{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T11:19:11Z","timestamp":1778152751818,"version":"3.51.4"},"reference-count":48,"publisher":"American Physiological Society","issue":"1","funder":[{"DOI":"10.13039\/501100001030","name":"National Heart Foundation of Australia","doi-asserted-by":"publisher","award":["Grant-In-Aid G 12M 6396"],"award-info":[{"award-number":["Grant-In-Aid G 12M 6396"]}],"id":[{"id":"10.13039\/501100001030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001030","name":"National Heart Foundation of Australia","doi-asserted-by":"publisher","award":["NHF 100409"],"award-info":[{"award-number":["NHF 100409"]}],"id":[{"id":"10.13039\/501100001030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"Department of Health, Australian Government | National Health and Medical Research Council (NHMRC)","doi-asserted-by":"publisher","award":["NHMRC 1089039"],"award-info":[{"award-number":["NHMRC 1089039"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2019,7,1]]},"abstract":"<jats:p> Exercise capacity is frequently reduced in people with diabetes mellitus (DM), and the contribution of pulmonary microvascular dysfunction remains undefined. We hypothesized that pulmonary microvascular disease, measured by a novel exercise echocardiography technique termed pulmonary transit of agitated contrast (PTAC), would be greater in subjects with DM and that the use of pulmonary vasodilator agent sildenafil would improve exercise performance by reducing right ventricular afterload. Forty subjects with DM and 20 matched controls performed cardiopulmonary exercise testing and semisupine exercise echocardiography 1 h after placebo or sildenafil ingestion in a double-blind randomized crossover design. The primary efficacy end point was exercise capacity (V\u0307o<jats:sub>2peak<\/jats:sub>) while secondary measures included pulmonary vascular resistance, cardiac output, and change in PTAC. DM subjects were aged 44\u2009\u00b1\u200913 yr, 73% male, with 16\u2009\u00b1\u200910 yr DM history. Sildenafil caused marginal improvements in echocardiographic measures of biventricular systolic function in DM subjects. Exercise-induced increases in pulmonary artery systolic pressure and pulmonary vascular resistance were attenuated with sildenafil, while heart rate (+2.4\u2009\u00b11.2 beats\/min, P = 0.04) and cardiac output (+322\u2009\u00b1\u200921 ml, P = 0.03) improved. However, the degree of PTAC did not change ( P = 0.93) and V\u0307o<jats:sub>2peak<\/jats:sub> did not increase following sildenafil as compared with placebo (V\u0307o<jats:sub>2peak<\/jats:sub>: 31.8\u2009\u00b1\u20099.7 vs. 32.1\u2009\u00b1\u20099.5 ml\u00b7min<jats:sup>\u22121<\/jats:sup>\u00b7kg<jats:sup>\u22121<\/jats:sup>, P = 0.42). We conclude that sildenafil administration causes modest acute improvements in central hemodynamics but does not improve exercise capacity. This may be due to the mismatch in action of sildenafil on the pulmonary arteries rather than the distal pulmonary microvasculature and potential adverse effects on peripheral oxygen extraction. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY This is one of the largest and most comprehensive studies of cardiopulmonary exercise performance in people with diabetes mellitus and to our knowledge the first to assess the effect of sildenafil using detailed echocardiographic measures during incremental exercise. Sildenafil attenuated the rise in pulmonary vascular resistance while augmenting cardiac output and intriguingly heart rate, without conferring any improvement in exercise capacity. The enhanced central hemodynamic indexes may have been offset by reduced peripheral O<jats:sub>2<\/jats:sub> extraction. <\/jats:p>","DOI":"10.1152\/japplphysiol.00947.2018","type":"journal-article","created":{"date-parts":[[2019,5,2]],"date-time":"2019-05-02T15:41:07Z","timestamp":1556811667000},"page":"1-10","source":"Crossref","is-referenced-by-count":2,"title":["Sildenafil enhances central hemodynamic responses to exercise, but not V\u0307<scp>o<\/scp><sub>2peak<\/sub>, in people with diabetes mellitus"],"prefix":"10.1152","volume":"127","author":[{"given":"Timothy J.","family":"Roberts","sequence":"first","affiliation":[{"name":"Department of Cardiology, St. Vincent\u2019s Hospital Melbourne, Fitzroy, Australia"},{"name":"St. Vincent\u2019s Department of Medicine, University of Melbourne, Fitzroy, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew T.","family":"Burns","sequence":"additional","affiliation":[{"name":"Department of Cardiology, St. Vincent\u2019s Hospital Melbourne, Fitzroy, Australia"},{"name":"St. Vincent\u2019s Department of Medicine, University of Melbourne, Fitzroy, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J.","family":"MacIsaac","sequence":"additional","affiliation":[{"name":"St. Vincent\u2019s Department of Medicine, University of Melbourne, Fitzroy, Australia"},{"name":"Department of Endocrinology and Diabetes, St. Vincent\u2019s Hospital Melbourne, Fitzroy, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew