Treatment of Limb Ischemia with Conducted Effects of Catheter-Based Endovascular Ultrasound

Matthew A. Muller, Koya Ozawa, James Hodovan, Matthew W. Hagen, David S.H. Giraud, Yue Qi, Aris Xie, Theodore R. Hobbs, Paul S. Sheeran, Jonathan R. Lindner

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Ultrasound (US) is known to stimulate endogenous shear-dependent pathways, and can lower microvascular resistance through mediators that are conducted downstream from US exposure. We hypothesized that endovascular US, already in use for thrombolysis in humans, can improve tissue perfusion in the setting of acute limb ischemia through downstream-conducted effects. Models of severe peripheral arterial disease were developed in mice and in rhesus macaques. An endovascular US catheter (2.3 MHz, 0.5–1.1 MPa) was used to expose the limb adductor in mice for 10 min or the femoral artery distal to stenosis in macaques for 15 min. Quantitative contrast-enhanced ultrasound perfusion imaging was performed to assess flow augmentation in the adductor muscle of mice and the calf muscle of macaques. Microvascular blood flow in the ischemic limb relative to the contralateral control limb was reduced to 22 ± 8% in mice and 36 ± 20% in macaques. US produced immediate 2.3- and 3-fold increases (p < 0.05) in the murine and macaque ischemic limbs, respectively. In macaques, perfusion in the ischemic limb was increased to a normal level. We conclude that non-cavitating US produced by endovascular catheters that are used to enhance thrombolysis in humans can reduce vascular resistance and increase limb perfusion in the setting of acute ischemia.

    Original languageEnglish (US)
    Pages (from-to)2277-2285
    Number of pages9
    JournalUltrasound in Medicine and Biology
    Volume47
    Issue number8
    DOIs
    StatePublished - Aug 2021

    Keywords

    • Limb ischemia
    • Peripheral artery disease
    • Therapeutic ultrasound

    ASJC Scopus subject areas

    • Radiological and Ultrasound Technology
    • Biophysics
    • Acoustics and Ultrasonics

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