Combination therapy involving G-CSF and erythropoietin synergically improve LV systolic function in heart failure after MI in rat

Combination therapy involving G-CSF and erythropoietin synergically improve LV systolic function in heart failure after MI in rat

Yoichi Sunagawa1, Tatsuya Morimoto1, Teruhisa Kawamura1, Tomohide Takaya1, Hiromichi Wada1, Tomoaki Kuwaki2, Shigeki Yanagi3, Akihiro Sugimoto3, Masaki Tsukashita3, Akira Marui3, Tadashi Ikeda3, Akira Shimatsu1, Masatoshi Fujita4, Toru Kita5, Koji Hasegawa1.

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

The 17th Asian Pacific Congress of Cardiology (Kyoto, Japan), 2009/05/21 (Poster).

Abstract

Introduction: 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 benefitial effects is required to apply this therapy in the clinical setting. We hypothesized that EPO stabilizes progenitor cells mobilized by G-CSF and potentiates benefitial effects of G-CSF on the heart.

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

Methods: One week after coronary ligation, we performed physiological studies by echocardiography in all surviving rats. Then, 36 MI rats were 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 three days per week and continued for six weeks.

Results: LV fractional shortening (FS) in MI was similar among the four groups before treatment. After treatment, compared with group I, LVFS increased by 11% in group II, by 12% in group III, and by 32% (p < 0.05) 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.