{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:32:14Z","timestamp":1791595934780,"version":"4.3.4"},"reference-count":79,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2024,10,1]]},"abstract":"<jats:p> Sickle cell disease (SCD) is characterized by central (cardiac) and peripheral vascular dysfunctions, significantly diminishing exercise capacity and quality of life. Although central cardiopulmonary abnormalities in SCD are known to reduce exercise capacity and quality of life; the impact of hemolysis and subsequent cell-free hemoglobin (Hb)-mediated peripheral vascular abnormalities on those outcomes are not fully understood. Despite the recognized benefits of exercise training for cardiovascular health and clinical management in chronic diseases like heart failure, there remains substantial debate on the advisability of regular physical activity for patients with SCD. This is primarily due to concerns that prolonged and\/or high-intensity exercise might trigger metabolic shifts leading to vaso-occlusive crises. As a result, exercise recommendations for patients with SCD are often vague or nonexistent, reflecting a gap in knowledge about the mechanisms of exercise intolerance and the impact of exercise training on SCD-related health issues. This mini-review sheds light on recent developments in understanding how SCD affects exercise tolerance, with a special focus on the roles of hemolysis and the release of cell-free hemoglobin in altering cardiovascular and skeletal muscle function. Also highlighted here is the emerging research on the therapeutic effects and safety of exercise training in patients with SCD. In addition, the review identifies future research opportunities to fill existing gaps in our understanding of exercise (in)tolerance in SCD. <\/jats:p>","DOI":"10.1152\/japplphysiol.00390.2024","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T08:00:39Z","timestamp":1724918439000},"page":"975-983","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Understanding exercise (in)tolerance in sickle cell disease: impacts of hemolysis and exercise training on skeletal muscle oxygen delivery"],"prefix":"10.1152","volume":"137","author":[{"given":"David C.","family":"Irwin","sequence":"first","affiliation":[{"name":"Cardiovascular and Pulmonary Research Group, Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward T. N.","family":"Calvo","sequence":"additional","affiliation":[{"name":"Department of Health and Kinesiology, Purdue University, West Lafayette, Indiana, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Belbis","sequence":"additional","affiliation":[{"name":"Department of Exercise Science, Aurora University, Aurora, Illinois, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina K. C.","family":"Ehrenfort","sequence":"additional","affiliation":[{"name":"Integrative Aerospace and Exercise Physiology Laboratory, Department of Human Factors, Embry-Riddle Aeronautical University, Daytona Beach, Florida, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"Noguer","sequence":"additional","affiliation":[{"name":"Laboratorie Interuniversitaire de Biologie de la Motricit\u00e9, Universit\u00e9 Savoie Mont Blanc (USMB), Chamb\u00e9ry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8823-1986","authenticated-orcid":false,"given":"Laurent A.","family":"Messonnier","sequence":"additional","affiliation":[{"name":"Laboratorie Interuniversitaire de Biologie de la Motricit\u00e9, Universit\u00e9 Savoie Mont Blanc (USMB), Chamb\u00e9ry, France"},{"name":"Institut Universitaire de France (IUF), Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul W.","family":"Buehler","sequence":"additional","affiliation":[{"name":"Department of Pathology and The Center for Blood Oxygen Transport and Hemostasis, Department of Pediatrics, The University of Maryland School of Medicine, Baltimore, Maryland, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7861-637X","authenticated-orcid":false,"given":"Daniel M.","family":"Hirai","sequence":"additional","affiliation":[{"name":"Department of Health and Kinesiology, Purdue University, West Lafayette, Indiana, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4446-6131","authenticated-orcid":false,"given":"Scott K.","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Integrative Aerospace and Exercise Physiology Laboratory, Department of Human Factors, Embry-Riddle Aeronautical University, Daytona Beach, Florida, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a010288"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.358"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-05-220921"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200610-1498OC"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23752"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2018.1.418"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3233\/CH-2011-1465"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1348\/135910702760213724"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2018.03.005"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2015.01.012"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052471"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2017.03.015"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2015.01.023"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0000000000001757"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1113\/JP275810"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0187833"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.2002036"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/89.2.221"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(55)90208-4"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0798-672"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.15.8757"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1001\/jama.294.1.81"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1021\/bi960442g"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/s0925-4439(99)00027-7"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00269.2018"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-04-495887"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25742"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1177\/10760296231186144"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.198622"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.127860"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2021.08.238"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1149005"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1919.sp001839"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1919.sp001844"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00013.2019"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2013.073874"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00290.2006"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00943.2011"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01222.2001"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1113\/JP279223"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/nm1202-799"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2017.05.006"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00893.2002"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.062042"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019001055"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25936"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1007\/s10974-022-09636-y"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00122.2020"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1249\/JES.0000000000000045"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.198382"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1080\/17461391.2014.966764"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0000000000000939"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-07-2839"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2023.1151268"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00074.2012"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1172\/JCI103489"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00395.2015"},{"key":"B58","first-page":"789","volume":"37","author":"Lange RD","year":"1951","journal-title":"J Lab Clin Med"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V59.5.1055.1055"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.36660\/abc.20200437"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2011.08728.x"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1113\/EP087169"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12594"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.3233\/CH-2012-1540"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0000000000001993"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.3233\/CH-141891"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(18)30163-7"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12123952"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8122155"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.4314\/ahs.v18i1.15"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2020.267047"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0250128"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118237"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2004.01307.x"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1179\/102453309X385133"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.06.025"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00901.2013"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00469.2015"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1177\/1043454219844243"}],"container-title":["Journal of Applied Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/japplphysiol.00390.2024","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T02:59:46Z","timestamp":1728010786000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/japplphysiol.00390.2024"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,1]]},"references-count":79,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,10,1]]}},"alternative-id":["10.1152\/japplphysiol.00390.2024"],"URL":"https:\/\/doi.org\/10.1152\/japplphysiol.00390.2024","relation":{},"ISSN":["8750-7587","1522-1601"],"issn-type":[{"value":"8750-7587","type":"print"},{"value":"1522-1601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,1]]},"assertion":[{"value":"2024-05-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-29","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}