Ce travail a été soutenu par des numéros d&#39;octroi de subventions et R01HL096593 K23HL72825 du National Heart, Lung, and Blood Institute. Le contenu relève de la seule responsabilité de l&#39;Université Thomas Jefferson et ne représentent pas nécessairement les vues officielles de la National Heart, Lung, and Blood Institute ou le National Institutes of Health.

Présentation de cas (obligatoire, le cas échéant): NA, ce qui est encore une procédure de recherche expérimentale, pas encore utilisé cliniquement. Diagnostic, évaluation et plan d&#39;(obligatoire, le cas échéant): NA, ce qui est encore une procédure de recherche expérimentale, pas encore utilisé cliniquement. Procédure (obligatoire): Cette partie doit comprendre une description étape par étape des procédures pertinentes, conformes aux lignes directrices ci-dessous. 1. Microscopie capillaire (Figure 1) <ol><li> Notre technique a été adaptée à partir de la capillaroscopie Serne et ses collègues 1. Un critère d&#39;exclusion pour cette procédure est la maladie vasculaire du collagène, depuis collagène vasculaire produit des changements connus capillaires 2. </li><li> Après un minimum de 10 heures à jeun et 20 min de repos assis, les mesures microvasculaires sont effectuées pour une demi-heure entre 7et 11 heures, dans une pièce à température, calme contrôlée (maintenue entre 21,5 à 22,5 ° C), avec le sujet en position assise et la main gauche au niveau du cœur. </li><li> Périunguéale capillaires de la peau dorsale de la troisième doigt sont visualisés en utilisant un stéréomicroscope (Olympus, Center Valley, PA), liée à une Insight SPOT 4 mégapixels appareil photo numérique monochrome (Numéro de modèle IN-1400: Instruments de diagnostic; Sterling Heights, MI), et un ordinateur portable (Dell Latitude D600: Dell à Austin, TX). Pour limiter le mouvement, la main gauche et avant-bras sont plus ou moins recouverte d&#39;une couverture pliée, et repose sur une autre couverture pliée placé à la base du microscope. </li><li> Éclairage nailbed est obtenue avec une lampe de 250 W halogène fibre optique (KL 2500LCD: Schott-FOSTEC; Elmsford, État de New York); éclairage supplémentaire à partir d&#39;un 150W fibre supplémentaire source optique à une lampe halogène (B &amp; B Microscopes, Ltd, Warrendale, Pennsylvanie) est utilisé chez les individus une pigmentation foncée. </li><li> De visualiser les capillaires, le3,2 x objectif (Olympus 3.2/0.07) est utilisé avec un système de grossissement total de 38.4x. </li><li> Grâce à un logiciel d&#39;imagerie SPOT fourni avec l&#39;appareil, clair / sombre contraste dans les images capillaires est améliorée en utilisant la même fonction standard du logiciel SPOT (étirement des niveaux clairs et foncés) pour maximiser la visibilité des capillaires dans toutes les matières. </li><li> Pour quantifier la densité capillaire, microphotographies numériques sont prises toutes les secondes 5.3 pendant chacune des trois étapes, au départ de repos, pendant une hyperémie réactive postocclusive, et pendant l&#39;occlusion veineuse. (A) Au départ de repos, microphotographies sont prises sur une période de trois minutes pour détecter les capillaires perfusés au repos. (B) Au cours hyperémie réactive postocclusive, microphotographies sont prises à quantifier fonctionnellement perfusé capillaires (de base plus réserve capillaires), comme suit. Tout d&#39;abord, un brassard d&#39;occlusion sur le bras gauche est gonflé à 40 mm de mercure au-dessus de la pression systolique pendant 10 min. Microphotographies sont alors prises au cours èmee première minute qui suit immédiatement la libération de l&#39;occlusion artérielle, de visualiser tous les fonctionnellement perfusé capillaires. Basse densité capillaire après une hyperémie réactive indique une déficience fonctionnelle recrutement capillaire, et la raréfaction donc fonctionnel. (C) Au cours de l&#39;occlusion veineuse microphotographies sont prises afin de quantifier la densité capillaire maximale, ce qui inclut à la fois perfusé (avec des globules rouges actifs (RBC) de mouvement) et non perfusés (rempli de stagnation, non mobiles RBC) capillaires 3 comme suit. Après dix minutes de repos après l&#39;intervention postocclusive hyperémie réactive, le brassard est gonflé à 60 mm Hg pendant 60 sec, passivement forçant le sang dans tous présents brevet capillaires et microphotographies ont été prises pendant ce temps. Depuis maximale densité capillaire comprend tous structurellement capillaires présents, une réduction de la densité capillaire maximale indique la raréfaction structurelle. </li><li> Densité capillaire est défini comme le nombre de capillaires par carré millimeter de la peau périunguéale, et est calculé comme la moyenne des quatre mesures obtenues à partir des quatre images plus clairement ciblés, moins déformés par le mouvement. Dans nos études, les valeurs typiques pour la numération des capillaires (capillaires / mm 2) ont été 55-80 pour base, 65-90 pour le post-ischémique et 90-105 pour l&#39;occlusion veineuse. Les valeurs pour le recrutement capillaire pour cent se situent généralement entre 5% et 25% (moyenne ~ 10-15%) et de capillaires perfusés pour cent entre 70% et 95% (moyenne ~ 80-90%), avec des valeurs étant plus faible chez les hypertendus que les normotendus. La reproductibilité de la méthode de comptage a été vérifiée avec trois observateurs qui ont effectué des évaluations indépendantes des manuels de photographies de 10 sujets différents (figure 2). Les observateurs ont été aveuglés à la pression sanguine et l&#39;identité de ces sujets. Après la formation, les comptages ultérieurs effectués indépendamment montré un niveau