Comparative study on heparin and a synthetic thrombin inhibitor no.805 (MD-805) in experimental antithrombin III-deficient animals

Kumada, Toshihiko; Abiko, Yasushi

doi:10.1016/0049-3848(81)90002-5

Cited by 54 publications

(30 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, knowledge of the blood level course of the various inhibitors is of vital importance for evaluating their antithrombotic effectiveness. Half-lives of 60 min for hirudin [18], 10 min for NAPAP [23] and 15 min for argidipine [24] were found in animals used in other studies. Con sequently, the course of anticoagulant activ ity measured ex vivo is almost the same for all three inhibitors.…”

Section: Discussionmentioning

confidence: 82%

Antithrombotic Effects of Three Thrombin Inhibitors in a Rat Model of Laser-Induced Thrombosis

Krupiński

Breddin²,

Markwardt³

et al. 1989

Pathophysiol Haemos Thromb

View full text Add to dashboard Cite

The antithrombotic effects of three thrombin inhibitors (hirudin, NAPAP and argidipine) were investigated in an experimental thrombosis model using laser lesions of rat mesenteric venules. Furthermore, their in vitro anticoagulant activity (partial thromboplastin time, thrombin time, Heptest, inhibition of factor Xa and factor Xa) in human platelet poor plasma (PPP) and their in vitro and ex vivo activities were studied in rat plasma. All three thrombin inhibitors showed significant and dose-dependent antithrombotic effects after intravenous injection, if venules were damaged, which lasted for more than 4 but less than 8 h. The anticoagulant effect observed in vitro did not differ much between human and rat PPP. The two synthetic thrombin inhibitors NAPAP and argidipine were about as effective as hirudin in vitro; however, the ex vivo effect after intravenous injection of hirudin in rats was more pronounced than that observed with the two synthetic thrombin inhibitors. The antithrombotic effect of all three thrombin inhibitors in the laser model lasted much longer than the anticoagulant activity. This fact needs further investigations in the future.

show abstract

Section: Discussionmentioning

confidence: 82%

Antithrombotic Effects of Three Thrombin Inhibitors in a Rat Model of Laser-Induced Thrombosis

Krupiński

Breddin²,

Markwardt³

et al. 1989

Pathophysiol Haemos Thromb

View full text Add to dashboard Cite

show abstract

“…This will be a principal advantage compared with heparin in condi tions with reduced antithrombin levels. This advantage has been experimentally proven in rats depleted in AT III immunologically [43].…”

Section: Discussionmentioning

confidence: 94%

Effect of Heparin, Hirudin, and a Synthetic Thrombin Inhibitor on Antithrombin III in Thrombin-Induced Disseminated Intravascular Coagulation in Rats

Hauptmann¹,

Brüggener²,

Markwardt³

1987

Pathophysiol Haemos Thromb

View full text Add to dashboard Cite

The effect of heparin, hirudin, and a synthetic thrombin inhibitor on antithrombin III, fibrinogen and platelets was studied in a rat model of disseminated intravascular coagulation (DIC) induced by thrombin infusion. Antithrombin III is consumed during thrombin infusion to a limited degree. Simultaneous administration of exogenous thrombin inhibitors ameliorates the consumption of fibrinogen and platelets. At high thrombin doses, tolerated only during additional administration of thrombin inhibitors, heparin leads to increased consumption of antithrombin III, whereas hirudin and the synthetic inhibitor do not. In every case, the thrombin effect on fibrinogen and platelets is inhibited.

show abstract

“…In other animal models, it has been demonstrated that its antithrombotic effect is independent of ATIII (38). In humans, it has been used for anticoagulation during cardiopulmonary bypass (39) and hemodialysis (40) and for the treatment of disseminated intravascular coagulation (39).…”

mentioning

confidence: 99%

Thrombin is an important mediator of platelet aggregation in stenosed canine coronary arteries with endothelial injury.

Eidt¹,

Allison²,

Noble³

et al. 1989

J. Clin. Invest.

237

View full text Add to dashboard Cite

Cyclic variations in coronary blood flow (CFVs) in dogs with experimental coronary artery stenosis and endothelial injury appear to result primarily from the aggregation of platelets at the site of stenosis followed by dislodgement and distal embolization. Using this canine model, we tested the hypotheses: (a) that thrombin is an important mediator of CFVs in dogs with coronary stenoses and endothelial injury; (b) that inhibition of thrombin with heparin, or MCI-9038, a selective thrombin inhibitor, abolishes CFVs in this model; and (c) that abolition of CFVs by thrombin inhibition is time dependent. CFVs, produced in open-chest dogs by placing a flow-reducing plastic constrictor around the left anterior coronary artery, were monitored for either 30 min (group I) or 3 h (group II) before treatment with either heparin or 4-methyl-14N'-+(3-methyl-1,2,3,4-tetrahydro-8-quinolinyl

show abstract

Comparative study on heparin and a synthetic thrombin inhibitor no.805 (MD-805) in experimental antithrombin III-deficient animals

Cited by 54 publications

References 14 publications

Antithrombotic Effects of Three Thrombin Inhibitors in a Rat Model of Laser-Induced Thrombosis

Antithrombotic Effects of Three Thrombin Inhibitors in a Rat Model of Laser-Induced Thrombosis

Effect of Heparin, Hirudin, and a Synthetic Thrombin Inhibitor on Antithrombin III in Thrombin-Induced Disseminated Intravascular Coagulation in Rats

Thrombin is an important mediator of platelet aggregation in stenosed canine coronary arteries with endothelial injury.

Contact Info

Product

Resources

About