Abstract 12327: Low-Intensity Pulsed Ultrasound Induces Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Porcine Model of Chronic Myocardial Ischemia
Background: Therapeutic angiogenesis represents a novel treatment for “no-option” patients with refractory ischemic heart disease. Recently, the low-intensity pulsed ultrasound (LIPUS) is used as non-invasive medical therapies for fracture and bone healing. Although the mechanical stimuli with acoustic pressure waves have been reported to induce angiogenesis, its clinical application to chronic myocardial ischemia remains unknown. In this study, we thus examined whether LIPUS induces angiogenesis in vitro and if so, whether it ameliorates chronic myocardial ischemia in vivo.
Methods and Results: We measured acoustic pressure of LIPUS by using a needle hydrophone. When increasing cycle number to 1, 16 and 32 at the intensity of 100 mW/cm2 (SPTA), peak negative-pressure generated by a 1.8 MHz transducer was decreased to 1.6, 0.8 and 0.6 MPa, respectively. Under those conditions, when cultured human umbilical vein endothelial cells were exposed to LIPUS for 20 min, mRNA expression of vascular endothelial growth factor (VEGF) peaked at 32-cycle 3 hours after irradiation (P=0.02)(Figure A). We then examined the effect of LIPUS in a porcine model of chronic myocardial ischemia with an ameroid constrictor placed around the left circumflex coronary artery (LCX). Four weeks after 20-mim irradiation of 32-cycle LIPUS to the ischemic LCX region by 2-dimensional scan at 3 different short axis levels, left ventricular ejection fraction (LVEF) was significantly improved in the LIPUS group (46±4% to 55±5%, n=7; P<0.05) without any adverse effects, whereas it remained unchanged in the control group (45±5% to 46±6%, n=7; P=0.31) (Figure B). Factor VIII staining showed that capillary density (/mm2) was significantly increased in the LIPUS group compared with the control group (1084±175 vs. 858±151, P<0.05 in the endocardium; 1051±104 vs. 834±104, P<0.05 in the epicardium).
Conclusions: These results suggest the therapeutic potential of LIPUS for ischemic heart disease.
- © 2011 by American Heart Association, Inc.