Low-Intensity Pulsed Ultrasound Induces Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Porcine Model of Chronic Myocardial Ischemia |
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| Authors: | Kenichiro Hanawa Kenta Ito Kentaro Aizawa Tomohiko Shindo Kensuke Nishimiya Yuhi Hasebe Ryuji Tuburaya Hideyuki Hasegawa Satoshi Yasuda Hiroshi Kanai Hiroaki Shimokawa |
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| Institution: | 1. Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.; 2. Division of Biomedical Measurements and Diagnostics, Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan.; 3. Department of Electronic Engineering, Graduate School of Engineering, Tohoku University, Sendai, Japan.; 4. National Cerebral and Cardiovascular Center, Osaka, Japan.; University of Bristol, United Kingdom, |
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| Abstract: | BackgroundAlthough a significant progress has been made in the management of ischemic heart disease (IHD), the number of severe IHD patients is increasing. Thus, it is crucial to develop new, non-invasive therapeutic strategies. In the present study, we aimed to develop low-intensity pulsed ultrasound (LIPUS) therapy for the treatment of IHD.Methods and ResultsWe first confirmed that in cultured human endothelial cells, LIPUS significantly up-regulated mRNA expression of vascular endothelial growth factor (VEGF) with a peak at 32-cycle (P<0.05). Then, we examined the in vivo effects of LIPUS in a porcine model of chronic myocardial ischemia with reduced left ventricular ejection fraction (LVEF) (n = 28). The heart was treated with either sham (n = 14) or LIPUS (32-cycle with 193 mW/cm2 for 20 min, n = 14) at 3 different short axis levels. Four weeks after the treatment, LVEF was significantly improved in the LIPUS group (46±4 to 57±5%, P<0.05) without any adverse effects, whereas it remained unchanged in the sham group (46±5 to 47±6%, P = 0.33). Capillary density in the ischemic region 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 (0.78±0.2 to 1.39±0.4 ml/min/g, P<0.05), but not in the control group (0.84±0.3 to 0.97±0.4 ml/min/g). Western blot analysis showed that VEGF, eNOS and bFGF were all significantly up-regulated only in the LIPUS group.ConclusionsThese results suggest that the LIPUS therapy is promising as a new, non-invasive therapy for IHD. |
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