title: Granulocyte colony-stimulating factor stabilizes cardiac electrophysiology and decreases infarct size during cardiac ischaemic/reperfusion in swine.
abstract: OBJECTIVE
  Effects of granulocyte colony-stimulating factor (G-CSF) on cardiac electrophysiology during ischaemic/reperfusion (I/R) period are unclear. We hypothesized that G-CSF stabilizes cardiac electrophysiology during I/R injury by prolonging the effective refractory period (ERP), increasing the ventricular fibrillation threshold (VFT) and decreasing the defibrillation threshold (DFT), and that the cardioprotection of G-CSF is via preventing cardiac mitochondrial dysfunction.
  
  
  METHODS
  In intact-heart protocol, pigs were infused with either G-CSF or vehicle (n = 7 each group) without I/R induction. In I/R protocol, pigs were infused with G-CSF (0.33 μg kg(-1 ) min(-1) ) or vehicle (n = 8 each group) for 30 min prior to a 45-min left anterior descending artery occlusion and at reperfusion. Diastolic pacing threshold (DPT), ERP, VFT and DFT were determined in all pigs before and during I/R period. Rat's isolated cardiac mitochondria were used to test the protective effect of G-CSF (100 nm) in H(2) O(2) -induced mitochondrial oxidative damage.
  
  
  RESULTS
  Neither G-CSF nor vehicle altered any parameter in intact-heart pigs. During ischaemic period, G-CSF significantly increased the DPT, ERP and VFT without altering the DFT. During reperfusion, G-CSF continued to increase the DPT without altering other parameters. The infarct size was significantly decreased in the G-CSF group, compared to the vehicle. G-CSF could also prevent cardiac mitochondrial swelling, decrease ROS production, and prevent mitochondrial membrane depolarization.
  
  
  CONCLUSIONS
  G-CSF increases the DPT, ERP and VFT and reduces the infarct size, thus stabilizing the myocardial electrophysiology, and preventing fatal arrhythmia during I/R. The protective mechanism could be via its effect in preventing cardiac mitochondrial dysfunction.
authors.affiliation: Cardiac Electrophysiology Unit, Department of Physiology, Chiang Mai University, Thailand.  
authors.forename: N
authors.initials: N
authors.lastname: Kanlop
authors.forename: S
authors.initials: S
authors.lastname: Thommasorn
authors.forename: S
authors.initials: S
authors.lastname: Palee
authors.forename: P
authors.initials: P
authors.lastname: Weerateerangkul
authors.forename: S
authors.initials: S
authors.lastname: Suwansirikul
authors.forename: S
authors.initials: S
authors.lastname: Chattipakorn
authors.forename: N
authors.initials: N
authors.lastname: Chattipakorn
mesh_terms: D000818:Animals; D054849:Cardiac Electrophysiology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics; D009203:Myocardial Infarction / Q000473:pathology* / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D011994:Recombinant Proteins; D015427:Reperfusion Injury / Q000473:pathology*; D013552:Swine
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor