title: Granulocyte-colony stimulating factor administration after myocardial infarction in a porcine ischemia-reperfusion model: functional and pathological effects of dose timing.
abstract: BACKGROUND
  Acute MI results in cardiomyocyte death, left ventricular (LV) dysfunction and adverse remodeling. The use of growth factors may prevent this. The aim of this study was to assess early and delayed administration of granulocyte colony-stimulating factor (G-CSF) in a porcine model of myocardial infarction (MI) and reperfusion.
  
  
  METHODS
  MI was induced by balloon occlusion followed by reperfusion. There were 3 groups: Control (n = 11), Early (n = 17), and Delayed treatment (n = 8). The Early group received G-CSF 10 microg/kg/d every other day for 20 days beginning immediately. The Delayed group received G-CSF 10 microg/kg/d daily for 10 days beginning on day 5. Magnetic resonance imaging was performed on days 5 and 56. LV end-diastolic volumes (EDV), end-systolic volumes, ejection fraction, expansion index, sphericity index, thinning ratio, and infarct mass were calculated. Histology was analyzed at 56 days.
  
  
  RESULTS
  At 56 days the change in EDV was 53% less in the Early (p = 0.005) and 24% greater in the Delayed (p = NS) group versus Control. The Delayed group also showed a 60% increase in normalized infarct mass (p = 0.055) and an 88% increase in expansion index (p = 0.003). Both groups had significantly less capillary density in the infarct border zone. The Delayed also had decreased arteriolar density in the mid scar.
  
  
  CONCLUSIONS
  Early treatment with G-CSF after MI decreases ventricular dilatation, while delayed treatment has a deleterious effect on LV remodeling. This may be related to changes in myocardial vascularity. The effects of G-CSF therapy and its dose timing help to elucidate the results of recent human trials.
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. n-beohar@northwestern.edu
authors.forename: Nirat
authors.initials: N
authors.lastname: Beohar
authors.forename: James D
authors.initials: JD
authors.lastname: Flaherty
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Davidson
authors.forename: Mladen
authors.initials: M
authors.lastname: Vidovich
authors.forename: Seema
authors.initials: S
authors.lastname: Singhal
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Rapp
authors.forename: Ata
authors.initials: A
authors.lastname: Erdogan
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Lee
authors.forename: Chidambaram
authors.initials: C
authors.lastname: Rammohan
authors.forename: Adam
authors.initials: A
authors.lastname: Brodsky
authors.forename: Edwin
authors.initials: E
authors.lastname: Wu
authors.forename: Karen
authors.initials: K
authors.lastname: Pieper
authors.forename: Renu
authors.initials: R
authors.lastname: Virmani
authors.forename: Robert O
authors.initials: RO
authors.lastname: Bonow
authors.forename: Jayesh
authors.initials: J
authors.lastname: Mehta
mesh_terms: D000818:Animals; D003287:Contrast Media; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000494:pharmacology*; D016014:Linear Models; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy*; D015425:Myocardial Reperfusion / Q000379:methods*; D013552:Swine; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D003287:Contrast Media; D016179:Granulocyte Colony-Stimulating Factor