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.After iv and sc administration, the LMWH showedthe most effective antithrombotic effects, whereas somewhat milder protection was observedwith unfractionated heparin and an highly anionic fraction.Studies with various testssuggest that plasma markers such as the platelet release proteins.products of thrombinactivation and prostaglandin metabolites may provide better indicators in the monitoringof the antithrombic actions of newer heparins and antithrombotic drugs.This modelprovides the most similar preclinical model to study the actions of heparin fractions.181 - ENOX0097Fareed J; Walenga JM; Williamson K; Emanuele RM; Kumar A; Hoppensteadt DStudies on the antithrombotic effects and pharmacokinetics of heparin fractions andfragments (ENG)SEMIN THROMB HEMOST, (1985) 11 (1) 56-74, 72REFThe pharmacokinetics of heparin differ markedly from those of its fractions both in manand, in experimental animal models.The route of administration determines the relativeavailability of different molecular species that exert the anti-Xa, anti-Iia,fibrinopeptide A generation inhibiting actions and the release of tissue plasminogenactivator-like activity from the endothelial cell lining.The bioavailability of heparinfractions has proved to be much greater than heparin after subcutaneous or intraperitonealadministration.The primate model offers a useful preclinical model for the pharmacologicevaluation of the LMWH fractions.Since the coagulation system and heparinizability indexof this model approximate a human response, the data may be used to reflect therapeuticand prophylactic responses, as well as to assess toxic effects, such as bleeding.182 - ENOX0030Aiach M; Dreyfus G; Michaud A; Relland J; Murawsky M; Leclerc M; Carpentier ALow molecular weight (LMW) heparin derivatives in experimental extra-corporeal circulation(ECC) (ENG)HAEMOSTASIS, (1984), 14 (4), 325-332, 19REFThe purpose of this study was to determine the biological action and potential use of lowmolecular weight (LMW) heparin in open heart surgery; an experimental study was conducted,using extracorporeal circulation (ECC) in sheep as an experimental model.18 sheep wererandomly selected to receive either LMW heparin (2 mg/kg), high dose heparin (HD; 160U/kg), or low dose heparin (LD; 60 U/kg).The LMW heparin regimen yielded an anti-Xaactivity similar to the HD heparin regimen and an anti-IIa activity similar to the LDheparin regimen.Conclusions were: heparin chain depolymerisation diminishes the anti-APTTactivity without altering the antithrombotic property; LMW heparin is an effectivealternative to heparin in cardiac surgery; the absence of postoperative circulatinganti-APTT activity might be associated with a reduced incidence of hemorrhagiccomplication, but was not demonstrated.2 - ANTITHROMBOTIC PROPERTIES183 - ENOX1298Bostwick J; Bentley R; Dunwiddie C; Leadley R JrInhibition of venous thrombus formation in the rabbit by antithrombotic agents withdifferent mechanisms of action (ENG)FASEB J, 91997) 11 (3) A313 AB: 1817The mechanism of thrombus formation was studied by measuring the antithrombotic effects ofintravenous administration of a factor Xa inhibitor (DX9065a, 30 microg/kg/min).a directthrombin inhibitor (hirulog, 1 mg/kg + 10 micro/kg/min), a low-molecular weight heparin(enoxaparin, 0.1 mg/kg + 100 microg/kg/min) and unfractionated heparin (10 U/kg + 1U/kg/min) on the prevention of thrombosis in vivo.Relative antithrombotic activity wasassessed by the ability of these agents to inhibit thrombus formation in a damaged segmentof the rabbit jugular vein.184 - ENOX1327Kasiewski C; Bostwick J; Bentley R; Dunwiddie C; Perrone M; Leadley RInhibition of repetitive thrombus formation in the stenosed canine coronary artery byenoxaparin, but not by unfractionated heparin (ENG)FASEBJ, (1997) 11 (3) A313 AB: 1818The results of this study indicate that enoxaparin.unlike heparin.prevents repetitiveplatelet-dependent thrombus formation in the dog with a lower degree of systemicanticoagulation than with heparin; thereby supporting the potential use of enoxaparin inthe treatment of arterial thrombotic disorders such as unstable angina.185 - ENOX1356Korompilias AV; Chen LE; Seaber AV; Urbaniak JRAntithrombotic potencies of enoxaparin in microvascular surgery: influence of dose andadministration methods on patency rate of crushed arterial anastomoses (ENG)J HAND SURG (AM), (1997) 22A (3) 540-546, 43REFThis study evaluated the influence of the dose and administration methods of enoxaparin,on the patency rate of crushed rat femoral arteries following anastomosis.An impact crushwith a 25 kg magnitude was applied to a 2 mm segment of 100 rat femoral arteries, followedby anastomosis.The arteries were divided into five groups: group 1 received systemicenoxaparin alone with a relatively high dose (45 IU) twice a day for 3 days; groups 2 and3 received topical irrigation with a lower (15 IU/mL) concentration and a higher (45IU/mL) concentration, respectively; group 4 received systemic and topical application at alower (15 IU) dose and concentration (15 IU/mL); and group 5 received systemic and topicalapplication at a higher (45 IU) dose and concentration (45 IU/mL).The results of thisstudy demonstrate the following: (1) topical irrigation with enoxaparin at a concentrationof 45 IU/mL three times higher than that recommended for clinical use adjusted by bodyweight (15 IU/mL) is effective for antithrombotic action: (2) a combination of systemicand local application does not offer additional benefit in the patency rate when comparedto local irrigation alone; (3) systemic administration alone does not prevent thrombusformation; and (4) enoxaparin is potentially useful to enhance the patency rate incompromised microvessels
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