Ultrasound-targeted microbubble destruction (UTMD) in combination with granulocyte colony-stimulating factor (G-CSF) improves cardiac function in myocardial infarction rats

Objectives: The aim of this study is to determine the effect of ultrasound-targeted microbubble destruction in combination with granulocyte colony-stimulating factor (G-CSF) on revascularization and cardiac function in myocardial infarction rats. Materials and Methods: A total of 40 Wistar rats were successfully constructed as myocardial infarction (MI) model and randomly divided into four groups. Group A, B, C, and D were treated for two weeks with ultrasound, microbubble and G-CSF (UTMD+G-CSF), or ultrasound and microbubble (UTMD), or G-CSF, or surgery control (SC), respectively. Then, the expression of myocardial CD34 was analyzed by immunohistochemistry (IHC) method; the level of microvessel density (MVD) in myocardium was counted; the expression of myocardial vascular endothelial growth factor (VEGF) and Irisin were detected by enzyme linked immunosorbent assay (ELISA), Western blot and quantitative real-time PCR (qPCR) assay. Additionally, cardiac function tests were conducted by echocardiography in all MI rats. Results: Serum Irisin levels of all the MI rats were significantly lower than the control, which indicated the successful construction of MI model. Significant differences (P < 0.05) between group A and other groups were obtained in this study. Massive expression of CD34, with the most obvious neovascularization (MVD: 231.20 +/- 24.48), was observed in group A by IHC; meanwhile, the highest expression of myocardial VEGF (3.23 +/- 0.21 ng/g) and Irisin (607.4 ng/mL) were measured by ELISA, which was confirmed by Western blot and qPCR assays, as the brightest band in group A was observed. Comparison of the left heart function revealed that increased ejection fraction (EF%) (56.78 +/- 7.23) and fractional shortening (FS) (28.23 +/- 4.98%) with decreased TDI-Tei (0.43 +/- 0.11) were appeared in group A when compared with other groups. Conclusions: Combined treatment of ultrasound-targeted microbubble destruction and G-CSF administration can promote revascularization and improve cardiac function in myocardial infarction rats.