEEP caused overdistension and atelectasis, with both levels worsening oxygenation and increasing PCIII mRNA expression. In the present nonrecruited ALI model, protective mechanical ventilation with lower and higher PEEP levels than required for better oxygenation increased Est, L and DeltaP2, L, the amount of atelectasis, and PCIII mRNA expression. PEEP selection titrated for a minimum elastance and maximum oxygenation may prevent lung injury while deviation from these settings may be harmful.

LungMAP: The Molecular Atlas of Lung Development Program.

Science.gov (United States)

Ardini-Poleske, Maryanne E; Clark, Robert F; Ansong, Charles; Carson, James P; Corley, Richard A; Deutsch, Gail H; Hagood, James S; Kaminski, Naftali; Mariani, Thomas J; Potter, Steven S; Pryhuber, Gloria S; Warburton, David; Whitsett, Jeffrey A; Palmer, Scott M; Ambalavanan, Namasivayam

2017-11-01

The National Heart, Lung, and Blood Institute is funding an effort to create a molecular atlas of the developing lung (LungMAP) to serve as a research resource and public education tool. The lung is a complex organ with lengthy development time driven by interactive gene networks and dynamic cross talk among multiple cell types to control and coordinate lineage specification, cell proliferation, differentiation, migration, morphogenesis, and injury repair. A better understanding of the processes that regulate lung development, particularly alveologenesis, will have a significant impact on survival rates for premature infants born with incomplete lung development and will facilitate lung injury repair and regeneration in adults. A consortium of four research centers, a data coordinating center, and a human tissue repository provides high-quality molecular data of developing human and mouse lungs. LungMAP includes mouse and human data for cross correlation of developmental processes across species. LungMAP is generating foundational data and analysis, creating a web portal for presentation of results and public sharing of data sets, establishing a repository of young human lung tissues obtained through organ donor organizations, and developing a comprehensive lung ontology that incorporates the latest findings of the consortium. The LungMAP website (www.lungmap.net) currently contains more than 6,000 high-resolution lung images and transcriptomic, proteomic, and lipidomic human and mouse data and provides scientific information to stimulate interest in research careers for young audiences. This paper presents a brief description of research conducted by the consortium, database, and portal development and upcoming features that will enhance the LungMAP experience for a community of users. Copyright © 2017 the American Physiological Society.

An approach to interstitial lung disease in India

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J N Pande

2014-07-01

Full Text Available Interstitial lung diseases are common and have varied etiology, clinical presentation, clinical course and outcome. They pose a diagnostic challenge to physicians and pulmonologists. Patients present with dry cough, exertional dyspnoea, interstitial lesions on X-ray of the chest and restrictive ventilatory defect on spirometry. A sharp decline in oxygen saturation with exercise is characteristic. Careful evaluation of the history of the patient and physical examination help in narrowing down diagnostic probabilities. HRCT of the chest has emerged as an important tool in the evaluation of these disorders. Idiopathic Interstitial Pneumonias (IIP are a group of conditions which are classified into several types based on pathological features. Bronchoscopic procedures are helpful in diagnosis of certain disorders but are of limited value in classification of IIP which requires surgical biopsy. Usual Interstitial Pneumonia (UIP, also referred to as Idiopathic Pulmonary Fibrosis, has a progressive course and an unfavourable outcome. Certain new drugs have recently become available for treatment of UIP. Our approach towards diagnosis and management of interstitial lung diseases based on personal experience over the past three decades is reported here. Key words: Usual interstitial pneumonia – sarcoidosis – pneumoconiosis – bronchoscopy – lung biopsy 

Pulmonary scan in evaluating alveolar-interstitial syndrome in ER

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Giovanni Volpicelli

2006-10-01

Full Text Available Diffuse comet-tail artifacts at lung ultrasound are due to thickened interlobular septa and extravascular lung water. This condition is typical of the alveolar-interstitial syndrome due to pulmonary edema, diffuse parenchymal lung disease or ARDS. Aim of our study is to assess the potential of bedside lung ultrasound to diagnose the alveolar-interstitial syndrome in patients admitted to our emergency medicine unit. The ultrasonic feature of multiple and diffuse comet-tail artifacts was investigated during 5 months, in 121 consecutive patients admitted to our unit. Each patient was studied bedside in a supine position, by 8 antero-lateral pulmonary intercostal scans. Ultrasonic results were compared with chest radiograph and clinical outcome. Lung ultrasound showed a sensitivity of 84% and a specificity of 98% in diagnosing the radiologic alveolar-interstitial syndrome. Corresponding figures in the identification of a disease involving lung interstitium were 83% and 96%. These preliminary data show that the study of comet-tail artifacts at lung ultrasound is a method reasonably accurate for diagnosing the alveolar-interstitial syndrome at bedside. This conclusion opens the hypothesis of the usefullness of bedside lung ultrasound in the evaluation of dyspnoeic patients in the emergency setting.

