Biomedical subjects

Mario Rüdiger

Publications and source records attributed to Mario Rüdiger.

At least 19 recordsLinked to original sources

PubMed2006

Perfluorocarbons decrease Chlamydophila pneumoniae-mediated inflammatory responses of rat type II pneumocytes in vitro.

Chlamydophila pneumoniae alter the expression of Toll-like receptor (TLR) 4 in alveolar type II (ATII)-cells. Subsequently nuclear factor kappaB (NF-kappaB) is activated and tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein 2 (MIP-2) are produced. Perfluorocarbons (PFC) are beneficial in animals with bacterial pneumonia and reduce production of TNF-alpha. Using isolated ATII-cells, it was studied whether PFC prevent C. pneumoniae-induced TNF-alpha and MIP-2 release and what the underlying pathway is. PF5080 preincubation prevented C. pneumoniae-induced secretion of TNF-alpha (43 +/- 10 versus 661 +/- 41 pg/mL) and MIP-2 (573 +/- 41 versus 4786 +/- 502 pg/mL). The C. pneumoniae-induced 2.2-fold increase of TNF-alpha Receptor 1 expression was reduced by PF5080. C. pneumoniae reduced cytoplasmatic IkappaBalpha (3.7 +/- 0.3 versus 14 +/- 1) and increased NF-kappaB p65 (31 +/- 7.5 versus 3.6 +/- 1.1) compared with control. PF5080 prevented NF-kappaB activation. TLR4 expression was 1.5-fold higher after C. pneumoniae incubation, but remained at control levels after PF5080 pretreatment. After 24 h of C. pneumoniae incubation, in 88 +/- 6% of cells bacteria were found in the perinuclear region and in 50% of these cells bacteria adhered to cellular surface. After PF5080 preincubation, C. pneumoniae were in 32 +/- 4% attached to and in 5 +/- 1% internalized in ATII-cells. Since PF5080 was found in ATII-cell membranes, PF5080 effect could be explained by an alteration of the cellular membrane, preventing activation of the inflammatory cascade.

Animals↗

PubMed2006

Observational study to compare the clinical efficacy of the natural surfactants Alveofact and Curosurf in the treatment of respiratory distress syndrome in premature infants.

INTRODUCTION: Natural surfactants have been shown to be superior to synthetic surfactants in the treatment of neonatal respiratory distress syndrome (RDS). In Germany, Alveofact (A) and Curosurf (C) are the most frequently used natural surfactant preparations. The aim of this retrospective, observational study was to compare the effects of A and C on gas exchange and outcome in premature infants. METHODS: During a 5-year period in our neonatal intensive care unit (NICU), 187 premature infants were treated with surfactant, with 82 receiving A and 105 receiving C. We recorded F(I)O(2) and gas exchange (PaO(2)/F(I)O(2) ratio, PaCO(2), SaO(2)) during the first 72h after surfactant application and the incidence of outcome parameters at day 28 (bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH grade III or IV), patent ductus arteriosus (PDA), pneumothorax, necrotizing enterocolites (NEC) and death). The differences between the patient groups were assessed by ANOVA or the calculation of relative risks. Bonferroni correction was used for multiple comparisons. RESULTS: There were no statistically significant differences between infants treated with A and C in mean gestational age (28.4 vs. 28.4 weeks), birth weight (1210 vs.1258 g) and time of first surfactant application (60 vs. 90 min postnatal). We observed no significant between group differences in course of F(I)O(2) and blood gases, or in incidence at day 28 of BPD (41.7% vs. 42.8%), IVH III/IV (18.3% vs. 14.3%), pneumothorax (9.8% vs. 4.8%), PDA (23.2% vs. 21.9%), PVL (7.3% vs. 9.5%) and death (17% vs. 17.1%). There were also no statistically significant differences in the subgroup of infants <28 weeks. The lower incidence of NEC in A compared with C (1.2% vs. 10.5%, P=0.01) was not statistically significant after Bonferroni correction. CONCLUSION: Independent of gestational age no significant difference in the clinical efficacy of A and C was observed.

Biological Products↗

PubMed2006

The Apgar score.

