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Titolo:
ANTITHROMBOTIC EFFICACY OF A RECOMBINANT NEMATODE ANTICOAGULANT PEPTIDE (RNAP5) IN CANINE MODELS OF THROMBOSIS AFTER SINGLE SUBCUTANEOUS ADMINISTRATION
Autore:
REBELLO SS; BLANK HS; ROTE WE; VLASUK GP; 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
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 1, volume: 283, anno: 1997,
pagine: 91 - 99
SICI:
0022-3565(1997)283:1<91:AEOARN>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
COAGULATION-FACTOR-XA; CORONARY-ARTERY THROMBOSIS; SMALL PROTEIN INHIBITOR; THROMBOEMBOLIC DISORDERS; ANCYLOSTOMA-CANINUM; VENOUS THROMBOSIS; PLATELET FACTOR-4; POTENT INHIBITOR; RABBIT MODEL; HEPARIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
34
Recensione:
Indirizzi per estratti:
Citazione:
S.S. Rebello et al., "ANTITHROMBOTIC EFFICACY OF A RECOMBINANT NEMATODE ANTICOAGULANT PEPTIDE (RNAP5) IN CANINE MODELS OF THROMBOSIS AFTER SINGLE SUBCUTANEOUS ADMINISTRATION", The Journal of pharmacology and experimental therapeutics, 283(1), 1997, pp. 91-99

Abstract

We describe the antithrombotic effects of recombinant nematode anticoagulant peptide (rNAP5), a selective and direct factor Xa inhibitor, after a single s.c. administration in canine models of arterial and venous thrombosis. The systemic anticoagulant effects of rNAP5 were evaluated initially in conscious dogs after s.c. dosing (0.03, 0.1 and 0.3 mg/kg) that resulted in a dose-dependent increase in the activated clotting time and the activated partial thromboplastin time. The antithrombotic effects of rNAP5 were evaluated in anesthetized dogs where saline or rNAP5 (0.03, 0.1 and 0.3 mg/kg s.c.) was administered 1 hr before the left circumflex coronary artery was subjected to electrolytic injury. In the saline group (n = 10), the left circumflex artery occluded in 79 +/- 9 min, and 5 of 10 animals progressed to sudden death due to ventricular fibrillation. rNAP5 significantly prolonged the time toocclusion in the 0.03 mg/kg (163 +/- 62 min) and 0.1 mg/kg (327 +/- 62) treatment groups (n = 6). In the 0.3 mg/kg group (n = 5), all of the injured vessels remained patent for 8 hr. There was a dose-dependentreduction in the thrombus mass in the rNAP5-treated animals as compared with controls, as well as a lower mortality rate. rNAP5, in the doses of 0.03 and 0.1 mg/kg, did not alter the bleeding time, whereas 0.3mg/kg produced a 5-fold increase. In a separate study, we evaluated the efficacy of rNAP5 (0.1 mg/kg) in the prevention of carotid artery and jugular vein thrombosis. In response to endothelial injury, the carotid artery and jugular vein in the saline group (n = 6) occluded in 142 +/- 16 and 100 +/- 11 min, respectively, compared with rNAP5, whichmaintained vessel patency in the carotid artery (6/6) and jugular vein (5/6) and significantly decreased the thrombus weights. The results demonstrate that rNAP5 has antithrombotic efficacy in canine models ofarterial and venous thrombosis after a single s.c. administration.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/11/20 alle ore 03:50:04