{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:27:40Z","timestamp":1760189260469},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"21","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1998,11,24]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            \u2014A 2-hour infusion of r-hirudin at the time of balloon angioplasty limits restenosis in atherosclerotic rabbits. Because thrombin activity in the vessel wall after angioplasty remains high for 48 to 72 hours, we hypothesized that a second infusion of hirudin at 24 hours would reduce restenosis more than early treatment alone.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            \u2014Femoral atherosclerosis was induced in 35 rabbits by air desiccation injury and a high-cholesterol diet. At the time of angioplasty, rabbits were randomly assigned to 1 of 4 groups: controls: heparin bolus, saline infusion at 24 hours; early hirudin: hirudin bolus+2 hours\u2019 infusion, saline infusion at 24 hours; delayed hirudin: heparin bolus, hirudin infusion\u00b1bolus at 24 hours; and early+delayed hirudin: hirudin bolus+2 hours\u2019 infusion, hirudin infusion\u00b1bolus at 24 hours. Rabbits were euthanized after 28 days. The early+delayed hirudin treatment group had less loss of minimal lumen diameter by angiography at 28 days. By histomorphometry, cross-sectional area narrowing by plaque was least in the early+delayed treatment group compared with controls (\n            <jats:italic>P<\/jats:italic>\n            =0.0001), early hirudin (\n            <jats:italic>P<\/jats:italic>\n            =0.01), or delayed hirudin (\n            <jats:italic>P<\/jats:italic>\n            =0.001). The early+delayed hirudin group also had a significant reduction in absolute plaque area and an improvement in lumen area compared with the other groups. No differences were observed between treatment groups with respect to the cross-sectional area encompassed by the internal or external elastic laminae.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014Combined early+delayed administration of hirudin significantly reduces angiographic restenosis and cross-sectional area narrowing by plaque compared with early or late treatment alone. These results suggest that restenosis after balloon angioplasty is markedly influenced by thrombin-mediated events not only occurring early but also extending beyond the first 24 hours in this model.\n          <\/jats:p>","DOI":"10.1161\/01.cir.98.21.2301","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:41:02Z","timestamp":1339461662000},"page":"2301-2306","update-policy":"http:\/\/dx.doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":18,"title":["Early Plus Delayed Hirudin Reduces Restenosis in the Atherosclerotic Rabbit More Than Early Administration Alone"],"prefix":"10.1161","volume":"98","author":[{"given":"Leonard M.","family":"Thome","sequence":"first","affiliation":[{"name":"From the Cardiovascular Division and the Department of Molecular Physiology and Cellular Biophysics (G.K.O.), Department of Medicine, University of Virginia, Charlottesville, and the Department of Anatomy and Cell Biology, Hadassah Medical School, Jerusalem, Israel (S.D.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence W.","family":"Gimple","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division and the Department of Molecular Physiology and Cellular Biophysics (G.K.O.), Department of Medicine, University of Virginia, Charlottesville, and the Department of Anatomy and Cell Biology, Hadassah Medical School, Jerusalem, Israel (S.D.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian G.","family":"Bachhuber","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division and the Department of Molecular Physiology and Cellular Biophysics (G.K.O.), Department of Medicine, University of Virginia, Charlottesville, and the Department of Anatomy and Cell Biology, Hadassah Medical School, Jerusalem, Israel (S.D.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Coleen A.","family":"McNamara","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division and the Department of Molecular Physiology and Cellular Biophysics (G.K.O.), Department of Medicine, University of Virginia, Charlottesville, and the Department of Anatomy and Cell Biology, Hadassah Medical School, Jerusalem, Israel (S.D.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Ragosta","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division and the Department of Molecular Physiology and Cellular Biophysics (G.K.O.), Department of Medicine, University of Virginia, Charlottesville, and the Department of Anatomy and Cell Biology, Hadassah Medical School, Jerusalem, Israel (S.D.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. David","family":"Gertz","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division and the Department of Molecular Physiology and Cellular Biophysics (G.K.O.), Department of Medicine, University of Virginia, Charlottesville, and the Department of Anatomy and Cell Biology, Hadassah Medical School, Jerusalem, Israel (S.D.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric R.","family":"Powers","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division and the Department of Molecular Physiology and Cellular Biophysics (G.K.O.), Department of Medicine, University of Virginia, Charlottesville, and the Department of Anatomy and Cell Biology, Hadassah Medical School, Jerusalem, Israel (S.D.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary K.","family":"Owens","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division and the Department of Molecular Physiology and Cellular Biophysics (G.K.O.), Department of Medicine, University of Virginia, Charlottesville, and the Department of Anatomy and Cell Biology, Hadassah Medical School, Jerusalem, Israel (S.D.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John E.","family":"Humphries","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division and the Department of Molecular Physiology and Cellular Biophysics (G.K.O.), Department of Medicine, University of Virginia, Charlottesville, and the Department of Anatomy and Cell Biology, Hadassah Medical School, Jerusalem, Israel (S.D.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian J.","family":"Sarembock","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division and the Department of Molecular Physiology and Cellular Biophysics (G.K.O.), Department of Medicine, University of Virginia, Charlottesville, and the Department of Anatomy and Cell Biology, Hadassah Medical School, Jerusalem, Israel (S.D.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114138"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116206"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.84.1.1829399"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.89.3.8124815"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1995.268.5.C1141"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.94.1.88"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.80.4.2529053"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4800(76)90072-1"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004424-198209000-00006"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.93.6.1194"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(97)00168-5"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.91.5.1444"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(96)00775-8"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.89.6.8205695"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198705283162204"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.95.7.1791"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.96.2.475"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.90.6.7994848"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199509213331203"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199509213331204"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.82.4.1476"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.CIR.98.21.2301","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T16:53:13Z","timestamp":1715532793000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.CIR.98.21.2301"}},"subtitle":["Potential Implications for Dosing of Antithrombin Agents"],"short-title":[],"issued":{"date-parts":[[1998,11,24]]},"references-count":21,"journal-issue":{"issue":"21","published-print":{"date-parts":[[1998,11,24]]}},"alternative-id":["10.1161\/01.CIR.98.21.2301"],"URL":"https:\/\/doi.org\/10.1161\/01.cir.98.21.2301","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,11,24]]},"assertion":[{"value":"1998-04-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-07-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-11-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}