Explore the source record for details and available documents.

Apgar Score↗

PubMed2005

A survey of transcutaneous blood gas monitoring among European neonatal intensive care units.

BACKGROUND: PCO2 and PO2 are important monitoring parameters in neonatal intensive care units (NICU). Compared to conventional blood gas measurements that cause significant blood loss in preterms, transcutaneous (tc) measurements allow continuous, non-invasive monitoring of blood gas levels. The aim of the study was to survey the usage and opinions among German speaking NICUs concerning tc blood gas monitoring. METHODS: A questionnaire was developed and sent to 56 head nurses of different NICUs in Germany, Switzerland and Austria. RESULTS: A completely answered questionnaire was obtained from 41 NICUs. In two of these units tc measurements are not performed. In most NICUs (77%), both PtcO2 and PtcCO2 are measured simultaneously. Most units change the sensors every 3 hours; however, the recommended temperature of 44 degrees C is used in only 15% of units. In only 8% of units are arterial blood gases obtained to validate tc values. Large variations were found concerning the targeted level of oxygen saturation [median upper limit: 95% (range 80-100%); median lower limit: 86% (range 75-93%)] and PO2 [median upper limit: 70 mmHg (range 45-90 mmHg); median lower limit: 44 mmHg (range 30-60 mmHg)]. CONCLUSION: Our survey shows that the use of tc monitors remains widespread among German speaking NICUs, despite earlier data suggesting that their use had been abandoned in many NICUs worldwide. In addition, we suggest that the current method of monitoring oxygenation may not prevent hyperoxemia in preterm infants.

Austria↗

PubMed2005

Chlamydophila pneumoniae induces expression of toll-like receptor 4 and release of TNF-alpha and MIP-2 via an NF-kappaB pathway in rat type II pneumocytes.

BACKGROUND: The role of alveolar type II cells in the regulation of innate and adaptive immunity is unclear. Toll-like receptors (TLRs) have been implicated in host defense. The purpose of the present study was to investigate whether Chlamydophila pneumoniae (I) alters the expression of TLR2 and/orTLR4 in type II cells in a (II) Rho-GTPase- and (III) NF-kappaB-dependent pathway, subsequently (IV) leading to the production of (IV) pro-inflammatory TNF-alpha and MIP-2. METHODS: Isolated rat type II pneumocytes were incubated with C. pneumoniae after pre-treatment with calcium chelator BAPTA-AM, inhibitors of NF-kappaB (parthenolide, SN50) or with a specific inhibitor of the Rho-GTPase (mevastatin). TLR2 and TLR4 mRNA expressions were analyzed by PCR. Activation of TLR4, Rac1, RhoA protein and NF-kappaB was determined by Western blotting and confocal laser scan microscopy (CLSM) and TNF-alpha and MIP-2 release by ELISA. RESULTS: Type II cells constitutively expressed TLR4 and TLR2 mRNA. A prominent induction of TLR4 but not TLR2 mRNA was detected after 2 hours of incubation with C. pneumoniae. The TLR4 protein expression reached a peak at 30 min, began to decrease within 1-2 hours and peaked again at 3 hours. Incubation of cells with heat-inactivated bacteria (56 degrees C for 30 min) significantly reduced the TLR4 expression. Treated bacteria with polymyxin B (2 mug/ml) did not alter TLR4 expression. C. pneumoniae-induced NF-kappaB activity was blocked by TLR4 blocking antibodies. TLR4 mRNA and protein expression were inhibited in the presence of BAPTA-AM, SN50 or parthenolide. TNF-alpha and MIP-2 release was increased in type II cells in response to C. pneumoniae, whereas BAPTA-AM, SN50 or parthenolide decreased the C. pneumoniae-induced TNF-alpha and MIP-2 release. Mevastatin inhibited C. pneumoniae-mediated Rac1, RhoA and TLR4 expression. CONCLUSION: The TLR4 protein expression in rat type II cells is likely to be mediated by a heat-sensitive C. pneumoniae protein that induces a fast Ca2+-mediated NF-kappaB activity, necessary for maintenance of TLR4 expression and TNF-alpha and MIP-2 release through possibly Rac and Rho protein-dependent mechanism. These results indicate that type II pneumocytes play an important role in the innate pulmonary immune system and in inflammatory response mechanism of the alveolus.

