Maintenance of patency after vascular trauma by topical irrigation with a peptide homologous to the carboxy-terminus of the fibrinogen gamma chain.
Synthetic peptides with amino acid sequences homologous to the carboxy-terminal sequence of the gamma chain of human fibrinogen were evaluated for their capacity to inhibit thrombus development. A 21-residue peptide effectively inhibited surface-mediated fibrin clot propagation in vitro. Since this effect was localized to the surface, we proceeded with in vivo evaluation, using site-specific topical application only. In a rat model of arterial trauma and microvascular repair, topical application of the 21-residue peptide significantly reduced the rate of thrombosis to 17%, as compared with a control rate of 83%; in comparison, a 12-residue homologue reduced the thrombosis rate only modestly to 61%, which was not significant compared with the control rate. These results indicate the feasibility of antithrombotic therapy with topically applied agents, an approach that may obviate the use of systemic anticoagulation in extremity-replantation surgery.
Cooley
B C
BC
Department of Orthopaedic Surgery, Medical College of Wisconsin, Milwaukee 53226.
Dollinger
B M
BM
Mlsna
J S
JS
Gould
J S
JS
D000287:Administration, Topical; D000595:Amino Acid Sequence; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001808:Blood Vessels / Q000293:injuries*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005340:Fibrinogen / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013927:Thrombosis / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D014654:Vascular Patency / Q000187:drug effects*; D014947:Wounds and Injuries / Q000150:complications*
D010455:Peptides; D005340:Fibrinogen