title: Early use of granulocyte colony stimulating factor improves survival in a rabbit model of chronic myocardial ischemia.
abstract: BACKGROUND
  Granulocyte colony stimulating factor (G-CSF) improves the survival of animals with myocardial infarction by inducing bone marrow stem cell mobilization and homing to infarcted areas. However, its precise mechanisms and direct effects on the ischemic myocardium remain unclear. In this study we investigated the direct effects and mechanisms of G-CSF in a rabbit model of chronic myocardial ischemia.
  
  
  METHODS
  Myocardial ischemia models were created by partial ligation of the left anterior descending coronary artery in Japanese white male rabbits. Rabbits were subcutaneously injected with 10 μg/kg of G-CSF (G-CSF group) or saline (control group) for 6 days after myocardial ischemia. Direct effects of G-CSF were analyzed by immunohistochemistry and terminal dUTP nick end-labeling (TUNEL).
  
  
  RESULTS
  Rabbits in the G-CSF group exhibited 75% survival compared to 40% in the control group (p<0.05). Immunohistochemistry of the ischemic myocardium showed increased homing of CD34+ cells on day 7 post-surgery and more vessels on day 28 post-surgery by anti-von Willebrand factor staining in the G-CSF group compared with the control group. Furthermore, an increased percentage of CD34+ cells were observed in peripheral blood and upregulation of vascular endothelial growth factor expression in ischemic tissue in the G-CSF group compared with the control group. TUNEL showed that the apoptotic index in the ischemic myocardium decreased in the G-CSF group compared with the control group on day 28 post-surgery.
  
  
  CONCLUSIONS
  In addition to increasing stem cell mobilization and homing to ischemic myocardium, G-CSF treatment after myocardial ischemia improves survival by accelerating neovascularization and reducing apoptosis.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Medical College in Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. zhaoqingbin05@163.com
authors.forename: Qingbin
authors.initials: Q
authors.lastname: Zhao
authors.forename: Chaofeng
authors.initials: C
authors.lastname: Sun
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
authors.forename: Yue
authors.initials: Y
authors.lastname: Wu
authors.forename: Yuling
authors.initials: Y
authors.lastname: Tian
authors.forename: Aiqun
authors.initials: A
authors.lastname: Ma
authors.forename: Zhiquan
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002908:Chronic Disease; D003331:Coronary Vessels / Q000502:physiology; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000494:pharmacology / Q000502:physiology; D007279:Injections, Subcutaneous; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D013268:Stimulation, Chemical; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D016179:Granulocyte Colony-Stimulating Factor