Abstract 13160: Low-intensity Pulsed Ultrasound Enhances Angiogenesis and Ameliorates Contractile Cardiac Function in Pressure-Overloaded Hearts in Mice

Abstract

Introduction: Chronic pressure overload causes relative ischemia with resultant left ventricular (LV) dysfunction. Because the number of patients with chronic heart failure of ischemic origin is increasing worldwide, development of novel therapeutic strategies for those patients are needed. We have previously demonstrated that low-intensity pulsed ultrasound (LIPUS) improves myocardial ischemia in a pig model of chronic myocardial ischemia through enhanced myocardial angiogenesis. We also have recently reported that the LIPUS ameliorates post-MI LV remodeling in a mouse model of acute myocardial infarction (AMI). In the present study, we thus examined whether LIPUS also ameliorates contractile cardiac function in pressure-overloaded hearts in mice. Methods and Results: Chronic LV pressure overload was induced with transverse aortic constriction (TAC) in mice. The heart was treated with either placebo or LIPUS three times in the first week after TAC and was subsequently repeated once a week for 8 weeks. At 8 weeks, LV fractional shortening (LVFS) was significantly depressed in the placebo group, which was significantly ameliorated in the LIPUS group (36.2±3.8 vs. 30.4±0.5%, P<0.05). Capillary density in the LV was significantly higher in the LIPUS group than in placebo group (4229±455 vs. 3243±143 /mm 2 , P<0.05). Perivascular fibrosis was attenuated in the LIPUS group compared with the placebo group (P<0.05). The mRNA expression of BNP and Collagen III (Iα) was lower in the LIPUS group than in the placebo group (both P<0.05). Western blot analysis revealed that VEGF, eNOS and Hif-1α were significantly up-regulated in the LIPUS group (all P<0.05 vs. placebo). Akt was also significantly activated in the LIPUS group (P<0.05 vs. placebo). No adverse effect related to LIPUS therapy was noted. Conclusions: These results indicate that the LIPUS therapy ameliorates contractile cardiac function in pressure overload-induced cardiac dysfunction, for which enhanced myocardial angiogenesis may be involved. Thus, the LIPUS therapy may be a promising, non-invasive therapeutic strategy for the treatment of cardiac dysfunction due to pressure overload.