{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T02:13:37Z","timestamp":1791684817147,"version":"4.3.4"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,9,3]],"date-time":"2018-09-03T00:00:00Z","timestamp":1535932800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007150","name":"United Therapeutics Corporation","doi-asserted-by":"publisher","award":["NIH U19AI090959"],"award-info":[{"award-number":["NIH U19AI090959"]}],"id":[{"id":"10.13039\/100007150","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Elevated pulmonary vascular resistance (<jats:styled-content style=\"fixed-case\">PVR<\/jats:styled-content>), platelet adhesion, coagulation activation, and inflammation are prominent features of xenolung rejection. Here, we evaluate the role of thromboxane and histamine on <jats:styled-content style=\"fixed-case\">PVR<\/jats:styled-content>, and their contribution to other lung xenograft injury mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Gal<jats:styled-content style=\"fixed-case\">TKO<\/jats:styled-content>.<jats:styled-content style=\"fixed-case\">hCD<\/jats:styled-content>46 single pig lungs were perfused ex vivo with fresh heparinized human blood: lungs were either treated with 1\u2010Benzylimidazole (1\u2010<jats:styled-content style=\"fixed-case\">BIA<\/jats:styled-content>) combined with histamine receptor blocker famotidine (n\u00a0=\u00a04) or diphenhydramine (n\u00a0=\u00a06), 1\u2010<jats:styled-content style=\"fixed-case\">BIA<\/jats:styled-content> alone (n\u00a0=\u00a06) or were left untreated (n\u00a0=\u00a09).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Six of the nine control experiments (Gal<jats:styled-content style=\"fixed-case\">TKO<\/jats:styled-content>.<jats:styled-content style=\"fixed-case\">hCD<\/jats:styled-content>46 untreated), \u201csurvived\u201d until elective termination at 4\u00a0hours. Without treatment, initial <jats:styled-content style=\"fixed-case\">PVR<\/jats:styled-content> elevation within the first 30\u00a0minutes resolved partially over the following hour, and increased progressively during the final 2\u00a0hours of perfusion. In contrast, 1\u2010<jats:styled-content style=\"fixed-case\">BIA<\/jats:styled-content>, alone or in addition to either antihistamine treatment, was associated with low stable <jats:styled-content style=\"fixed-case\">PVR<\/jats:styled-content>. Combined treatments significantly lowered the airway pressure when compared to untreated reference. Although platelet and neutrophil sequestration and coagulation cascade activation were not consistently altered by any intervention, increased terminal wet\/dry weight ratio in untreated lungs was significantly blunted by combined treatments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Combined thromboxane and histamine pathway blockade prevents <jats:styled-content style=\"fixed-case\">PVR<\/jats:styled-content> elevation and significantly inhibits loss of vascular barrier function when Gal<jats:styled-content style=\"fixed-case\">TKO<\/jats:styled-content>.<jats:styled-content style=\"fixed-case\">hCD<\/jats:styled-content>46 lungs are perfused with human blood. Platelet activation and platelet and neutrophil sequestration persist in all groups despite efficient complement regulation, and appear to occur independent of thromboxane and histamine antagonism. Our work identifies thromboxane and histamine as key mediators of xenolung injury and defines those pathways as therapeutic targets to achieve successful xenolung transplantation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/xen.12458","type":"journal-article","created":{"date-parts":[[2018,9,3]],"date-time":"2018-09-03T11:25:00Z","timestamp":1535973900000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Thromboxane and histamine mediate <scp>PVR<\/scp> elevation during xenogeneic pig lung perfusion with human blood"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8943-4750","authenticated-orcid":false,"given":"Lars","family":"Burdorf","sequence":"first","affiliation":[{"name":"Division of Cardiac Surgery Department of Surgery University of Maryland School of Medicine, and VA Maryland Health Care System  Baltimore Maryland"},{"name":"Center for Transplantation Sciences and Division 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