élevé de consensus. Moyenne des divergences inter-juges et intra-évaluateurs étaient d&#39;ordeR 2-3 de capillaires / mm 2, et les coefficients de corrélation intra étaient tous supérieurs à 0,90. Variations à court terme des mesures capillaroscopie étaient du même ordre de grandeur que les écarts inter-juges et intra-évaluateur (environ 2 capillaires / mm 2), mais à plus long terme de variation observée au cours de 2-3 ans était un ordre de grandeur (environ 15 capillaires / mm 2), ce qui indique que les changements longitudinaux peuvent être facilement distingués des variations rater. Fiabilité des deux mesures de la fonction capillaire était également élevée (coefficient de corrélation intraclasse = 0,84 pour cent pour le recrutement capillaire et 0,82 pour cent pour perfusion capillaires). </li><li> Les enquêteurs ont désormais utiliser une méthode informatique permettant de quantifier la densité capillaire en utilisant Image-Pro Plus un logiciel d&#39;imagerie (version 6.2, Media Cybernetics, Inc, Bethesda, MD: Figure 3). Les corrélations de Pearson entre la valeur initiale, post-ischémique et maladie veinocompte la congestion nous fait avec le logiciel et comptages manuels correspondants dans 10 sujets étaient de 0,78, 0,78, et 0,71 respectivement (p &lt;0,05), ce qui indique un accord raisonnable entre les deux méthodes. Fiabilité des comptes informatiques est légèrement inférieur à celui des comptages manuels mais reste élevé (coefficient de corrélation intraclasse = 0,91 pour référence, 0,86 pour le post-ischémique, et de 0,84 pour l&#39;occlusion veineuse). Nous avons également des données non publiées démontrant l&#39;association de comptes automatisés présentant plusieurs facteurs de risque cardiovasculaires tels que l&#39;hypertension, dont nous sommes en train de préparer pour la publication. </li><li> Le tableau 1 résume les mesures de la densité capillaire et calculs. Recrutement pour cent capillaire est évaluée en divisant l&#39;augmentation de la densité capillaire induit par une hyperémie réactive postocclusive (postocclusive réactif densité capillaire moins hyperémie densité capillaire de base), par la densité maximale capillaire (observé pendant passive veinonous occlusion). Pour cent perfusé capillaires représente la proportion de toutes les personnes présentes capillaires qui sont perfusés (fonctionnellement actif), et est calculé en divisant postocclusive réactive densité capillaire hyperémie par la densité maximale capillaire. Recrutement pour cent à la fois capillaire et perfusé pour cent capillaires refléter le nombre de capillaires fonctionnels. Des valeurs plus faibles pour ces mesures indiquent fonctionnelle raréfaction capillaire. </li></ol> 2. Évaluation fonction endothéliale <ol><li> La fonction endothéliale est évaluée avant et après une hyperémie réactive postocclusive, en utilisant des mesures non invasives pléthysmographie de débit sanguin selon le procédé de Sivertsson, 4, qui utilise la stimulation dépendant de l&#39;endothélium d&#39;une hyperémie réactive pour induire une vasodilatation. </li><li> Avec le sujet en position assise après 10 min de repos en position couchée, une jauge de mercure dans le caoutchouc étiré souche à 10% au-delà de sa longueur au repos est bouclée around du sujet avant-bras 5 cm en dessous du pli du coude. </li><li> La jauge de contrainte est reliée à un pléthysmographe (CE-4: DE Hokanson, Inc; Bellevue), qui à son tour est relié à un enregistreur Doppler (CW-1; DE Hokanson, Inc; Belleveue, WA). </li><li> Un brassard d&#39;occlusion supérieure est appliquée, et le bras est suspendu confortablement au niveau du coeur à l&#39;aide d&#39;un bandage élingue reliée à un pôle réglable par voie intraveineuse. Systolique et diastolique et le rythme cardiaque sont obtenus avec une manchette DINAMAP ProCare 100 automatique BP (GE Healthcare, Piscataway, NJ) placé sur le bras opposé. </li><li> Un brassard pédiatrique autour du poignet est gonflé à 200 mm Hg pour obturer l&#39;écoulement de la main. Le brassard est gonflé à haute 50 mm Hg, dégonflé pendant 1,5 sec, puis regonflé rapidement avant chaque mesure du débit sanguin avant-bras, obtenu grâce à l&#39;expansion de la jauge de contrainte placée autour de l&#39;avant-bras. </li><li> Le flux sanguin avant-bras (FBF) est mesuré au départ reposé (FBF base) et un nouveaut postocclusive hyperémie induite par la vasodilatation maximale (FBF max). Pour les mesures de base du flux sanguin, quatre courbes consécutives FBF sont obtenus en 30 secondes (FBF base). </li><li> La manchette d&#39;occlusion est alors gonflé à 40 mm de mercure au-dessus de la pression systolique pendant 10 min. Suite à la publication de l&#39;occlusion artérielle (postocclusive hyperémie réactive), quatre courbes FBF consécutifs sont obtenus dans les 30 premières secondes d&#39;écoulement (FBF max). </li><li> Le ratio FBF max / FBF base est calculé comme une estimation de la vasodilatation, en divisant la moyenne des quatre valeurs max FBF par la moyenne des quatre valeurs de base FBF. 5 Résistance vasculaire avant-bras à la vasodilatation maximale (FVR max) est calculé comme la la pression artérielle moyenne (PAM) divisé par la FBF max. FBF max pendant une hyperémie réactive est directement liée à la perfusion après FBF maximum intra-artérielle d&#39;acétylcholine, un vasodilatateur endothélium-dépendant. 6 </sup&gt; En conséquence, la FBF max et le rapport FBF max / FBF de base sont acceptées mesures non invasives de la fonction endothéliale. 6-8 en outre, à la fois FBF max et max FVR refléter les changements des artères de résistance structurelles (augmentation de paroi / lumen ratio) 9. </li></ol>

