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

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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 100μg/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.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (30740010, 30871072 and 81070121), the Tianjin Municipal Science and Technology Committee (09ZCZDSF04200), and intramural research programs from the Medical College of Chinese People’s Armed Police Forces (WJZ2007-3 and WKH2009Z01).

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Authors and Affiliations

  1. Institute of Cardiovascular Diseases, Pingjin Hospital, Medical College of Chinese People’s Armed Police Forces, 220 Cheng-Lin Road, Tianjin, 300162, China

    Hong-Mei Liu, Tao Luo, Xin Zhou, Lin Cai, Tie-Min Jiang & Yu-Ming Li

  2. Division of Cardiology, No. 254 Hospital of PLA, Tianjin, China

    Tao Luo

  3. Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China

    Ti-Gang Huang

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  1. Hong-Mei Liu
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  2. Tao Luo
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  3. Xin Zhou
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Correspondence to Yu-Ming Li.

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Hong-Mei Liu and Tao Luo contributed equally to this work.

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Liu, HM., Luo, T., Zhou, X. et al. Disassociation Between Left Ventricular Mechanical and Electrical Properties in Ischemic Rat Heart After G-CSF Treatment. Cardiovasc Drugs Ther 25, 203–214 (2011). https://doi.org/10.1007/s10557-011-6294-8

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