{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:30:08Z","timestamp":1753878608635,"version":"3.41.2"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T00:00:00Z","timestamp":1637107200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microcirculation"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>It remains unknown whether the cutaneous microvascular responses are different between patients with scleroderma\u2010associated pulmonary arterial hypertension (SSc\u2010PAH) and SSc without pulmonary hypertension (PH).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We included 59 patients with SSc between March 2013 and September 2019. We divided patients into 4\u00a0groups: (a) no PH by right heart catheterization (RHC) (<jats:italic>n<\/jats:italic>\u00a0=\u00a08), (b) no PH by noninvasive screening tests (<jats:italic>n<\/jats:italic>\u00a0=\u00a016), (c) treatment na\u00efve PAH (<jats:italic>n<\/jats:italic>\u00a0=\u00a016), and (d) PAH under treatment (<jats:italic>n<\/jats:italic>\u00a0=\u00a019). Microvascular studies using laser Doppler flowmetry (LDF) were done immediately after RHC or at the time of an outpatient clinic visit (group b).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The median (IQR) age was 59 (54\u201368) years, and 90% were females. The responses to local thermal stimulation and postocclusive reactive hyperemia, acetylcholine, and sodium nitroprusside iontophoresis were similar among groups. The microvascular response to treprostinil was more pronounced in SSc patients without PH by screening tests (% change: 340 (214\u2013781)) compared with SSc\u2010PAH (na\u00efve\u00a0+\u00a0treatment) (Perfusion Units (PU) % change: 153 (94\u2013255) % [<jats:italic>p<\/jats:italic>\u00a0=\u00a0.01]). The response to A\u2010350619 (a soluble guanylate cyclase (sGC) activator) was significantly higher in patients with SSc without PH by screening tests (PU % change: 168 (46\u20131,296)) than those with SSc\u2010PAH (PU % change: 22 (15\u201357) % [<jats:italic>p<\/jats:italic>\u00a0=\u00a0.006]). The % change in PU with A350619 was directly associated with cardiac index and stroke volume index (<jats:italic>R<\/jats:italic>: 0.36, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.03 and 0.39, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.02, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Patients with SSc\u2010PAH have a lower cutaneous microvascular response to a prostacyclin analog treprostinil and the sGC activator A\u2010350619 when compared with patients with SSc and no evidence of PH on screening tests, presumably due to a peripheral reduction in prostacyclin receptor expression and nitric oxide bioavailability.<\/jats:p><\/jats:sec>","DOI":"10.1111\/micc.12734","type":"journal-article","created":{"date-parts":[[2021,11,6]],"date-time":"2021-11-06T18:33:47Z","timestamp":1636223627000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cutaneous iontophoresis of vasoactive medications in patients with scleroderma\u2010associated pulmonary arterial hypertension"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7648-7738","authenticated-orcid":false,"given":"Sami","family":"Al Abdi","sequence":"first","affiliation":[{"name":"Cleveland Clinic Fairview Hospital Cleveland Clinic Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allaa","family":"Almoushref","sequence":"additional","affiliation":[{"name":"Internal medicine Department University of Connecticut Hartford Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tawfeq","family":"Naal","sequence":"additional","affiliation":[{"name":"Atrium Health Wake Forest Baptist Winston\u2010Salem North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Celia A.","family":"Melillo","sequence":"additional","affiliation":[{"name":"Inflammation and Immunity Department Cleveland Clinic Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kulwant S.","family":"Aulak","sequence":"additional","affiliation":[{"name":"Inflammation and Immunity Department Cleveland Clinic Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mostafa K.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Chest Diseases Faculty of Medicine Assiut University Assiut Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soumya","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Department of Rheumatic and Immunologic Diseases Orthopaedic and Rheumatologic Institute Cleveland Clinic Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin B.","family":"Highland","sequence":"additional","affiliation":[{"name":"Department of Pulmonary, Allergy and Critical Care Medicine. 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