<ol>
	<li>Serne, E. H., Gans, R. O., ter Maaten, J. C., ter Wee, P. M., Donker, A. J., Stehouwer, C. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Capillary+recruitment+is+impaired+in+essential+hypertension+and+relates+to+insulin's+metabolic+and+vascular+actions.">Capillary recruitment is impaired in essential hypertension and relates to insulin's metabolic and vascular actions.</a> Cardiovasc. Res. 49, 161-168 (2001).</li><li>Bollinger, A., Fagrell, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Clinical Capillaroscopy: A guide to its use in clinical research and practice. , (1990).</li><li>Antonios, T. F., Rattray, F. E., Singer, D. R., Markandu, N. D., Mortimer, P. S., MacGregor, G. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Maximization+of+skin+capillaries+during+intravital+video-microscopy+in+essential+hypertension:+comparison+between+venous+congestion,+reactive+hyperaemia+and+core+heat+load+tests.">Maximization of skin capillaries during intravital video-microscopy in essential hypertension: comparison between venous congestion, reactive hyperaemia and core heat load tests.</a> Clin. Sci. (Lond). 97, 523-528 (1999).</li><li>Sivertsson, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+hemodynamic+importance+of+structural+vascular+changes+in+essential+hypertension.">The hemodynamic importance of structural vascular changes in essential hypertension.</a> Acta. Physiol. Scand. Suppl. 343, 1-56 (1970).</li><li>Raitakari, O. T., Celermajer, D. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Testing+for+endothelial+dysfunction.">Testing for endothelial dysfunction.</a> Ann. Med. 32, 293-304 (2000).</li><li>Tousoulis, D., Antoniades, C., Stefanadis, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evaluating+endothelial+function+in+humans:+a+guide+to+invasive+and+non-invasive+techniques.">Evaluating endothelial function in humans: a guide to invasive and non-invasive techniques.</a> Heart. 91, 553-558 (2005).</li><li>Higashi, Y., Sasaki, S., Nakagawa, K., Matsuura, H., Kajiyama, G., Oshima, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+noninvasive+measurement+of+reactive+hyperemia+that+can+be+used+to+assess+resistance+artery+endothelial+function+in+humans.">A noninvasive measurement of reactive hyperemia that can be used to assess resistance artery endothelial function in humans.</a> Am. J. Cardiol. 87, 121-125 (2001).</li><li>Higashi, Y., Yoshizumi, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=New+methods+to+evaluate+endothelial+function:+method+for+assessingendothelial+function+in+humans+using+a+strain-gauge+plethysmography:+nitric+oxide-dependent+and+independent+vasodilation.">New methods to evaluate endothelial function: method for assessingendothelial function in humans using a strain-gauge plethysmography: nitric oxide-dependent and independent vasodilation.</a> J. Pharmacol. Sci. 93, 399-404 (2003).</li><li>Lind, L., Sarabi, M., Millgard, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Methodological+aspects+of+the+evaluation+of+endothelium+dependent+vasodilatation+in+the+human+forearm.">Methodological aspects of the evaluation of endothelium dependent vasodilatation in the human forearm.</a> Clin. Physiol. 18, 81-87 (1998).</li><li>Cheng, C., Diamond, J. J., Falkner, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+capillary+rarefaction+in+mild+blood+pressure+elevation.">Functional capillary rarefaction in mild blood pressure elevation.</a> Clinical and Translational Science. 1, 75-79 (2008).</li><li>Cheng, C., Daskalakis, C., Falkner, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Capillary+rarefaction+in+treated+and+untreated+hypertensive+subjects.">Capillary rarefaction in treated and untreated hypertensive subjects.</a> Therapeutic Advances in Cardiovascular Disease. 2, 79-88 (2008).</li><li>Antonios, T. F., Singer, D. R., Markandu, N. D., Mortimer, P. S., MacGregor, G. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rarefaction+of+skin+capillaries+in+borderline+essential+hypertension+suggests+an+early+structural+abnormality.">Rarefaction of skin capillaries in borderline essential hypertension suggests an early structural abnormality.</a> Hypertension. 34, 655-658 (1999).</li><li>Noon, J. P., Walker, B. R., Webb, D. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impaired+microvascular+dilatation+and+capillary+rarefaction+in+young+adults+with+a+predisposition+to+high+blood+pressure.">Impaired microvascular dilatation and capillary rarefaction in young adults with a predisposition to high blood pressure.</a> J. Clin. Invest. 99, 1873-1879 (1997).</li><li>Antonios, T. F., Rattray, F. M., Singer, D. R., Markandu, N. D., Mortimer, P. S., MacGregor, G. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rarefaction+of+skin+capillaries+in+normotensive+offspring+of+individuals+with+essential+hypertension.">Rarefaction of skin capillaries in normotensive offspring of individuals with essential hypertension.