Disassociation Between Left Ventricular Mechanical and Electrical Properties in Ischemic Rat Heart After G-CSF Treatment

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 100ىg/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/dtmax (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.