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We hypothesized that: increased dead\u2010space results from the spatial redistribution of pulmonary perfusion, not ventilation; such redistribution is not related to thromboembolism (ie, areas with perfusion\u00a0=\u00a00 and infinite ventilation\u2010perfusion ratio, <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/aas13702-math-0001.png\" xlink:title=\"urn:x-wiley:00015172:media:aas13702:aas13702-math-0001\"\/>), but rather to moderate shifts of perfusion increasing <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/aas13702-math-0002.png\" xlink:title=\"urn:x-wiley:00015172:media:aas13702:aas13702-math-0002\"\/> in non\u2010dependent regions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Five healthy anesthetized sheep received protective ventilation for 20\u00a0hours, while endotoxin was continuously infused. Maps of voxel\u2010level lung ventilation, perfusion, <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/aas13702-math-0003.png\" xlink:title=\"urn:x-wiley:00015172:media:aas13702:aas13702-math-0003\"\/>, CO<jats:sub>2<\/jats:sub> partial pressures, and alveolar dead\u2010space fraction were estimated from positron emission tomography at baseline and 20\u00a0hours.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Alveolar dead\u2010space fraction increased during the 20\u00a0hours (+0.05, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.031), mainly in non\u2010dependent regions (+0.03, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.031). This was mediated by perfusion redistribution away from non\u2010dependent regions (\u22125.9%, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.031), while the spatial distribution of ventilation did not change, resulting in increased <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/aas13702-math-0004.png\" xlink:title=\"urn:x-wiley:00015172:media:aas13702:aas13702-math-0004\"\/> in non\u2010dependent regions. The increased alveolar dead\u2010space derived mostly from areas with intermediate <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/aas13702-math-0005.png\" xlink:title=\"urn:x-wiley:00015172:media:aas13702:aas13702-math-0005\"\/> (0.5\u2264<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/aas13702-math-0006.png\" xlink:title=\"urn:x-wiley:00015172:media:aas13702:aas13702-math-0006\"\/>\u226410), not areas of nearly \u201ccomplete\u201d dead\u2010space (<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/aas13702-math-0007.png\" xlink:title=\"urn:x-wiley:00015172:media:aas13702:aas13702-math-0007\"\/>&gt;10).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In this early ARDS model, increases in alveolar dead\u2010space occur within 20\u00a0hours due to the regional redistribution of perfusion and not ventilation. This moderate redistribution suggests changes in the interplay between active and passive perfusion redistribution mechanisms (including hypoxic vasoconstriction and gravitational effects), not the appearance of thromboembolism. Hence, the association between mortality and increased dead\u2010space possibly arises from the former, reflecting gas\u2010exchange inefficiency due to perfusion heterogeneity. Such heterogeneity results from the injury and exhaustion of compensatory mechanisms for perfusion redistribution.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aas.13702","type":"journal-article","created":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T13:33:00Z","timestamp":1601299980000},"page":"100-108","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Physiological mechanism and spatial distribution of increased alveolar dead\u2010space in early ARDS: An experimental study"],"prefix":"10.1111","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1867-9846","authenticated-orcid":false,"given":"Alessandro","family":"Beda","sequence":"first","affiliation":[{"name":"Postgraduate Program of Electrical Engineering Federal University of Minas Gerais Belo Horizonte Minas Gerais 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