Tyler J Loftus1, Elizabeth S Miller2, Jessica K Millar3, Kolenkode B Kannan4, Ines G Alamo5, Philip A Efron6, Alicia M Mohr7. 1. University of Florida, Department of Surgery and Sepsis and Critical Illness Research Center, Gainesville, FL, USA. Electronic address: Tyler.Loftus@surgery.ufl.edu. 2. University of Florida, Department of Surgery and Sepsis and Critical Illness Research Center, Gainesville, FL, USA. Electronic address: Elizabeth.Miller@surgery.ufl.edu. 3. University of Florida, College of Medicine, Gainesville, FL, USA. Electronic address: jmillara5@ufl.edu. 4. University of Florida, Department of Surgery and Sepsis and Critical Illness Research Center, Gainesville, FL, USA. Electronic address: Kolenkode.Kannan@surgery.ufl.edu. 5. University of Florida, Department of Surgery and Sepsis and Critical Illness Research Center, Gainesville, FL, USA. Electronic address: ialamo518@gmail.com. 6. University of Florida, Department of Surgery and Sepsis and Critical Illness Research Center, Gainesville, FL, USA. Electronic address: philip.efron@surgery.ufl.edu. 7. University of Florida, Department of Surgery and Sepsis and Critical Illness Research Center, Gainesville, FL, USA. Electronic address: alicia.mohr@surgery.ufl.edu.
Abstract
BACKGROUND: Attenuating post-injury neuroendocrine stress abrogates persistent injury-associated anemia. Our objective was to examine the mechanisms by which propranolol and clonidine modulate this process. We hypothesized that propranolol and clonidine would decrease bone marrow expression of high-mobility group box-1 (HMGB1) and increase expression of stem cell factor (SCF) and B-cell lymphoma-extra large (Bcl-xL). METHODS: Male Sprague-Dawley rats were allocated to naïve control, lung contusion followed by hemorrhagic shock (LCHS), or LCHS plus daily chronic restraint stress (LCHS/CS) ±propranolol, ±clonidine. Day seven bone marrow expression of HMGB1, SCF, and Bcl-xL was assessed by polymerase chain reaction. RESULTS: Following LCHS, HMGB1 was decreased by propranolol (49% decrease, p = 0.012) and clonidine (54% decrease, p < 0.010). SCF was decreased following LCHS/CS, and was increased by propranolol (629% increase, p < 0.001) and clonidine (468% increase, p < 0.001). Bcl-xL was decreased following LCHS/CS, and was increased by propranolol (59% increase, p = 0.006) and clonidine (77% increase, p < 0.001). CONCLUSIONS: Following severe trauma, propranolol and clonidine abrogate persistent injury-associated anemia by modulating bone marrow cytokines, favoring effective erythropoiesis.
BACKGROUND:Attenuating post-injury neuroendocrine stress abrogates persistent injury-associated anemia. Our objective was to examine the mechanisms by which propranolol and clonidine modulate this process. We hypothesized that propranolol and clonidine would decrease bone marrow expression of high-mobility group box-1 (HMGB1) and increase expression of stem cell factor (SCF) and B-cell lymphoma-extra large (Bcl-xL). METHODS: Male Sprague-Dawley rats were allocated to naïve control, lung contusion followed by hemorrhagic shock (LCHS), or LCHS plus daily chronic restraint stress (LCHS/CS) ±propranolol, ±clonidine. Day seven bone marrow expression of HMGB1, SCF, and Bcl-xL was assessed by polymerase chain reaction. RESULTS: Following LCHS, HMGB1 was decreased by propranolol (49% decrease, p = 0.012) and clonidine (54% decrease, p < 0.010). SCF was decreased following LCHS/CS, and was increased by propranolol (629% increase, p < 0.001) and clonidine (468% increase, p < 0.001). Bcl-xL was decreased following LCHS/CS, and was increased by propranolol (59% increase, p = 0.006) and clonidine (77% increase, p < 0.001). CONCLUSIONS: Following severe trauma, propranolol and clonidine abrogate persistent injury-associated anemia by modulating bone marrow cytokines, favoring effective erythropoiesis.
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