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Titolo:
ORALLY EFFECTIVE CVS-1123 PREVENTS CORONARY-ARTERY THROMBOSIS IN THE CONSCIOUS DOG
Autore:
COUSINS GR; FRIEDRICHS GS; SUDO Y; REBELLO SS; ROTE WE; VLASUK GP; NOLAN TG; MENDOZA C; LUCCHESI BR;
Indirizzi:
UNIV MICHIGAN,SCH MED,DEPT PHARMACOL,1301C MED SCI RES BLDG 3 ANN ARBOR MI 48109 UNIV MICHIGAN,SCH MED,DEPT PHARMACOL ANN ARBOR MI 48109 CORVAS INT SAN DIEGO CA 00000
Titolo Testata:
Circulation
fascicolo: 7, volume: 94, anno: 1996,
pagine: 1705 - 1712
SICI:
0009-7322(1996)94:7<1705:OECPCT>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
PLASMINOGEN-ACTIVATOR; ENDOTHELIAL-CELLS; CANINE HEART; FACTOR-XA; INHIBITORS; RECEPTOR; THROMBOLYSIS; REOCCLUSION; HEPARIN; MODEL;
Keywords:
THROMBOSIS; PLATELETS; ELECTRICAL STIMULATION; ISCHEMIA; MYOCARDIAL INFARCTION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
33
Recensione:
Indirizzi per estratti:
Citazione:
G.R. Cousins et al., "ORALLY EFFECTIVE CVS-1123 PREVENTS CORONARY-ARTERY THROMBOSIS IN THE CONSCIOUS DOG", Circulation, 94(7), 1996, pp. 1705-1712

Abstract

Background We examined the oral efficacy of a direct thrombin inhibitor, CVS-1123 [(CH3CH2CH2)(2)-CH-CO-Asp (OCH3)-Pro-Arg-CHO; MW, 575]. The object was to determine whether thrombin inhibition could reduce the incidence of occlusive coronary artery thrombosis in response to arterial wall injury. Methods and Results Arterial wall injury was induced in conscious dogs by a 150-mu A anodal current applied to the intimal surface of the circumflex coronary artery 30 minutes after oral CVS-1123 (20 mg/kg every 8 hours for three doses; n=11) or placebo containing diluent (n=10). Dogs were monitored for 8 hours and at 24 hours. The coronary artery remained patent for 24 hours in 8 of 11 CVS-1123-treated dogs. All dogs (n=10) in the placebo group developed a sustained, occlusive arterial thrombus. Two hours after the initial oral dose, the plasma CVS-1123 concentration was 13+/-1 mu g/mL, reaching a maximum of 15+/-1 mu g/mL after the second dose and 4.4+/-0.5 mu g/mL at 24hours. Ex vivo platelet aggregation to gamma-thrombin was inhibited and activated partial thromboplastin time was increased after treatmentwith CVS-1123 (P<.05). Conclusions The direct thrombin inhibitor CVS-1123 is effective after oral administration in reducing the incidence of primary thrombus formation in an experimental model of arterial wall injury. Thrombin-specific inhibitors, such as CVS-1123, may be alternative antithrombotic agents in clinical settings in which heparin-associated thrombosis is a complicating factor or when long-term anticoagulation is required.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/11/20 alle ore 00:36:16