{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T16:28:33Z","timestamp":1764001713615},"reference-count":0,"publisher":"Georg Thieme Verlag KG","issue":"07","funder":[{"name":"Australian National Health and Medical Research Council Biomedical (CJ Martin) Overseas Fellowship","award":["ID #252926"],"award-info":[{"award-number":["ID #252926"]}]},{"name":"British Heart Foundation and the Medical Research Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2009]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Vein grafts are used to bypass coronary arterial stenosis, but many grafts thrombose soon after surgery. A model was developed in the pig to allow continuous measurement of blood flow and production of flow-restricting thrombi (cyclic flow reductions; CFRs). Saphenous vein lumen was exposed to adenovirus ex vivo, to over-express human tissue plasminogen activator (h-tPA), with \u03b2-galactosidase adenovirus as a control. The vein segmen ts were engrafted into carotid arteries and examined 0,1 or 3 days later (4\u20137 animals\/group). Untransduced grafts examined on the day of surgery developed repeated CFRs at both normal and restricted flow, but their frequency declined in grafts examined after 3 days. Adenovirus transduction was evident as \u03b2-galactosidase or h-tPA expression 1 day after engraftment. Blood flow was increased 1.4-fold in h-tPA transduced grafts after 1 day [control 390 (280\u2013510), h-tPA 550 (450\u2013660) ml\/min; p=0.02 (expressed as mean (95% confidence intervals)]. CFRs were less severe (p=0.002) in the h-tPA transduced grafts than \u03b2-galactosidase-transduced grafts. CFRs were also less frequent in unstenosed undamaged h-tPA grafts [control 17 (6.1\u201329), h-tPA 7.6 (1.7\u201314) CFR\/hr; p=0.02], but this difference was reduced after damage or stenosis. CFRs formed faster in h-tPA than in \u03b2-galactosidase-transduced grafts [control 14 (11\u201317), h-tPA 23 (19\u201327) ml\/min2; p&lt;0.001], and resolved twofold faster [control 25 (22\u201330), h-tPA 48 (39\u201360) ml\/min2; p&lt;0.001]. Hence, in this model, local gene therapy with h-tPA increased graft blood flow and decreased measures of early graft thrombosis, namely quicker CFR resolution and decreased frequency and severity.<\/jats:p>","DOI":"10.1160\/th08-11-0772","type":"journal-article","created":{"date-parts":[[2009,6,4]],"date-time":"2009-06-04T10:40:37Z","timestamp":1244112037000},"page":"145-152","source":"Crossref","is-referenced-by-count":13,"title":["Reduction of early vein graft thrombosis by tissue plasminogen activator gene transfer"],"prefix":"10.1160","volume":"102","author":[{"given":"Marcella J.","family":"Wyatt","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew C.","family":"Newby","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita C.","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2017,11,24]]},"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1160\/TH08-11-0772.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,24]],"date-time":"2018-10-24T20:24:43Z","timestamp":1540412683000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1160\/TH08-11-0772"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009]]},"references-count":0,"journal-issue":{"issue":"07","published-online":{"date-parts":[[2017,12,15]]},"published-print":{"date-parts":[[2009]]}},"URL":"https:\/\/doi.org\/10.1160\/th08-11-0772","relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009]]}}}