Animals↗

PubMed2005

Contact of Chlamydophila pneumoniae with type II cell triggers activation of calcium-mediated NF-kappa B pathway.

Nuclear factor-kappa B (NF-kappa B) plays an important role in inflammation, proliferation and regulation of apoptosis. The purpose of the present study on type II cells was to investigate whether Chlamydophila pneumoniae contact induces (I) a Ca2+ release, that (II) disrupts F-actin/beta-tubulin cytoskeletal association with NF-kappa B/I kappa B alpha, leading to (III) a subsequent NF-kappa B activation. Incubation of rat type II pneumocytes with C. pneumoniae caused an intracellular calcium release within seconds. Confocal laser scanning microscopy (CLSM) revealed that bacterial contact with cell surface leads to a disappearance of the microvilli and disturbs the co-localization between F-actin and NF-kappa B (p65). Using semi-quantitative CLSM, we show that at 10-30 min I kappa B alpha was decreased and p65 or p50 was simultaneously translocated from cytoplasm to the nucleus, resulting in a 19-fold and 17-fold increase versus control cells. During this time no bacteria were internalized into type II cells. The pre-treatment of cells with BAPTA-AM inhibited C. pneumoniae-mediated calcium release. BAPTA-AM or SN50 prevented the C. pneumoniae-induced changes in F-actin cytoskeleton and inhibited NF-kappa B activation. Paclitaxel reduced C. pneumoniae-mediated changes of beta-tubulin cytoskeleton and activation of NF-kappa B. These results suggest that calcium-mediated cytoskeleton reorganization is involved in C. pneumoniae-induced NF-kappa B activation in type II cells.

Actins↗

PubMed2005

Inertance measurements by jet pulses in ventilated small lungs after perfluorochemical liquid (PFC) applications.

Perfluorochemical liquid (PFC) liquids or aerosols are used for assisted ventilation, drug delivery, lung cancer hyperthermia and pulmonary imaging. The aim of this study was to investigate the effect of PFC liquid on the inertance (I) of the respiratory system in newborn piglets using partial liquid ventilation (PLV) with different volumes of liquid. End-inspiratory (I(in)) and end-expiratory (I(ex)) inertance were measured in 15 ventilated newborn piglets (age < 12 h, mean weight 724 +/- 93 g) by brief flow pulses before and 80 min after PLV using a PFC volume (PF5080, 3 M) of 10 ml kg(-1) (N = 5) or 30 ml kg(-1) (N = 10). I was calculated from the imaginary part of the measured respiratory input impedance by regression analysis. Straight tubes with 2-4 mm inner diameter were used to validate the equipment in vitro by comparison with the analytically calculated values. In vitro measurements showed that the measuring error of I was <5% and that the reproducibility was better than 1.5%. The correlation coefficient of the regression model to determine I was >0.988 in all piglets. During gas ventilation, I(in) and I(ex) (mean +/- SD) were 31.7 +/- 0.8 Pa l(-1) s(2) and 33.3 +/- 2.1 Pa l(-1) s(2) in the 10 ml group and 32.4 +/- 0.8 Pa l(-1) s(2) and 34.0 +/- 2.5 Pa l(-1) s(2) in the 30 ml group. However, I of the 3 mm endotracheal tube (ETT) used was already 26.4 Pa l(-1) s(2) (about 80% of measured I). During PLV, there was a minimal increase of I(in) to 33.1 +/- 2.5 Pa l(-1) s(2) in the 10 ml group and to 34.5 +/- 2.7 Pa l(-1) s(2) in the 30 ml group. In contrast, the increase of I(ex) was dramatically larger (p < 0.001) to 67.7 +/- 13.3 Pa l(-1) s(2) and to 74.8 +/- 9.3 Pa l(-1) s(2) in the 10 ml and 30 ml groups, respectively. Measurements of I by jet pulses in intubated small animals are reproducible. PFC increases the respiratory inertance, but the magnitude depends considerably on its spatial distribution which changes during the breathing cycle. Large differences between I(in) and I(ex) are an indicator for liquid in airways or the ETT.