Effects of simulated microgravity on surfactant and water balance of lung in animals with different resistance to stress

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Bryndina, Irina; Vasilieva, Natalia

Weightlessness is accompanied by redistribution of blood flow in lung, changes of lung volumes and gas exchange (Prisk et al., 2002; Grigoriev, Baranov, 2003). On the other hand, it is known that microgravity is considered as a kind of moderate stress (Grigoriev et al., 2004). Stress response may differ in animals resistant or vulnerable to stress (Sudakov, 2007). To study the effects of simulated microgravity upon lung, we used 20 male albino rats tested for behavior in the "open field" and than divided into active (stress resistant - SR ) and passive (stress vulnerable - CV) groups. Two mouse lines were used with similar goal - C57Bl/6 and BALB/c mice (n=16). According to data obtained earlier, BALB/c mice referred as more stress vulnerable, in contrast to C57BL/6 mice, which are considered to be relatively stress resistant (Flint et al., 2007). We have previously shown that changes in lung surfactant system after psychosocial stress or long-term immobilization are less pronounced in stress resistant rats (Vasilieva, Bryndina, 2012). The aim of this work is to study the properties and biochemical composition of pulmonary surfactant and lung water balance in rats and mice with different stress resistance in antiorthostatic suspension (AOS) of short and long duration. Simulated microgravity was reproduced according to procedure of Ilyin-Novikov in modification of Morey-Holton. The duration of exposure was 10 days for rats and 30 days for mice. The properties of pulmonary surfactant were assessed by the evaluation of surface activity (surface tension - ST), the content of total phospholipids (PL) and their fractions. Simultaneously we calculated the gravimetric water balance indices: lung coefficient, "dry residue" and wet-to-dry ratio. Total and extravascular lung fluid and pulmonary blood supply were estimated as well. The experiments demonstrated that there was a decrease of surface tension of surfactant films after 10-day AOS in both groups of rats (to a greater

High frequency oscillatory ventilation with lung volume optimization in very low birth weight newborns – a nine-year experience

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José Nona

2009-09-01

Full Text Available Objective: To evaluate the clinical outcome of very low birth weight newborns, submitted to high frequency oscillatory ventilation with a strategy of early lung volume optimization. Methods: Descriptive prospective study in a nine-year period, between 1999 January 1st to 2008 January 1st. All the very low birth weight newborns were born in Dr. Alfredo da Costa Maternity, Lisbon, Portugal, were admitted to the Neonatal Intensive Care Unit and submitted to high frequency oscillatory ventilation with early lung volume optimization; these newborns were followed-up since birth and their charts were analyzed periodically until hospital discharge. Rresults: From a total population of 730 very low birth weight inborns, 117 babies died (16% and 613 survived (84%. The median of birth weight was 975 g and the gestational age median was 28 weeks. For the survivors, the median ventilation and oxygenation times were 3 and 18 days, respectively. The incidence of chronic lung disease was 9.5%, with nine newborns discharged on oxygen therapy. The incidence of intraventricular hemorrhage III – IV (total population group was 11.5% and the incidence of retinopathy of prematurity grade 3 or higher was 8.0%. Cconclusions: High frequency oscillatory ventilation with early lung volume optimization strategy reduced the need of respiratory support, and improved pulmonary and global outcomes in very low birth weight infants with respiratory distress syndrome.

Lung volumes and emphysema in smokers with interstitial lung abnormalities.

