L. E. Bible2, L. V. Pasupuleti2, A. V. Gore2, Z. C. Sifri2, A. M. Mohr1 1University Of Florida,General Surgery,Gainesville, FL, USA 2New Jersey Medical School,Newark, NJ, USA
Introduction: Following injury, hematopoietic progenitor cells (HPC) mobilize to the peripheral blood from the bone marrow (BM) and then home to the injured tissue. We have previously shown that propranolol decreases HPC mobilization and improves BM function following acute injury in rodent models. These acute injury models do not reflect the prolonged period of critical illness following severe traumatic injury. Using our unique lung injury (LC)/hemorrhagic shock (HS)/chronic restraint stress (CRS) model, we hypothesize that daily propranolol administration following LC/CRS and LCHS/CRS will reduce prolonged HPC mobilization without worsening lung healing.
Methods: Male Sprague-Dawley rats (n=5-9/group) underwent six days of CRS after undergoing LC or LCHS. CRS consists of a daily two hour period of restraint within a cylinder that is interrupted every 30 minutes by alarms and repositioning. Each day following their intervention, the rats received intraperitoneal propranolol (10mg/kg). On day seven the peripheral blood was analyzed for granulocyte-colony stimulating factor (G-CSF) via ELISA and for HPC mobilization using c-kit and CD71 flow cytometry, and the lungs were examined histologically to grade injury.
Results: As previously shown, seven days following LC and LCHS, the addition of CRS significantly increased HPC mobilization which is associated with persistently elevated G-CSF and worsened lung injury scores (Table). The addition of propranolol to LC/CRS and LCHS/CRS models significantly reduces HPC mobilization in peripheral blood (Table). In addition, the administration of propranolol following LC/CRS and LCHS/CRS restores G-CSF levels to that of naïve animals without worsening lung injury scores.
Conclusion: Daily propranolol administration following both LC/CRS and LCHS/CRS reduces prolonged HPC mobilization from the bone marrow and decreases plasma G-CSF levels. Despite the reduction of HPC mobilization, the lung healing did not worsen. Alleviating chronic stress with propranolol may be a future therapeutic target to improve healing following severe injury.