Administration, Inhalation↗

PubMed2005

Inhibition of TNFalpha in vivo prevents hyperoxia-mediated activation of caspase 3 in type II cells.

BACKGROUND: The mechanisms during the initial phase of oxygen toxicity leading to pulmonary tissue damage are incompletely known. Increase of tumour necrosis factor alpha (TNFalpha) represents one of the first pulmonary responses to hyperoxia. We hypothesised that, in the initial phase of hyperoxia, TNFalpha activates the caspase cascade in type II pneumocytes (TIIcells). METHODS: Lung sections or freshly isolated TIIcells of control and hyperoxic treated rats (48 hrs) were used for the determination of TNFalpha (ELISA), TNF-receptor 1 (Western blot) and activity of caspases 8, 3, and 9 (colorimetrically). NF-kappaB activation was determined by EMSA, by increase of the p65 subunit in the nuclear fraction, and by immunocytochemistry using a monoclonal anti-NF-kappaB-antibody which selectively stained the activated, nuclear form of NF-kappa B. Apoptotic markers in lung tissue sections (TUNEL) and in TIIcells (cell death detection ELISA, Bax, Bcl-2, mitochondrial membrane potential, and late and early apoptotic cells) were measured using commercially available kits. RESULTS: In vivo, hyperoxia activated NF-kappaB and increased the expression of TNFalpha, TNF-receptor 1 and the activity of caspase 8 and 3 in freshly isolated TIIcells. Intratracheal application of anti-TNFalpha antibodies prevented the increase of TNFRI and of caspase 3 activity. Under hyperoxia, there was neither a significant change of cytosolic cytochrome C or of caspase 9 activity, nor an increase in apoptosis of TIIcells. Hyperoxia-induced activation of caspase 3 gradually decreased over two days of normoxia without increasing apoptosis. Therefore, activation of caspase 3 is a temporary effect in sublethal hyperoxia and did not mark the "point of no return" in TIIcells. CONCLUSION: In the initiation phase of pulmonary oxygen toxicity, an increase of TNFalpha and its receptor TNFR1 leads to the activation of caspase 8 and 3 in TIIcells. Together with the hyperoxic induced increase of Bax and the decrease of the mitochondrial membrane potential, activation of caspase 3 can be seen as sensitisation for apoptosis. Eliminating the TNFalpha effect in vivo by anti-TNFalpha antibodies prevents the pro-apoptotic sensitisation of TIIcells.

Animals↗

PubMed2004

Naturally derived commercial surfactants differ in composition of surfactant lipids and in surface viscosity.

Pulmonary surfactant biophysical properties are best described by surface tension and surface viscosity. Besides lecithin, surfactant contains a variety of minor lipids, such as plasmalogens, polyunsaturated fatty acid-containing phospholipids (PUFA-PL), and cholesterol. Plasmalogens and cholesterol improve surface properties of lipid mixtures significantly. High PUFA-PL and plasmalogen content in tracheal aspirate of preterm infants reduces the risk of developing chronic lung disease. Different preparations are available for exogenous surfactant substitution; however, little is known about lipid composition and surface viscosity. Thus lipid composition and surface properties (measured by oscillating drop surfactometer) of three commercial surfactant preparations (Alveofact, Curosurf, Survanta) were compared. Lipid composition exhibited strong differences: Survanta had the highest proportion of disaturated PL and total neutral lipids and the lowest proportion of PUFA-PL. Highest plasmalogen and PUFA-PL concentrations were found in Curosurf (3.8 +/- 0.1 vs. 26 +/- 1 mol%) compared with Alveofact (0.9 +/- 0.3 vs. 11 +/- 1) and Survanta (1.5 +/- 0.2 vs. 6 +/- 1). In Survanta samples, viscosity increased >8 x 10(-6) kg/s at surface tension of 30 mN/m. Curosurf showed only slightly increased surface viscosity below surface tensions of 25 mN/m, and viscosity did not reach 5 x 10(-6) kg/s. By adding defined PL to Survanta, we obtained a Curosurf-like lipid mixture (without plasmalogens) that exhibited biophysical properties like Curosurf. Different lipid compositions could explain some of the differences in surface viscosity. Therefore, PL pattern and minor surfactant lipids are important for biophysical activity and should be considered when designing synthetic surfactant preparations.

