{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T05:58:14Z","timestamp":1768715894091,"version":"3.49.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Using a clinical model of deep arterial injury, we assessed the ability of exogenous and endogenous tissue plasminogen activator (t-PA) to limit acute in situ thrombus formation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              Ex vivo thrombus formation was assessed in the Badimon chamber at low and high shear rates in 2 double-blind randomized cross-over studies of 20 healthy volunteers during extracorporeal administration of recombinant t-PA (0, 40, 200, and 1000 ng\/mL) or during endogenous t-PA release stimulated by intra-arterial bradykinin infusion in the presence or absence of oral enalapril. Recombinant t-PA caused a dose-dependent reduction in thrombus area under low and high shear conditions (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001 for all). Intra-arterial bradykinin increased plasma t-PA concentrations in the chamber effluent (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.01 for all versus saline) that was quadrupled in the presence of enalapril (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.0001 versus placebo). These increases were accompanied by an increase in plasma D-dimer concentration (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.005 for all versus saline) and, in the presence of enalapril, a reduction in thrombus area in the low shear (16\u00b15;\n              <jats:italic>P<\/jats:italic>\n              =0.03) and a trend toward a reduction in the high shear chamber (13\u00b17%;\n              <jats:italic>P<\/jats:italic>\n              =0.07).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Using a well-characterized clinical model of coronary arterial injury, we demonstrate that endogenous t-PA released from the vascular endothelium enhances fibrinolysis and limits in situ thrombus propagation. These data support a crucial role for the endogenous fibrinolytic system in vivo and suggest that continued exploration and manipulation of its therapeutic potential are warranted.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.112.300395","type":"journal-article","created":{"date-parts":[[2013,3,8]],"date-time":"2013-03-08T06:01:12Z","timestamp":1362722472000},"page":"1105-1111","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Endogenous Tissue Plasminogen Activator Enhances Fibrinolysis and Limits Thrombus Formation in a Clinical Model of Thrombosis"],"prefix":"10.1161","volume":"33","author":[{"given":"Andrew J.","family":"Lucking","sequence":"first","affiliation":[{"name":"From the Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyle R.","family":"Gibson","sequence":"additional","affiliation":[{"name":"From the Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elspeth E.","family":"Paterson","sequence":"additional","affiliation":[{"name":"From the Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dana","family":"Faratian","sequence":"additional","affiliation":[{"name":"From the Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher A.","family":"Ludlam","sequence":"additional","affiliation":[{"name":"From the Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas A.","family":"Boon","sequence":"additional","affiliation":[{"name":"From the Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith A.A.","family":"Fox","sequence":"additional","affiliation":[{"name":"From the Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David E.","family":"Newby","sequence":"additional","affiliation":[{"name":"From the Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199905203402007"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V85.12.3510.bloodjournal85123510"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1646611"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.72.6.1346"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1648920"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1657722"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.15.1936"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.638478"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1136\/heart.87.1.48"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000065195.22904.FA"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(00)00126-7"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.143248"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V88.5.1525.1525"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.6.3.312"},{"key":"e_1_3_4_16_2","first-page":"706","article-title":"Characterization of a tubular flow chamber for studying platelet interaction with biologic and prosthetic materials: deposition of indium 111-labeled platelets on collagen, subendothelium, and expanded polytetrafluoroethylene.","volume":"110","author":"Badimon L","year":"1987","unstructured":"Badimon L, Turitto V, Rosemark JA, Badimon JJ, Fuster V. 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