• 1

    Cines DB, Pollak ES & Buck CA, et al. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 1998;91:35273561.

  • 2

    Dejana E, Corada M, Lampugnani MG. Endothelial cell-to-cell junctions. FASEB J 1995;9:910918.

  • 3

    Widlansky ME, Gokce N & Keaney JF Jr, et al. The clinical implications of endothelial dysfunction. J Am Coll Cardiol 2003;42:11491160.

  • 4

    Shaul PW. Regulation of endothelial nitric oxide synthase: location, location, location. Annu Rev Physiol 2002;64:749774.

  • 5

    Kuvin JT, Patel AR & Sliney KA, et al. Peripheral vascular endothelial function testing as a noninvasive indicator of coronary artery disease. J Am Coll Cardiol 2001;38:18431849.

    • Search Google Scholar
    • Export Citation
  • 6

    Vita JA, Keaney JF & Larson MG, et al. Brachial artery vasodilator function and systemic inflammation in the Framingham offspring study. Circulation 2004;110:36043609.

    • Search Google Scholar
    • Export Citation
  • 7

    Johnson SR, Harvey PJ & Floras JS, et al. Impaired brachial artery endothelium dependent flow mediated dilation in systemic lupus erythematosus: preliminary observations. Lupus 2004;13:590593.

    • Search Google Scholar
    • Export Citation
  • 8

    Duffy TC, Kirby R, Rudloff E. Critical role of the vascular endothelial cell in health and disease: a review article. J Vet Emerg Crit Care 2004;14:8499.

    • Search Google Scholar
    • Export Citation
  • 9

    Consentino F, Volpe M. Hypertension, stroke, and endothelium. Curr Hypertens Rep 2005;7:6871.

  • 10

    Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980;288:373376.

    • Search Google Scholar
    • Export Citation
  • 11

    Ganz P, Vita JA. Testing endothelial vasomotor function: nitric oxide, a multipotent molecule. Circulation 2003;108:20492053.

  • 12

    Moncada S, Higgs A. Mechanisms of disease: the L-argininenitric oxide pathway. N Engl J Med 1993;329:20022012.

  • 13

    Waldman SA, Murad R. Biochemical mechanisms underlying vascular smooth muscle relaxation: the guanylate cyclase-cyclic GMP system. J Cardiovasc Pharmacol 1988;12:S115S118.

    • Search Google Scholar
    • Export Citation
  • 14

    Davies PF, Barbee KA & Volin MV, et al. Spatial relationships in early signaling events of flow-mediated endothelial mechanotransduction. Annu Rev Physiol 1997;59:527549.

    • Search Google Scholar
    • Export Citation
  • 15

    Loscalzo J. What we know and don't know about L-arginine and NO. Circulation 2000;101:21262129.

  • 16

    Panza JA, Quyyumi AA & Brush JE, et al. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med 1990;323:17721773.

    • Search Google Scholar
    • Export Citation
  • 17

    Verma S, Anderson TJ. Fundamentals of endothelial function for the clinical cardiologist. Circulation 2002;105:546549.

  • 18

    Fischer D, Rossa S & Landmesser U, et al. Endothelial dysfunction in patients with chronic heart failure is independently associated with increased incidence of hospitalization, cardiac transplantation, or death. Eur Heart J 2005;26:6569.

    • Search Google Scholar
    • Export Citation
  • 19

    Benjamin EJ, Larson MG & Keyes MJ, et al. Clinical correlates and heritability of flow-mediated dilation in the community: the Framingham heart study. Circulation 2004;109:613619.

    • Search Google Scholar
    • Export Citation
  • 20

    Kaiser L, Spickard RC, Olivier NB. Heart failure depresses endothelium-dependent responses in canine femoral artery. Am J Physiol Heart Circ Physiol 1989;256:H962H967.

    • Search Google Scholar
    • Export Citation
  • 21

    Kiuchi K, Sato N & Shannon RP, et al. Depressed beta-adrenergic receptor- and endothelium-mediated vasodilation in conscious dogs with heart failure. Circ Res 1993;73:10131023.

    • Search Google Scholar
    • Export Citation
  • 22

    Nikolaidis LA, Mathier MA & Doverspike A, et al. Coronary blood flow responses are impaired independent of NO and endothelial function in conscious dogs with dilated cardiomyopathy. J Card Fail 2005;11:313321.

    • Search Google Scholar
    • Export Citation
  • 23

    de Laforcade AM, Freeman LM, Rush JE. Serum nitrate and nitrite in dogs with spontaneous cardiac disease. J Vet Intern Med 2003;17:315318.

    • Search Google Scholar
    • Export Citation
  • 24

    Pedersen HD, Schutt T & Sondergaard R, et al. Decreased plasma concentration of nitric oxide metabolites in dogs with untreated mitral regurgitation. J Vet Intern Med 2003;17:178184.

    • Search Google Scholar
    • Export Citation
  • 25

    Corretti MC, Anderson TJ & Benjamin EJ, et al. Guidelines for the ultrasound assessment of endothelial-dependent flow mediated vasodilation of the brachial artery. J Am Coll Cardiol 2002;39:257265.

    • Search Google Scholar
    • Export Citation
  • 26

    Sorensen KE, Celermajer DS & Spielgelhalter DJ, et al. Noninvasive measurement of human endothelial dependent arterial responses: accuracy and reproducibility. Br Heart J 1995;74:247253.

    • Search Google Scholar
    • Export Citation
  • 27

    Moens AL, Goovaerts I & Claeys MJ, et al. Flow-mediated vasodilation: a diagnostic instrument, or an experimental tool? Chest 2005;127:22542263.

