{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:38:20Z","timestamp":1790678300111,"version":"4.1.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[1998,10,1]],"date-time":"1998-10-01T00:00:00Z","timestamp":907200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1998,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Dexfenfluramine and fenfluramine greatly increase the risk of developing pulmonary hypertension (PHT). The mechanism of anorexigen-associated PHT (AA-PHT) and the reason PHT occurs in a minority of people exposed are unknown. Anorexigens are weak pulmonary vasoconstrictors, but they become potent when synthesis of the endogenous vasodilator nitric oxide (NO) is suppressed. We hypothesized NO deficiency predisposes affected individuals to develop AA-PHT. A prospective, case-control, study was performed on consecutive patients with AA-PHT (n = 9). Two sex-matched control groups were selected: patients with primary PHT (P-PHT, n = 8) and normal volunteers (n = 12). Lung NO production (VNO) and systemic plasma oxidation products of NO (NOx) were measured at rest and during exercise. AA-PHT developed 17 \u00b1 6 mo after a short course of anorexigen (6 \u00b1 2 mo) and was irreversible. VNO was lower in AA-PHT than in P-PHT and correlated inversely with PVR (p &amp;lt; 0.05). The apparent VNO deficiency may have resulted from increased oxidative inactivation of NO in patients with AA-PHT, as their NOx levels were elevated (p &amp;lt; 0.05) in inverse proportion to VNO (r2 = 0.55; p &amp;lt; 0.02). In susceptible persons, anorexigens can cause an irreversible syndrome of PHT, hypoxemia, and systemic vascular complications after brief exposures. These patients have a relative NO deficiency years after discontinuing the anorexigen, perhaps explaining their original susceptibility.<\/jats:p>","DOI":"10.1164\/ajrccm.158.4.9802113","type":"journal-article","created":{"date-parts":[[2013,4,4]],"date-time":"2013-04-04T13:47:41Z","timestamp":1365083261000},"page":"1061-1067","source":"Crossref","is-referenced-by-count":93,"title":["Nitric Oxide Deficiency in Fenfluramine- and Dexfenfluramine-induced Pulmonary Hypertension"],"prefix":"10.1093","volume":"158","author":[{"given":"STEPHEN L.","family":"ARCHER","sequence":"first","affiliation":[{"name":"Cardiology Division, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; Department of Medicine (Cardiology), Veterans Affairs Medical Center, and University of Minnesota, Minneapolis, Minnesota; Hopital Cochin, Departement de Physiologie Respiratoire, and Hopital Robert Debr\u00e9, Service de R\u00e9animation Pediatrique, Paris; and Service des Maladies Vasculaires Pulmonaires, H\u00f4pital Antoine-B\u00e9cl\u00e8re, Clamart, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KHIER","family":"DJABALLAH","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; Department of Medicine (Cardiology), Veterans Affairs Medical Center, and University of Minnesota, Minneapolis, Minnesota; Hopital Cochin, Departement de Physiologie Respiratoire, and Hopital Robert Debr\u00e9, Service de R\u00e9animation Pediatrique, Paris; and Service des Maladies Vasculaires Pulmonaires, H\u00f4pital Antoine-B\u00e9cl\u00e8re, Clamart, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MARC","family":"HUMBERT","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; Department of Medicine (Cardiology), Veterans Affairs Medical Center, and University of Minnesota, Minneapolis, Minnesota; Hopital Cochin, Departement de Physiologie Respiratoire, and Hopital Robert Debr\u00e9, Service de R\u00e9animation Pediatrique, Paris; and Service des Maladies Vasculaires Pulmonaires, H\u00f4pital Antoine-B\u00e9cl\u00e8re, Clamart, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"KENNETH WEIR","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; Department of Medicine (Cardiology), Veterans Affairs Medical Center, and University of Minnesota, Minneapolis, Minnesota; Hopital Cochin, Departement de Physiologie Respiratoire, and Hopital Robert Debr\u00e9, Service de R\u00e9animation Pediatrique, Paris; and Service des Maladies Vasculaires Pulmonaires, H\u00f4pital Antoine-B\u00e9cl\u00e8re, Clamart, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MURIEL","family":"FARTOUKH","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; Department of Medicine (Cardiology), Veterans Affairs Medical Center, and University of Minnesota, Minneapolis, Minnesota; Hopital Cochin, Departement de Physiologie Respiratoire, and Hopital Robert Debr\u00e9, Service de R\u00e9animation Pediatrique, Paris; and Service des Maladies Vasculaires Pulmonaires, H\u00f4pital Antoine-B\u00e9cl\u00e8re, Clamart, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JOSETTE","family":"DALL'AVA-SANTUCCI","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; Department of Medicine (Cardiology), Veterans Affairs Medical Center, and University of Minnesota, Minneapolis, Minnesota; Hopital Cochin, Departement de Physiologie Respiratoire, and Hopital Robert Debr\u00e9, Service de R\u00e9animation Pediatrique, Paris; and Service des Maladies Vasculaires Pulmonaires, H\u00f4pital Antoine-B\u00e9cl\u00e8re, Clamart, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JEAN-CHRISTOPHE","family":"MERCIER","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; Department of Medicine (Cardiology), Veterans Affairs Medical