title: Beta-blockade prevents hematopoietic progenitor cell suppression after hemorrhagic shock.
abstract: BACKGROUND
  Severe injury is accompanied by sympathetic stimulation that induces bone marrow (BM) dysfunction by both suppression of hematopoietic progenitor cell (HPC) growth and loss of cells via HPC mobilization to the peripheral circulation and sites of injury. Previous work demonstrated that beta-blockade (BB) given prior to tissue injury both reduces HPC mobilization and restores HPC colony growth within the BM. This study examined the effect and timing of BB on BM function in a hemorrhagic shock (HS) model.
  
  
  METHODS
  Male Sprague-Dawley rats underwent HS via blood withdrawal, maintaining the mean arterial blood pressure at 30-40 mm Hg for 45 min, after which the extracted blood was reinfused. Propranolol (10 mg/kg) was given either prior to or immediately after HS. Blood pressure, heart rate, BM cellularity, and death were recorded. Bone marrow HPC growth was assessed by counting colony-forming unit-granulocyte-, erythrocyte-, monocyte-, megakaryocyte (CFU-GEMM), burst-forming unit-erythroid (BFU-E), and colony-forming unit-erythroid (CFU-E) cells.
  
  
  RESULTS
  Administration of BB prior to injury restored HPC growth to that of naïve animals (CFU-GEMM 59 ± 11 vs. 61 ± 4, BFU-E 68 ± 9 vs. 73 ± 3, and CFU-E 81 ± 35 vs. 78 ± 14 colonies/plate). Beta-blockade given after HS increased the growth of CFU-GEMM, BFU-E, and CFU-E significantly and improved BM cellularity compared with HS alone. The mortality rate was not increased in the groups receiving BB.
  
  
  CONCLUSIONS
  Administration of propranolol either prior to injury or immediately after resuscitation significantly reduced post-shock BM suppression. After HS, BB may improve BM cellularity by decreasing HPC mobilization. Therefore, the early use of BB post-injury may play an important role in attenuating the BM dysfunction accompanying HS.
authors.affiliation: Department of Surgery, Division of Trauma, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey 07103, USA.
authors.forename: Ihab O
authors.initials: IO
authors.lastname: Elhassan
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Hannoush
authors.forename: Ziad C
authors.initials: ZC
authors.lastname: Sifri
authors.forename: Eyone
authors.initials: E
authors.lastname: Jones
authors.forename: Walter D
authors.initials: WD
authors.lastname: Alzate
authors.forename: Pranela
authors.initials: P
authors.lastname: Rameshwar
authors.forename: David H
authors.initials: DH
authors.lastname: Livingston
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Mohr
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000818:Animals; D001853:Bone Marrow / Q000502:physiology; D004195:Disease Models, Animal; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D008297:Male; D011433:Propranolol / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D012376:Rodent Diseases / Q000188:drug therapy; D012771:Shock, Hemorrhagic / Q000188:drug therapy*
chemical_list: D000319:Adrenergic beta-Antagonists; D011433:Propranolol