Science.gov (United States)

Washko, George R; Hunninghake, Gary M; Fernandez, Isis E; Nishino, Mizuki; Okajima, Yuka; Yamashiro, Tsuneo; Ross, James C; Estépar, Raúl San José; Lynch, David A; Brehm, John M; Andriole, Katherine P; Diaz, Alejandro A; Khorasani, Ramin; D'Aco, Katherine; Sciurba, Frank C; Silverman, Edwin K; Hatabu, Hiroto; Rosas, Ivan O

2011-03-10

Cigarette smoking is associated with emphysema and radiographic interstitial lung abnormalities. The degree to which interstitial lung abnormalities are associated with reduced total lung capacity and the extent of emphysema is not known. We looked for interstitial lung abnormalities in 2416 (96%) of 2508 high-resolution computed tomographic (HRCT) scans of the lung obtained from a cohort of smokers. We used linear and logistic regression to evaluate the associations between interstitial lung abnormalities and HRCT measurements of total lung capacity and emphysema. Interstitial lung abnormalities were present in 194 (8%) of the 2416 HRCT scans evaluated. In statistical models adjusting for relevant covariates, interstitial lung abnormalities were associated with reduced total lung capacity (-0.444 liters; 95% confidence interval [CI], -0.596 to -0.292; Ppulmonary disease (COPD) (odds ratio, 0.53; 95% CI, 0.37 to 0.76; P<0.001). The effect of interstitial lung abnormalities on total lung capacity and emphysema was dependent on COPD status (P<0.02 for the interactions). Interstitial lung abnormalities were positively associated with both greater exposure to tobacco smoke and current smoking. In smokers, interstitial lung abnormalities--which were present on about 1 of every 12 HRCT scans--were associated with reduced total lung capacity and a lesser amount of emphysema. (Funded by the National Institutes of Health and the Parker B. Francis Foundation; ClinicalTrials.gov number, NCT00608764.).

Effect of CPAP in a Mouse Model of Hyperoxic Neonatal Lung Injury

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Reyburn, Brent; Fiore, Juliann M. Di; Raffay, Thomas; Martin, Richard J.; Y.S., Prakash; Jafri, Anjum; MacFarlane, Peter M.

2015-01-01

Background Continuous positive airway pressure [CPAP] and supplemental oxygen have become the mainstay of neonatal respiratory support in preterm infants. Although oxygen therapy is associated with respiratory morbidities including bronchopulmonary dysplasia [BPD], the long-term effects of CPAP on lung function are largely unknown. We used a hyperoxia-induced mouse model of BPD to explore the effects of daily CPAP during the first week of life on later respiratory system mechanics. Objective To test the hypothesis that daily CPAP in a newborn mouse model of BPD improves longer term respiratory mechanics. Methods Mouse pups from C57BL/6 pregnant dams were exposed to room air [RA] or hyperoxia [50% O2, 24hrs/day] for the first postnatal week with or without exposure to daily CPAP [6cmH2O, 3hrs/day]. Respiratory system resistance [Rrs] and compliance [Crs] were measured following a subsequent 2 week period of room RA recovery. Additional measurements included radial alveolar counts and macrophage counts. Results Mice exposed to hyperoxia had significantly elevated Rrs, decreased Crs, reduced alveolarization, and increased macrophage counts at three weeks compared to RA treated mice. Daily CPAP treatment significantly improved Rrs, Crs and alveolarization, and decreased lung macrophage infiltration in hyperoxia-exposed pups. Conclusions We have demonstrated that daily CPAP had a longer term benefit on baseline respiratory system mechanics in a neonatal mouse model of BPD. We speculate that this beneficial effect of CPAP was the consequence of a decrease in the inflammatory response and resultant alveolar injury associated with hyperoxic newborn lung injury. PMID:26394387

Measurement of lung function in awake 2-4-year-old asthmatic children during methacholine challenge and acute asthma

DEFF Research Database (Denmark)

Klug, B; Bisgaard, H

1996-01-01

This study evaluated three techniques for testing of lung function in young awake children. We compared measurements by the forced or impulse oscillation technique (IOS), the interrupter technique (IT), and transcutaneous measurements of oxygen (tcPo2) with concomitant measurements of specific ai...

Functional and biocompatibility performances of an integrated Maglev pump-oxygenator.

