{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T03:31:09Z","timestamp":1783481469151,"version":"3.55.0"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"25","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,6,18]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    This study describes a novel mechanism for the formation of cardiogenic lung edema, a potentially fatal complication of left heart disease that was previously attributed to passive fluid filtration across an intact alveolo-capillary barrier. Instead, we demonstrate that a major part of cardiogenic edema results from active epithelial secretion of Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    and secondary fluid flux into the alveolar space. Transepithelial Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    secretion is triggered by inhibition of epithelial Na\n                    <jats:sup>+<\/jats:sup>\n                    uptake and mediated via cystic fibrosis transmembrane conductance regulator (CFTR) and Na\n                    <jats:sup>+<\/jats:sup>\n                    -K\n                    <jats:sup>+<\/jats:sup>\n                    -2Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    cotransporter 1 (NKCC1), providing a mechanistic explanation for extrarenal effects of furosemide in lung edema.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1216382110","type":"journal-article","created":{"date-parts":[[2013,5,4]],"date-time":"2013-05-04T00:28:49Z","timestamp":1367627329000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":69,"title":["Chloride transport-driven alveolar fluid secretion is a major contributor to cardiogenic lung edema"],"prefix":"10.1073","volume":"110","author":[{"given":"Esther A.","family":"Solymosi","sequence":"first","affiliation":[{"name":"The Keenan Research Centre at the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, Canada M5B 1W8;"},{"name":"Institute of Physiology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 14195 Berlin, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie M.","family":"Kaestle-Gembardt","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 14195 Berlin, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istv\u00e1n","family":"Vad\u00e1sz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Giessen Lung Center, 35392 Giessen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liming","family":"Wang","sequence":"additional","affiliation":[{"name":"The Keenan Research Centre at the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, Canada M5B 1W8;"},{"name":"German Heart Institute Berlin, 13353 Berlin, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Neye","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 14195 Berlin, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile Julie Adrienne","family":"Chupin","sequence":"additional","affiliation":[{"name":"The Keenan Research Centre at the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, Canada M5B 1W8;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Rozowsky","sequence":"additional","affiliation":[{"name":"The Keenan Research Centre at the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, Canada M5B 1W8;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramona","family":"Ruehl","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Giessen Lung Center, 35392 Giessen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arata","family":"Tabuchi","sequence":"additional","affiliation":[{"name":"The Keenan Research Centre at the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, Canada M5B 1W8;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Schulz","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology I, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, 85764 Neuherberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andras","family":"Kapus","sequence":"additional","affiliation":[{"name":"The Keenan Research Centre at the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, Canada M5B 1W8;"},{"name":"Departments of fSurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rory E.","family":"Morty","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang M.","family":"Kuebler","sequence":"additional","affiliation":[{"name":"The Keenan Research Centre at the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, Canada M5B 1W8;"},{"name":"Institute of Physiology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 14195 Berlin, Germany;"},{"name":"German Heart Institute Berlin, 13353 Berlin, Germany;"},{"name":"Departments of fSurgery and"},{"name":"Physiology, University of Toronto, Toronto, ON, Canada M5S 1A8; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,5,3]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.107.168724"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00008.2007"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.2001.281.3.L591"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1999.87.4.1301"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00003.2002"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200304-562OC"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.67.032003.154107"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2006-0347OC"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000164554.21993.AC"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00178.2005"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200407-954OC"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00562.2002"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.96.6.1847"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0600855103"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.163.6.2004035"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2006-0080SF"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.119.2.199"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/354526a0"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.44.26626"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.0051j.x"},{"key":"e_1_3_3_21_2","first-page":"L1127","article-title":"cAMP activation of chloride and fluid secretion across the rabbit alveolar epithelium","volume":"275","author":"Nielsen VG","year":"1998","unstructured":"VG Nielsen, MD Duvall, MS Baird, S Matalon, cAMP activation of chloride and fluid secretion across the rabbit alveolar epithelium. Am J Physiol 275, L1127\u2013L1133 (1998).","journal-title":"Am J Physiol"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002329900500"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.62.1.515"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI109608"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(79)90049-3"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2003.09.074"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3378-07.2008"},{"key":"e_1_3_3_28_2","first-page":"343","article-title":"CFTR regulation of ENaC","volume":"70","author":"Donaldson SH","year":"2002","unstructured":"SH Donaldson, EG Poligone, MJ Stutts, CFTR regulation of ENaC. Methods Mol Med 70, 343\u2013364 (2002).","journal-title":"Methods Mol Med"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1028"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21011"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1982.53.1.258"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1992.262.5.C1228"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-002-0956-0"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00256.2002"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00030.2012"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.54.030192.002105"},{"key":"e_1_3_3_37_2","first-page":"417","article-title":"Severe acute interstitial pulmonary edema from Moduretic (amiloride plus hydrochlorothiazide)","volume":"57","author":"Kounis NG","year":"1986","unstructured":"NG Kounis, S Nikolaou, G Zavras, D Siablis, Severe acute interstitial pulmonary edema from Moduretic (amiloride plus hydrochlorothiazide). Ann Allergy 57, 417\u2013418 (1986).","journal-title":"Ann Allergy"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1998.274.3.L369"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2008-0005OC"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp052699"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0707992"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpainsymman.2007.10.017"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1186\/cc8930"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004210050331"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1216382110","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T21:38:48Z","timestamp":1649799528000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1216382110"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5,3]]},"references-count":44,"journal-issue":{"issue":"25","published-print":{"date-parts":[[2013,6,18]]}},"alternative-id":["10.1073\/pnas.1216382110"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1216382110","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,5,3]]},"assertion":[{"value":"2013-05-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}