{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T07:52:58Z","timestamp":1740124378179,"version":"3.37.3"},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,5,8]],"date-time":"2014-05-08T00:00:00Z","timestamp":1399507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TRR127-C6"],"award-info":[{"award-number":["TRR127-C6"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Xenogenic activation of hemostasis (<jats:styled-content style=\"fixed-case\">XAH<\/jats:styled-content>) represents a major hurdle for the transplantation of discordant animal organs into humans as it results in thrombotic microangiopathy (<jats:styled-content style=\"fixed-case\">TMA<\/jats:styled-content>). We have previously shown that recombinant human\u2010activated protein C (rh<jats:styled-content style=\"fixed-case\">APC<\/jats:styled-content>) mitigates <jats:styled-content style=\"fixed-case\">XAH<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">TMA<\/jats:styled-content> in an <jats:italic>ex vivo<\/jats:italic> model of pig\u2010to\u2010human kidney transplantation. However, the use of rh<jats:styled-content style=\"fixed-case\">APC<\/jats:styled-content> may not be feasible in a perioperative setting due to possible bleeding complications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we explored the effects of another natural inhibitor of coagulation, human recombinant antithrombin (rh<jats:styled-content style=\"fixed-case\">AT<\/jats:styled-content>), in comparison with rh<jats:styled-content style=\"fixed-case\">APC<\/jats:styled-content>. Unmodified porcine kidneys (n\u00a0=\u00a025) were perfused <jats:italic>ex vivo<\/jats:italic> with porcine blood, human blood, or human blood supplemented with rh<jats:styled-content style=\"fixed-case\">APC<\/jats:styled-content> or rh<jats:styled-content style=\"fixed-case\">AT<\/jats:styled-content>. Surrogate parameters of organ survival, markers of <jats:styled-content style=\"fixed-case\">XAH<\/jats:styled-content> (D\u2010 Dimer, thrombin\u2010antithrombin complex [<jats:styled-content style=\"fixed-case\">TAT<\/jats:styled-content>], fibrinogen, antithrombin activity, plasminogen), endothelial cell and platelet activation (E\u2010selectin, P\u2010selectin), platelet function tests and histological signs of <jats:styled-content style=\"fixed-case\">TMA<\/jats:styled-content> were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Perfusion was feasible for &gt;\u00a0240\u00a0min in all experiments with autologous porcine blood, but limited to 126\u00a0\u00b1\u00a078 min with human blood due to increased vascular resistance. Addition of rh<jats:styled-content style=\"fixed-case\">AT<\/jats:styled-content> protected from <jats:styled-content style=\"fixed-case\">TMA<\/jats:styled-content> and allowed for perfusion times &gt;\u00a0240\u00a0min. In addition, there were less signs of <jats:styled-content style=\"fixed-case\">XAH<\/jats:styled-content> with reduced release of P\u2010selectin and overexpression of E\u2010selectin, whereas the progressive loss of platelet function, observed during discordant perfusion, was prevented. The effect of rh<jats:styled-content style=\"fixed-case\">AT<\/jats:styled-content> was dose\u2010dependent with maximum protection obtained at 3\u00a0IU\/ml.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In conclusion, in this <jats:italic>ex vivo<\/jats:italic> model of discordant xenotransplantation, rh<jats:styled-content style=\"fixed-case\">AT<\/jats:styled-content> reduced <jats:styled-content style=\"fixed-case\">XAH<\/jats:styled-content> and prevented <jats:styled-content style=\"fixed-case\">TMA<\/jats:styled-content> in doses that appear feasible for use in clinical or preclinical transplantation settings.<\/jats:p><\/jats:sec>","DOI":"10.1111\/xen.12104","type":"journal-article","created":{"date-parts":[[2014,5,8]],"date-time":"2014-05-08T07:06:57Z","timestamp":1399532817000},"page":"367-375","source":"Crossref","is-referenced-by-count":7,"title":["Recombinant human antithrombin prevents xenogenic activation of hemostasis in a model of pig\u2010to\u2010human kidney transplantation"],"prefix":"10.1111","volume":"21","author":[{"given":"Wolf","family":"Ramackers","sequence":"first","affiliation":[{"name":"Department of General, Visceral and Transplantation Surgery Hannover Medical School Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Friedrich","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Hannover Medical School Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Klose","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplantation Surgery Hannover Medical School Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Vondran","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplantation Surgery Hannover Medical School Hannover 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