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Biomedical subjects

B Lachmann

Publications and source records attributed to B Lachmann.

At least 19 recordsLinked to original sources

Dose-response comparisons of five lung surfactant factor (LSF) preparations in an animal model of adult respiratory distress syndrome (ARDS).

1. We have examined the effects of five different lung surfactant factor (LSF) preparations in the rat lung lavage model. In this model repetitive lung lavage leads to lung injury with some similarities to adult respiratory distress syndrome with poor gas exchange and protein leakage into the alveolar spaces. These pathological sequelae can be reversed by LSF instillation soon after lavage. 2. The tested LSF preparations were: two bovine: Survanta and Alveofact: two synthetic: Exosurf and a protein-free phospholipid based LSF (PL-LSF) and one Recombinant LSF at doses of 25, 50 and 100 mg kg-1 body weight and an untreated control group. 3. Tracheotomized rats (10-12 per dose) were pressure-controlled ventilated (Siemens Servo Ventilator 900C) with 100% oxygen at a respiratory rate of 30 breaths min-1, inspiration expiration ratio of 1:2, peak inspiratory pressure (PIP) of 28 cmH2O at positive end-expiratory pressure (PEEP) of 8 cmH2O. Two hours after LSF administration, PEEP and in parallel PIP was reduced from 8 to 6 (1st reduction), from 6 to 3 (2nd reduction) and from 3 to 0 cmH2O (3rd reduction). 4. Partial arterial oxygen pressure (PaO2, mmHg) at 5 min and 120 min after LSF administration and during the 2nd PEEP reduction (PaO2(PEEP23/3)) were used for statistical comparison. All LSF preparations caused a dose-dependent increase for the PaO2(120'), whereas during the 2nd PEEP reduction only bovine and recombinant LSF exhibited dose-dependency. Exosurf did not increase PaO2 after administration of the highest dose. At the highest dose Exosurf exerted no further improvement but rather a tendency to relapse. The bovine and the Recombinant LSF are superior to both synthetic LSFpreparations.5. In this animal model and under the described specific ventilatory settings, even between bovine LSFpreparations there are detectable differences that are pronounced when compared to synthetic LSFwithout any surfactant proteins. We conclude that the difference between bovine and synthetic LSFpreparations can be overcome by addition of the surfactant protein C.

Animals

Influence of pulmonary surfactant on in vitro bactericidal activities of amoxicillin, ceftazidime, and tobramycin.

The influence of a natural pulmonary surfactant on antibiotic activity was investigated to assess the possible use of exogenous surfactant as a vehicle for antibiotic delivery to the lung. The influence of surfactant on the bactericidal activity of amoxicillin was tested against Staphylococcus aureus and Streptococcus pneumoniae, and the influence of surfactant on the activities of ceftazidime and tobramycin was tested against Klebsiella pneumoniae, Pseudomonas aeruginosa, S. aureus, and S. pneumoniae. In vitro antibiotic activity was determined by killing curve studies in media with and without surfactant. Amoxicillin and ceftazidime activities were not changed in the presence of surfactant, except for a decreased killing rate of S. pneumoniae by ceftazidime in medium with additional rabbit serum. In contrast, killing curves with low concentrations of tobramycin (0.25x and 1x the MIC) showed a decreased level of activity of tobramycin against all pathogens tested in the presence of surfactant. With higher tobramycin concentrations (4x the MIC) killing rates were decreased less or were unchanged in the presence of surfactant. Concluding from the results of the study, both amoxicillin and ceftazidime can be combined with surfactant without the loss of activity. For mixing surfactant with tobramycin, dosages should be adjusted to overcome the partial inactivation of tobramycin by surfactant.

Amoxicillin

Respiratory and haemodynamic effects of conventional volume controlled PEEP ventilation, pressure regulated volume controlled ventilation and low frequency positive pressure ventilation with extracorporeal carbon dioxide removal in pigs with acute ARDS.

The purpose of this study was to evaluate whether any benefit of low frequency positive pressure ventilation with extracorporeal carbon dioxide removal (LFPPV-ECCO2R) existed over either volume controlled ventilation (VCV) with measured best-PEEP or pressure regulated volume controlled ventilation (PRVCV) with an inspiration/expiration (I/E) ratio of 4:1, with respect to arterial oxygenation, lung mechanics and haemodynamics, in acute respiratory failure. Fifteen adult pigs were used for the study. Respiratory failure was induced by surfactant depletion by repeated lung lavage. The different therapeutic approaches were applied randomly to each pig for 1 h. Measurements of gas exchange, airway pressures and haemodynamics were performed during ventilatory and haemodynamic steady state. Paco2 was kept constant in all modes. At almost similar total-PEEP, Pao2 values were significantly higher with LFPPV-ECCO2R compared to VCV with best-PEEP. Peak inspiratory pressure (PIP) and intrapulmonary pressure amplitude defined as the difference between PIP and total-PEEP were significantly lower with PRVCV and LFPPV-ECCO2R compared to VCV with best-PEEP. There was no significant difference between the modes concerning cardiocirculatory parameters. PRVCV with I/E ratio of 4:1 and LFPPV-ECCO2R proved to be better modes to achieve better gas exchange and lower PIP at lower intrapulmonary pressure amplitudes. It is concluded that PRVCV is an adequate form of treatment under these experimental conditions imitating acute respiratory failure, without necessitating other invasive measures.

Acute Disease

Improvement of pulmonary gas exchange after surfactant replacement in rats with Pneumocystis carinii pneumonia.

The effect of intratracheal surfactant instillation on pulmonary function in rats with pneumocystis carinii pneumonia (PCP) was investigated. In these animals which developed PCP with severe respiratory failure after s.c. administration of cortisone acetate over 8-12 weeks, pulmonary function could be improved by surfactant instillation, as measured by an increase in PaO2. Histological examination showed that alveoli of rats with PCP which received no surfactant treatment are filled with foamy edema, whereas after surfactant treatment alveoli are stabilized and well-aerated. These results indicate that surfactant therapy could be used in patients with severe PCP to overcome an acute stage of respiratory distress while at the same time surfactant could serve as a carrier substance for antimicrobial drugs to attain high intra-alveolar and low systemic antimicrobial drug concentrations.

Animals

Acute respiratory failure during pneumonia induced by Sendai virus.

In this study a model of acute respiratory failure due to viral pneumonia in rats, closely resembling ARDS, is presented. Severe respiratory failure with lethal outcome in four days was induced by infection concentrated Sendai virus aerosol. This model permits evaluation of different therapeutical approaches for improving gas exchange during ARDS. Furthermore, preliminary results of surfactant substitution therapy in this model are presented.

Animals