I. G. Alamo1, K. B. Kannan1, T. J. Loftus1, H. Ramos1, P. A. Efron1, A. Mohr1 1University Of Florida,Trauma,Gainesville, FL, USA
Introduction:
Following severe trauma, critically injured patients develop a persistent injury-associated anemia associated with a prolonged hypercatecholamine state. Propranolol has been previously been shown to improve bone marrow (BM) progenitor cell growth, reduce hematopoietic progenitor cell (HPC) mobilization, and improve anemia. Clonidine, an alpha 2-adrenergic agonist, is sympatholytic and inhibits norepinephrine release. This study sought to investigate the effect of daily clonidine administration on BM dysfunction in a combined lung contusion (LC), hemorrhagic shock (HS), and chronic stress (CS) rodent model.
Methods:
Male Sprague-Dawley rats (n=4-6/group) were subjected to CS, LCHS, and LCHS/CS ± daily clonidine (75ug/kg). Animals underwent two hours of daily restraint stress until the day of sacrifice (day 7). BM cellularity and growth of BM CFU-GEMM, BFU-E and CFU-E colonies were assessed. Peripheral blood was analyzed for hemoglobin (Hgb) and flow cytometry for mobilization of HPCs (CD71+CD117+). Data was presented as mean±SD; *p<0.05 vs. untreated counterpart by t-test.
Results:
Seven days after LCHS alone, BM cellularity and CFU-GEMM, BFU-E, and CFU-E growth remains 10-15% suppressed as compare to naïve (Table). With the addition of clonidine, BM cellularity improved by 19% and BFU-E and CFU-E colony growth was restored to naïve levels. In the more severe and clinically relevant model of LCHS/CS, after seven days there is a 27% suppression of BM cellularity and persistent anemia. Daily administration of clonidine following LCHS/CS resulted in a 26% improvement in BM cellularity and a significant recovery in BM CFU-GEMM, BFU-E, and CFU-E colony growth by 16, 37, and 32% (Table). Furthermore, the use of clonidine following LCHS/CS led to an 85% decrease in HPC mobilization to the peripheral blood and significantly improved Hgb (13.9±0.5* vs. 10.6±0.8 g/dL).
Conclusion:
Following lung contusion, hemorrhagic shock, and chronic stress, the use of clonidine increased BM cellularity, prevented prolonged suppression of BM HPC growth, reduced mobilization of HPC, and improved anemia. Clonidine has been shown to be protective by reducing the sympathetic effects on BM function following trauma and chronic stress. Therefore, reduction of the prolonged hypercatecholamine state following trauma is therapeutic goal that is beneficial for BM function.