</a> Heart. 89, 175-178 (2003).</li><li>de Jongh, R. T., Ijzerman, R. G., Serne, E. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Visceral+and+truncal+subcutaneous+adipose+tissue+are+associated+with+impaired+capillary+recruitment+in+healthy+individuals.">Visceral and truncal subcutaneous adipose tissue are associated with impaired capillary recruitment in healthy individuals.</a> J. Clin. Endocrinol. Metab. 91, 5100-5106 (2006).</li><li>de Jongh, R. T., Serne, E. H., Ijzerman, R. G., de Vries, G., Stehouwer, C. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Free+fatty+acid+levels+modulate+microvascular+function:+relevance+for+obesity-associated+insulin+resistance,+hypertension,+and+microangiopathy.">Free fatty acid levels modulate microvascular function: relevance for obesity-associated insulin resistance, hypertension, and microangiopathy.</a> Diabetes. 53, 2873-2882 (2004).</li><li>de Jongh, R. T., Serne, E. H., RG, I. J., Stehouwer, C. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microvascular+function:+a+potential+link+betweensalt+sensitivity,+insulin+resistance+and+hypertension.">Microvascular function: a potential link betweensalt sensitivity, insulin resistance and hypertension.</a> J. Hypertens. 25, 1887-1893 (2007).</li><li>Ijzerman, R. G., Voordouw, J. J., Van Weissenbruch, M. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=TNF-alpha+levels+are+associated+withskin+capillary+recruitment+in+humans:+a+potential+explanation+for+the+relationship+between+TNF-alpha+and+insulin+resistance.">TNF-alpha levels are associated withskin capillary recruitment in humans: a potential explanation for the relationship between TNF-alpha and insulin resistance.</a> Clin. Sci. (Lond). 110, 361-368 (2006).</li><li>Yvonne-Tee, G. B., Rasool, A. H., Halim, A. S., Rahman, A. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Noninvasive+assessment+of+cutaneous+vascular+function+in+vivo+using+capillaroscopy,+plethysmography+and+laser-Doppler+instruments:+its+strengths+and+weaknesses.">Noninvasive assessment of cutaneous vascular function in vivo using capillaroscopy, plethysmography and laser-Doppler instruments: its strengths and weaknesses.</a> Clin. Hemorheol. Microcirc. 34, 457-473 (2006).</li><li>Wilkinson, I. B., Webb, D. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Venous+occlusion+plethysmography+in+cardiovascular+research:+methodology+and+clinical+applications.">Venous occlusion plethysmography in cardiovascular research: methodology and clinical applications.</a> Br. J. Clin. Pharmacol. 52, 631-646 (2001).</li><li>Thijssen, D. H., Bleeker, M. W., Smits, P., Hopman, M. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reproducibility+of+blood+flow+and+post-occlusive+reactive+hyperaemia+as+measured+by+venous+occlusion+plethysmography.">Reproducibility of blood flow and post-occlusive reactive hyperaemia as measured by venous occlusion plethysmography.</a> Clin. Sci. (Lond). 108, 151-157 (2005).</li><li>Leslie, S. J., Attina, T., Hultsch, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+two+plethysmography+systems+in+assessment+of+forearm+blood+flow.">Comparison of two plethysmography systems in assessment of forearm blood flow.</a> J. Appl. Physiol. 96, 1794-179 (2004).</li><li>James, M. A., Tullett, J., Hemsley, A. G., Shore, A. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+aging+and+hypertension+on+the+microcirculation.">Effects of aging and hypertension on the microcirculation.</a> Hypertension. 47, 968-9674 (2006).</li><li>Debbabi, H., Uzan, L., Mourad, J. J., Safar, M., Levy, B. I., Tibirica, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Increased+skin+capillary+density+in+treated+essential+hypertensive+patients.">Increased skin capillary density in treated essential hypertensive patients.</a> Am. J. Hypertens. 19, 477-483 (2006).</li><li>Serne, E. H., Gans, R. O., ter Maaten, J. C., Tangelder, G. J., Donker, A. J., Stehouwer, C. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impaired+skincapillary+recruitment+in+essential+hypertension+is+caused+by+both+functional+and+structural+capillary+rarefaction.">Impaired skincapillary recruitment in essential hypertension is caused by both functional and structural capillary rarefaction.</a> Hypertension. 38, 238-242 (2001).</li><li>Carpentier, P. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=New+techniques+for+clinical+assessment+of+the+peripheral+microcirculation.">New techniques for clinical assessment of the peripheral microcirculation.</a> Drugs. 58, 17-22 (2001).</li><li>Shore, A. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Capillaroscopy+and+the+measurement+of+capillary+pressure.">Capillaroscopy and the measurement of capillary pressure.</a> Br. J. Clin. Pharmacol. 50, 501-513 (2000).</li></ol>

