{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:38:38Z","timestamp":1760240318645,"version":"build-2065373602"},"reference-count":33,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,5,2]],"date-time":"2019-05-02T00:00:00Z","timestamp":1556755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT Funda\u00e7\u00e3o Ci\u00eancia e Tecnologia IP","award":["UID\/DTP\/04567\/2016"],"award-info":[{"award-number":["UID\/DTP\/04567\/2016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Modelling is essential for a better understanding of microcirculatory pathophysiology. In this study we tested our hyperoxia-mouse model with healthy and non-healthy mice. Animals (n = 41) were divided in groups\u2014a control group, with 8 C57\/BL6 non-transgenic male mice, a diabetic group (DB), with 8 C57BLKsJ-db\/db obese diabetic mice and the corresponding internal controls of 8 age-matched C57BLKsJ-db\/+ mice, and a cardiac hypertrophy group (CH), with 9 FVB\/NJ c\u03b1-MHC-NHE-1 transgenic mice prone to develop cardiac failure and 8 age-matched internal controls. After anesthesia, perfusion data was collected by laser Doppler flowmetry (LDF) during rest (Phase 1), hyperoxia (Phase 2), and recovery (Phase 3) and compared. The LDF wavelet transform components analysis (WA) has shown that cardiorespiratory, myogenic, and endothelial components acted as main markers. In DB group, db\/+ animals behave as the Control group, but WA already demonstrated significant differences for myogenic and endothelial components. Noteworthy was the increase of the sympathetic components in the db\/db set, as in the cardiac overexpressing NHE1 transgenic animals, reported as a main component of these pathophysiological processes. Our model confirms that flow motion has a universal nature. The LDF component\u2019s WA provides a deeper look into vascular pathophysiology reinforcing the model\u2019s reproducibility, robustness, and discriminative capacities.<\/jats:p>","DOI":"10.3390\/ijms20092178","type":"journal-article","created":{"date-parts":[[2019,5,2]],"date-time":"2019-05-02T03:15:22Z","timestamp":1556766922000},"page":"2178","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Characterizing Vascular Dysfunction in Genetically Modified Mice through the Hyperoxia Model"],"prefix":"10.3390","volume":"20","author":[{"given":"Luis","family":"Monteiro Rodrigues","sequence":"first","affiliation":[{"name":"CBIOS\u2014Universidade Lus\u00f3fona\u2019s Research Center for Biosciences and Health Technologies, Campo Grande, 1749 024 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3258-5851","authenticated-orcid":false,"given":"Henrique","family":"Nazar\u00e9 Silva","sequence":"additional","affiliation":[{"name":"CBIOS\u2014Universidade Lus\u00f3fona\u2019s Research Center for Biosciences and Health Technologies, Campo Grande, 1749 024 Lisboa, Portugal"},{"name":"Pharmacological Sciences Department\u2014Universidade de Lisboa, Faculty of Pharmacy, Av Prof Gama Pinto 1649 003 Lisboa, Portugal"}]},{"given":"Hugo","family":"Ferreira","sequence":"additional","affiliation":[{"name":"IBEB\u2014Biophysics and Biomedical Engineering Institute, Universidade de Lisboa Faculty of Sciences, Campo Grande 1749 016 Lisboa, Portugal"}]},{"given":"Alain-Pierre","family":"Gadeau","sequence":"additional","affiliation":[{"name":"INSERM U1034, Adaptation cardiovasculaire \u00e0 l\u2019isch\u00e9mie, F-33600 Pessac, France"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1111\/j.1365-201X.2005.01405.x","article-title":"Acute hyperoxaemia-induced effects on regional blood flow, oxygen consumption and central circulation in man","volume":"183","author":"Rousseau","year":"2005","journal-title":"Acta Physiol. Scand."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/j.1748-1716.2007.01710.x","article-title":"Human cardiovascular dose-response to supplemental oxygen","volume":"191","author":"Bak","year":"2007","journal-title":"Acta Physiol. (Oxford)"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.mvr.2015.04.001","article-title":"Regarding the quantification of peripheral microcirculation--Comparing responses evoked in the in vivo human lower limb by postural changes, suprasystolic occlusion and oxygen breathing","volume":"99","author":"Silva","year":"2015","journal-title":"Microvasc. