G4120, an Arg-Gly-Asp containing pentapeptide, enhances arterial eversion graft recanalization with recombinant tissue-type plasminogen activator in dogs.
The effects of G4120, a cyclic Arg-Gly-Asp (RGD) containing peptide which inhibits fibrinogen binding to the platelet receptor GPIIb/IIIa, on thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) were investigated in a combined arterial and venous thrombosis model in heparinized dogs. The arterial thrombus model consisted of a 3 cm everted (inside-out) carotid arterial segment inserted into a transsected femoral artery which occludes within 30 min with platelet-rich material and which is resistant to recanalization with 0.5 mg/kg rt-PA. The venous thrombus was a 125I-fibrin labeled whole blood clot produced in the contralateral femoral vein. In 5 dogs given an intravenous bolus of 0.05 mg/kg G4120 followed by a continuous infusion of 0.05 mg/kg per hour for 3 h (group I), arterial occlusion persisted throughout a 4 h observation period and was still present at 24 h in all dogs; the extent of venous clot lysis after 120 min was 27 +/- 7%. In 5 dogs given the same infusion of G4120 in combination with 0.5 mg/kg rt-PA over 60 min, recanalization of the arterial graft occurred in all dogs, within 13 +/- 2 min and persisted throughout the observation period of 4 h (p = 0.01 versus G4120 or rt-PA alone); at 24 h, however, all grafts were occluded. Venous clot lysis in this group was 75 +/- 8% (p = 0.002 versus G4120 alone and p = NS versus rt-PA alone). Pathologic analysis revealed platelet-rich or mixed thrombus with platelet-rich and erythrocyte-rich zones.(ABSTRACT TRUNCATED AT 250 WORDS)
Lu
H R
HR
Center for Thrombosis and Vascular Research, University of Leuven, Belgium.
Gold
H K
HK
Wu
Z
Z
Yasuda
T
T
Pauwels
P
P
Rapold
H J
HJ
Napier
M
M
Bunting
S
S
Collen
D
D
D000595:Amino Acid Sequence; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000473:pathology; D002339:Carotid Arteries / Q000637:transplantation*; D004195:Disease Models, Animal; D004285:Dogs; D004351:Drug Resistance / Q000502:physiology; D004357:Drug Synergism; D005263:Femoral Artery / Q000601:surgery*; D005268:Femoral Vein / Q000601:surgery*; D006487:Hemostasis / Q000187:drug effects; D007262:Infusions, Intravenous; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013927:Thrombosis / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
D009842:Oligopeptides; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator