Augmentation of limb perfusion and reversal of tissue ischemia produced by ultrasound-mediated microbubble cavitation

J. Todd Belcik, Brian H. Mott, Aris Xie, Yan Zhao, Sajeevani Kim, Nathan J. Lindner, Azzdine Ammi, Joel M. Linden, Jonathan Lindner

    Research output: Contribution to journalArticle

    22 Citations (Scopus)

    Abstract

    Background - Ultrasound can increase tissue blood flow, in part, through the intravascular shear produced by oscillatory pressure fluctuations. We hypothesized that ultrasound-mediated increases in perfusion can be augmented by microbubble contrast agents that undergo ultrasound-mediated cavitation and sought to characterize the biological mediators. Methods and Results - Contrast ultrasound perfusion imaging of hindlimb skeletal muscle and femoral artery diameter measurement were performed in nonischemic mice after unilateral 10-minute exposure to intermittent ultrasound alone (mechanical index, 0.6 or 1.3) or ultrasound with lipid microbubbles (2×108 IV). Studies were also performed after inhibiting shear- or pressure-dependent vasodilator pathways, and in mice with hindlimb ischemia. Ultrasound alone produced a 2-fold increase (P2a receptors and epoxyeicosatrienoic acids had minimal effect. Limb nitric oxide production and muscle phospho-endothelial nitric oxide synthase increased in a stepwise fashion by ultrasound and ultrasound with microbubbles. In mice with unilateral hindlimb ischemia (40%-50% reduction in flow), ultrasound (mechanical index, 1.3) with microbubbles increased perfusion by 2-fold to a degree that was greater than the control nonischemic limb. Conclusions - Increases in muscle blood flow during high-power ultrasound are markedly amplified by the intravascular presence of microbubbles and can reverse tissue ischemia. These effects are most likely mediated by cavitation-related increases in shear and activation of endothelial nitric oxide synthase.

    Original languageEnglish (US)
    Article numbere002979
    JournalCirculation: Cardiovascular Imaging
    Volume8
    Issue number4
    DOIs
    StatePublished - Apr 22 2015

    Fingerprint

    Microbubbles
    Ischemia
    Extremities
    Perfusion
    Hindlimb
    Nitric Oxide Synthase Type III
    Pressure
    Muscles
    Perfusion Imaging
    Femoral Artery
    Vasodilator Agents
    Contrast Media
    Ultrasonography
    Nitric Oxide
    Skeletal Muscle
    Lipids
    Acids

    Keywords

    • microbubbles
    • nitric oxide
    • peripheral arterial disease
    • ultrasound

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine
    • Radiology Nuclear Medicine and imaging

    Cite this

    Augmentation of limb perfusion and reversal of tissue ischemia produced by ultrasound-mediated microbubble cavitation. / Belcik, J. Todd; Mott, Brian H.; Xie, Aris; Zhao, Yan; Kim, Sajeevani; Lindner, Nathan J.; Ammi, Azzdine; Linden, Joel M.; Lindner, Jonathan.

    In: Circulation: Cardiovascular Imaging, Vol. 8, No. 4, e002979, 22.04.2015.

    Research output: Contribution to journalArticle

    Belcik, J. Todd ; Mott, Brian H. ; Xie, Aris ; Zhao, Yan ; Kim, Sajeevani ; Lindner, Nathan J. ; Ammi, Azzdine ; Linden, Joel M. ; Lindner, Jonathan. / Augmentation of limb perfusion and reversal of tissue ischemia produced by ultrasound-mediated microbubble cavitation. In: Circulation: Cardiovascular Imaging. 2015 ; Vol. 8, No. 4.
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