However, in order to achieve anti-inflammatory effects higher doses of these agents may be required than required for anticoagulant use.Second, due to differences between the studied drugs aerosol characteristics may differ between the treatment groups. Third, in our selleck chemicals study the agents were first administered before induction of pneumonia. Pre-treatment models are useful when exploring novel approaches and mechanisms, post-treatment models more closely resemble the clinical situation.The fact that the animals were treated intermittently in 6- or 24-hour intervals is another limitation to our study. Although this limited bronchoalveolar coagulation, continuous administration may have been more effective in order to achieve anti-inflammatory effects. Also, during nebulization the rats may have ingested some of the medication.

Plasma-derived AT and rh-aPC are most likely to be inactivated immediately by gastric enzymes. Heparin and danaparoid may be absorbed from the digestive tract in small quantities [39]. During each nebulization the animals were exposed to a constant oxygen flow (2 L/min) for a period of 10 minutes. The difference in treatment frequency between the AT-treated animals and the other groups therefore lead to a difference in exposure to oxygen, which in turn may have affected bacterial outgrowth as demonstrated previously [40]. This oxygen effect, however, cannot, explain the persistant inhibition of bacterial growth in vitro.Another limitation of the study is inherent to the fact that our rat model of pneumonia at best mimics the clinical situation.

In our model healthy animals of the same sex, age and weight are challenged with a high dose of viable log-phase bacteria inducing pneumonia over a short period of time in a reproducible manner, and clinical factors, such as antimicrobial therapy, mechanical ventilation, fluid management and other supportive interventions are not accounted for. Despite the limitations of our model, our results are in line with previous investigations [1].Although the incidence of bacteremia was higher in the heparin- and danaparoid-treated groups statistical significance was not reached. Our study, however, may have been underpowered to detect effects on bacterial dissemination.A limitation of our in vitro investigation is that S. pneumoniae has a different behavior in vitro compared with in vivo.

For example, bacteria have been observed to reach competence (i.e. obtain the ability to kill their non-competent siblings) in rich medium in vitro in early logarithmic growth, which is not seen Dacomitinib in vivo, where nutrients are generally limited [41,42]. As the peptide which induces competence, competence stimulating peptide, is cationic, it is not unthinkable that its normal activity is altered or diminished in the presence of SPS in our in vitro experiments.