Animals↗

PubMed2004

Changes in FiO2 affect PaO2 with minor alterations in cerebral concentration of oxygenated hemoglobin during liquid ventilation in healthy piglets.

OBJECTIVE: To measure the impact of changes in the fraction of inspired oxygen (FiO2) on systemic and cerebral oxygen supply in gas and liquid ventilated healthy animals. DESIGN: Interventional prospective animal study. SETTING: University research laboratory. PARTICIPANTS: Ten healthy, new-born piglets. INTERVENTIONS: Variations in FiO2 during conventional mechanical ventilation (CMV) followed by partial liquid ventilation (PLV) with two different filling volumes of PF 5080 (10 vs. 30 ml/kg). MEASUREMENTS AND RESULTS: Arterial blood gases were obtained 15 min after changing FiO2 and concentrations of cerebral oxygenated and total hemoglobin were determined with near infrared spectroscopy. During CMV an increase in FiO2 1.0 was associated with a constant rise in PaO2 but only a small increase in the cerebral concentration of oxygenated Hb. Initiation of PLV (at FiO2 of 1.0) caused a rapid drop in PaO2 towards values that were similar to CMV at FiO2 of 0.5. At FiO2 of 0.5 a reduction in oxygenated Hb was found in the 30 ml/kg filling group. Complete filling of the lungs with PFC caused a significant drop in total cerebral Hb concentration. CONCLUSIONS. According to our data, PLV in healthy lungs should be performed with a FiO2 of 1.0 and a small filling volume to avoid deterioration in cerebral oxygen supply.

Animals↗

PubMed2004

Perfluorocarbon species and nebulizer type influence aerosolization rate and particle size of perfluorocarbon aerosol.

PURPOSE: Aerosolization of perfluorocarbons (PFC) has been proven beneficial in vivo. The present in vitro study was performed to investigate, how PFC-aerosolization is affected by type of nebulizer and PFC properties. MATERIALS AND METHODS: Aerosolization rate was studied of 4 different PFC that were nebulized using 3 different jet nebulizers (operating at different flows: 4.1; 7.1; 13 l/min) and one ultrasonic nebulizer. Distribution of aerosol particle size was determined with a laser diffraction device. RESULTS: Between the studied nebulizers, considerable differences in the aerosolization rate were found. Aerosolization rate was significantly lower for PFOB (0.48-1.24 mL/min), when compared with PF 5080, RM 101 and FC 77 (1.33-4.75 mL/min). The ultrasonic nebulizer did not generate an aerosol but rather PFC vapor. Lowest mass median diameter (MMD) was found for PFOB and varied between the jet nebulizers from 2.2 and 3.7 microm, with a small range in particle size (maximum of 7.3 microm). FC 77 had highest MMD (3.5 to 9.2 microm) and greatest range of particle size of up to 13 microm. CONCLUSIONS: Our in vitro data show that aerosolization rate depends mainly on density of PFC and the flow of nebulizer. Particle size distribution is affected by PFC properties. Our result may explain controversial results of published in vivo studies.

Administration, Inhalation↗

PubMed2004

Measurements of evaporated perfluorocarbon during partial liquid ventilation by a zeolite absorber.

