title: Disassociation between left ventricular mechanical and electrical properties in ischemic rat heart after G-CSF treatment.
abstract: OBJECTIVE
  The effect of granulocyte colony-stimulating factor (G-CSF) on post-infarct ventricular remodeling remains controversial. We hypothesized that the timing of G-CSF administration after myocardial ischemia plays an important role in determining its efficacy.
  
  
  METHODS
  Rat myocardial ischemia was induced by 60 min coronary ligation and reperfusion. Surviving animals received G-CSF after 1 h (E-G) or 24 h (D-G) of reperfusion randomly at 100 μg/kg/d for five consecutive days. 7 days or 3 months post-ischemia, rat hearts were quickly removed for ex vivo electrophysiological measurements or histological analysis (collagen disposition and angiogenesis) and metalloproteinase-2 and -9 activity assays (gelatin zymography). Left ventricular (LV) invasive hemodynamic analysis was performed in 3-month recovery animals before sacrifice.
  
  
  RESULTS
  At 3 months post ischemia, LV mechanical remodeling was further impaired with early G-CSF administration (0.65 ± 0.17%, 13.21 ± 7.36 mmHg, -4,684 ± 1,560 mmHg/s) compared with the control group (0.28 ± 0.12%, 6.45 ± 3.43 mmHg, -6,267 ± 1,111 mmHg/s) and D-G group (0.34 ± 0.12%, 7.90 ± 5.33 mmHg, -6,227 ± 1,075 mmHg/s) as shown by increased expansion index (P < 0.01), deterioration of myocardial function with increased LVDP (P < 0.05), and decreased -dP/dt (max) (P < 0.05). By contrast, there was a significant increase in electrical properties including monophasic action potential (MAP) 90 dispersion (12.58 ± 4.46 vs. 30.56 ± 6.17 ms at 7 days; 18.54 ± 4.31 vs. 34.78 ± 5.24 ms at 3 months; P < 0.05 for both) and inducibility of ventricular arrhythmias (4.78 ± 1.19 vs. 11.58 ± 2.76 ms at 3 months; P < 0.05) with early G-CSF treatment compared with the control group.
  
  
  CONCLUSIONS
  Both early and delayed administrations of G-CSF can improve electrophysiological properties after myocardial ischemia, but have no beneficial effects on LV mechanical remodeling.
authors.affiliation: Institute of Cardiovascular Diseases, Pingjin Hospital, Medical College of Chinese People's Armed Police Forces, 220 Cheng-Lin Road, Tianjin, 300162, China.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Luo
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Lin
authors.initials: L
authors.lastname: Cai
authors.forename: Ti-Gang
authors.initials: TG
authors.lastname: Huang
authors.forename: Tie-Min
authors.initials: TM
authors.lastname: Jiang
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Li
mesh_terms: D000818:Animals; D004334:Drug Administration Schedule; D055724:Electrophysiological Phenomena / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000209:etiology; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D016179:Granulocyte Colony-Stimulating Factor