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Updated: Jun 2, 2026
A Model of Long-Term Ventricular Fibrillation in Isolated Rat Hearts
Published on: February 17, 2023
Disassociation between left ventricular mechanical and electrical properties in ischemic rat heart after G-CSF
Hong-Mei Liu1, Tao Luo, Xin Zhou
1Institute of Cardiovascular Diseases, Pingjin Hospital, Medical College of Chinese People's Armed Police Forces, 220 Cheng-Lin Road, Tianjin, 300162, China.
Insights
Granulocyte colony-stimulating factor (G-CSF) administration after myocardial ischemia did not improve ventricular remodeling. Early G-CSF treatment worsened mechanical remodeling and increased arrhythmias, despite improving electrical properties.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Myocardial Infarction Therapy
Background:
- The role of granulocyte colony-stimulating factor (G-CSF) in post-myocardial infarction ventricular remodeling is debated.
- The timing of G-CSF administration may influence its therapeutic efficacy after ischemia.
Purpose of the Study:
- To investigate the impact of early versus delayed G-CSF administration on ventricular remodeling following myocardial ischemia in a rat model.
- To assess the effects of G-CSF timing on both mechanical and electrical properties of the heart post-infarction.
Main Methods:
- Myocardial ischemia was induced in rats via coronary ligation and reperfusion.
- Granulocyte colony-stimulating factor (G-CSF) was administered either 1 hour (early) or 24 hours (delayed) after reperfusion.
- Ventricular remodeling, electrophysiological properties, and cardiac function were evaluated at 7 days and 3 months post-ischemia.
Main Results:
- Early G-CSF administration significantly impaired left ventricular (LV) mechanical remodeling and cardiac function at 3 months compared to controls.
- Both early and delayed G-CSF treatments improved electrophysiological properties, including reduced action potential dispersion and arrhythmia inducibility.
- No beneficial effects on LV mechanical remodeling were observed with either early or delayed G-CSF administration.
Conclusions:
- While G-CSF can enhance electrophysiological properties post-myocardial ischemia, it does not improve ventricular mechanical remodeling.
- Early G-CSF administration may even be detrimental to mechanical remodeling and cardiac function, while increasing arrhythmia risk.
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.