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00134-010-2034-y","article-title":"Oxygen: When is more the enemy of good?","volume":"37","author":"Branson","year":"2011","journal-title":"Intensive. Care Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Humbert, P., Fanian, F., Maibach, H., and Agache, P. (2017). Studying the Oscillatory Components of Human Skin Microcirculation. Agache\u2019s Measuring the Skin, Springer. Chapter 55.","DOI":"10.1007\/978-3-319-32383-1"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e13736","DOI":"10.14814\/phy2.13736","article-title":"Observations on the perfusion recovery of regenerative angiogenesis in an ischemic limb model under hyperoxia","volume":"6","author":"Rodrigues","year":"2018","journal-title":"Physiol. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1023\/A:1009681002818","article-title":"Correlation integral and frequency analysis of cardiovascular functions","volume":"4","author":"Stefanovska","year":"1997","journal-title":"Open Syst. Inf. Dyn."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.mvr.2009.07.005","article-title":"Detrended fluctuation analysis of laser Doppler flowmetry time series","volume":"78","author":"Esen","year":"2009","journal-title":"Microvasc. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6142","DOI":"10.1118\/1.3512796","article-title":"Multiscale entropy of laser Doppler flowmetry signals in healthy human subjects","volume":"37","author":"Humeau","year":"2010","journal-title":"Med. Phys."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"H1277","DOI":"10.1152\/ajpheart.1998.274.4.H1277","article-title":"Frequency response characteristics of sympathetically mediated vasomotor waves in humans","volume":"274","author":"Stauss","year":"1998","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.mvr.2006.05.006","article-title":"Low frequency oscillations of the laser Doppler perfusion signal in human skin","volume":"72","author":"Kvandal","year":"2006","journal-title":"Microvasc. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1006\/mvre.1998.2139","article-title":"Oscillations in the human cutaneous blood perfusion signal modified by endothelium-dependent and endothelium-independent vasodilators","volume":"57","author":"Kvernmo","year":"1999","journal-title":"Microvasc. Res."},{"key":"ref_13","first-page":"121","article-title":"Application of wavelet transform and its advantages compared to Fourier transform","volume":"13","author":"Sifuzzaman","year":"2012","journal-title":"J. Phys. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Bernjak, A., and Stefanovska, A. (2007). Importance of wavelet analysis in laser Doppler flowmetry time series. Conf. Proc. IEEE Eng. Med. Biol. Soc., 4064\u20134067.","DOI":"10.1109\/IEMBS.2007.4353226"},{"key":"ref_15","first-page":"1","article-title":"Anesthesia effects on the low frequency blood flow oscillations in mouse skin","volume":"1","author":"Astashev","year":"2018","journal-title":"Skin Res. Technol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1038\/hr.2014.91","article-title":"Deactivation of carotid body chemoreceptors by hyperoxia decreases blood pressure in hypertensive patients","volume":"37","author":"Sinski","year":"2014","journal-title":"Hypertens. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1097\/HJH.0b013e328350136c","article-title":"Peripheral chemoreflex activation contributes to sympathetic baroreflex impairment in chronic heart failure","volume":"30","author":"Despas","year":"2012","journal-title":"J. Hypertens."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"72","DOI":"10.14712\/23362936.2014.25","article-title":"Autonomic nervous system under ketamine\/xylazine and pentobarbital anaesthesia in a Wistar rat model: A chronobiological view","volume":"114","author":"Svorc","year":"2013","journal-title":"Prague Med. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1113\/JP270818","article-title":"Principles and standards for reporting animal experiments in The Journal of Physiology and Experimental Physiology","volume":"593","author":"Grundy","year":"2015","journal-title":"J. Physiol."