UNLABELLED: During partial liquid ventilation (PLV) the knowledge of the quantity of exhaled perfluorocarbon (PFC) allows a continuous substitution of the PFC loss to achieve a constant PFC level in the lungs. The aim of our in vitro study was to determine the PFC loss in the mixed expired gas by an absorber and to investigate the effect of the evaporated PFC on ventilatory measurements. METHOD: To simulate the PFC loss during PLV, a heated flask was rinsed with a constant airflow of 4 L min(-1) and PFC was infused by different speeds (5, 10, 20 mL h(-1)). An absorber filled with PFC selective zeolites was connected with the flask to measure the PFC in the gas. The evaporated PFC volume and the PFC concentration were determined from the weight gain of the absorber measured by an electronic scale. The PFC-dependent volume error of the CO2SMO plus neonatal pneumotachograph was measured by manual movements of a syringe with volumes of 10 and 28 mL with a rate of 30 min(-1). RESULTS: Under steady state conditions there was a strong correlation (r2 = 0.999) between the infusion speed of PFC and the calculated PFC flow rate. The PFC flow rate was slightly underestimated by 4.3% (p < 0.01). However, this bias was independent from PFC infusion rate. The evaporated PFC volume was precisely measured with errors < 1%. The volume error of the CO2SMO-Plus pneumotachograph increased with increasing PFC content for both tidal volumes (p < 0.01). However for PFC flow rates up to 20 mL/h the error of the measured tidal volumes was < 5%. CONCLUSIONS: PFC selective zeolites can be used to quantify accurately the evaporated PFC volume during PLV. With increasing PFC concentrations in the exhaled air the measurement errors of ventilatory parameters have to be taken into account.

Absorption↗

PubMed2004

Current limitations of volumetric capnography in surfactant-depleted small lungs.

OBJECTIVE: To investigate the suitability of volumetric capnography for assessing alveolar gas exchange in very small, surfactant-depleted lungs. DESIGN: Prospective animal trial. SETTINGS: Animal laboratory in a university setting. SUBJECTS: Twenty-one ventilated newborn piglets (age <12 hrs; median weight, 890 g; range, 560-1435 g). INTERVENTIONS: Bronchoalveolar lavage with instillation of 30 mL/kg normal saline. Ventilatory, circulatory, and lung mechanic variables were measured before and 0, 30, and 60 mins after bronchoalveolar lavage. MEASUREMENTS AND MAIN RESULTS: The alveolar deadspace fraction calculated by the Bohr and the Bohr/Enghoff equations increased three-fold (p<.001) after bronchoalveolar lavage in capnograms with distinct alveolar plateau, whereas in capnograms without alveolar plateau no statistical significant difference was seen. The main problem of capnography in small and especially stiff lungs was the high number of discarded records exclusively caused by a missing alveolar plateau. Rates of discarded records of capnography were 9.5% before lavage and increased (p<.01) to 52.4%, 47.6%,42.8% after bronchoalveolar lavage (0, 30, and 60 mins). With decreasing exhalation time, the number of discarded records increased significantly. No plateau was seen in >75% of recorded files with exhalation times <200 msecs. The effect of bronchoalveolar lavage on all variables measured was quite different, with the highest impact on required ventilatory settings, calculated oxygenation variables, and compliance. The effect of bronchoalveolar lavage on arterio-alveolar CO2 difference, CO2 production, and alveolar deadspace was much lower and statistically significant only in capnograms with alveolar plateau. CONCLUSIONS: Volumetric capnography is a useful tool to detect impaired alveolar gas exchange in surfactant-depleted small lungs. However, the method failed if there was no alveolar plateau in the volumetric capnogram especially in stiff lungs with short exhalation times.

Analysis of Variance↗

PubMed2004

Extrasystoles: side effect of kangaroo care?

OBJECTIVE: To present an unpublished reason for an arrhythmic electrocardiogram (ECG) recording during kangaroo care in a preterm infant. DESIGN: Case report. PATIENT: Preterm infant. MEASUREMENTS AND MAIN RESULTS: A preterm infant exhibited cardiac arrhythmia on the ECG monitor during kangaroo care, leading to interruption of kangarooing. Arrhythmia disappeared after placing the baby back into the incubator. The most likely reasons for arrhythmia were excluded. However, arrhythmia reappeared upon continuation of kangaroo care. ECG monitoring revealed the reason for the monitoring error. CONCLUSIONS: ECG monitoring during kangaroo care should cause error because of superimposed electric activity from the parent. Oxygen saturation represents a more reliable method of monitoring during kangaroo care.

Cardiac Complexes, Premature↗

PubMed2003

Aerosolization of perfluorocarbons during mechanical ventilation: an in vitro study.