Les auteurs n&#39;ont pas de conflits d&#39;intérêts financiers liés à la conduite ou la publication de ce travail de divulgation.

La capillaroscopie (microscopie capillaire) est une mesure non-standard de la structure capillaire. Cependant, actuellement, il n&#39;existe pas de méthodes normalisées pour l&#39;évaluation directe de structure.Furthermore capillaire, microscopie capillaire a été largement utilisé pour l&#39;évaluation directe de capillarydensity dans un nombre important et croissant de travaux publiés 12, 13, 10, 11, 14-18 . En outre, nous avons validé la technique de microscopie capillaire en corrélant les résul...

non-invasive assessment of microvascular and endothelial function

Les auteurs ont utilisé des techniques capillaroscopie et l&#39;avant-bras du flux sanguin à étudier le rôle de la dysfonction microvasculaire dans la pathogenèse des maladies cardiovasculaires. La capillaroscopie est un non-invasive, la méthodologie relativement peu coûteux pour visualiser directement la microcirculation. Recrutement pour cent capillaire est évaluée en divisant l&#39;augmentation de la densité capillaire induit par postocclusive réactif hyperémie (postocclusive densité capillaire réactif hyperémie moins densité capillaire de base), par la densité maximale capillaire (observé au cours de l&#39;occlusion veineuse passive). Pour cent perfusé capillaires représente la proportion de toutes les personnes présentes capillaires qui sont perfusés (fonctionnellement actif), et est calculé en divisant postocclusive réactive densité capillaire hyperémie par la densité maximale capillaire. Recrutement pour cent à la fois capillaire et perfusé pour cent capillaires refléter le nombre de capillaires fonctionnels. Le débit sanguin (FBF) technique provides accepté mesures non invasives de la fonction endothéliale: Le rapport FBF max / FBF base est calculé comme une estimation de la vasodilatation, en divisant la moyenne des quatre valeurs max FBF par la moyenne des quatre valeurs de base FBF. La résistance vasculaire avant-bras à la vasodilatation maximale (FVR max) est calculé comme la pression artérielle moyenne (PAM) divisé par la FBF max. Tant la capillaroscopie et les techniques de l&#39;avant-bras sont facilement acceptable pour les patients et peuvent être apprises rapidement. La fonction endothéliale microvasculaire et les mesures obtenues en utilisant les méthodes décrites dans cet article peuvent avoir une utilité dans l&#39;avenir cliniques des patients cardiovasculaires de réduction des risques des stratégies. Comme nous l&#39;avons publié des rapports qui démontrent que la dysfonction endothéliale microvasculaire et se trouvent dans les premiers stades de l&#39;hypertension, y compris la pré-hypertension, les mesures de la fonction endothéliale microvasculaire et peut éventuellement aider à l&#39;identification précoce, Le risque de la stratification et de la prévention à la phase terminale pathologie vasculaire, avec ses conséquences potentiellement fatales.

Les différences dans l&#39;apparence de la microvascularisation entre les individus normotendus et hypertendus sont facilement visibles en comparant les figures 4 et 5. La figure 4 montre le réseau typique de droite capillaires en rangées bien organisées chez un individu normotendus. En revanche, la figure 5 montre un schéma plus dérangé des capillaires rétréci, enroulés. Les auteurs ont un intérêt continu dans le rôle de la dys...

Watch this Scientific Journal Video about Non-invasive Assessment of Microvascular and Endothelial Function at JoVE.com

Non-invasive Assessment of Microvascular and Endothelial Function

La capillaroscopie est un non-invasive, la méthodologie relativement peu coûteux pour visualiser directement la microcirculation. La technique de l&#39;écoulement du sang fournit l&#39;avant-bras acceptées mesures non invasives de la fonction endothéliale.

Non-invasive d&#39;évaluation de la fonction endothéliale microvasculaire et

The authors have utilized capillaroscopy and forearm blood flow techniques to investigate the role of microvascular dysfunction in pathogenesis of ...

non-invasive-assessment-of-microvascular-and-endothelial-function

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JoVE Journal

Medicine

16.1K vues.  Thomas Jefferson University. La capillaroscopie est un non-invasive, la méthodologie relativement peu coûteux pour visualiser directement la microcirculation. La technique de l'écoulement du sang fournit l'avant-bras acceptées mesures non invasives de la fonction endothéliale.

Vidéo: Non-invasive Assessment of Microvascular and Endothelial Function

An in vivo Rodent Model of Contraction-induced Injury and Non-invasive Monitoring of Recovery

Muscle strains are one of the most common complaints treated by physicians. A muscle injury is typically diagnosed from the patient history and physical exam alone, however the clinical presentation can vary greatly depending on the extent of injury, the patient's pain tolerance, etc. In patients with muscle injury or muscle disease, assessment of muscle damage is typically limited to clinical signs, such as tenderness, strength, range of motion, and more recently, imaging studies. Biological markers, such as serum creatine kinase levels, are typically elevated with muscle injury, but their levels do not always correlate with the loss of force production. This is even true of histological findings from animals, which provide a "direct measure" of damage, but do not account for all the loss of function. Some have argued that the most comprehensive measure of the overall health of the muscle in contractile force. Because muscle injury is a random event that occurs under a variety of biomechanical conditions, it is difficult to study. Here, we describe an in vivo animal model to measure torque and to produce a reliable muscle injury. We also describe our model for measurement of force from an isolated muscle in situ. Furthermore, we describe our small animal MRI procedure.

An in vivo Rodent Model of Contraction-induced Injury and Non-invasive Monitoring of Recovery

An in vivo animal model of injury is described. The method takes advantage of the subcutaneous position of the fibular nerve. Velocity, timing of muscle activation, and arc of motion are all pre-determined and synchronized using commercial software. Post injury changes are monitored in vivo using MR imaging/spectroscopy.

Une In vivo</emModèle de rongeur> de contraction induite par des blessures et de surveillance non invasive de récupération

Muscle strains are one of the most  common complaints treated by physicians. A muscle injury is typically diagnosed from the patient history and  physical ...