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Zhang, Tao; Cheng, Guangming; Koert, Andrew; Zhang, Juntao; Gellman, Barry; Yankey, G Kwame; Satpute, Aditee; Dasse, Kurt A; Gilbert, Richard J; Griffith, Bartley P; Wu, Zhongjun J

2009-01-01

To provide respiratory support for patients with lung failure, a novel compact integrated pump-oxygenator is being developed. The functional and biocompatibility performances of this device are presented. The pump-oxygenator is designed by combining a magnetically levitated pump/rotor with a uniquely configured hollow fiber membrane bundle to create an assembly free, ultracompact, all-in-one system. The hemodynamics, gas transfer and biocompatibility performances of this novel device were investigated both in vitro in a circulatory flow loop and in vivo in an ovine animal model. The in vitro results showed that the device was able to pump blood flow from 2 to 8 L/min against a wide range of pressures and to deliver an oxygen transfer rate more than 300 mL/min at a blood flow of 6 L/min. Blood damage tests demonstrated low hemolysis (normalized index of hemolysis [NIH] approximately 0.04) at a flow rate of 5 L/min against a 100-mm Hg afterload. The data from five animal experiments (4 h to 7 days) demonstrated that the device could bring the venous blood to near fully oxygen-saturated condition (98.6% +/- 1.3%). The highest oxygen transfer rate reached 386 mL/min. The gas transfer performance was stable over the study duration for three 7-day animals. There was no indication of blood damage. The plasma free hemoglobin and platelet count were within the normal ranges. No gross thrombus is found on the explanted pump components and fiber surfaces. Both in vitro and in vivo results demonstrated that the newly developed pump-oxygenator can achieve sufficient blood flow and oxygen transfer with excellent biocompatibility.

Gallic Acid Induces a Reactive Oxygen Species-Provoked c-Jun NH2-Terminal Kinase-Dependent Apoptosis in Lung Fibroblasts

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Chen, Chiu-Yuan; Chen, Kun-Chieh; Yang, Tsung-Ying; Liu, Hsiang-Chun; Hsu, Shih-Lan

2013-01-01

Idiopathic pulmonary fibrosis is a chronic lung disorder characterized by fibroblasts proliferation and extracellular matrix accumulation. Induction of fibroblast apoptosis therefore plays a crucial role in the resolution of this disease. Gallic acid (3,4,5-trihydroxybenzoic acid), a common botanic phenolic compound, has been reported to induce apoptosis in tumor cell lines and renal fibroblasts. The present study was undertaken to examine the role of mitogen-activated protein kinases (MAPKs) in lung fibroblasts apoptosis induced by gallic acid. We found that treatment with gallic acid resulted in activation of c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and protein kinase B (PKB, Akt), but not p38MAPK, in mouse lung fibroblasts. Inhibition of JNK using pharmacologic inhibitor (SP600125) and genetic knockdown (JNK specific siRNA) significantly inhibited p53 accumulation, reduced PUMA and Fas expression, and abolished apoptosis induced by gallic acid. Moreover, treatment with antioxidants (vitamin C, N-acetyl cysteine, and catalase) effectively diminished gallic acid-induced hydrogen peroxide production, JNK and p53 activation, and cell death. These observations imply that gallic acid-mediated hydrogen peroxide formation acts as an initiator of JNK signaling pathways, leading to p53 activation and apoptosis in mouse lung fibroblasts. PMID:23533505

Chorioamnionitis and subsequent lung function in preterm infants.

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Marcus H Jones

Full Text Available OBJECTIVE: To explore the relationship between prematurity, gender and chorioamnionitis as determinants of early life lung function in premature infants. METHODS: Placenta and membranes were collected from preterm deliveries (<37 weeks gestational age and evaluated for histological chorioamnionitis (HCA. Patients were followed and lung function was performed in the first year of life by Raised Volume-Rapid Thoracic Compression Technique. RESULTS: Ninety-five infants (43 males born prematurely (median gestational age 34.2 weeks were recruited. HCA was detected in 66 (69% of the placentas, and of these 55(58% were scored HCA Grade 1, and 11(12% HCA Grade 2. Infants exposed to HCA Grade 1 and Grade 2, when compared to those not exposed, presented significantly lower gestational ages, higher prevalence of RDS, clinical early-onset sepsis, and the use of supplemental oxygen more than 28 days. Infants exposed to HCA also had significantly lower maximal flows. There was a significant negative trend for z-scores of lung function in relation to levels of HCA; infants had lower maximal expiratory flows with increasing level of HCA. (p = 0.012 for FEF50, p = 0.014 for FEF25-75 and p = 0.32 for FEV0.5. Two-way ANOVA adjusted for length and gestational age indicated a significant interaction between sex and HCA in determining expiratory flows (p<0.01 for FEF50, FEF25-75 and p<0.05 for FEV0.5. Post-hoc comparisons revealed that female preterm infants exposed to HCA Grade 1 and Grade 2 had significant lower lung function than those not exposed, and this effect was not observed among males. CONCLUSIONS: Our findings show a sex-specific negative effect of prenatal inflammation on lung function of female preterm infants. This study confirms and expands knowledge upon the known association between chorioamnionitis and early life chronic lung disease.