I.","family":"MacIsaac","sequence":"additional","affiliation":[{"name":"Department of Cardiology, St. Vincent\u2019s Hospital Melbourne, Fitzroy, Australia"},{"name":"St. Vincent\u2019s Department of Medicine, University of Melbourne, Fitzroy, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David L.","family":"Prior","sequence":"additional","affiliation":[{"name":"Department of Cardiology, St. Vincent\u2019s Hospital Melbourne, Fitzroy, Australia"},{"name":"St. Vincent\u2019s Department of Medicine, University of Melbourne, Fitzroy, Australia"},{"name":"National Centre for Sports Cardiology, Fitzroy, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3906-3784","authenticated-orcid":false,"given":"Andr\u00e9","family":"La Gerche","sequence":"additional","affiliation":[{"name":"Department of Cardiology, St. Vincent\u2019s Hospital Melbourne, Fitzroy, Australia"},{"name":"St. Vincent\u2019s Department of Medicine, University of Melbourne, Fitzroy, Australia"},{"name":"National Centre for Sports Cardiology, Fitzroy, Australia"},{"name":"Baker Heart and Diabetes Institute, Melbourne, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.647172"},{"key":"B2","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.2337\/dc16-er09","volume":"39","author":"American Diabetes Association","year":"2016","journal-title":"Diabetes Care"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1001\/jama.287.6.719"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1378\/chest.06-2674"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0b013e3181e52e69"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.114.001602"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2014-306851"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2014.02.007"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.25.8.1336"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-965131"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.28.7.1643"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa050010"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv317"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-141-3-200408030-00005"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.063412"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.983866"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv336"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2007.0227"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00806.2005"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvv123"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(99)00043-0"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1089\/ham.2011.0011"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.109.934273"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/s00421-011-1930-3"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.022535"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.112.980037"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00457.2010"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.626226"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jhh.1001244"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.655266"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/0895-7061(95)00022-H"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(97)00251-9"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2012.04.002"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(99)00774-2"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.112.969071"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.2024"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0b013e3181942051"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-012-9234-4"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1089\/ham.2005.6.43"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.2337\/dc17-1904"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.wem.2016.01.006"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000036027.71527.3E"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv134"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.921"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.643536"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000152262.22968.72"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/nm1175"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1055\/s-0035-1559774"}],"container-title":["Journal of Applied Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/japplphysiol.00947.2018","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,20]],"date-time":"2019-09-20T22:36:34Z","timestamp":1569018994000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/japplphysiol.00947.2018"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,1]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,7,1]]}},"alternative-id":["10.1152\/japplphysiol.00947.2018"],"URL":"https:\/\/doi.org\/10.1152\/japplphysiol.00947.2018","relation":{},"ISSN":["8750-7587","1522-1601"],"issn-type":[{"value":"8750-7587","type":"print"},{"value":"1522-1601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,1]]}}}