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    A new model of peripheral arterial disease: sustained impairment of nutritive microcirculation and its recovery by chronic electrical stimulation.

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    Authors
    Brown, Margaret D.
    Kelsall, C.J.
    Milkiewicz, M.
    Anderson, Stephen I.
    Hudlicka, Olga
    Issue Date
    2005
    
    Metadata
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    Abstract
    OBJECTIVES: To develop a model of peripheral arterial disease (PAD) in rat skeletal muscle with sustained impairment of microcirculatory perfusion, and to ascertain whether increased muscle activity can reverse the impairment. METHODS: Three weeks after iliac ligation in rats, the ipsilateral femoral artery was ligated (double ligation, DL), and in some animals, muscle activity was increased by electrical stimulation for 2 weeks (10 Hz, 15 min on, 85 mins off, 7 times per day). Diameter changes of precapillary arterioles to vasoactive agonists and capillary perfusion (flow intermittency, capillary red cell velocity [V(rbc)], and diameters) were measured in extensor digitorum longus muscle and compared with 5 weeks iliac only ligation (single ligation, SL) and controls. Total muscle endothelial nitric oxide synthase (eNOS) was estimated by Western blotting. RESULTS: Whereas single ligation increased intermittency of capillary flow with little effect on V(rbc) and shear stress, DL completely eliminated increases in V(rbc) and shear stress after muscle contractions. Arterial dilation to sodium nitroprusside was attenuated similarly in SL and DL; in SL, acetylcholine induced constriction and bradykinin an attenuated dilation, but in DL vessels were unresponsive to either. Chronic stimulation returned all microcirculatory parameters in DL to normal and increased levels of eNOS protein by 75%. CONCLUSIONS: Femoral artery ligation following iliac ligation impairs arteriolar vasodilator capacity, capillary perfusion, and shear-dependent function of microcirculatory endothelium more than iliac ligation alone and is more representative of long-standing ischemia in PAD. Chronic intermittent electrical stimulation can normalize these derangements.
    Citation
    Microcirculation, 2005, 12(4): 373-381
    Publisher
    Taylor & Francis (Informa Healthcare)
    Journal
    Microcirculation
    URI
    http://hdl.handle.net/2436/20980
    DOI
    10.1080/10739680590934817
    PubMed ID
    16020083
    Additional Links
    http://www.informaworld.com/smpp/title~content=t713723262
    Type
    Journal article
    Language
    en
    ISSN
    1073-9688
    ae974a485f413a2113503eed53cd6c53
    10.1080/10739680590934817
    Scopus Count
    Collections
    Research Institute in Healthcare Science

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