RESUMEN
The effect of antibiotics on the acute lung injury induced by virulent Pseudomonas aeruginosa PA103 was quantitatively analyzed in a rat model. Lung injury was induced by the instillation of PA103 directly into the right lower lobes of the lungs of anesthetized rats. The alveolar epithelial injury, extravascular lung water, and total plasma equivalents were measured as separate, independent parameters of acute lung injury. Four hours after the instillation of PA103, all the parameters were increased linearly depending on the dose of P. aeruginosa. Next, we examined the effects of intravenously administered antibiotics on the parameters of acute lung injury in D-galactosamine-sensitized rats. One hour after the rats received 10(7) CFU of PA103, an intravenous bolus injection of aztreonam (60 mg/kg) or imipenem-cilastatin (30 mg/kg) was administered. Despite an MIC indicating resistance, imipenem-cilastatin improved all the measurements of lung injury; in contrast, aztreonam, which had an MIC indicating sensitivity, did not improve any of the lung injury parameters. The antibiotics did not generate different quantities of plasma endotoxin; therefore, endotoxin did not appear to explain the differences in lung injury. This in vivo model is useful to quantitatively compare the efficacies of parenteral antibiotic administration on Pseudomonas airspace infections.
Asunto(s)
Quimioterapia Combinada/uso terapéutico , Enfermedades Pulmonares/patología , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa/efectos de los fármacos , Animales , Aztreonam/farmacología , Aztreonam/uso terapéutico , Cilastatina/farmacología , Cilastatina/uso terapéutico , Combinación Cilastatina e Imipenem , Modelos Animales de Enfermedad , Combinación de Medicamentos , Quimioterapia Combinada/farmacología , Imipenem/farmacología , Imipenem/uso terapéutico , Enfermedades Pulmonares/microbiología , Masculino , Pruebas de Sensibilidad Microbiana , Monobactamas/farmacología , Monobactamas/uso terapéutico , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/patogenicidad , Ratas , Ratas Sprague-DawleyRESUMEN
The mechanical properties of frozen mannitol, L-iditol, dulcitol, and sorbitol solutions were measured as a function of temperature during warming (after freezing) using a thermal mechanical analyzer (TMA). The mannitol sample first underwent a contractive phase starting at 30 degrees C and ending at -25 degrees C. This was followed by an initially rapid, then less rapid expansive phase which continued until melting occurred. These events provide direct evidence that mannitol solutions undergo an expansion during warming after "fast" freezing and also corroborate the vial breakage observed when mannitol solutions are frozen and thawed or freeze-dried in glass vials. Of the other stereoisomers studied, only dulcitol had an expansive phase although at a slower rate than mannitol. Its solution was found to cause vial breakage also but only at fill volumes higher than mannitol fill volumes. TMA is a useful technique for studying dimensional changes in the frozen state, with important implications for solving vial breakage problems in freeze-drying.