Therapeutic ultrasound promotes reperfusion and angiogenesis in a rat model of peripheral arterial disease

Babak Nazer, Farzin Ghahghaie, Risa Kashima, Tatiana Khokhlova, Camilo Perez, Lawrence Crum, Tom Matula, Akiko Hata

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Background: Shock wave therapy (SWT) is an acoustic technology clinically used for the non-invasive treatment of ischemic heart disease (IHD). Therapeutic ultrasound (TUS) has more recently been developed for the same indication, although its effects on reperfusion and angiogenesis have yet to be directly compared to those of SWT. Methods and Results: TUS and SWT acoustic parameters were matched, and their ability to promote angiogenesis and reperfusion in a rat hindlimb ischemia model was compared. After left femoral artery excision, 3-weekly TUS, SWT or sham treatments (n=10 rats each) of the left hindlimb were performed for 2 weeks. Laser Doppler perfusion imaging demonstrated improved perfusion with TUS (66±4% L:R hindlimb perfusion, mean ± SEM, P=0.02), but not with SWT (59±4%, P=0.13) compared with sham (50±4%). Immunohistochemistry of CD31 demonstrated increased microvascular density with TUS (222.6 vessels/high-power field, P=0.001) and SWT (216.9, P=0.01) compared to sham-treated rats (196.0). Tissue vascular endothelial growth factor mRNA levels were elevated in the left hindlimb of TUS-, but not SWT- or sham-treated rats. Conclusions: Direct comparison demonstrates that TUS is more effective than SWT at promoting reperfusion, whereas both therapies promote angiogenesis in ischemic gastrocnemius muscle. These results suggest that TUS may be more effective than SWT for the treatment of IHD and peripheral arterial disease.

Original languageEnglish (US)
Pages (from-to)2043-2049
Number of pages7
JournalCirculation Journal
Issue number9
StatePublished - Aug 25 2015
Externally publishedYes


  • Angiogenesis
  • Ischemic heart disease
  • Peripheral arterial disease
  • Shock wave therapy
  • Ultrasound

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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