A new bioactive molecule for improving vascular graft patency: exploratory trials in dogs.
Myxalin is a new bioactive molecule that we have isolated from the culture medium of Myxococcus xanthus, a non-pathogenic Gram negative bacterium. This glycopeptide possesses an antithrombotic effect in vivo and has been shown to promote human endothelial cell growth in vitro. With the object of exploring its ability to improve vascular graft healing and patency, myxalin was immobilized on 6 mm diameter knitted polyester prostheses using gelatin as a carrier, and the prosthesis was then implanted as an infrarenal abdominal arterial substitute in dogs for a period of 2 weeks. Two additional series of implantations were conducted for control purposes: one with gelatin-coated prostheses without myxalin, the other following normal preclotting of the polyester grafts. In order to select adequate sterilization conditions which can preserve the biological activity of myxalin, the prostheses were sterilized according to 3 different sterilization processes (gamma radiation and ethylene oxide either at 63 degrees C or 37 degrees C). At the sacrifice, all grafts were patent. The myxalin treated prostheses exhibited improved blood compatibility in terms of fewer thrombotic deposits and significant inhibition of platelet and fibrinogen uptake on their luminal surfaces. In addition, the development of a thin collagenous internal capsule with endothelial cells secreting high levels of prostacyclin was observed at both anastomoses of the myxalin-treated grafts sterilized by gamma radiation.
Akoum
A
A
Department of Surgery, Laval University, Québec.
Guidoin
R
R
King
M W
MW
Marois
Y
Y
Sigot
M
M
Sigot-Luizard
M F
MF
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D001792:Blood Platelets / Q000378:metabolism; D001807:Blood Vessel Prosthesis; D004285:Dogs; D005340:Fibrinogen / Q000378:metabolism; D006020:Glycopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D008855:Microscopy, Electron, Scanning; D016941:Myxococcus xanthus / Q000378:metabolism; D013927:Thrombosis / Q000517:prevention & control; D013928:Thromboxane A2 / Q000096:biosynthesis; D014654:Vascular Patency / Q000187:drug effects*
D001426:Bacterial Proteins; D006020:Glycopeptides; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D005340:Fibrinogen