{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T11:15:06Z","timestamp":1762254906525,"version":"build-2065373602"},"reference-count":29,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T00:00:00Z","timestamp":1721606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011019","name":"National Research, Development and Innovation Office of Hungary","doi-asserted-by":"publisher","award":["2020-1.1.6-J\u00d6V\u0150-2021-00013","TKP2021-EGA-23","RRF-2.3.1-21-2022-00003","RRF-2.3.1-21-2022-00004"],"award-info":[{"award-number":["2020-1.1.6-J\u00d6V\u0150-2021-00013","TKP2021-EGA-23","RRF-2.3.1-21-2022-00003","RRF-2.3.1-21-2022-00004"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund","award":["2020-1.1.6-J\u00d6V\u0150-2021-00013","TKP2021-EGA-23","RRF-2.3.1-21-2022-00003","RRF-2.3.1-21-2022-00004"],"award-info":[{"award-number":["2020-1.1.6-J\u00d6V\u0150-2021-00013","TKP2021-EGA-23","RRF-2.3.1-21-2022-00003","RRF-2.3.1-21-2022-00004"]}]},{"name":"European Union","award":["2020-1.1.6-J\u00d6V\u0150-2021-00013","TKP2021-EGA-23","RRF-2.3.1-21-2022-00003","RRF-2.3.1-21-2022-00004"],"award-info":[{"award-number":["2020-1.1.6-J\u00d6V\u0150-2021-00013","TKP2021-EGA-23","RRF-2.3.1-21-2022-00003","RRF-2.3.1-21-2022-00004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Numerous research projects focused on the management of acute pulmonary hypertension as Coronavirus Disease 2019 (COVID-19) might lead to hypoxia-induced pulmonary vasoconstriction related to acute respiratory distress syndrome. For that reason, inhalative therapeutic options have been the subject of several clinical trials. In this experimental study, we aimed to examine the hemodynamic impact of the inhalation of the SIN-1A formulation (N-nitroso-N-morpholino-amino-acetonitrile, the unstable active metabolite of molsidomine, stabilized by a cyclodextrin derivative) in a porcine model of acute pulmonary hypertension. Landrace pigs were divided into the following experimental groups: iNO (inhaled nitric oxide, n = 3), SIN-1A-5 (5 mg, n = 3), and SIN-1A-10 (10 mg, n = 3). Parallel insertion of a PiCCO system and a pulmonary artery catheter (Swan-Ganz) was performed for continuous hemodynamic monitoring. The impact of iNO (15 min) and SIN-1A inhalation (30 min) was investigated under physiologic conditions and U46619-induced acute pulmonary hypertension. Mean pulmonary arterial pressure (PAP) was reduced transiently by both substances. SIN-1A-10 had a comparable impact compared to iNO after U46619-induced pulmonary hypertension. PAP and PVR decreased significantly (changes in PAP: \u221230.1% iNO, \u221222.1% SIN-1A-5, \u221231.2% SIN-1A-10). While iNO therapy did not alter the mean arterial pressure (MAP) and systemic vascular resistance (SVR), SIN-1A administration resulted in decreased MAP and SVR values. Consequently, the PVR\/SVR ratio was markedly reduced in the iNO group, while SIN-1A did not alter this parameter. The pulmonary vasodilatory impact of inhaled SIN-1A was shown to be dose-dependent. A larger dose of SIN-1A (10 mg) resulted in decreased PAP and PVR in a similar manner to the gold standard iNO therapy. Inhalation of the nebulized solution of the new SIN-1A formulation (stabilized by a cyclodextrin derivative) might be a valuable, effective option where iNO therapy is not available due to dosing difficulties or availability.<\/jats:p>","DOI":"10.3390\/ijms25147981","type":"journal-article","created":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T11:40:36Z","timestamp":1721734836000},"page":"7981","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Comparative Investigation of the Pulmonary Vasodilating Effects of Inhaled NO Gas Therapy and Inhalation of a New Drug Formulation Containing a NO Donor Metabolite (SIN-1A)"],"prefix":"10.3390","volume":"25","author":[{"given":"Attila","family":"Ol\u00e1h","sequence":"first","affiliation":[{"name":"Heart and Vascular Center, Semmelweis University, 1122 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e1lint Andr\u00e1s","family":"Barta","sequence":"additional","affiliation":[{"name":"Heart and Vascular Center, Semmelweis University, 1122 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mih\u00e1ly","family":"Ruppert","sequence":"additional","affiliation":[{"name":"Heart and Vascular Center, Semmelweis University, 1122 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex Ali","family":"Sayour","sequence":"additional","affiliation":[{"name":"Heart and Vascular Center, Semmelweis University, 1122 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D\u00e1vid","family":"Nagy","sequence":"additional","affiliation":[{"name":"Heart and Vascular Center, Semmelweis University, 1122 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5913-8456","authenticated-orcid":false,"given":"T\u00edmea","family":"B\u00e1lint","sequence":"additional","affiliation":[{"name":"Heart and Vascular Center, Semmelweis University, 1122 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgina Vikt\u00f3ria","family":"Nagy","sequence":"additional","affiliation":[{"name":"Heart and Vascular Center, Semmelweis University, 1122 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7879-2920","authenticated-orcid":false,"given":"Istv\u00e1n","family":"Pusk\u00e1s","sequence":"additional","affiliation":[{"name":"Cyclolab Ltd., 1097 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7734-5440","authenticated-orcid":false,"given":"Lajos","family":"Szente","sequence":"additional","affiliation":[{"name":"Cyclolab Ltd., 1097 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9521-3628","authenticated-orcid":false,"given":"Levente","family":"Sz\u0151cs","sequence":"additional","affiliation":[{"name":"Cyclolab Ltd., 1097 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6703-3550","authenticated-orcid":false,"given":"Tam\u00e1s","family":"Sohajda","sequence":"additional","affiliation":[{"name":"Cyclolab Ltd., 1097 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5132-6009","authenticated-orcid":false,"given":"Endre","family":"Zima","sequence":"additional","affiliation":[{"name":"Heart and Vascular Center, Semmelweis University, 1122 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6514-0723","authenticated-orcid":false,"given":"B\u00e9la","family":"Merkely","sequence":"additional","affiliation":[{"name":"Heart and Vascular Center, Semmelweis University, 1122 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tam\u00e1s","family":"Radovits","sequence":"additional","affiliation":[{"name":"Heart and Vascular Center, Semmelweis University, 1122 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1055\/a-1661-0240","article-title":"Pulmonary Hypertension and COVID-19","volume":"42","author":"Castiglione","year":"2022","journal-title":"Hamostaseologie"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1111\/aas.13819","article-title":"Acute pulmonary hypertension and short-term outcomes in severe Covid-19 patients needing intensive care","volume":"65","author":"Norderfeldt","year":"2021","journal-title":"Acta Anaesthesiol. 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