Synergistic effects of granulocyte-colony stimulating factor and erythropoietin on left ventricular systolic function in rat myocardial infarction

Synergistic effects of granulocyte-colony stimulating factor and erythropoietin on left ventricular systolic function in rat myocardial infarction

Yoichi Sunagawa1, Tatsuya Morimoto1, Tomohide Takaya1, Tomoaki Kuwaki2, Shigeki Yanagi3, Akira Marui3, Tadashi Ikeda3, Masatoshi Fujita4, Toru Kita5, Koji Hasegawa1.

  1. Kyoto Medical Center, National Hospital Organization, Kyoto, Japan.
  2. Research Division, Kirin Pharma Company, Tokyo, Japan.
  3. Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  4. School of Health Sciences, Faculty of Medicine, Kyoto University, Kyoto, Japan.
  5. Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

第12回日本心不全学会学術集会 (東京), 2008/10/16 (ポスター).

Abstract

Introduction: Granulocyte-colony stimulating factor (G-CSF) mobilizes multipotential progenitor cells in bone marrow to the heart. While G-CSF can improve left ventricular (LV) function after myocardial infarction (MI), further augmentation of its beneficial effects is required to apply this therapy in the clinical setting. We hypothesized that erythropoietin (EPO) stabilizes progenitor cells in the heart by its anti-apoptotic action.

Objective: The purpose of this study was to examine the effect of G-CSF/EPO combination therapy on LV function in MI.

Methods: Rats were subjected to sham operation or MI by occlusion of the left anterior descending coronary artery. One week later, we performed LV functional studies by echocardiography in all surviving rats. The MI rats were then randomly assigned to 4 groups; I: saline (n = 9), II: G-CSF (4.5 ug/kg/day) alone (n = 9), III: EPO (3000 U/kg/day) alone (n = 9), and IV: both G-CSF and EPO (n = 9). Subcutaneous injections of these agents were performed three days per week and continued for six weeks.

Results: After treatment, LVFS increased by 11% in the G-CSF group and by 12% in the EPO group compared with the saline-treated group. Notably, LVFS increased by 32% (p < 0.05) in the G-CSF/EPO combination therapy group. Moreover, peri-vascular fibrosis was significantly inhibited in the G-CSF/EPO combination therapy group.

Conclusion: Combined treatment with G-CSF and EPO synergistically improves LV systolic function in rat chronic MI.