OBJECTIVE: Inhalation of perfluorocarbons (PFC) has been suggested as a new and promising technique of PFC delivery in animal models of severe lung injury. However, no in vitro data were available on the efficacy of PFC aerosolization during mechanical ventilation. Therefore, the aim of the in vitro study was to investigate the influence of physical properties of PFC and the ventilatory settings on the amount of PFC delivered into the lung. DESIGN: In vitro lung model study. SETTING: University research laboratory. MEASUREMENTS AND RESULTS: Two different PFC (PF 5080 and PFOB) were aerosolized with a PariBoy jet nebulizer. Using a PFC selective adsorber, the effect of endotracheal tube size (2 mm and 3 mm diameter) on delivery of PFC was investigated. PFC delivery was estimated by continuous measurement of weight gain of the adsorber (adsorption rate). Finally, the influence of respiratory rate and tidal volume on adsorption rate (AR) was studied. AR was significantly reduced by a decreasing tube diameter and ranged from 1.45+/-0.03 ml/min (no tube) to 0.93+/-0.03 ml/min (2.0 mm) for PF 5080 (vapor pressure 51 mmHg) and from 0.49+/-0.06 ml/min to 0.32+/-0.04 ml/min for PFOB (11 mmHg). PFC-aerosolization into a ventilatory circuit with simulation of spontaneous tidal breathing (minute volume 600 ml) reduced AR to 0.16+/-0.02 ml/min. During mechanical ventilation, changes in respiratory rate and tidal volume, which reduce minute ventilation, caused a decrease in AR. CONCLUSION: The amount of PFC that can be delivered into the lung by aerosolization is very small and is influenced by PFC properties, tube size, and ventilatory settings.

Administration, Inhalation↗

PubMed2003

Chlamydia pneumoniae affect surfactant trafficking and secretion due to changes of type II cell cytoskeleton.

Understanding the surfactant dysfunction by gram-negative bacteria pulmonary infection, the intracellular fate of Chlamydia pneumoniae (Cpn), its interaction with uptake, recycling, and secretion of surfactant and with the cytoskeleton of type II pneumocytes was investigated. Bacteria colocalized with surfactant protein (SP)-A-mediated endocytosed lipid and early endosomes (EEA1- and Rab5-positive) after 3 and 6 h of infection. No specific contact with late endosomes (Rab7- and M6PR-positive), lysosomal, or lamellar body markers (CD63, 3C9) was found after 12 h of infection. In Cpn-infected cells, SP-A-mediated lipid uptake was significantly increased. After SP-A-mediated lipid uptake followed by "re-secretion," 90% of the internalized lipid remained intracellularly. SP-A and lipid did strongly colocalize with early endosomes. Internalized SP-A cannot be resecreted rapidly to plasma membrane, and lipid is not transported toward late endosomes (Rab7- and M6PR-positive) or lamellar bodies (CD63- and 3C9-positive). These results indicate that increased surfactant internalization is caused by an inhibition in intracellular surfactant transport. Accumulation of SP-A-mediated lipid was associated with changes in beta-tubulin. Increases in surfactant secretion were associated with changes in F-actin. We postulate that Cpn infection of type II cells causes changes of the cytoskeleton, and that these effects are associated with alterations in intracellular transport and secretion of surfactant.

Actin Cytoskeleton↗

PubMed2003

Perfluorocarbons are taken up by isolated type II pneumocytes and influence its lipid synthesis and secretion.

