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

2.50
Hdl Handle:
http://hdl.handle.net/2436/20980
Title:
A new model of peripheral arterial disease: sustained impairment of nutritive microcirculation and its recovery by chronic electrical stimulation.
Authors:
Brown, Margaret D.; Kelsall, C.J.; Milkiewicz, M.; Anderson, Stephen I.; Hudlicka, Olga
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
Issue Date:
2005
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:
Article
Language:
en
ISSN:
1073-9688
Appears in Collections:
Diabetes, Physiology and Molecular Medicine Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorBrown, Margaret D.-
dc.contributor.authorKelsall, C.J.-
dc.contributor.authorMilkiewicz, M.-
dc.contributor.authorAnderson, Stephen I.-
dc.contributor.authorHudlicka, Olga-
dc.date.accessioned2008-03-18T11:21:09Z-
dc.date.available2008-03-18T11:21:09Z-
dc.date.issued2005-
dc.identifier.citationMicrocirculation, 2005, 12(4): 373-381en
dc.identifier.issn1073-9688-
dc.identifier.pmid16020083-
dc.identifier.doi10.1080/10739680590934817-
dc.identifier.urihttp://hdl.handle.net/2436/20980-
dc.description.abstractOBJECTIVES: 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.en
dc.language.isoenen
dc.publisherTaylor & Francis (Informa Healthcare)en
dc.relation.urlhttp://www.informaworld.com/smpp/title~content=t713723262en
dc.subjectArteriolesen
dc.subjectCapillary perfusionen
dc.subjectCapillary shear stressen
dc.subjectEndothelial-dependent dilationen
dc.subjectIschemiaen
dc.subjectSkeletal muscleen
dc.subject.meshAnimalsen
dc.subject.meshDisease Models, Animalen
dc.subject.meshElectric Stimulationen
dc.subject.meshEndothelium, Vascularen
dc.subject.meshFemoral Arteryen
dc.subject.meshMicrocirculationen
dc.subject.meshMuscle Contractionen
dc.subject.meshMuscle, Skeletalen
dc.subject.meshNitric Oxide Synthaseen
dc.subject.meshNitric Oxide Synthase Type IIIen
dc.subject.meshPeripheral Vascular Diseasesen
dc.subject.meshRatsen
dc.subject.meshRats, Sprague-Dawleyen
dc.subject.meshVasodilationen
dc.titleA new model of peripheral arterial disease: sustained impairment of nutritive microcirculation and its recovery by chronic electrical stimulation.en
dc.typeArticleen
dc.identifier.journalMicrocirculationen

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