I. G. Alamo1, K. B. Kannan1, T. J. Loftus1, H. Ramos1, P. A. Efron1, A. M. Mohr1, A. M. Mohr1 1University Of Florida,Trauma,Gainesville, FL, USA
Introduction: Following severe injury, a norepinephrine (NE)-mediated hypercatecholamine state develops that is associated with dysfunctional erythroid maturation and manifests as a persistent injury-associated anemia. Previously, the reduction of the effects of NE, by propranolol (BB) or clonidine, has led to improvements in erythroid bone marrow function. The erythropoietin receptor (EPOr) is necessary for the maturation of early to late erythroid progenitor cells. In a clinically relevant rodent of lung contusion (LC)/hemorrhagic shock (HS)/chronic stress (CS), we hypothesize that both BB and clonidine improve erythroid maturation by modulating the expression of EPOr.
Methods: Propranolol (BB) a non-selective beta adrenergic blocker, was given to competitively block NE binding following LCHS and LCHS/CS ± BB (10mg/kg) in male Sprague Dawley rodents. To centrally deplete NE release, clonidine, an alpha 2-agonist, was also given to rats following LCHS and LCHS/CS ± clonidine (75ug/kg). Animals underwent two hours of daily restraint stress until the day of sacrifice on day 7. Bone marrow EPOr mRNA and EPOr protein expression as well as bone marrow BFU-E and CFUE-E colony growth were assessed. Data was presented as mean±SD; *p<0.05 vs. untreated counterpart by t-test.
Results:Daily administration of BB following LCHS/CS improved bone marrow EPOr mRNA and EPOr protein expression by 94 and 96% (Figure). Similarly, the use of clonidine following LCHS/CS increased EPOr mRNA and EPOr protein expression by 90 and 96% (Figure). When BM EPOr expression was restored in the LCHS/CS+BB and LCHS/CS+clonidine groups, bone marrow BFU-E and CFU-E colony growth was similar to that of naïve animals (Figure).
Conclusion:The addition of chronic stress to severe trauma negatively impacts bone marrow EPOr expression and erythroid colony growth. However, both daily propranolol and clonidine restore EPOr expression, which improves BFU-E and CFU-E colony growth. Modulation of the hypercatecholaminemia state following severe trauma and chronic stress may provide a therapeutic alternative to improve erythroid maturation.
