Surfactant replacement therapy improves pulmonary mechanics in end-stage influenza A pneumonia in mice.

Surfactant replacement therapy may be a promising approach for treatment of respiratory failure caused by viral pneumonia. This study in mice demonstrates that during the development of lethal influenza A pneumonia, thorax-lung compliance (Ctl/kg) and lung volume at 5 cm H2O PEEP (V5/kg) significantly decrease (28 and 54%, respectively), whereas lung water content significantly increases (25%). Surfactant replacement therapy during the end stage of pneumonia significantly increases Ctl/kg (31%) and V5/kg (21%). Instillation of the vehicle for surfactant in control animals does not significantly affect Ctl/kg (5% decrease), but it significantly decreases V5/kg (25% decrease). Further, a new method for postmortem measurement of lung volumes in small laboratory animals based on Archimedes' principle is presented.

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.

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.

Oral immunization with polyvalent bacterial lysate and infection with Streptococcus pneumoniae: influence on interferon-gamma and PMN elastase concentrations in murine bronchoalveolar lavage fluid.

We recently demonstrated that oral immunization with a polyvalent bacterial lysate (Paspat oral) significantly reduces mortality rates in mice, infected with Streptococcus pneumoniae or influenza A virus. In this study it is demonstrated that oral immunization with the same bacterial lysate reduces the intrapulmonary inflammatory reaction to infection with S. pneumoniae, assessed by measurement of PMN elastase in bronchoalveolar lavage fluid. Furthermore, it is demonstrated that oral immunization with Paspat oral increases intrapulmonary IFN-gamma concentrations.

In vivo and in vitro inactivation of bovine surfactant by an anti-surfactant monoclonal antibody.

In this study the importance of a low-weight surfactant protein (11 kDa) is demonstrated by selectively blocking this protein with a monoclonal antibody. In adult rats respiratory failure was induced by repeated bronchoalveolar lavage to remove all pulmonary surfactant. It was shown that surfactant mixed with the antibody was not capable of restoring lung function when compared with surfactant alone or surfactant mixed with control serum. Using the pulsating bubble surfactometer, it could be demonstrated that surfactant mixed with this antibody had a significant higher minimum surface tension when compared with surfactant alone, or surfactant mixed with an unrelated mouse immunoglobulin G (IgG). The inhibition of surfactant function by the monoclonal antibody suggests the importance of the 11 kDa protein for normal surfactant function.

Intratracheal surfactant administration restores gas exchange in experimental adult respiratory distress syndrome associated with viral pneumonia.

The effect of intratracheal surfactant administration was studied in rats with adult respiratory distress syndrome associated with infection with nebulized Sendai virus. Thirty-six hours after infection, animals (n = 7) showed severely impaired gas exchange and acidosis during artificial ventilation (PaO2 = 152.2 +/- 18.7, PaCO2 = 65.3 +/- 19.2, pH = 7.26 +/- 0.11) with a pressure-controlled mode, standard frequency of 35/min, peak airway pressure of 15 cm H2O (15/0), inspiratory/expiratory ratio of 1:2, and F1O2 = 1. Gas exchange improved (P = 0.02) with increased ventilator pressures with PEEP (25/4). Forty-eight hours after infection, blood gas tensions could no longer be significantly improved by these same ventilator settings (PaO2 = 123.8 +/- 31.0, PaCO2 = 95.1 +/- 43.6, pH = 7.12 +/- 0.16, n = 9). At this time, surfactant replacement dramatically increased arterial oxygenation within 5 min (PaO2 = 389.4 +/- 79.9) and resulted in a fourfold increase in PaO2 within 2 h. It is concluded that intratracheal surfactant administration is a promising approach in the treatment of respiratory failure during adult respiratory distress syndrome associated with viral pneumonia.

Effects of antisurfactant antibodies on the course of mild respiratory distress syndrome.

The role of surfactant-associated proteins in surfactant function was studied by selectively blocking these proteins with monoclonal antibodies. Four monoclonal antibodies, M1, M2, M3, and M4 were identified and their reactivities examined by Western blot analysis. M1, M2, and M4 bind, respectively, 8-, 10- and both 10- and 34-kD proteins. M3 antibody did not recognize a protein as assayed by this technique. These antibodies were then administered intratracheally to adult rats that had been partially depleted of lung surfactant by broncholavage. None of these antibodies had any deleterious effect on pulmonary function. On the other hand, M4 antibody significantly improved gas exchange. Possible mechanisms by which antibody may effect such improvement are discussed.

Effect of surfactant replacement on Pneumocystis carinii pneumonia in rats.