},{"key":"ref_20","unstructured":"Krisch, J.A. (2019, April 30). How Much Do Sex Differences Matter in Mouse Studies? The scientist feb 24. Available online: https:\/\/www.the-scientist.com\/news-analysis\/how-much-do-sex-differences-matter-in-mouse-studies-31974."},{"key":"ref_21","first-page":"856","article-title":"Effects of atropine on xylazine-pentobarbital anesthesia in dogs: Preliminary study","volume":"46","author":"Hsu","year":"1985","journal-title":"Am. J. Vet. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"715","DOI":"10.2337\/diacare.19.7.715","article-title":"Impaired peripheral vasomotion in diabetes","volume":"19","author":"Stansberry","year":"1996","journal-title":"Diabetes Care"},{"key":"ref_23","first-page":"1007","article-title":"Sympathetic nerve activity in type 2 diabetes mellitus; a promising potential therapeutic target","volume":"1","author":"Kobayashi","year":"2014","journal-title":"Austin J. Endocrinol. Diabetes"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1161\/01.CIR.0000081775.72651.B6","article-title":"Relation between cardiac sympathetic activity and hypertensive left ventricular hypertrophy","volume":"108","author":"Schlaich","year":"2003","journal-title":"Circulation"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1007\/s11892-003-0006-0","article-title":"Diabetic neuropathy and microcirculation","volume":"3","author":"Hile","year":"2003","journal-title":"Curr. Diab. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2579","DOI":"10.1113\/jphysiol.2009.169011","article-title":"Decreased microvascular vasomotion and myogenic response in rat skeletal muscle in association with acute insulin resistance","volume":"587","author":"Newman","year":"2009","journal-title":"J. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1042\/CS20030037","article-title":"Cutaneous vascular reactivity is reduced in aging and in heart failure: Association with inflammation","volume":"105","author":"Andersson","year":"2003","journal-title":"Clin. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"82","DOI":"10.3724\/SP.J.1263.2011.00082","article-title":"Deteriorated function of cutaneous microcirculation in chronic congestive heart failure","volume":"8","author":"Edvinsson","year":"2011","journal-title":"J. Geriatr. Cardiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1161\/CIRCRESAHA.108.175141","article-title":"Activation of Na+\/H+ exchanger 1 is sufficient to generate Ca2+ signals that induce cardiac hypertrophy and heart failure","volume":"103","author":"Nakamura","year":"2008","journal-title":"Circ. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/978-1-62703-068-7_4","article-title":"Diabetes in mice with monogenic obesity: The db\/db mouse and its use in the study of cardiac consequences","volume":"933","author":"Belke","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"131","DOI":"10.2174\/1573399810666140508121012","article-title":"Leptin- and leptin receptor-deficient rodent models: Relevance for human type 2 diabetes","volume":"10","author":"Wang","year":"2014","journal-title":"Curr. Diabetes Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1006\/bulm.1998.0047","article-title":"Wavelet-based analysis of human blood flow dynamics","volume":"60","author":"Bracic","year":"1998","journal-title":"Bull Math. Biol."},{"key":"ref_33","unstructured":"Silva, H., Renault, M., Ferreira, H., Bujan, M.J., Gadeau, A., and Rodrigues, L.M. (2016). Hyperoxia evokes opposite hind limbs vascular responses in the murine model of ischemia. ISBS 40th World Congress Abstract Book. Biomed. Biopharm. Res., 15."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/9\/2178\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:48:44Z","timestamp":1760186924000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/9\/2178"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,2]]},"references-count":33,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2019,5]]}},"alternative-id":["ijms20092178"],"URL":"https:\/\/doi.org\/10.3390\/ijms20092178","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2019,5,2]]}}}