OBJECTIVE: Because alveoli fill with perfluorocarbons during liquid ventilation, an uptake of perfluorocarbons by type II pneumocytes can be postulated that might affect synthesis and secretion of pulmonary surfactant. The study was performed to answer the following questions: Do isolated type II pneumocytes take up perfluorocarbons? Do perfluorocarbons affect lipid synthesis of type II cells? Do perfluorocarbons change surfactant secretion of type II pneumocytes? DESIGN: Controlled experiments that used isolated type II pneumocytes. SETTING: Experimental laboratory of a university hospital. SUBJECTS: Male Wistar rats. INTERVENTIONS: To study perfluorocarbon uptake, isolated type II cells were incubated with fluorescence-labeled perfluorocarbons and examined with a laser scanning microscope. The effect of perfluorocarbons on biosynthesis of phospholipids and triglycerides was measured by incubating cells that were pulse-labeled with [H]-palmitic acid for 30 secs, with two different perfluorocarbons (PF 5080 or RM 101) for 10 mins. The effect of perfluorocarbon incubation on lipid secretion was studied by transmission electron microscopy. To quantify secretion, adherent type II pneumocytes (containing radioactively labeled phospholipids) were incubated with perfluorocarbons, and extra- and intracellular radioactivity was measured. MEASUREMENTS AND MAIN RESULTS: We found a significant uptake of labeled perfluorocarbons into lamellar bodies within 10 mins. Both perfluorocarbon species significantly (p <.05) reduced the biosynthesis of phospholipids when compared with control. Perfluorocarbon incubation did not affect mitochondrial activity, tested by MitoTracker staining. Transmission electron microscopy revealed changes that suggest an increased secretion of surfactant by type II cells. Studies with radioactively labeled surfactant revealed a significantly (p <.01) higher amount of extracellular lipids after RM 101 and PF 5080 treatment (RM 101, 17 +/- 7.9%; PF 5080, 9 +/- 1.9%) compared with control (5.3 +/- 1.9%). CONCLUSIONS: Our results suggest that perfluorocarbons are taken up by type II pneumocytes and cause an increased secretion of surfactant, despite a relative reduction in the synthesis of phospholipids.

Animals↗

PubMed2003

Measurement of changes in respiratory mechanics during partial liquid ventilation using jet pulses.

OBJECTIVE: To compare the changes in respiratory mechanics within the breathing cycle in healthy lungs between gas ventilation and partial liquid ventilation using a special forced-oscillation technique. DESIGN: Prospective animal trial. SETTINGS: Animal laboratory in a university setting. SUBJECTS: A total of 12 newborn piglets (age, <12 hrs; mean weight, 725 g). INTERVENTIONS: After intubation and instrumentation, lung mechanics of the anesthetized piglets were measured by forced-oscillation technique at the end of inspiration and the end of expiration. The measurements were performed during gas ventilation and 80 mins after instillation of 30 mL/kg perfluorocarbon PF 5080. MEASUREMENTS AND MAIN RESULTS: Brief flow pulses (width, 10 msec; peak flow, 16 L/min) were generated by a jet generator to measure the end-inspiratory and the end-expiratory respiratory input impedance in the frequency range of 4-32 Hz. The mechanical variables resistance, inertance, and compliance were determined by model fitting, using the method of least squares. At least in the lower frequency range, respiratory mechanics could be described adequately by an RIC single-compartment model in all piglets. During gas ventilation, the respiratory variables resistance and inertance did not differ significantly between end-inspiratory and end-expiratory measurements (mean [sd]: 4.2 [0.7] vs. 4.1 [0.6] kPa x L(-1) x sec, 30.0 [3.2] vs. 30.7 [3.1] Pa x L(-1) x sec2, respectively), whereas compliance decreased during inspiration from 14.8 (2.0) to 10.2 (2.4) mL x kPa(-1) x kg(-1) due to a slight lung overdistension. During partial liquid ventilation, the end-inspiratory respiratory mechanics was not different from the end-inspiratory respiratory mechanics measured during gas ventilation. However, in contrast to gas ventilation during partial liquid ventilation, compliance rose from 8.2 (1.0) to 13.0 (3.0) mL x kPa(-1) x kg(-1) during inspiration. During expiration, when perfluorocarbon came into the upper airways, both resistance and inertance increased considerably (mean with 95% confidence interval) by 34.3% (23.1%-45.8%) and 104.1% (96.0%-112.1%), respectively. CONCLUSIONS: The changes in the respiratory mechanics within the breathing cycle are considerably higher during partial liquid ventilation compared with gas ventilation. This dependence of lung mechanics from the pulmonary gas volume hampers the comparability of dynamic measurements during partial liquid ventilation, and the magnitude of these changes cannot be detected by conventional respiratory-mechanical analysis using time-averaged variables.

Airway Resistance↗