title: Daily propranolol prevents prolonged mobilization of hematopoietic progenitor cells in a rat model of lung contusion, hemorrhagic shock, and chronic stress.
abstract: BACKGROUND
  Propranolol has been shown previously to decrease the mobilization of hematopoietic progenitor cells (HPCs) after acute injury in rodent models; however, this acute injury model does not reflect the prolonged period of critical illness after severe trauma. Using our novel lung contusion/hemorrhagic shock/chronic restraint stress model, we hypothesize that daily administration of propranolol will decrease prolonged mobilization of HPCs without worsening lung healing.
  
  
  METHODS
  Male Sprague-Dawley rats underwent 6 days of restraint stress after undergoing lung contusion or lung contusion/hemorrhagic shock. Restraint stress consisted of a daily 2-hour period of restraint interrupted every 30 minutes by alarms and repositioning. Each day after the period of restraint stress, the rats received intraperitoneal propranolol (10 mg/kg). On day 7, peripheral blood was analyzed for granulocyte-colony stimulating factor (G-CSF) and stromal cell-derived factor 1 via enzyme-linked immunosorbent assay and for mobilization of HPCs using c-kit and CD71 flow cytometry. The lungs were examined histologically to grade injury.
  
  
  RESULTS
  Seven days after lung contusion and lung contusion/hemorrhagic shock, the addition of chronic restraint stress significantly increased the mobilization of HPC, which was associated with persistently increased levels of G-CSF and increased lung injury scores. The addition of propranolol to lung contusion/chronic restraint stress and lung contusion/hemorrhagic shock/chronic restraint stress models greatly decreased HPC mobilization and restored G-CSF levels to that of naïve animals without worsening lung injury scores.
  
  
  CONCLUSIONS
  The daily administration of propranolol after both lung contusion and lung contusion/hemorrhagic shock subjected to chronic restraint stress decreased the prolonged mobilization of HPC from the bone marrow and decreased plasma G-CSF levels. Despite the decrease in mobilization of HPC, lung healing did not worsen. Alleviating chronic stress with propranolol may be a future therapeutic target to improve healing after severe injury.
authors.affiliation: Department of Surgery, Division of Trauma, Rutgers-New Jersey Medical School, Newark, NJ.
authors.forename: Letitia E
authors.initials: LE
authors.lastname: Bible
authors.affiliation: Department of Surgery, Division of Trauma, Rutgers-New Jersey Medical School, Newark, NJ.
authors.forename: Latha V
authors.initials: LV
authors.lastname: Pasupuleti
authors.affiliation: Department of Surgery, Division of Trauma, Rutgers-New Jersey Medical School, Newark, NJ.
authors.forename: Amy V
authors.initials: AV
authors.lastname: Gore
authors.affiliation: Department of Surgery, Division of Trauma, Rutgers-New Jersey Medical School, Newark, NJ.
authors.forename: Ziad C
authors.initials: ZC
authors.lastname: Sifri
authors.affiliation: Department of Surgery, Division of Acute Care Surgery, University of Florida, Gainesville, FL.
authors.forename: Kolenkode B
authors.initials: KB
authors.lastname: Kannan
authors.affiliation: Department of Surgery, Division of Acute Care Surgery, University of Florida, Gainesville, FL. Electronic address: alicia.mohr@surgery.ufl.edu.
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Mohr
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D054377:Chemokine CXCL12 / Q000097:blood; D003288:Contusions / Q000150:complications / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000502:physiology; D007274:Injections, Intraperitoneal; D055370:Lung Injury / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D011433:Propranolol / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D015415:Biomarkers; C575935:CXCL12 protein, rat; D054377:Chemokine CXCL12; D016179:Granulocyte Colony-Stimulating Factor; D011433:Propranolol