Abstract 15155: Acidic Fibroblast Growth Factor Delivered by Ultrasound Targeted Microbubble Destruction Increases Microvascular Densities and Improves Left Ventricular Systolic and Diastolic Function in Diabetic Cardiomyopathy in Rats

Abstract

BACKGROUND AND OBJECTIVES: We sought to pursue enhancing angiogenesis and tissue growth and repair to improve microcirculation and left ventricular (LV) function to treat diabetic cardiomyopathy (DCM) by delivering acidic fibroblast growth factor (aFGF) using ultrasound-targeted microbubble destruction (UTMD) technology.

METHODS: A total of 60 SD rats were randomized into 5 groups. Diabetes mellitus (DM) and DCM were induced by intra-peritoneal injection of streptozotocin 8 weeks prior to treatment. Treatment included intravenous injection of mixture of aFGF and SonoVue and simultaneous transthoracic ultrasound irradiation to selectively deliver aFGF into the myocardium. Group assignments were: Group A (DCM + no UTMD treatment); Group B (aFGF only), Group C (aFGF + SonoVue only), Group D (aFGF + SonoVue + ultrasound irradiation) and Group E (No streptozotocin or other treatment). The animals were evaluated by transthoracic echocardiography for LV chamber size, fractional shortening (FS), radial (r) and circumferential (c) strain (S) and strain rate (SR); by catheterization for LV pressures and dp/dt; and by immunohistochemistry for myocardial microvascular density (MVD). RESULTS: Compared with control group (Group E), Group A to D showed significant LV systolic dysfunction (P<0.05) after streptozotocin and before UTMD treatment. The Table showed that aFGF/UTMD treatment (Group D), but not aFGF alone (Group B) or aFGF + SonoVue alone (Group C), was associated with a significant improvement in MVD, LVFS, Sr/Sc, SRr/SRc, LVEDP, +dp/dt and -dp/dt (P<0.05 to P<0.01, Table) compared with no therapy Group A, although these variables were significantly different from normal control (Group E) 4 weeks after UTMD treatment. CONCLUSIONS: Our study suggests delivery of aFGF by UTMD enhances angiogenesis and left ventricular systolic and diastolic function in rats with DCM. This approach may provide a new efficacious therapeutic strategy for DCM.