Abstract 12873: Low-Intensity Pulsed Ultrasound Induces Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Porcine Model of Chronic Myocardial Ischemia
Background: The number of patients with severe ischemic heart disease has been rapidly increasing worldwide. The low-intensity pulsed ultrasound (LIPUS) is currently used as a non-invasive therapy for bone fracture, and mechanical stimuli with acoustic pressure waves have been recently reported to induce angiogenesis. In this study, we thus aimed to develop the LIPUS therapy for the treatment of ischemic heart disease.
Methods and Results: In cultured human vascular endothelial cells, LIPUS (1, 16, and 32-cycle at the intensity of 100 mW/cm2 for 20 min) up-regulated mRNA expression of vascular endothelial growth factor (VEGF) with a peak noted at 32-cycle LIPUS 3 hours after the treatment (P=0.02) (Figure). Based on the in vitro study, the in vivo effect of LIPUS was examined in a porcine model of chronic myocardial ischemia with an ameroid constrictor placed around the left circumflex coronary artery(n=17). The ischemic region was treated with either sham treatment (n=8) or LIPUS (20-mim irradiation with 32-cycle) by 2-dimensional scan (n=9) at 3 different short axis levels. Four weeks after the treatment, left ventricular ejection fraction significantly improved in the LIPUS group (47±4 to 57±5%, P<0.05) without any adverse effects, whereas it remained unchanged in the control group (46±5% to 47±6%, P=0.33) (Figure). Factor VIII staining revealed that capillary density was significantly increased in the LIPUS group compared with the control group (1084±175 vs. 858±151/mm2, P<0.05). Regional myocardial blood flow was also significantly improved in the LIPUS group (0.89±0.49 to 1.49±0.53 ml/min/g, P<0.05), whereas it remained unchanged in the control group (0.87±0.29 to 0.97±0.39 ml/min/g, P=0.32). There were no adverse effects of the LIPUS study, such as myocardial injury and/or arrhythmias.
Conclusions: These results suggest that the LIPUS therapy is effective and safe for the treatment of ischemic heart disease.
- © 2012 by American Heart Association, Inc.