Recherche

Médecine

Non-invasive Optical Measurement of Cerebral Metabolism and Hemodynamics in Infants

Perinatal brain injury remains a significant cause of infant mortality and morbidity, but there is not yet an effective bedside tool that can accurately screen for brain injury, monitor injury evolution, or assess response to therapy. The energy used by neurons is derived largely from tissue oxidative metabolism, and neural hyperactivity and cell death are reflected by corresponding changes in cerebral oxygen metabolism (CMRO2). Thus, measures of CMRO2 are reflective of neuronal viability and provide critical diagnostic information, making CMRO2 an ideal target for bedside measurement of brain health.
Brain-imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) yield measures of cerebral glucose and oxygen metabolism, but these techniques require the administration of radionucleotides, so they are used in only the most acute cases.
Continuous-wave near-infrared spectroscopy (CWNIRS) provides non-invasive and non-ionizing radiation measures of hemoglobin oxygen saturation (SO2) as a surrogate for cerebral oxygen consumption. However, SO2 is less than ideal as a surrogate for cerebral oxygen metabolism as it is influenced by both oxygen delivery and consumption. Furthermore, measurements of SO2 are not sensitive enough to detect brain injury hours after the insult 1,2, because oxygen consumption and delivery reach equilibrium after acute transients 3. We investigated the possibility of using more sophisticated NIRS optical methods to quantify cerebral oxygen metabolism at the bedside in healthy and brain-injured newborns. More specifically, we combined the frequency-domain NIRS (FDNIRS) measure of SO2 with the diffuse correlation spectroscopy (DCS) measure of blood flow index (CBFi) to yield an index of CMRO2 (CMRO2i) 4,5.
With the combined FDNIRS/DCS system we are able to quantify cerebral metabolism and hemodynamics. This represents an improvement over CWNIRS for detecting brain health, brain development, and response to therapy in neonates. Moreover, this method adheres to all neonatal intensive care unit (NICU) policies on infection control and institutional policies on laser safety. Future work will seek to integrate the two instruments to reduce acquisition time at the bedside and to implement real-time feedback on data quality to reduce the rate of data rejection.

We combined frequency-domain near-infrared spectroscopy measures of cerebral hemoglobin oxygenation with diffuse correlation spectroscopy measures of cerebral blood flow index to estimate an index of oxygen metabolism. We tested the utility of this measure as a bedside screening tool to evaluate the health and development of the newborn brain.

Non-invasive de mesure optique du métabolisme cérébral et hémodynamique chez les nourrissons

Perinatal brain injury remains a significant cause of infant mortality  and morbidity, but there is not yet an effective bedside tool that can  accurately ...

Murine Spinotrapezius Model to Assess the Impact of Arteriolar Ligation on Microvascular Function and Remodeling

The murine spinotrapezius is a thin, superficial skeletal support muscle that extends from T3 to L4, and is easily accessible via dorsal skin incision. Its unique anatomy makes the spinotrapezius useful for investigation of ischemic injury and subsequent microvascular remodeling. Here, we demonstrate an arteriolar ligation model in the murine spinotrapezius muscle that was developed by our research team and previously published1-3. For certain vulnerable mouse strains, such as the Balb/c mouse, this ligation surgery reliably creates skeletal muscle ischemia and serves as a platform for investigating therapies that stimulate revascularization. Methods of assessment are also demonstrated, including the use of intravital and confocal microscopy. The spinotrapezius is well suited to such imaging studies due to its accessibility (superficial dorsal anatomy) and relative thinness (60-200 &mu;m). The spinotrapezius muscle can be mounted en face, facilitating imaging of whole-muscle microvascular networks without histological sectioning. We describe the use of intravital microscopy to acquire metrics following a functional vasodilation procedure; specifically, the increase in arterilar diameter as a result of muscle contraction. We also demonstrate the procedures for harvesting and fixing the tissues, a necessary precursor to immunostaining studies and the use of confocal microscopy.

We demonstrate a novel arterial ligation model in murine spinotrapezius muscle, including a step-by-step procedure and description of required instrumentation. We describe the surgery and relevant outcome measurements relating to vascular network remodeling and functional vasodilation using intravital and confocal microscopy.

Modèle murin Spinotrapezius pour évaluer l&#39;impact de la ligature artériolaire sur la fonction microvasculaire et Rénovation

The murine spinotrapezius is a thin, superficial skeletal support muscle that extends from T3 to L4, and is easily accessible via dorsal skin incision. ...

A Methodological Approach to Non-invasive Assessments of Vascular Function and Morphology

The endothelium is the innermost lining of the vasculature and is involved in the maintenance of vascular homeostasis. Damage to the endothelium may predispose the vessel to atherosclerosis and increase the risk for cardiovascular disease. Assessments of peripheral endothelial function are good indicators of early abnormalities in the vascular wall and correlate well with assessments of coronary endothelial function. The present manuscript details the important methodological steps necessary for the assessment of microvascular endothelial function using laser Doppler imaging with iontophoresis, large vessel endothelial function using flow-mediated dilatation, and carotid atherosclerosis using carotid artery ultrasound. A discussion on the methodological considerations for each of the techniques is also presented, and recommendations are made for future research.

The present article describes the methodological considerations for several non-invasive assessments of vascular function and morphology that are commonly used in medical research to assess different stages of atherosclerosis.

Une approche méthodologique pour les évaluations non invasifs de la fonction vasculaire et de morphologie

The endothelium is the innermost lining of the vasculature and is involved in the maintenance of vascular homeostasis.  Damage to the endothelium may ...

