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We sought to determine if abnormal ventilatory chemoreflex control contributes to EX-inT in volume-overload HF rats. Cardiac function, hypercapnic (HCVR) and hypoxic (HVR) ventilatory responses, and exercise tolerance were assessed at the end of a 6\u00a0week exercise training program. At the conclusion of the training program, exercise tolerant HF rats (HF\u2009+\u2009EX-T) exhibited improvements in cardiac systolic function and reductions in HCVR, sympathetic tone, and arrhythmias. In contrast, HF rats that were exercise intolerant (HF\u2009+\u2009EX-inT) exhibited worse diastolic dysfunction, and showed no improvements in cardiac systolic function, HCVR, sympathetic tone, or arrhythmias at the conclusion of the training program. In addition, HF\u2009+\u2009EX-inT rats had impaired HVR which was associated with increased arrhythmia susceptibility and mortality during hypoxic challenges (~\u200960% survival). Finally, we observed that exercise tolerance in HF rats was related to carotid body (CB) function as CB ablation resulted in impaired exercise capacity in HF\u2009+\u2009EX-T rats. Our results indicate that: (i) exercise may have detrimental effects on cardiac function in HF-EX-inT, and (ii) loss of CB chemoreflex sensitivity contributes to EX-inT in HF.<\/jats:p>","DOI":"10.1038\/s41598-021-93791-8","type":"journal-article","created":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T06:03:36Z","timestamp":1626242616000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Exercise intolerance in volume overload heart failure is associated with low carotid body mediated chemoreflex drive"],"prefix":"10.1038","volume":"11","author":[{"given":"David C.","family":"Andrade","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esteban","family":"D\u00edaz-Jara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilo","family":"Toledo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla G.","family":"Schwarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherin V.","family":"Pereyra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo S.","family":"D\u00edaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah J.","family":"Marcus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando C.","family":"Ortiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang\u00e9lica P.","family":"R\u00edos-Gallardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domiziana","family":"Ortolani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Del Rio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,14]]},"reference":[{"key":"93791_CR1","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1152\/japplphysiol.00189.2017","volume":"123","author":"DC Andrade","year":"2017","unstructured":"Andrade, D. 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