title: Effects of heparin, dermatan sulfate and of their association on the inhibition of venous thrombosis growth in the rabbit.
abstract: This study compares the ability of unfractionated heparin, of dermatan sulfate, and of their simultaneous administration delivered as continuous intravenous infusion or as a single bolus injection to inhibit the growth of a standardized venous thrombosis in the rabbit. When delivered as continuous intravenous infusion for 4 h, heparin and dermatan sulfate inhibited thrombus growth in a dose dependent manner. The maximum antithrombotic effect of heparin was achieved at the dose of 0.15 mg kg-1 h-1 (25 U kg-1 h-1) which generated a mean plasma concentration of 1.8 micrograms ml-1 (0.31 U ml-1) and a 1.8 fold prolongation of the activated partial thromboplastin time (APTT) in comparison to the pretreatment value. A comparable antithrombotic effect was obtained with dermatan sulfate at the dose of 2 mg kg-1 h-1. This dose generated a mean plasma concentration of 30 micrograms ml-1 and a 1.3 fold APTT prolongation. Increasing these doses up to 10 fold did not improve the antithrombotic effect which did not overpass 60-70% of the controls. When the compounds were delivered simultaneously, the maximum antithrombotic effect (64%) was obtained with the following association: 0.06 mg kg-1 h-1 (10 U kg-1 h-1) for heparin and 1 mg kg-1 h-1 for dermatan sulfate. Increasing these doses up to 4 to 5 fold did not improve the antithrombotic effect. Heparin, dermatan sulfate and the association of both were also delivered as single bolus injections and the resultant antithrombotic effect was determined 4 h after saline infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Laboratoire d'Hémostase, Centre de Transfusion Sanguine, Toulouse, France.
authors.forename: D
authors.initials: D
authors.lastname: Carrie
authors.forename: C
authors.initials: C
authors.lastname: Caranobe
authors.forename: A M
authors.initials: AM
authors.lastname: Gabaig
authors.forename: M
authors.initials: M
authors.lastname: Larroche
authors.forename: B
authors.initials: B
authors.lastname: Boneu
mesh_terms: D000818:Animals; D003871:Dermatan Sulfate / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006493:Heparin / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007601:Jugular Veins; D008297:Male; D010314:Partial Thromboplastin Time; D011817:Rabbits; D013927:Thrombosis / Q000188:drug therapy*
chemical_list: D003871:Dermatan Sulfate; D006493:Heparin