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It has been argued that the reduction in saline contrast bubbles through IPAVA is due to altered in vivo microbubble dynamics with hyperoxia reducing bubble stability, rather than closure of IPAVA. To definitively determine whether breathing hyperoxia decreases saline contrast bubble stability in vivo, the present study included individuals with and without patent foramen ovale (PFO) to determine if hyperoxia also eliminates left heart contrast in people with an intracardiac right-to-left shunt. Thirty-two participants consisted of 16 without a PFO; 8 females, 8 with a PFO; 4 females, and 8 with late-appearing left-sided contrast (4 females) completed five, 4-min bouts of constant-load cycle ergometer exercise (males: 250 W, females: 175 W), breathing an [Formula: see text] = 0.21, 0.40, 0.60, 0.80, and 1.00 in a balanced Latin Squares design. Q<jats:sub>IPAVA<\/jats:sub> was assessed at rest and 3 min into each exercise bout via transthoracic saline contrast echocardiography and our previously used bubble scoring system. Bubble scores at [Formula: see text]= 0.21, 0.40, and 0.60 were unchanged and significantly greater than at [Formula: see text]= 0.80 and 1.00 in those without a PFO. Participants with a PFO had greater bubble scores at [Formula: see text]= 1.00 than those without a PFO. These data suggest that hyperoxia-induced decreases in Q<jats:sub>IPAVA<\/jats:sub> during exercise occur when [Formula: see text] \u2265 0.80 and is not a result of altered in vivo microbubble dynamics supporting the idea that hyperoxia closes Q<jats:sub>IPAVA<\/jats:sub>. <\/jats:p>","DOI":"10.1152\/ajpregu.00014.2023","type":"journal-article","created":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T12:53:05Z","timestamp":1684155185000},"page":"R96-R105","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Hyperoxia-induced stepwise reduction in blood flow through intrapulmonary, but not intracardiac, shunt during exercise"],"prefix":"10.1152","volume":"325","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0791-9779","authenticated-orcid":false,"given":"James T.","family":"Davis","sequence":"first","affiliation":[{"name":"Indiana University School of Medicine, Department of Anatomy, Cell Biology and 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