The effects of propranolol and clonidine on bone marrow expression of hematopoietic cytokines following trauma and chronic stress

Am J Surg. 2019 Nov;218(5):858-863. doi: 10.1016/j.amjsurg.2019.02.023. Epub 2019 Feb 21.

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.

Keywords: Bone marrow; Erythropoiesis; Injury; Stress; Trauma.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anemia / etiology
  • Anemia / prevention & control
  • Animals
  • Biomarkers / metabolism
  • Bone Marrow / drug effects*
  • Bone Marrow / metabolism
  • Chronic Disease
  • Clonidine / pharmacology*
  • Clonidine / therapeutic use
  • Contusions / drug therapy
  • Contusions / physiopathology
  • Cytokines / metabolism*
  • Drug Therapy, Combination
  • Erythropoiesis / drug effects
  • Hematinics / pharmacology*
  • Hematinics / therapeutic use
  • Lung Injury / drug therapy
  • Lung Injury / physiopathology*
  • Male
  • Propranolol / pharmacology*
  • Propranolol / therapeutic use
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Restraint, Physical
  • Shock, Hemorrhagic / drug therapy
  • Shock, Hemorrhagic / physiopathology
  • Stress, Physiological / physiology*
  • Treatment Outcome

Substances

  • Biomarkers
  • Cytokines
  • Hematinics
  • Propranolol
  • Clonidine