title: The antiapoptotic effect of granulocyte colony-stimulating factor reduces infarct size and prevents heart failure development in rats.
abstract: OBJECTIVE
  Granulocyte colony-stimulating factor (G-CSF) reduces myocardial injury and improves cardiac function after myocardial infarction (MI). We investigated the early alterations provided by G-CSF and the chronic repercussions in infarcted rats.
  
  
  METHODS
  Male Wistar rats (200-250g) received vehicle (MI) or G-CSF (MI-GCSF) (50 μg/kg, sc) at 7, 3 and 1 days before MI surgery. Afterwards MI was produced and infarct size was measured 1 and 15 days after surgery. Expression of anti- and proapoptotic proteins was evaluated immediately before surgery. 24 hours after surgery, apoptotic nuclei were evaluated. Two weeks after MI, left ventricular (LV) function was evaluated, followed by in situ LV diastolic pressure-volume evaluation.
  
  
  RESULTS
  Infarct size was decreased by 1 day pre-treatment before occlusion (36±2.8 vs. 44±2.1% in MI; P<0.05) and remained reduced at 15 days after infarction (28±2.2 vs. 36±1.4% in MI; P<0.05). G-CSF pretreatment increased Bcl-2 and Bcl-xL protein expression, but did not alter Bax in LV. Apoptotic nuclei were reduced by treatment (Sham: 0.46±0.42, MI: 15.5±2.43, MI-GCSF: 5.34±3.34%; P<0.05). Fifteen days after MI, cardiac function remained preserved in G-CSF pretreated rats. The LV dilation was reduced in MI-G-CSF group as compared to MI rats, being closely associated with infarct size.
  
  
  CONCLUSIONS
  The early beneficial effects of G-CSF were essentials to preserve cardiac function at a chronic stage of myocardial infarction.
authors.affiliation: Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, Brazil. marcelobaldo@ymail.com
authors.forename: Marcelo Perim
authors.initials: MP
authors.lastname: Baldo
authors.forename: Ana P C
authors.initials: AP
authors.lastname: Davel
authors.forename: Danilo M
authors.initials: DM
authors.lastname: Damas-Souza
authors.forename: José E
authors.initials: JE
authors.lastname: Nicoletti-Carvalho
authors.forename: Silvana
authors.initials: S
authors.lastname: Bordin
authors.forename: Hernandes F
authors.initials: HF
authors.lastname: Carvalho
authors.forename: Sérgio L
authors.initials: SL
authors.lastname: Rodrigues
authors.forename: Luciana V
authors.initials: LV
authors.lastname: Rossoni
authors.forename: José G
authors.initials: JG
authors.lastname: Mill
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006333:Heart Failure / Q000517:prevention & control*; D007962:Leukocytes / Q000166:cytology; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000601:surgery; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D016179:Granulocyte Colony-Stimulating Factor