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Low-intensity pulsed ultrasound induces angiogenesis and ameliorates left ventricular dysfunction in a porcine model of chronic myocardial ischemia.

Hanawa K, Ito K, Aizawa K, Shindo T, Nishimiya K, Hasebe Y, Tuburaya R, Hasegawa H, Yasuda S, Kanai H, Shimokawa H - PLoS ONE (2014)

Bottom Line: 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).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).

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.

ABSTRACT

Background: Although 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 results: We 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.

Conclusions: These results suggest that the LIPUS therapy is promising as a new, non-invasive therapy for IHD.

No MeSH data available.


Related in: MedlinePlus

LIPUS therapy increased the density of factor VIII-positive capillaries in the ischemic myocardium.(A, B) Factor VIII staining of the LCx region from the control (A) and the LIPUS group (B). Scale bar represents 20 µm. C. Capillary density was significantly higher in the LIPUS group than in the control group in the ischemic lateral wall. Results are expressed as mean ± SEM (n = 7 each).
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pone-0104863-g005: LIPUS therapy increased the density of factor VIII-positive capillaries in the ischemic myocardium.(A, B) Factor VIII staining of the LCx region from the control (A) and the LIPUS group (B). Scale bar represents 20 µm. C. Capillary density was significantly higher in the LIPUS group than in the control group in the ischemic lateral wall. Results are expressed as mean ± SEM (n = 7 each).

Mentions: There was no difference in the coronary artery dominance between the 2 groups; in the control group, right dominant in 0, balanced type in 7, left dominant in 2 and in the LIPUS group, right dominant in 0, balanced type in 7, and left dominant in 2 [17]. At 4 weeks after ameroid implantation, coronary angiography demonstrated a total occlusion of the LCx, which was perfused via collateral vessels with severe delay in both the control (Figure S3A) and the LIPUS groups (Figure S3B). However, at 8 weeks, the LIPUS group (Figure S3D), but not the control group (Figure S3C), showed a marked development of coronary collateral vessels in the ischemic LCx region, with an increased Rentrop score (Figure S3E) and an increased number of visible coronary arteries in the region (Figure S3F). Factor VIII staining showed that the number of factor VIII-positive capillaries was increased only in the LIPUS group (Figure 5A and 5B). Quantitative analysis demonstrated that the number of capillaries in the ischemic lateral wall region at 8 weeks was significantly higher in the LIPUS group than in the control group (Control, 858±151 vs. LIPUS, 1084±175/mm2, P<0.05), whereas it was unchanged in the non-ischemic IVS region in both groups (Control, 751±20 vs. LIPUS, 785±45/mm2, P = 0.27) (Figure 5C).


Low-intensity pulsed ultrasound induces angiogenesis and ameliorates left ventricular dysfunction in a porcine model of chronic myocardial ischemia.

Hanawa K, Ito K, Aizawa K, Shindo T, Nishimiya K, Hasebe Y, Tuburaya R, Hasegawa H, Yasuda S, Kanai H, Shimokawa H - PLoS ONE (2014)

LIPUS therapy increased the density of factor VIII-positive capillaries in the ischemic myocardium.(A, B) Factor VIII staining of the LCx region from the control (A) and the LIPUS group (B). Scale bar represents 20 µm. C. Capillary density was significantly higher in the LIPUS group than in the control group in the ischemic lateral wall. Results are expressed as mean ± SEM (n = 7 each).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4128732&req=5

pone-0104863-g005: LIPUS therapy increased the density of factor VIII-positive capillaries in the ischemic myocardium.(A, B) Factor VIII staining of the LCx region from the control (A) and the LIPUS group (B). Scale bar represents 20 µm. C. Capillary density was significantly higher in the LIPUS group than in the control group in the ischemic lateral wall. Results are expressed as mean ± SEM (n = 7 each).
Mentions: There was no difference in the coronary artery dominance between the 2 groups; in the control group, right dominant in 0, balanced type in 7, left dominant in 2 and in the LIPUS group, right dominant in 0, balanced type in 7, and left dominant in 2 [17]. At 4 weeks after ameroid implantation, coronary angiography demonstrated a total occlusion of the LCx, which was perfused via collateral vessels with severe delay in both the control (Figure S3A) and the LIPUS groups (Figure S3B). However, at 8 weeks, the LIPUS group (Figure S3D), but not the control group (Figure S3C), showed a marked development of coronary collateral vessels in the ischemic LCx region, with an increased Rentrop score (Figure S3E) and an increased number of visible coronary arteries in the region (Figure S3F). Factor VIII staining showed that the number of factor VIII-positive capillaries was increased only in the LIPUS group (Figure 5A and 5B). Quantitative analysis demonstrated that the number of capillaries in the ischemic lateral wall region at 8 weeks was significantly higher in the LIPUS group than in the control group (Control, 858±151 vs. LIPUS, 1084±175/mm2, P<0.05), whereas it was unchanged in the non-ischemic IVS region in both groups (Control, 751±20 vs. LIPUS, 785±45/mm2, P = 0.27) (Figure 5C).

Bottom Line: 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).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).

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.

ABSTRACT

Background: Although 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 results: We 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.

Conclusions: These results suggest that the LIPUS therapy is promising as a new, non-invasive therapy for IHD.

No MeSH data available.


Related in: MedlinePlus