ABSTRACT
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.
Subject(s)
Parainfluenza Virus 1, Human/pathogenicity , Paramyxoviridae Infections/etiology , Pneumonia, Viral/etiology , Respiratory Distress Syndrome/etiology , Respiratory Insufficiency/etiology , Animals , Disease Models, Animal , Male , Pulmonary Gas Exchange/drug effects , Pulmonary Surfactants/therapeutic use , Rats , Rats, Sprague-Dawley , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/physiopathology , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/physiopathologyABSTRACT
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.
Subject(s)
Paramyxoviridae Infections/complications , Pneumonia, Viral/complications , Pulmonary Gas Exchange/drug effects , Pulmonary Surfactants/therapeutic use , Respiratory Distress Syndrome/complications , Animals , Hydrogen-Ion Concentration , Lung/pathology , Male , Parainfluenza Virus 1, Human , Paramyxoviridae Infections/pathology , Pneumonia, Viral/physiopathology , Pulmonary Surfactants/administration & dosage , Rats , Rats, Inbred Strains , Respiratory Distress Syndrome/drug therapy , TracheaABSTRACT
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.