  • 28

    Elkayam U, Khan S & Mehboob A, et al. Impaired endothelium-mediated vasodilation in heart failure: clinical evidence and the potential for therapy. J Card Fail 2002;8:1520.

    • Search Google Scholar
    • Export Citation
  • 29

    Kuvin JT, Karas RH. Clinical utility of endothelial function testing: ready for prime time? Circulation 2003;107:32433247.

  • 30

    Glasser SP, Arnett DK & McVeigh GE, et al. Vascular compliance and cardiovascular disease: a risk factor of a marker? Am J Hypertens 1997;10:11751189.

    • Search Google Scholar
    • Export Citation
  • 31

    Vita JA, Keaney JF Jr. Endothelial function: a barometer for cardiovascular risk? Circulation 2002;106:640642.

  • 32

    Kelm M. Flow-mediated dilatation in human circulation: diagnostic and therapeutic aspects. Am J Physiol Heart Circ Physiol 2002;282:H1H5.

    • Search Google Scholar
    • Export Citation
  • 33

    Dean AS, Margulies KB & Nicholas JJ, et al. Impaired vasoreactivity in end-stage heart failure patients on intravenous inotropic support. J Card Fail 2005;11:351357.

    • Search Google Scholar
    • Export Citation
  • 34

    Fernández del Palacio MJ, Fuentes VL & Bonagura JD, et al. Evaluation of transcutaneous Doppler ultrasonography for the measurement of blood flow in the femoral artery. Am J Vet Res 2003;64:4350.

    • Search Google Scholar
    • Export Citation
  • 35

    Bartko JJ, Carpenter WT Jr. On the methods and theory of reliability. J Nerv Ment Dis 1976;163:307317.

  • 36

    Diggle P, Liang K-Y, Zeger S. Analysis of longitudinal data. Oxford, England: Clarendon Press, 1994;78116.

  • 37

    Cohen J. Statistical power analysis for the behavioral sciences. New York: Academic Press Inc, 1977;7982.

  • 38

    Hiltawsky KM, Wiegratz A & Enderle MD, et al. Real-time detection of vessel diameter with ultrasound. Biomed Tech (Berl) 2003;48:141146.

  • 39

    Lee K, Choi M & Yoon Y, et al. Spectral waveform analysis of major arteries in conscious dogs by Doppler ultrasonography. Vet Radiol Ultrasound 2004;45:166171.

    • Search Google Scholar
    • Export Citation
  • 40

    Mitchell GF, Parise H & Vita JA, et al. Local shear stress and brachial artery flow-mediated dilation: the Framingham Heart Study. Hypertension 2004;44:134139.

    • Search Google Scholar
    • Export Citation
  • 41

    Ishibashi Y, Takahashi N & Shimada T, et al. Short duration of reactive hyperemia in the forearm of subject with multiple cardiovascular risk factors. Circ J 2006;70:115123.

    • Search Google Scholar
    • Export Citation
  • 42

    Hiss K, Steioff K & Loehn M, et al. Transcutaneous vascular ultrasound in hypercholesterolaemic rabbits: a new method to evaluate endothelial function. Lab Anim 2006;40:8086.

    • Search Google Scholar
    • Export Citation
  • 43

    Kao YH, Mohler ER, Arger PH, Sehgal CM. Brachial artery: measurement of flow-mediated dilatation with cross-sectional US-technical validation. Radiology 2003;228:895900.

    • Search Google Scholar
    • Export Citation
  • 44

    Mullen MJ, Kharbanda RK & Corss J, et al. Heterogenous nature of flow-mediated dilatation in human conduit arteries in vivo: relevance to endothelial dysfunction in hypercholesterolemia. Circ Res 2001;88:145151.

    • Search Google Scholar
    • Export Citation

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Use of a flow-mediated vasodilation technique to assess endothelial function in dogs

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  • 1 Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536.
  • | 2 Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536.
  • | 3 Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536.
  • | 4 Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536.
  • | 5 University of Massachusetts Medical School, Worcester, MA 01655.

Abstract

Objective—To develop and assess the reproducibility of a protocol to noninvasively test endothelial function in dogs on the basis of the flow-mediated vasodilation (FMD) procedure used in humans.

Animals—5 healthy spayed female dogs.

Procedures—Luminal arterial diameter and blood flow velocity in the brachial and femoral arteries were measured with ultrasonography. The within-dog reproducibility of these ultrasonographic measurements was tested. An occlusion period of 1, 3, or 5 minutes with an inflatable cuff was used to create the FMD response. Measurements made at 15, 30, and 60 seconds following release of the occlusion were compared with measurements made immediately prior to each occlusion to assess the FMD response.

Results—Within-dog reproducibility of measurements revealed moderate to high correlations. Change from baseline in luminal arterial diameter was most substantial when measured at 30 seconds following release of occlusion, whereas blood flow velocity changes were maximal when measured at 15 seconds following release. The brachial imaging site provided a larger number of significant FMD responses than the femoral site. The 3-minute occlusion period provided equal or better responses than the 5-minute occlusion period.

Conclusions and Clinical Relevance—Ultrasonographic measurement of the FMD responses was a feasible and reproducible technique and significant changes from baseline were detected. The FMD responses in dogs were most substantial when performed at the brachial artery with blood flow velocity and luminal arterial diameter changes from baseline measured at 15 and 30 seconds, respectively, following release of a 3-minute occlusion period.

Contributor Notes

Supported in part by a National Institutes of Health short-term training grant (No. T35 DK07635) and the Barkley Fund.

Address correspondence to Dr. Freeman.