Synergistic effects of G-CSF and erythropoietin on left ventricular systolic function in heart failure after rat myocardial infarction

Synergistic effects of G-CSF and erythropoietin on left ventricular systolic function in heart failure after rat myocardial infarction

Yoichi Sunagawa1, Tatsuya Morimoto1, Teruhisa Kawamura1, Tomohide Takaya1, Hiromichi Wada1, Tomoaki Kuwai3, Shigeki Yanagi4, Akihiro Sugimoto4, Masaki Tsukashita4, Akira Marui4, Tadashi Ikeda4, Akira Shimatsu1, Masatoshi Fujita5, Toru Kita2, Koji Hasegawa1.

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

第73回日本循環器学会学術集会 (大阪), 2009/03/21 (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 may improve left ventricular (LV) function after myocardial infarction (MI), further augmentation of its beneficial effects is required to apply this therapy to the clinical setting. We hypothesized that erythropoietin (EPO) stabilizes progenitor cells and preserves LV function by its anti-inflammatory or anti-apoptotic action.

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

Methods: One week after coronary ligation, we performed echocardiography in all surviving rats. The 36 MI rats were the randomly assigned to 4 groups; I: saline, II: G-CSF (4.5 ug/kg/day) alone, III: EPO (3000 U/kg/day) alone, and IV: both G-CSF and EPO. Subcutaneous injections of these agents were performed 3 days per week and continued for 6 weeks.

Results: Endpoint measurements performed at 7 weeks after coronary ligation revealed that LV functional shortening was larger than 50 um in diameter was the highest in group IV. Perivascular fibrosis was significantly reduced in groups II and III compared with group I. This reduction was further augmented in group IV.

Conclusion: G-CSF and EPO had synergistic effects on the improvement of LV systolic function in heart failure after rat MI.