Conclusion
Early Buse following injury and shock at a dose of at least 5mg/kg is required to maintain BM cellularity and HPC growth, prevent HPC mobilization, and reduce plasma G-CSF levels. This suggests that propranolol exerts its BM protective effect in a dose and time dependent fashion in a rodent model. Finally, heart rate may be a valuable clinical marker to assess effective dosing of propranolol.
Methods
Male Sprague-Dawley rats were subjected to a combined lung contusion (LC), hemorrhagic shock (HS) model ± BB. In our dose response experiments, animals received BB at 1, 2.5, 5, or 10 mg/kg immediately following resuscitation. In our therapeutic window experiments, following LCHS rats were given BB immediately, 1 hour, or 3 hours following resuscitation. BM and peripheral blood (PB) were collected in all animals to measure cellularity, BM HPC growth, circulating HPCs, and plasma G-CSF levels.
Results
Propranolol at 5 and 10 mg/kg significantly reduced HPC mobilization, restored BM cellularity and BM HPC growth, and decreased plasma G-CSF levels. Propranolol at 5 and 10 mg/kg also significantly decreased heart rate. When BB was administered beyond 1 hour after LCHS, its protective effects on cellularity, BM HPC growth, HPC mobilization, and plasma G-CSF levels were greatly diminished.