Center, and University of Minnesota, Minneapolis, Minnesota; Hopital Cochin, Departement de Physiologie Respiratoire, and Hopital Robert Debr\u00e9, Service de R\u00e9animation Pediatrique, Paris; and Service des Maladies Vasculaires Pulmonaires, H\u00f4pital Antoine-B\u00e9cl\u00e8re, Clamart, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GERALD","family":"SIMONNEAU","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; Department of Medicine (Cardiology), Veterans Affairs Medical Center, and University of Minnesota, Minneapolis, Minnesota; Hopital Cochin, Departement de Physiologie Respiratoire, and Hopital Robert Debr\u00e9, Service de R\u00e9animation Pediatrique, Paris; and Service des Maladies Vasculaires Pulmonaires, H\u00f4pital Antoine-B\u00e9cl\u00e8re, Clamart, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"TUAN DINH-XUAN","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; Department of Medicine (Cardiology), Veterans Affairs Medical Center, and University of Minnesota, Minneapolis, Minnesota; Hopital Cochin, Departement de Physiologie Respiratoire, and Hopital Robert Debr\u00e9, Service de R\u00e9animation Pediatrique, Paris; and Service des Maladies Vasculaires Pulmonaires, H\u00f4pital Antoine-B\u00e9cl\u00e8re, Clamart, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[1998,10,1]]},"reference":[{"key":"2026032709043416200_B1","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/S0889-8529(05)70360-1","article-title":"Prevalence of obesity.","volume":"25","author":"VanItallie","year":"1996","journal-title":"Endocrin. Metab. Clin. North Am."},{"key":"2026032709043416200_B2"},{"key":"2026032709043416200_B3","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1056\/NEJM199608293350901","article-title":"Appetite-suppressant drugs and the risk of primary pulmonary hypertension.","volume":"335","author":"Abenhaim","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"2026032709043416200_B4","first-page":"897","article-title":"Pulmonary hypertension, \u201cplexogenic pulmonary arteriopathy\u201d and the appetite depressant drug aminorex: post or propter.","volume":"15","author":"Gurtner","year":"1979","journal-title":"Bull. Eur. Physiopathol. Res."},{"key":"2026032709043416200_B5","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1056\/NEJM199708283370904","article-title":"Fatal pulmonary hypertension associated with short-term use of fenfluramine and phentermine.","volume":"337","author":"Mark","year":"1997","journal-title":"N. Engl. J. 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Physiol."},{"key":"2026032709043416200_B9","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1096\/fasebj.7.2.8440411","article-title":"Measurement of nitric oxide in biological models.","volume":"7","author":"Archer","year":"1993","journal-title":"FASEB J."},{"key":"2026032709043416200_B10","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1378\/chest.110.4.930","article-title":"Origins of breath nitric oxide in humans.","volume":"110","author":"Dillon","year":"1996","journal-title":"Chest"},{"key":"2026032709043416200_B11","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1378\/chest.111.1.44","article-title":"Exhaled nitric oxide during exercise in primary pulmonary hypertension and pulmonary fibrosis.","volume":"111","author":"Riley","year":"1997","journal-title":"Chest"},{"key":"2026032709043416200_B12","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/BF01907748","article-title":"Long term effects of the anorectic agent fenfluramine alone and in combination with aminorex on pulmonary and systemic circulation of the pig.","volume":"74","author":"Mlczoch","year":"1979","journal-title":"Basic Res. 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Heart J."},{"key":"2026032709043416200_B23","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1183\/09031936.94.07081501","article-title":"Primarily nasal origin of exhaled nitric oxide and absence in Kartagener's syndrome.","volume":"7","author":"Lundberg","year":"1994","journal-title":"Eur. Respir. J."},{"key":"2026032709043416200_B24","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1038\/nm0495-370","article-title":"High nitric oxide production in human paranasal sinuses.","volume":"1","author":"Lundberg","year":"1995","journal-title":"Nat. Med."},{"key":"2026032709043416200_B25","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1164\/ajrccm\/148.5.1210","article-title":"Endogenous nitric oxide in single exhalations and the change during exercise.","volume":"148","author":"Persson","year":"1993","journal-title":"Am. Rev. Respir. 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Med."}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/158\/4\/1061\/67435603\/ajrccm_158_4_1061.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/158\/4\/1061\/67435603\/ajrccm_158_4_1061.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T13:05:36Z","timestamp":1774616736000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/158\/4\/1061\/8530284"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,10,1]]},"references-count":28,"journal-issue":{"issue":"4","published-online":{"date-parts":[[1998,10,1]]},"published-print":{"date-parts":[[1998,10,1]]}},"URL":"https:\/\/doi.org\/10.1164\/ajrccm.158.4.9802113","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[1998,10]]},"published":{"date-parts":[[1998,10,1]]}}}