The effect of intratracheal surfactant instillation on pulmonary function in rats with Pneumocystis carinii pneumonia (PCP) was investigated. In those animals which developed PCP with severe respiratory failure after administration of cortisone acetate s.c. over 8-12 weeks, pulmonary function was improved by surfactant instillation. PaO2 values 30 min after surfactant instillation were significantly higher compared to pretreatment values and also compared to PaO2 values of rats 30 min after receiving saline (482.9 mmHg +/- 44.7, 170.7 mmHg +/- 39.3 and 67.2 mmHg +/- 17.4, respectively). Histological examination showed that alveoli of rats with PCP which received no exogenous surfactant are filled with foamy edema, whereas after exogenous surfactant alveoli are stabilized and well-aerated. These results indicate that exogenous surfactant may help patients with severe PCP to overcome an acute stage of respiratory distress.

Protection against influenza A virus infection in mice by oral immunization with a polyvalent bacterial lysate.

A study is presented which investigated whether oral immunization with a polyvalent bacterial lysate (Paspat oral) can sufficiently enhance cell-mediated defense mechanisms to protect mice against influenza A virus infection. It was found that oral immunization reduced mortality due to influenza A infection with 15-70%, depending on the quantity of virus administered and and the moment of infection. Cyclosporin A severely reduced the protective effect of oral immunization, suggesting that a major effect of oral immunization in these studies is T-cell activation. The effect of oral immunization on macrophageal activity was evaluated by measuring cyclic-AMP in alveolar macrophages (AMs) obtained by bronchoalveolar lavage. Before infection, basal activity levels of AMs in immunized mice were significantly lower than in controls. Five days after infection, however, basal activity level of AMs in immunized mice was significantly higher than AM activity in controls. Stimulation of AMs with PGE2 significantly reduced cellular activity in both groups, before and after infection. However, cellular activity of AMs from immunized animals was less reduced than cellular activity of control macrophages. Activity of AMs of immunized animals was significantly more reduced by histamine than activity of control macrophages. It is concluded that oral immunization with Paspat oral stimulates T-cell-dependent immune mechanisms, resulting in protection against influenza A virus infection in mice.

Induction of a mucosal immune response by oral immunization. An overview.

The function of secretory antibodies is to prevent or limit the entrance of pathogens into the internal milieu of the body. The mucosal immune system may be stimulated by orally applied immunomodulators. Oral immunization circumvents the stringent criteria for injectable vaccines and large populations can be immunized simultaneously. Oral immunization may improve the chances in eliminating severe respiratory diseases, venereal diseases and infectious diarrhoea. In this overview the results of 144 international publications are discussed critically.

Oral immunization with a polyvalent bacterial lysate can reduce mortality by infection with S. pneumoniae or influenza A in mice.

We investigated the effect of oral immunization in of mice which were exposed to S. pneumoniae or influenza A. The results suggest that oral immunization reduces the mortality rate. We believe that this effect is partially due to nonspecific defense mechanisms.

Safety and efficacy of xenon in routine use as an inhalational anaesthetic.

40 patients (24 male, 16 female, aged 21-59 years) of American Society of Anesthesiologists class I or II who were undergoing routine surgery took part in a randomised, double-blind comparison of the anaesthetic efficacy and potency of xenon and nitrous oxide and their effects on the circulatory and respiratory systems. During anaesthesia, for each rise in blood pressure of more than 20% of the preanaesthetic (baseline) value, the patient received 0.1 mg fentanyl. The total amount of fentanyl required per patient was used as an index of the anaesthetic potency of the study gases. Patients in the xenon group required on average only 0.05 mg fentanyl, whereas those in the nitrous oxide group required 0.24 mg fentanyl; the duration of anaesthesia was similar in the two groups. Changes in blood pressure were significantly greater throughout the study in the nitrous oxide than in the xenon group. Thorax-lung compliance fell during the study period in the nitrous oxide group but not in the xenon group. Thus, xenon is a potent and effective anaesthetic which can be safely used under routine conditions.

Oral immunization with bacterial lysate against infection with Streptococcus pneumoniae in mice.

The protective effect of oral immunization against infection with Streptococcus pneumoniae was investigated in mice. Two bacterial lysates, one with an additional lysate of Candida albicans, were investigated. Intranasal inoculation of adult Balb-C mice with a S. pneumoniae type I strain resulted in a lethal infection, with deaths occurring from the 2nd until the 6th day after infection. Oral immunization resulted in a significant decrease in mortality rate (18-48% reduction). No significant difference in mortality rates was observed between the groups immunized with different lysates in the same concentrations.