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Exercise tolerance depends on integrated oxygen transport and utilization, which are impaired in heart transplant recipients. We synthesize evidence supporting that the combined effects of impaired pulmonary gas exchange, reduced haemoglobin concentration, heart denervation, chronic calcineurin inhibition, decreased muscle capillary density, and detraining from limited physical activity contribute to: (1) reduced pulmonary diffusion and alveolar ventilation\u2013perfusion mismatch that contribute to hypoxemia and increased ventilatory demand; (2) impaired convective oxygen delivery due to anaemia and to heart denervation that limits cardiac output; (3) deficits in endothelial function and reduced muscle capillarization that contribute to diminished convective and diffusive oxygen transport within skeletal muscle. Using Wagner's model, which describes oxygen transport from the atmosphere to muscle mitochondrion, we develop the hypothesis that the persistent reduction in aerobic capacity in heart transplant recipients reflects the combined and interactive effects of impaired convective oxygen transport and reduced muscle oxygen diffusive capacity, rather than a single dominant limitation. This basis generates testable physiological targets for interventions aimed at improving functional capacity after transplantation.<\/jats:p>","DOI":"10.1113\/ep093964","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:24:23Z","timestamp":1791545063000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exercise intolerance and impaired aerobic capacity in heart transplant recipients"],"prefix":"10.1113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2081-0708","authenticated-orcid":false,"given":"Fred W.","family":"Kolkhorst","sequence":"first","affiliation":[{"name":"School of Exercise and Nutritional Sciences San Diego State University  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2175-3445","authenticated-orcid":false,"given":"Daniel T.","family":"Cannon","sequence":"additional","affiliation":[{"name":"School of Exercise and Nutritional Sciences San Diego State University  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7884-0726","authenticated-orcid":false,"given":"Harry B.","family":"Rossiter","sequence":"additional","affiliation":[{"name":"Respiratory Research Center The Lundquist Institute for Biomedical Innovation at Harbor\u2212UCLA Medical Center  Torrance California USA"},{"name":"Division of Respiratory and Critical Care Medicine, Department of Medicine Harbor\u2212UCLA Medical Center  Torrance California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00280.2016"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.118.6.1661"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/hj.1998.v136.89731"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.3.2032"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa010519"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1998.84.6.1967"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008483-200011000-00007"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(93)90189-8"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2007.09.032"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP279135"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP285650"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2011.05.020"},{"key":"e_1_2_10_14_1","first-page":"1073","article-title":"Basis for aerobic impairment in patients after heart transplantation","volume":"14","author":"Bussi\u00e8res L. 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