A Novel Pleiotropic Anti-Inflammatory Drug to Reduce ARDS Incidence
Abstract
In year one our trauma/hemorrhagic shock (T/HS) injury model was highly effective at causing acute respiratory distress syndrome(ARDS) in all Control groups. However, TRB-N0224 treatment, although it lowered both plasma and bronchoalveolar lavage (BALF) IL-6 levels, resulted in no significant improvement in clinical outcome, which was assessed by lung function (i.e lung compliance or PaO2/FiO2 ratio) or histopathology. We postulated that there were two problems with the study: 1) the stress of the gavage was an additional trauma in an already severe T/HS model and 2) the T/HS model causes severe damage to the gut, which significantly reduced TRB-N0224 adsorption. To solve these problems we requested a one-year no-cost extension to use an intravenous formulation of TRB-N0224 that, if our postulate was correct, would solve both of our problems. The results from these experiments were encouraging but not dramatic. The IP formulation of TRB-N0224 significantly reduced the Active and Total MMP-9 in the Bronchoalveolar Fluid (BALF) and Plasma and Interleukin-6 in the BALF and plasma, which translated into a reduction in lung histopathology. Although these are very positive results all of the rats in the TRBN0224treatment group died before the end of the 4-hr study period. It is possible that our T/HS model was too severe and that if we reduced the length of HS the positive molecular signal would result in reduced mortality.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2018
- Accession Number
- AD1064856
Entities
People
- Gary F Nieman
Organizations
- State University of New York