Non-invasive Assessment of the Efficacy of New Therapeutics for Intestinal Pathologies Using Serial Endoscopic Imaging of Live Mice

Animal models of inflammatory bowel disease (IBD) and colorectal cancer (CRC) have provided significant insight into the cell intrinsic and extrinsic mechanisms that contribute to the onset and progression of intestinal diseases. The identification of new molecules that promote these pathologies has led to a flurry of activity focused on the development of potential new therapies to inhibit their function. As a result, various pre-clinical mouse models with an intact immune system and stromal microenvironment are now heavily used. Here we describe three experimental protocols to test the efficacy of new therapeutics in pre-clinical models of (1) acute mucosal damage, (2) chronic colitis and/or colitis-associated colon cancer, and (3) sporadic colorectal cancer. We also outline procedures for serial endoscopic examination that can be used to document the therapeutic response of an individual tumor and to monitor the health of individual mice. These protocols provide complementary experimental platforms to test the effectiveness of therapeutic compounds shown to be well tolerated by mice.

We describe methods for longitudinal monitoring of the efficacy of therapeutics for the treatment of colonic pathologies in mice using a rigid endoscope. This protocol can be readily used for the characterization of the therapeutic response of an individual tumor in live mice and also for monitoring potential disease relapse.

Évaluation non invasive de l&#39;efficacité de nouveaux traitements pour les pathologies intestinales en utilisant l&#39;imagerie endoscopique de série de souris vivantes

Animal models of inflammatory bowel disease (IBD) and colorectal cancer (CRC) have provided significant insight into the cell intrinsic and extrinsic ...

Ultrasound Assessment of Endothelial Function: A Technical Guideline of the Flow-mediated Dilation Test

Cardiovascular disease is the primary cause of mortality and a major cause of disability worldwide. The dysfunction of the vascular endothelium is a pathological condition characterized mainly by a disruption in the balance between vasodilator and vasoconstrictor substances and is proposed to play an important role in the development of atherosclerotic cardiovascular disease. Therefore, a precise evaluation of endothelial function in humans represents an important tool that could help better understand the etiology of multiple cardio-centric pathologies.
Over the past twenty-five years, many methodological approaches have been developed to provide an assessment of endothelial function in humans. Introduced in 1989, the FMD test incorporates a forearm occlusion and subsequent reactive hyperemia that promotes nitric oxide production and vasodilation of the brachial artery. The FMD test is now the most widely utilized, non-invasive, ultrasonic assessment of endothelial function in humans and has been associated with future cardiovascular events.
Although the FMD test could have clinical utility, it is a physiological assessment that has inherited several confounding factors that need to be considered. This article describes a standardized protocol for determining FMD including the recommended methodology to help minimize the physiological and technical issues and improve the precision and reproducibility of the assessment.

The flow mediated dilation (FMD) test is the most commonly utilized, non-invasive, ultrasound assessment of endothelial function in humans. Although the FMD test has been related with the prediction of future cardiovascular disease and events, it is a physiological assessment with many inherent confounding factors that need to be considered.

Évaluation échographique de la fonction endothéliale: Une ligne directrice technique du Dilatation Test de débit à médiation

Cardiovascular disease is the primary cause of mortality and a major cause of disability worldwide. The dysfunction of the vascular endothelium is a ...

Non-invasive Assessments of Subjective and Objective Recovery Characteristics Following an Exhaustive Jump Protocol

Fast recovery after strenuous exercise is important in sports and is often studied via cryotherapy applications. Cryotherapy has a significant vasoconstrictive effect, which seems to be the leading factor in its effectiveness. The resulting enhanced recovery can be measured by using both objective and subjective parameters. Two commonly measured subjective characteristics of recovery are delayed-onset muscle soreness (DOMS) and ratings of perceived exertion (RPE). Two important objective recovery characteristics are countermovement jump (CMJ) performance and peak power output (PPO). Here, we provide a detailed protocol to induce muscular exhaustion of the frontal thighs with a self-paced, 3 x 30 countermovement jump protocol (30-s rest between each set). This randomized controlled trial protocol explains how to perform local cryotherapy cuff application (+ 8 &#176;C for 20 min) and thermoneutral cuff application (+ 32 &#176;C for 20 min) on both thighs as two possible post-exercise recovery modalities. Finally, we provide a non-invasive protocol to measure the effects of these two recovery modalities on subjective (i.e., DOMS of both frontal thighs and RPE) and objective recovery (i.e., CMJ and PPO) characteristics 24, 48, and 72 h post-application. The advantage of this method is that it provides a tool for researchers or coaches to induce muscular exhaustion, without using any expensive devices; to implement local cooling strategies; and to measure both subjective and objective recovery, without using invasive methods. Limitations of this protocol are that the 30 s rest period between sets is very short, and the cardiovascular demand is very high. Future studies may find the assessment of maximum voluntary contractions to be a more sensitive assessment of muscular exhaustion compared to CMJs.

This protocol describes the procedure for non-invasive recovery assessments during a 72 h recovery period. This protocol induces muscular exhaustion of the frontal thighs using countermovement jumps and uses either local cold-cuff or thermoneutral-cuff application as a recovery modality.

Évaluations non invasives des caractéristiques subjectives et objectives de récupération suite à un protocole de saut exhaustif

Fast recovery after strenuous exercise is important in sports and is often studied via cryotherapy applications. Cryotherapy has a significant ...

