ABSTRACT
We studied repeatedly the development of bronchial hyperreactivity (BHR) and bronchoalveolar lavage fluid (BALF) in rats undergoing different modes of ovalbumin exposures. Treatment was two intraperitoneal injections of ovalbumin in Groups 1-3, followed by one ovalbumin aerosolization in Groups 2 and 3, while rats in Group 4 received repeated ovalbumin aerosols after one single intraperitoneal injection. BHR was assessed longitudinally on day 0 (before treatment) and on day 14 (Groups 1 and 2) or 20 (Groups 3 and 4) and cellular influx was estimated from BALF. No BHR or change in BALF cellular profile was detected in Groups 1-3. However, the infiltration of inflammatory cells, associated with BHR (PC(100) 8.9+/-1.3 microg/kg vs. 4.2+/-1.1 microg/kg), was observed in Group 4. The BHR was always associated with increased number of eosinophils in the BALF. The substantial interindividual variability confirmed the need for a technique that permits follow-up of lung responsiveness and BALF profile. This approach evidenced strong associations between the severity of BHR and the eosinophilia.
Subject(s)
Airway Resistance/physiology , Bronchial Hyperreactivity/immunology , Bronchial Hyperreactivity/physiopathology , Bronchoalveolar Lavage Fluid , Ovalbumin/immunology , Respiratory Mechanics/physiology , Airway Resistance/drug effects , Animals , Bronchial Hyperreactivity/drug therapy , Bronchoconstrictor Agents/pharmacology , Bronchoconstrictor Agents/therapeutic use , Cell Count/methods , Disease Models, Animal , Dose-Response Relationship, Drug , Eosinophils/drug effects , Methacholine Chloride/pharmacology , Methacholine Chloride/therapeutic use , Neutrophils/drug effects , Ovalbumin/classification , Ovalbumin/pharmacology , Rats , Rats, Wistar , Time FactorsABSTRACT
Gram-negative bacterial endotoxin lipopolysaccharide (LPS) administration has been used as an animal model of sepsis-related acute lung injury and adult respiratory distress syndrome (ALI/ARDS). This paper describes the lung histology following lung injury induced by the intraperitoneal (i.p.) administration of endotoxin to rats, in comparison with earlier findings. ALI was induced by the i.p. administration of Esherichia coli LPS 2 (n = 8) or 3 (n = 5) mg/kg, whereas physiological saline was administered to the control animals (n = 5). Eighteen hours after the LPS injections, the animals were euthanized. The lungs and heart were removed in one block for histological study (hematoxylin and eosin [H&E], periodic acid-Schiff [PAS], Mason's trichrome; light microscopy). The lung tissue injury (bronchial wall, vessels, alveoli, interstitium) was graded via a scoring system (0 to 3+). The control animals showed intact lung tissue. Ten of the 13 LPS group had bronchus-associated lymphoid tissue (BALT) hyperplasia. Pathological signs of ALI/ARDS, diffuse alveolar damage (DAD) and emphysema, were observed in 5 and 8 cases, respectively. LPS injection induces primarily BALT hyperplasia and also the less characteristic DAD. This rat model is suitable for the investigation not only of ALI/ARDS but also of BALT hyperplasia occurring as a consequence of chronic pulmonary inflammatory processes.
Subject(s)
Acute Lung Injury/pathology , Lipopolysaccharides/pharmacology , Respiratory Distress Syndrome/pathology , Acute Lung Injury/chemically induced , Animals , Bronchial Diseases/pathology , Disease Models, Animal , Emphysema/etiology , Hyperplasia/etiology , Pulmonary Alveoli/pathology , Rats , Respiratory Distress Syndrome/chemically inducedABSTRACT
Lung function and bronchoalveolar lavage (BAL) fluid are commonly analyzed to assess the severity of lung disease in sacrificed animals. The input impedance of the respiratory system (Z(rs)) was measured and BAL fluid was collected in intubated, anesthetized, mechanically ventilated rats on three occasions 1 week apart. Measurements were performed in control animals (group C), while lung injury was induced in the other group (group LPS) by i.p. injection of lipopolysaccharide (LPS) before the second measurement. The airway resistance (R(aw)), tissue damping (G) and elastance (H) were determined from the Z(rs) spectra. The total cell counts (TC) from 0.3- to 0.4-ml BAL fluid were also determined. R(aw) exhibited no significant change in either group C (-6.7+/-3.6[S.E.]%) or LPS (-0.9+/-3.7%). Reproducible G and H values were obtained in group C (2.5+/-5.3%, -7.0+/-4.4%), while G and H increased in group LPS (18.4+/-6.5%, 14.9+/-13.8%, p<0.05). The changes in TC followed a similar pattern to those observed in G, with no change in group C (-7.9+/-30%), but with a marked increase in group LPS (580+/-456%, p<0.05). The method devised for repeated BAL measurements in another group of rats without intubation and muscle relaxant resulted in similar results in BAL profile. We conclude that longitudinal follow-up of the airway and tissue mechanics and inflammatory cells in the BAL fluid are feasible in rats. The current method allows an early detection of lung injury, even in a relatively mild form.
