{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T03:50:10Z","timestamp":1787197810266,"version":"build-2736575974"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100008895","name":"Tertiary Education Trust Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008895","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008460","name":"National Center for Complementary and Integrative Health","doi-asserted-by":"publisher","award":["K24AT009893"],"award-info":[{"award-number":["K24AT009893"]}],"id":[{"id":"10.13039\/100008460","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tertiary Education Trust Fund"},{"DOI":"10.13039\/100008460","name":"National Center for Complementary and Integrative Health","doi-asserted-by":"publisher","award":["K24AT009893"],"award-info":[{"award-number":["K24AT009893"]}],"id":[{"id":"10.13039\/100008460","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Acute changes in cardiopulmonary hemodynamics that include tricuspid regurgitant jet velocity (TRV) elevation measured by Doppler echocardiography are often encountered during sickle cell vasoocclusive pain and acute chest syndrome (ACS). Arginine and nitric oxide depletion develop in patients with these complications. Arginine administration may therefore improve nitric oxide bioavailability and potentiate pulmonary vasodilatation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate effects of l-arginine supplementation on Doppler indices of cardiopulmonary hemodynamics in children with sickle cell anemia experiencing pain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This was a prospective, double-blinded, randomized placebo-controlled trial of oral arginine in children with sickle cell anemia age 5\u201317 years hospitalized with severe pain and\/or ACS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Blood biomarkers and Doppler echocardiographic indices of cardiopulmonary hemodynamics were measured before and after supplementation. The mean change in TRV, pulmonary artery systolic pressure, mean pulmonary artery pressure, and other indices of cardiopulmonary hemodynamics were tested with paired Student\u2019s t test and correlated with markers of arginine bioavailability using Pearson correlation. Sixty-six children were randomized into arginine versus placebo groups. An elevated TRV\u2009\u2a7e\u20092.5 m\/s was seen in 40 (61%) patients. A Day 5 Doppler echocardiogram was performed in 47 patients who remained hospitalized. A greater reduction in median TRV occurred in the arginine group than placebo (22.2%, n\u2009=\u200922 vs. 3.8%, n\u2009=\u200925; p\u2009&amp;lt;\u20090.01). A larger percentage increase in global arginine bioavailability was associated with a lower TRV after 5 days of supplementation (r\u2009=\u2009\u22120.533; P\u2009=\u20090.001). Significant differences in multiple indices of cardiopulmonary hemodynamics and mean N-terminal pro B-type brain natriuretic peptide were also noted after arginine therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Oral arginine supplementation improves cardiopulmonary hemodynamics during sickle cell disease vasoocclusive pain and ACS.Clinical trial registered with Pan African Clinical Trial Registry https:\/\/pactr.samrc.ac.za\/Search.aspx (PACTR201611001864290).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202108-1930oc","type":"journal-article","created":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T11:57:47Z","timestamp":1650023867000},"page":"70-80","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":28,"title":["Arginine Therapy and Cardiopulmonary Hemodynamics in Hospitalized Children with Sickle Cell Anemia: A Prospective, Double-blinded, Randomized Placebo-controlled Clinical Trial"],"prefix":"10.1093","volume":"206","author":[{"given":"Richard","family":"Onalo","sequence":"first","affiliation":[{"name":"Cardiology Unit, Department of Paediatrics, Faculty of Clinical Sciences, University of Abuja, Abuja, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoinette","family":"Cilliers","sequence":"additional","affiliation":[{"name":"Division of Paediatric Cardiology, Department of Paediatrics, Chris Hani Baragwanath Academic Hospital, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Cooper","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, University of the Witwatersrand, Johannesburg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6019-2858","authenticated-orcid":false,"given":"Claudia 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