Lung cancer mimicking lung abscess formation on CT images.

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Taira, Naohiro; Kawabata, Tsutomu; Gabe, Atsushi; Ichi, Takaharu; Kushi, Kazuaki; Yohena, Tomofumi; Kawasaki, Hidenori; Yamashiro, Toshimitsu; Ishikawa, Kiyoshi

2014-01-01

Male, 64 FINAL DIAGNOSIS: Lung pleomorphic carcinoma Symptoms: Cough • fever - Clinical Procedure: - Specialty: Oncology. Unusual clinical course. The diagnosis of lung cancer is often made based on computed tomography (CT) image findings if it cannot be confirmed on pathological examinations, such as bronchoscopy. However, the CT image findings of cancerous lesions are similar to those of abscesses.We herein report a case of lung cancer that resembled a lung abscess on CT. We herein describe the case of 64-year-old male who was diagnosed with lung cancer using surgery. In this case, it was quite difficult to distinguish between the lung cancer and a lung abscess on CT images, and a lung abscess was initially suspected due to symptoms, such as fever and coughing, contrast-enhanced CT image findings showing a ring-enhancing mass in the right upper lobe and the patient's laboratory test results. However, a pathological diagnosis of lung cancer was confirmed according to the results of a rapid frozen section biopsy of the lesion. This case suggests that physicians should not suspect both a lung abscesses and malignancy in cases involving masses presenting as ring-enhancing lesions on contrast-enhanced CT.

No effect of artificial gravity on lung function with exercise training during head-down bed rest

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Su, Longxiang; Guo, Yinghua; Wang, Yajuan; Wang, Delong; Liu, Changting

2016-04-01

The aim of this study is to explore the effectiveness of microgravity simulated by head-down bed rest (HDBR) and artificial gravity (AG) with exercise on lung function. Twenty-four volunteers were randomly divided into control and exercise countermeasure (CM) groups for 96 h of 6° HDBR. Comparisons of pulse rate, pulse oxygen saturation (SpO2) and lung function were made between these two groups at 0, 24, 48, 72, 96 h. Compared with the sitting position, inspiratory capacity and respiratory reserve volume were significantly higher than before HDBR (0° position) (P function over the HDBR observation time. Postural changes can lead to variation in lung volume and ventilation function, but a HDBR model induced no changes in pulmonary function and therefore should not be used to study AG countermeasures.

Lung Transplantation in Cystic Fibrosis and the Impact of Extracorporeal Circulation.

Science.gov (United States)

Jauregui, Alberto; Deu, Maria; Romero, Laura; Roman, Antonio; Moreno, Antonio; Armengol, Manuel; Solé, Juan

2018-03-10

Lung disease is the major cause of death among cystic fibrosis (CF) patients, affecting 80% of the population. The impact of extracorporeal circulation (ECC) during transplantation has not been fully clarified. This study aimed to evaluate the outcomes of lung transplantation for CF in a single center, and to assess the impact of ECC on survival. We performed a retrospective observational study of all trasplanted CF patients in a single center between 1992 and 2011. During this period, 64 lung transplantations for CF were performed. Five- and 10-year survival of trasplanted patients was 56.7% and 41.3%, respectively. Pre-transplantation supplemental oxygen requirements and non-invasive mechanical ventilation (NIMV) do not seem to affect survival (P=.44 and P=.63, respectively). Five- and 10-year survival among patients who did not undergo ECC during transplantation was 75.69% and 49.06%, respectively, while in those did undergo ECC during the procedure, 5- and 10-year survival was 34.14% and 29.87%, respectively (P=.001). PaCO 2 is an independent risk factor for the need for ECC. The survival rates of CF patients undergoing lung transplantation in our hospital are similar to those described in international registries. Survival is lower among patients receiving ECC during the procedure. PaCO 2 is a risk factor for the need for ECC during lung transplantation. Copyright © 2018 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.