{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T16:24:49Z","timestamp":1759335889704,"version":"3.40.3"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1996,1]]},"abstract":"<jats:p><jats:italic>Background<\/jats:italic>Fibrinogen receptor antagonists block the fibrinogen-platelet interaction at the GPIIb\/IIIa receptors and inhibit thrombus formation. SC-54701 is the active metabolite of SC-54684A, an orally active fibrinogen receptor antagonist. We compared the efficacy of SC-54701A (SCa, hydrochloride salt) with that of aspirin (ASA) or heparin and with combination therapy in a canine model of continuous current injury.<\/jats:p><jats:p><jats:italic>Methods and Results<\/jats:italic>Sixty-six dogs were used (6 per treatment). SCa (15-minute loading dose followed by [\/\/] infusion [\u03bcg\/kg per minute]: (0.87\/\/0.39=1\u00d7SCa; 0.52\/\/0.23=0.6\u00d7SCa; and 0.425\/\/0.20=0.5\u00d7SCa), ASA (2.8 mg\/kg), heparin (200 U\/kg plus 1000 U\/h), or saline (0.1 mL\/kg) was administered intravenously. Experimental time was 180 minutes of current. Time to occlusion was increased (<jats:italic>P<\/jats:italic>&lt;.05) by SCa (T=incidence of thrombosis) (1\u00d7SCa, &gt;180 minutes [T=0]; 0.6\u00d7SCa, 158\u00b115 minutes [T=2]; 0.5\u00d7SCa, 130\u00b122 minutes [T=4]), heparin (114\u00b116 minutes [T=5]), and ASA plus heparin (130\u00b111 minutes [T=5]) relative to saline (58\u00b17 minutes [T=6]). Time to occlusion for the SCa treatments was increased compared with ASA (64\u00b17 minutes [T=6]). When 0.5\u00d7SCa was administered with ASA plus heparin, time to occlusion was &gt;180 minutes [T=0]. SCa provided complete protection at \u226590% inhibition of ex vivo collagen-induced platelet aggregation. Cyclic flow variations were minimal with SCa or any treatment involving 0.5\u00d7SCa and ASA.<\/jats:p><jats:p><jats:italic>Conclusions<\/jats:italic>SCa has dose-dependent antithrombotic efficacy and inhibits ex vivo platelet aggregation. ASA, heparin, or saline was ineffective in this model. SCa (0.5\u00d7) plus ASA and heparin maximized the antithrombotic effect of this lower dose of SCa.<\/jats:p>","DOI":"10.1161\/01.cir.93.1.129","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:34:42Z","timestamp":1339461282000},"page":"129-134","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["The Protective Dose of the Potent GPIIb\/IIIa Antagonist SC-54701A Is Reduced When Used in Combination With Aspirin and Heparin in a Canine Model of Coronary Artery Thrombosis"],"prefix":"10.1161","volume":"93","author":[{"given":"Leo G.","family":"Frederick","sequence":"first","affiliation":[{"name":"From the Department of Cardiovascular Diseases Research, Searle, Skokie, Ill."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osman D.","family":"Suleymanov","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Diseases Research, Searle, Skokie, Ill."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucy W.","family":"King","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Diseases Research, Searle, Skokie, Ill."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita K.","family":"Salyers","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Diseases Research, Searle, Skokie, Ill."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy S.","family":"Nicholson","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Diseases Research, Searle, Skokie, Ill."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larry P.","family":"Feigen","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Diseases Research, Searle, Skokie, Ill."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198103193041201"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198610163151602"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(86)80121-8"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-8703(81)90310-0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(81)90065-5"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(85)80552-0"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-8703(77)80410-9"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-8703(81)90653-0"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.71.4.3971539"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.80.1.2661053"},{"key":"e_1_3_2_11_2","first-page":"235","volume":"231","year":"1971","unstructured":"Smith JB, Willis AL. Aspirin selectively inhibits prostaglandin production in human platelets. Nature. 1971;231:235-237.","journal-title":"Nature"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt1975184485"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1661629"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.77.3.3124975"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI109597"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V55.5.841.841"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-198507000-00019"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.91.2.403"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.81.2.2105175"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.82.1.2114233"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1097\/00019501-199309000-00008"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.54.3.947567"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.69.6.1161"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.79.1.2910540"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.55.5.6488486"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0049-3848(94)90256-9"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.78.3.3136953"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198810273191701"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)50603-7"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8493523"},{"key":"e_1_3_2_31_2","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/S0022-3565(25)39536-4","volume":"267","year":"1993","unstructured":"Feigen LP, Nicholson NS, King LW, Campion JG, Tjoeng FS, Panzer-Knodle SG. SC-49992, a mimetic of the peptide arginine-glycine-aspartic acid-phenylalanine that blocks platelet aggregation, enhances recombinant tissue plasminogen activator-induced thrombolysis and prevents reocclusion in a canine model of coronary artery thrombosis. J Pharmacol Exp Ther. 1993;267:1191-1197.","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1642390"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.89.1.8281661"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.91.2.403"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1648925"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(93)90695-W"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.65.2.7053882"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.CIR.93.1.129","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T20:02:58Z","timestamp":1743364978000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.CIR.93.1.129"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,1]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1996,1]]}},"alternative-id":["10.1161\/01.CIR.93.1.129"],"URL":"https:\/\/doi.org\/10.1161\/01.cir.93.1.129","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"type":"print","value":"0009-7322"},{"type":"electronic","value":"1524-4539"}],"subject":[],"published":{"date-parts":[[1996,1]]},"assertion":[{"value":"1995-04-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1995-08-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1996-01-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}