Assessment of Human Adipose Tissue Microvascular Function Using Videomicroscopy

While obesity is closely linked to the development of metabolic and cardiovascular disease, little is known about mechanisms that govern these processes. It is hypothesized that pro-atherogenic mediators released from fat tissues particularly in association with central/visceral adiposity may promote pathogenic vascular changes locally and systemically, and the notion that cardiovascular disease may be the consequence of adipose tissue dysfunction continues to evolve. Here, we describe a unique method of videomicroscopy that involves analysis of vasodilator and vasoconstrictor responses of intact small human arterioles removed from the adipose depot of living human subjects. Videomicroscopy is used to examine functional properties of isolated microvessels in response to pharmacological or physiological stimuli using a pressured system that mimics in vivo conditions. The technique is a useful approach to gain understanding of the pathophysiology and molecular mechanisms that contribute to vascular dysfunction locally within the adipose tissue milieu. Moreover, abnormalities in the adipose tissue microvasculature have also been linked with systemic diseases. We applied this technique to examine depot-specific vascular responses in obese subjects. We assessed endothelium-dependent vasodilation to both increased flow and acetylcholine in adipose arterioles (50 - 350 &#181;m internal diameter, 2 - 3 mm in length) isolated from two different adipose depots during bariatric surgery from the same individual. We demonstrated that arterioles from visceral fat exhibit impaired endothelium-dependent vasodilation compared to vessels isolated from the subcutaneous depot. The findings suggest that the visceral microenvironment is associated with vascular endothelial dysfunction which may be relevant to clinical observation linking increased visceral adiposity to systemic disease mechanisms. The videomicroscopy technique can be used to examine vascular phenotypes from different fat depots as well as compare findings across individuals with different degrees of obesity and metabolic dysfunction. The method can also be used to examine vascular responses longitudinally in response to clinical interventions.

Videomicroscopy systems are used to examine functional properties of isolated adipose tissue arterioles in response to physiological and pharmacological stimuli. This technique can be used to examine microvascular phenotypes in different adipose tissue domains in obese humans.

Évaluation de la fonction microvasculaire tissu adipeux humain en utilisant la vidéomicroscopie

While obesity is closely linked to the development of metabolic and cardiovascular disease, little is known about mechanisms that govern these processes. ...

Non-invasive Assessment of Dorsiflexor Muscle Function in Mice

Assessment of skeletal muscle contractile function is an important measurement for both clinical and research purposes. Numerous conditions can negatively affect skeletal muscle. This can result in a loss of muscle mass (atrophy) and/or loss of muscle quality (reduced force per unit of muscle mass), both of which are prevalent in chronic disease, muscle-specific disease, immobilization, and aging (sarcopenia). Skeletal muscle function in animals can be evaluated by a range of different tests. All tests have limitations related to the physiological testing environment, and the selection of a specific test often depends on the nature of the experiments. Here, we describe an in vivo, non-invasive technique involving a helpful and easy assessment of force frequency-curve (FFC) in mice that can be performed on the same animal over time. This permits monitoring of disease progression and/or efficacy&#160;of a potential therapeutic treatment.

Measurement of rodent skeletal muscle contractile function is a useful tool that can be used to track disease progression as well as efficacy of therapeutic intervention. We describe here the non-invasive, in vivo assessment of the dorsiflexor muscles that can be repeated over time in the same mouse.

Évaluation non invasif de la fonction musculaire de dorsifléchisseurs chez la souris

Assessment of skeletal muscle contractile function is an important measurement for both clinical and research purposes. Numerous conditions can negatively ...

A Computerized Functional Skills Assessment and Training Program Targeting Technology Based Everyday Functional Skills

Today, many functional skills are technology-based, so development of a technology-based training program has broad importance. Here we present a computerized functional skills training program that was paired in half of the participants with a commercially available cognitive training (CCT) program.
Non-impaired older individuals (NC) aged 60+ (n=45) and similarly aged individuals with mild cognitive impairment (MCI; n=50) were randomized to receive 12 weeks of twice-weekly computerized functional skills training (CFST) or 12 weeks of twice-weekly sessions split between CCT and CFST. Skills trained were use of an ATM; internet banking; ticket kiosk; telephone and internet prescription refill; medication management; and internet shopping. As with previous functional capacity assessments, we focus on completion time for each simulation.
51 participants completed the training program, either by mastering all 6 tasks (34) or completing 12 weeks of training. 44 more participants completed 4 or more training sessions so they were also analyzed for improvement up to their last training session. Completion time for all 6 tests significantly improved from the baseline assessment to the final training session in both groups of participants (all p&#60;0.001 with an average improvement in task completion time of 45%). Further, there was no differential improvement in MCI and NC in the 6 tests from baseline to end of training (all t&#60;1.66, all p&#62;0.12). Finally, combined CCT plus CFST did not differ from CSFT alone on any of the percent-change score measures (all t&#60;1.64, all p&#62;0.11).
Both NC and MCI groups evidenced substantial improvements in performance. CCT supplementation led to similar functional gains with half as many training sessions. The NC participants proceeded through the training fairly rapidly even without CCT supplementation; MCI participants required more training but learned equivalently. These findings suggest that even in cases with memory impairments, functional skills can be efficiently learned with training.

This training protocol uses computerized training to teach technology-related everyday functional skills. These skills include financial skills, travel and transit, as well as medication management.

Un programme informatisé d’évaluation et de formation des compétences fonctionnelles ciblant la technologie basée sur les compétences fonctionnelles quotidiennes