These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Combination of platelet fibrinogen receptor antagonist and direct thrombin inhibitor at low doses markedly improves thrombolysis.
    Author: Nicolini FA, Lee P, Rios G, Kottke-Marchant K, Topol EJ.
    Journal: Circulation; 1994 Apr; 89(4):1802-9. PubMed ID: 8149546.
    Abstract:
    BACKGROUND: We evaluated the effects of a novel platelet fibrinogen receptor antagonist, Integrelin, and a direct thrombin inhibitor, recombinant hirudin, given together with recombinant tissue plasminogen activator (rTPA) in a canine experimental model of intracoronary thrombosis. We tested the hypothesis that combination of both agents at low doses would have an additive antithrombotic effect, resulting in a significant improvement in the efficacy of rTPA. METHODS AND RESULTS: Thirty-two dogs with an electrically induced coronary thrombus were treated with rTPA (1 mg/kg over 20 minutes) together with one of the following adjunctive treatments in a random fashion. Eight dogs received saline for 90 minutes; Integrelin (5 micrograms.kg-1.min-1 for 90 minutes) was given to 8 dogs; 8 dogs received recombinant hirudin (20 micrograms.kg-1.min-1 for 90 minutes); and 8 dogs were treated with a low-dose combination of Integrelin (2.5 micrograms.kg-1.min-1) plus recombinant hirudin (10 micrograms.kg-1.min-1) for 90 minutes. Integrelin or recombinant hirudin, when given as single adjunct to rTPA, enhanced the lysis of the occlusive thrombus, causing full restoration of coronary blood flow (100% of its baseline value) for 29 +/- 16 and 26 +/- 5 minutes, respectively, whereas coronary blood flow was fully restored for only 5 +/- 1 minutes in dogs receiving rTPA plus saline (both P < .05). However, either Integrelin or recombinant hirudin failed to modify the reocclusion rate (57% and 63%, respectively) compared with saline (83%; all P = NS). Conversely, the low-dose combination therapy led to complete restoration of coronary blood flow for 92 +/- 19 minutes (P < .01 versus all treatments) and significantly reduced the reocclusion rate (25%; P < .05 versus saline). CONCLUSIONS: These data show that inhibition of specific pathways of platelet and thrombin activity improves the extent and duration of rTPA-induced thrombolysis in the electrolytic canine model. Furthermore, our findings suggest that low doses of platelet IIb/IIIa and direct thrombin antagonists in combination may be used successfully during thrombolysis.
    [Abstract] [Full Text] [Related] [New Search]