Biomedical subjects

Wolfram Burkhardt

Publications and source records attributed to Wolfram Burkhardt.

6 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↗

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↗

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

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↗

PubMed2002

Cerebral oxygenation is affected by filling mode and perfluorochemical volume in partial liquid ventilation of healthy piglets.

Intrapulmonary administration of perfluorochemicals (PFC) has been suggested for reasons other than respiratory insufficiency. PFC application has been described to affect cerebral Hb concentration, however, data for healthy lungs are missing. Newborn piglets were randomized into 3 groups (30-ml slow-filling, 10-ml slow-filling and 30-ml rapid-filling), orally intubated and mechanically ventilated. Partial liquid ventilation (PLV) was initiated by filling the lung with PF5080 (10 or 30 ml/kg) at a rate of 1.5 ml/min (slow filling) or within 45 s (rapid filling). Vital signs, blood gases, tidal volume (VT) and changes in the cerebral concentration of oxygenated hemoglobin (HbO(2)) and total Hb were determined for up to 20 min. Rapid administration of PFC caused an immediate drop in HbO(2), PaO(2) and VT. The concentration of oxygenated and total Hb increased thereafter and remained high. We found a slow increase in PaCO(2), HbO(2) and total Hb in the 30-ml slow-filling group, but almost no changes in the 10-ml slow filling group (except for a decrease in PaO(2)). According to our data, PLV with 10 ml/kg should be preferred since cerebral alterations are minimal. If complete filling of the lung is needed PFC should be administered slowly to minimize side effects.

Animals↗